Focal dermal hypoplasia: inheritance from father to daughter

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Primary cutaneous nocardiosis caused by Nocardia brasiliensis following a wasp sting

Summary

We report a case of an 87-year-old woman who presented with painful erythema of her right forearm 10 days after she had been stung by a wasp on her right hand. The lesion had rapidly deteriorated during the week before presentation, and treatment with antibiotics and glucocorticoids did not improve the condition. After careful evaluation, we performed cultures from the lesion aspiration, and morphological and genetic analysis of bacteria cultures confirmed a bacterial infection with Nocardia brasiliensis. The patient recovered after 3 weeks. Primary cutaneous nocardiosis due to Nocardia spp. is relatively uncommon in clinics, but it was the distance of the lesions from the affected area of the wasp sting that has made this an even rarer case and of interest to report.

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The role of fillers in the management of acne scars

Summary

Acne scars are present in 95% of patients with acne, and can cause profound psychosocial morbidity. Fillers are commonly used for facial soft tissue augmentation, and there is increasing interest in their use for the treatment of acne scars, particularly for the atrophic subtype. We review the evidence for the use of temporary, semi-permanent and permanent fillers for acne scars. The use of permanent methylmethacrylate fillers for acne scarring is supported by a randomized controlled trial, and is approved by the United States Food and Drug Administration. There is initial evidence supporting the use of poly-L-lactic acid and hyaluronic acid fillers, but evidence is still lacking about the use of polyacrylamide and polyalkylimide fillers.

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Erythema elevatum diutinum in a healthy child

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An unusual and potentially fatal cause of scalp crusting

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Extensive levamisole-induced vasculitis

Summary

Levamisole (an increasingly frequent contaminant of cocaine) can cause antineutrophil cytoplasmic antibody-associated vasculitis. Dermatologists should consider a diagnosis of cocaine/levamisole-associated cutaneous vasculopathy syndrome in cases of purpura of the ears and/or extensive retiform purpura in drug users. We report a case of particularly severe levamisole-induced necrotic purpura and immunological abnormalities in a 40-year-old woman.

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‘Super bloom’ dermatitis

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Role of nail bed methotrexate injections in isolated nail psoriasis: conventional drug via an unconventional route

Summary

Nail psoriasis can be a debilitating condition; however, in patients with isolated nail involvement, the use of toxic systemic therapies such as methotrexate may not be justified. We report on 4 patients (30 involved nails between them), who were treated with injections of methotrexate (0.1 mL of a 25 mg/mL solution) into the nail bed at 3-weekly intervals. Mean baseline Nail Psoriasis Severity Index (NAPSI) was 4.77 (range 2–8, cumulative score 143; n = 30); dropping successively at each visit to 2.43 (range 0–4, cumulative score 73; n = 30) at 15 weeks. The decline in mean NAPSI from 4.87 to 2.17 was statistically significant (P < 0.001; Friedman analysis). Reported adverse effects were pain, injection site pigmentation and nail bed haemorrhage. Administration of specific targeted therapy to the nail bed may help manage nail psoriasis effectively.

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Preoperative Radiotherapy Is Not Associated with Increased Post-mastectomy Short-term Morbidity: Analysis of 77,902 Patients

Background: Neoadjuvant radiotherapy (NRT) enhances breast-conserving surgery outcomes, reducing local recurrence of breast cancer and increasing median survival. However, its effect on postoperative morbidity remains under-studied. We sought to assess the impact of NRT on 30-day postoperative morbidity after mastectomy. Methods: We analyzed data from women undergoing mastectomy (with or without immediate reconstruction) using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) 2005–2011 datasets. ACS-NSQIP is a prospective, risk-adjusted, outcomes-based registry. Data included demographic and perioperative factors. Outcomes studied included surgical site (wound and prosthesis/flap complications), systemic (cardiac, respiratory, neurological, urinary, and venous thromboembolism events), and overall morbidity. Logistic regression was used to estimate the unadjusted odds ratio (uOR) and adjusted odds ratio (aOR) between NRT and postoperative 30-day morbidity. Results: The study population included 77,902 women, of which 61,039 (78.4%) underwent mastectomy only and 16,863 (21.6%) underwent mastectomy with immediate breast reconstruction. NRT was administered to 266 (0.4%) mastectomy-only and 75 (0.4%) immediate breast reconstruction patients. In the mastectomy-only group, there were no significant differences in the rates of postoperative surgical site morbidity (aOR = 1.41; 95% confidence interval (CI): 0.76–2.63; P = 0.276), systemic morbidity (aOR = 0.72; 95% CI: 0.40–1.26; P = 0.252), and overall morbidity (aOR = 0.85; 95% CI: 0.54–1.33; P = 0.477) between NRT and control groups. Similarly, no significant differences were found for these three outcomes in the immediate breast reconstruction population. Statistical power for every comparison was >80%. Conclusions: This study suggests that NRT is not associated with significantly higher 30-day postoperative complications among breast cancer patients undergoing mastectomy with or without immediate breast reconstruction.

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Natural pomegranate juice reduces inflammation, muscle damage and increase platelets blood levels in active healthy Tunisian aged men

Publication date: Available online 7 April 2017
Source:Alexandria Journal of Medicine
Author(s): Ammar Achraf, Chtourou Hamdi, Mouna Turki, Osama Abdelkarim, Fatma Ayadi, Anita Hoekelmann, Sourou Yaich, Nizar Souissi
Currently, it's well established that aging is associated with various health problems that may interfere with the maintenance of a good nutritional status. Otherwise, pomegranate (POM) was shown to prevent or treat various disease risk factors in adults. However, its efficacy is still not well widespread in elderly population. Therefore, the purpose of the present study is to investigate the effect of natural pomegranate juice (POMj) rich in polyphenols on the blood levels of selected biochemical parameters using older adults.Twelve active healthy aged men (age: 60±5years) volunteered to participate in this randomized study. Before and after the supplementation period fasting blood samples were collected, heart rate (HR) and systolic arterial pressure (SAP) were recorded. Supplements of placebo (PLA) or POMj were taken twice daily (250ml×2) for 15days.Paired simple t-test showed a significant difference between PLA and POMj supplementation effects on systolic blood pressure (SAP), creatinine (CRE), hematological and muscle damage parameters and C-reactive protein (CRP) (p<0.01) with lower values using POMj. Similarly, a significant differences were shown for platelets PLT (p<0.01) with higher values using POMj supplementation. POMj rich in polyphenols seems to have a power anti-inflammatory effect and to be an effective treatment for patients who suffer from the thrombocyto-penia disease. Therefore, aged populations are advised to add natural POMj to their daily nutrition behavior.



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Protective role of Spondias mombin leaf and Cola acuminata seed extracts against scopolamine-induced cognitive dysfunction

Publication date: Available online 6 April 2017
Source:Alexandria Journal of Medicine
Author(s): Ismail O. Ishola, Bukola O. Ikuomola, Olufunmilayo O. Adeyemi
The leaves of Spondias mombin L. (Anacardiaceae) when chewed with Cola acuminata (P. Beauv.) Schott & Endl. (Sterculiaceae) seeds have memory enhancing and anti-ageing properties. This study sought to investigate the protective effect of hydroethanolic leaf extract of Spondias mombin (SM) and Cola acuminata seed extract (CA) against scopolamine-induced cognitive dysfunction. SM or CA (50, 100 or 200mg/kg, p.o.) or SM+CA (50mg/kg, p.o.) was administered to rats for 3 consecutive days. One hour post-treatment on day 3, scopolamine (3mg/kg i.p) was administered and 5min later, the Y-maze test or Morris water maze test (MWM; days 3–7) was conducted. The rat's brains were isolated for the estimation of oxidative-nitritive stress status following the MWM task. The antioxidant capacity of SM and CA was also evaluated in vitro using the 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO) and ferric ion reducing power (FRAP) assays. Pretreatment of rats with SM, CA or SM+CA significantly ameliorated the learning and memory impairment induced with scopolamine as evidenced in Y-maze and MWM paradigms. Moreover, SM, CA or SM+CA significantly attenuated the oxidative-nitritive stress induced by scopolamine, evidenced in the decrease in malondialdehyde and nitrite levels and restoration of glutathione, catalase and superoxide dismutase levels. Furthermore, SM and CA showed promising free radical scavenging effect against DPPH and moderate antioxidant activity in NO and FRAP tests. This study showed that Spondias mombin and Cola acuminata have significant protective effect against scopolamine-induced memory deficit that could be attributed to their antioxidant properties.



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Sexual function of pregnant women in the third trimester

Publication date: Available online 7 April 2017
Source:Alexandria Journal of Medicine
Author(s): Nülüfer Erbil
IntroductionPhysical, hormonal and psychological changes during pregnancy can affect a woman's sexuality as well as a couple's sexual relationship. The aim of this study was to examine sexual function of pregnant women in the third trimester of pregnancy.MethodsThe data of descriptive and cross-sectional study was collected via a questionnaire form and Female Sexual Function Index. A score≤26.55 is classified as female sexual dysfunction. A total of 125 volunteer healthy and married pregnant women in third trimester of pregnancy who admitted to the antenatal policlinics were included in this study.ResultsThe determined that 92% of participants had sexual dysfunction. The Female Sexual Function Index and domains scores in the 28th-31st, 32nd-35th and 36th and higher gestational weeks of pregnancy were as follows: sexual desire scores, 2.50, 2.77 and 2.40; sexual arousal scores, 2.26, 2.72 and 1.69; lubrication scores, 2.61, 3.42 and 1.97; orgasm scores, 2.51, 2.85 and 1.78; sexual satisfaction scores, 3.17, 3.77 and 2.66; pain scores, 2.44, 2.72 and 1.66, and total Female Sexual Function Index scores were 15.51, 18.29, 12.26, respectively. Sexual arousal (p=0.008), lubrication (p=0.001), orgasm (p=0.031), sexual satisfaction (p=0.005), pain (p=0.049) and total Female Sexual Function Index score (p=0.004) were the lowest in 36th and higher gestational weeks, and only sexual desire did not differ (p=0.191).ConclusionsSexual function of pregnant women in the third trimester were negatively effected. Health professionals should be trained to evaluate sexual difficulties in pregnant women and to recommend possible solutions.



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Polμ deficiency induces moderate shortening of P53−/− mouse lifespan and modifies tumor spectrum

Publication date: Available online 10 April 2017
Source:DNA Repair
Author(s): Beatriz Escudero, Diego Herrero, Yaima Torres, Susana Cañón, Antonio Molina, Rosa M. Carmona, Javier Suela, Luis Blanco, Enrique Samper, Antonio Bernad
Non-homologous end joining (NHEJ) is the main mechanism for double strand break (DSB) DNA repair. The error-prone DNA polymerase mu (Polμ) is involved in immunoglobulin variable region rearrangement and in general, NHEJ in non-lymphoid cells. Deletion of NHEJ factors in P53^−/− mice, which are highly prone to development of T cell lymphoma, generally increases cancer incidence and shifts the tumor spectrum towards aggressive pro-B lymphoma. In contrast, Polμ deletion increased sarcoma incidence, proportionally reducing pro-B lymphoma development on the P53-deficient background. Array comparative genomic hybridization (aCGH) analyses showed DNA copy number alterations in both P53^−/− and Polμ^−/−P53^−/− lymphomas. Our results also indicate that the increase in sarcoma incidence in Polμ^−/−P53^−/− mice could be associated with Cdk4 and Kub3 amplification and overexpression. These results identify a role for Polμ in the prevention of sarcomagenesis on a murine P53-deficient background, in contrast to most other NHEJ factors.



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Gender differences in risk factors for cigarette smoking initiation in childhood

Publication date: September 2017
Source:Addictive Behaviors, Volume 72
Author(s): Marie-Pierre Sylvestre, Robert J. Wellman, Erin K. O'Loughlin, Erika N. Dugas, Jennifer O'Loughlin
IntroductionWe investigated whether established risk factors for initiating cigarette smoking during adolescence (parents, siblings, friends smoke; home smoking rules, smokers at home, exposure to smoking in cars, academic performance, susceptibility to smoking, depressive symptoms, self-esteem, school connectedness, use of other tobacco products) are associated with initiation in preadolescents, and whether the effects of these factors differ by gender.MethodsIn spring 2005, baseline data were collected in self-report questionnaires from 1801 5th grade students including 1553 never-smokers (mean age=10.7years), in the longitudinal AdoQuest I Study in Montréal, Canada. Follow-up data were collected in the fall and spring of 6th grade (2005–2006). Poisson regression analyses with robust variance estimated the effects of each risk factor on initiation and additive interactions with gender were computed to assess the excess risk of each risk factor in girls compared to boys.Results101 of 1399 participants in the analytic sample (6.7% of boys; 7.7% of girls) initiated smoking during follow-up. After adjustment for age, gender and maternal education, all risk factors except academic performance and school connectedness were statistically significantly associated with initiation. Paternal and sibling smoking were associated with initiation in girls only, and girls with lower self-esteem had a significant excess risk of initiating smoking in 6th grade.ConclusionsRisk factors for smoking initiation in preadolescents mirror those in adolescents; their effects do not differ markedly by gender. Preventive programs targeting children should focus on reducing smoking in the social environment and the dangers of poly-tobacco use.



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Toxicity of triptolide and the molecular mechanisms involved

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Chen Xi, Shaojun Peng, Zhengping Wu, Qingping Zhou, Jie Zhou
Triptolide (TP), a major active and toxic ingredient isolated from the traditional Chinese herb Tripterygium wilfordii Hook f. (TWHF). A widespread application of TP raises the question on the safety of its use in clinical settings. The metabolism of TP is mediated by hepatic cytochrome P450s, and a strong correlation exists between TP toxicity and CPY3A. Toxicity of TP and the molecular mechanisms of its toxic effects have been studied in recent years. Studies have demonstrated that TP exposure results in injury of various organs, including the liver, kidney, testes, ovary, and heart in animals and even in humans, according to clinical case reports. Moreover, on the cellular level, TP has been reported to be associated with diverse toxic effects, encompassing membrane damage, mitochondrial disruption, metabolism dysfunction, endoplasmic reticulum stress, oxidative stress, apoptosis and autophagy. This review presents an overview of the current findings related to TP toxicity with an emphasis on biological targets and the molecular mechanisms that may be involved, thus providing a systematic understanding of the mechanisms by which TP affects cells and tissues in vitro and in vivo.



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Diabetes associated with male reproductive system damages: Onset of presentation, pathophysiological mechanisms and drug intervention

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Guang-Jiang Shi, Zhi-Mei Li, Jie Zheng, Jian Chen, Xiao-Xu Han, Jing Wu, Guang-Yong Li, Qing Chang, Yu-Xiang Li, Jian-Qiang Yu
Diabetes mellitus (DM) is a major health problem that affects patients' quality of life quality throughout the world due to its many complications. Reproductive dysfunction is one of the major secondary complications in both diabetic animals and human beings. Furthermore, DM has recently broken the age barrier and has been heavily diagnosed in children and young persons of reproductive age. In the past few years, many studies on DM in male reproductive functions in both diabetic men and experimental diabetic animals have been published. It is recognized that sustained hyperglycemia, which impairs reproductive function in diabetic men, is at risk of developing. DM harmfully affects male reproductive functions in multiple areas; these may include spermatogenesis, sperm maturation, fertility capability, penile erection, and ejaculation. Traditional medicine and folklore worldwide have used numerous medicinal plants to manage the diabetic reproductive dysfunction because bioactive phyto-constituents are affluent in many places. Unfortunately, the exact reasons for diabetic male reproductive dysfunction are not completely understood and currently there are no treatments in reproductive medicine specifically for such lesions. The aim of this review is to summarize current research findings of DM on reproductive functions, to elaborate the underlying mechanisms related to these diseases via in vivo and in vitro studies, and to describe the ameliorative effects of medicinal plants or their products. The review findings provide a systematic understanding of DM on the reproductive functions and lay the theoretical foundation for developing the direction of reproductive medicine.



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A peek into the drug development scenario of endometriosis – A systematic review

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Luxitaa Goenka, Melvin George, Maitrayee Sen
Purpose and objectiveEndometriosis is a gynaecological disease that is characterised by the presence of endometrium like tissue-epithelium and stroma that develops outside the uterine cavity, which is responsible for pelvic pain and infertility. Even though several medical therapies exist for the treatment of endometriosis, each of the drug class has its own limitations such as cost of treatment, side-effects and its short-term effect on the symptoms of endometriosis. In this review, we have attempted to summarize the current status and challenges of drug development for endometriosis.MethodsA systematic review was done and all the RCTs were selected from the identified hits. We included studies that explored the usage of therapeutic drugs on endometriosis patients from inception till November 2016. The search term used was 'Endometriosis' using PubMed and Clinicaltrials.gov. For the final analysis, 60 articles were analyzed and we identified the newly emerging drug therapies for endometriosis treatment and have briefed their current status and challenges in drug development for endometriosis. The quality of the selected studies was assessed based on the degree of bias.ResultsThe current classes of drugs that have shown promising therapeutic results include Gonadotropin- releasing hormone (GnRH) antagonists, aromatase inhibitors (AI), and selective progesterone and estrogen receptor modulators, dopamine receptor-2-agonists and statins. The drugs that failed midway during development include tanezumab, rosiglitazone, infliximab, pentoxifylline, telapristone acetate, asoprisnil and raloxifene.ConclusionFrom the literature review, it appears that the most promising molecules for the treatment of endometriosis in the near future include elagolix, mifepristone, TAK-385, KLH-2109 and ASP1707 and cabergoline. It remains to be seen if these molecules would succeed large phase 3 clinical trials and overcome the regulatory hurdles to become an essential tool in the gynaecologist's armamentarium against endometriosis.



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Comparison of self-reported signs of facial ageing among Caucasian women in Australia versus those in the USA, the UK and Canada

Abstract

Background/Objectives

Australians are more exposed to higher solar UV radiation levels that accelerate signs of facial ageing than individuals who live in temperate northern countries. The severity and course of self-reported facial ageing among fair-skinned Australian women were compared with those living in Canada, the UK and the USA.

Methods

Women voluntarily recruited into a proprietary opt-in survey panel completed an internet-based questionnaire about their facial ageing. Participants aged 18–75 years compared their features against photonumeric rating scales depicting degrees of severity for forehead, crow's feet and glabellar lines, tear troughs, midface volume loss, nasolabial folds, oral commissures and perioral lines. Data from Caucasian and Asian women with Fitzpatrick skin types I–III were analysed by linear regression for the impact of country (Australia versus Canada, the UK and the USA) on ageing severity for each feature, after controlling for age and race.

Results

Among 1472 women, Australians reported higher rates of change and significantly more severe facial lines (P ≤ 0.040) and volume-related features like tear troughs and nasolabial folds (P ≤ 0.03) than women from the other countries. More Australians also reported moderate to severe ageing for all features one to two decades earlier than US women.

Conclusions

Australian women reported more severe signs of facial ageing sooner than other women and volume-related changes up to 20 years earlier than those in the USA, which may suggest that environmental factors also impact volume-related ageing. These findings have implications for managing their facial aesthetic concerns.

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Ginkgo biloba L. attenuates spontaneous recurrent seizures and associated neurological conditions in lithium-pilocarpine rat model of temporal lobe epilepsy through inhibition of mammalian target of rapamycin pathway hyperactivation

Publication date: 23 May 2017
Source:Journal of Ethnopharmacology, Volume 204
Author(s): Arindam Ghosh Mazumder, Pallavi Sharma, Vikram Patial, Damanpreet Singh
Ethnopharmacological relevanceGinkgo biloba L. (Ginkgoaceae) has been widely used in traditional medicine for variety of neurological conditions particularly behavioral and memory impairments.Aim of the studyThe present study was envisaged to explore the effect of a standardized fraction of Ginkgo biloba leaves (GBbf) in rat model of lithium-pilocarpine induced spontaneous recurrent seizures, and associated behavioral impairments and cognitive deficit.Materials and methodsRats showing appearance of spontaneous recurrent seizures following lithium pilocarpine (LiPc)-induced status epilepticus (SE) were treated with different doses of GBbf or vehicle for subsequent 4 weeks. The severity of seizures and aggression in rats were scored following treatment with GBbf. Further, open field, forced swim, novel object recognition and Morris water maze tests were conducted. Histopathological, protein levels and gene expression studies were performed in the isolated brains.ResultsTreatment with GBbf reduced seizure severity score and aggression in epileptic animals. Improved spatial cognitive functions and recognition memory, along with reduction in anxiety-like behavior were also observed in the treated animals. Histopathological examination by Nissl staining showed reduction in neuronal damage in the hippocampal pyramidal layer. The dentate gyrus and Cornu Ammonis 3 regions of the hippocampus showed reduction in mossy fiber sprouting. GBbf treatment attenuated ribosomal S6 and pS6 proteins, and hippocampal mTOR, Rps6 and Rps6kb1 mRNA levels.ConclusionsThe results of present study concluded that GBbf treatment suppressed lithium-pilocarpine induced spontaneous recurrent seizures severity and incidence with improved cognitive functions, reduced anxiety-like behavior and aggression. The effect was found to be due to inhibition of mTOR pathway hyperactivation linked with recurrent seizures.

Graphical abstract

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Calcium Rules.

Author: Hidalgo, Cecilia PhD

Page: 1379-1381

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Treat the Patient, Not the Angiogram.

Author: Grantham, J. Aaron MD

Page: 1382-1384

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Percutaneous Coronary Interventions for Chronic Total Occlusions: As the Technology Expands, Our Responsibilities Increase.

Author: Bass, Theodore A. MD

Page: 1385-1387

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Risk of Heart Failure With Preserved Ejection Fraction in Older Women After Contemporary Radiotherapy for Breast Cancer.

Author: Saiki, Hirofumi MD, PhD; Petersen, Ivy A. MD; Scott, Christopher G. MS; Bailey, Kent R. PhD; Dunlay, Shannon M. MD, MS; Finley, Randi R. CMD, RTT; Ruddy, Kathryn J. MD, MPH; Yan, Elizabeth MD; Redfield, Margaret M. MD

Page: 1388-1396

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Detailed Echocardiographic Phenotyping in Breast Cancer Patients: Associations With Ejection Fraction Decline, Recovery, and Heart Failure Symptoms Over 3 Years of Follow-Up.

Author: Narayan, Hari K. MD; Finkelman, Brian PhD; French, Benjamin PhD; Plappert, Theodore RCVS; Hyman, David BA; Smith, Amanda M. BA, MA; Margulies, Kenneth B. MD; Ky, Bonnie MD, MSCE

Page: 1397-1412

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Good News, Bad News, but Not Fake News.

Author: Plana, Juan Carlos MD; Barac, Ana MD, PhD

Page: 1413-1416

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Evaluation of Cell Therapy on Exercise Performance and Limb Perfusion in Peripheral Artery Disease: The CCTRN PACE Trial (Patients With Intermittent Claudication Injected With ALDH Bright Cells).

Author: Perin, Emerson C. MD, PhD; Murphy, Michael P. MD; March, Keith L. MD, PhD; Bolli, Roberto MD; Loughran, John MD; Yang, Phillip C. MD; Leeper, Nicholas J. MD; Dalman, Ronald L. MD; Alexander, Jason MD; Henry, Timothy D. MD; Traverse, Jay H. MD; Pepine, Carl J. MD; Anderson, R. David MD; Berceli, Scott MD, PhD; Willerson, James T. MD; Muthupillai, Raja PhD; Gahremanpour, Amir MD; Raveendran, Ganesh MD, MPH; Velasquez, Omaida MD; Hare, Joshua M. MD; Hernandez Schulman, Ivonne MD; Kasi, Vijaykumar S. MD, PhD; Hiatt, William R. MD; Ambale-Venkatesh, Bharath PhD; Lima, Joao A. MD; Taylor, Doris A. PhD; Resende, Micheline PhD; Gee, Adrian P. PhD; Durett, April G. MS; Bloom, Jeanette MBA; Richman, Sara; G'Sell, Patricia RN; Williams, Shari RN; Khan, Fouzia MBBS; Gyang Ross, Elsie MD, MS; Santoso, Michelle R. BS; Goldman, JoAnne RT; Leach, Dana DNP; Handberg, Eileen PhD; Cheong, Benjamin MD; Piece, Nichole RN; DiFede, Darcy RN; Bruhn-Ding, Barb RN; Caldwell, Emily RN; Bettencourt, Judy MPH; Lai, Dejian PhD; Piller, Linda MD, MPH; Simpson, Lara PhD; Cohen, Michelle MPH; Sayre, Shelly L. MPH; Vojvodic, Rachel W. MPH; Moye, Lem MD, PhD; Ebert, Ray F. PhD; Simari, Robert D. MD; Hirsch, Alan T. MD; For the Cardiovascular Cell Therapy Research Network (CCTRN)

Page: 1417-1428

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Every PACE Counts: Learning About Blood Cells and Blood Flow in Peripheral Artery Disease.

Author: Breton-Romero, Rosa PhD; Hamburg, Naomi M. MD, MS

Page: 1429-1431

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Predictors of Death in Contemporary Adult Patients With Eisenmenger Syndrome: A Multicenter Study.

Author: Kempny, Aleksander MD; Hjortshoj, Cristel Sorensen MD, PhD; Gu, Hong MD, PhD; Li, Wei MD, PhD; Opotowsky, Alexander R. MD; Landzberg, Michael J. MD; Jensen, Annette Schophuus PhD; Sondergaard, Lars MD, DMSc; Estensen, Mette-Elise MD, PhD; Thilen, Ulf MD, PhD; Budts, Werner MD; Mulder, Barbara J. MD, PhD; Blok, Ilja MD; Tomkiewicz-Pajak, Lidia MD, PhD; Szostek, Kamil MSc; D'Alto, Michele MD, PhD; Scognamiglio, Giancarlo MD; Prokselj, Katja MD; Diller, Gerhard-Paul MD, PhD, MSc; Dimopoulos, Konstantinos MD, PhD, MSc; Wort, Stephen J. MA, MBBS, PhD; Gatzoulis, Michael A. MD, PhD

Page: 1432-1440

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Improving Survival in Patients With Eisenmenger Syndrome: Are We Any Closer?.

Author: Lange, Richard A. MD, MBA; Brickner, M. Elizabeth MD

Page: 1441-1443

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Infarcted Myocardium-Primed Dendritic Cells Improve Remodeling and Cardiac Function After Myocardial Infarction by Modulating the Regulatory T Cell and Macrophage Polarization.

Author: Choo, Eun Ho MD; Lee, Jun-Ho MS; Park, Eun-Hye MS; Park, Hyo Eun MS; Jung, Nam-Chul PhD; Kim, Tae-Hoon MD, PhD; Koh, Yoon-Seok MD, PhD; Kim, Eunmin PhD; Seung, Ki-Bae MD, PhD; Park, Cheongsoo PhD; Hong, Kwan-Soo PhD; Kang, Kwonyoon PhD; Song, Jie-Young PhD; Seo, Han Geuk PhD; Lim, Dae-Seog PhD; Chang, Kiyuk MD, PhD

Page: 1444-1457

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Permanent Leadless Cardiac Pacemaker Therapy: A Comprehensive Review.

Author: Tjong, Fleur V.Y. MD; Reddy, Vivek Y. MD

Page: 1458-1470

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Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association.

Author: Siscovick, David S. MD, MPH, FAHA, Chair; Barringer, Thomas A. MD, FAHA; Fretts, Amanda M. PhD, MPH; Wu, Jason H.Y. PhD, MSc, FAHA; Lichtenstein, Alice H. DSc, FAHA; Costello, Rebecca B. PhD, FAHA; Kris-Etherton, Penny M. PhD, RD, FAHA; Jacobson, Terry A. MD, FAHA; Engler, Mary B. PhD, RN, MS, FAHA; Alger, Heather M. PhD; Appel, Lawrence J. MD, MPH, FAHA; Mozaffarian, Dariush MD, DrPH, FAHA; On behalf of the American Heart Association Nutrition Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Epidemiology and Prevention; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology

Page: e867-e884

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Daily Total Physical Activity and Incident Cardiovascular Disease in Japanese Men and Women: Japan Public Health Center-Based Prospective Study.

Author: Kubota, Yasuhiko MD; Iso, Hiroyasu MD, PhD, MPH; Yamagishi, Kazumasa MD, PhD; Sawada, Norie MD, PhD; Tsugane, Shoichiro MD, PhD; for the JPHC Study Group (Japan Public Health Center)

Page: 1471-1473

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Letter by Lozano et al Regarding Article, "Prasugrel Versus Ticagrelor in Patients With Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention: Multicenter Randomized PRAGUE-18 Study".

Author: Lozano, Inigo MD, PhD; Rondan, Juan MD, PhD; Vegas, Jose M. MD

Page: e885-e886

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Response by Motovska et al to Letter Regarding Article, "Prasugrel Versus Ticagrelor in Patients With Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention: Multicenter Randomized PRAGUE-18 Study".

Author: Motovska, Zuzana MD, PhD; Hlinomaz, Ota MD, CSc; Kala, Petr MD, PhD; On behalf of the PRAGUE-18 Investigators

Page: e887-e888

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Letter by Brown and Ezekowitz Regarding Article, "Development and Evolution of a Hierarchical Clinical Composite End Point for the Evaluation of Drugs and Devices for Acute and Chronic Heart Failure: A 20-Year Perspective".

Author: Brown, Paul M. MSc; Ezekowitz, Justin A. MBBCh, MSc

Page: e889-e891

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Response by Packer to Letter Regarding Article, "Development and Evolution of a Hierarchical Clinical Composite End Point for the Evaluation of Drugs and Devices for Acute and Chronic Heart Failure: A 20-Year Perspective".

Author: Packer, Milton MD

Page: e892-e893

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Growth rates dependence of macro/microstructures and mechanical properties of Ti-47Al-2Nb-2Cr-0.2Er alloy directionally solidified by cold crucible

Publication date: 5 July 2017
Source:Materials & Design, Volume 125
Author(s): Qiang Wang, Hongsheng Ding, Hailong Zhang, Shiqiu Liu, Ruirun Chen, Jingjie Guo, Hengzhi Fu
IntermetallicsTi-47Al-2Nb-2Cr-0.2Er alloys are prepared at different growth rates ranging from 0.6mm/min to 1.2mm/min via cold crucible directional solidification with the power of 50kW. The macro/microstructure evolutions and mechanical properties of the directionally solidified ingots are studied in details. The angles between the columnar grains and the growth direction increase gradually from the center to the edge of the ingot. The lamellae orientations show no distinct variations under the growth rates of 0.6–1.0mm/min, while the lamellae orientation deviates significantly from the growth direction at the growth rate of 1.2mm/min. The interlamellar spacing is inverse proportional to the growth rate. The alloy with finer interlamellar spacing shows higher nanoindentation hardness. The corresponding relationship between nanoindentation hardness (HN) and interlamellar spacing (λ) can be fitted by HN=36.3λ^−0.254. Hindrance of the semi-coherent interface to dislocation movement results in higher tensile strength of the alloy and the larger tensile elongation can be attributed to the improvement of the deformation uniformity.

Graphical abstract

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Shape evolution of 3D flower-like gold microstructures from gold nanosheets via oriented attachment

Publication date: 5 July 2017
Source:Materials & Design, Volume 125
Author(s): Supeera Nootchanat, Chutiparn Lertvachirapaiboon, Vittaya Amornkitbamrung, Pikaned Uppachai, Sanong Ekgasit, Kanet Wongravee
Herein, we present a shape evolution of 3D flower-like gold microstructures (3D-FLGMSs) from gold nanosheets induced by H2O2 with the presence of starch. A systematic investigation of the influence of the parameters on the size, morphology and structural evolution of 3D-FLGMSs was presented. Under the starch-stabilized environment, H2O2 plays a key role on the formation of 3D-FLGMSs as it promotes a rapid generation of small nanosheets with starch-bound {111} facet at the very early stage. At a high concentration of H2O2, the nanosheets undergo oriented attachment and transform into a large primary gold nanosheets with imperfect facet-binding. The oriented attachment (OA) and subsequent epitaxial growth of nanopetals from the imperfects turns the primary nanosheets into 3D-FLGMSs with lateral size as large as 30μm within 120min. Without starch, quasi-microspheres of gold with diameters of 5–7μm are the sole product. In addition, the 3D-FLGMSs can be employed as SERS substrates which allow the detection limit of Rhodamine 6G (R6G) at the concentration as low as 0.1μM. The developed green synthetic method utilizes non-toxic reducing and stabilizing agents while limiting the discharge of harmful chemical wastes.

Graphical abstract

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Exploring parental behavior and child interactive engagement: A study on children with a significant cognitive and motor developmental delay

Publication date: May 2017
Source:Research in Developmental Disabilities, Volume 64
Author(s): Ines Van keer, Stephy Colla, Karla Van Leeuwen, Carla Vlaskamp, Eva Ceulemans, Karel Hoppenbrouwers, Annemie Desoete, Bea Maes
Background and aimsParenting factors are one of the most striking gaps in the current scientific literature on the development of young children with significant cognitive and motor disabilities. We aim to explore the characteristics of, and the association between, parental behavior and children's interactive engagement within this target group.Methods and proceduresTwenty-five parent-child dyads (with children aged 6–59 months) were video-taped during a 15-min unstructured play situation. Parents were also asked to complete the Parental Behavior Scale for toddlers. The video-taped observations were scored using the Child and Maternal Behavior Rating Scales.Outcomes and resultsLow levels of parental discipline and child initiation were found. Parental responsivity was positively related to child attention and initiation.Conclusions and implicationsCompared to children with no or other levels of disabilities, this target group exhibits large differences in frequency levels and, to a lesser extent, the concrete operationalization of parenting domains. Further, this study confirms the importance of sensitive responsivity as the primary variable in parenting research.



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A new species of Scopulariopsis and its synergistic effect on pathogenicity of Verticillium dahliae on cotton plants

Publication date: Available online 10 April 2017
Source:Microbiological Research
Author(s): Xiao-Lin Li, Mohammad Reza Ojaghian, Jing-Ze Zhang, Shui-Jin Zhu
A new species, Scopulariopsis gossypii, was found to be present in the vascular bundles of cotton plants (Gossypium hirsutum) infected by Verticillium dahliae which is an economically important pathogen in Hangzhou, China. The fungus was only present in the diseased plants, but it never became isolated from the healthy plants. Scanning electron microscopy showed that the fungus was present in parenchyma cells enclosing vessels in dark brown vascular tissues of stems, and produced asexual conidia within the tissues. Phylogenetic analysis of combined nuclear ribosomal D1/D2 region of the 28S rDNA as well as translation elongation factor 1-alpha (TEF1) and beta-tubulin (TUB) gene showed that S. gossypii represents an undescribed species of Scopulariopsis, Microascaceae. In this study, characteristics of sexual and asexual stages of the fungus were described, illustrated and compared with similar taxa. In addition, the molecular and morphological analyses indicated that S. gossypii was a distinct species of Scopulariopsis. The pathogenicity tests proved by inoculation of wounded roots confirmed that S. gossypii was an opportunistic pathogen causing leaf interveinal chlorosis and vascular browning of cotton plants. However S. gossypii did not infect host with undamaged roots. Moreover, coinoculation with S. gossypii and V. dahliae significantly increased disease severity.



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Inhibition of heat shock protein 90 rescues glucocorticoid-induced bone loss through enhancing bone formation

Publication date: Available online 10 April 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Haixiao Chen, Ji Xing, Xinhua Hu, Lihua Chen, Haiyan Lv, Chengyun Xu, Dun Hong, Ximei Wu
Endogenous glucocorticoids (GCs) support normal bone development and bone mass maintenance, whereas long-term exposure to pharmacological dosages of GCs uncouples bone formation and resorption, resulting in GC-induced osteoporosis (GIOP). Heat shock protein 90 (HSP90) chaperoning glucocorticoid receptor (GR) signaling prompts us to speculate that HSP90 plays critical roles in GC-mediated bone formation and GIOP. In the present study, inhibition of HSP90 activity by 17-Demethoxy-17-allyaminogeldanmycin (17-AAG) or knockdown of HSP90 expression by siRNAs attenuated dexamethasone(Dex)-induced GR nuclear accumulation and transcriptional output of GR signaling, whereas overexpression of HSP90α or HSP90β enhanced GR transactivity in C3H10T1/2 cells. Though 17-AAG itself enhanced osteoblastic differentiation, it restored the Dex(10⁻⁸M)-induced and Dex(10⁻⁶M)-negated osteoblastic differentiation in C3H10T1/2 cells and primary calvarial osteoblasts. Moreover, systemic administration of 17-AAG to mice induced not only osteoclastogenesis but also osteoblastogenesis, whereas bone formation possibly exceeded bone resorption, eventually leading to the increased bone masses. Likewise, systemic administration of 17-AAG to mice restored GC-negated osteoblastogenesis and enhanced GC-induced osteoclastogenesis, similarly, 17-AAG-induced bone formation possibly exceeded both 17-AAG- and GC-induced bone resorption, eventually resulting in rescue of GIOP. Together, the present study has revealed that inhibition of HSP90 restores GIOP through enhancing bone formation, and our findings may help to shed light on the pathogenesis of GIOP and provide targets for the therapeutic intervention of the disease.



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NEUROACTIVE STEROID LEVELS AND PSYCHIATRIC AND ANDROLOGICAL FEATURES IN POST-FINASTERIDE PATIENTS.

Publication date: Available online 10 April 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Roberto Cosimo Melcangi, Daniele Santi, Roberto Spezzano, Maria Grimoldi, Tommaso Tabacchi, Maria Letizia Fusco, Silvia Diviccaro, Silvia Giatti, Giuseppe Carrà, Donatella Caruso, Manuela Simoni, Guido Cavaletti
Recent reports show that, in patients treated with finasteride for male pattern hair loss, persistent side effects including sexual side effects, depression, anxiety and cognitive complaints may occur. We here explored the psychiatric and andrological features of patients affected by post-finasteride syndrome (PFS) and verified whether the cerebrospinal fluid (CSF) and plasma levels of neuroactive steroids (i.e., important regulators of nervous function) are modified. We found that eight out of sixteen PFS male patients considered suffered from a DSM-IV major depressive disorder (MDD). In addition, all PFS patients showed erectile dysfunction (ED); in particular, ten patients showed a severe and six a mild-moderate ED. We also reported abnormal somatosensory evoked potentials of the pudendal nerve in PFS patients with severe ED, the first objective evidence of a neuropathy involving peripheral neurogenic control of erection. Testicular volume by ultrasonography was normal in PFS patients. Data obtained on neuroactive steroid levels also indicate interesting features. Indeed, decreased levels of pregnenolone, progesterone and its metabolite (i.e., dihydroprogesterone), dihydrotestosterone and 17beta-estradiol and increased levels of dehydroepiandrosterone, testosterone and 5alpha-androstane-3alpha,17beta-diol were observed in CSF of PFS patients. Neuroactive steroid levels were also altered in plasma of PFS patients, however these changes did not reflect exactly what occurs in CSF. Finally, finasteride did not only affect, as expected, the levels of 5alpha-reduced metabolites of progesterone and testosterone, but also the further metabolites and precursors suggesting that this drug has broad consequence on neuroactive steroid levels of PFS patients.



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The activity of selective sigma-1 receptor ligands in seizure models in vivo

Publication date: 15 June 2017
Source:Behavioural Brain Research SreeTestContent1, Volume 328
Author(s): Edijs Vavers, Baiba Svalbe, Lasma Lauberte, Ilmars Stonans, Ilga Misane, Maija Dambrova, Liga Zvejniece
Sigma-1 receptor (Sig1R) is a ligand-regulated protein which, since its discovery, has been widely studied as a novel target to treat neurological disorders, including seizures. However, the roles and mechanisms of Sig1R in the regulation of seizures are not fully understood. The aim of the present study was to test and compare effects of often used selective Sig1R ligands in models of experimentally induced seizures. The anti-seizure activities and interactions of selective Sig1R agonist PRE-084, selective Sig1R antagonist NE-100 and novel positive allosteric Sig1R modulator E1R were evaluated in pentylenetetrazol (PTZ) and (+)-bicuculline (BIC)-induced seizure models in mice.Sig1R antagonist NE-100 at a dose of 25mg/kg demonstrated pro-convulsive activity on PTZ-induced seizures. Agonist PRE-084 did not change the thresholds of chemoconvulsant-induced seizures. Positive allosteric modulator E1R at a dose of 50mg/kg showed anti-convulsive effects on PTZ- and BIC-induced clonic and tonic seizures. The anti-seizure activity of E1R was blocked by NE-100. Surprisingly, NE-100 at a dose of 50mg/kg induced convulsions, but E1R significantly alleviated the convulsive behaviour induced by NE-100.In conclusion, the selective Sig1R antagonist NE-100 induced seizures that could be partially attenuated by positive allosteric Sig1R modulator. Our results confirm that Sig1R could be a novel molecular target for new anti-convulsive drugs.



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Dissociable effects of systemic and orbitofrontal administration of adrenoceptor antagonists on yohimbine-induced motor impulsivity

Publication date: 15 June 2017
Source:Behavioural Brain Research SreeTestContent1, Volume 328
Author(s): Wendy K. Adams, Michael M. Barrus, Fiona D. Zeeb, Paul J. Cocker, James Benoit, Catharine A. Winstanley
The α2-adrenoceptor antagonist, yohimbine, is commonly used as a pharmacological stressor. Its behavioural effects are typically attributed to elevated noradrenaline release via blockade of central, inhibitory autoreceptors. We have previously reported that yohimbine increases motor impulsivity in rats on the five-choice serial reaction time task (5CSRTT), a cognitive behavioural assessment which measures motor impulsivity and visuospatial attention. Furthermore, this effect depended on cyclic adenomonophosphate (cAMP) signalling via cAMP response element binding (CREB) protein in the orbitofrontal cortex (OFC). However, the role of specific adrenoceptors in this effect is not well-characterised. We therefore investigated whether the pro-impulsive effects of systemic yohimbine could be reproduced by direct administration into the OFC, or attenuated by intra-OFC or systemic administration of prazosin and propranolol—antagonists at the α1- and β-adrenoceptor, respectively. Male Long-Evans rats were trained on the 5CSRTT and implanted with guide cannulae aimed at the OFC. Systemically administered α1- or β-adrenoceptor antagonists attenuated yohimbine-induced increases in premature responding. In contrast, local infusion of yohimbine into the OFC reduced such impulsive responding, while blockade of α1- or β-adrenoceptors within the OFC had no effect on either basal or yohimbine-stimulated motor impulsivity. Direct administration of selective antagonists at the α1-, α2- or β-adrenoceptor into the OFC therefore produce clearly dissociable effects from systemic administration. Collectively, these data suggest that the pro-impulsivity effect of yohimbine can be modulated by adrenergic signalling in brain areas outside of the OFC, in addition to non-adrenergic signalling pathways within the OFC.



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Effects of social deprivation on social and depressive-like behaviors and the numbers of oxytocin expressing neurons in rats

Publication date: 15 June 2017
Source:Behavioural Brain Research SreeTestContent1, Volume 328
Author(s): Yaminah D. Gilles, Eva K. Polston
Social isolation is a known stressor that negatively impacts the well-being of social species. In rodents, social deprivation experienced either before or after weaning profoundly impacts adult behavioral and neuroendocrine profiles. This study compared the effects of post-natal and post-weaning social deprivation on behavioral profiles and hypothalamic oxytocin (OT) neurons. Male and female Sprague–Dawley rats were assigned to two post-natal groups, maternally separated (MS) or non-MS. MS pups were separated from their mothers for 4h daily during post-natal days 2–21 while non-MS litters remained undisturbed. Animals were then weaned and assigned to single or group housing conditions (SH/GH). Social behaviors were evaluated two weeks later and at 2–3 months of age, depressive-like behavioral profiles were assessed using the forced swim and sucrose preference tests. Animals were euthanized, and hypothalamic OT neurons were quantified. Post-weaning isolation significantly impacted behavioral profiles, with SH animals displaying more social behaviors than GH animals. SH animals also exhibited more immobility behavior in the forced swim test and a decreased sucrose preference. Effects of sex and MS were relatively limited. Correlation analyses revealed an inverse relationship between the display of antagonistic social behaviors and the numbers of OT cells in the anterior parvicellular division of the paraventricular nucleus (PVNap). There were no correlations between numbers of OT neurons and prosocial or depressive-like behaviors. Our results demonstrate a rapid and persistent disruption of behaviors in SH animals and suggest that some of these effects may be associated with numbers of OT neurons in the PVNap.



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Recognition memory-induced gene expression in the perirhinal cortex: A transcriptomic analysis

Publication date: 15 June 2017
Source:Behavioural Brain Research SreeTestContent1, Volume 328
Author(s): Hannah Scott, Mark F. Rogers, Helen L. Scott, Colin Campbell, Elizabeth C. Warburton, James B. Uney
We have used transcriptome analysis to identify genes and pathways that are activated during recognition memory formation in the perirhinal cortex. Rats were exposed to objects either repeatedly, so that the objects become familiar, or to novel objects in a bow-tie maze over six consecutive days. On the final day, one hour after the last exposure to the series of objects, RNA from the perirhinal cortex was sequenced to compare the transcriptome of naïve control rats and rats exposed to either novel or familiar stimuli. Differentially expressed genes were identified between group Novel and group Familiar rats. These included genes coding for transcription factors, GDNF receptors and extracellular matrix-related proteins. Moreover, differences in alternative splicing were also detected between the two groups, which suggests that this post-transcriptional mechanism may play a role in the consolidation of object recognition memory. To conclude, this study shows that RNA sequencing can be used as a tool to identify differences in gene expression in behaving animals undergoing the same task but encountering different exposures.



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Chronic social stress leads to altered sleep homeostasis in mice

Publication date: 1 June 2017
Source:Behavioural Brain Research SreeTestContent1, Volume 327
Author(s): Nadja Olini, Iru Rothfuchs, Damiano Azzinnari, Christopher R. Pryce, Salome Kurth, Reto Huber
Disturbed sleep and altered sleep homeostasis are core features of many psychiatric disorders such as depression. Chronic uncontrollable stress is considered an important factor in the development of depression, but little is known on how chronic stress affects sleep regulation and sleep homeostasis. We therefore examined the effects of chronic social stress (CSS) on sleep regulation in mice. Adult male C57BL/6 mice were implanted for electrocortical recordings (ECoG) and underwent either a 10-day CSS protocol or control handling (CON). Subsequently, ECoG was assessed across a 24-h post-stress baseline, followed by a 4-h sleep deprivation, and then a 20-h recovery period. After sleep deprivation, CSS mice showed a blunted increase in sleep pressure compared to CON mice, as measured using slow wave activity (SWA, electroencephalographic power between 1–4Hz) during non-rapid eye movement (NREM) sleep. Vigilance states did not differ between CSS and CON mice during post-stress baseline, sleep deprivation or recovery, with the exception of CSS mice exhibiting increased REM sleep during recovery sleep. Behavior during sleep deprivation was not affected by CSS. Our data provide evidence that CSS alters the homeostatic regulation of sleep SWA in mice. In contrast to acute social stress, which results in a faster SWA build-up, CSS decelerates the homeostatic build up. These findings are discussed in relation to the causal contribution of stress-induced sleep disturbance to depression.



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High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Bruna C. Favoretto, Adriana A.C. Casabuono, José A. Portes-Junior, Jacqueline F. Jacysyn, Alicia S. Couto, Eliana L. Faquim-Mauro
Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. Our data showed the presence of glycoconjugates with high mannose- and complex-type N-linked oligosaccharide chains and phosphorylcholine residues on PI. In addition, these N-linked glycoconjugates inhibited the DCs maturation induced by LPS. The binding and internalization of PI-Alexa were decreased on DCs previously incubated with mannan, anti-DC-SIGN and/or anti-MR antibodies. In agreement with this, the incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished the down-modulatory effect of PI on these cells. It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs.



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Resection of colorectal liver metastases after second-line chemotherapy: is it worthwhile? A LiverMetSurvey analysis of 6415 patients

Publication date: June 2017
Source:European Journal of Cancer, Volume 78
Author(s): René Adam, Bin Yi, Pasquale F. Innominato, Eduardo Barroso, Christophe Laurent, Felice Giuliante, Lorenzo Capussotti, Réal Lapointe, Jean-Marc Regimbeau, Santiago Lopez-Ben, Helena Isoniemi, Catherine Hubert, Jen-Kou Lin, Thomas Gruenberger, Dominique Elias, Oleg G. Skipenko, Alfredo Guglielmi
PurposePatient outcome after resection of colorectal liver metastases (CLM) following second-line preoperative chemotherapy (PCT) performed for insufficient response or toxicity of the first-line, is little known and has here been compared to the outcome following first-line.Patients and methodsFrom January 2005 to June 2013, 5624 and 791 consecutive patients of a prospective international cohort received 1 and 2 PCT lines before CLM resection (group 1 and 2, respectively). Survival and prognostic factors were analysed.ResultsAfter a mean follow-up of 30.1 months, there was no difference in survival from CLM diagnosis (median, 3-, and 5-year overall survival [OS]: 58.6 months, 76% and 49% in group 2 versus 58.9 months, 71% and 49% in group 1, respectively, P = 0.32). After hepatectomy, disease-free survival (DFS) was however shorter in group 2: 17.2 months, 27% and 15% versus 19.4 months, 32% and 23%, respectively (P = 0.001). Among the initially unresectable patients of group 1 and 2, no statistical difference in OS or DFS was observed. Independent predictors of worse OS in group 2 were positive primary lymph nodes, extrahepatic disease, tumour progression on second line, R2 resection and number of hepatectomies/year <50. Positive primary nodes, synchronous and bilateral metastases were predictors of shorter DFS. Initial unresectability did not impact OS or DFS in group 2.ConclusionCLM resection following second-line PCT, after oncosurgically favourable selection, could bring similar OS compared to what observed after first-line. For initially unresectable patients, OS or DFS is comparable between first- and second-line PCT. Surgery should not be denied after the failure of first-line chemotherapy.



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Adjunction of a MEK inhibitor to Vemurafenib in the treatment of metastatic melanoma results in a 60% reduction of acute kidney injury

Abstract

Introduction

A combined therapy MEK inhibitor, Cobimetinib (CB) and BRAF inhibitor, Vemurafenib (VMF), results in an improvement in progression-free survival among patients with BRAF V600-mutated metastatic melanoma. VMF skin adverse effects attributed to ERK paradoxical activation are decreased by the adjunction of CB. The aim of this study was to determine if this combination also improved the renal side effects of VMF.

Patients and methods

To investigate the incidence of acute kidney injury (AKI), we conducted a retrospective observational monocentric study in Lyon Sud University Hospital in France. We included 38 patients with metastatic BRAF-mutated melanomas treated by VMF and CB between March 2015 and June 2016. According to the NCI-CTCAE classification, AKI was defined as an increase in serum creatinine exceeding the baseline concentration by 1.5-fold. Serum creatinine was measured before treatment, then on a monthly basis during treatment, and 1 month after treatment discontinuation. Patients were divided into two main groups: AKI-positive (AKI+) and AKI-negative (AKI−), and further subdivided into three groups according to AKI severity (stage 1–5).

Results

Of 38 patients, 29 (76%) were AKI−, and all 9 AKI+ patients (24%) were diagnosed within the first trimester of treatment. Three-quarters of AKI (n = 7, 77%) had stage 1 AKI and the remaining 23% stage 2 AKI. Pre-treatment renal function was significantly better in AKI+ group: 105 vs. 80 ml/min/1.73m² AKI−, p = 0.009. Compared to previous results, the AKI incidence under the combined VMF–CB vs. VMF monotherapy was reduced by 60%.

Conclusion

We reported a reduced incidence and severity of nephrotoxicity of the association inhibitors of BRAF and MEK compared to a BRAF inhibitor monotherapy.

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Advanced Heart Failure in the ACHD Population: Finding the Fellows Role in a Growing Field

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JACC Instructions for Authors

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Early Invasive Versus Selective Strategy for Non-ST-Segment Elevation Acute Coronary Syndrome: The ICTUS Trial

AbstractBackground

The ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes) trial compared early invasive strategy with a selective invasive strategy in patients with non–ST-segment elevation acute coronary syndrome (NSTE-ACS) and an elevated cardiac troponin T. No long-term benefit of an early invasive strategy was found at 1 and 5 years.

Objectives

The aim of this study was to determine the 10-year clinical outcomes of an early invasive strategy versus a selective invasive strategy in patients with NSTE-ACS and an elevated cardiac troponin T.

Methods

The ICTUS trial was a multicenter, randomized controlled clinical trial that included 1,200 patients with NSTE-ACS and an elevated cardiac troponin T. Enrollment was from July 2001 to August 2003. We collected 10-year follow-up of death, myocardial infarction (MI), and revascularization through the Dutch population registry, patient phone calls, general practitioners, and hospital records. The primary outcome was the 10-year composite of death or spontaneous MI. Additional outcomes included the composite of death or MI, death, MI (spontaneous and procedure-related), and revascularization.

Results

Ten-year death or spontaneous MI was not statistically different between the 2 groups (33.8% vs. 29.0%, hazard ratio [HR]: 1.12; 95% confidence interval [CI]: 0.97 to 1.46; p = 0.11). Revascularization occurred in 82.6% of the early invasive group and 60.5% in the selective invasive group. There were no differences in additional outcomes, except for a higher rate of death or MI in the early invasive group compared with the rates for the selective invasive group (37.6% vs. 30.5%; HR: 1.30; 95% CI: 1.07 to 1.58; p = 0.009), driven by a higher rate of procedure-related MI in the early invasive group (6.5% vs. 2.4%; HR: 2.82; 95% CI: 1.53 to 5.20; p = 0.001).

Conclusions

In patients with NSTE-ACS and elevated cardiac troponin T levels, an early invasive strategy has no benefit over a selective invasive strategy in reducing the 10-year composite outcome of death or spontaneous MI, and a selective invasive strategy may be a viable option in selected patients.

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Reply: Baseline or Post-Procedural High-Sensitivity Troponin? Probably Both

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Non-ST-Segment Elevation Acute Coronary Syndromes: Lessons Learned Over the Last Decade

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Is Atrial Fibrillation a Preventable Disease?

Abstract

Atrial fibrillation (AF) is an increasing burden worldwide. However, AF prevention has not been emphasized enough in clinical practice or guidelines. In this paper, the authors review the associations of modifiable lifestyle factors, including alcohol abuse, smoking, physical inactivity, and unhealthy psychological stress, with the risk for AF development. The authors also review the associations of cardiovascular risk factors that can be better managed, including obesity and overweight, high blood pressure, diabetes, dyslipidemia, obstructive sleep apnea, and other cardiovascular diseases, with the risk for AF. The conclusion is that a high proportion of AF can be prevented by combining strategies, focusing on the high-risk population for better risk factor management, and emphasizing healthy lifestyle choices in the whole population.

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Burden of Readmissions Among Patients With Critical Limb Ischemia

AbstractBackground

Readmissions constitute a major health care burden among critical limb ischemia (CLI) patients.

Objectives

This study aimed to determine the incidence of readmission and factors affecting readmission in CLI patients.

Methods

All adult hospitalizations with a diagnosis code for CLI were included from State Inpatient Databases from Florida (2009 to 2013), New York (2010 to 2013), and California (2009 to 2011). Data were merged with the directory available from the American Hospital Association to obtain detailed information on hospital-related characteristics. Geographic and routing analysis was performed to evaluate the effect of travel time to the hospital on readmission rate.

Results

Overall, 695,782 admissions from 212,241 patients were analyzed. Of these, 284,189 were admissions with a principal diagnosis of CLI (primary CLI admissions). All-cause readmission rates at 30 days and 6 months were 27.1% and 56.6%, respectively. The majority of these were unplanned readmissions. Unplanned readmission rates at 30 days and 6 months were 23.6% and 47.7%, respectively. The major predictors of 6-month unplanned readmissions included age, female sex, black/Hispanic race, prior amputation, Charlson comorbidity index, and need for home health care or rehabilitation facility upon discharge. Patients covered by private insurance were least likely to have a readmission compared with Medicaid/no insurance and Medicare populations. Travel time to the hospital was inversely associated with 6-month unplanned readmission rates. There was a significant interaction between travel time and major amputation as well as travel time and revascularization strategy; however, the inverse association between travel time and unplanned readmission rate was evident in all subgroups. Furthermore, length of stay during index hospitalization was directly associated with the likelihood of 6-month unplanned readmission (odds ratio for log-transformed length of stay: 2.39 [99% confidence interval: 2.31 to 2.47]).

Conclusions

Readmission among patients with CLI is high, the majority of them being unplanned readmissions. Several demographic, clinical, and socioeconomic factors play important roles in predicting readmissions.

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Prediction of Systemic Septic Embolism in Patients With Left-Sided Infective Endocarditis

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Readmissions for Critical Limb Ischemia: Hear No Evil?

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Reply: Cost Effectiveness of Nonstatin-to-Statin Therapy

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Risk Stratification for Patients in Cardiogenic Shock After Acute Myocardial Infarction

AbstractBackground

Mortality in cardiogenic shock (CS) remains high. Early risk stratification is crucial to make adequate treatment decisions.

Objectives

This study sought to develop an easy-to-use, readily available risk prediction score for short-term mortality in patients with CS, derived from the IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock) trial.

Methods

The score was developed using a stepwise multivariable regression analysis.

Results

Six variables emerged as independent predictors for 30-day mortality and were used as score parameters: age >73 years, prior stroke, glucose at admission >10.6 mmol/l (191 mg/dl), creatinine at admission >132.6 μmol/l (1.5 mg/dl), Thrombolysis In Myocardial Infarction flow grade <3 after percutaneous coronary intervention, and arterial blood lactate at admission >5 mmol/l. Either 1 or 2 points were attributed to each variable, leading to a score in 3 risk categories: low (0 to 2), intermediate (3 or 4), and high (5 to 9). The observed 30-day mortality rates were 23.8%, 49.2%, and 76.6%, respectively (p < 0.0001). Validation in the IABP-SHOCK II registry population showed good discrimination with an area under the curve of 0.79. External validation in the CardShock trial population (n = 137) showed short-term mortality rates of 28.0% (score 0 to 2), 42.9% (score 3 to 4), and 77.3% (score 5 to 9; p < 0.001) and an area under the curve of 0.73. Kaplan-Meier analysis revealed a stepwise increase in mortality between the different score categories (0 to 2 vs. 3 to 4: p = 0.04; 0 to 2 vs. 5 to 9: p = 0.008).

Conclusions

The IABP-SHOCK II risk score can be easily calculated in daily clinical practice and strongly correlated with mortality in patients with infarct-related CS. It may help stratify patient risk for short-term mortality and might, thus, facilitate clinical decision making. (Intraaortic Balloon Pump in Cardiogenic Shock II [IABP-SHOCK II]; NCT00491036)

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The Aging Cardiovascular System: Understanding It at the Cellular and Clinical Levels

Abstract

Cardiovascular disease (CVD) presents a great burden for elderly patients, their caregivers, and health systems. Structural and functional alterations of vessels accumulate throughout life, culminating in increased risk of developing CVD. The growing elderly population worldwide highlights the need to understand how aging promotes CVD in order to develop new strategies to confront this challenge. This review provides examples of some major unresolved clinical problems encountered in daily cardiovascular practice as we care for elderly patients. Next, the authors summarize the current understanding of the mechanisms implicated in cardiovascular aging, and the potential for targeting novel pathways implicated in endothelial dysfunction, mitochondrial oxidative stress, chromatin remodeling, and genomic instability. Lastly, the authors consider critical aspects of vascular repair, including autologous transplantation of bone marrow-derived stem cells in elderly patients.

http://ift.tt/2oYqEOv

Risk Prediction in AMI Shock: Goldilocks and the Search for "Just Right"

http://ift.tt/2oZQCOK

Manuscripts Based on Datasets Shared by Clinical Research Studies

http://ift.tt/2oYEZub

Left Ventricular Assist Device as a Bridge to Recovery for Patients With Advanced Heart Failure

AbstractBackground

Left ventricular assist devices (LVADs) have been used as an effective therapeutic option in patients with advanced heart failure, either as a bridge to transplantation, as destination therapy, or in some patients, as a bridge to recovery.

Objectives

This study evaluated whether patients undergoing an LVAD bridge-to-recovery protocol can achieve cardiac and physical functional capacities equivalent to those of healthy controls.

Methods

Fifty-eight male patients—18 implanted with a continuous-flow LVAD, 16 patients with LVAD explanted (recovered patients), and 24 heart transplant candidates (HTx)—and 97 healthy controls performed a maximal graded cardiopulmonary exercise test with continuous measurements of respiratory gas exchange and noninvasive (rebreathing) hemodynamic data. Cardiac function was represented by peak exercise cardiac power output (mean arterial blood pressure x cardiac output) and functional capacity by peak exercise O₂ consumption.

Results

All patients demonstrated a significant exertional effort as demonstrated with the mean peak exercise respiratory exchange ratio >1.10. Peak exercise cardiac power output was significantly higher in healthy controls and explanted LVAD patients compared with other patients (healthy 5.35 ± 0.95 W; explanted 3.45 ± 0.72 W; LVAD implanted 2.37 ± 0.68 W; and HTx 1.31 ± 0.31 W; p < 0.05), as was peak O₂ consumption (healthy 36.4 ± 10.3 ml/kg/min; explanted 29.8 ± 5.9 ml/kg/min; implanted 20.5 ± 4.3 ml/kg/min; and HTx 12.0 ± 2.2 ml/kg/min; p < 0.05). In the LVAD explanted group, 38% of the patients achieved peak cardiac power output and 69% achieved peak O₂ consumption within the ranges of healthy controls.

Conclusions

The authors have shown that a substantial number of patients who recovered sufficiently to allow explantation of their LVAD can even achieve cardiac and physical functional capacities nearly equivalent to those of healthy controls.

http://ift.tt/2oYDPyD

Prethrombotic State in Young Very Low-Risk Patients With Atrial Fibrillation

http://ift.tt/2oYqFSz

On the Road to Full Cardiac Recovery With Mechanical Unloading: Are We There Yet?

http://ift.tt/2oZEZag

Baseline or Post-Procedural High-Sensitivity Troponin?: Probably Both

http://ift.tt/2oYGqJc

Estimating Left Ventricular Filling Pressure by Echocardiography

AbstractBackground

The diagnosis of heart failure may be challenging because symptoms are rather nonspecific. Elevated left ventricular (LV) filling pressure may be used to confirm the diagnosis, but cardiac catheterization is often not practical. Echocardiographic indexes are therefore used as markers of filling pressure.

Objectives

This study investigated the feasibility and accuracy of comprehensive echocardiography in identifying patients with elevated LV filling pressure.

Methods

We conducted a multicenter study of 450 patients with a wide spectrum of cardiac diseases referred for cardiac catheterization. Left atrial volume index, in combination with flow velocities and tissue Doppler velocities, was used to estimate LV filling pressure. Invasively measured pressure was used as the gold standard.

Results

Mean left ventricular ejection fraction (LVEF) was 47%, with 209 patients having an LVEF <50%. Invasive measurements showed elevated LV filling pressure in 58% of patients. Clinical assessment had an accuracy of 72% in identifying patients with elevated filling pressure, whereas echocardiography had an accuracy of 87% (p < 0.001 vs. clinical assessment). The combination of clinical and echocardiographic assessment was incremental, with a net reclassification improvement of 1.5 versus clinical assessment (p < 0.001).

Conclusions

Echocardiographic assessment of LV filling pressure is feasible and accurate. When combined with clinical data, it leads to a more accurate diagnosis, regardless of LVEF.

http://ift.tt/2oYyffX

Cost Effectiveness of Nonstatin-to-Statin Therapy

http://ift.tt/2oYyeZr

A Novel Strategy to Co-target Estrogen Receptor and Nuclear Factor κB Pathways with Hybrid Drugs for Breast Cancer Therapy

Abstract

Nearly 75% of breast tumors express estrogen receptor (ER), and will be treated with endocrine therapy, such as selective estrogen receptor modulator (SERM), tamoxifen, or aromatase inhibitors. Despite their proven success, as many as 40–50% of ER+ tumors fail to respond to endocrine therapy and eventually recur as aggressive, metastatic cancers. Therefore, preventing and/or overcoming endocrine resistance in ER+ tumors remains a major clinical challenge. Deregulation or activation of the nuclear factor κB (NFκB) pathway has been implicated in endocrine resistance and poor patient outcome in ER+ tumors. As a consequence, one option to improve on existing anti-cancer treatment regimens may be to introduce additional anti-NFκB activity to endocrine therapy drugs. Our approach was to design and test SERM-fumarate co-targeting hybrid drugs capable of simultaneously inhibiting both ER, via the SERM, raloxifene, and the NFκB pathway, via fumarate, in breast cancer cells. We find that the hybrid drugs display improved anti-NFκB pathway inhibition compared to either raloxifene or fumarate. Despite some loss in potency against the ER pathway, these hybrid drugs maintain anti-proliferative activity in ER+ breast cancer cells. Furthermore, these drugs prevent clonogenic growth and mammosphere formation of ER+ breast cancer cells. As a proof-of-principle, the simultaneous inhibition of ER and NFκB via a single bifunctional hybrid drug may represent a viable approach to improve the anti-inflammatory activity and prevent therapy resistance of ER-targeted anti-cancer drugs.

http://ift.tt/2ojQTh6

Nanoparticulate Tetrac Inhibits Growth and Vascularity of Glioblastoma Xenografts

Abstract

Thyroid hormone as L-thyroxine (T₄) stimulates proliferation of glioma cells in vitro and medical induction of hypothyroidism slows clinical growth of glioblastoma multiforme (GBM). The proliferative action of T₄ on glioma cells is initiated nongenomically at a cell surface receptor for thyroid hormone on the extracellular domain of integrin αvβ3. Tetraiodothyroacetic acid (tetrac) is a thyroid hormone derivative that blocks T₄ action at αvβ3 and has anticancer and anti-angiogenic activity. Tetrac has been covalently bonded via a linker to a nanoparticle (Nanotetrac, Nano-diamino-tetrac, NDAT) that increases the potency of tetrac and broadens the anticancer properties of the drug. In the present studies of human GBM xenografts in immunodeficient mice, NDAT administered daily for 10 days subcutaneously as 1 mg tetrac equivalent/kg reduced tumor xenograft weight at animal sacrifice by 50%, compared to untreated control lesions (p < 0.01). Histopathological analysis of tumors revealed a 95% loss of the vascularity of treated tumors compared to controls at 10 days (p < 0.001), without intratumoral hemorrhage. Up to 80% of tumor cells were necrotic in various microscopic fields (p < 0.001 vs. control tumors), an effect attributable to devascularization. There was substantial evidence of apoptosis in other fields (p < 0.001 vs. control tumors). Induction of apoptosis in cancer cells is a well-described quality of NDAT. In summary, systemic NDAT has been shown to be effective by multiple mechanisms in treatment of GBM xenografts.

http://ift.tt/2nyuQV2

Japanese Immigrant with Abdominal Pain

Publication date: Available online 10 April 2017
Source:The Journal of Emergency Medicine
Author(s): Joshua McClain, Zachary D.W. Dezman




http://ift.tt/2oZdCx3

Diagnostic and Prognostic Significance of Computerized Cytologic Morphometry of the Thyroid Neoplasm

Condition:   Computerized Cytomorphometry
Intervention:   Other: computerized cytomorphometry
Sponsor:   National Taiwan University Hospital
Recruiting - verified April 2017

http://ift.tt/2oXTGOg

Studying Survivorship Care Plans in Head and Neck Cancer

Condition:   Head and Neck Cancer
Intervention:   Other: educational materials
Sponsor:   Duke University
Not yet recruiting - verified March 2017

http://ift.tt/2ojX9ne

The Microbiome in Subfertility and Assisted Reproductive Technologies (ART)

Conditions:   Infertility;   Subfertility
Intervention:   Other: 3 Sampling points
Sponsor:   Universitair Ziekenhuis Brussel
Recruiting - verified April 2017

http://ift.tt/2oYkiym

Cephalometric and dental arch changes to Haas-type rapid maxillary expander anchored to deciduous vs permanent molars: a multicenter, randomized controlled trial

Abstract

Objective

To assess radiographic changes and dental arch changes with Haas-type rapid maxillary expansion (H-RME) anchored to deciduous versus permanent molars in children with unilateral posterior crossbite.

Methods

In all, 70 patients with unilateral posterior crossbite were randomly allocated to group GrE (H-RME on second deciduous molars) or Gr6 (H-RME on first permanent molars) and compared between T0 (before treatment) and T1 (at the RME removal; i.e., 10 months after the end of the activation of the screw). At T0 and T1, cephalometric head films were digitally traced, dental casts were scanned, and rotations of the upper first molars, of the upper central, and of the upper lateral incisors on the models were measured.

Results

Between T0 and T1, the cephalometric analysis showed a significant decrease of the angulation of the upper central incisors to the SN line and to the palatal plane in GrE together with a significant increase of the lower incisors to the mandibular plane (IMPA). The digital dental cast analysis showed that the central and lateral incisors mesiorotated significantly more in GrE than in Gr6. Patients in GrE also showed a statistically significant distorotation of the upper first permanent molars after RME.

Conclusions

GrE showed a significant and spontaneous retraction and alignment of the upper central and lateral incisors compared to Gr6. This is probably due to a more pronounced expansion in the anterior area and more accentuated pressure of the upper lip in GrE. IMPA increased significantly in GrE vs Gr6. GrE also showed a more significant distorotation of the upper first permanent molars compared to Gr6. This is probably due to the design of the H-RME in GrE, where the screw is more anteriorly positioned and the bands are absent on the upper first permanent molars which are, therefore, free to adapt to the best occlusal situation.

Trial registration

ClinicalTrials.gov Identifier NCT02798822.

http://ift.tt/2ojtqN1

Treatment effects of various prescriptions and techniques for fixed orthodontic appliances

Abstract

Purpose

Although several prescriptions and techniques exist for comprehensive fixed appliance treatment, their treatment effects have not yet been adequately assessed in an evidence-based manner. The aim of this systematic review was to assess the therapeutic and adverse effects of various prescriptions or techniques for orthodontic appliances from randomized clinical trials on human patients.

Methods

Eight databases were searched up to July 2016 for randomized trials assessing any orthodontic prescriptions or techniques in human patients. After elimination of duplicate studies, data extraction, and risk of bias assessment according to the Cochrane guidelines, random effects meta-analyses with mean differences (MD) and their 95% confidence intervals (CIs) were performed.

Results

Compared to Roth preadjusted appliances, both Begg and modified Begg appliances were associated with statistically significantly worse occlusal outcome assessed with Peer Assessment Review (PAR) scores (1 trial, MD 3.1 points, 95% CI 1.9–4.3 points and 1 trial, MD 2.4 points, 95% CI 1.2–3.6 points, respectively) with low quality of evidence, due to bias and imprecision. Compared to a partially programmed fixed orthodontic appliance, a fully programmed appliance was associated with a statistically significant, but clinically irrelevant increase in treatment duration (1 trial, MD 2.4 months, 95% CI 0.6–4.2 months), supported by high quality of evidence. However, caution is needed in the interpretation of these results as only a limited number of small trials with methodological issues were available.

Conclusions

Based on existing trials, there is limited evidence to support any robust clinical recommendation regarding the prescriptions or techniques for fixed orthodontic appliances.

Registration: PROSPERO (CRD42016042727).

Funding: None.

http://ift.tt/2oZ5Z9W

Cephalometric and dental arch changes to Haas-type rapid maxillary expander anchored to deciduous vs permanent molars: a multicenter, randomized controlled trial

Abstract

Objective

To assess radiographic changes and dental arch changes with Haas-type rapid maxillary expansion (H-RME) anchored to deciduous versus permanent molars in children with unilateral posterior crossbite.

Methods

In all, 70 patients with unilateral posterior crossbite were randomly allocated to group GrE (H-RME on second deciduous molars) or Gr6 (H-RME on first permanent molars) and compared between T0 (before treatment) and T1 (at the RME removal; i.e., 10 months after the end of the activation of the screw). At T0 and T1, cephalometric head films were digitally traced, dental casts were scanned, and rotations of the upper first molars, of the upper central, and of the upper lateral incisors on the models were measured.

Results

Between T0 and T1, the cephalometric analysis showed a significant decrease of the angulation of the upper central incisors to the SN line and to the palatal plane in GrE together with a significant increase of the lower incisors to the mandibular plane (IMPA). The digital dental cast analysis showed that the central and lateral incisors mesiorotated significantly more in GrE than in Gr6. Patients in GrE also showed a statistically significant distorotation of the upper first permanent molars after RME.

Conclusions

GrE showed a significant and spontaneous retraction and alignment of the upper central and lateral incisors compared to Gr6. This is probably due to a more pronounced expansion in the anterior area and more accentuated pressure of the upper lip in GrE. IMPA increased significantly in GrE vs Gr6. GrE also showed a more significant distorotation of the upper first permanent molars compared to Gr6. This is probably due to the design of the H-RME in GrE, where the screw is more anteriorly positioned and the bands are absent on the upper first permanent molars which are, therefore, free to adapt to the best occlusal situation.

Trial registration

ClinicalTrials.gov Identifier NCT02798822.

http://ift.tt/2ojtqN1

Treatment effects of various prescriptions and techniques for fixed orthodontic appliances

Abstract

Purpose

Although several prescriptions and techniques exist for comprehensive fixed appliance treatment, their treatment effects have not yet been adequately assessed in an evidence-based manner. The aim of this systematic review was to assess the therapeutic and adverse effects of various prescriptions or techniques for orthodontic appliances from randomized clinical trials on human patients.

Methods

Eight databases were searched up to July 2016 for randomized trials assessing any orthodontic prescriptions or techniques in human patients. After elimination of duplicate studies, data extraction, and risk of bias assessment according to the Cochrane guidelines, random effects meta-analyses with mean differences (MD) and their 95% confidence intervals (CIs) were performed.

Results

Compared to Roth preadjusted appliances, both Begg and modified Begg appliances were associated with statistically significantly worse occlusal outcome assessed with Peer Assessment Review (PAR) scores (1 trial, MD 3.1 points, 95% CI 1.9–4.3 points and 1 trial, MD 2.4 points, 95% CI 1.2–3.6 points, respectively) with low quality of evidence, due to bias and imprecision. Compared to a partially programmed fixed orthodontic appliance, a fully programmed appliance was associated with a statistically significant, but clinically irrelevant increase in treatment duration (1 trial, MD 2.4 months, 95% CI 0.6–4.2 months), supported by high quality of evidence. However, caution is needed in the interpretation of these results as only a limited number of small trials with methodological issues were available.

Conclusions

Based on existing trials, there is limited evidence to support any robust clinical recommendation regarding the prescriptions or techniques for fixed orthodontic appliances.

Registration: PROSPERO (CRD42016042727).

Funding: None.

http://ift.tt/2oZ5Z9W

Micropollutants and chemical residues in organic and conventional meat

Publication date: 1 October 2017
Source:Food Chemistry, Volume 232
Author(s): Gaud Dervilly-Pinel, Thierry Guérin, Brice Minvielle, Angélique Travel, Jérôme Normand, Marie Bourin, Eric Royer, Estelle Dubreil, Sophie Mompelat, Frédéric Hommet, Marina Nicolas, Vincent Hort, Chanthadary Inthavong, Mailie Saint-Hilaire, Claude Chafey, Julien Parinet, Ronan Cariou, Philippe Marchand, Bruno Le Bizec, Eric Verdon, Erwan Engel
The chemical contamination levels of both conventional and organic meats were assessed. The objective was to provide occurrence data in a context of chronic exposure. Environmental contaminants (17 polychlorinated dibenzodioxins/dibenzofurans, 18 polychlorinated biphenyls (PCBs), 3 hexabromocyclododecane (HBCD) isomers, 6 mycotoxins, 6 inorganic compounds) together with chemical residues arising from production inputs (75 antimicrobials, 10 coccidiostats and 121 pesticides) have been selected as relevant compounds. A dedicated sampling strategy, representative of the French production allowed quantification of a large sample set (n=266) including both conventional (n=139) and organic (n=127) raw meat from three animal species (bovine, porcine, poultry). While contamination levels below regulatory limits were measured in all the samples, significant differences were observed between both species and types of farming. Several environmental contaminants (Dioxins, PCBs, HBCD, Zn, Cu, Cd, Pb, As) were measured at significantly higher levels in organic samples.

Graphical abstract

http://ift.tt/2oqVmig

Ancient settlement activities as important sources of nutrients (P, K, S, Zn and Cu) in Eastern Mediterranean ecosystems – The case of biblical Tel Burna, Israel

Publication date: September 2017
Source:CATENA, Volume 156
Author(s): Ladislav Smejda, Michal Hejcman, Jan Horak, Itzhaq Shai
Human settlement activities are connected with the accumulation of nutrients in archaeological soils. We address the question of whether the large-scale mapping of the elemental composition of the topsoil in contemporary rangeland can be used for the detection of ancient settlement activities.Using portable X-ray fluorescence (pXRF), we mapped the elemental composition of contemporary soils over an area of 67ha in and around the Bronze and Iron Age settlement of Tel Burna (identified as probably corresponding with biblical Libnah).Ancient settlement activities substantially increased concentrations of nutrients (P, K, S, Zn and Cu) in the contemporary topsoil owing to the deposition of biomass ashes and organic wastes. Increased concentrations of elements were detected 2500 years after the site was abandoned and we can therefore suppose that changes in the elemental composition of the soil caused by ancient settlement activities are irreversible on a timescale in which human societies operate. Ancient settlement activities increased concentrations of nutrients in contemporary soil to the same level as recent intensive fertiliser application on an adjacent arable field used for vegetable production. Concentrations of nutrients higher than those on the tell summit were recorded only in recent cattle resting areas with intensive deposition of cattle faeces. Changes in the elemental composition of the soil caused by ancient settlement activities consequently result in differential nutrient availability for contemporary vegetation, affecting ecosystem functions for thousands of years. Using pXRF, large-scale mapping of the elemental composition of the topsoil layer at archaeological sites can help to identify the extent and provide basic information on the character of past human activities in the affected landscape units.



http://ift.tt/2or8vId

Tumor-Infiltrating Lymphocytes and Overall Survival in Surgically Resected Stage II and III Non–Small Cell Lung Cancer

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): B. Sepesi, E. Parra Cuentes, J.R. Canales, C. Behrens, A. Correa, M. Antonoff, D.L. Gibbons, J. Heymach, W. Hofstetter, R. Mehran, D.C. Rice, J. Roth, A.A. Vaporciyan, G. Walsh, A. Weissferdt, N. Kalhor, C. Moran, S.G. Swisher, I. Wistuba




http://ift.tt/2nUWFlL

Defining Prognostic Biomarkers and Optimal Adjuvant Treatment for Gynecologic Cancer

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): Sushil Beriwal, Ann Klopp, Loren Mell




http://ift.tt/2oqs2J2

Table of Contents

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1





http://ift.tt/2oYbUyP

Clinical Development of Cancer Drugs in Combination With External Beam Radiation Therapy: US Food and Drug Administration Perspective

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): Amanda J. Walker, Hyun Kim, Haleh Saber, Paul G. Kluetz, Geoffrey Kim, Richard Pazdur




http://ift.tt/2ojxR91

Dry Eye Syndrome After Proton Therapy of Ocular Melanomas

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): Juliette Thariat, Celia Maschi, Sara Lanteri, Marie Laure Peyrichon, Stephanie Baillif, Joel Herault, Julia Salleron, Jean Pierre Caujolle
PurposeTo investigate whether proton therapy (PT) performs safely in superotemporal melanomas, in terms of risk of dry-eye syndrome (DES).Methods and MaterialsTumor location, DES grade, and dose to ocular structures were analyzed in patients undergoing PT (2005-2015) with 52 Gy (prescribed dose, not accounting for biologic effectiveness correction of 1.1). Prognostic factors of DES and severe DES (sDES, grades 2-3) were determined with Cox proportional hazard models. Visual acuity deterioration and enucleation rates were compared by sDES and tumor locations.ResultsMedian follow-up was 44 months (interquartile range, 18-60 months). Of 853 patients (mean age, 64 years), 30.5% had temporal and 11.4% superotemporal tumors. Five-year incidence of DES and sDES was 23.0% (95% confidence interval [CI] 19.0%-27.7%) and 10.9% (95% CI 8.2%-14.4%), respectively. Multivariable analysis showed a higher risk for sDES in superotemporal (hazard ratio [HR] 5.82, 95% CI 2.72-12.45) and temporal tumors (HR 2.63, 95% CI 1.28-5.42), age ≥70 years (HR 1.90, 95% CI 1.09-3.32), distance to optic disk ≥5 mm (HR 2.71, 95% CI 1.52-4.84), ≥35% of retina receiving 12 Gy (HR 2.98, 95% CI 1.54-5.77), and eyelid rim irradiation (HR 2.68, 95% CI 1.49-4.80). The same risk factors were found for DES. Visual acuity deteriorated more in patients with sDES (0.86 ± 1.10 vs 0.64 ± 0.98 logMAR, P=.034) but not between superotemporal/temporal and other locations (P=.890). Enucleation rates were independent of sDES (P=.707) and tumor locations (P=.729).ConclusionsSevere DES was more frequent in superotemporal/temporal melanomas. Incidence of vision deterioration and enucleation was no higher in patients with superotemporal melanoma than in patients with tumors in other locations. Tumor location should not contraindicate PT.



http://ift.tt/2ojBNqa

In Regard to Dr Vapiwala

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): Richard Jennelle, Eric L. Chang




http://ift.tt/2nV08km

Adjuvant Therapy in High-Risk Stage III Cutaneous Melanoma

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): Christopher A. Barker




http://ift.tt/2ojNe1a

Prospective Trial of Circulating Tumor Cells as a Biomarker for Early Detection of Recurrence in Patients with Locally Advanced Non–Small Cell Lung Cancer Treated with Chemoradiation Therapy

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): C. Chinniah, L. Aguarin, P. Cheng, C. DeCesaris, A. Cutillo, A.T. Berman, M. Frick, W.P. Levin, K.A. Cengel, S.M. Hahn, J.F. Dorsey, G.D. Kao, C.B. Simone




http://ift.tt/2oXXeje

Radiation Therapy Followed by Ipilimumab Is Appropriate

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): Jay S. Cooper




http://ift.tt/2oqxvzo

Issue Highlights

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1





http://ift.tt/2ojQPfx

Encourage Enrollment in Clinical Trials of Neoadjuvant or Adjuvant Systemic Therapy, and Consider Adjuvant Radiation Therapy to Prevent Morbid Recurrence

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): Christopher J. Anker




http://ift.tt/2ojIQis

Consider Adjuvant Intensity Modulated Radiation Therapy to the Lymph Node Basin, Especially If the Melanoma Is BRAF Wild Type

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): Matthew Foote




http://ift.tt/2oqrliP

Adjuvant Therapy in High-Risk Stage III Cutaneous Melanoma

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): Fabrice Kaufmann, Simone M. Goldinger




http://ift.tt/2ojQOZ1

In Regard to Shaverdian et al

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): E. Michael D. Scott




http://ift.tt/2nUVTVX

Adjuvant and Neoadjuvant Therapy in High-Risk Stage III Cutaneous Melanoma

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): Vernon K. Sondak, Nikhil I. Khushalani




http://ift.tt/2oqI99d

Heterogeneity and Variation in Resistance Mechanisms Among 223 Epidermal Growth Factor Receptor–Mutant Non–Small Cell Lung Cancer Patients With > 1 Post-Resistance Biopsy

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): Z. Piotrowska, K. Stirling, R. Heist, M. Campo, C. Rizzo, S.R. Digumarthy, M. Lanuti, F.J. Fintelmann, I. Lennes, A. Farago, J. Gainor, C.G. Azzoli, J. Temel, M. Mino-Kenudson, D. Dias-Santagata, R. Corcoran, A. Shaw, J.A. Engelman, A. Hata, L.V. Sequist




http://ift.tt/2oYemWi

The Ever-Evolving Role of the Academic Clinical Physicist

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): Eric E. Klein, Jonas Fontenot, Nesrin Dogan




http://ift.tt/2ojDEvd

Reirradiation of Thoracic Cancers with Intensity Modulated Proton Therapy

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): J.C. Ho, Q.N. Nguyen, H. Li, P.K. Allen, X. Zhang, X.R. Zhu, D.R. Gomez, S.H. Lin, M.T. Gillin, R.U. Komaki, Z. Liao, S.M. Hahn, J.Y. Chang




http://ift.tt/2nV5SKN

Racial Disparities in the Treatment and Outcome of Stage I Non–Small Cell Lung Cancer

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): S.M. Dalwadi, G. Lewis, E.B. Butler, B.S. Teh, A. Farach




http://ift.tt/2oYenJQ

Brain Metastasis Velocity: A Novel Prognostic Metric Predictive of Overall Survival and Freedom From Whole-Brain Radiation Therapy After Distant Brain Failure Following Upfront Radiosurgery Alone

Publication date: 1 May 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 98, Issue 1
Author(s): Michael Farris, Emory R. McTyre, Christina K. Cramer, Ryan Hughes, David M. Randolph, Diandra N. Ayala-Peacock, J. Daniel Bourland, Jimmy Ruiz, Kounosuke Watabe, Adrian W. Laxton, Stephen B. Tatter, Xiaobo Zhou, Michael D. Chan
PurposePrior statistical models attempted to identify risk factors for time to distant brain failure (DBF) or time to salvage whole-brain radiation therapy (WBRT) to predict the benefit of early WBRT versus stereotactic radiosurgery (SRS) alone. We introduce a novel clinical metric, brain metastasis velocity (BMV), for predicting clinical outcomes after initial DBF following upfront SRS alone.Methods and MaterialsBMV was defined as the cumulative number of new brain metastases that developed over time since first SRS in years. Patients were classified by BMV into low-, intermediate-, and high-risk groups, consisting of <4, 4 to 13, and >13 new metastases per year, respectively. Histology, number of metastases at the time of first SRS, and systemic disease status were assessed for effect on BMV.ResultsOf 737 patients treated at our institution with upfront SRS without WBRT, 286 had ≥1 DBF event. A lower BMV predicted for improved overall survival (OS) following initial DBF (log-rank P<.0001). Median OS for the low, intermediate, and high BMV groups was 12.4 months (95% confidence interval [CI], 10.4-16.9 months), 8.2 months (95% CI, 5.0-9.7 months), and 4.3 months (95% CI, 2.6-6.7 months), respectively. Multivariate analysis showed that BMV remained the dominant predictor of OS, with a hazard ratio of 2.75 for the high BMV group (95% CI, 1.94-3.89; P<.0001) and a hazard ratio of 1.65 for the intermediate BMV group (95% CI, 1.18-2.30; P<.004). A lower BMV was associated with decreased rates of salvage WBRT (P=.02) and neurologic death (P=.008). Factors predictive for a higher BMV included ≥2 initial brain metastases (P=.004) and melanoma histology (P=.008).ConclusionsBMV is a novel metric associated with OS, neurologic death, and need for salvage WBRT after initial DBF following upfront SRS alone.



http://ift.tt/2oqpL0o

Acyclovir for treatment of lichen planus

http://ift.tt/2oREcLL

Therapy with anti-interleukin-31 receptor A antibody for atopic dermatitis

http://ift.tt/2o0430g

Possible use of epigallocatechin-3-gallate (EGCG) as prevention of radio dermatitis in radiotherapy treated breast cancer patients

http://ift.tt/2oRG7Ab

Cost of Deep Brain Stimulation Infection Resulting in Explantation

Background: Deep brain stimulation (DBS) hardware infection is a serious complication, often resulting in multiple hardware salvage attempts, hospitalizations, and long-term antibiotic therapy. Objectives: We aimed to quantify the costs of DBS hardware-related infections in patients undergoing eventual device explantation. Methods: Of 362 patients who underwent 530 electrode placements (1 January 2010 to 30 December 2014), 16 (4.4%) had at least 2 hardware salvage procedures. Most (n = 15 [93.8%]) required complete explantation due to recurrent infection. Financial data (itemized hospital and physician costs) were available for 13 patients and these were analyzed along with the demographic data. Results: Each patient underwent 1-5 salvage procedures (mean 2.5 ± 1.4; median 2). The mean total cost for a patient undergoing the median number of revisions (n = 2), device explantation, and subsequent reimplantation after infection clearance was USD 75,505; just over half this cost (54.2% [USD 40,960]) was attributable to reimplantation, and nearly one-third (28.9% [USD 21,816]) was attributable to hardware salvage procedures. Operating-room costs were the highest cost category for hardware revision and explantation. Medical and surgical supplies accounted for the highest reimplantation cost. Conclusions: DBS infection incurs significant health care costs associated with hardware salvage attempts, explantation, and reimplantation. The highest cost categories are operating-room services and medical and surgical supplies.
Stereotact Funct Neurosurg 2017;95:117-124

http://ift.tt/2o0eOiS

Cancer Gene Therapy

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TABLE OF CONTENTS

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Volume 24, Issue 3 (March 2017)

In this issue
Editorial
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Editorial

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The challenges of solid tumor for designer CAR-T therapies: a 25-year perspective

Richard P Junghans

Cancer Gene Ther 2017 24: 89-99; 10.1038/cgt.2016.82

Full Text

Reviews

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Myeloid-derived suppressor cells and their role in pancreatic cancer

M Pergamo and G Miller

Cancer Gene Ther 2017 24: 100-105; advance online publication, December 2, 2016; 10.1038/cgt.2016.65

Abstract | Full Text

T-cell programming in pancreatic adenocarcinoma: a review

Y D Seo and V G Pillarisetty

Cancer Gene Ther 2017 24: 106-113; advance online publication, December 2, 2016; 10.1038/cgt.2016.66

Abstract | Full Text

Immunosuppression in liver tumors: opening the portal to effective immunotherapy

P Guha, J Reha and S C Katz

Cancer Gene Ther 2017 24: 114-120; advance online publication, December 2, 2016; 10.1038/cgt.2016.54

Abstract | Full Text

Chimeric antigen receptors for treatment of glioblastoma: a practical review of challenges and ways to overcome them

S Sengupta, G Mao, Z S Gokaslan and P Sampath

Cancer Gene Ther 2017 24: 121-129; advance online publication, October 21, 2016; 10.1038/cgt.2016.46

Abstract | Full Text

Current status of immunotherapy for gastrointestinal stromal tumor

Y Tan, J C Trent, B A Wilky, D A Kerr and A E Rosenberg

Cancer Gene Ther 2017 24: 130-133; advance online publication, February 10, 2017; 10.1038/cgt.2016.58

Abstract | Full Text

Gene-expression profiling to predict responsiveness to immunotherapy

N B Jamieson and A V Maker

Cancer Gene Ther 2017 24: 134-140; advance online publication, November 11, 2016; 10.1038/cgt.2016.63

Abstract | Full Text

Combinatorial immunotherapy for melanoma

D D George, V A Armenio and S C Katz

Cancer Gene Ther 2017 24: 141-147; advance online publication, November 11, 2016; 10.1038/cgt.2016.56

Abstract | Full Text

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