bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of exenatide on weight and appetite in overweight adolescents and young adults with Prader‐Willi syndrome
Authors: Salehi P. , Hsu I. , Azen C. G. , Mittelman S. D. , Geffner M. E. , Jeandron D. 
Published: April 2016

SummaryBackgroundPrader–Willi syndrome (PWS) is associated with hyperphagia and hyperghrelinemia with major morbidity because of obesity without effective medical treatment targeting hyperphagia. Exenatide (Byetta [synthetic Exendin‐4]; AstraZeneca, Wilmington DE) is a GLP‐1 receptor agonist which reduces appetite and weight and may be an effective treatment in PWS.ObjectiveThe objective of this study is to determine the effect of a 6‐month trial of exenatide on appetite, weight and gut hormones in youth with PWS.MethodsTen overweight and obese subjects with PWS (13–25 years) were recruited for a 6‐month open‐label, non‐randomized, longitudinal study conducted at Children's Hospital Los Angeles. Exenatide was given using standard diabetes dosing without dietary modifications. Weight, body mass index (BMI), truncal fat, appetite and plasma acylated ghrelin were measured over 6 months. Mixed meal tolerance tests were performed at 0 and 6 months.ResultsAppetite scores significantly decreased from baseline (32.2 ± 8.7) after 1, 3 and 6 moths of treatment (27.5 ± 8.8, 25.4 ± 9.3, and 25.4 ± 7.2 respectively; p = 0.004). Hemoglobin A1c decreased significantly after treatment, but weight, BMI z‐score and adiposity did not. There was no significant change in ghrelin.ConclusionsThis is the first longitudinal investigation of the effects of exenatide in subjects with PWS. It was effective in decreasing appetite, without change in weight or BMI in the short term. Larger, controlled, longer‐term trials in patients with PWS are needed to confirm the efficacy and safety of exenatide and to evaluate whether its use might induce weight loss when given in conjunction with behavioural modification.
Clinical experience of surgically treating giant neurofibromatosis‐1
Authors: Chen Baoguo , Xu Minghuo , Song Huifeng , Gao Quanwen 
Published: April 2016

AbstractThe surgical treatment for giant neurofibromatosis‐1 (NF‐1) requires comprehensive measures. Presently, there is no systematic description of surgical treatment. Because of its high level of risk, we want to share our clinical experience. From 2011 to 2014, patients (n = 8, 5 female and 3 male patients, aging from 31 to 45 years‐old) were included in the study. The tumours were located on the trunk (n = 5) or face (n = 3). In addition to routine examination, blood storage was also prepared. Preoperative consultation from related departments was critical at first. Related artery embolisation was also carried out. In the operation, we checked thromboelastography, based on which reasonable blood component transfusion was implemented. Autologous blood transfusion was also ready. An instrument of copper needle or ring ligation was used to reduce haemorrhage before the surgery. Protruding or drooping portions of the tumours were excised. A pressurised bandage was applied when the surgery was completed. After the surgery, besides the routine monitoring of vital signs, re‐haemorrhage should be detected in time. Then, we should decide whether blood transfusion or surgery was required again. Expanders were implanted in one female patient with facial injuries before removing the tumour. Then, expanded flaps were applied to repair the secondary wound. According to the above clinical route, after an average of 1‐year follow‐up, no patients died, and other unforeseen events did not occur. Wounds healed well in all patients. The tumor was excised as much as possible. No facial nerve paralysis occurred in the facial sites. Expanded flaps necrosis WAS not encountered. It is essential to design the educational clinical route for treating NF‐1 when a giant protruding tumour is advised to be excised, which can minimise the risk of surgery and assure us of the maximum range of resection.
Myocardial protective effects of a c‐Jun N‐terminal kinase inhibitor in rats with brain death
Authors: Guo Wenzhi , Cao Shengli , Yan Bing , Zhang Gong , Li Jie , Zhao Yongfu , Zhang Shuijun 
Published: April 2016

AbstractTo investigate whether the mitochondrial apoptotic pathway mediates myocardial cell injuries in rats under brain death (BD), and observe the effects and mechanisms of the c‐Jun N‐terminal kinase (JNK) inhibitor SP600125 on cell death in the heart. Forty healthy male Sprague‐Dawley (SD) rats were randomized into four groups: sham group (dural external catheter with no BD); BD group (maintain the induced BD state for 6 hrs); BD + SP600125 group (intraperitoneal injection of SP600125 10 mg/kg 1 hr before inducing BD, and maintain BD for 6 hrs); and BD + Dimethyl Sulphoxide (DMSO) group (intraperitoneal injection of DMSO 1 hr before inducing BD, and maintain BD for 6 hrs). Real‐time quantitative PCR was used to evaluate mRNA levels of Cyt‐c and caspase‐3. Western blot analysis was performed to examine the levels of mitochondrial apoptosis‐related proteins p‐JNK, Bcl‐2, Bax, Cyt‐c and Caspase‐3. TUNEL assay was employed to evaluate myocardial apoptosis. Compared with the sham group, the BD group exhibited increased mitochondrial apoptosis‐related gene expression, accompanied by the elevation of p‐JNK expression and myocardial apoptosis. As the vehicle control, DMSO had no treatment effects. The BD + SP600125 group had decreased p‐JNK expression, and reduced mitochondrial apoptosis‐related gene expression. Furthermore, the apoptosis rate of myocardial cells was reduced. The JNK inhibitor SP600125 could protect myocardial cells under BD through the inhibition of mitochondrial apoptosis‐related pathways.
Phloroglucinol protects retinal pigment epithelium and photoreceptor against all‐trans‐retinal–induced toxicity and inhibits A2E formation
Authors: Cia David , Cubizolle Aurélie , Crauste Céline , Jacquemot Nathalie , Guillou Laurent , Vigor Claire , Angebault Claire , Hamel Christian P. , Vercauteren Joseph , Brabet Philippe 
Published: April 2016

AbstractAmong retinal macular diseases, the juvenile recessive Stargardt disease and the age‐related degenerative disease arise from carbonyl and oxidative stresses (COS). Both stresses originate from an accumulation of all‐trans‐retinal (atRAL) and are involved in bisretinoid formation by condensation of atRAL with phosphatidylethanolamine (carbonyl stress) in the photoreceptor and its transformation into lipofuscin bisretinoids (oxidative stress) in the retinal pigment epithelium (RPE). As atRAL and bisretinoid accumulation contribute to RPE and photoreceptor cell death, our goal is to select powerful chemical inhibitors of COS. Here, we describe that phloroglucinol, a natural phenolic compound having anti‐COS properties, protects both rat RPE and mouse photoreceptor primary cultures from atRAL‐induced cell death and reduces hydrogen peroxide (H2O2)‐induced damage in RPE in a dose‐dependent manner. Mechanistic analyses demonstrate that the protective effect encompasses decrease in atRAL‐induced intracellular reactive oxygen species and free atRAL levels. Moreover, we show that phloroglucinol reacts with atRAL to form a chromene adduct which prevents bisretinoid A2E synthesis in vitro. Taken together, these data show that the protective effect of phloroglucinol correlates with its ability to trap atRAL and to prevent its further transformation into deleterious bisretinoids. Phloroglucinol might be a good basis to develop efficient therapeutic derivatives in the treatment of retinal macular diseases.
Impact of pregnancy and oestrogen on psoriasis and potential therapeutic use of selective oestrogen receptor modulators for psoriasis
Authors: Lin X. , Huang T. 
Published: April 2016

AbstractMajority of female patients show improvement of psoriasis during pregnancy. This is demonstrated to be correlated with high levels of oestrogen. Even in male patient, oestrogen level is inversely correlated with the severity of psoriasis. However, a minority of female psoriatic patients still experience worsening during pregnancy. Oestrogen might improve psoriasis by suppressing the T‐cell immune response, reducing the keratinocyte (KC) cytokine and chemokine production, restoring the balance of redox and enhancing the skin barrier. However, it might worsen the disease by stimulating KC proliferation and promoting angiogenesis. This complex role of oestrogen in the pathogenesis of psoriasis might explain why the two opposite effects of pregnancy coexist. Data shows that the number of improving patients with psoriasis in pregnancy is double the number of the worsening patients, suggesting that oestrogen may be potentially useful in the treatment of psoriasis. However, oestrogen is not considered suitable as a long‐term treatment subject to negative side‐effects. This review discusses current studies on taking selective oestrogen receptor mediators as a novel potential therapeutic option for psoriasis.
Methods to Succeed in Effective Knowledge Translation in Clinical Practice
Authors: Kitson Alison L. , Harvey Gillian 
Published: April 2016

AbstractPurposeTo explore the evidence around facilitation as an intervention for the successful implementation of new knowledge into clinical practice.Organizing ConstructThe revised version of the Promoting Action on Research Implementation in Health Services (PARIHS) framework, called the integrated or i‐PARIHS framework, is used as the explanatory framework. This framework posits that evidence is a multidimensional construct embedded within innovation and operationalized by clinicians (individuals and within teams), working across multiple layers of context. Facilitation is the active ingredient that promotes successful implementation.FindingsAn emerging body of evidence supports facilitation as a mechanism to getting new knowledge into clinical practice. Facilitation roles are divided into beginner, experienced, and expert facilitators. Facilitators can be internal or external to the organization they work in, and their skills and attributes complement other knowledge translation (KT) roles. Complex KT projects require facilitators who are experienced in implementation methods.ConclusionsFacilitation is positioned as the active ingredient to effectively introduce new knowledge into a clinical setting. Levels of facilitation experience are assessed in relation to the complexity of the KT task. Three core facilitation roles are identified, and structured interventions are established taking into account the nature and novelty of the evidence, the receptiveness of the clinicians, and the context or setting where the new evidence is to be introduced.Clinical RelevanceRoles such as novice, experienced, and expert facilitators have important and complementary parts to play in enabling the successful translation of evidence into everyday practice in order to provide effective care for patients.
Reducing Preventable Hospitalizations With Two Models of Transitional Care
Authors: Morrison Jessica , Palumbo Mary Val , Rambur Betty 
Published: April 2016

AbstractPurposeTransitional care is an emerging model of health care designed to decrease preventable adverse events and associated utilization of health care through temporary follow‐up after hospital discharge. This study describes the approaches and outcomes of two distinct transitional care programs serving different populations: one is provided by master's‐prepared clinical nurse specialists (CNS) with a chronic disease self‐management focus, another by physicians specializing in palliative care (PPCs). Existing research has shown that transitional care programs with intensive follow‐up reduce hospitalizations, emergency department (ED) visits, and costs. Few studies, however, have included side‐by‐side descriptions of the efficacy of transitional care programs varying by healthcare providers or program focus.DesignThis is a retrospective cohort study comparing the number of ED visits and hospitalizations in the 120 days before and after the intervention for patients enrolled in each transitional care program. Each program included post‐hospitalization home visits, but included differences in program focus (chronic disease vs. palliative), assessment and interventions, and population (rural vs. urban). Data from participants in the CNS program (September 2014 to December 2014) were analyzed (n = 98). The average age of participants was 69 years and 65% were female. Data were collected from patients from the PPC program from September 2014 to April 2015 (n = 71). Thirty participants died within 120 days after the intervention and were excluded; the remaining 41 were included in the analysis. Participants had an average age of 81 years and 63% were female.MethodsFor the CNS program, a secondary analysis of existing data was performed. For the PPC program, a review of patient charts was done to collect data on encounters. A Wilcoxon matched‐pairs signed‐rank test was performed to test for significance.FindingsPatients in the CNS intervention had significantly fewer ED visits (p < .005) and hospitalizations (p < .005) in the 4 months after the intervention than in the 4 months before the intervention. Patients in the PPC program had a nonsignificant reduction in ED visits (p = .327) and a significant reduction in hospitalizations postintervention (p = .03).ConclusionsBoth transitional programs have value in decreasing rehospitalizations. The CNS intervention also significantly reduced ED visits for their target population. Further study with randomized controlled trials is needed to allow for a better understanding of the healthcare workforce best fitted to enhance transitional care outcomes. Future study to examine the cost savings of each of the interventions is also needed.Clinical RelevanceTransitional care programs have the potential to prevent unnecessary utilization of health care at the critical periods of transition that leave patients vulnerable to adverse events and poor outcomes.
Metabolic syndrome and metabolic risk profile according to polycystic ovary syndrome phenotype
Authors: Bil Enes , Dilbaz Berna , Cirik Derya Akdag , Ozelci Runa , Ozkaya Enis , Dilbaz Serdar 
Published: April 2016

AbstractAimIt is unknown which phenotype of polycystic ovary syndrome (PCOS) has a greater metabolic risk and how to detect this risk. The aim of this study was therefore to compare the incidence of metabolic syndrome (MetS) and metabolic risk profile (MRP) for different phenotypes.MethodsA total of 100 consecutive newly diagnosed PCOS women in a tertiary referral hospital were recruited. Patients were classified into four phenotypes according to the Rotterdam criteria, on the presence of at least two of the three criteria hyperandrogenism (H), oligo/anovulation (O) and PCO appearance (P): phenotype A, H + O + P; phenotype B, H + O; phenotype C, H + P; phenotype D, O + P. Prevalence of MetS and MRP were compared among the four groups.ResultsBased on Natural Cholesterol Education Program Adult Treatment Panel III diagnostic criteria, MetS prevalence was higher in phenotypes A and B (29.6% and 34.5%) compared with the other phenotypes (10.0% and 8.3%; P < 0.001). Although the prevalence of obesity was similar, the number of patients with homeostatic model assessment insulin resistance index (HOMA‐IR) >3.8 was significantly higher in androgenic PCOS phenotypes. After logistic regression analysis, visceral adiposity index (VAI) was the only independent predictor of MetS in PCOS (P = 0.002). VAI was also significantly higher in phenotype B, when compared with the others (P < 0.01).ConclusionPhenotypes A and B had the highest risk of MetS among the four phenotypes, and VAI may be a predictor of metabolic risk in PCOS women.
Polyphosphate is involved in cell cycle progression and genomic stability in Saccharomyces cerevisiae
Authors: Bru Samuel , Martínez‐Laínez Joan Marc , Hernández‐Ortega Sara , Quandt Eva , Torres‐Torronteras Javier , Martí Ramón , Canadell David , Ariño Joaquin , Sharma Sushma , Jiménez Javier , Clotet Josep 
Published: April 2016

SummaryPolyphosphate (polyP) is a linear chain of up to hundreds of inorganic phosphate residues that is necessary for many physiological functions in all living organisms. In some bacteria, polyP supplies material to molecules such as DNA, thus playing an important role in biosynthetic processes in prokaryotes. In the present study, we set out to gain further insight into the role of polyP in eukaryotic cells. We observed that polyP amounts are cyclically regulated in Saccharomyces cerevisiae, and those mutants that cannot synthesise (vtc4Δ) or hydrolyse polyP (ppn1Δ, ppx1Δ) present impaired cell cycle progression. Further analysis revealed that polyP mutants show delayed nucleotide production and increased genomic instability. Based on these findings, we concluded that polyP not only maintains intracellular phosphate concentrations in response to fluctuations in extracellular phosphate levels, but also muffles internal cyclic phosphate fluctuations, such as those produced by the sudden demand of phosphate to synthetize deoxynucleotides just before and during DNA duplication. We propose that the presence of polyP in eukaryotic cells is required for the timely and accurate duplication of DNA.
CRISPR‐Cas9‐modified pfmdr1 protects Plasmodium falciparum asexual blood stages and gametocytes against a class of piperazine‐containing compounds but potentiates artemisinin‐based combination therapy partner drugs
Authors: Ng Caroline L. , Siciliano Giulia , Lee Marcus C. S. , de Almeida Mariana J. , Corey Victoria C. , Bopp Selina E. , Bertuccini Lucia , Wittlin Sergio , Kasdin Rachel G. , Le Bihan Amélie , Clozel Martine , Winzeler Elizabeth A. , Alano Pietro , Fidock David A. 
Published: April 2016

SummaryEmerging resistance to first‐line antimalarial combination therapies threatens malaria treatment and the global elimination campaign. Improved therapeutic strategies are required to protect existing drugs and enhance treatment efficacy. We report that the piperazine‐containing compound ACT‐451840 exhibits single‐digit nanomolar inhibition of the Plasmodium falciparum asexual blood stages and transmissible gametocyte forms. Genome sequence analyses of in vitro‐derived ACT‐451840‐resistant parasites revealed single nucleotide polymorphisms in pfmdr1, which encodes a digestive vacuole membrane‐bound ATP‐binding cassette transporter known to alter P. falciparum susceptibility to multiple first‐line antimalarials. CRISPR‐Cas9 based gene editing confirmed that PfMDR1 point mutations mediated ACT‐451840 resistance. Resistant parasites demonstrated increased susceptibility to the clinical drugs lumefantrine, mefloquine, quinine and amodiaquine. Stage V gametocytes harboring Cas9‐introduced pfmdr1 mutations also acquired ACT‐451840 resistance. These findings reveal that PfMDR1 mutations can impart resistance to compounds active against asexual blood stages and mature gametocytes. Exploiting PfMDR1 resistance mechanisms provides new opportunities for developing disease‐relieving and transmission‐blocking antimalarials.
Ozonated water reduces susceptibility in tomato plants to Meloidogyne incognita by the modulation of the antioxidant system
Authors: Veronico Pasqua , Paciolla Costantino , Sasanelli Nicola , De Leonardis Silvana , Melillo Maria Teresa 
Published: April 2016

SummaryFew studies have been carried out on the effect of ozonated water (O3wat) on the oxidative stress of root systems and, in particular, in combination with biotic stress. The aim of this study was to determine whether aqueous ozone is effective in the control of root‐knot nematode (RKN) infection and to investigate the concomitant changes in the basal defence system. A tomato cultivar susceptible to Meloidogyne incognita was treated with O3wat as a soil drench. No negative effects were seen following ozone application in comparison with the control under the exposure conditions used. The treatment reduced significantly the nematode infection rate and induced changes in the morphology of nematode feeding sites, some of which were characterized by visible symptoms of senescence. The antioxidant response, as well as parameters of oxidative damage, were examined in untreated and O3wat‐treated galls at 2, 4 and 7 days after inoculation and compared with uninfected roots. High levels of reactive oxygen species (ROS), H2O2 and malondialdehyde were generated in galls in response to combined abiotic and biotic stresses. Throughout the experimental period, the activities and relative transcript levels of the antioxidant enzymes catalase, superoxide dismutase and ascorbate peroxidase produced different responses when exposed to ozone treatment and/or infection. The results demonstrate how O3wat protects tomato against the RKN M. incognita through the modulation of basal defence mechanisms.
The efficacy and safety of clotrimazole vaginal tablet vs. oral fluconazole in treating severe vulvovaginal candidiasis
Authors: Zhou Xiaofang , Li Ting , Fan Shangrong , Zhu Yuxia , Liu Xiaoping , Guo Xuedong , Liang Yiheng 
Published: April 2016

SummaryTo compare the efficacy and safety of two doses of clotrimazole vaginal tablet 500 mg with two doses of oral fluconazole 150 mg in treating severe vulvovaginal candidiasis (SVVC), 240 consecutive patients with SVVC were studied at the Department of Obstetrics and Gynaecology of Peking University Shenzhen Hospital between June 2014, and September 2015. Patients were randomly assigned in a 1 : 1 ratio to receive treatment with either two doses of clotrimazole vaginal tablet or two doses of oral fluconazole. The clinical cure rates in the clotrimazole group and the fluconazole group at days 7–14 follow‐up were 88.7% (102/115) and 89.1% (98/110) respectively; the clinical cure rates at days 30–35 in the two groups were 71.9% (82/114) and 78.0% (85/109) respectively. The mycological cure rates at days 7–14 follow‐up in the two groups were 78.3% (90/115) and 73.6% (81/110) respectively. The mycological cure rates of the patients at days 30–35 in the two groups were 54.4% (62/114) and 56.0% (61/109) respectively (P > 0.05). The adverse events of clotrimazole were mainly local. This study demonstrated that two doses of clotrimazole vaginal tablet 500 mg were as effective as two doses of oral fluconazole 150 mg in the treatment of patients with SVVC and could be an appropriate treatment for this disorder.
Smegma Pearls in Young Uncircumcised Boys
Authors: Sonthalia Sidharth , Singal Archana 
Published: April 2016

AbstractDeposition of smegma in the subpreputial region is common in young uncircumcised boys. Although the term “smegma pearls” has been used colloquially for this entity, there is an apparent lack of reference to smegma pearls and their characteristics in the extant scientific literature. We present a series of six Indian boys with smegma pearls and discuss their possible origin, course, and management.
Case Report of Focal Epithelial Hyperplasia (Heck's Disease) with Polymerase Chain Reaction Detection of Human Papillomavirus 13
Authors: Brehm Mary A. , Gordon Katie , Firan Miahil , Rady Peter , Agim Nnenna 
Published: April 2016

AbstractFocal epithelial hyperplasia (FEH), or Heck's disease, is an uncommon benign proliferation of oral mucosa caused by the human papillomavirus (HPV), particularly subtypes 13 and 32. The disease typically presents in young Native American patients and is characterized by multiple asymptomatic papules and nodules on the oral mucosa, lips, tongue, and gingiva. The factors that determine susceptibility to FEH are unknown, but the ethnic and geographic distribution of FEH suggests that genetic predisposition, particularly having the human lymphocytic antigen DR4 type, may be involved in pathogenesis. We report a case of FEH with polymerase chain reaction detection of HPV13 in a healthy 11‐year‐old Hispanic girl and discuss the current understanding of disease pathogenesis, susceptibility, and treatment.