bluuebunny/crossref_metadata_2025 huggingface dataset:
Krüppel-Like Factor 4 Is a Regulator of Proinflammatory Signaling in Fibroblast-Like Synoviocytes through Increased IL-6 Expression
Authors: Luo Xinjing , Chen Jie , Ruan Jianwei , Chen Yongfeng , Mo Xuanrong , Xie Jiangwen , Lv Guoju
Published: June 2016

Human fibroblast-like synoviocytes play a vital role in joint synovial inflammation in rheumatoid arthritis (RA). Proinflammatory cytokines induce fibroblast-like synoviocyte activation and dysfunction. The inflammatory mediator Krüppel-like factor 4 is upregulated during inflammation and plays an important role in endothelial and macrophage activation during inflammation. However, the role of Krüppel-like factor 4 in fibroblast-like synoviocyte activation and RA inflammation remains to be defined. In this study, we identify the notion that Krüppel-like factor 4 is higher expressed in synovial tissues and fibroblast-like synoviocytes from RA patients than those from osteoarthritis patients.In vitro, the expression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes is induced by proinflammatory cytokine tumor necrosis factor-α. Overexpression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes robustly induced interleukin-6 production in the presence or absence of tumor necrosis factor-α. Conversely, knockdown of Krüppel-like factor 4 markedly attenuated interleukin-6 production in the presence or absence of tumor necrosis factor-α. Krüppel-like factor 4 not only can bind to and activate the interleukin-6 promoter, but also may interact directly with nuclear factor-kappa B. These results suggest that Krüppel-like factor 4 may act as a transcription factor mediating the activation of fibroblast-like synoviocytes in RA by inducing interleukin-6 expression in response to tumor necrosis factor-α.
Liquid Biopsy of Hepatocellular Carcinoma: Circulating Tumor-Derived Biomarkers
Authors: Yin Chang-Qing , Yuan Chun-Hui , Qu Zhen , Guan Qing , Chen Hao , Wang Fu-Bing
Published: June 2016

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide due to latent liver disease, late diagnosis, and nonresponse to systemic treatments. Till now, surgical and/or biopsy specimens are still generally used as a gold standard by the clinicians for clinical decision-making. However, apart from their invasive characteristics, tumor biopsy only mirrors a single spot of the tumor, failing to reflect current cancer dynamics and progression. Therefore, it is imperative to develop new diagnostic strategies with significant effectiveness and reliability to monitor high-risk populations and detect HCC at an early stage. In the past decade, the potent utilities of “liquid biopsy” have attracted intense concern and were developed to evaluate cancer progression in several clinical trials. “Liquid biopsies” represent a series of noninvasive tests that detect cancer byproducts easily accessible in peripheral blood, mainly including circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) that are shed into the blood from the tumor sites. In this review, we focus on the recent developments in the field of “liquid biopsy” as well as the diagnostic and prognostic significance of CTCs and cfNAs in HCC patients.
Bacteriological Contaminants of Some Fresh Vegetables Irrigated with Awetu River in Jimma Town, Southwestern Ethiopia
Authors: Weldezgina Desta , Muleta Diriba
Published: June 2016

The main purposes of this study were to determine the bacteriological load and safety of some fresh vegetables irrigated with Awetu River in Jimma town, southwestern Ethiopia. Water and vegetable samples were collected from three different irrigation sites and analyzed for their bacteriological contaminants following standard procedures. The maximum overall means of aerobic mesophilic bacteria, Enterobacteriaceae, aerobic spore formers, staphylococci, and total and fecal coliform counts were 8.06, 7.10, 6.54, and 2.97 log CFU g−1 and 1036 and 716 MPN 100 mL−1, respectively. The microflora of vegetable samples was dominated by Bacillus species (32.7%) followed by Enterobacteriaceae (25%) and Micrococcus (16%). Staphylococcus aureus and Salmonella spp. were detected in 24.0% and 20.7% of the samples, respectively. All the Staphylococcus aureus isolates were resistant to ampicillin, cefuroxime sodium, and penicillin G (100.0% each). All the Salmonella isolates were also resistant to tetracycline, erythromycin, cefuroxime sodium, and penicillin G (100.0% each). The findings reveal that the river water used for irrigation in this study is a possible preharvest source of contamination to fresh vegetables which potentially constitutes a health risk to consumers.
Familial Pemphigus Vulgaris Occured in a Father and Son as the First Confirmed Cases
Authors: Eskiocak Ali Haydar , Ozkesici Birgul , Uzun Soner
Published: June 2016

Pemphigus vulgaris (PV) is a chronic autoimmune bullous disease of the skin and mucous membranes. Although there is some evidence pointing towards a genetic predisposition by some human leukocyte antigen (HLA) genes, familial occurrence of PV is very rare. Most of the familial PV cases so far reported have been in mother and daughter and in siblings. PV in father and son, as presented here, has not been reported in the literature before, except an unconfirmed report. The diagnosis of PV was established by histologic, cytologic studies and enzyme linked immunosorbent assay (ELISA) in Case1and by ELISA and BIOCHIP indirect immunofluorescence test in Case2. The son was responsive to moderate doses of methylprednisolone, with the treatment continuing with tapered doses. The father was in a subclinic condition; consequently, only close follow-up was recommended. HLA typing studies revealed identical HLA alleles of HLA-DR4 (DRB1⁎04) and HLA-DQB1⁎03in both of our cases; this had been found to be associated with PV in prior studies. Familial occurrences of PV and related HLA genes indicate the importance of genetic predisposition. The first occurrence of confirmed familial PV in father and son is reported here.
Extremely Rare Form of Impaction Bilateral Kissing Molars: Report of a Case and Review of the Literature
Authors: Zerener Tamer , Bayar Gurkan Rasit , Altug Hasan Ayberk , Kiran Serkan
Published: June 2016

Kissing molars (KM) or rosette formation is a term that is used to describe impacted teeth contacting occlusal surfaces in a single follicular space and their roots pointing in opposite directions. In some cases kissing molars can be seen but occurrence of bilateral kissing molars is extremely rare phenomenon in the dental literature and the aetiology of this phenomenon is still unknown. In this paper we describe a case and review of the literature and discuss the management of this pathology. In our case, extremely rare form of impacted bilateral kissing molars was extracted surgically. The decision of extraction of asymptomatic kissing molars represents surgical dilemma. There may be many surgical complications; on the other hand in some cases surgical intervention is unavoidable. Few treatment options were described in the literature. This phenomenon can be sign of various medical conditions that may require further investigation. In this paper, our treatment option is in agreement with the literature suggesting the surgical removal of both teeth at either side of the mandible.
Chaperone-Mediated Autophagy and Mitochondrial Homeostasis in Parkinson’s Disease
Authors: Yang Ruixin , Gao Guodong , Mao Zixu , Yang Qian
Published: June 2016

Parkinson’s disease (PD), a complex neurodegenerative disorder, is pathologically characterized by the formation of Lewy bodies and loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Mitochondrial dysfunction is considered to be one of the most important causative mechanisms. In addition, dysfunction of chaperone-mediated autophagy (CMA), one of the lysosomal proteolytic pathways, has been shown to play an important role in the pathogenesis of PD. An exciting and important development is recent finding that CMA and mitochondrial quality control may be linked. This review summarizes the studies revealing the link between autophagy and mitochondrial function. Discussions are focused on the connections between CMA and mitochondrial failure and on the role of MEF2D, a neuronal survival factor, in mediating the regulation of mitochondria in the context of CMA. These new findings highlight the need to further explore the possibility of targeting the MEF2D-mitochondria-CMA network in both understanding the PD pathogenesis and developing novel therapeutic strategies.
Elbasvir/Grazoprevir: A Review of the Latest Agent in the Fight against Hepatitis C
Authors: Bell Allison M. , Wagner Jamie L. , Barber Katie E. , Stover Kayla R.
Published: June 2016

Hepatitis C virus (HCV) is estimated to affect up to 150 million people worldwide. Despite worldwide prevalence, treatment modalities prior to 2011 remained suboptimal, with low virologic response rates and intolerable side effect profiles. Fortunately, the landscape of treatment for chronic hepatitis C has rapidly evolved since the introduction of HCV NS3/4 protease inhibitors in 2011. Elbasvir, a NS5A inhibitor, combined with grazoprevir, a NS3/4A protease inhibitor, is the latest FDA-approved therapy for patients with genotype 1 or 4 chronic hepatitis C, with or without compensated cirrhosis. This review will focus on the current literature and clinical evidence supporting elbasvir/grazoprevir as first-line therapy in patients with genotypes 1 and 4 chronic hepatitis C.
Qingchang Wenzhong Decoction Ameliorates Dextran Sulphate Sodium‐Induced Ulcerative Colitis in Rats by Downregulating the IP10/CXCR3 Axis‐Mediated Inflammatory Response
Authors: Mao Tang-you , Shi Rui , Zhao Wei-han , Guo Yi , Gao Kang-li , Chen Chen , Xie Tian-hong , Li Jun-xiang
Published: June 2016

Qingchang Wenzhong Decoction (QCWZD) is an effective traditional Chinese medicine prescription. Our previous studies have shown that QCWZD has significant efficacy in patients with mild‐to‐moderate ulcerative colitis (UC) and in colonic mucosa repair in UC rat models. However, the exact underlying mechanism remains unknown. Thus, this study was conducted to determine QCWZD’s efficacy and mechanism in dextran sulphate sodium‐ (DSS‐) induced UC rat models, which were established by 7‐day administration of 4.5% DSS solution. QCWZD was administered daily for 7 days, after which the rats were euthanized. Disease activity index (DAI), histological score (HS), and myeloperoxidase (MPO) level were determined to evaluate UC severity. Serum interferon gamma‐induced protein 10 (IP10) levels were determined using ELISA kits. Western blotting and real‐time polymerase chain reaction were, respectively, used to determine colonic protein and gene expression of IP10, chemokine (cys‐x‐cys motif) receptor (CXCR)3, and nuclear factor‐ (NF‐) κB p65. Intragastric QCWZD administration ameliorated DSS‐induced UC, as evidenced by decreased DAI, HS, and MPO levels. Furthermore, QCWZD decreased the protein and gene expression of IP10, CXCR3, and NF‐κB p65. Overall, these results suggest that QCWZD ameliorates DSS‐induced UC in rats by downregulating the IP10/CXCR3 axis‐mediated inflammatory response and may be a novel UC therapy.
Using an Interactive Systems Framework to Expand Telepsychology Innovations in Underserved Communities
Authors: Garney Whitney R. , McCord Carly E. , Walsh Michaela V. , Alaniz Angela B.
Published: June 2016

Literature indicates that the use of promising innovations in mental health care can be improved. The advancement of telepsychology is one innovation that has been utilized as a method to reduce rural health disparities and increase the number of people with access to mental health services. This paper describes a successful pilot telepsychology program implemented in a rural community to increase access to mental health services and the model’s replication and expansion into four additional communities using concepts described in an Interactive Systems Framework. The Interactive Systems Framework highlights how building local capacity specific to organizational functioning and innovations are necessary to support, deliver, and disseminate innovations within new settings. Based on the knowledge gained from this telepsychology innovation, the application of an Interactive Systems Framework and funding mechanisms are discussed.
Cryopreservation of Bone Marrow Mononuclear Cells Alters Their Viability and Subpopulation Composition but Not Their Treatment Effects in a Rodent Stroke Model
Authors: Yang Bing , Parsha Kaushik , Schaar Krystal , Satani Nikunj , Xi Xiaopei , Aronowski Jaroslaw , Savitz Sean I.
Published: June 2016

The systemic administration of autologous bone marrow (BM) derived mononuclear cells (MNCs) is under investigation as a novel therapeutic modality for the treatment of ischemic stroke. Autologous applications raise the possibility that MNCs could potentially be stored as a banked source. There have been no studies that investigate the effects of cryopreservation of BM‐MNCs on their functional abilities in stroke models. In the present study, C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAo) for 60 minutes and then divided into two treatment groups: fresh MNCs versus cryopreserved MNCs. BM‐MNCs were collected at 22 hours after MCAo and were stored in liquid nitrogen for 12 months in cryopreserved MNCs group. BM‐MNCs cellular viability, composition, and phenotype of the various subpopulations of mice BM‐MNCs were evaluated by flow cytometry, and the behavioral recovery of stroke animals was tested with freshly harvested MNCs versus cryopreserved MNCs by corner test and ladder rung test. We found that long‐term cryopreservation negatively impacts the cellular viability of bone marrow MNCs. Cryopreservation also alters the cellular composition of various subpopulations within the MNCs. However, despite the changes observed in cryopreserved cells, both fresh and frozen MNCs have similar beneficial effect on behavioral and histological outcomes.
Turning Disaster into an Opportunity for Quality Improvement in Essential Intrapartum and Newborn Care Services in the Philippines: Pre- to Posttraining Assessments
Authors: Castillo M. S. , Corsino M. A. , Calibo A. P. , Zeck W. , Capili D. S. , Andrade L. C. , Reyes K. A. , Alfonso R. C. , Ponferrada M. B. , Silvestre M. A.
Published: June 2016

Background.On 8 November 2013, supertyphoon Haiyan made landfall in the Philippines, severely disrupting health service delivery. Reestablishment of essential services for birthing mothers and their newborns became high priority.Methodology.Following a baseline assessment, an Essential Intrapartum and Newborn Care (EINC) training package was implemented and posttraining assessments (1 and 3 months after training) were undertaken.Results.Baseline assessments (n=56facilities) revealed gaps in provider’s skill and shortage of life-saving commodities. Facilities lacked newborn bags/masks (9%), towels (6%), and magnesium sulfate (39%). Service providers lacked skills in partograph use (54%), antenatal steroid (44%) use, and breastfeeding initiation (50%). At 3 months after training (n=51facilities), dramatic increases in correct partograph use (to 92%), antenatal steroid use (to 98%), breastfeeding initiation (to 86%), kangaroo mother care (to 94%), availability of magnesium sulfate (to 94%), and bag/masks (to 88%) were documented. Gaps persisted for skills in assisted vaginal delivery and removal of placental fragments.Conclusion.Health services were severely disrupted after supertyphoon Haiyan. Our study demonstrates that essential birthing services and quality improvements to strengthen local health systems can be restored in a timely manner even in immediate postdisaster settings.
Increased Gustatory Response Score in Obesity and Association Levels with IL-6 and Leptin
Authors: Remla Nesrine , Hadjidj Zeyneb , Ghezzaz Kamel , Moulessehoul Soraya , Aribi Mourad
Published: June 2016

Background. The aim of this study was to investigate the relationship between the circulating IL-6 and leptin levels with taste alteration in young obese patients.Methods. A retrospective case-control study was conducted in thirty obese patients and thirty age- and sex-matched healthy controls.Results. Circulating levels of IL-6 and leptin were significantly increased in obese patients than in controls. However, catalase and ORAC levels were significantly decreased in obese patients compared to controls. Additionally, obese participants had high scores for the detection of fats (gustatory response scores [GRS];p<0.001). Moreover, IL-6 and leptin were strongly associated with GRS alteration among patients with GRS 4 (resp., OR =17.5 [95% CI, 1.56–193.32;p=0.007]; OR = 16 [95% CI, 1.69–151.11;p=0.006]). For the Mantel-Haenszel common odds ratio estimate (MH OR), IL-6 and leptin were strongly associated with obesity, in patients with either GRS 4 or GRS > 4 (resp., MH OR = 8.77 [95% CI, 2.06–37.44;p=0.003]; MH OR = 5.76 [95% CI, 1.64–20.24;p=0.006]).Conclusions. In a low grade inflammation linked to obesity, taste alteration is associated with high levels of IL-6 and leptin.
Predictive Factors of Development of Graves’ Ophthalmopathy for Patients with Juvenile Graves’ Disease
Authors: Jarusaitiene Dalia , Verkauskiene Rasa , Jasinskas Vytautas , Jankauskiene Jurate
Published: June 2016

Background. Due to low incidence of Graves’ ophthalmopathy (GO) among children, the manifestation is poorly analyzed, posing a risk to late identification of insidious disease.Purposes. To identify predictive factors that may influence the development of GO in pediatric and young patients with Graves’ disease (GD).Methods. A cross-sectional study of patients newly diagnosed with pediatric or juvenile GD during 2002–2012 was conducted at the Hospital of Lithuanian University of Health Sciences. Ocular evaluation was based on European Group on Graves’ Orbitopathy survey. The ocular manifestations were analyzed in relation to demographic, environmental, and clinical factors.Results. In total, 130 patients with juvenile GD were included; 29.2% had GO. Median age at GD onset was 17 yrs (IQR 4–29). Main symptoms of GO were eyelids retraction (73.7%), proptosis (65.8%), injection of conjunctiva (42.1%), and eyeball motility disturbance (21.1%). Major significant and independent risk factors for GO development were high initial concentration of FT4 (OR = 5.963), TTHAb (OR = 6.358), stress (OR = 6.030), and smoking (OR = 7.098).Conclusion. The major factors that could influence GO development were smoking, stress, and increased levels of initial TRAb, FT4. Slight proptosis, retraction of eyelids, and conjunctive injection were found as predominant ophthalmological symptoms in juvenile GO.
Current Antioxidant Treatments in Organ Transplantation
Authors: Shi Shaojun , Xue Feng
Published: June 2016

Oxidative stress is one of the key mechanisms affecting the outcome throughout the course of organ transplantation. It is widely believed that the redox balance is dysregulated during ischemia and reperfusion (I/R) and causes subsequent oxidative injury, resulting from the formation of reactive oxygen species (ROS). Moreover, in order to alleviate organ shortage, increasing number of grafts is retrieved from fatty, older, and even non‐heart‐beating donors that are particularly vulnerable to the accumulation of ROS. To improve the viability of grafts and reduce the risk of posttransplant dysfunction, a large number of studies have been done focusing on the antioxidant treatments for the purpose of maintaining the redox balance and thereby protecting the grafts. This review provides an overview of these emerging antioxidant treatments, targeting donor, graft preservation, and recipient as well.
miR-196b Is Epigenetically Silenced during the Premalignant Stage of Lung Carcinogenesis
Authors: Tellez Carmen S. , Juri Daniel E. , Do Kieu , Picchi Maria A. , Wang Teresa , Liu Gang , Spira Avrum , Belinsky Steven A.
Published: June 2016

miRNA silencing by promoter hypermethylation may represent a mechanism by which lung cancer develops and progresses, but the miRNAs involved during malignant transformation are unknown. We previously established a model of premalignant lung cancer wherein we treated human bronchial epithelial cells (HBEC) with low doses of tobacco carcinogens. Here, we demonstrate that next-generation sequencing of carcinogen-transformed HBECs treated with the demethylating agent 5-aza-2′deoxycytidine revealed miR-196b and miR-34c-5p to be epigenetic targets. Bisulfite sequencing confirmed dense promoter hypermethylation indicative of silencing in multiple malignant cell lines and primary tumors. Chromatin immunoprecipitation studies further demonstrated an enrichment in repressive histone marks on the miR-196b promoter during HBEC transformation. Restoration of miR-196b expression by transfecting transformed HBECs with specific mimics led to cell-cycle arrest mediated in part through transcriptional regulation of the FOS oncogene, and miR-196b reexpression also significantly reduced the growth of tumor xenografts. Luciferase assays demonstrated that forced expression of miR-196b inhibited the FOS promoter and AP-1 reporter activity. Finally, a case–control study revealed that methylation of miR-196b in sputum was strongly associated with lung cancer (OR = 4.7, P < 0.001). Collectively, these studies highlight miR-196b as a tumor suppressor whose silencing early in lung carcinogenesis may provide a selective growth advantage to premalignant cells. Targeted delivery of miR-196b could therefore serve as a preventive or therapeutic strategy for the management of lung cancer. Cancer Res; 76(16); 4741–51. ©2016 AACR.
PTK6 Inhibition Suppresses Metastases of Triple-Negative Breast Cancer via SNAIL-Dependent E-Cadherin Regulation
Authors: Ito Koichi , Park Sun Hee , Nayak Anupma , Byerly Jessica H. , Irie Hanna Y.
Published: June 2016

Patients with triple-negative breast cancers (TNBC) are at high risk for recurrent or metastatic disease despite standard treatment, underscoring the need for novel therapeutic targets and strategies. Here we report that protein tyrosine kinase 6 (PTK6) is expressed in approximately 70% of TNBCs where it acts to promote survival and metastatic lung colonization. PTK6 downregulation in mesenchymal TNBC cells suppressed migration and three-dimensional culture growth, and enhanced anoikis, resistance to which is considered a prerequisite for metastasis. PTK6 downregulation restored E-cadherin levels via proteasome-dependent degradation of the E-cadherin repressor SNAIL. Beyond being functionally required in TNBC cells, kinase-active PTK6 also suppressed E-cadherin expression, promoted cell migration, and increased levels of mesenchymal markers in nontransformed MCF10A breast epithelial cells, consistent with a role in promoting an epithelial–mesenchymal transition (EMT). SNAIL downregulation and E-cadherin upregulation mediated by PTK6 inhibition induced anoikis, leading to impaired metastatic lung colonization in vivo. Finally, effects of PTK6 downregulation were phenocopied by treatment with a recently developed PTK6 kinase inhibitor, further implicating kinase activity in regulation of EMT and metastases. Our findings illustrate the clinical potential for PTK6 inhibition to improve treatment of patients with high-risk TNBC. Cancer Res; 76(15); 4406–17. ©2016 AACR.
Chromatin Remodeling Factor LSH Drives Cancer Progression by Suppressing the Activity of Fumarate Hydratase
Authors: He Xiaozhen , Yan Bin , Liu Shuang , Jia Jiantao , Lai Weiwei , Xin Xing , Tang Can-e , Luo Dixian , Tan Tan , Jiang Yiqun , Shi Ying , Liu Yating , Xiao Desheng , Chen Ling , Liu Shao , Mao Chao , Yin Gang , Cheng Yan , Fan Jia , Cao Ya , Muegge Kathrin , Tao Yongguang
Published: June 2016

Chromatin modification is pivotal to the epithelial–mesenchymal transition (EMT), which confers potent metastatic potential to cancer cells. Here, we report a role for the chromatin remodeling factor lymphoid-specific helicase (LSH) in nasopharyngeal carcinoma (NPC), a prevalent cancer in China. LSH expression was increased in NPC, where it was controlled by the Epstein–Barr virus-encoded protein LMP1. In NPC cells in vitro and in vivo, LSH promoted cancer progression in part by regulating expression of fumarate hydratase (FH), a core component of the tricarboxylic acid cycle. LSH bound to the FH promoter, recruiting the epigenetic silencer factor G9a to repress FH transcription. Clinically, we found that the concentration of TCA intermediates in NPC patient sera was deregulated in the presence of LSH. RNAi-mediated silencing of FH mimicked LSH overexpression, establishing FH as downstream mediator of LSH effects. The TCA intermediates α-KG and citrate potentiated the malignant character of NPC cells, in part by altering IKKα-dependent EMT gene expression. In this manner, LSH furthered malignant progression of NPC by modifying cancer cell metabolism to support EMT. Cancer Res; 76(19); 5743–55. ©2016 AACR.
Phosphate Kinetics in Hemodialysis: Application of Delayed Pseudo One-Compartment Model
Authors: Poleszczuk Jan , Debowska Malgorzata , Wojcik-Zaluska Alicja , Ksiazek Andrzej , Zaluska Wojciech
Published: June 2016

Background/Aims: Various body-regulating mechanisms try to counteract rapid changes in serum phosphate levels during hemodialysis (HD). Neither recently proposed nor other existing standard compartment models are able to capture clinically observed intradialytic serum phosphate rebound. Methods: Phosphate serum concentration was frequently measured during 75 HD sessions in 25 patients. Time delay was introduced into the standard pseudo one-compartment model in order to reflect the time needed for the body-regulating mechanism to affect serum phosphate level. Results: Measured serum phosphate concentration at the end of 4 h dialysis session was on average larger than 1 h earlier (p value = 0.015). The model with time delay reproduced successfully 19 out of 21 and 9 out of 10 sessions with and without recorded intradialytic rebound, respectively. Conclusion: The intradialytic serum phosphate rebound is associated with the time delay reflecting efficacy of body-regulating mechanisms, that is, the larger the delay the larger is the intradialytic rebound.
Neonatal Haemophagocytic Lymphohistiocytosis Associated with Maternal Adult-Onset Still's Disease
Authors: Lin Anna , Ma Terence Ping Yuen , Cheng Frankie Wai Tsoi , Ng Pak Cheung
Published: June 2016

Neonatal haemophagocytic lymphohistiocytosis (HLH) is a rare but potentially lethal condition. We recently encountered a preterm infant who developed severe HLH associated with maternal adult-onset Still's disease, which to our knowledge has not been previously reported. The infant presented with fever, generalised lymphadenopathy, transient erythematous skin rash, hepatosplenomegaly, ascites, pancytopenia, marked hyperferritinaemia, and hypofibrinogenaemia, which were features similar to maternal presentation during late pregnancy. Whole gene exome sequencing screening for familial HLH (PRF1, STX11, STXBP2, and MUNC13D genes) was negative. We postulated that factors such as auto-antibodies, antigens, or inflammatory mediators transmitted vertically from the mother could have triggered the intense inflammation in the infant. The infant responded promptly to dexamethasone, etoposide, and cyclosporin A, without the need for bone marrow transplantation. Neonatologists should be alerted to the rare diagnosis of HLH in the presence of active maternal diseases, including infection or autoimmune conditions, especially in association with fever, cytopenia, and hepatosplenomegaly.
Increased Urokinase-Type Plasminogen Activator Receptor Expression on Circulating Monocytes Is Correlated with Clinical Instability and Long-Term Adverse Cardiac Events in Patients with Coronary Artery Disease
Authors: Zhang Yan , Chen Wei , Chen Lian-feng , Wang Xuan , Hsu Jeffrey , Fang Li-gang , Fang Quan
Published: June 2016

Objectives: This study sought to investigate the clinical correlates and prognostic roles of urokinase-type plasminogen activator receptor (uPAR) on circulating monocytes in patients with coronary artery disease (CAD). Methods: 263 angina patients were included in this study. The percentage of uPAR expressing monocytes (PUEM) and the mean fluorescence intensity (MFI) index of uPAR were measured using flow cytometry. Patient follow-up was on average 604 days. Major adverse cardiac events (MACE) were defined as a composite of cardiac death, reinfarction, acute heart failure and hospitalization for revascularization. Results: The PUEM and MFI index levels were significantly more elevated in acute coronary syndrome patients than in stable ones. uPAR expressions on circulating monocytes at admission were correlated to inflammatory biomarkers and myocardial necrosis. Logistic regression analysis revealed that PUEM ≥15% (OR 21.96, 95% CI 7.31-65.98, p < 0.001) and uPAR MFI index ≥3.00 (OR 3.54, 95% CI 1.18-10.59, p = 0.024) were independent determinants of clinical instability in patients with CAD. When followed up, a high PUEM level at admission was an independent prognostic parameter for long-term MACE (HR 3.99, 95% CI 1.31-12.11, p = 0.015). Conclusions: uPAR expression on circulating monocytes is associated with clinical instability and myocardial necrosis and independently predicts the risk of MACE in patients with CAD.
Prevalence of Mild Cognitive Impairment and Its Subtypes among Chinese Older Adults: Role of Vascular Risk Factors
Authors: Ma Fei , Wu Tianfeng , Zhao Jiangang , Ji Lu , Song Aili , Zhang Meilin , Huang Guowei
Published: June 2016

Background/Aims: The prevalence of mild cognitive impairment (MCI) and its subtypes among Chinese older adults, and the contribution of vascular risk factors (VRF) and vascular disorders to MCI remain unclear. This study aims to investigate the prevalence of MCI and its different subtypes, and clarify the role of VRF and vascular diseases in the occurrence of MCI. Methods: A random sample of 5,214 nondementia (DSM-IV) individuals aged ≥65 years underwent neuropsychological assessments and clinical examinations. MCI, including amnestic MCI-single domain (aMCI-SD), amnestic MCI-multiple domains (aMCI-MD), nonamnestic MCI-single domain (naMCI-SD), and nonamnestic MCI-multiple domains (naMCI-MD), was defined according to modifications of the Petersen criteria. VRF (smoking, obesity, and diabetes) and vascular disorders (myocardial infarction, atrial ﬁbrillation, stroke, and hypertension) were assessed based on information through self-report and medical records. Data were analyzed using multivariate logistic regression. Results: The prevalence of MCI was 11.33% (95% CI: 8.21-14.43), and that of aMCI-SD, aMCI-MD, naMCI-SD, and naMCI-MD was 4.48% (95% CI: 2.24-6.74), 2.09% (95% CI: 0.80-3.38), 4.22% (95% CI: 1.38-7.08), and 0.53% (95% CI: 0.32-0.75), respectively. The prevalence of MCI is higher in women than in men. Multivariate logistic regression analysis shows that VRF and vascular diseases were significantly related to increase the odds of MCI and its specific subtype. Conclusions: The prevalence of MCI is almost 11% among Chinese older adults. VRF and vascular disorders are associated with MCI, especially naMCI.
Listening to Schneiderian Voices: A Novel Phenomenological Analysis
Authors: Rosen Cherise , Chase Kayla A. , Jones Nev , Grossman Linda S. , Gin Hannah , Sharma Rajiv P.
Published: June 2016

Background/Aims: This paper reports on analyses designed to elucidate phenomenological characteristics, content and experience specifically targeting participants with Schneiderian voices conversing/commenting (VC) while exploring differences in clinical presentation and quality of life compared to those with voices not conversing (VNC). Methods: This mixed-method investigation of Schneiderian voices included standardized clinical metrics and exploratory phenomenological interviews designed to elicit in-depth information about the characteristics, content, meaning, and personification of auditory verbal hallucinations. Results: The subjective experience shows a striking pattern of VC, as they are experienced as internal at initial onset and during the longer-term course of illness when compared to VNC. Participants in the VC group were more likely to attribute the origin of their voices to an external source such as God, telepathic communication, or mediumistic sources. VC and VNC were described as characterological entities that were distinct from self (I/we vs. you). We also found an association between VC and the positive, cognitive, and depression symptom profile. However, we did not find a significant group difference in overall quality of life. Conclusions: The clinical portrait of VC is complex, multisensory, and distinct, and suggests a need for further research into the biopsychosocial interface between subjective experience, socioenvironmental constraints, individual psychology, and the biological architecture of intersecting symptoms.
Paternal Uniparental Disomy of Chromosome 14 with Hypospadias
Authors: Yuan Haiming , Xie Yingjun , Li Qian , Hu Xizi , Li Xinwei , Sun Xiaofang , Zhao Weiwei
Published: June 2016

Paternal uniparental disomy 14 (patUPD14) is a distinct, clinically recognizable syndrome. Using a clinical SNP microarray, we identified patUPD14 in a boy with a normal karyotype presenting cardiomyopathy and facial anomalies, a specific configuration of the thoracic ribs (‘coat hanger sign'), and hypospadias. Analyses of polymorphic microsatellites confirmed the diagnosis of patUPD14. We discuss the functions of the genes included in the rearrangement and their involvement in the pathogenesis of these disorders, especially hypospadias. ESR2 single nucleotide polymorphisms (rs944050; 2681-4A>G) have been associated with an increased risk of hypospadias in previous studies. The patient's ESR2 (rs944050) genotype is GG, whereas the parents both exhibit an AG genotype. This report sheds light on the genetic phenomenon in which the combination of a polymorphism and UPD can lead to new phenotypes, such as hypospadias.
Safety and Efficacy of a Novel Double-Stapling Technique for Distal Esophageal Resection and Esophago-Jejunal Anastomosis
Authors: Gentilli Sergio , Franchello Alessandro , Portigliotti Luca , Ferrari Maurizio , Oldani Alberto
Published: June 2016

Background: The purpose of this study was to evaluate safety and efficacy of a new esophagojejunal anastomosis (EJA) technique allowing the insertion of the anvil of a common circular stapler without hand-sewn securing. Methods: From August 2014 to May 2015, 20 consecutive patients with esophagogastric junction adenocarcinoma underwent surgery. EJA was performed using a new technique; the free margins of the esophageal stump were suspended and the anvil of a circular stapler on a new dedicated and registered support bar (characterized by a push-rod making possible to hook-unhook the anvil of the circular stapler) was inserted into the lumen. Subsequently, the linear suturing stapler was closed over the bar and fired to suture the distal stump of the esophagus; the bar was retracted and the push-rod of the anvil was pulled out through the linear suture. Finally, the anastomosis was performed using a circular stapler. Results: There were no intraoperative complications, and R0 resection was achieved in all cases. Postoperative course has been uneventful for 18 patients (90%). Only 1 patient (5%) developed fistula, conservatively treated. Conclusions: Our preliminary clinical experience suggested that this technique was safe and efficient (for all online suppl. material, see www.karger.com/doi/10.1159/000446856).
Modeling the Burden of Abdominal Aortic Aneurysm in the USA in 2013
Authors: Stuntz Mark
Published: June 2016

Objectives: Abdominal aortic aneurysm (AAA) is a pathological condition characterized by an abnormal, localized dilatation of the lower part of the aorta. Due to a lack of data on the natural history of AAA and risk of death from other cardiovascular diseases attributable to AAA, the true number of AAA-attributable deaths may be higher than currently estimated. This study aims to produce more realistic estimates of the burden of AAA. Methods: A disease-modeling software, DisMod II, was used to assess the AAA burden via a multistate life table. Inputs included population, all-cause mortality, size- and sex-specific AAA prevalence, and relative risk of death estimates for persons with AAA compared with persons without AAA. Results: There were 2,347,339 prevalent cases of AAA in the USA in 2013 (95% CI: 2,131,964-2,524,116), resulting in 41,371 deaths attributable to AAA (95% CI: 34,090-49,234). Females constituted 21.1% of prevalent cases and 45.2% of deaths, compared with males constituting 78.9% of prevalent cases and 54.8% of deaths. Conclusions: This work shows that the burden of mortality attributable to AAA is more than twice the current estimates from the American Heart Association. Females account for a disproportionately high percentage of deaths despite constituting a low percentage of prevalent cases.
The J-Curve Phenomenon in Hypertension
Authors: Kang Yuan-Yuan , Wang Ji-Guang
Published: June 2016

Almost immediately after antihypertensive therapy was proven effective in preventing cardiovascular events, the J-curve issue emerged as a hot topic. The Hypertension Optimal Treatment (HOT) trial attempted to address this question (diastolic blood pressure <80, <85, and <90 mm Hg) but ended up with a post hoc analysis indicating a nadir of 138.5 mm Hg systolic and 82.6 mm Hg diastolic blood pressure. Nevertheless, this observational finding was supported by the results of observational studies in the general population and by post hoc analyses of antihypertensive treatment trials. The currently ongoing Systolic Hypertension Optimal Treatment (SHOT) trial investigates whether the relationship between systolic blood pressure and stroke recurrence is linear or J-shaped by treating systolic blood pressure to <125, <135, and <145 mm Hg in patients with a history of recent stroke. This trial may provide additional but probably inconclusive evidence, because optimal blood pressure might differ between individuals and across outcomes. Nevertheless, a universal beneficial, instead of optimal, level of blood pressure for antihypertensive treatment may exist approximating 130/80 mm Hg and should be investigated by comparing 130/80 mm Hg with 140/90 mm Hg as a target blood pressure in hypertensive patients with the simultaneous use of modern blood pressure measuring techniques, such as home and ambulatory blood pressure monitoring.
The 100 Most-Cited Articles in Visceral Surgery: A Systematic Review
Authors: Müller Martin , Gloor Beat , Candinas Daniel , Malinka Thomas
Published: June 2016

Background: Even though citation analysis has several limitations, it is a commonly used tool to determine the impact of scientific articles in different research fields. Objective: The study aims to identify and systematically review the 100 most cited articles in the field of visceral surgery focusing on papers that modified therapeutic concepts and influenced the surgeons' decision making. Methods: The 100 most cited clinical articles in visceral surgery were identified using Journal Citation Reports and Science Citation Index Expanded of the Web of Science (Thomson Reuters, Philadelphia, Pa., USA). Data for characterization of the articles were determined: Number of citations, research topic, journal, publication time, authorship, country of origin, type of article and level of evidence if reasonable. Results: The 100 most cited articles were published in 17 journals; 72 articles were found in the 3 journals: New England Journal of Medicine (38), Annals of Surgery (21) and Lancet (13). The oldest article was published in 1908 in Annals of Surgery (ranked 76th) and the most recent in 2012 in Lancet (65th). Eighty articles were published between 1990 and 2010. The number of citations ranged from 667 to 4,666 (median 925). The leading country of origin was the United States with 39 articles, followed by articles originating from more than one country (30). There were 45 interventional studies (27 randomized controlled trials), 32 observational studies, 19 reviews and 4 guidelines, definitions or classifications. The level of evidence was low (IV) in 42 articles and high in 35 articles (Ia or Ib). A high number of citations did not reflect a high level of evidence. Conclusions: The topics and research questions of the identified articles covered a large area of visceral surgery. Some of the milestones in visceral surgery were identified. The high impact measured by citations did not reflect a high quality of research (level of evidence) in a considerable number of publications.
Appropriate Bowel Preparation for Laparotomy Gynecologic Surgery: A Prospective, Surgeon-Blinded Randomized Study
Authors: Suadee Wasakorn , Suprasert Prapaporn
Published: June 2016

Objective: To compare the surgeon's satisfaction during gynecological laparotomy surgery and patient's satisfaction as well as quality of life (QOL) among 3 groups of bowel preparations: no enema vs. sodium chloride enema vs. soap-suds enema (SSE). Materials and Method: Three hundred and thirty three women undergoing gynecological laparotomy surgery and without risks to bowel lumen entry between November 2014 and October 2015 were randomized to receive no enema (n = 111), sodium chloride enema (n = 111) or SSE (n = 111) for bowel preparation. Surgeons, who were blinded for the type of bowel preparation, assessed the surgical visualization and the efficacy of bowel packing. The patients' satisfaction and the QOL were also assessed on the days of admission, operation, post-operation, and discharge. Results: The patients' features of the 3 groups were well balanced. The surgeon's satisfaction was rated excellent as 56.8, 63.1 and 65.8% in the no-enema, sodium chloride and SSE groups (p = 0.830), respectively. The patients in the no-bowel-preparation group were satisfied more significantly than the other groups (p = 0.001). No significant differences in QOL were observed among the 3 groups. Conclusion: The type of bowel preparation for exploratory gynecologic surgery did not affect the surgical visualization and the QOL of the patients.
Primary Retroperitoneal Cystoadenocarcinoma: A Systematic Review
Authors: Pellegrino Benedetta , Sikokis Angelica , Bersanelli Melissa , Leonetti Alessandro , Leonardi Francesco , Di Meglio Giovanni , Buti Sebastiano
Published: June 2016

Background/Aims: The aim of this study was to perform a systematic review on primary retroperitoneal cystoadenocarcinoma (PRC), which is an extremely rare disease. Methods: According to PRISMA guidelines, all the literature about PRC from 1977 to 2015 was reviewed. Thirty articles were selected; characteristics of the patients were collected and described; time to recurrence and overall survival (OS) were investigated when available. Results: Thirty seven patients were included of whom 33 were females; the median age at presentation was 43. PRC was more common in postmenopausal women. Surgery was the standard therapy; the role of chemotherapy and/or radiotherapy was uncertain. Thirty percent of the patients relapsed after 58 months from the surgery; the rupture of the cyst occurred in 13% of the cases and it was associated with poor prognosis as well as premenopausal status. At 125 months from the diagnosis, 72% of the patients were alive and the median OS was not reached. Conclusions: The present systematic review about PRC is the first performed until the date of drafting this paper. We described some clinical features of PRC and their possible prognostic value. No conclusive data can be presented due to the small population analyzed and to publication bias.
Approaches to Cope with Stress and Depression in Individuals with Urinary Incontinence
Authors: Bilgic Dilek , Kızılkaya Beji Nezihe , Ozbas Ayfer , Cavdar İkbal , Yalcin Onay
Published: June 2016

Aim: The aim of study was to assess individuals with urinary incontinence (UI) with respect to depression and to determine coping mechanisms with stress. Methods: One hundred sixty female and 110 male participants that applied to Istanbul Faculty of Medicine, Urology and Urogynecology Department with UI complaints and accepted to participate in the study were included in the study. Depressive symptoms were assessed with Center for Epidemiological Studies Depression Scale (CES-D). The mechanisms of coping with stress were evaluated using Ways of Coping with Stress Inventory (WCSI). Results: Females (57.5%) scored 16 points and more from the CES-D scale, while the rate was significantly higher in males (79.1%). The scores obtained in 5 subdimensions of the WCSI showed that females utilized a desperate approach (female 1.39 ± 0.63, male 1.11 ± 0.51, p < 0.000), self-confident approach (female 1.98 ± 0.60, male 1.70 ± 0.42, p < 0.000), and social support approach (female 1.90 ± 0.57, male 1.48 ± 0.44, p < 0.000) statistically and significantly more than males in coping with stress. Conclusion: Males experienced more depression symptoms when compared to females. Females were significantly more self-confident and utilized social support mechanisms and desperate approaches more than males in order to cope with stress.
Real-Time qPCR-Based Detection of Circulating Tumor Cells from Blood Samples of Adjuvant Breast Cancer Patients: A Preliminary Study
Authors: Andergassen Ulrich , Zebisch Michael , Kölbl Alexandra C. , König Alexander , Heublein Sabine , Schröder Lennard , Hutter Stefan , Friese Klaus , Jeschke Udo
Published: June 2016

Background: Circulating tumor cells (CTCs) are cells that detach from a primary tumor, circulate through the blood stream and lymphatic vessels, and are considered to be the main reason for remote metastasis. Due to their origin, tumor cells have different gene expression levels than the surrounding blood cells. Therefore, they might be detectable in blood samples from breast cancer patients by real-time quantitative polymerase chain reaction (RT-qPCR). Materials and Methods: Blood samples of healthy donors and adjuvant breast cancer patients were withdrawn and the cell fraction containing white blood cells and tumor cells was enriched by density gradient centrifugation. RNA was isolated and reverse transcribed to cDNA, which was then used in TaqMan real-time PCR against cytokeratin (CK)8, CK18 and CK19. 18S and GAPDH were used as controls. Results: All 3 CKs were, on average, found to be significantly higher expressed in adjuvant breast cancer samples compared to negative controls, probably due to the presence of CTCs. Unfortunately, gene expression levels could not be correlated to tumor characteristics. Conclusions: RT-qPCR could make up a new approach for the detection of CTCs from blood samples of breast cancer patients, but a correlation of the PCR data to gold standard methods in CTC detection would help to further improve the informative value of the qPCR results.