bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphological ontogeny of Peloribates longipilosus (Acari, Oribatida, Haplozetidae)
Authors: Seniczak Stanisław , Seniczak Anna , Kaczmarek Sławomir
Published: March 2018

The morphological ontogeny of Peloribates longipilosus Csiszár, 1962, in Csiszár & Jeleva, 1962 is described and illustrated. The juveniles of this species have most prodorsal and gastronotal setae long and some gastronotal setae with excentrosclerites. The larva has 12 pairs of gastronotal setae, including h3, whereas the nymphs have 15 pairs. The larva has excentrosclerites at one pair of setae (c2), whereas nymphs have them at 11 pairs (c1,c2, d- l- and h-series). The notogaster of adult loses seta c3 and 14 pairs of long setae remain, and this setal pattern is the most primitive in Haplozetidae, other species have 10, 11 or 13 pairs of notogastral setae.
MyD88 Signaling in T Cells Is Critical for Effector CD4 T Cell Differentiation following a Transitional T Follicular Helper Cell Stage
Authors: Mandraju Rajakumar , Jain Aakanksha , Gao Yajing , Ouyang Zhiming , Norgard Michael V. , Pasare Chandrashekhar
Published: March 2018

Activation of CD4 T cells by dendritic cells leads to their differentiation into various effector lineages. The nature of the effector lineage is determined by the innate cues provided by dendritic cells to newly primed T cells. Although the cytokines necessary for several effector lineages have been identified, the innate cues that drive T follicular helper (Tfh) lineage cell development remain unclear. Here we found that following priming, CD4 T cells undergoing clonal expansion acquire a transient Tfh-like phenotype before differentiating into other effector lineages. In addition, we found that T cell-intrinsic myeloid differentiation antigen 88 (MyD88) signaling, which occurs downstream of interleukin-1 (IL-1) and IL-18 receptors, is critical for the primed CD4 T cells to transition out of the temporary Tfh lineage. Mice with T cell-specific deletion of MyD88 have a higher proportion of Tfh cells and germinal center (GC) B cells. These exaggerated Tfh cell and GC B cell responses, however, do not lead to protective immunity against infections. We demonstrate that T cell-intrinsic MyD88 is critical for effector lineage differentiation as well as production of the cytokines that are necessary for class switching. Overall, our study establishes that following priming and clonal expansion, CD4 T cells undergo a transitional Tfh-like phase and that further differentiation into effector lineages is dictated by T cell-intrinsic MyD88-dependent cues.
Effectiveness of implementation interventions in improving physician adherence to guideline recommendations in heart failure: a systematic review
Authors: Shanbhag Deepti , Graham Ian D , Harlos Karen , Haynes R. Brian , Gabizon Itzhak , Connolly Stuart J , Van Spall Harriette Gillian Christine
Published: March 2018

Background

The uptake of guideline recommendations that improve heart failure (HF) outcomes remains suboptimal. We reviewed implementation interventions that improve physician adherence to these recommendations, and identified contextual factors associated with implementation success.

Methods

We searched databases from January 1990 to November 2017 for studies testing interventions to improve uptake of class I HF guidelines. We used the Cochrane Effective Practice and Organisation of Care and Process Redesign frameworks for data extraction. Primary outcomes included: proportion of eligible patients offered guideline-recommended pharmacotherapy, self-care education, left ventricular function assessment and/or intracardiac devices. We reported clinical outcomes when available.

Results

We included 38 studies. Provider-level interventions (n=13 studies) included audit and feedback, reminders and education. Organisation-level interventions (n=18) included medical records system changes, multidisciplinary teams, clinical pathways and continuity of care. System-level interventions (n=3) included provider/institutional incentives. Four studies assessed multi-level interventions. We could not perform meta-analyses due to statistical/conceptual heterogeneity. Thirty-two studies reported significant improvements in at least one primary outcome. Clinical pathways, multidisciplinary teams and multifaceted interventions were most consistently successful in increasing physician uptake of guidelines. Among randomised controlled trials (RCT) (n=10), pharmacist and nurse-led interventions improved target dose prescriptions. Eleven studies reported clinical outcomes; significant improvements were reported in three, including a clinical pathway, a multidisciplinary team and a multifaceted intervention. Baseline assessment of barriers, staff training, iterative intervention development, leadership commitment and policy/financial incentives were associated with intervention effectiveness. Most studies (n=20) had medium risk of bias; nine RCTs had low risk of bias.

Conclusion

Our study is limited by the quality and heterogeneity of the primary studies. Clinical pathways, multidisciplinary teams and multifaceted interventions appear to be most consistent in increasing guideline uptake. However, improvements in process outcomes were rarely accompanied by improvements in clinical outcomes. Our work highlights the need for improved research methodology to reliably assess the effectiveness of implementation interventions.
What is the value of fibre-endoscopic evaluation of swallowing (FEES) in neurological patients? A cross-sectional hospital-based registry study
Authors: Braun Tobias , Juenemann Martin , Viard Maxime , Meyer Marco , Fuest Sven , Reuter Iris , Kaps Manfred , Prosiegel Mario , Tanislav Christian
Published: March 2018

Objectives

Fibre-endoscopic evaluation of swallowing (FEES) to detect dysphagia is gaining more and more importance as a diagnostic tool. Therefore, we have investigated the impact of FEES in neurological patients in a clinical setting.

Design

Cross-sectional hospital-based registry.

Setting

Primary acute care in a neurological department of a German university hospital.

Participants

241patients with various neurological diseases who underwent FEES procedure.

Primary and secondary outcome measures

Dysphagia and related comorbidities.

Results

267 FEES were performed in 241 patients with various neurological diagnoses. Dysphagia was diagnosed in 68.9% of the patients. In only 33.1% of the patients, appropriate oral diet was chosen prior to FEES. A relevant dysphagia occurred more often in patients with structural brain lesions (83.1% vs 65.3%, P=0.001), patients with dysphagia had a longer hospitalisation (median 18 (IQR 12–30) vs 15 days (IQR 9.75–22.75), P=0.005) and had a higher mortality (8.4% vs 1.3%, P=0.041). When the oral diet was changed, we observed a lower pneumonia rate (36% vs 50%, P=0.051) and a lower mortality (3.7% vs 11.3%, P=0.043) in comparison to no change of oral diet. A restriction of oral diet was identified more often in older patients (median 75 years (IQR 66.3–82 years) vs median 72 years (IQR 60–79 years), P=0.01) and in patients with structural brain lesions (86.8% vs 73.1%, P=0.05).

Conclusion

On clinical investigation, dysphagia was misjudged for the majority of the patients. FEES might help to compensate this drawback, revising the diet regime in nearly 70% of the patients.
The influence of hazardous drinking on psychological functioning, stress and sleep during and after treatment in patients with mental health problems: a secondary analysis of a randomised controlled intervention study
Authors: Strid Catharina , Andersson Claes , Öjehagen Agneta
Published: March 2018

Objectives

Hazardous drinking could negatively affect health and lead to alcohol use disorders, but it is unclear how hazardous drinking affects treatment outcomes of depression and anxiety and stress-related mental health problems. The aim of this study was to examine whether hazardous drinking, measured by Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), influences the outcomes of repeated assessments of psychological functioning (Outcome Questionnaire-45), stress (Perceived Stress Scale) and sleep (Karolinska Sleep Questionnaire), during and after treatment in patients with mental ill health.

Methods

The study was conducted within REGASSA, a randomised controlled trial aimed at comparing Internet-based cognitive–behaviour therapy and physical exercise with treatment as usual on primary care patients with mental ill health. The study involved 871 participants who completed the AUDIT at baseline and who were assessed repeatedly during and after treatment on psychological functioning, stress and sleep by interactive voice response, a computerised, automated telephone technology.

Results

At baseline, hazardous drinkers were more depressed and had lower scores on psychological functioning than non-hazardous drinkers, while there were no differences on stress and sleep. During the follow-ups, hazardous drinking negatively influenced perceived stress, that is, hazardous drinkers seemed to have less treatment effect on stress, and the results remained after controlling for depression. There were no differences during the follow-ups regarding psychological functioning and sleep.

Conclusions

Hazardous drinking negatively influenced perceived stress. The findings of the study emphasise the importance of screening for alcohol habits in mental ill-health patients, since risky drinking may affect the outcomes of treatment.

Trial registration number

DRKS00008745; Post-results.
Treatment effects of systematic two-stent and provisional stenting techniques in patients with complex coronary bifurcation lesions: rationale and design of a prospective, randomised and multicentre DEFINITION II trial
Authors: Zhang Jun-Jie , Gao Xiao-Fei , Han Ya-Ling , Kan Jing , Tao Ling , Ge Zhen , Tresukosol Damras , Lu Shu , Ma Li-Kun , Li Feng , Yang Song , Zhang Jun , Munawar Muhammad , Li Li , Zhang Rui-Yan , Zeng He-Song , Santoso Teguh , Xie Ping , Jin Ze-Ning , Han Leng , Yin Wei-Hsian , Qian Xue-Song , Li Qi-Hua , Hong Lang , Paiboon Chotnoparatpat , Wang Yan , Liu Li-Jun , Zhou Lei , Wu Xue-Ming , Wen Shang-Yu , Lu Qing-Hua , Yuan Jun-Qiang , Chen Liang-Long , Lavarra Francesco , Rodríguez Alfredo E , Zhou Li-Min , Ding Shi-Qin , Vichairuangthum Kitigon , Zhu Yuan-Sheng , Yu Meng-Yue , Chen Chan , Sheiban Imad , Xia Yong , Tian Yu-Long , Shang Zheng-Lu , Jiang Qing , Zhen Yong-Hong , Wang Xin , Ye Fei , Tian Nai-Liang , Lin Song , Liu Zhi-Zhong , Chen Shao-Liang
Published: March 2018

Introduction

Provisional stenting (PS) for simple coronary bifurcation lesions is the mainstay of treatment. A systematic two-stent approach is widely used for complex bifurcation lesions (CBLs). However, a randomised comparison of PS and two-stent techniques for CBLs has never been studied. Accordingly, the present study is designed to elucidate the benefits of two-stent treatment over PS in patients with CBLs.

Methods and analysis

This DEFINITION II study is a prospective, multinational, randomised, endpoint-driven trial to compare the benefits of the two-stent technique with PS for CBLs. A total of 660 patients with CBLs will be randomised in a 1:1 fashion to receive either PS or the two-stent technique. The primary endpoint is the rate of 12-month target lesion failure defined as the composite of cardiac death, target vessel myocardial infarction (MI) and clinically driven target lesion revascularisation. The major secondary endpoints include all causes of death, MI, target vessel revascularisation, in-stent restenosis, stroke and each individual component of the primary endpoints. The safety endpoint is the occurrence of definite or probable stent thrombosis.

Ethics and dissemination

The study protocol and informed consent have been approved by the Institutional Review Board of Nanjing First Hospital, and accepted by each participating centre. Written informed consent was obtained from all enrolled patients. Findings of the study will be published in a peer-reviewed journal and disseminated at conferences.

Trial registration number

NCT02284750; Pre-results.
Reducing distress and improving social functioning in daily life in people with auditory verbal hallucinations: study protocol for the ‘Temstem’ randomised controlled trial
Authors: Jongeneel Alyssa , Scheffers Dorien , Tromp Nynke , Nuij Chani , Delespaul Philippe , Riper Heleen , van der Gaag Mark , van den Berg David
Published: March 2018

Introduction

Auditory verbal hallucinations (AVH) are prevalent experiences that can induce distress and impede social functioning. While most voice hearers benefit from antipsychotic medication or cognitive–behavioural therapy, additional effective interventions are needed to reduce the burden of experiencing AVH. ‘Temstem’ is an easily accessible and useable smartphone application that was developed by designers in close cooperation with voice hearers and experts. By using language games, Temstem aims to reduce distress and improve social functioning.

Methods

This is a single-blind multicentre randomised controlled trial with two arms: ‘Temstem+AVH monitoring’ versus ‘AVH monitoring’ (total n=100). Participants are adult patients who suffer daily from AVH and will be recruited in outpatient units. Primary assessment in daily life is made by the Experience Sampling Method (ESM) and daily monitoring with the PsyMate app. During an ESM period of 6 days, participants assess their mental state (including AVH and context) several times a day by filling in short questionnaires. There are three 6-day ESM periods: at baseline (week 0–1), post-treatment (weeks 5–6) and follow-up (weeks 9–10). In addition, during the entire 10-week study period, all participants monitor their AVH two times a day with a short assessment via the PsyMate app. Participants in the Temstem+AVH monitoring condition are provided with the Temstem app from week 1 to 6. Other assessments made at baseline, post-treatment and follow-up are based on questionnaires and a clinical interview.

Ethics and dissemination

The results from this study will provide an evaluation of the effectiveness of Temstem, a non-invasive and easily accessible app for voice hearers, and insight into the determinants of optimal use. Results will be disseminated unreservedly, irrespective of the magnitude or direction of the effects. This study protocol was approved by the Medical Ethics Committee of the VU University Medical Centre (METC number: 2015.435/NL53684.029.15).

Trial registration number

ISRCTN75717636; Pre-results.
Prognosis prediction with two calculations of Palliative Prognostic Index: further prospective validation in hospice cancer patients with multicentre study
Authors: Subramaniam Sivakumar , Dand Pauline , Ridout Martin , Cawley Declan , Miller Sophie , Valli Paola , Bright Rebecca , O’Neill Brendan , Wilcocks Tricia , Parker Georgina , Harris Dee
Published: March 2018

Objectives

In palliative care settings, predicting prognosis is important for patients and clinicians. The Palliative Prognostic Index (PPI), a prognostic tool calculated using clinical indices alone has been validated within cancer population. This study was to further test the discriminatory ability of the PPI (ie, its ability to determine whether a subject will live more or less than a certain amount of time) in a larger sample but with a palliative care context and to compare predictions at two different points in time.

Methods

Multicentre, prospective, observational study in 10 inpatient hospices in the UK. The PPI score was calculated on the day of admission (PPI1) and again once on days 3–5 of inpatient stay (PPI2). Patients were followed up for 6 weeks or until death, whichever was earlier.

Results

Of the 1164 patients included in the study, 962 had both scores available. The results from PPI2showed improved sensitivity, specificity, positive predictive value and negative predictive value compared with PPI1. For PPI1versus PPI2, area under receiver operator character curve (ROC) for <21 days were 0.73 versus 0.82 and for ≥42 days prediction 0.72 versus 0.80. The median survival days for patients with PPI1≤4, 4.5–6 and >6 were 38 (31 to 44), 17 (14 to 19) and 5 (4 to 7).

Conclusion

This study showed improved discriminatory ability using the PPI score calculated between day 3and day5 of admission compared with that calculated on admission. This study further validated PPI as a prognostic tool within a palliative care population and showed recording at two time points improved accuracy.
Cerebellar Purkinje cell degeneration in a mule foal (Equus mulus mulus)
Authors: Suñol Anna , Sanmarti Fierro Julia , Foiani Greta , Morales Carles , Montoliu Patricia
Published: March 2018

A case of a mule foal with cerebellar Purkinje cell degeneration is described. A one‐day‐old mule foal was presented with lateral recumbency, obtunded mentation, poor metabolic status (general weakness, congestive mucous membranes, tachycardia, weak pulse, hypomotility and hypothermia) and cerebellar signs. After receiving medical treatment, the foal’s overall condition markedly improved but severe cerebellar ataxia and intention tremors were still present. Three weeks later, physical examination was normal but neurological signs had worsened and the foal was subjected to euthanasia. Postmortem findings revealed lesions consistent with corticocerebellar Purkinje cell degeneration. This is the first case report describing this condition in a mule.
Generic transformation models for some intact rock properties
Authors: Ching Jianye , Li Kuang-Hao , Phoon Kok-Kwang , Weng Meng-Chia
Published: March 2018

A global intact rock database of nine parameters, including uniaxial compressive strength and Young’s modulus, is compiled from 184 studies. This database, labeled as “ROCK/9/4069”, consists of 27.5% igneous rock, 59.4% sedimentary rock, and 13.1% metamorphic rock. The vast majority (>95%) of intact rocks in the database are in their natural moisture contents. About 14% of the data points are for weathered rocks and about 4% are foliated metamorphic rock. It is found that most existing transformation models are data-specific or site-specific in the sense that they fit well to their own calibration databases, but do not necessarily fit well to ROCK/9/4069. One can infer that transformation models for intact rocks are more data–site dependent than those for soils. It is evident that ROCK/9/4069 has coverage wider than most existing transformation models. The ROCK/9/4069 database is then adopted to calibrate the bias and variability of existing transformation models. Transformation models with relatively large application ranges and relatively small transformation uncertainties are selected as generic transformation models. These generic models can be valuable for scenarios where site-specific models are not available, e.g., construction projects with insufficient budget or the preliminary design stage of a project.
Vildagliptin/pioglitazone combination improved the overall glycemic control in type I diabetic rats
Authors: Abdelhamid Amir Mohamed , Abdelaziz Rania Ramadan , Salem Hatem Abdelrahman Ali
Published: March 2018

Type I diabetes (TID) is generally assumed to be caused by an immune associated, if not directly immune-mediated, destruction of pancreatic β-cells. In patients with long-term diabetes, the pancreas lacks insulin-producing cells and the residual β-cells are unable to regenerate. Patients with TID are subjected to a lifelong insulin therapy which shows risks of hypoglycemia, suboptimal control and ketosis. In this study, we investigated the potential role of vildagliptin (Vilda) alone or in combination with pioglitazone (Pio), as treatment regimens for TID using streptozotocin (STZ)-induced TID model in rats. Daily oral administration of Vilda (5 mg/kg) alone or in combination with Pio (20 mg/kg) for 7 weeks significantly reduced blood glucose levels and HbA1c. It increased serum insulin levels and decreased serum glucagon. It also showed a strong antioxidant activity. Immunohistochemical analysis showed a marked improvement in β-cells in treated groups when compared with the diabetic group, which appeared in the normal cellular and architecture restoration of β-cells in the islets of Langerhans. Vilda alone or in combination with Pio has the ability to improve the overall glycemic control in type I diabetic rats and may be considered a hopeful and effective remedy for TID.
The von Hippel–Lindau Tumor Suppressor Protein
Authors: Kaelin William G.
Published: March 2018

The von Hippel–Lindau (VHL) gene is a two-hit tumor suppressor gene and is linked to the development of the most common form of kidney cancer, clear cell renal carcinoma; blood vessel tumors of the retina, cerebellum, and spinal cord called hemangioblastomas; and tumors of the sympathoadrenal nervous system called paragangliomas. The VHL gene product, pVHL, is the substrate recognition subunit of a cullin-dependent ubiquitin ligase that targets the α subunits of hypoxia-inducible factor (HIF) for destruction when oxygen is plentiful. Mounting evidence implicates HIF2 in the pathogenesis of pVHL-defective tumors and has provided a conceptual foundation for the development of drugs to treat them that inhibit HIF2-responsive gene products such as VEGF and, more recently, HIF2 itself. pVHL has additional, noncanonical functions that are cancer relevant, including roles related to the primary cilium, chromosome stability, extracellular matrix formation, and survival signaling.
Reduced skeletal muscle phosphocreatine concentration in type 2 diabetic patients: a quantitative image-based phosphorus-31 MR spectroscopy study
Authors: Ripley Erika M. , Clarke Geoffrey D. , Hamidi Vala , Martinez Robert A. , Settles Floyd D. , Solis Carolina , Deng Shengwen , Abdul-Ghani Muhammad , Tripathy Devjit , DeFronzo Ralph A.
Published: March 2018

Mitochondrial function has been examined in insulin-resistant (IR) states including type 2 diabetes mellitus (T2DM). Previous studies using phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in T2DM reported results as relative concentrations of metabolite ratios, which could obscure differences in phosphocreatine ([PCr]) and adenosine triphosphate concentrations ([ATP]) between T2DM and normal glucose tolerance (NGT) individuals. We used an image-guided 31P-MRS method to quantitate [PCr], inorganic phosphate [Pi], phosphodiester [PDE], and [ATP] in vastus lateralis (VL) muscle in 11 T2DM and 14 NGT subjects. Subjects also received oral glucose tolerance test, euglycemic insulin clamp, 1H-MRS to measure intramyocellular lipids [IMCL], and VL muscle biopsy to evaluate mitochondrial density. T2DM subjects had lower absolute [PCr] and [ATP] than NGT subjects (PCr 28.6 ± 3.2 vs. 24.6 ± 2.4, P < 0.002, and ATP 7.18 ± 0.6 vs. 6.37 ± 1.1, P < 0.02) while [PDE] was higher, but not significantly. [PCr], obtained using the traditional ratio method, showed no significant difference between groups. [PCr] was negatively correlated with HbA1c ( r = −0.63, P < 0.01) and fasting plasma glucose ( r = −0.51, P = 0.01). [PDE] was negatively correlated with Matsuda index ( r = −0.43, P = 0.03) and M/I ( r = −0.46, P = 0.04), but was positively correlated with [IMCL] ( r = 0.64, P < 0.005), HbA1c, and FPG ( r = 0.60, P = 0.001). To summarize, using a modified, in vivo quantitative 31P-MRS method, skeletal muscle [PCr] and [ATP] are reduced in T2DM, while this difference was not observed with the traditional ratio method. The strong inverse correlation between [PCr] vs. HbA1c, FPG, and insulin sensitivity supports the concept that lower baseline skeletal muscle [PCr] is related to key determinants of glucose homeostasis.
Image Quality Assessment Based on Joint Quality-Aware Representation Construction in Multiple Domains
Authors: Shang Xiaobao , Zhao Xinyu , Ding Yong
Published: March 2018

Image quality assessment that aims to evaluate the image quality automatically by a computational model plays a significant role in image processing systems. To meet the need of accuracy and effectiveness, in the proposed method, complementary features including histogram of oriented gradient, edge information, and color information are employed for joint representation of the image quality. Afterwards, the dissimilarities of the extracted features between the distorted and reference images are quantified. Finally, support vector regression is used for distortion indices fusion and objective quality mapping. Experimental results validate that the proposed method outperforms the state-of-the-art methods in terms of consistency with subjective perception and robustness across various databases and different distortion types.
Matrix Metalloproteinase-9 Is a Predictive Factor for Systematic Hypertension and Heart Dysfunction in Patients with Obstructive Sleep Apnea Syndrome
Authors: Wang Shuhui , Li Shisheng , Wang Bin , Liu Jiajia , Tang Qinglai
Published: March 2018

Patients with obstructive sleep apnea syndrome (OSAS) showed higher prevalence in cardiovascular diseases due to aberrant hypoxia and oxidative stress. However, not all OSAS patients end up with cardiovascular disorders, and identification of novel biomarker will be invaluable for differentiating patients at risk. Here we tested the serum matrix metalloproteinase-9 (MMP-9) levels in 47 untreated OSAS patients and found that the MMP-9 level was positively correlated with severity of OSAS, which was consistent with hypoxia degree and duration. Besides, the MMP-9 level was higher in patients complicated with systematic hypertension (P < 0.001). Furthermore, we selected those OSAS patients without any cardiovascular dysfunction (n=35) and followed up for up to five years. By the end of follow-up, 12 patients had hypertension onset and 3 patients had left ventricular hypertrophy. By analyzing the clinical outcomes with MMP-9 expression, we demonstrated that high serum MMP-9 in OSAS patients was a risk factor for occurrence of cardiovascular diseases. In addition, we cultured the vascular endothelial cells (VEC) from rat aorta in hypoxia condition to investigate whether MMP-9 was elevated due to hypoxia in OSAS patients. Cellular results revealed that the expression, secretion, and activity of MMP-9 were all upregulated by hypoxia and can cleave the beta2-adrenergic receptor (β2AR) on VEC surface. Our results not only determined MMP-9 as a risk factor for cardiovascular diseases in OSAS patients, but also showed the possible involvement of hypoxia-MMP-9-β2AR signaling axis.
Bioaccumulation of Heavy Metals in Water, Sediments, and Tissues and Their Histopathological Effects on Anodonta cygnea (Linea, 1876) in Kabul River, Khyber Pakhtunkhwa, Pakistan
Authors: Khan Muhammad Iftikhar , Khisroon Muhammad , Khan Ajmal , Gulfam Naila , Siraj Muhammad , Zaidi Farrah , Ahmadullah  , Abidullah  , Fatima Syeda Hira , Noreen Shumaila , Hamidullah  , Shah Zafar Ali , Qadir Fazli
Published: March 2018

The present investigation aimed to assess the concentrations of selected heavy metals in water and sediments and their bioaccumulation in tissues of freshwater mussels and their histopathological effects on the digestive gland, gills, and gonads of Anodonta cygnea. Water, sediments, and freshwater mussel samples were collected at four sites, that is, reference and polluted sites, along the Kabul River, Khyber Pakhtunkhwa. The polluted sites were receiving effluents from the industrial, agricultural, municipal, and domestic sources. The order of metals in the water was Zn>Pb>Ni>Cu>Mn>Fe>Cr>Cd, in sediments the order was Fe>Zn>Cr>Ni>Mn>Pb>Cu>Cd, and in the soft tissues the order was Fe>Zn>Mn>Pb>Cu>Cr>Ni>Cd. Histopathological alterations observed in polluted sites of Kabul River were inflammation, hydropic vacuolation, and lipofuscin pigments (in digestive gland), gill lamellar fusion, dilated hemolymphatic sinus, clumping, and generation of cilia and hemocytic infiltration (in gills), and atresia, necrosis, granulocytoma, hemocytic infiltration, and lipofuscin pigments (in gonads). The histopathological alterations in the organs of Anodonta cygnea can be considered as reliable biomarkers in biomonitoring of heavy metal pollution in aquatic ecosystems.
Neuronal Proteomic Analysis of the Ubiquitinated Substrates of the Disease-Linked E3 Ligases Parkin and Ube3a
Authors: Martinez Aitor , Ramirez Juanma , Osinalde Nerea , Arizmendi Jesus M. , Mayor Ugo
Published: March 2018

Both Parkin and UBE3A are E3 ubiquitin ligases whose mutations result in severe brain dysfunction. Several of their substrates have been identified using cell culture models in combination with proteasome inhibitors, but not in more physiological settings. We recently developed theUbbiostrategy to isolate ubiquitinated proteins in flies and have now identified by mass spectrometry analysis the neuronal proteins differentially ubiquitinated by those ligases. This is an example of how flies can be used to provide biological material in order to reveal steady state substrates of disease causing genes. Collectively our results provide new leads to the possible physiological functions of the activity of those two disease causing E3 ligases. Particularly, in the case of Parkin the novelty of our data originates from the experimental setup, which is not overtly biased by acute mitochondrial depolarisation. In the case of UBE3A, it is the first time that a nonbiased screen for its neuronal substrates has been reported.
Suppression of IL-6 Gene by shRNA Augments Gemcitabine Chemosensitization in Pancreatic Adenocarcinoma Cells
Authors: Xing Hai-Bo , Tong Meng-Ting , Wang Jing , Hu Hong , Zhai Chong-Ya , Huang Chang-Xin , Li Da
Published: March 2018

Pancreatic adenocarcinoma has an exceedingly poor prognosis, accounting for five-year survival of less than 5%. Presently, improving the efficacy of pancreatic adenocarcinoma treatment has been the focus of medical researchers worldwide. Recently, it has been suggested that deregulation of interleukin- (IL-) 6 is caused by a key gene involved in the beginning and development of pancreatic adenocarcinoma. Herein, we investigated whether suppression of IL-6 could augment gemcitabine sensitivity in the PANC-1 cells. We found considerably higher expression of IL-6 in pancreatic adenocarcinoma tissues than that in the adjacent nontumorous tissues. Suppression of IL-6 by shRNA resulted in apoptosis as well as inhibition of cell proliferation and tumorigenicity. In addition, suppression of IL-6 remarkably promoted antitumor effect of gemcitabine, indicating that the combination of shRNA targeting IL-6 with gemcitabine may provide a potential clinical approach for pancreatic cancer therapy.
Modelling Cooperative Tumorigenesis inDrosophila
Authors: Richardson Helena E. , Portela Marta
Published: March 2018

The development of human metastatic cancer is a multistep process, involving the acquisition of several genetic mutations, tumour heterogeneity, and interactions with the surrounding microenvironment. Due to the complexity of cancer development in mammals, simpler model organisms, such as the vinegar fly,Drosophila melanogaster, are being utilized to provide novel insights into the molecular mechanisms involved. In this review, we highlight recent advances in modelling tumorigenesis using theDrosophilamodel, focusing on the cooperation of oncogenes or tumour suppressors, and the interaction of mutant cells with the surrounding tissue in epithelial tumour initiation and progression.
Comorbidities and Ethnocultural Factors Limit the Physical Activity of Rural Sri Lankan Patients with Diabetes Mellitus
Authors: Medagama Arjuna , Galgomuwa Manoj
Published: March 2018

South Asians have high prevalence of diabetes, cardiovascular risk, and physical inactivity. Reasons for physical inactivity have not been explored among Asians living within their endogenous environments. During phase 1 of the study, we assessed the physical activity (PA) of the population using a quantitative, descriptive, cross-sectional research method. During phase 2 of the study, a qualitative method with in-depth interviews was used to collect data on barriers of PA. Four hundred patients with type 2 diabetes, comprising 113 (28.2%) males and 287 (71.7%) females, were enrolled. The overall prevalence of physical inactivity was 21.5% (males: 15.9%, females: 23.7%). The majority (44.8%) of the study population was active and 33.8% were minimally active. The mean weekly MET minutes was 4381.6 (SD 4962). The qualitative study (n=45) identified health-related issues—lifestyle and time management and social embarrassment, prioritizing household activities over PA as significant factors that limited PA.
Numerical Research on Convective Heat Transfer and Resistance Characteristics of Turbulent Duct Flow Containing Nanorod-Based Nanofluids
Authors: Yuan Fangyang , Lin Jianzhong , Yu Jianfeng
Published: March 2018

A coupled numerical model for nanorod-based suspension flow is constructed, and the convective heat transfer and resistance characteristics of the nanofluid duct flow are investigated. The numerical results are verified by experimental results and theoretical models. Most of nanorods are located randomly in the bulk fluid, while particles near the wall aligned with the flow direction. Friction factor of nanofluids with nanorods increases with higher particle volume concentration or aspect ratio, but the increment reduces when the Reynolds number gets larger. The relative Nusselt number is obtained to characterize the intensity of convective heat transfer. The results show that the Nusselt number of nanofluids increases when the particle volume concentration or aspect ratio becomes larger. Compared to increasing the aspect ratio of nanorods, increasing the particle volume concentration would be more effective on enhancing the convective heat transfer intensity in industrial applications although it will cause a slight increase of resistance.
Predictive Factors of Secondary Normocalcemic Hyperparathyroidism after Roux-en-Y Gastric Bypass
Authors: Casella Claudio , Molfino Sarah , Mittempergher Francesco , Cappelli Carlo , Portolani Nazario
Published: March 2018

Objective. Aim of this study is to evaluate determinants of secondary normocalcemic hyperparathyroidism (SNHPT) persistence in patients who have undergone Roux-en-Y gastric bypass on vertical-banded gastroplasty.Methods. 226 consecutive patients submitted to bariatric surgery were prospectively enrolled and divided in two groups on the basis of preoperative presence of SNHPT. For each patient, we evaluated anthropometric and laboratory parameters. Calcium metabolism (calcemia, PTH, and 25-hydroxy vitamin D serum levels) was studied before surgery and at 6-month intervals (6, 12, and 18 months) as surgical follow-up.Results. Based on presurgical SNHPT presence or absence, we definedgroup 1—201 patients andgroup 2—25 patients, respectively. Among thegroup 1, 153 (76%) recovered from this endocrinopathy within 6 months after surgery (group 3), while the remaining 48 patients (24%) had persistent SNHPT (group 4). Comparing the anthropometric and laboratory data ofgroup 3withgroup 2, the only statistically significant factor was the elapsed time since a prior effective medically controlled diet that led to a steady and substantial weight loss. We found also a statistically significant difference (p<0.05) betweengroup 3andgroup 4in term of % of weight loss and PTH levels.Conclusions. Patients suitable for bariatric surgery must have history of at least one efficient medically controlled diet, not dating back more than 5 years before surgery. This elapsed time represent the cut-off time within which it is possible to recover from SNHPT in the first semester after Roux-en-Y gastric bypass on vertical-banded gastroplasty. The treatment of vitamin D insufficiency and the evaluation of SNHPT before bariatric surgery should be recommended. The clinical significance of preoperative SNHPT and in particular SNHPT after bariatric surgery remains undefined and further studies are required.
Effect of Lead on Human Middle Ear Epithelial Cells
Authors: Kim Shin Hye , Shin Sun Hwa , Go Yoon Young , Chae Sung-Won , Song Jae-Jun
Published: March 2018

Lead is a ubiquitous metal in the environment, but no studies have examined lead toxicity on the middle ear. Here, we investigated lead toxicity and its mechanism in human middle ear epithelial cells (HMEECs). Moreover, we investigated the protective effects of amniotic membrane extract (AME) and chorionic membrane extract (CME) against lead toxicity in HMEECs. Cell viability was analyzed using the cell counting kit, and reactive oxygen species (ROS) activity was measured using a cellular ROS detection kit. After lead(II) acetate trihydrate treatment, mRNA levels of various genes were assessed by semiquantitative real-time polymerase chain reaction. Following treatment with AME or CME after lead exposure, the changes in cell viability, ROS activity, and gene expression were analyzed. Exposure to >100 μg/mL of lead(II) acetate trihydrate caused a significant decrease in cell viability and increased ROS production in HMEECs. Lead exposure significantly increased the mRNA expression of genes encoding inflammatory cytokines and mucins. Administration of AME or CME restored cell viability, reduced ROS activity, and ameliorated mRNA levels. Our findings suggest that environmental lead exposure is related to the development of otitis media, and AME and CME may have antioxidative and anti-inflammatory effects against lead toxicity.
Myopia Progression Risk: Seasonal and Lifestyle Variations in Axial Length Growth in Czech Children
Authors: Rusnak Stepan , Salcman Vaclav , Hecova Lenka , Kasl Zdenek
Published: March 2018

The growth in the prevalence of myopia leads to the growth of socioeconomic stress in society. It is important to detect any potential risk factors leading to myopia onset and progression. Among the potential risk factors, the lack of natural daylight exposure and the lack of the physical activity together with excess of near-work activities in children are the most prevalent. In the study, the axial length growth depending on the season and the type of behaviour was measured. The assessment was performed in 12-year-old children, 398 eyes of whom were included and measured during the winter and summer period. The children were categorized by the amount of time spent on near-work, physical, and outdoor activity. Results. Statistically significantly higher (p<0.0001) axial length growth was observed during the winter period. Statistically significantly (p<0.0001) more frequently, the eyeball growth has been proved during the winter season. According to the way of spending leisure time, no statistically significant difference was reported within the individual subgroups in the development of the eyeball length during the observed period. However, statistically significant differences were ascertained in the eyeball initial length within various groups. Conclusion. The lack of daylight exposure may lead to myopia progression.
CT and MRI Findings of Soft Tissue Adult Fibrosarcoma in Extremities
Authors: Wang Hexiang , Nie Pei , Dong Cheng , Li Jie , Huang Yonghua , Hao Dapeng , Xu Wenjian
Published: March 2018

Objective. To characterize and evaluate CT and MRI features of extremity soft tissue adult fibrosarcoma. Methods. CT and MRI images from 10 adult patients with pathologically proven fibrosarcomas were retrospectively analyzed with regard to tumor location, size, number, shape, margins, attenuation, signal intensity, and enhancement patterns on MR images. Additionally, the relationships between lesions, deep fascia, and change in adjacent bones were also assessed. Results. Nineteen tumor lesions in 10 patients were selected for this study. Eighteen lesions were lobulated and one was oval in shape. Most cases were located under the deep fascia, including seven cases that had a nodular lump adjacent to the deep fascia and one case that had broken lesion through the deep fascia. On CT, the adult fibrosarcomas mostly showed iso-attenuated soft tissue masses (n=6). On MRI, all the cases (n=9) displayed low signal on T1-weighted imaging (T1WI) and heterogeneous low and high intensity signals on T2-weighted imaging (T2WI), with band-like areas of low signal on both T1WI and T2WI. On contrast-enhanced MRI images, three cases showed heterogeneous peripheral enhancement and one case demonstrated a spoke-wheel-like enhancement. Eight cases showed muscle edema signals in the peritumoral muscle and one case involved adjacent bone. Conclusion. CT and MR imaging have respective advantages in diagnosing adult fibrosarcoma. Combined application of CT and MR is recommended for patients with suspected adult fibrosarcoma.
A Novel Bimodal Imaging Agent Targeting HER2 Molecule of Breast Cancer
Authors: Lv Wei , Shen Yamei , Yang Hengli , Yang Rui , Cai Wenbin , Zhang Jian , Yuan Lijun , Duan Yunyou , Zhang Li
Published: March 2018

Nanobubble (NB), a newly developed nanoscaled ultrasound contrast agent (UCA) for molecular imaging, has been widely researched for these years. Targeting it with functional molecule, nanobubble can adhere selectively to cellular epitopes and receptors outside the vasculature via enhanced permeability and retention (EPR) effect of tumor blood vessel. To enhance the targeting rate of our previous prepared NBs-Affibody for HER2 (+) breast cancer imaging, we introduced a near-infrared fluorescent (NIRF) dye, IR783, in this study to enhance tumor-specific targeting rate and provide a promising modality for dual-mode imaging. The prepared IR783-NBs-Affibody presented a uniform nanoscale size around 482.7 ± 54.3 nm, good biosecurity, and stability over time. The encapsulation efficiency (EE) of IR-783 was 15.09% in the conjugates leading to a successful NIR fluorescence and ultrasound enhancement imaging ex vivo. IR783-NBs-Affibody was able to automatically accumulate on BT474 cells with a highly increased targeting rate of 85.4% compared with previous NBs-Affibody of 26.6%, while Affibody-guided HER2 binding was only found in HER2-positive cell lines (BT474 and T-47D). The newly developed IR783-NBs-Affibody is characterized with favorable HER2 targeting ability and bimodal imaging capability for breast cancer. Thus, IR783-NBs-Affibody holds great potential in molecular diagnosis for patients with breast cancer.
Exercise Training Mitigates Water Pipe Smoke Exposure‐Induced Pulmonary Impairment via Inhibiting NF‐κB and Activating Nrf2 Signalling Pathways
Authors: Nemmar Abderrahim , Al-Salam Suhail , Yuvaraju Priya , Beegam Sumaya , Ali Badreldin H.
Published: March 2018

Water pipe smoking is a tobacco smoking method commonly used in Eastern countries and is gaining popularity in Europe and North America, in particular among adolescents and young adults. Several clinical and experimental studies have reported that exposure to water pipe smoke (WPS) induces lung inflammation and impairment of pulmonary function. However, the mechanisms of such effects are not understood, as are data on the possible palliative effect of exercise training. The present study evaluated the effects of regular aerobic exercise training (treadmill: 5 days/week, 40 min/day) on subchronic exposure to WPS (30 minutes/day, 5 days/week for 2 months). C57BL/6 mice were exposed to air or WPS with or without exercise training. Airway resistance measured using forced oscillation technique was significantly and dose‐dependently increased in the WPS‐exposed group when compared with the air‐exposed one. Exercise training significantly prevented the effect of WPS on airway resistance. Histologically, the lungs of WPS‐exposed mice had focal moderate interstitial inflammatory cell infiltration consisting of neutrophil polymorphs, plasma cells, and lymphocytes. There was a mild increase in intra‐alveolar macrophages and a focal damage to alveolar septae in some foci. Exercise training significantly alleviated these effects and also decreased the WPS‐induced increase of tumor necrosis factor α and interleukin 6 concentrations and attenuated the increase of 8‐isoprostane in lung homogenates. Likewise, the lung DNA damage induced by WPS was significantly inhibited by exercise training. Moreover, exercise training inhibited nuclear factor kappa‐B (NF‐κB) expression induced by WPS and increased that of nuclear factor erythroid 2‐related factor 2 (Nrf2). Our findings suggest that exercise training significantly mitigated WPS‐induced increase in airway resistance, inflammation, oxidative stress, and DNA damage via mechanisms that include inhibiting NF‐κB and activating Nrf2 signalling pathways.
Epithelial-Mesenchymal Transition during Metastasis of HPV-Negative Pharyngeal Squamous Cell Carcinoma
Authors: Ihler Friedrich , Gratz Ronja , Wolff Hendrik A. , Weiss Bernhard G. , Bertlich Mattis , Kitz Julia , Salinas Gabriela , Rave-Fränk Margret , Canis Martin
Published: March 2018

In epithelial tumors, a shift towards a mesenchymal phenotype has been associated with increased invasiveness and metastasis. It is assumed that this phenomenon plays a major role in disease progression and ultimately prognosis. This study investigated epithelial-mesenchymal transition (EMT) in human papillomavirus- (HPV-) negative pharyngeal squamous cell carcinoma. Tissue was obtained from one hypopharyngeal primary tumor and a regional lymph node metastasis during surgery with curative intention. A cell culture was established from the primary tumor and mesenchymal growth conditions were emulated. Gene expression profiling was performed (Human 8 × 60 K design array, Agilent Technologies) and EMT was assessed by a gene set (MSigDB: M5930, Hallmark_epithelial_mesenchymal_transition), applying gene set expression analysis (GSEA). Immunohistochemical staining and flow cytometry of CD44 and E-cadherin were compared in primary tumor, metastasis, and cell cultures. Primary tumor and metastasis were highly positive for CD44. A loss of E-cadherin occurred in the metastasis. Flow cytometry showed the appearance of a population without E-cadherin in spheroid colonies. In GSEA, the EMT phenotype was enriched in the primary tumor compared to metastasis and cell cultures (FDR < 25%,p< 5%). EMT showed variable expression during metastasis. It may thereby be a dynamic state in HPV-negative pharyngeal squamous cell carcinoma that is active only during the process of metastasis itself. Thereby, the primary tumor as well as the metastasis may exhibit fewer EMT properties.
Application of Calcium Sulfate for Dead Space Management in Soft Tissue: Characterisation of a Novel In Vivo Response
Authors: Oliver Rema A. , Lovric Vedran , Christou Chris , Aiken Sean S. , Cooper John J. , Walsh William R.
Published: March 2018

Management of dead space (DS) is a fundamental aspect of surgery. Residual DS following surgery can fill with hematoma and provide an environment for bacterial growth, increasing the incidence of postoperative infection. Materials for managing DS include polymethyl-methacrylate (PMMA), which is nonresorbing and requires removal in a second surgical procedure. The use of calcium sulfate (CS) offers the advantage of being fully absorbed and does not require subsequent surgical removal. As CS has historically been used as a bone void filler, there are some concerns for the risk of heterotopic ossification (HO) when implanted adjacent to soft tissue. This study assessed the osteoinductive potential of CS and identified and characterised residual material present in muscle tissue using histology, energy-dispersive X-ray spectroscopy analysis, and scanning electron microscopy (SEM). CS beads with and without antibiotic were implanted in intramuscular sites in both athymic rats and New Zealand white rabbits. At 28 days after implantation in the rat model, no signs of osteoinduction were observed. In the rabbit model, at 21 days after implantation, almost complete bead absorption and presence of a “halo” of material in the surrounding muscle tissue were confirmed. Our results suggested that the halo of material was a calcium phosphate precipitate, not HO.