bluuebunny/crossref_metadata_2025 huggingface dataset:
Annona muricata Leaf Extract Triggered Intrinsic Apoptotic Pathway to Attenuate Cancerous Features of Triple Negative Breast Cancer MDA‐MB‐231 Cells
Authors: Kim Jee Young , Dao Thien T. P. , Song Kwangho , Park Sait Byul , Jang Hyeri , Park Min Kyoung , Gan Soo Ueng , Kim Yeong Shik
Published: July 2018

Annona muricata L., known as graviola, is an evergreen plant of the tropical regions and is a rich source of natural products. Graviola has various biological activities, and it is best known for its anticancer activity. This study aimed to investigate the effects of crude graviola extract in vitro on breast cancer cells; in particular, we aimed to identify an agent against triple negative breast cancer (TNBC). We used the TNBC MDA‐MB‐231 cell line as the experimental model and the ER(+) non‐TNBC MCF‐7 breast cancer cell line as the control. We identified annonaceous acetogenins, including annonacin isomers, characteristic to this plant by using liquid chromatography tandem mass spectrometry (LC/MS/MS). We observed a significant decrease in the cell viability in both cell lines within 48 h, whereas impaired cell motility and invasiveness were observed only in the MDA‐MB‐231 cell line. While the MCF‐7 cells showed an ER‐dependent mechanism of apoptosis, the apoptosis of MDA‐MB‐231 cells was governed by an intrinsic apoptotic pathway triggered by graviola leaf extract (GLE).
Synthesis of N-Tetradecyl-1,10-phenathrolinium-Based New Salts for Biological Applications
Authors: Abebe Atakilt , Atlabachew Minaleshewa , Liyew Misganaw , Ferede Elsabet
Published: July 2018

New organic salts were synthesized by quaternizing 1,10-phenanthroline using 1-bromotetradecane. The first step yielded an organic salt of formula [C26H37N2]Br. Anion exchange reaction using Li[(CF3SO2)2N] resulted in a more stable salt of formula [C26H37N2][(CF3SO2)2N]. The organic salts were investigated by spectrometry (1H, 13C, 19F NMR, X-ray photoelectron spectroscopy (XPS), UV-Vis, and matrix-assisted laser desorption/ionization mass spectroscopy (MALDI MS), CHNSBr elemental analysis, and thermal analysis (TGA and DSC). The thermal characterization showed the melting and decomposition points of [C26H37N2][(CF3SO2)2N] to be 48°C and 290°C, respectively, which indicates it is an ionic liquid with large liquidus range. The biological activities of the salts were investigated against two Gram-positive (Staphylococcus aureus and Streptococcus pyogenes) and two Gram-negative (Escherichia coli and Klebsiella pneumoniae) bacteria, and they are found to be active against all of them. They were compared with [Cu(1,10-phenanthroline)2Cl]Cl. They are found more active against the Gram-negative bacteria. The salts demonstrated minimum inhibitory concentration as low as 50 µg/L. These results suggest the synthesized salts can be considered as a better alternative to certain transition metal complex drugs. This minimizes the concern of introducing metal ions into the organism.
Development of a New Molecular Marker for the Resistance to Tomato Yellow Leaf Curl Virus
Authors: Nevame Adedze Yawo Mawunyo , Xia Lu , Nchongboh Chofong Gilbert , Hasan Muhammad Mahmudul , Alam Md. Amirul , Yongbo Li , Wenting Zhang , Yafei He , Emon Reza Mohammad , Ismail Mohd Razi , Efisue Andrew , Gang Sun , Wenhu Li , Longting Si
Published: July 2018

Tomato yellow leaf curl virus(TYLCV) responsible for tomato yellow leaf curl disease (TYLCD) causes a substantial decrease in tomato (Solanum lycopersicumL.) yield worldwide. The use of resistant variety as a sustainable management strategy has been advocated. Tremendous progress has been made in genetically characterizing the resistance genes (Rgene) in tomato. Breeding tomato for TYLCV resistance has been based mostly onTy-3as a race-specific resistance gene by introgression originating from wild tomato species relatives. Improvement or development of a cultivar is achievable through the use of marker-assisted selection (MAS). Therefore, precise and easy use of gene-targeted markers would be of significant importance for selection in breeding programs. The present study was undertaken to develop a new marker based onTy-3gene sequence that can be used for MAS in TYLCV resistant tomato breeding program. The new developed marker was named ACY. The reliability and accuracy of ACY were evaluated against those ofTy-3linked marker P6-25 through screening of commercial resistant and susceptible tomato hybrids, and genetic segregation using F2 population derived from a commercial resistant hybrid AG208. With the use of bioinformatics and DNA sequencing analysis tools, deletion of 10 nucleotides was observed inTy-3gene sequence for susceptible tomato variety. ACY is a co-dominant indel-based marker that produced clear and strong polymorphic band patterns for resistant plant distinguishing it from its susceptible counterpart. The obtained result correlates with 3:1 segregation ratio of single resistant dominant gene inheritance, which depicted ACY as gene-tag functional marker. This marker is currently in use for screening 968 hybrids varieties and one thousand breeding lines of tomato varieties stocked in Jiangsu Green Port Modern Agriculture Development Company (Green Port). So far, ACY has been used to identify 56 hybrids and 51 breeding lines. These newly detected breeding lines were regarded as potential source of resistance for tomato breeding. This work exploited the sequence ofTy-3and subsequently contributed to the development of molecular marker ACY to aid phenotypic selection. We thus recommend this marker to breeders, which is suitable for marker-assisted selection in tomato.
Association between Participants’ Characteristics, Patient-Reported Outcomes, and Clinical Outcomes in Youth with Sickle Cell Disease
Authors: Badawy Sherif M. , Barrera Leonardo , Cai Stephanie , Thompson Alexis A.
Published: July 2018

Background. Sickle cell disease (SCD) is a chronic debilitating illness. SCD-related complications result in substantial impairment in quality of life (QOL). Our study objective was to assess the relationship of participants’ characteristics, QOL, hydroxyurea adherence, and SCD-related clinical outcomes in youth with SCD. Procedure. A single-center cross-sectional study. Thirty-four youth with SCD enrolled from clinic between January and December 2015. Participants completed PROMIS® measures and ©Modified Morisky Adherence Scale. Results. Participants had a mean age of 14.8 (SD 2.9) years and 41% were female. Participants’ age correlated with fatigue (rs=0.48; P=0.006), pain (rs=0.32; P=0.07), and anxiety (rs=0.33; P=0.06) scores. Participants with chronic pain had worse upper extremity physical function (P=0.05), pain (P=0.04), anxiety (P=0.05), and depression (P=0.05). Males reported significantly higher hydroxyurea adherence (5.4 versus 3.6, P=0.02) compared to females. Participants with chronic pain had more frequent hospitalizations (P=0.02), emergency room visits (P=0.04), and longer total length of hospital stays over 12-month period (P=0.01). Conclusions. Older and female participants had worse QOL scores, and males reported higher hydroxyurea adherence. Participants with chronic pain reported significant impairment in different QOL domains and had increased healthcare utilization. Future longitudinal studies examining the relationship between participants’ characteristics, QOL, hydroxyurea adherence, and SCD-related clinical outcomes are needed.
Automatic Estimation Method for Intersection Saturation Flow Rate Based on Video Detector Data
Authors: Wang Linhong , Wang Yunhao , Bie Yiming
Published: July 2018

Saturation flow rate (SFR) is a fundamental parameter to the level of service evaluation, lane capacity calculation, and signal timing plan optimization at signalized intersections. It is affected by a variety of factors including weather conditions, lane width, and the type of the driver. How to accurately estimate the SFR remains one of the most important tasks in traffic engineering. Existing studies generally rely on the field measurement method which requires a large number of people collecting data at the intersection. As a result, the method incurs a high economic cost and cannot adapt to the dynamic change of SFR. In recent years, video detectors have been widely installed at intersections which are capable of recording the time each vehicle passes the stop line, the number plate of each vehicle, and the vehicle type. This paper therefore aims to propose an automatic estimation method for the SFR based on video detector data in order to overcome the limitation of the field measurement method. A prerequisite for estimating the SFR is to recognize the saturation headway. We consider the actual vehicle headway as time series and build an auxiliary regression equation whose parameters are estimated through the ordinary least squares method. We employ the Dickey-Fuller test to verify whether the headways in the time series are saturation headways. An iterative method using quantiles is proposed to filter out abnormal data. The SFR is finally calculated using the average value of saturation headways. To demonstrate the proposed method, we conduct a case study using data from an intersection with three entrance lanes in Qujing city, Yunnan Province, China. The overall estimation process is displayed and the impacts of quantile selection and data duration on the estimation accuracy are analyzed.
Robust Consensus for Nonlinear Multiagent Systems with Uncertainty and Disturbance
Authors: Li Zhiqiang , Xu Chengjie , Liu Chen , Xu Haichuan
Published: July 2018

This paper investigates robust consensus for nonlinear multiagent systems with uncertainty and disturbance. The consensus evolution behavior is studied under general consensus protocol when each node is disturbed by the relative states between the node and its neighbors. At first, the robust consensus condition is obtained and the convergency analysis is given by using Lyapunov stability theory and matrix theory. Then, the practical consensus is investigated and the bound of the error states is presented. Finally, two numerical simulation examples are given to illustrate the proposed theoretical results.
Ethnobotanical Study of Medicinal Plants Used to Treat Human Diseases in Berbere District, Bale Zone of Oromia Regional State, South East Ethiopia
Authors: Jima Tilahun Tolossa , Megersa Moa
Published: July 2018

This paper reports an ethnobotanical study that focused on the traditional medicinal plants used by local communities to treat human diseases. Ethnobotanical study of medicinal plants was carried out from June 25 to September 5, 2015, in Berbere district of Oromia region, Ethiopia. The study focused on documentation of medicinal plants used to treat various human diseases in the study area. Ethnobotanical data were collected using semistructured interviews, group discussion, guided field walks, and observations with participants. Preference ranking, paired comparison, direct matrix ranking, and informant consensus factors (ICF) were used to analyze the importance of some plant species. A total of 70 medicinal plants, distributed in 56 genera and 46 families, were collected and identified. Plant family with the highest medicinal plants in the study area used for various diseases treatment was Euphorbiaceae (11.4%). The result of growth form analysis showed that shrubs constituted the highest proportion of medicinal plants (48.6%). Roots, 43 (44.8%), were the most frequently utilized plant parts for preparation of traditional herbal medicines. Crushing was a widely used mode of preparation of traditional remedies where oral administration (37.5%) was the dominant route. The highest informants consensus factor (ICF) values were linked to gonorrhea and syphilis disease (0.95); the lowest was linked with external parasites and wound (0.69). Local people in the study area possess traditional knowledge of medicinal plants to treat various human ailments; however, agricultural expansion and disinterest of young generation became the major threat to medicinal plants. It is, therefore, necessary to preserve this indigenous knowledge on traditional medicines by proper documentation, identification of plant species used, and herbal preparation. To save medicinal plants from further loss, involving local communities in cultivation of the most utilized medicinal plants is recommended.
The Incidence and Risk Factors of Acute Kidney Disease after Total Knee Arthroplasty with Early Postoperative Volume Supplement
Authors: Wu Kuan-Ting , Chen Chung-Yang , Chen Bradley , Wang Jun-Wen , Lin Po-Chun , Yen Shih-Hsiang
Published: July 2018

Background. Etiology of acute kidney disease (AKD) after total knee arthroplasty (TKA) was considered as multifactorial. However, the role of early postoperative volume supplement in AKD rate has not been investigated. The purpose of this study was to evaluate the incidence and risk factors of AKD in patients with early volume supplement following TKA. Methods. This was a retrospective study with 458 patients who underwent unilateral TKA. All the patients received 6% tetrastarch, 7.5ml/kg, early in the postoperative period. Postoperative AKD was defined as the postoperative creatinine level ≥ 1.5 times compared with preoperative data. Potential variables associated with AKD were analyzed by multivariate logistic regression model to identify the AKD risk factors in TKA patients after early postoperative volume supplement. Results. The AKD rate was 3.3% (15 patients) in all patients. Age (OR = 1.09; P = .031) and coronary artery disease (CAD) (OR = 3.63; P = .034) were associated with increased risk of development of postoperative AKD. Other comorbidities as hypertension, diabetes, and CKD were not statistically significant risk factors. Conclusion. Our study demonstrated that age and CAD were independent risk factors of AKD in TKA patients. However, the common risk factors as hypertension, diabetes, and CKD were not significantly associated with AKD after TKA if early postoperative supplement of tetrastarch is administered.
Tomographic Image Reconstruction Based on Minimization of Symmetrized Kullback-Leibler Divergence
Authors: Kasai Ryosuke , Yamaguchi Yusaku , Kojima Takeshi , Yoshinaga Tetsuya
Published: July 2018

Iterative reconstruction (IR) algorithms based on the principle of optimization are known for producing better reconstructed images in computed tomography. In this paper, we present an IR algorithm based on minimizing a symmetrized Kullback-Leibler divergence (SKLD) that is called Jeffreys’ J-divergence. The SKLD with iterative steps is guaranteed to decrease in convergence monotonically using a continuous dynamical method for consistent inverse problems. Specifically, we construct an autonomous differential equation for which the proposed iterative formula gives a first-order numerical discretization and demonstrate the stability of a desired solution using Lyapunov’s theorem. We describe a hybrid Euler method combined with additive and multiplicative calculus for constructing an effective and robust discretization method, thereby enabling us to obtain an approximate solution to the differential equation. We performed experiments and found that the IR algorithm derived from the hybrid discretization achieved high performance.
Effects of Single-Nucleotide Polymorphisms in Cytokine, Toll-Like Receptor, and Progesterone Receptor Genes on Risk of Miscarriage
Authors: Razdaibiedina Anastasiia , Khobzey Mykhaylo , Tkachenko Victoria , Vorobiova Iryna
Published: July 2018

Spontaneous abortion is a complex, multifactorial pathology, where various genetic, neural, endocrine, and immunological factors are involved. Cytokines, Toll-like receptors, and progesterone receptors play critical roles in embryonic implantation and development. A delicate, stage-specific equilibrium of these proteins is required for successful pregnancy outcome. However, genetic variation from one individual to another results in variation in levels of Th1/Th2 cytokines, strength of identification of infectious agents by Toll-like receptors, and quality of progesterone recognition. Thus, a complex study encompassing effects of major SNPs of cytokine, TLR, and PGR genes on the risk of miscarriage is needed. In this study, we investigated SNPs of 9 genes (TLR2 G753A, TLR4 C399T, TLR9 G2848A, TGF-β1 C509T, PGR PROGINS, IL-6 G174C, IL-8 C781T, IL-10 C592A, and TNFα G308A) in 106 women, whose pregnancy ended in miscarriage, and 74 women, who delivered in term without any pregnancy complication. All participants are from Ukrainian population. As a result, TLR9 and IL-10 SNPs have been found to play critical roles in the development of spontaneous abortion. TLR2, TLR4, IL-6, IL-8, and PGR SNPs were identified as secondary factors that can also affect the risk of miscarriage. There was no association found between TGF-β1 and TNFα polymorphisms and miscarriage.
Blind Corner Propagation Model for IEEE 802.11p Communication in Network Simulators
Authors: Jaktheerangkoon Sanchai , Na Nakorn Kulit , Rojviboonchai Kultida
Published: July 2018

Vehicular Ad Hoc Network (VANET) has been developed to enhance quality of road transportation. The development of safety applications could reduce number of road accidents. IEEE 802.11p is a promising standard for intervehicular communication, which would enable the connected-vehicle applications. However, in the well-known network simulators such as NS3 and Omnet, there is no propagation model that can simulate the IEEE 802.11p communication at blind corner realistically. Thus, in this paper, we conducted the real-world experiments of IEEE 802.11p in order to construct the model to describe the characteristics of the IEEE 802.11p communication at the blind corners. According to the experimental results, we observe that the minimum distance between the vehicle and the corner can effectively be represented as the key parameter in the model. Moreover, we have a variable parameter for adjusting the impact of the obstruction which could be different at each type of blind corners. The simulation results using our proposed model are compared with those using the existing obstacle model. The results showed that our proposed model is much more closely aligned with the real experimental results.
Tyrosine Kinase Inhibitors Increase MCL1 Degradation and in Combination with BCLXL/BCL2 Inhibitors Drive Prostate Cancer Apoptosis
Authors: Arai Seiji , Jonas Oliver , Whitman Matthew A. , Corey Eva , Balk Steven P. , Chen Sen
Published: July 2018

Purpose: Clinically available BH3 mimetic drugs targeting BCLXL and/or BCL2 (navitoclax and venetoclax, respectively) are effective in some hematologic malignancies, but have limited efficacy in solid tumors. This study aimed to identify combination therapies that exploit clinical BH3 mimetics for prostate cancer.

Experimental Design: Prostate cancer cells or xenografts were treated with BH3 mimetics as single agents or in combination with other agents, and effects on MCL1 and apoptosis were assessed. MCL1 was also targeted directly using RNAi, CRISPR, or an MCL1-specific BH3 mimetic, S63845.

Results: We initially found that MCL1 depletion or inhibition markedly sensitized prostate cancer cells to apoptosis mediated by navitoclax, but not venetoclax, in vitro and in vivo, indicating that they are primed to undergo apoptosis and protected by MCL1 and BCLXL. Small-molecule EGFR kinase inhibitors (erlotinib, lapatinib) also dramatically sensitized to navitoclax-mediated apoptosis, and this was associated with markedly increased proteasome-dependent degradation of MCL1. This increased MCL1 degradation appeared to be through a novel mechanism, as it was not dependent upon GSK3β-mediated phosphorylation and subsequent ubiquitylation by the ubiquitin ligases βTRCP and FBW7, or through other previously identified MCL1 ubiquitin ligases or deubiquitinases. Inhibitors targeting additional kinases (cabozantinib and sorafenib) similarly caused GSK3β-independent MCL1 degradation, and in combination with navitoclax drove apoptosis in vitro and in vivo.

Conclusions: These results show that prostate cancer cells are primed to undergo apoptosis and that cotargeting BCLXL and MCL1, directly or indirectly through agents that increase MCL1 degradation, can induce dramatic apoptotic responses. Clin Cancer Res; 24(21); 5458–70. ©2018 AACR.
Creation of a Balloon-Expandable Bifurcated Covered Stent to Treat a Complex Left Anastomotic Stricture in a Lung Transplant Recipient
Authors: Kern Ryan , Sakata Kenneth , Peters Steve G. , Midthun David , Mullon John , Edell Eric
Published: July 2018

Airway complications after lung transplant occur in approximately 10–15% of the recipients and often occur at the anastomosis, largely due to ischemia. To decrease anastomotic ischemia, surgeons minimize the length of the donor bronchus. However, a shortened donor bronchus creates technical challenges if a stent is required to treat an airway complication. We present a case of a lung transplant recipient with the combination of left main stem bronchial malacia and a triad of severe strictures at the left anastomosis, entrance to the left upper lobe, and left lower lobe. After failing several attempts using other modalities, success was achieved with in situ creation of a bifurcated fully covered balloon-expandable metallic stent. We describe a novel technique of punching a side branch hole through the wall of the stent to allow a left upper lobe stent to be placed through a stent directed into the left lower lobe in a Y configuration with a good clinical outcome.
Trichoscopy of Dark Scalp
Authors: Ocampo-Garza Jorge , Tosti Antonella
Published: July 2018

Trichoscopy (dermoscopy of the hair and scalp) is a technique that improves diagnostic accuracy and follow-up with hair and scalp disorders. Although several studies of trichoscopy have been made in Caucasian and Asian populations, little has been published regarding trichoscopy findings in skin of color, despite the great prevalence of hair diseases in populations with this kind of skin. The aim of this review was to describe the trichoscopic features of normal scalp and of hair disorders in patients with dark skin phototypes. This will help dermatologists to distinguish between unique trichoscopic features of dark skin, and allow them to provide more accurate diagnoses and treatments for these patients.
Atypical Case of Rosai-Dorfman Disease of the Lacrimal Gland with Adjacent Bone Erosion
Authors: Dahrouj Mohammad , Jakobiec Frederick A. , Wolkow Natalie , Starks Victoria S. , Lee Nahyoung Grace
Published: July 2018

Background/Aims: Rosai-Dorfman disease (RDD) is a rare, self-limited disorder of unknown etiology that affects children and young adults worldwide and typically manifests as chronic, painless cervical lymphadenopathy. Orbital involvement is very rare and may be an isolated extranodal manifestation or associated with concurrent systemic disease. Adjacent bone involvement is most exceptional, and secondary optic neuropathy has never been reported. Methods: This is a case report with review of the literature. Results: We present a 32-year-old man who, over a 3-month period, developed worsening vision, headache, and vertical diplopia. On examination, there was decreased vision with dyschromatopsia, proptosis, and hypotropia of the left eye. CT scan of the orbits revealed a soft tissue mass inseparable from the lacrimal gland with adjacent bone erosion. Histopathologic evaluation revealed a diffuse infiltrate of histiocytes, lymphocytes, plasma cells, and neutrophils with peripolesis and emperipolesis (tunneling of lymphocytes and plasma cells in the histiocytes’ cytoplasm without destruction), consistent with RDD. Resolution of symptoms as well as of the optic neuropathy was achieved with oral corticosteroids. Conclusion: RDD is an important diagnosis that must be considered in the differential diagnosis of an orbital mass.
Transoral Robotic Surgery for Oropharyngeal Cancer
Authors: Paleri Vinidh , Fox Hannah , Winter Stuart
Published: July 2018

Transoral robotic surgery has shown significant promise in the management of oropharyngeal cancer since its description in 2007. The oncological efficacy of this procedure has been proven in several single-centre studies, multicentre collaborative publications and systematic reviews. The rapid take-up of transoral robotic surgery shows greater acceptance by professionals and is associated with a relatively short learning curve. This overview discusses the rationale and principles underlying the use of transoral robotic surgery in primary and recurrent oropharyngeal cancer and the emerging role for this technique in diagnosing the unknown primary site, and summarizes ongoing research in this field.
Methods of Blood Pressure Assessment Used in Milestone Hypertension Trials
Authors: Chen Yi , Lei Lei , Wang Ji-Guang
Published: July 2018

In the present review, we summarized the blood pressure (BP) measurement protocols of contemporary outcome trials in hypertension. In all these trials, clinic BP was used for the diagnosis and therapeutic monitoring of hypertension. In most trials, BP was measured in the sitting position with mercury sphygmomanometers or automated electronic BP monitors by trained observers. BP readings were taken on each occasion at least twice with a 30-to-60-s interval after 5 min of rest. Details regarding the arm side, cuff size, and the timing of BP measurement were infrequently reported. If clinic BP continues being used in future hypertension trials, the measurement should strictly follow current guidelines. The observers must be trained and experienced, and the device should be validated by automated electronic BP monitors. On each occasion, BP readings should be taken 2–3 times. The time interval between successive measurements has to be 30–60 s, and the resting period before the measurement should be at least 5 min in the supine or seated position and 1–3 min standing. BP should usually be measured in the seated position. The higher arm side and an appropriate size cuff should be chosen and noted. BP should be measured at defined trough hours. Automated office BP measurement has recently been used and seems to have less white-coat effect. The out-of-office BP measurement, either ambulatory or home BP monitoring, was only used in a subset of study participants of few hypertension trials. Future trials should consider these novel office or out-of-office BP measurements in guiding the therapy and preventing cardiovascular events.
Gender Differences in Anxiety and Depression before and after Alcohol Detoxification: Anxiety and Depression as Gender-Related Predictors of Relapse
Authors: Oliva Francesco , Nibbio Gabriele , Vizzuso Paola , Jaretti Sodano Alessandro , Ostacoli Luca , Carletto Sara , Picci Rocco Luigi
Published: July 2018

Background/Aims: The aim of this prospective study was to estimate gender differences in anxiety, depression, and alcohol use severity among patients with alcohol use disorder (AUD) before and after detoxification program and within 12 months after discharge. Methods: AUD severity, state and trait anxiety, and depression were assessed in 187 patients entering an inpatient alcohol detoxification program. Follow-up assessments were performed at 6 and 12 months after discharge. A between- and within-subjects analyses explored gender differences. The predictive value of anxiety and depression for alcohol relapse was analyzed by logistic and linear regression in both genders. Results: Females had higher levels of anxiety and depression than males both at admission and after discharge. Trait anxiety and depression significantly increased 6 months after discharge in males and females respectively. Both state and trait anxiety levels at the 6-month follow-up predicted alcohol relapse at the 12-month follow-up in males. Conversely, in females, depression level at the 6-month follow-up was a predictor of relapse at the 12-month follow-up. Conclusions: In both genders, the psychopathological dimension that showed the most significant worsening at 6-month follow-up (i.e., anxiety in males and depression in females) was found to be a significant predictor of relapse at the 12-month follow-up.
Developing an Arabic Screening Test for Adult-Onset Chronic Aphasia
Authors: Abou-Elsaad Tamer , Baz Hemmat  , Belal Tamer , Elsherbeny Sara
Published: July 2018

Aim: To develop a time-efficient Arabic test battery for adult-onset chronic aphasia that provides information about the type and the severity of the disorder. Patient and Methods: A total of 90 participants were recruited and divided into 3 groups. The groups consisted of 30 adult-onset post-stroke chronic aphasic patients, 30 adult non-aphasic adults with central neurological disorders, and a group of 30 non-brain-damaged healthy adults. All participants were assessed using the Mansoura Arabic Screening Aphasia Test (MASAT), which consists of 4 main sections: (1) language expression abilities including repetition and naming items, (2) language comprehension questions, (3) fluency, and (4) reading, writing and calculation items. The content validity, internal consistency, clinical validity, and convergent validity of the MASAT were evaluated. Results: The MASAT demonstrated statistically high reliability and validity. The high α-values in all subtotal scores among the 3 groups were judged to denote excellent intercorrelation among the screening test items. Conclusion: The MASAT is a valid and a reliable brief assessment tool that can be completed on the first clinic appointment that detects the type and severity of Arabic-speaking aphasic patients.
External Validation and Clinical Usefulness of First Trimester Prediction Models for the Risk of Preeclampsia: A Prospective Cohort Study
Authors: Meertens Linda J.E. , Scheepers Hubertina C.J. , van Kuijk Sander M.J. , Aardenburg Robert , van Dooren Ivo M.A. , Langenveld Josje , van Wijck Annemieke M. , Zwaan Iris , Spaanderman Marc E.A. , Smits Luc J.M.
Published: July 2018

Introduction: This study assessed the external validity of all published first trimester prediction models for the risk of preeclampsia (PE) based on routinely collected maternal predictors. Moreover, the potential utility of the best-performing models in clinical practice was evaluated. Material and Methods: Ten prediction models were systematically selected from the literature. We performed a multicenter prospective cohort study in the Netherlands between July 1, 2013, and December 31, 2015. Eligible pregnant women completed a web-based questionnaire before 16 weeks’ gestation. The outcome PE was established using postpartum questionnaires and medical records. Predictive performance of each model was assessed by means of discrimination (c-statistic) and a calibration plot. Clinical usefulness was evaluated by means of decision curve analysis and by calculating the potential impact at different risk thresholds. Results: The validation cohort contained 2,614 women of whom 76 developed PE (2.9%). Five models showed moderate discriminative performance with c-statistics ranging from 0.73 to 0.77. Adequate calibration was obtained after refitting. The best models were clinically useful over a small range of predicted probabilities. Discussion: Five of the ten included first trimester prediction models for PE showed moderate predictive performance. The best models may provide more benefit compared to risk selection as used in current guidelines.
Quercetin Shows the Pharmacological Activity to Simultaneously Downregulate the Inflammatory and Fibrotic Responses to Tissue Injury in Association with its Ability to Target Multi-Kinases
Authors: Song Ju-Yong , Truong Do Vinh , Yang Beom-Seok
Published: July 2018

Aim: Previous studies have suggested that quercetin is effective for treating diverse chronic disorders including organ fibrosis and airway and cardiovascular disorders. To access the pharmacological background for its broad efficacy, we examined the ability of quercetin to modulate the inflammatory and fibrotic responses associated with organ injury that commonly underlie the pathogenesis of those disorders. Methods: A cutaneous wound model on rabbit ear was used for in vivo study. Quercetin was topically applied to the wounds, and the number of macrophages and myofibroblasts and the size of the hypertrophic scar formed were estimated. An in vitro study examined the ability of quercetin to inhibit cell-signaling pathways that activate RAW264.7 macrophages and primary dermal fibroblasts and the tyrosine kinase activity of discoidin domain receptor 2. Results: Quercetin reduced the population of macrophages and myofibroblasts and the scar formation in cutaneous wound healing. Quercetin suppressed the signaling pathways activating RAW264.7 macrophages and dermal fibroblasts, which is associated with its inhibition of multiple tyrosine kinases to regulate the pathways. This pharmacological activity of quercetin to simultaneously inhibit the inflammatory and fibrotic responses upon tissue damage by targeting multi-kinases could be the action mechanism to support its broad efficacy for various chronic disorders.
Degradation of Monocyte Chemoattractant Protein-1 by Tryptase Co-Released in Immunoglobulin E-Dependent Activation of Primary Human Cultured Mast Cells
Authors: Tam Issan Yee San , Ng Chun Wai , Lau Hang Yung Alaster , Tam See-Ying
Published: July 2018

Background: Mast cells are key immune effector cells which release chemokines, proteases, and other inflammatory mediators upon activation by immunological stimuli. The aim of this study was to investigate the effects of co-releasing proteases on the kinetics of release of the chemokine monocyte chemoattractant protein-1 (MCP-1) in immunoglobulin E (IgE)-mediated activation of human mast cells. Methods: Homogenous populations of mature and functional primary human mast cells were generated from CD34+ progenitors originated from buffy coats of healthy adult donors. The releases of MCP-1 from human mast cells in basal conditions and in response to FcεRI cross-linking were assessed at different time points. The effects of different types of protease inhibitors on MCP-1 release from these mast cells under stimulated or unstimulated conditions were also investigated. Results: Cultured human mast cells released MCP-1 in basal conditions and its levels increased in a time-dependent manner. When stimulated by FcεRI cross-linking, the levels of MCP-1 detected in the medium gradually decreased over time after the initial peak induction. Such a decline in MCP-1 levels after IgE-dependent activation was completely prevented by pretreatment with a cocktail of protease inhibitors or the specific tryptase inhibitor APC366. Conclusions: Direct regulation of MCP-1 expression by co-release of tryptase in cultured human mast cells upon IgE-dependent activation demonstrates a role of the serglycin:serine protease axis in modulation of inflammatory reactions through proteolytic degradation of mediators such as chemokines.
Dietary Sodium Intake and Serum Uric Acid: A Mini-Review
Authors: Lei Lei , Wang Ji-Guang
Published: July 2018

The aim of the present review is to summarize recent studies on the relationship between dietary sodium intake and serum uric acid concentration. In short-term dietary sodium intervention studies, including a recent further analysis of a previously published trial, high dietary sodium intake (200 mmol/day), compared with a low sodium diet (20–60 mmol/day), resulted in a significant reduction in serum uric acid, being approximately 20–60 μmol/L. This finding, though consistent across short-term studies, is in contradiction to the long-term observational evidence on the relationship between dietary sodium intake and serum uric acid. Indeed, in a population-based prospective study, high dietary sodium intake was associated with a higher serum uric acid concentration. If serum uric acid would be followed up, several currently ongoing long-term randomized dietary sodium intervention studies may shed some light on how dietary sodium intake interacts with serum uric acid in the development of hypertension.
Sensitivity of Initial Thoracentesis for Malignant Pleural Effusion Stratified by Tumor Type in Patients with Strong Evidence of Metastatic Disease
Authors: Grosu Horiana B , Kazzaz Farah , Vakil Erik , Molina Sofia , Ost David
Published: July 2018

Background: Thoracentesis with cytological examination of pleural fluid is the initial test of choice for evaluation of pleural effusions in patients with suspected malignant pleural effusion (MPE). There is limited data on the sensitivity of thoracentesis stratified by tumor type. A better understanding of stratified sensitivities is of clinical interest, and may guide early and appropriate referral for pleural biopsy. Objective: The primary objective was sensitivity of thoracentesis with pleural fluid cytology stratified by tumor type. Methods: This is a retrospective cohort study of consecutive patients with a solid tumor malignancy with proven or strong suspicion for metastatic disease with new pleural effusions that underwent an initial thoracentesis. Only patients with metastatic disease were included. Results: Of the 725 patients examined, 63% had pleural fluid cytology positive for malignancy. Sensitivity of thoracentesis varied from a low of 0.38 (95% CI 0.13–0.68) in head and neck malignancy, 0.38 (95% CI 0.15–0.65) in sarcoma, and 0.53 (95% CI 0.34–0.72) in renal cancer to a high of 93 (95% CI 88–97) in breast cancer, and 100 (95% CI 0.82–100) in pancreatic cancer. Factors associated with an increased risk of MPE included larger amount of fluid drained (p = 0.014) and higher pleural fluid protein (p = 0.002). The only factor associated with decreased risk of MPE if first cytology was negative for malignancy was the presence of contralateral effusion (p = 0.005). Conclusions: Sensitivity of thoracentesis for solid tumors varies significantly depending on the type of tumor and is lowest in those with sarcomas, head and neck malignancies, and renal cell cancers.
Single-Centre Experience of Testosterone Therapy for Boys with Hypogonadism
Authors: Lucas-Herald Angela K. , Mason Eliot , Beaumont Paula , Mason Avril , Shaikh M. Guftar , Wong Sze C. , Ahmed S. Faisal
Published: July 2018

Background: Hypogonadism in boys is one of the commonest conditions encountered in paediatric endocrinology. Aims: To study variations in management in a contemporary group of boys at a single specialist centre. Methods: Retrospective review of case records of all boys treated with testosterone at a tertiary endocrine service from 2012 to 2017. Results: Of the 358 boys reviewed for hypogonadism, 46 (13%) were initiated on testosterone therapy at a median age (range) of 14.2 years (12.1, 17.7). Indications for therapy included a functional delay of puberty that was constitutional in 17 (37%) or related to chronic disease in 10 (22%) or organic hypogonadism due to primary gonadal failure in 7 (15%), multiple pituitary hormone deficiency in 6 (13%), and isolated hypogonadotropic hypogonadism in 6 (13%). Of the 46 boys, 40 (89%) were started on intramuscular testosterone, 4 (9%) on oral testosterone, and 1 (2%) on transdermal gel. Of the 19 boys (40%) with organic hypogonadism re­quiring long-term therapy, 12 (63%) had assessment of liver function, 6 (32%) had a haematocrit, and 2 (11%) had a DXA scan in the year of commencing treatment. Conclusions: Testosterone therapy is administered in about 13% of boys reviewed for hypogonadism and its monitoring requires standardisation.
The Clinical Efficacy of Mindfulness-Based Treatments for Alcohol and Drugs Use Disorders: A Meta-Analytic Review of Randomized and Nonrandomized Controlled Trials
Authors: Cavicchioli Marco , Movalli Mariagrazia , Maffei Cesare
Published: July 2018

Introduction: The current study aims to evaluate if and to what extent mindfulness-based interventions (MBIs) could promote an incremental effectiveness compared to interventions usually provided in clinical practice to treat Alcohol and Drugs Use Disorders. In line with this aim, we accomplished a meta-analytic review of randomized and nonrandomized controlled trials, considering primary and secondary outcomes that comprehensively operationalize treatment efficacy. Methods: We conducted the online research up to August 31st 2017. Adequate procedures for Cohen’s d computation were applied. Heterogeneity indexes, moderators, bias of publication, and Orwin’s fail-safe number were also estimated. Results: Thirty-seven studies were included (n = 3,531 patients). We observed null effect sizes for attrition rate and overall mental health. Small effect sizes were detected in abstinence, levels of perceived stress, and avoidance coping strategies. Moderate effect sizes were revealed in anxiety and depressive symptoms. Large effect sizes were associated to levels of perceived craving, negative affectivity, and post-traumatic symptoms. Conclusion: MBIs seemed to show clinically significant advantages compared to other clinical approaches in relation to specific primary and secondary outcomes. Conversely, treatment retention was independent of the therapeutic approach.
Clinical Management of Chronic Kidney Disease Patients in Italy: Results from the IRIDE Study
Authors: Cozzolino Mario , Bolasco Piergiorgio , Ronco Claudio , Conte Giuseppe , Menè Paolo , Mereu Maria Cristina , Di Luca Marina , Roccatello Dario , Rosati Alberto , Jommi Claudio , Costanzo Anna Maria , Gualberti Giuliana , di Luzio Paparatti Umberto , Remuzzi Giuseppe
Published: July 2018

Background: Lack of adequate management of chronic kidney disease (CKD) often results in delayed diagnosis and inadequate treatment. This study assessed the clinical management and outcome of stages 1–5 CKD patients. Methods: Patients were prospectively followed for 3 years in 25 nephrology centers across Italy. Clinical characteristics were measured at baseline and every 6 months. Outcome measures included CKD staging, presence of comorbidities, treatment, mineral bone disorder (MBD) parameters, and patient outcomes. Results: Of 884 enrolled patients (59.7% males, aged 66.2 ± 14.6 years), 587 (66.4%) completed the study. The majority of patients were referred by a general practitioner (44.7%) and had stage 3 or 4 CKD (40.9 and 23.8% respectively). Data reveal that 91.3% of patients had at least 1 concomitant disease, most frequently hypertension (80.1%) and dyslipidemia (42.5%); 94.6% of patients were receiving cardiovascular medication and 52.6% were receiving lipid-lowering medication. Approximately 40% of patients had proteinuria and intact parathyroid hormone levels outside the normal range. As expected, stages 4 and 5 CKD patients had a higher prevalence of proteinuria (68 and 74%), MBD (59 and 88%) and anemia (28 and 73%), as well as a higher risk of hospitalization (34.3 and 51.9%) and need for dialysis (69.5 and 70%). The overall probability of survival over 36 months was 90.6%. Conclusions: This is the first Italian prospective study performed with a large cohort of CKD patients over a 3-year period. Considering the multifactorial burden of diseases associated with CKD patients, the need for greater attention to CKD and related disorders is paramount.
Angelman Syndrome-Affected Individual with a Numerically Normal Karyotype and Isodisomic Paternal Uniparental Disomy of Chromosome 15 due to Maternal Robertsonian Translocation (14;15) by Monosomy Rescue
Authors: Bramswig Nuria C. , Buiting Karin , Bechtel Natalie , Horsthemke Bernhard , Rostasy Kevin , Wieczorek Dagmar
Published: July 2018

Angelman syndrome (AS) is a neurodevelopmental disorder caused by deletion of the maternally inherited 15q11q13 region, paternal uniparental disomy 15 [upd(15)pat], an imprinting defect of the maternal chromosome region 15q11q13, or a pathogenic mutation of the maternal UBE3A allele. Predisposing factors for upd(15)pat, such as nonhomologous robertsonian translocation involving chromosome 15, have been discussed, but no evidence for this predisposition has been published. In the present study, chromosomal analysis was performed in a child with AS, both parents, and the maternal grandparents. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was employed on DNA of the index individual, and microsatellite analysis was carried out on DNA of the index individual and his parents. The cytogenetic analysis showed that the mother and maternal grandfather are carriers of a rob(14;15). The index individual has a numerically normal karyotype, but MS-MLPA and microsatellite analyses confirmed the clinical diagnosis of AS and revealed a pattern highly suggestive of isodisomic upd(15)pat. This is the first report of an AS-affected individual with isodisomic upd(15)pat and a numerically normal karyotype that most likely results from a rob(14;15)-associated meiotic error in the maternal germline followed by monosomy 15 rescue in the early embryo.
Frequency of Complete Atrioventricular Block Complicating ST-Elevation Myocardial Infarction in Patients Undergoing Primary Percutaneous Coronary Intervention
Authors: Chera Hymie H. , Mitre Cristina A. , Nealis Justin , Mironov Alex , Budzikowski Adam S.
Published: July 2018

Objectives: ST-segment elevation myocardial infarction (STEMI) can be associated with many conduction disturbances including complete atrioventricular block (CAVB). CAVB complicating STEMI resulted in an increased mortality before the modern era of primary percutaneous coronary intervention (PCI). The aim of this study was to ascertain the rate and risk factors for CAVB in STEMI patients undergoing rapid reperfusion with PCI. Methods: We analyzed 223 patients presenting with STEMI. Patient characteristics, procedural characteristics, and in-hospital data were compared between patients with and without CAVB. Results: Out of 223 patients, 174 underwent PCI; the majority (87%) was African-American. CAVB was present in 8 patients (4.6%), and 6 of them had RCA occlusion. Independent predictors of CAVB included diabetes mellitus, female gender, lower systolic and diastolic blood pressure, and inferior-lateral/lateral STEMI. Ten patients (5.7%) required temporary pacing at presentation; only 1 patient required permanent pacing before discharge. No patient with anterior STEMI developed CAVB. Conclusions: The incidence and in-hospital mortality rate of CAVB in patients with STEMI who underwent primary PCI was reduced when compared to data from the thrombolytic era. This may be due to faster flow recovery in the infarct-related artery achieved with PCI.
Pembrolizumab in Recurrent Squamous Cell Carcinoma of the Vulva: Case Report and Review of the Literature
Authors: Shields Lisa B.E. , Gordinier Mary E.
Published: July 2018

Advanced vulvar cancer is associated with a very poor prognosis. Surgical resection is the mainstay of treatment, with radiation indicated for areas at high risk for recurrence. When surgical and radiation options have been exhausted, the effectiveness of systemic chemotherapy is poor. No biologic or targeted agents have been approved for the management of advanced or recurrent vulvar cancer. Pembrolizumab, a humanized monoclonal antibody against programmed death 1 (PD-1), has been successfully used as a target of tumor immune therapy in small cell lung cancer and melanoma. We present the first case in the literature of a patient with recurrent vulvar cancer who was treated successfully with pembrolizumab. Caris next-generation testing revealed a PD-L1 and PD-1 mutation (PD-L1 positive, 2+, 100%). She attained a complete clinical remission after 2 cycles, and a CT scan after 6 cycles revealed a significant response by RECIST criteria. After completing 10 cycles, treatment was stopped due to complications of severe malnutrition related to narcotic abuse. A CT scan 10 weeks after the final treatment revealed no adenopathy. Pembrolizumab is a safe and effective chemotherapeutic agent to treat recurrent vulvar carcinoma.