bluuebunny/crossref_metadata_2025 huggingface dataset:
Revival of Calcium-Binding Proteins for Neuromorphology: Secretagogin Typifies Distinct Cell Populations in the Avian Brain
Authors: Gáti Georgina , Lendvai Dávid , Hökfelt Tomas , Harkany Tibor , Alpár Alán
Published: April 2017

In the vertebrate nervous system, the Ca2+-binding proteins parvalbumin, calbindin and calretinin have been extensively used to elaborate the molecular diversity of neuronal subtypes. Secretagogin is a phylogenetically conserved Ca2+-binding protein, which marks neuronal populations largely distinct from other Ca2+-binding proteins in mammals. Whether secretagogin is expressed in nonmammalian vertebrates, particularly in birds, and, if so, with a brain cytoarchitectonic design different from that of mammals is unknown. Here, we show that secretagogin is already present in the hatchlings' brain with continued presence into adulthood. Secretagogin-immunoreactive neurons primarily accumulate in the olfactory bulb, septum, subpallial amygdala, hippocampus, hypothalamus, habenular nuclei and deep layers of the optic tectum of adult domestic chicks (Gallus domesticus). In the olfactory bulb, secretagogin labels periglomerular neurons as well as a cell continuum ascending dorsomedially, reaching the ventricular wall. Between the hippocampus and septal nuclei, the interconnecting thin septal tissue harbors secretagogin-immunoreactive neurons that contact the ventricular wall with their ramifying dendritic processes. Secretagogin is also present in the neuroendocrine hypothalamus, with particularly rich neuronal clusters seen in its suprachiasmatic and infundibular nuclei. Secretagogin expression identified a hitherto undescribed cell contingent along intratelencephalic cell-free laminae separating brain regions or marking the palliosubpallial boundary, as well as a dense neuronal population in the area corticoidea lateralis. In both the telencephalon and midbrain, secretagogin complemented the distribution of the canonical ‘neuronal' Ca2+-binding proteins. Our findings identify novel neuronal subtypes, connectivity patterns in brain areas functionally relevant to olfaction, orientation, behavior as well as endocrine functions, which will help refine existing concepts on the neuronal diversity and organizational principles of the avian brain.
Sustained Low-Efficiency Daily Diafiltration for Diabetic Nephropathy Patients with Acute Kidney Injury
Authors: Chen Xinghua , Ma Te'an
Published: April 2017

Objective: To investigate the efficacy, safety and cost of treating patients with acute kidney injury (AKI) and diabetic nephropathy (DN) with continuous renal replacement therapy (CRRT) or sustained low-efficiency daily diafiltration with hemofiltration (SLEDD-f). Subjects and Methods: Medical records of patients with AKI/DN from January 2006 to December 2012 were reviewed. Fifty-five patients who received CRRT and 52 who received SLEDD-f were included in the study. CRRT and SLEDD-f were performed for 20-72 h per session and 8-10 h per session, respectively. Mortality and renal function recovery rates were evaluated 30 days after the initiation of renal replacement therapy (RRT) and APACHE-II and SOFA scores, anticoagulant dose, inflammatory indices and cost were calculated at baseline and at the end of RRT. Results: Of the 55 patients treated with CRRT, 49 (89.1%) had a 30-day survival rate and 30 (54.5%) had a 30-day renal recovery rate. Of the 52 patients with SLEDD-f, these rates were 92.3% (n = 48) and 61.5% (n = 32), respectively. The dosage of low-molecular-weight heparin in the CRRT and SLEDD-f groups was 15,230 ± 1,460 and 6,320 ± 490 U/day, respectively. The cost of hemopurification and the total cost for patients treated with CRRT was CNY 28,628 ± 5,576 (USD 4,210 ± 820) and CNY 38,828 ± 6,324 (USD 5,710 ± 930), respectively. These were higher than those for patients treated with SLEDD-f at CNY 13,260 ± 1,564 (USD 1,950 ± 230) and CNY 19,720 ± 2,652 (USD 2,900 ± 390), respectively. Conclusions: SLEDD-f offered a similar chance of renal recovery and also had further advantages such as a lower heparin dosage, a shorter therapy time and lower hospitalization costs for patients than CRRT. Studies with larger, randomized sample sizes are needed to confirm these findings.
Pathophysiological Decrease in the Regional Cerebral Blood Flow in Hashimoto's Encephalopathy: A Multiple-Case SPECT Study
Authors: Muramatsu Tomoko , Ikawa Masamichi , Yoneda Makoto , Sugimoto Katsuya , Matsunaga Akiko , Yamamura Osamu , Hamano Tadanori , Okazawa Hidehiko , Nakamoto Yasunari
Published: April 2017

Background: The aim of this study was to evaluate the changes in regional cerebral blood flow (rCBF) in multiple cases of Hashimoto's encephalopathy (HE). Methods: Seven untreated patients with HE and 10 age-matched healthy controls underwent brain single photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]iodoamphetamine. All patients had anti-NH2-terminal of α-enolase autoantibodies (Abs), which served as a useful diagnostic marker for HE, in addition to anti-thyroid Abs in their sera and responded to corticosteroid therapy. The obtained SPECT images were compared between the patients and the controls using 3D-SSP analysis. Results: The rCBF of all patients with HE was significantly decreased in the bilateral anterior cingulate areas and left prefrontal cortex compared with the controls (p < 0.05). Focusing on the HE patients with acute neuropsychiatric symptoms (n = 5) such as consciousness disturbance and/or psychosis, the decreased rCBF in these areas was more significant, and the rCBF in the right frontal cortex was also decreased. Conclusion: Statistical analysis of these multiple-case SPECT images revealed the regions of decreased CBF associated with clinical symptoms, especially acute neuropsychiatric symptoms, in HE patients. This study shed light on the pathophysiological decrease in rCBF observed in HE.
Preferential Silent Survival of Intracellular Bacteria in Hemoglobin-Primed Macrophages
Authors: Subramanian Karthik , Winarsih Imelda , Keerthani Chandrakumaran , Ho Bow , Ding Jeak Ling
Published: April 2017

Hemolysis releases hemoglobin (Hb), a prooxidant, into circulation. While the heme iron is a nutrient for the invading pathogens, it releases ROS, which is both microbicidal and cytotoxic, making it a double-edged sword. Previously, we found a two-pass detoxification mechanism involving the endocytosis of Hb into monocytes in collaboration with vascular endothelial cells to overcome oxidative damage. This prompted us to examine the effect of Hb priming on host cell viability and intracellular bacterial clearance during a hemolytic infection. Here, we demonstrate that Hb-primed macrophages harbor a higher intracellular bacterial load but with suppressed apoptosis. p-ERK and p-p38 MAPK were significantly downregulated, with concomitant impairment of Bax and downstream caspases. The Hb-primed cells harboring intracellular bacteria upregulated anti-inflammatory IL-10 and downregulated proinflammatory TNF-α, which further enhanced the infectivity of the neighboring cells. Our findings suggest that opportunistic intracellular pathogens exploit the Hb-scavenging machinery of the host to silently persist within the circulating phagocytes by suppressing apoptosis while escaping immune surveillance.
Phase I/II Trial of Irinotecan and S-1 Combination Chemotherapy as a Second-Line Treatment for Advanced Colorectal Cancer
Authors: Takii Yasumasa , Yamazaki Toshiyuki , Okada Takayuki , Tani Tatsuo , Funakoshi Kazuhiro , Maruyama Satoshi , Hasegawa Jun , Akazawa Kouhei , Hatakeyama Katsuyoshi ,   for the Niigata Colorectal cancer Chemotherapy Study Group (NCCSG)
Published: April 2017

Background: This study attempted to determine the therapeutic dosage of irinotecan and S-1 (IRIS) as a second-line treatment for colorectal cancer (CRC). Methods: S-1 was administered on days 1-14 of a 28-day cycle. Irinotecan was administered on days 1 and 15. The irinotecan dose was then escalated to determine the maximum-tolerated dose and the recommended dose at a fixed dosage of S-1 (80 or 65 mg·m-2·day-1). The S-1 dose was reduced to 65 mg·m-2·day-1 when dose-limiting toxicities were observed at 80 mg·m-2· day-1 and the irinotecan dose was increased. Results: The recommended dose was 65 mg/m2 for S-1 and 75 mg/m2 for irinotecan. Twenty-one patients were treated at the recommended dose. The overall response rate was 28.6%. Conclusion: This modified IRIS regimen is considered effective with acceptable toxicities for advanced CRC resistant to treatment with 5-fluorouracil/leucovorin or uracil and tegafur/leucovorin.
Improved FcγRIIb Targeting Functionally Translates into Enhanced Inhibition of Basophil Activation
Authors: Buschor Patrick , Eggel Alexander , Zellweger Fabian , Stadler Beda M. , Vogel Monique
Published: April 2017

Background: Mast cells and basophils express the high-affinity IgE receptor, FcεRI, as well as the low-affinity IgG receptor, FcγRIIb. While FcεRI is responsible for IgE-dependent degranulation upon coaggregation with allergens, FcγRIIb has been shown to downregulate degranulation through cross-linking with FcεRI. A previously developed fusion protein consisting of an anti-IgE DARPin linked to the human IgG1-Fc part (DE53-Fc) has been shown to simultaneously target FcεRI and FcγRIIb with low affinity and to thereby prevent basophil activation. The affinity of a ligand for its receptor is known to be critical for the functional consequences of the binding. So we generated two mutated DE53-Fc molecules with either an improved (DE53-Fc mut+) or a reduced (DE53-Fc mut-) binding to FcγRIIb and assessed their potential to inhibit IgE-dependent basophil activation. Methods: DE53-Fc was modified by introducing single site-directed point mutations in the Fc part. The mutated constructs were used to assess kinetic parameters as well as the inhibitory capacity on basophil activation and the production of leukotriene C4 (LTC4) and IL-13. Results: DE53-Fc mut+ showed increased affinity for FcγRIIb as well as an enhanced potential to inhibit IgG1 binding to FcγRIIb, resulting in improved efficacy in functional assays. Furthermore, DE53-Fc mut+ decreased de novo-synthesized LTC4 as well as the cytokine IL-13, suggesting that it might be an inhibitor of the allergic late-phase reaction. Conclusion: Our data suggest that improved binding to FcγRIIb at constant low-affinity binding to IgE leads to more efficient coaggregation of FcεRI-FcγRIIb and results in the enhanced inhibition of basophil activation.
Epidemiology and Pathogenesis of Otitis Media: Construction of a Phenotype Landscape
Authors: Bhutta Mahmood F.
Published: April 2017

Otitis media (OM) represents a complex set of clinically defined disease phenotypes. Epidemiological and pathological data suggest that inflammation of the middle ear occurs on a continuum of disease. Here I review epidemiological data and apply mathematical modelling to better define the interrelation of OM phenotypes, including the relationship of upper respiratory tract infection to acute OM (AOM), of AOM to OM with effusion, and of recurrent OM to chronicity of effusion. I use these mathematical models to represent OM graphically as a ‘landscape of disease'. This novel nosology may enable clinicians and researchers to better conceptualise middle ear inflammation in its various forms, although the limits of its application are also discussed.
A Phase I Study of Capecitabine Combined with CPT-11 in Metastatic Breast Cancer Pretreated with Anthracyclines and Taxanes
Authors: Kashiwaba Masahiro , Inaba Toru , Komatsu Hideaki , Ishida Kazushige , Kawagishi Ryoko , Matsui Yusuke , Uesugi Noriyuki , Sugai Tamotsu , Wakabayashi Go
Published: April 2017

Objective: A dose escalation study of biweekly irinotecan (CPT-11) combined with capecitabine was performed to determine the maximum tolerated dose (MTD) and recommended dose (RD) for metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes. Methods: Escalating doses of CPT-11 (80-120 mg/m2) were administered on days 1 and 15. Capecitabine was administered at a fixed dose of 1,657 mg/m2/day for 21 consecutive days, followed by 7 days of rest. We treated 3-6 patients at a particular dose level until the MTD was determined. Results: Twenty patients were treated. The MTD was determined to be 100 mg/m2, as 3 of 6 patients developed dose-limiting toxicities, grade 3 leukopenia, neutropenia, photophobia, fatigue and diarrhea. The RD for the phase II study was thus determined to be 90 mg/m2. The response rate was 41.7%. Conclusions: Combination therapy with CPT-11 and capecitabine was well tolerated with a promising response rate for MBC that had been treated previously with anthracyclines and taxanes. A multi-center phase II study is warranted to evaluate the efficacy and safety of this combination therapy with pharmacokinetic assessment.
Long-Term Improvement of Speech Perception with the Fine Structure Processing Coding Strategy in Cochlear Implants
Authors: Kleine Punte Andrea , De Bodt Marc , Van de Heyning Paul
Published: April 2017

Aims: To investigate the long-term effects of the fine structure processing (FSP) coding strategy on speech perception in noise and quality of life in experienced cochlear implant (CI) users. Methods: In a prospective comparative clinical trial, 32 experienced postlingually deafened CI recipients were upgraded from the Tempo+ to the Opus 2 audio processor, implementing FSP in one group and high-definition continuous interleaved sampling (HDCIS) coding strategy in another group with identical frequency ranges. Speech perception in noise testing and the Speech, Spatial and Qualities (SSQ) questionnaire were administered at 0, 6, 12 and 24 months after the upgrade. Results: FSP yielded significant long-term improvement of speech perception in noise of in total 13.2 dB from 16.2 dB SNR at the upgrade to 3.0 dB SNR after 24 months of FSP experience. No significant improvement of speech perception in noise over time was measured for the HDCIS group. With the SSQ questionnaire, a significant benefit of the FSP coding strategy was observed. Conclusions: The FSP coding strategy as implemented in the Med-EL Opus 2 audio processor improves speech perception in noise. This beneficial effect of FSP on speech perception in noise is not immediate but is significant after 12 months and further improves up to 24 months after implementation of FSP.
Cocaine Constriction of Rat Basilar Artery in situ: Roles of Nitric Oxide and Endothelin-1
Authors: Yoon SeongHun , Zuccarello Mario , Rapoport Robert M.
Published: April 2017

This study investigated whether cocaine constriction of rat basilar artery in situ is mediated by nitric oxide (NO) inhibition and/or endothelin (ET)-1 release. Cocaine (3-100 µmol/l) concentration-dependently constricted the basilar artery to a maximum of 18%. Nω-nitro-L-arginine (100 µmol/l) was without effect on constriction to 3 and 10 µmol/l cocaine. PD145065 (1 and 10 µmol/l), an ETA/B receptor antagonist, variably and at most partially inhibited the 100 µmol/l cocaine constriction. Capsaicin denervation of sensory nerves innervating the basilar, which contain ET-1 and NO synthase, also failed to influence cocaine constriction. These findings suggest that cocaine constriction of cerebral vessels (1) varies with respect to the involvement of ET-1 release and (2) unlike findings in the peripheral vasculature, the constriction is not mediated by inhibition of NO.
Additive Interactions between 1-Methyl-1,2,3,4-Tetrahydroisoquinoline and Clobazam in the Mouse Maximal Electroshock-Induced Tonic Seizure Model - An Isobolographic Analysis for Parallel Dose-Response Relationship Curves
Authors: Andres-Mach Marta , Haratym-Maj Agnieszka , Zagaja Mirosław , Luszczki Jarogniew J.
Published: April 2017

Background: The aim of this study was to characterize the anticonvulsant effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTHIQ) in combination with clobazam (CLB) in the mouse maximal electroshock-induced seizure (MES) model. Methods: The anticonvulsant interaction profile between 1-MeTHIQ and CLB in the mouse MES model was determined using an isobolographic analysis for parallel dose-response relationship curves. Results: Electroconvulsions were produced in albino Swiss mice by a current (sine wave, 25 mA, 500 V, 50 Hz, 0.2-second stimulus duration) delivered via auricular electrodes by a Hugo Sachs generator. There was an additive effect of the combination of 1-MeTHIQ with CLB (at the fixed ratios of 1:3, 1:1 and 3:1) in the mouse MES-induced tonic seizure model. Conclusions: The additive interaction of the combination of 1-MeTHIQ with CLB (at fixed-ratios of 1:3, 1:1 and 3:1) in the mouse MES model seems to be pharmacodynamic in nature and worth of considering in further clinical practice.
Paclitaxel and Carboplatin Treatment for Advanced Ovarian Cancer during Pregnancy
Authors: Ruiz Ramos Jesus , Roma Eva , Palomar Laura , Poveda Jose Luis
Published: April 2017

Ovarian carcinoma during pregnancy is a rare event that should be treated. In these cases, due to the lack of information available, doubts about the safety of mother and fetus are present. In this report, a 42-year-old woman who was diagnosed with a stage III ovarian carcinoma received six cycles of chemotherapy with carboplatin and paclitaxel from the 16th until 36th week of gestation. At 38 weeks, a normal male baby was born. There were no abnormalities during birth and during a 2-month follow-up period. This case adds to the available literature and supports the use of these chemotherapy agents during pregnancy, if the risk-benefit balance is appropriate.
Efficacy of Cognitive Behaviour Therapy versus Anxiety Management for Body Dysmorphic Disorder: A Randomised Controlled Trial
Authors: Veale David , Anson Martin , Miles Sarah , Pieta Maria , Costa Ana , Ellison Nell
Published: April 2017

Background: The evidence base for the efficacy of cognitive behaviour therapy (CBT) for treating body dysmorphic disorder (BDD) is weak. Aims: To determine whether CBT is more effective than anxiety management (AM) in an outpatient setting. Method: This was a single-blind stratified parallel-group randomised controlled trial. The primary endpoint was at 12 weeks, and the Yale-Brown Obsessive Compulsive Scale for BDD (BDD-YBOCS) was the primary outcome measure. Secondary measures for BDD included the Brown Assessment of Beliefs Scale (BABS), the Appearance Anxiety Inventory (AAI) and the Body Image Quality of Life Inventory (BIQLI). The outcome measures were collected at baseline and week 12. The CBT group, unlike the AM group, had 4 further weekly sessions that were analysed for their added value. Both groups then completed measures at their 1-month follow-up. Forty-six participants with a DSM-IV diagnosis of BDD, including those with delusional BDD, were randomly allocated to either CBT or AM. Results: At 12 weeks, CBT was found to be significantly superior to AM on the BDD-YBOCS [β = -7.19; SE (β) = 2.61; p < 0.01; 95% CI = -12.31 to -2.07; d = 0.99] as well as the secondary outcome measures of the BABS, AAI and BIQLI. Further benefits occurred by week 16 within the CBT group. There were no differences in outcome for those with delusional BDD or depression. Conclusions: CBT is an effective intervention for people with BDD even with delusional beliefs or depression and is more effective than AM over 12 weeks.
Short QT Syndrome Manifesting with Neonatal Atrial Fibrillation and Bradycardia
Authors: Villafañe Juan , Fischbach Peter , Gebauer Roman
Published: April 2017

Objectives: Atrial fibrillation (AF) is rare during childhood and usually associated with other cardiovascular pathology. In lone AF, the ventricular response rate is usually rapid. We sought to describe a subset of children who present with early-onset AF and a slow ventricular response rate who were found to have the short QT syndrome (SQTS). Methods: Using a MEDLINE/PubMed search, children with AF, a structurally normal heart and bradycardia were identified. Demographics, clinical presentation, electrocardiographic (ECG) findings, electrophysiologic testing, genetic analysis and follow-up assessment were collected on each child for analysis. Results: Four children were identified in the literature and combined with 2 other children followed by the authors. All had a short QT interval and those who were tested were found to have a gain-of-function mutation in the KCNQ1 gene. Conclusions: We describe a subclass of children with SQTS who present with AF and a slow ventricular response. Medical therapy has not been effective in maintaining sinus rhythm. The long-term outcome remains unknown for these children. This condition may present in utero as persistent bradycardia with postnatal ECG showing a very short QT interval.
The Left Atrium: From the Research Laboratory to the Clinic
Authors: Boudoulas Konstantinos Dean , Paraskevaidis Ioannis A. , Boudoulas Harisios , Triposkiadis Filippos K.
Published: April 2017

Studies of left atrial (LA) function, until the latter part of the 20th century, were mostly limited to experimental animal models and to studies related to clinical research in the cardiac catheterization laboratory. For this reason, LA function has received considerably less attention than left ventricular (LV) functions, even though evidence suggests that LA myopathy and failure may exist as an isolated entity, precede and/or coexist with LV myopathy. The introduction of echocardiography and Doppler echocardiography in clinical practice has contributed significantly to our understanding of LA function and its interrelationships with the LV, aorta, pulmonary artery and other parts of the cardiovascular system. In addition, LA with the secretion of atrial natriuretic peptides is playing an important role in cardiovascular and neurohumoral homeostasis. Today, it is well known that LA structural and functional abnormalities that are present in many diseases and disorders constitute a powerful prognostic indicator. As technology (echocardiography, magnetic resonance imaging, computed tomography and others) continues to evolve, it is expected that, in the near future, LA structure and function will be routinely used as LV function is used today.
Lymph-Node Ratio Classification Strongly Correlates with Cancer Survivals of Patients Who Underwent R0 Resection for Gastric Cancer with More than 15 Nodes Harvested
Authors: Lorenzon Laura , Mercantini Paolo , Ferri Mario , La Torre Marco , Sparagna Alessandra , Balducci Genoveffa , Cavallini Marco , Ziparo Vincenzo
Published: April 2017

Background: During the last few years, the gastric cancer nodal staging has been extensively revised. Lately, a new system emerged in this field with the purpose of implementing the prognostic stratification: the lymph-node ratio (LNR). The aim of this study was to investigate the prognostic value of the LNR in relation to cancer survivors undergoing resection for gastric adenocarcinoma. Methods: Off 227 patients undergoing surgical resection for gastric cancer at our Department, 129 curative gastric resections with more than 15 nodes harvested were selected. The LNR was calculated and patients were stratified into 6 subgroups based on the ratio values. The subgroups were compared for data analysis. Survivals were calculated by the Kaplan-Meier method, and the mean follow-up period was 40 months. ROC curves were calculated in order to analyze the performance of the LNR system. Results: LNR stratification correlated with the stage of the disease, with the rate of patients undergoing chemotherapy and patients presenting with a relapse of disease at follow-up. Moreover, an increased ratio correlated with a worse overall, a disease-free and a disease-specific survival of the patients. The ROC curves documented a significant performance of the stratification system with the endpoints of disease-free and disease-specific survivals. Conclusion: LNR stratification correlated with cancer-related survivals in our case series. It is a reliable system that might improve current nodal staging and thereby the identification of patients with a higher risk of recurrence or cancer-related mortality.
Effectiveness of Therapeutic Selective Neck Dissection in Laryngeal Cancer
Authors: Allegra Eugenia , Franco Teresa , Domanico Rossana , La Boria Alessandro , Trapasso Serena , Garozzo Aldo
Published: April 2017

Background: The aim of this study was to evaluate the effectiveness of selective neck dissection (SND) in patients with laryngeal cancer and clinically positive cervical nodes. Subjects and Methods: A retrospective review of the clinical records of 58 consecutive untreated patients affected by laryngeal carcinoma and submitted to surgical treatment was performed. Results: Twenty-six (44.8%) patients received monolateral neck dissection and 32 (55.2%) bilateral neck dissection. A total of 90 hemineck dissections were performed. Histopathological examination revealed that 25 of the 58 patients had negative nodes (pN0) and 33 had positive nodes (pN+). Extracapsular spread was found in 12 of the 33 pN+ patients. Twenty-eight of the 58 (48.2%) patients were submitted to adjuvant radiotherapy. Six of the 58 patients submitted to neck dissection had neck recurrence (rate of 10.3%). The only independent prognostic factor for neck recurrence was extracapsular spread. For the 58 patients, the 5-year overall survival was 50% and the disease-specific survival 68.9%. The 5-year disease-specific survival was 76% for pN0 patients and 63.6% for pN+ patients. Conclusions: SND can represent a therapeutic procedure because it has shown oncological results comparable to those of comprehensive neck dissection, especially when SND is combined with adjuvant radiotherapy.
Antibiotic Resistance of Gram-Negative Bacilli Isolated from Pediatric Patients with Nosocomial Bloodstream Infections in a Mexican Tertiary Care Hospital
Authors: Ares Miguel Ángel , Alcántar-Curiel Maria Dolores , Jiménez-Galicia César , Rios-Sarabia Nora , Pacheco Sabino , De la Cruz Miguel Ángel
Published: April 2017

Background: Gram-negative bacilli are the most common bacteria causing nosocomial bloodstream infections (NBSIs) in Latin American countries. Methods: The antibiotic resistance profiles of Gram-negative bacilli isolated from blood cultures in pediatric patients with NBSIs over a 3-year period in a tertiary care pediatric hospital in Mexico City were determined using the VITEK-2 system. Sixteen antibiotics were tested to ascertain the resistance rate and the minimum inhibitory concentration using the Clinical Laboratory Standards Institute (CLSI) broth micro-dilution method as a reference. Results: A total of 931 isolates were recovered from 847 clinically significant episodes of NBSI. Of these, 477 (51.2%) were caused by Gram-negative bacilli. The most common Gram-negative bacilli found were Klebsiella pneumoniae (30.4%), Escherichia coli (18.9%), Enterobacter cloacae (15.1%), Pseudomonas aeruginosa (9.9%), and Acinetobacter baumannii (4.6%). More than 45 and 60% of the K. pneumoniae and E. coli isolates, respectively, were resistant to cephalosporins, and 64% of the E. coli isolates were resistant to fluoroquinolones. A. baumannii exhibited low rates of resistance to antibiotics tested. In the E. cloacae and P. aeruginosa isolates, no rates of resistance higher than 38% were observed. Conclusions: In this study, we found that the proportion of NBSIs due to antibiotic-resistant organisms is increasing in a tertiary care pediatric hospital of Mexico.
The Assessment of Eating Behaviour in Children Who Are Obese: A Psychological Approach. A Position Paper from the European Childhood Obesity Group
Authors: Braet Caroline , O'Malley Grace , Weghuber Daniel , Vania Andrea , Erhardt Éva , Nowicka Paulina , Mazur Artur , Frelut Marie Laure , Ardelt-Gattinger Elisabeth
Published: April 2017

Objective: This paper introduces health professionals to the different psychological models thought to influence eating behaviour in the absence of hunger in children who are obese and to propose a method of assessing these behaviours in practice. Methods: Clinical researchers from the European Childhood Obesity Group (ECOG) adopted an evidence-based approach to examine the literature concerning the assessment of eating behaviour in children who are obese. Studies published in English were filtered out of the medical and psychological literature from 1960 to the present, and the resulting bibliography was searched for relevant articles. Key themes from the current evidence were compiled and classified according to the underpinning psychological models. Based on the current evidence and the authors' combined clinical experience, a three-staged approach to assessment was agreed by consensus. Results: Valid and reliable tools for assessing and monitoring each of the three identified models (Dietary Restraint Theory, Emotional Eating and the Diathesis-Stress Model) are suggested for use in clinical practice, and the ECOG three-staged approach to assessing eating behaviours in the absence of hunger is described. Conclusions: This paper presents practical guidance on how to assess eating behaviour in the absence of hunger in children who are clinically obese and suggests a focus for future research.
Instant Reocclusion following Mechanical Thrombectomy of in situ Thromboocclusion and the Role of Low-Dose Intra-Arterial Tirofiban
Authors: Kang Dong-Hun , Kim Yong-Won , Hwang Yang-Ha , Park Sung-Pa , Kim Yong-Sun , Baik Seung Kug
Published: April 2017

Background: An in situ thromboocclusion (IST) is defined as an infarct extensively involving all or most of a stenosed arterial territory, which is one major stroke mechanism related to intracranial atherosclerosis (ICAS). We focused on ISTs occurring in major cerebral arteries and analyzed their rate of instant reocclusion during mechanical thrombectomy (MT) compared with non-ISTs. Also, we introduced a treatment strategy of low-dose intra-arterial tirofiban administration to prevent such reocclusion following repeat recanalization, and evaluated its safety and efficacy. Methods: We analyzed 168 consecutive patients treated with MT over a 2-year period from May 2011 to April 2013. During MT, if angiography following a successful recanalization showed stenosis at the occlusion site, we performed additional angiographic runs every 10 min for 30 min after the recanalization. Then, if angiography revealed reocclusion, we performed a repeat recanalization, using the same MT technique but additionally followed by low-dose intra-arterial tirofiban infusion. Time-of-flight MR angiography or CT angiography was performed to confirm any underlying ICAS at the occlusion site 5-7 days after the procedure. The patients who had confirmed underlying ICAS were included in the IST cohort. Results: Of 168 enrolled patients, we excluded 36 who could not be checked for underlying ICAS at the occlusion site for one of the following reasons: recanalization failure (n = 11), rescue stenting after tirofiban failure (n = 5) and lack of follow-up vascular imaging (n = 20). The incidence of IST was 30.3% (40/132). All IST patients were confirmed to have underlying ICAS by follow-up vascular imaging. Instant reocclusion after successful recanalization was significantly more frequent in the IST cohort [26/40 (65%) vs. 3/92 (3.3%); p < 0.001]. Regarding the efficacy of low-dose intra-arterial tirofiban infusion, 85.7% of the reocclusion patients finally achieved a thrombolysis in cerebral infarction score 2/3 recanalization, but in the remaining 14.3% of the cases, the condition was refractory to the procedure and required rescue stenting. There were no cases of symptomatic intracranial hemorrhage following the procedure. Conclusions: In situ thromboocclusion was characterized by a significantly higher chance of instant reocclusion during MT. In such cases, low-dose intra-arterial tirofiban administration may be effective and safe. However, future confirmation by prospective multicenter trials seems necessary.
Hyperhomocysteinemia and Risk of Cognitive Decline: A Meta-Analysis of Prospective Cohort Studies
Authors: Nie Tian , Lu Ting , Xie Lu , Huang Panpan , Lu Yuan , Jiang Minhai
Published: April 2017

Objective: To evaluate the association between hyperhomocysteinemia (HHcy) and risk of cognitive decline. Methods: Electronic databases such as PubMed and EMBASE were searched for prospective cohort studies that involved the relationship between HHcy and risk of cognitive decline. Adjusted risk ratios (RRs) and corresponding 95% confidence intervals (95% CIs) were calculated by Review Manager 5.2.7. Subgroup analyses were conducted on stratification of some important variables. Results: Fourteen publications were included in the analysis. The pooled RR was 1.53 (95% CI, 1.23-1.91; p = 0.0002) for patients with HHcy compared to subjects without HHcy. Subgroup analyses indicated that the pooled RRs were 1.51 (95% CI, 1.10-2.05; p = 0.01) for more than five-year follow-up studies and 1. 56 (95% CI, 1.13-2.14; p = 0.007) for less than five-year follow-up studies. The pooled RRs were 1.66 (95% CI, 1.21-2.26; p = 0.001) for studies excluding the confounder of B vitamins and 1.34 (95% CI, 1.08-1.66; p = 0.008) for non-excluded studies. In terms of region, the pooled RR was 1.60 (95% CI, 1.21-2.13; p = 0.001) for European and American countries, while the pooled RR was 1.27 (95% CI, 1.02-1.59; p = 0.03) for other regions. Conclusion: As one of the independent risk factors, HHcy was associated with an increased risk of cognitive decline.
Response of Schizophrenic Patients to Dynamic Facial Expressions: An Event-Related Potentials Study
Authors: Fukuta Mayuko , Kirino Eiji , Inoue Reiichi , Arai Heii
Published: April 2017

Objective: Patients with schizophrenia have an impaired ability to respond to faces and may specifically show an impaired response to dynamic facial expressions. Here we investigated the responses of schizophrenic patients and healthy controls to dynamic facial images using event-related potentials (ERPs). Methods: We showed 13 schizophrenic patients and 13 healthy controls visual stimuli comprising facial expressions that continually changed from neutral to emotional. Results: N200 latencies and P100-N200 peak-to-peak amplitudes in controls were prolonged or greater for dynamic emotions in comparison with those for static stimuli, but the group with schizophrenia showed no significant differences in responses to dynamic and static emotions. A significant negative correlation was observed between N200 latencies for dynamic negative emotion and PANSS (positive and negative syndrome scale) general psychopathology scale scores. Conclusions: A combination of hypersensitivity to static emotions and hyposensitivity to dynamic emotions in people with schizophrenia might underlie the absence of differences in response to these stimuli. A tendency in the schizophrenic group to hypersensitivity to static emotions might arise from the enhanced fear and arousal characteristics of this group; their hyposensitivity to dynamic emotions might result from controlled attentional bias away from facial expressions to reduce fear and anxiety.
Oxidative Stress Induced by Lipid Peroxidation Is Related with Inflammation of Demyelination and Neurodegeneration in Multiple Sclerosis
Authors: Wang Pin , Xie Keqin , Wang Cunfu , Bi Jianzhong
Published: April 2017

Background: Multiple sclerosis (MS) is a chronic autoimmune demyelination disorder of the central nervous system (CNS) and its etiology remains unknown. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines, which contribute to the development and progression of multiple sclerosis. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress is involved in the inflammation leading demyelination and neurodegeneration in the pathogenesis of multiple sclerosis. Summary: The present study aims to determine two biochemical markers of oxidative stress: TAC and MDA and to show their correlations whether oxidative stress reaction occurs in the demyelination through analyzing samples including peripheral blood and cerebrospinal fluid (CSF) from patients with relapsing-remitting MS (RR-MS). Totally, there were 20 patients in the control groups made from individuals with normal pressure hydrocephalus. Thirty MS patients diagnosed with McDonald diagnostic criteria (2010) treated with methylprednisolone were included in this study. Data were stratified by the degree of severity in order to clarify the role of oxidative stress in the mechanisms of MS and to assess its potential as a biomarker. Thirty clinically definite RRMS patients were enrolled in this study. Levels of MDA, GSH, total antioxidant capacity TAC, GSH-Px and ROS, were determined in serum of the control group and RRMS patients in 7 days before MP (methylprednisolone) treatment and one month after MP treatment. Statistical analysis was performed with one-way analysis of variance (ANOVA), followed by LSD's post hoc tests. Key Messages: Oxidative stress precedes the inflammatory response in the multiple sclerosis patients. And methylprednisolone treatment can decrease brain antioxidant enzymes to reduce the neuroinflammatory attack.
Blockade of the Monocyte Chemoattractant Protein-1 Receptor Pathway Ameliorates Myocardial Injury in Animal Models of Ischemia and Reperfusion
Authors: Al-Amran Fadhil G. , Manson Mandel Z. , Hanley Tennent K. , Hainz Douglas L.
Published: April 2017

Background: Myocardial infarction is accompanied by inflammatory responses that lead to the recruitment of leukocytes and subsequent myocardial damage and healing. Monocyte chemoattractant protein-1 (MCP-1, also known as CC chemokine ligand 2) and its receptor CC chemokine receptor 2 play a central role in the inflammatory response and myocardial injury after ischemia/reperfusion (I/R). Methods: Male adult C57BL/6 mice were anesthetized, and the left anterior descending coronary artery was ligated for 30 min. After reperfusion for 3 days, the ischemia and infarct sizes were determined. Results: The treatment of C57BL/6 mice with anti-MCP-1 reduced the infarct size and lessened myocardial inflammation. Furthermore, anti-MCP-1 prevented I/R-induced caspase-3/7 and -8 activities and reduced apoptosis. The treatment of operated mice with anti-MCP-1 shortly before the induction of myocardial ischemia resulted in a reversal of the infarction and improvements in histologic parameters. Conclusion: These findings demonstrate a pathogenic role for MCP-1 in animal models of I/R and support the consideration of MCP-1 as a therapeutic target in myocardial ischemia.
Dissemination of Psychotherapy for Trauma Spectrum Disorders in Postconflict Settings: A Randomized Controlled Trial in Rwanda
Authors: Jacob Nadja , Neuner Frank , Maedl Anna , Schaal Susanne , Elbert Thomas
Published: April 2017

Background: Dissemination of psychotherapeutic modules to local counselors seems a key requirement for coping with mental health disasters in conflict regions. We tested a train-the-trainer (TTT) dissemination model for the treatment of posttraumatic stress disorder (PTSD). Methods: We randomly assigned widowed or orphaned survivors of the 1994 Rwandan genocide with a PTSD diagnosis to narrative exposure therapy (NET) treatment (NET-1, n = 38) or to a 6-month waiting list (WL) condition to be followed by treatment (WL/NET-2, n = 38). Expert therapists trained a first dissemination generation of local Rwandan psychologists in NET complemented by 2 sessions of interpersonal psychotherapy modules. Under the supervision of the experts, these Rwandan psychologists (a) provided NET to the NET-1 participants and (b) subsequently trained and supervised a second generation of local psychologists. This second dissemination generation provided treatment to the WL/NET-2 group. The primary outcome measure was the Clinician-Administered PTSD Scale total score before therapy and at 3- and 12-month follow-ups. Results: At the 3-month follow-up, the NET-1 participants suffered significantly and substantially less from PTSD symptoms than the participants in the WL group. The treatment gains of NET-1 were maintained and increased at follow-up, with a within-group effect size of Cohen's d = 1.47 at the 12-month follow-up. After treatment by the second dissemination generation of therapists, the WL/NET-2 participants improved to an extent similar to that of the NET-1 group at follow-ups, with an effect size of Cohen's d = 1.37 at the 12-month follow-up. Conclusions: A TTT model of PTSD treatment dissemination can be effective in resource-poor postconflict societies.
Predictors of Coronary Artery Disease in Patients with Behçet's Disease
Authors: Pandey Ambarish , Garg Jalaj , Krishnamoorthy Parasuram , Palaniswamy Chandrasekar , Doshi Jay , Lanier Gregg , Ahmad Hasan
Published: April 2017

Background: Behçet's disease (BD) is a multisystem vasculitis of unknown etiology. We aimed to determine the prevalence and predictors of coronary artery disease (CAD) in patients with BD. Methods: All adult patients diagnosed with BD from the National Inpatient Sample database using the International Classification of Diseases 9th revision (ICD-9 code 136.1) during 2009-2010 were included in the analysis. We analyzed the demographics, traditional risk factors, prevalence, and predictors of CAD in patients with BD using ICD-9 codes. Results: The prevalence of BD among adults was 0.006% (n = 2,540) of all in-hospital admissions in the USA. The mean age was 43.9 years, with women (45 years) being older than men (40 years) (p < 0.001). Traditional risk factors prevalent in our study were hypertension (35%), hyperlipidemia (17.4%), diabetes mellitus (13.8%), smoking (13.1%), and obesity (7.2%). The prevalence of CAD was 12.1%. Hypertension (OR = 2.20, p = 0.03) and hyperlipidemia (OR = 2.34, p = 0.02) were found to be independent predictors of CAD in a multimodel regression analysis. Conclusion: In patients with BD, traditional risk factors associated with CAD were similar to what is expected in the overall population. However, the young age of patients with CAD in this population suggests an accelerated course of atherosclerosis in BD.
Clinicopathologic Review of Non-Myxoma Cardiac Tumors: A 10-Year Single-Center Experience
Authors: Anvari Maryam Sotoudeh , Naderan Mohammad , Eslami Shahr Babaki Amir , Shoar Saeed , Boroumand Mohammad Ali , Abbasi Kyomars
Published: April 2017

Objective: To report the prevalence, clinical presentation and histological characteristics of non-myxoma cardiac tumors in a major tertiary heart center. Method: Review of the medical profiles of 36,930 patients admitted to our hospital between 2003 and 2013 yielded a total of 86 cases of cardiac tumors (63 cases of myxomas and 23 cases of non-myxoma tumors). Clinical presentations and histological features were presented exclusively for primary and secondary tumors. Results: Of 23 enrolled patients with non-myxoma tumors, 5 had primary tumors and 18 had secondary or metastatic tumors. The most frequent origins of the secondary tumors were breast cancer, lymphoma, leukemia and lung cancer. Most secondary tumors had pericardial involvement, and only one tumor involved the left atrium. Sarcomas, including spindle-cell sarcoma and liposarcoma, comprised the majority of the primary malignant tumors. None of these tumors had pericardial involvement, and, except for one case, all were confined to the left side of the heart. All patients were symptomatic on admission, with dyspnea being the most frequent presenting symptom. Conclusion: Metastatic cardiac tumors were more prevalent than the primary ones, with fibromas constituting the largest proportion of the primary tumors and breast cancer being the prevalent cause of metastasis.
Validity of a Screening Question for Head Tremor: An Analysis of Four Essential Tremor Case Samples
Authors: Louis Elan D. , Michalec Monika
Published: April 2017

Background: The goal of this study was to assess the validity of a screening question for head tremor in essential tremor (ET). There are no published data on this topic, and the knowledge will guide future epidemiological investigations of this disorder. Methods: These analyses utilized four distinct patient samples: a population-based study in northern Manhattan, a study of the environmental epidemiology of ET, a genetics study, and a brain repository. Sensitivity was the proportion of ET cases with head tremor on examination who self-reported head tremor. Results: The sensitivity of the screening question for head tremor was lowest in the population-based study (31.6%), and higher as well as somewhat similar across the remaining studies (46.7 to 62.2%). Higher sensitivity was associated with tremor of longer duration, presence of voice tremor on examination, female gender, and lower education. The use of the screening question would have increased case ascertainment during the screening phase of these four studies by 1.9, 4.1, 10.2, and 20.3%. Conclusions: A screening question for head tremor had low-to-moderate sensitivity in ET. The use of such a screening questionnaire, however, has the potential to increase case ascertainment by as much as 20% in some screening settings.
Heart Failure as First Sign of Development of Cardiac Metastases in a Patient with Diagnosis of Papillary Thyroid Carcinoma on Treatment with Tyrosine-Kinase Inhibitors: Differential Diagnoses and Clinical Management
Authors: Bruixola Gema , Segura Ángel , Caballero Javier , Andrés Ana , Reche Encarnación , Escoín Corina , Díaz-Beveridge Roberto
Published: April 2017

Background: Cardiac metastases from papillary thyroid carcinoma are very uncommon. Their incidence is rising due to improvements in survival and diagnosis; nevertheless, our patient is the fourth case reported up to date. There are no clinical trials available in this scenario. Therefore, treatment choice is made based on clinical experience and case reports; notably, the largest case report series was prior to the approval for using tyrosine-kinase inhibitors in thyroid cancer. Patient: A 73-year-old lady had dedifferentiated papillary thyroid cancer with ongoing sorafenib. After 9 months on this treatment, she presented with dyspnea and heart failure. Differential diagnosis included infection, progression of disease and cardiotoxicity. After a comprehensive assessment (echocardiography, computed tomography, PET, magnetic resonance), we found progression of lung disease, and the appearance of heart metastases. Results: After recovering from the basal status, she started on second-line treatment with sunitinib, which was well-tolerated. She achieved stable disease with a decrease in tumor marker levels. Conclusions: We should include cardiac metastases in the differential diagnosis of heart failure in cancer patients. Magnetic resonance imaging is the gold standard for assessment. Sorafenib is the mainstay of the first-line therapy in metastatic thyroid cancer, achieving long-term disease control with good tolerance. Sunitinib could be a safe second-line treatment option (not cardiotoxicity related) with promising results. Therefore, our report presents a sequence of treatment with tyrosine-kinase inhibitors in metastatic thyroid carcinoma with an encouraging outcome, which deserves further investigation.