bluuebunny/crossref_metadata_2025_split huggingface dataset:
L-Carnitine–Mediated Tumor Cell Protection and Poor Patient Survival Associated with OCTN2 Overexpression in Glioblastoma Multiforme
Authors: Fink Matthias A. , Paland Heiko , Herzog Susann , Grube Markus , Vogelgesang Silke , Weitmann Kerstin , Bialke Angela , Hoffmann Wolfgang , Rauch Bernhard H. , Schroeder Henry W.S. , Bien-Möller Sandra 
Published: January 2019

Abstract

Purpose:
Apoptotic dysregulation, redox adaptive mechanisms, and resilience to hypoxia are major causes of glioblastoma (GBM) resistance to therapy. Commonly known as crucial factors in energy metabolism, OCTN2 (SLC22A5) and its substrate L-carnitine (LC) are increasingly recognized as actors in cytoprotection. This study provides a comprehensive expression and survival analysis of the OCTN2/LC system in GBM and clarifies the system's impact on GBM progression.

Experimental Design:
OCTN2 expression and LC content were measured in 121 resected human GBM specimens and 10 healthy brain samples and analyzed for prognostic significance. Depending on LC administration, the effects of hypoxic, metabolic, and cytotoxic stress on survival and migration of LN18 GBM cells were further studied in vitro. Finally, an orthotopic mouse model was employed to investigate inhibition of the OCTN2/LC system on in vivo GBM growth.

Results:
Compared with healthy brain, OCTN2 expression was increased in primary and even more so in recurrent GBM on mRNA and protein level. High OCTN2 expression was associated with a poor overall patient survival; the unadjusted HR for death was 2.7 (95% CI, 1.47–4.91; P &lt; 0.001). LC administration to GBM cells increased their tolerance toward cytotoxicity, whereas siRNA-mediated OCTN2 silencing led to a loss of tumor cell viability. In line herewith, OCTN2/LC inhibition by meldonium resulted in reduced tumor growth in an orthotopic GBM mouse model.

Conclusions:
Our data indicate a potential role of the OCTN2/LC system in GBM progression and resistance to therapy, and suggests OCTN2 as a prognostic marker in patients with primary GBM.
Incidence and Prevalence of Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Systematic Review and Meta-Analysis
Authors: Broers Merel C. , Bunschoten Carina , Nieboer Daan , Lingsma Hester F. , Jacobs Bart C. 
Published: January 2019

<b><i>Background:</i></b> Prevalence and incidence rates of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are required to determine the impact of CIDP on society. We aimed to estimate the prevalence and incidence of CIDP worldwide and to determine the effect of diagnostic criteria on prevalence and incidence. <b><i>Method:</i></b> A systematic review was conducted for all published incidence and prevalence studies on CIDP until May 18, 2017. Methodological quality was assessed using the Methodological Evaluation of Observational Research checklist. We performed a random effect meta-analysis to estimate pooled prevalence and incidence rates. <b><i>Results:</i></b> Of the 907 studies, 11 were included in the systematic review, 5 in the meta-analysis of incidence (818 cases; 220,513,514 person-years) and 9 in the meta-analysis of prevalence (3,160 cases; 160,765,325 population). These studies had a moderate quality. The pooled crude incidence rate was 0.33 per 100,000 person-years (95% CI 0.21–0.53; <i>I</i><sup>2</sup> = 95.7%) and the pooled prevalence rate was 2.81 per 100,000 (95% CI 1.58–4.39; <i>I</i><sup>2</sup> = 99.1%). Substantial heterogeneity in incidence and prevalence across studies seems to be partly explained by using different diagnostic criteria. <b><i>Conclusion:</i></b> These findings provide a starting point to estimate the social burden of CIDP and demonstrate the need to reach consensus on diagnostic criteria for CIDP.
Cortical Perfusion and Tubular Function as Evaluated by Magnetic Resonance Imaging Correlates with Annual Loss in Renal Function in Moderate Chronic Kidney Disease
Authors: Prasad Pottumarthi V. , Li Lu-Ping , Thacker Jon M. , Li Wei , Hack Bradley , Kohn Orly , Sprague Stuart M. 
Published: January 2019

<b><i>Background:</i></b> Chronic hypoxia is a well-recognized factor in the pathogenesis of chronic kidney disease (CKD). Loss of microcirculation is thought to lead to enhanced renal hypoxia, which in turn results in the development of fibrosis, a hallmark of progressive CKD. To evaluate the role of functional magnetic resonance imaging (MRI), we performed perfusion, oxygenation, and diffusion MRI measurements in individuals with diabetes and stage 3 CKD. <b><i>Methods:</i></b> Fifty-four subjects (41 individuals with diabetes and stage 3 CKD and 13 healthy controls) participated in this study. Data with blood oxygenation level dependent (BOLD), arterial spin labeling perfusion and diffusion MRI were acquired using a 3T scanner. <b><i>Results:</i></b> Renal cortical perfusion was reduced in CKD compared to the controls (109.54 ± 25.38 vs. 203.17 ± 27.47 mL/min/100 g; <i>p</i> &#x3c; 0.001). Cortical apparent diffusion coefficient showed no significant reduction in CKD compared to controls (1,596.10 ± 196.64 vs. 1,668.72 ± 77.29 × 10<sup>–6</sup> mm<sup>2</sup>/s; <i>p</i> = 0.45) but was significantly associated with perfusion. Cortical R2* values were modestly increased in CKD (20.76 ± 4.08 vs. 18.74 ± 2.37 s<sup>–1</sup>; <i>p</i> = 0.12). Within the CKD group, R2*_Medulla and R2*_Kidney were moderately and negatively associated with estimated glomerular filtration rate. There was a significant association between cortical perfusion and medullary response to furosemide with annual loss of renal function, used as an estimate of CKD progression. <b><i>Conclusions:</i></b> Subjects with a moderate degree of CKD had significantly lower renal perfusion. Diffusion and BOLD MRI showed more modest differences between the groups. Individuals with progressive CKD had lower perfusion and response to furosemide.
TECHNOLOGICAL ASPECTS OF TABLETS CREATION BASED ON FLAMMULINA VELUTIPES BIOMASS DRY POWDER
Authors: Butkevych T. A. , Syatynya М. L. , Popovych V. P. 
Published: January 2019

The aim of the work. To study the pharmaco-technological properties of granulate and tablets based on Flammulina velutipes biomass dry powder, to develop the composition and technology of the medication.
Materials and Methods. Research of granules and tablets pharmaco-technological properties (sieve analysis, bulk density, tapped density, compressibility index, Hausner ratio, flowability of tablet mass, average weight, resistance to crushing, friability and disintegration of tablets) was carried out in accordance to the requirements of State Pharmacopoeia of Ukraine 2nd edition.
Results and Discussion. The determined pharmaco-technological parameters of the granulate indicate good values ​​of the bulk density, tapped density, compressibility index, Hausner ratio and flowability. An intermediate product undergoes a tabletting process to produce a qualitative finished product of satisfactory appearance (plain, cylindrical tablets with a facet, yellowish-white color with brown inclusions, with a height of 4 mm, and diameter of 10 mm), a constant average mass (1.0 g), and strength (68 N).
Conclusions. The pharmaco-technological properties of tablet mass (granulate) and Flammulina velutipes biomass dry powder tablets (sieve analysis, bulk density, tapped density, compressibility index, Hausner ratio, flowability, average weight, resistance to crushing, friability and disintegration) were studied. The composition and technology of Flammulina velutipes biomass dry powder tablets have been developed, pharmaco-technological parameters of their quality have been studied, technological block diagram of industrial production has been developed.
ВИВЧЕННЯ ВПЛИВУ ДОПОМІЖНИХ РЕЧОВИН НА ФАРМАКО-ТЕХНОЛОГІЧНІ ХАРАКТЕРИСТИКИ ТАБЛЕТОК L-АРГІНІНУ З ТІОТРИАЗОЛІНОМ
Authors: Khromylova O. V. 
Published: January 2019

Мета роботи. Вивчення впливу допоміжних речовин на стираність, стійкість до роздавлювання і час розпадання таблеток таблеток L-аргініну з тіотриазоліном.
Матеріали і методи. У дослідженнях використовували: L-аргінін (виробник: Sigma-Aldrich, США), тіотриазолін (виробник: Державне підприємство «Завод хімічних реактивів» Науково-технологічного комплексу «Інститут монокристалів» НАН України), сертифіковані допоміжні речовини, як вітчизняного, так і закордонного виробництва.
Результати й обговорення. Дисперсійний аналіз результатів дослідження за показниками стираності таблеток, стійкості таблеток до роздавлювання і часу розпадання таблеток L-аргініну з тіотриазоліном допоміг на основі порівняння отриманих середніх значень рівнів вивчених факторів вибрати кращі допоміжні речовини: маніт із зразків наповнювачів на основі цукрів, крохмаль картопляний із зразків розпушувачів, МКЦ 301 – з групи регуляторів вологи, з групи зв’язуючих речовин обрано 3 % розчин ГПМЦ 2910.
Висновки. За результатами проведених досліджень ми вивчили вплив чотирьох груп допоміжних речовин на стираність, стійкість до роздавлювання та час розпадання таблеток L-аргініну з тіотриазоліном, отриманних методом вологої грануляції. Дисперсійний аналіз результатів експериментальних даних допоміг вибрати допоміжні речовини, які забезпечують необхідні фармако-технологічні вимоги, що висуваються до таблеткової лікарської форми ДФУ.
Lipoprotein(a) Levels and the Risk of Myocardial Infarction Among 7 Ethnic Groups
Authors: Paré Guillaume , Çaku Artuela , McQueen Matthew , Anand Sonia S. , Enas Enas , Clarke Robert , Boffa Michael B. , Koschinsky Marlys , Wang Xingyu , Yusuf Salim ,   On behalf of the INTERHEART Investigators
Published: January 2019

Background:
Lipoprotein(a) [Lp(a)] levels predict the risk of myocardial infarction (MI) in populations of European ancestry; however, few data are available for other ethnic groups. Furthermore, differences in isoform size distribution and the associated Lp(a) concentrations have not fully been characterized between ethnic groups.

Methods:
We studied 6086 cases of first MI and 6857 controls from the INTERHEART study that were stratified by ethnicity and adjusted for age and sex. A total of 775 Africans, 4443 Chinese, 1352 Arabs, 1856 Europeans, 1469 Latin Americans, 1829 South Asians, and 1221 Southeast Asians were included in the study. Lp(a) concentration was measured in each participant using an assay that was insensitive to isoform size, with isoform size being assessed by Western blot in a subset of 4219 participants.

Results:

Variations in Lp(a) concentrations and isoform size distributions were observed between populations, with Africans having the highest Lp(a) concentration (median=27.2 mg/dL) and smallest isoform size (median=24 kringle IV repeats). Chinese samples had the lowest concentration (median=7.8 mg/dL) and largest isoform sizes (median=28). Overall, high Lp(a) concentrations (>50 mg/dL) were associated with an increased risk of MI (odds ratio, 1.48; 95% CI, 1.32–1.67;
P
<0.001). The association was independent of established MI risk factors, including diabetes mellitus, smoking, high blood pressure, and apolipoprotein B and A ratio. An inverse association was observed between isoform size and Lp(a) concentration, which was consistent across ethnic groups. Larger isoforms tended to be associated with a lower risk of MI, but this relationship was not present after adjustment for concentration. Consistent with variations in Lp(a) concentration across populations, the population-attributable risk of high Lp(a) for MI varied from 0% in Africans to 9.5% in South Asians.

Conclusions:
Lp(a) concentration and isoform size varied markedly between ethnic groups. Higher Lp(a) concentrations were associated with an increased risk of MI and carried an especially high population burden in South Asians and Latin Americans. Isoform size was inversely associated with Lp(a) concentration, but did not significantly contribute to risk.
Imaging Characteristics of Mismatch Lesions: An Angiographic and Intravascular Ultrasound Analysis of 1369 Coronary Lesions
Authors: Phan Tan Quang , Nguyen Lan Hieu , Nguyen Lan Viet , Lee Wang Soo , Won Hoyoun , Cho Iksung , Shin Seung Yong , Sharmin Saima , Thottian Julian Johny , Kim Sang-Wook 
Published: January 2019

Objectives:To evaluate the angiographic and intravascular ultrasound (IVUS) characteristics of coronary mismatch lesions.Background:Better understanding about the characteristics of mismatch lesions may help to achieve more accurate lesion assessment and, thereby, to improve the outcomes of percutaneous coronary intervention (PCI).Methods:Angiographic and IVUS data from 1369 lesions were analyzed. Mismatch lesion was defined as the difference between proximal and distal reference lumen diameters of ≥1.0 mm or ≥30% of the distal reference lumen diameter.Results:The incidence of mismatch lesions was 20.1% (275/1369). Compared to nonmismatch group, mismatch group had longer lesions (21.3 [6.4] mm vs 18.4 [6.4] mm, P < .001) with smaller minimum lumen diameter (0.87 [0.29] mm vs 1.10 [0.31] mm, P < .001) and more severe diameter stenosis (78.8% [9.2%] vs 66.3% [10.3%], P < .001). On IVUS, mismatch group had larger lumen area (18.7 [5.0] vs 15.8 [5.1] mm2, P < .001) but lower plaque burden at the proximal reference segment (41.0% [9.2%] vs 45.7% [9.9%], P < .001) and smaller lumen area (4.83 [1.89] vs 7.36 [2.89] mm, P < .001) but higher plaque burden at the distal reference segment (42.9% [10.4%] vs 41.4% [10.1%], P = .023). Multivariable logistic regression analysis showed that mismatch lesions were frequently accompanied by diffuse lesions (odds ratio [OR] = 2.50; 95% confidence interval [CI]: 1.83-3.40; P < .001), bifurcation lesions (OR = 5.83; 95% CI: 4.40-7.74; P < .001), and lesions with a low TIMI flow grade (OR = 1.70; 95% CI: 1.08-2.67; P = .022) or severe diameter stenosis (OR = 3.05; 95% CI: 2.10-4.43; P < .001).Conclusions:Mismatch lesions are quite common and characterized by greater lesion complexity compared with nonmismatch lesions. Further studies may be necessary to address the impact of this lesion type on the outcome of PCI.
Peripheral Vestibulopathy Presenting as Acute Vertigo and Spontaneous Nystagmus with Negative Video Head Impulse Test
Authors: Lee Jung‐Yup , Kim Chang‐Hee , Park Jin Su , Kim Min‐Beom 
Published: January 2019

ObjectiveTo analyze acute vertigo showing spontaneous nystagmus with negative video head impulse test (vHIT).Study DesignRetrospective chart analysis.SettingTertiary referral hospital.Subjects and MethodsOver 16 months, 155 patients were identified with acute vertigo with spontaneous nystagmus. Of these 155, 30 (19.4%) were enrolled in this study because they did not show gain loss or catch‐up saccades in both sides of the horizontal vHIT. Results of vestibular function tests (videonystagmography, horizontal vHIT, caloric test, and cervical vestibular‐evoked myogenic potential [cVEMP]) and pure tone audiometry were analyzed. For all cases, magnetic resonance imaging with diffusion‐weighted imaging was checked.ResultsPatients consisted of 17 with Ménière's disease and 7 with sudden sensorineural hearing loss with vertigo (SSNHL_V), and only 3 patients were finally diagnosed as having acute vascular stroke. Except for the loss of hearing on the lesion side, the direction of nystagmus or cVEMP asymmetry showed very different results. All 7 patients with SSNHL_V did not have canal paresis in the caloric test, but cVEMP amplitude was smaller on the lesion side for 6 patients.ConclusionsFor patients with acute vertigo presenting spontaneous nystagmus with negative horizontal vHIT, it is important not only to focus on the diagnosis of acute vascular stroke but also to evaluate hearing because of the high possibility of Ménière's disease or SSNHL_V.
Surgical management of esophageal perforation: role of primary closure
Authors: Huu Vinh Vu , Viet Dang Quang Nguyen , Van Khoi Nguyen 
Published: January 2019

Objective Esophageal perforation is a life-threatening condition associated with high mortality and morbidity. Ambiguous clinical presentation is one of the most common causes of delayed and difficult diagnosis of esophageal perforation. In this retrospective single-center study, we reviewed the outcome of primary closure in patients with esophageal perforation between 2009 and 2017. Methods The data of 65 patients attending our department of thoracic surgery (from 2009 to 2017) for esophageal perforation were reviewed. Primary repair was attempted in 63 patients irrespective of the site of perforation and time interval between injury and hospital admission. In intrathoracic lesions, continuous mediastinal and pleural irrigation was undertaken, whereas in cervical perforations, gauze packing and local irrigation were performed. Jejunotomy was carried out in patients with inadequate healing. Results Of the 65 patients, 63 underwent primary closure and 2 were left to heal spontaneously. The majority of patients ( n = 44) had an esophageal perforation at the thoracic level, and only one was admitted early (<24 h after injury). Among the 63 patients managed with primary closure, 55 had satisfactory healing with one surgery. Healing was delayed in the other 10 patients. No mortality was reported. Conclusions Esophageal perforation can be well managed by primary closure, irrespective of the time interval between injury and hospital admission and the site of perforation. Conservative management might lead to an increased rate of complications such as empyema or necrotizing mediastinitis, and increased morbidity and mortality.
A genetic deletion of the serotonin transporter differentially influences the behavioural effects of MDMA
Authors: Pettie Michaela , Oakly Alana , Harper David N , Ellenbroek Bart A 
Published: January 2019

Background: While (±)-3,4-methylenedioxymethamphetamine (MDMA) primarily induces serotonin release, it also affects dopamine and noradrenaline transmission. It is, however, unclear what role each of these neurotransmitters play in the behavioural profile of MDMA. Methods: In this study we used the drug discrimination (DD) and the acoustic startle (ASR) paradigms to examine the behaviour of rats with and without a genetic deletion of the serotonin transporter SERT (SERT−/− and SERT+/+ rats). In DD, rats were trained to respond on different levers following an injection of 1.5 mg/kg MDMA, or saline. After acquisition, they were given a challenge dose of 0.5 mg/kg amphetamine (AMPH). In the ASR paradigm, SERT+/+ and SERT−/− rats were given 0, 5 or 10 mg/kg MDMA. Results: In DD, significantly fewer SERT−/− rats acquired MDMA discrimination. When the acquirers were challenged with AMPH, SERT+/+ showed partial, while SERT−/− rats showed full generalisation to MDMA. In the ASR paradigm, MDMA significantly reduced prepulse inhibition and startle habituation in SERT+/+ rats, while having no effect in SERT−/− rats. Conclusion: Together these data suggest that in wildtype rats the interoceptive cues of MDMA are primarily mediated by serotonin and to a lesser extent by dopamine and noradrenaline, while the effects in the startle paradigm are almost exclusively mediated via serotonin. Together, these data contribute to our understanding of the complex pharmacodynamics of MDMA.
Water Metabolism
Authors: Phillips P. J. 
Published: January 2019

Total body water is finely regulated and controls of intake and output are maximally activated by small osmotic changes. Sensors in the hypothalamus invoke the fluid repletion or depletion reactions through changes in thirst, urine concentration and solute intake. Antidiuretic hormone controls urinary concentration and is released mainly in response to osmotic stimuli. However, the threshold and sensitivity of this response are affected by non osmotic stimuli. Urine concentration varies in response to antidiuretic hormone only if the distal tubule, collecting duct and hypertonic medullary interstitum are intact. The capacity to conserve or excrete water depends on the osmolar load and an efficient urinary concentrating or diluting mechanism. Disorders of thirst are uncommon and often associated with abnormal antidiuretic hormone secretion. Disorders of urine concentration and dilution are common in illness and reflect abnormalities of antidiuretic hormone secretion or the renal mechanisms generating the osmotic gradient. When urine concentrating capacity is impaired ( true or nephrogenic diabetes insipidus) water depletion occurs only when thirst fails or access to water is denied. When urine diluting ability is impaired, water excess occurs when the osmolar load and minimum urinary osmolality generated are inadequate for the fluid intake. Hyper-osmolality and hypo-osmolality are usually caused by abnormal water metabolism although they may be associated with abnormalities of solute metabolism. The various clinical syndromes are determined by the primary disease, and the associated fluid volume and osmolar abnormalities.
Intra-Operative Fluid and Electrolyte Requirements
Authors: Davidson George M. 
Published: January 2019

The intravenous administration of Hartmann's solution at a rate sufficient to maintain the hourly urine volume between 0.5 and 1.0 ml/ kg/ hr is recommended during major operations. Intra-operative extracellular volume expansion followed by the administration of sodium containing fluids for 48 hours postoperatively decreases the incidence of haemodynamic instability and acute renal failure and results in normal water and sodium excretion by the kidney throughout the peri-operative period. Abnormal extracellular volume may exist prior to induction of anaesthesia particularly in patients with pre-existing cardiovascular, renal and hepatic disease. In these patients the suggested fluid regime should be administered with care and may require diuretic therapy. If the operative blood loss in adults is less than one litre, no blood may be necessary. If the loss is between one and 2 litres packed red cells may be sufficient, whereas with a greater loss, filtered whole blood, coagulation factors and platelet infusions may be required. When possible, transfusions of stored autologous blood is recommended for elective operations.
Hydrogen Ion Metabolism
Authors: Worthley L. I. G. 
Published: January 2019

The renal and respiratory systems regulate acid base homeostasis by modifying the bicarbonate buffer pair HCO3- and CO2; other buffer systems adjust to alterations in this pair. The pH change following addition of metabolic acid, or base, is modified initially by the body's buffers. Subsequent respiratory compensation, by retention or excretion of CO2, modifies further this change before renal corrective responses finally occur. A primary respiratory acid base change is modified initially by cellular buffers, with renal compensatory mechanisms adjusting slowly to this change. However correction of the respiratory pH disorder only occurs with correction of the primary disease process. The body's capacity, therefore, to adjust to a metabolic acid base defect, appears greater than that observed with a primary respiratory pH abnormality. Treatment in all acid base disorders focuses initially upon the primary diseases process; thereafter therapeutic manipulation of the HCO3 -, CO2 buffer pair, to aid the body's compensatory processes, can be considered.