bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicentric Giant Cell Tumor of Bone: Synchronous and Metachronous Presentation
Authors: Wirbel Reiner , Blümler Frank , Lommel Dirk , Syré Guido , Krenn Veit
Published: September 2013

A 27-year-old man treated 2.5 years ago for synchronous multicentric giant cell tumor of bone located at the right proximal humerus and the right 5th finger presented now with complaints of pain in his right hip and wrist of two-month duration. Radiology and magnetic resonance revealed multicentric giant cell tumor lesions of the right proximal femur, the left ileum, the right distal radius, and the left distal tibia. The patient has an eighteen-year history of a healed osteosarcoma of the right tibia that was treated with chemotherapy, resection, and allograft reconstruction. A literature review establishes this as the first reported case of a patient with synchronous and metachronous multicentric giant cell tumor who also has a history of osteosarcoma.
Knowledge, Health Beliefs, and Self-Efficacy regarding Osteoporosis in Perimenopausal Women
Authors: Endicott Renée D.
Published: September 2013

The aims of this pilot study were to (1) determine if having a family history of osteoporosis impacts knowledge, health beliefs, and self-efficacy regarding osteoporosis among perimenopausal women aged 42–52 and to (2) describe the impact of an osteoporosis-specific educational intervention had on the knowledge, health beliefs, and self-efficacy of this population. Participants completed three surveys measuring knowledge, health beliefs, and self-efficacy related to osteoporosis before and two months after the educational program. At baseline, no differences were noted in knowledge of osteoporosis among women with and without a family history of osteoporosis, although women with a family history perceived a greater susceptibility for developing osteoporosis than women without the family history. Findings indicate that both groups increased in knowledge of osteoporosis (P<.001). Benefits of calcium increased in the women without a family history of osteoporosis (P<.001) and benefits of exercise increase in women with a family history of osteoporosis (P=.007). There were no significant statistical findings regarding self-efficacy between the two groups of women. Findings indicate that an osteoporosis-specific educational program improves perimenopausal women’s knowledge and some health beliefs.
Craniomandibular Disorders and Mandibular Reference Position in Orthodontic Treatment
Authors: Bourzgui Farid , Aghoutan Hakima , Diouny Samir
Published: September 2013

The aim of this paper is to bring into focus the literature on the choice of the mandibular reference position in orthodontic treatment; of a particular reference to this paper is intercuspal position, centric relation position, or therapeutic position. To give a comprehensive account of the literature review on craniomandibular disorders (CMD), we have relied on books and articles using both Google Scholar and PubMed. Selection criteria included a combination of Mesh and type of article. Article classification was made by two authors, using the following structure outline: prevalence of craniomandibular disorders, its etiology and pathophysiology, occlusion and craniomandibular disorders, orthodontic treatment and CMD, and the mandibular reference position in orthodontics. An important conclusion that emerged from the present literature review is that CMD do not seem to be directly related to orthodontic treatment, and their appearance cannot be predicted or prevented by any means. Therefore, orthodontists must adopt a mandibular reference suitable to their patients and which best respects the balance existing in the stomatognathic system.
Synthesis, Spectroscopic, and Biological Studies on New Zirconium(IV) Porphyrins with Axial Ligand
Authors: Bajju Gauri D. , Devi Gita , Katoch Sapna , Bhagat Madhulika , Deepmala  , Ashu  , Kundan Sujata , Anand Sunil Kumar
Published: September 2013

A series of parasubstituted tetraphenylporphyrin zirconium(IV) salicylate complexes (SA/5-SSAZr(IV)RTPP, R = p-H, p-CH3, p-NO2, p-Cl, SA = salicylate, and 5-SSA = 5-sulfosalicylate) have been synthesized, and the spectral properties of free base porphyrins, their corresponding metallated, and axially ligated zirconium(IV) porphyrin compounds were compared with each other. A detailed analysis of ultraviolet-visible (UV-vis), proton nulcear magnetic resonance (1H NMR) spectroscopy, infrared (IR) spectroscopy, and elemental analysis suggested the transformation from free base porphyrins to zirconium(IV) porphyrins. The ability of the metal in this complex for extra coordination of solvent molecules was confirmed by ESI-MS spectra. Besides the fluorescence, cyclic voltammetry, and thermogravimetric studies, the complexes were also screened for antimicrobial and anticancer activities. Among all the complexes, 5-SSAZr(p-NO2TPP) shows high antibacterial activity.
The Efficacy of On-Site Evaluation for Identification of Transplant Pancreas
Authors: Berg Natasha , Gehl Jim , Vande Haar Mark , Balco Michael , Kulesza Peter
Published: September 2013

Objective: Pancreatic transplantation has been relatively uncommon until the last 2 decades, but is now an accepted therapeutic intervention for type I diabetes. Core biopsies of pancreas transplants are frequently performed to rule out rejection, which is a leading cause of graft failure. Often, it is difficult to localize the graft for biopsy by imaging. Our objective was to determine whether on-site assessment by cytopathology can assist in procedure protocols for biopsy of pancreas transplants. Study Design: We reviewed cytology and surgical pathology reports from 68 instances of pancreas transplant biopsy at our institution and evaluated the correlation between cytology (fine needle aspiration, touch preparation or both) and the final core biopsy. Results: Pancreatic tissue was identified by on-site assessment in 56/68 cases and was present on core biopsy in 53/68 cases. There were 3 cases where fine needle aspiration/touch preparation results were not concordant with final core biopsy results. The positive predictive value of a positive on-site assessment was 96.4%. More importantly, the negative predictive value of on-site assessment was 100%. Conclusions: On-site evaluation by cytopathology is highly effective for the identification of transplant pancreas. In cases where no pancreatic tissue is identified by on-site assessment, relocalization of the biopsy needle is recommended.
Lisinopril Protects Against the Adriamycin Nephropathy and Reverses the Renalase Reduction: Potential Role of Renalase in Adriamycin Nephropathy
Authors: Han Pengxun , Sun Huili , Xu Yuanzhao , Zeng Youjia , Yi Wuyong , Wu Jia , Shao Mumin , Li Shunmin , Yi Tiegang
Published: September 2013

Aims: To investigate the potential role of renalase in adriamycin nephropathy and the effect of lisinopril on the regulation of renalase. Methods: Adriamycin nephropathy was induced in male Wistar rats (n=12) by a single injection of adriamycin at 2 mg/kg body weight. Rats were then randomly assigned to a model group or a treatment group, to which were administered distilled water or the angiotensin converting enzyme inhibitor lisinopril, respectively, for 12 weeks. Six normal rats served as controls. At the end of study, physiological parameters and systolic blood pressure were measured. Glomerulosclerosis and tubulointerstitial injury were assessed by histopathology Renalase protein expression in kidney was quantified by immunohistochemistry and immunoblotting. The serum concentration and urinary excretion of renalase were determined by enzyme-linked immunosorbent assay. Results: In model group rats, proteinuria and systolic blood pressure were elevated. Increased serum renalase concentration was observed; however, renalase protein expression in the kidney was significantly decreased. Compared with the model group, decreased proteinuria, lower systolic blood pressure, and fewer morphologic lesions were detected in the treatment group. Although levels of serum renalase were similar, accumulation of renalase in urine and kidney tissue increased notably in the treatment group compared with the model group. Conclusions: This study suggests that renalase may be involved in the process of adriamycin-induced renal injuries. Lisinopril may attenuate adriamycin-induced kidney injury by controlling blood pressure, which may be partially attributed to the renalase expression and secretion.
Use of Language Tests when Identifying Specific Language Impairment in Primary Health Care
Authors: Hannus Sinikka , Kauppila Timo , Pitkäniemi Janne , Launonen Kaisa
Published: September 2013

Objective: To evaluate the ability of language tests to identify children with specific language impairment (SLI) in primary health care. All the language tests presently in clinical use in Finland were applied. Method: All the children with SLI living in one city in Finland constituted the cohort. Test scores were collected from 83 subjects drawn from a birth cohort of 4,553 children. Finally 31 case-control pairs were studied. All SLI diagnoses were set in secondary health care. Test scores of 14 language tests were examined that, together with subtests, included 39 different tasks. Results: Out of 39 performed tests, the difference in test scores between children with SLI and their matched controls was statistically significant in 26 tests. A group of six tests had good sensitivity and moderate specificity for SLI diagnosis and they correctly classified children with SLI to either F80.1 or F80.2 diagnosis category. Conclusion: The results suggest that most of the language tests in Finnish identify children with SLI and, furthermore, that these tests identify language deficits that are consistent with those found in other studies. More studies with larger age-matched populations are needed.
Enhanced Recovery in Gastrointestinal Surgery: Upper Gastrointestinal Surgery
Authors: Dorcaratto Dimitri , Grande Luís , Pera Manuel
Published: September 2013

Over the last 20 years, a new concept of perioperative patient care based on a construct of evidence-based interventions referred to as ‘enhanced recovery after surgery' (ERAS) has been developed. The main pillars of ERAS programs include optimal postoperative pain management and early enteral feeding and mobilization after surgery. Several studies, mostly based on experiences with patients undergoing colonic resection, suggest that ERAS implementation is feasible and safe. However, there are very few well-designed studies that have evaluated the usefulness of ERAS programs after major upper abdominal surgery. The present review focuses on the discussion of the most relevant and recently published data on the application of ERAS programs in pancreatic, hepatic, esophageal and gastric surgery. A total of 23 articles have been reviewed by the authors. The high frequency and the potentially hazardous nature of some postoperative complications associated with major upper abdominal surgery and the lack of well-designed randomized controlled trials are limiting factors for the application of ERAS. However, the present results indicate that the implementation of ERAS programs in pancreatic, hepatic, esophageal and gastric surgery patients contributes to a reduction in complications, length of hospital stay and costs without an increase in mortality or readmission rates.
Techniques of DNA Methylation Analysis with Nutritional Applications
Authors: Mansego Maria L. , Milagro Fermín I. , Campión Javier , Martínez J. Alfredo
Published: September 2013

Epigenetic mechanisms are likely to play an important role in the regulation of metabolism and body weight through gene-nutrient interactions. This review focuses on methods for analyzing one of the most important epigenetic mechanisms, DNA methylation, from single nucleotide to global measurement depending on the study goal and scope. In addition, this study highlights the major principles and methods for DNA methylation analysis with emphasis on nutritional applications. Recent developments concerning epigenetic technologies are showing promising results of DNA methylation levels at a single-base resolution and provide the ability to differentiate between 5-methylcytosine and other nucleotide modifications such as 5-hydroxymethylcytosine. A large number of methods can be used for the analysis of DNA methylation such as pyrosequencing™, primer extension or real-time PCR methods, and genome-wide DNA methylation profile from microarray or sequencing-based methods. Researchers should conduct a preliminary analysis focused on the type of validation and information provided by each technique in order to select the best method fitting for their nutritional research interests.
Pancreaticojejunostomy versus Pancreaticogastrostomy after Pancreaticoduodenectomy: A Systematic Review and Meta-Analysis
Authors: He Tieying , Zhao Yang , Chen Qilong , Wang Xiyan , Lin Hai , Han Wei
Published: September 2013

Background and Objectives: The method of pancreatic reconstruction after pancreaticoduodenectomy (PD) is closely associated with postoperative morbidity, mortality, and patient's quality of life. The objective of this study is to evaluate which anastomosis approach - pancreaticogastrostomy (PG) or pancreaticojejunostomy (PJ) is a better option of choice in terms of postoperative complications. Methods: Articles comparing PG and PJ that were published by July 2011 were retrieved and subjected to a systematic review and meta-analysis. Results: Four randomized controlled trials (RCTs) and 22 observational clinical studies (OCSs) were included. RCTs showed that the PG group had significantly lower incidence rates of postoperative intra-abdominal fluid collection (p = 0.003, relative risk (RR) 0.50, 95% CI 0.31-0.79) and multiple intra-abdominal complications (p = 0.0007, RR 0.26, 95% CI 0.12-0.56) than the PJ group. OCSs demonstrated significant differences between PG and PJ in terms of frequencies of postoperative biliary fistula, intra-abdominal fluid collection, pancreatic fistula, morbidity, and mortality. The overall analysis revealed significant differences in frequencies of intra-luminal hemorrhage (p = 0.03, OR 2.82, 95% CI 1.08-7.33) and grade B/C pancreatic fistula (p = 0.002, OR 0.42, 95% CI 0.24-0.73) between the two groups. Conclusions: Current literature has no adequate evidence to prove that PG is superior to PJ for patients undergoing PD in terms of postoperative complications. A standardized classification of pancreatic fistula and other intra-abdominal complications may enable an objective, valid comparison between PG and PJ.
Neuroscience of Exercise: From Neurobiology Mechanisms to Mental Health
Authors: Matta Mello Portugal Eduardo , Cevada Thais , Sobral Monteiro-Junior Renato , Teixeira Guimarães Thiago , da Cruz Rubini Ercole , Lattari Eduardo , Blois Charlene , Camaz Deslandes Andrea
Published: September 2013

The neuroscience of exercise is a growing research area that is dedicated to furthering our understanding of the effects that exercise has on mental health and athletic performance. The present study examined three specific topics: (1) the relationship between exercise and mental disorders (e.g. major depressive disorder, dementia and Parkinson's disease), (2) the effects of exercise on the mood and mental health of athletes, and (3) the possible neurobiological mechanisms that mediate the effects of exercise. Positive responses to regular physical exercise, such as enhanced functional capacity, increased autonomy and improved self-esteem, are frequently described in the recent literature, and these responses are all good reasons for recommending regular exercise. In addition, physical exercise may improve both mood and adherence to an exercise program in healthy individuals and might modulate both the performance and mental health of athletes. Exercise is associated with the increased synthesis and release of both neurotransmitters and neurotrophic factors, and these increases may be associated with neurogenesis, angiogenesis and neuroplasticity. This review is a call-to-action that urges researchers to consider the importance of understanding the neuroscience of physical exercise and its contributions to sports science.
The Tibetan Herbal Formula Padma Digestin in Functional Dyspepsia: An Open-Label Study
Authors: Meier Rémy , Hengstler Peter , Weber Felix , Maurer Hermann , Bommeli Cordelia , Brignoli Reto
Published: September 2013

Background: The etiology of functional dyspepsia (FD) is multi-factorial. Its prevalence is high and it considerably impairs the patients' quality of life. The treatment options are limited. Padma Digestin, a multi-herbal formula from Tibetan Medicine, is traditionally used in malabsorption and dyspeptic symptoms as they do occur in FD, but as yet no clinical data exist on the formula. The aim of this study was to evaluate the safety, tolerability, and efficacy of Padma Digestin in patients with FD in a prospective, open, clinical phase III trial. Patients and Methods: Patients were recruited by general practitioners, internists, and gastroenterologists and treated with 2 × 3 capsules of Padma Digestin daily for 6 weeks. Dyspeptic symptoms were analyzed using the Domestic/International Gastroenterology Surveillance Study (DIGEST) questionnaire extended by the 2 symptoms stomach cramps and lack of appetite. The quality of life was assessed using the Psychological General Well-Being Index (PGWBI-S) questionnaire (short version). Results: 37 patients were admitted and efficacy could be assessed in 31. In the overall efficacy assessment, the Padma Digestin treatment led to a statistically highly significant reduction of the respective most bothersome symptom scores regarding frequency, severity, and impairment of daily activities (p < 0.01). The treatment also led to significant improvements of the individual symptoms of postprandial fullness, nausea, localized and diffuse epigastric pain, stomach cramps, and lack of appetite. The onset of improvement was after a median of 7 days; time until disappearance of the symptoms was after a median of 22 days. The global efficacy and tolerability were rated as good or very good by the doctors and the patients in 84% and 78%, respectively. The PGWBI-S increased from 55 ± 19.5% to 70.5 ± 15.5%, which is nearly the normal value (73.5 ± 15.4%). As for safety, 11 patients reported a total of 17 adverse events (AE), 1 of which was serious but unrelated to the study medication. The AE were mild or moderate. The safety laboratory data showed no statistically significant or otherwise relevant changes. Conclusions: The results show that the formula Padma Digestin has a high tolerability and efficacy in FD symptoms and positively influences psychological well-being and thus quality of life. It therefore represents a much needed extension of the therapeutic repertoire in FD.
Global Epidemiology of Amyotrophic Lateral Sclerosis: A Systematic Review of the Published Literature
Authors: Chiò A. , Logroscino G. , Traynor B.J. , Collins J. , Simeone J.C. , Goldstein L.A. , White L.A.
Published: September 2013

Background: Amyotrophic lateral sclerosis (ALS) is relatively rare, yet the economic and social burden is substantial. Having accurate incidence and prevalence estimates would facilitate efficient allocation of healthcare resources. Objective: To provide a comprehensive and critical review of the epidemiological literature on ALS. Methods: MEDLINE and EMBASE (1995-2011) databases of population-based studies on ALS incidence and prevalence reporting quantitative data were analyzed. Data extracted included study location and time, design and data sources, case ascertainment methods and incidence and/or prevalence rates. Medians and interquartile ranges (IQRs) were calculated, and ALS case estimates were derived using 2010 population estimates. Results: In all, 37 articles met the inclusion criteria. In Europe, the median incidence rate (/100,000 population) was 2.08 (IQR 1.47-2.43), corresponding to an estimated 15,355 (10,852-17,938) cases. Median prevalence (/100,000 population) was 5.40 (IQR 4.06-7.89), or 39,863 (29,971-58,244) prevalent cases. Conclusions: Disparity in rates among ALS incidence and prevalence studies may be due to differences in study design or true variations in population demographics such as age and geography, including environmental factors and genetic predisposition. Additional large-scale studies that use standardized case ascertainment methods are needed to more accurately assess the true global burden of ALS.
A Surgical Model for Isolating the Pig Liver in vivo for Gene Therapy
Authors: Carreño O. , Sendra L. , Montalvá E. , Miguel A. , Orbis F. , Herrero M.J. , Noguera I. , Aliño S.F. , Lopez-Andujar R.
Published: September 2013

Several studies report results that suggest the need of vascularization blocking for efficient gene transfer to the liver, especially in nonviral gene therapy. In this study, we describe a surgical strategy for in vivo isolation of the pig liver, resulting in a vascular watertight organ that allows the evaluation of several gene injection conditions. The hepatic artery and portal, suprahepatic and infrahepatic cava veins were dissected. Then, liver vascularization was excluded for 5-7 min. In that time, we first injected 200 ml saline solution containing the p3c-eGFP plasmid (20 µg/ml) simultaneously through two different catheters placed in the portal and cava veins, respectively. Vital constants were monitored during the surgery to assess the safety of the procedure. Basal systolic/diastolic blood pressures were 92.8/63.2 mm Hg and dropped to 40.7/31.3 mm Hg at the end of vascular exclusion; the mean basal heart rate was 58 bpm, reaching 95 bpm when the blood pressure was low. Oxygen saturation was maintained above 98% during the intervention, and no relevant changes were observed in the ECG tracing. Peak plasma AST (aspartate aminotransferase) and ALT (alanine aminotransferase) levels were observed after 24 h (151 and 57 IU, respectively). These values were higher, but not relevant, in 60 ml/s injection than in 20 ml/s injection. Efficiency of gene transfer was studied with simultaneous (cava and portal veins) injection of eGFP gene at flow rates of 20 and 60 ml/s. Liver tissue samples were collected 24 h after injection and qPCR was carried out on each lobe sample. The results confirmed the efficiency of the procedure. Gene delivery differed between 20 ml/s (9.9-31.0 eGFP DNA copies/100 pg of total DNA) and 60 ml/s injections (0.6-1.1 eGFP DNA copies/100 pg of total DNA). Gene transcription showed no significant differences between 20 ml/s (15,701.8-21,475.8 eGFP RNA copies/100 ng of total RNA) and 60 ml/s (12,014-36,371 eGFP RNA copies/100 ng of total RNA). The procedure is not harmful for animals and it offers a wide range of gene delivery options because it allows different perfusion ways (anterograde and retrograde) and different flow rates to determine the optimal conditions of gene transfer. This strategy permits the use of cell therapy and viral or non-viral liver gene therapy, especially appropriated to a wide variety of inherited or acquired diseases because of the liver's ability to produce and deliver proteins to the bloodstream.
Correlation between Peak Intraocular Pressure of the Water Drinking Test and Peak Intraocular Pressure Induced by Intravenous Methylprednisolone Pulse Therapy
Authors: Kowsarnia Saeedeh , Aflaky Elham , Banifatemi Mohammad , Razeghinejad M. Reza
Published: September 2013

Purpose: It was the aim of this study to determine any possible correlation between the peaks and changes in intraocular pressure (IOP) of a water drinking test and intravenous methylprednisolone pulse therapy (IVMPT) IOP response. Methods: Patients with rheumatic disorders scheduled for IVMPT with normal ocular examination received a WDT before and after 3 days of IVMPT. The maximum value of IOPs detected during the WDT or IVMPT was regarded as peak IOP, and IOP change was defined as the difference between peak IOP and baseline IOP. Results: The mean ± standard deviation (SD) IOPs on the first (21.9 ± 4.6 mm Hg; p = 0.04), second (21.9 ± 4.1 mm Hg; p = 0.03) and third (21.3 ± 4.2 mm Hg; p = 0.01) days of 20 enrolled patients were greater than that at baseline (19.3 ± 2.8 mm Hg). The mean ± SD of peak IVMPT IOP response was 23.9 ± 3.7 mm Hg, and IVMPT IOP change was 4.6 ± 3.7 mm Hg. These values for the first and second WDTs were 22.9 ± 4.9 and 3.9 ± 4.07 as well as 24.1 ± 4.6 and 3.00 ± 2.9 mm Hg, respectively. A significant correlation was observed between the first WDT and IVMPT IOP changes (r = 0.5, p = 0.007) and peak IOPs (r = 0.6, p = 0.001). Conclusion: WDT, a low-cost and feasible test in clinical practice, may be a useful tool in determining the IOP peak and change following IVMPT.
Association between EEG Abnormalities and CSF Biomarkers in a Memory Clinic Cohort
Authors: Kramberger Milica Gregoric , Kåreholt Ingemar , Andersson Thomas , Winblad Bengt , Eriksdotter Maria , Jelic Vesna
Published: September 2013

Background: The aim of the study was to describe distinct electroencephalogram (EEG) phenotypes defined after routine visual EEG analysis in a large memory clinic cohort and to investigate their relationship to cerebrospinal fluid (CSF) biomarkers. Methods: Patients with Alzheimer's disease (n = 131), mild cognitive impairment (n = 285), subjective cognitive impairment (n = 310), and mixed dementia (n = 29) were assessed clinically with neuroimaging, EEG and CSF investigations. EEG phenotypes were based on frequency of background activity (BA) and presence and degree of episodic abnormalities (EA). Results: BA and EA differed significantly (p < 0.001) between diagnostic groups. A lower CSF amyloid β42/phospho-tau ratio and higher total tau were associated with slower BA (p < 0.01) and a higher degree of EA (p < 0.04). Conclusions: Slowing of BA in combination with EA seems to be related to biological markers of neurodegeneration.
Antiplatelet Therapy for Carotid Artery Stenting
Authors: Enomoto Yukiko , Yoshimura Shinichi
Published: September 2013

Carotid artery stenting (CAS) is less invasive and has a lower incidence of systemic complications such as myocardial infarction compared with carotid endarterectomy. However, CAS is known to have a high incidence of ischemic complications due to distal thromboembolism. Progress has been made in the development of various distal protection devices and protection methods aimed at preventing thromboembolism. Similar to these methods, perioperative antiplatelet therapy is also able to play a very important role in the prevention of ischemic events. Dual antiplatelet therapy has become standard for perioperative management of CAS.
Tibetische Rezepturen als pleiotrope Signaturen - Einsatz von Netzwerk-Arzneien bei Multimorbidität
Authors: Schwabl Herbert , Vennos Cécile , Saller Reinhard
Published: September 2013

Multimorbide Zustände (≥2 chronische Erkrankungen gleichzeitig) können vor dem Hintergrund des Netzwerkmodells des Organismus als komplexe Krankheitsmuster aufgefasst und als charakteristische Signaturen abgebildet werden. Lebende Systeme wie der menschliche Organismus werden aus der Sicht der Systemtheorie als Netzwerke von interagierenden Teilen betrachtet. Diese können wiederum selbst Unternetzwerke sein und verschiedenen Komplexitätsstufen zugeordnet werden. Sie reichen z.B. vom Gen über das Transkriptom, Proteom, Metabolom und Epigenom bis hin zum Netzwerk der gesamten molekularen Interaktionen, dem sogenannten Interaktom. Bei der Multimorbidität betrifft die Krankheitssignatur verschiedene Netzwerke auf allen Stufen, z.B. Zellsysteme, Organe und funktionelle Systeme. Basierend auf dieser Semiotik können auch Arzneimitteln bestimmte Wirksignaturen bzw. Wirkprofile zugeordnet werden. Eine Pharmakonsignatur repräsentiert die physikalisch-chemischen Reize, die das System zu einer Reaktion veranlassen, sowie die Verbindungen, über die das vernetzte Gesamtsystem auf allen Hierarchiestufen beeinflusst wird. Phytotherapeutika, die chemisch gesehen Vielstoffgemische darstellen, besitzen besonders komplexe Signaturen. Als Multi-Target-Arzneien mit pleiotropem Wirkprofil greifen sie auf den unterschiedlichen Systemstufen des Netzwerks therapeutisch ein, weshalb sie auch als Netzwerk-Arzneien bezeichnet werden. Als Beispiel für Phytotherapeutika mit besonders komplexer pleiotroper Signatur können Pflanzenrezepturen traditioneller Medizinsysteme wie der Tibetischen Medizin herangezogen werden. Hier wird auch aus traditioneller Sicht eine Krankheitssignatur mit einer korrespondierenden Arzneimittelsignatur in Beziehung gesetzt, jedoch basierend auf dem traditionellen energetischen Verständnis von Krankheiten. Moderne Forschungsergebnisse geben deutliche Hinweise auf eine ausgesprochen breit gefächerte Signatur Tibetischer Arzneimittel und liefern somit die logische Grundlage für ihren Einsatz im Rahmen integrativer Behandlungsansätze bei Krankheiten mit ebenfalls komplexer Signatur, z.B. bei Multimorbidität. Der vorgestellte systemtheoretische Ansatz stellt eine Methode dar, die Anschlussfähigkeit traditioneller und komplementärmedizinischer Methoden an die anderen Disziplinen der modernen Medizin zu ermöglichen.
Is Vertebral Artery Hypoplasia a Predisposing Factor for Posterior Circulation Cerebral Ischemic Events? A Comprehensive Review
Authors: Katsanos Aristeidis H. , Kosmidou Maria , Kyritsis Athanassios P. , Giannopoulos Sotirios
Published: September 2013

Vertebral artery hypoplasia is not currently considered an independent risk factor for stroke. Emerging evidence suggest that vertebral artery hypoplasia may contribute to posterior circulation ischemic events, especially when other risk factors coexist. In the present literature review, we present published data to discuss the relationship between a hypoplastic vertebral artery and posterior circulation cerebral ischemia. Despite difficulties and controversies in the accurate definition and prevalence estimation of vertebral artery hypoplasia, ultrasound studies reveal that the reduced blood flow observed ipsilateral to the hypoplastic vertebral artery may result in local cerebral hypoperfusion and subsequent focal neurological symptomatology. That risk of cerebral ischemia is related to the severity of the hypoplasia, suggesting that the smaller of paired arteries are more vulnerable to occlusion. Existing cohort studies further support clinical observations that hypoplastic vertebral artery enhances synergistically the vascular risk for posterior circulation ischemic events and is closely associated with both atherosclerotic and prothrombotic processes.
Dynamic and Dual Effects of Glycated Hemoglobin on Estimated Glomerular Filtration Rate in Type 2 Diabetic Outpatients
Authors: Lee Chia-Lin , Li Tsai-Chung , Lin Shih-Yi , Wang Jun-Sing , Lee I-Te , Tseng Li-Nien , Song Yuh-Min , Tsai Shang-Feng , Sheu Wayne H-H
Published: September 2013

Background: Diabetic nephropathy is the leading cause of incident end-stage renal disease in Taiwan. Previous studies on the consistent benefits of glycemic control in diabetic nephropathy focused primarily on delaying microalbuminuria. However, this effect on glomerular filtration rate (GFR) remains controversial. This study aims to establish a model that explains the controversial effects of glycated hemoglobin (HbA1C) on GFR. Methods: This retrospective cohort study followed subjects with type 2 diabetes mellitus, who were enrolled between June 2006 and December 2006, for 4 years. The effects of HbA1C on estimated GFR (eGFR) were examined both cross-sectionally and longitudinally. The dual effects of HbA1C on eGFR, and how renal function interferes with these effects, were investigated. Results: Of the 1,992 subjects enrolled, 1,699 completed the follow-up. HbA1C was positively correlated with eGFR in the cross-sectional study (β coefficient = 1.44, 95% CI: 0.71-2.17, p = 0.0001). In the longitudinal study, higher baseline HbA1C resulted in a greater decline in eGFR. The annual eGFR decline rates were -1.89, -1.29, and -0.68 ml/min/1.73 m2/year for baseline HbA1C >9, 7 to ≤9, and ≤7%, respectively. The eGFR value was simultaneously affected by concurrent (β coefficient = 0.78, 95% CI: 0.48-1.08, p < 0.0001) and preceding HbA1C (-0.52, -0.82 to -0.23, p < 0.0001). The positive effects of concurrent HbA1C on eGFR reached statistical significance at all stages of chronic kidney disease (CKD); however, the negative effects of preceding HbA1C only applied to CKD stages 3 and 4. Conclusions: We developed a new model that demonstrates how preceding and concurrent HbA1C simultaneously affect eGFR in opposing ways. The dynamic effects varied among different CKD stages. The deterioration in eGFR at CKD stages 3 and 4 may be postponed by intensive glycemic control. Further prospective studies may be necessary to clarify the specific CKD stage(s) that will benefit from intensive glycemic control.
Assessing Working Memory via N-Back Task in Euthymic Bipolar I Disorder Patients: A Review of Functional Magnetic Resonance Imaging Studies
Authors: Cremaschi Laura , Penzo Beatrice , Palazzo Mariacarlotta , Dobrea Cristina , Cristoffanini Marta , Dell'Osso Bernardo , Altamura A. Carlo
Published: September 2013

Bipolar disorder (BD) is a chronic and highly disabling mood disorder, associated with the highest suicide rate among psychiatric disorders. Even though neurobiological bases of BD have still to be further elucidated, recent neuroimaging studies provided compelling evidence about functional correlates of cognitive deficits in BD patients, with working memory (WM) impairment being one of the most commonly reported findings. Such dysfunctions are likely to persist beyond acute phases of the illness, so they qualify as endophenotypic markers for the disorder. This review sought to synthesize, through a MEDLINE search up to December 2012, published functional magnetic resonance imaging (fMRI) studies on WM networks, conducted through N-back task in euthymic BD I patients and including a control comparison group. Eight studies meeting the search criteria were identified. Despite heterogeneity across findings, particularly in relation to task performance (i.e. accuracy and reaction time), most studies reported a loss of connectivity in BD patients' prefrontal networks, traditionally involved in WM, as well as patterns of abnormal activation in the dorso/ventrolateral prefrontal cortex, other prefrontal areas and the parietal and temporal cortex. These findings suggest the involvement of intact secondary systems in order to overcome lack of integrity across WM circuits in BD patients. Further investigation in the field is warranted.
Risk Prediction of Subsequent Early Stroke in Patients with Transient Ischemic Attacks
Authors: Chatzikonstantinou Anastasios , Wolf Marc E. , Schaefer Anke , Hennerici Michael G.
Published: September 2013

Background: Prognostic clinical scores (ABCD2 and ABCD3-I), as well as specific clinical signs and symptoms (e.g. fluctuations) have been used to predict early stroke risk in patients admitted to hospital after transient ischemic attacks (TIAs). We compared the utility of these scores and signs for prognosis and outcome. Methods: 235 patients with TIAs admitted to our Comprehensive Stroke Center entered the study. Patients were monitored over 3 days with detailed brain imaging [diffusion-weighted imaging (DWI) was performed either directly on admission or within 24 h from admission and was repeated in cases of stroke recurrence], vascular ultrasound imaging, repeated neurological scoring and continuous ECG monitoring. Duration, fluctuation of symptoms, clinical patterns of initial signs and/or symptoms as well as general patient characteristics and stroke risk factors, including atrial fibrillation (AF), were analyzed and recorded in our stroke databank. Fluctuation of symptoms was defined as the complete remitting and relapsing of TIA symptoms for ≥2 times in the acute phase within the first 24 h. This differs from the ‘dual TIA' definition of the ABCD3-I score, which is defined as ‘an earlier TIA within 7 days of the index event'. ABCD2 and ABCD3-I scores were calculated and the patients were placed into three categories: ‘low', ‘moderate' and ‘high' risk for every score. Risk associations were assessed by the χ2 test and the φ-coefficient. Results: Out of 235 patients, 17 patients (7.2%) experienced an early stroke during hospitalization (mean duration 7.4 ± 2.7 days). ABCD2 scores failed to predict early stroke (p = 0.544). ABCD3-I scores correlated better with early stroke recurrences (p = 0.021). Positive DWI findings (6/17; 35.3%), presence of carotid stenosis (3/17; 17.6%) or AF (1/17; 5.9%) alone failed to predict early stroke. Fluctuations of symptoms, however, showed a significant prediction for early stroke after TIA: 13/17 (76.5%) patients (p < 0.001). The combination of symptom fluctuation and MR-DWI-positive findings (4/17; 23.5%) also turned out to be statistically significant in this regard (p = 0.003), while the combination of symptom fluctuations with carotid stenosis ≥50% did not (p = 0.151). Combining fluctuations with carotid stenosis and DWI-positive findings did not improve the result (p = 0.029). Conclusions: While the ABCD3-I score is indeed very useful, symptom fluctuations seem to be the best available and an easily accessible and applicable parameter for individual prediction of a high early stroke risk after TIAs.
The Role of Liquid-Based Preparation in the Evaluation of Endometrial Cytology
Authors: Norimatsu Yoshiaki , Yanoh Kenji , Kobayashi Tadao K.
Published: September 2013

Objective: Liquid-based preparation (LBP) of the endometrial lesions is an important diagnostic tool for a variety of endometrial abnormalities because of its simplicity and high quali-quantitative diagnostic yield. We aimed to investigate the LBP method for endometrial cytology to evaluate both benign and abnormal endometrial lesions. Study Design: LBP is a semiautomated methodology that has recently become widely available and has gained popularity as a method of collecting and processing both gynecologic and nongynecologic cellular specimens. Results: Some peculiar endometrial cytoarchitectural features were described using LBPs. These were advantageous to screen as compared to conventional slides due to a smaller screening area and an excellent quality of cell preparations. Conclusions: LBP is a useful tool in the cellular diagnosis and follow-up of endometrial abnormalities, which remains complementary to the emerging molecular diagnostic cytopathology. The study of LBPs from endometrial cytology could be challenging since it is affected by numerous look-alikes and diagnostic pitfalls. This review discusses these various entities and takes into consideration the ancillary techniques that may be useful in the diagnostic procedure.
Influence of the Hand Squeeze and Mask Distensibility on Tidal Volume Measurements during Neonatal Mask Ventilation
Authors: van Vonderen Jeroen J. , Kamar Rita , Schilleman Kim , Walther Frans J. , Hooper Stuart B. , te Pas Arjan B.
Published: September 2013

Background: During mask ventilation, the mask volume can vary as it is pressurized or when it is squeezed. The change in volume of the mask may affect tidal volumes delivered and difference in inspired (Vti) and expired tidal volumes (Vte). Objectives: To investigate whether hand squeeze and distensibility of the mask during ventilation influences tidal volume measurements. Methods: For both experiments, we ventilated a leak-free mask ventilation model using pressures of 25/5 cm H2O through a t-piece. Vti and Vte were measured. (A) Two consultants performed mask ventilation with (1) consistent hand squeeze, (2) release during inflation and squeeze during expiration, (3) squeeze during inflation, release during expiration, and (4) gentle squeeze. Results: (B) Thirty caregivers performed mask ventilation. Experiment A: Vti was different during consistent hold (1) 8.1 ml (0.4) and loose grip (4) 8.2 ml (0.3), compared to squeezing during inflation (2) 18.9 ml (1.9), or expiration (3) 6.4 ml (3.5). Variance in difference between Vti and Vte occurred only when the mask was squeezed during inflation (-47.4% (101.5)). Experiment B: volumes measured were consistent (intraindividual CV 3-5%, interindividual CV 9-10%). When comparing gas flow rate of 6-10 l/min, volumes increased by approximately 8%, differences in Vti and Vte were small with both flow settings (-0.9% (-3.9-1.4) and -0.6% (-3.3-1.8); n.s.). Conclusion: Variation in mask hold during mask ventilation can influence volume measurement, but this hardly occurs when testing caregivers.
The Vitreous, the Retinal Interface in Ocular Health and Disease
Authors: de Smet Marc D. , Gad Elkareem Ashraf M. , Zwinderman Aeilko H.
Published: September 2013

The vitreous is a complex structure whose composition and appearance change with age. Anomalous adhesions between the posterior vitreous face and the retinal surface are the cause of numerous vitreoretinal complications, while the presence of an intact posterior hyaloid provides a scaffold for vascular growth and anteroposterior traction. This review summarizes what is known about the biochemistry of the vitreous, the process of posterior vitreous detachment (PVD) development, and the available clinical approaches to examining the vitreous and its interface. A pooled analysis of studies looking at the presence of a complete, partial or absent PVD in a number of macular and retinal diseases allows us to establish odds ratios for these various states. From this emerge both protective and disease-associated states in conditions such as proliferative diabetic retinopathy, macular edema, and age-related macular degeneration. With the emergence of pharmacological means to separate the posterior hyaloid, a better understanding of the possible role of the vitreous in tractional syndromes is required.
Risk of Stroke with Thiazolidinediones: A Ten-Year Nationwide Population-Based Cohort Study
Authors: Lu Chien-Jung , Sun Yu , Muo Chih-Hsin , Chen Rong-Chi , Chen Pei-Chun , Hsu Chung Y.
Published: September 2013

Background: Thiazolidinediones (TZDs) - rosiglitazone and pioglitazone - a class of insulin sensitizer for treating type 2 diabetes, have been reported to exhibit neuroprotective effects in preclinical studies and have good effects in the control of blood sugar for diabetic patients with insulin resistance. However, clinical trials and observational studies have raised the possibility of higher stroke risk in patients treated with rosiglitazone. Whether pioglitazone poses similar stroke risk remains uncertain. Most of the studies on cardiovascular effects of TZDs were based on studies in the USA and Europe. The present study aimed to compare the stroke risk among diabetic patients on TZD to those on non-TZD medications in an Asian population. Methods: The study cohort included 15,981 patients with a diagnosis of diabetes without prior stroke, acute myocardial infarction (AMI) or heart failure who were followed from 2001 to 2010. Patients were classified by their prescriptions into rosiglitazone, pioglitazone and non-TZD groups. The study end points included ischemic and hemorrhagic stroke. In view of the reported association of heart failure and AMI with rosiglitazone, these 2 end points were also included in the present study. Cox hazard proportional models were used to estimate the risk of developing the end points. Likelihood ratio test was used to examine the age-drug interactions. Dose-response effects were evaluated by comparing the incidence rates among patients with different cumulative exposures to TZD. Results: During the 10-year follow-up, the rosiglitazone group showed significantly higher risk of ischemic stroke (multivariate adjusted hazard ratio, HR = 1.39; 95% confidence interval, CI = 1.16-1.66) and heart failure (HR = 1.59; 95% CI = 1.18-2.14) than the non-TZD group. The pioglitazone group did not show significant difference from the non-TZD group in ischemic stroke (HR = 0.97; 95% CI = 0.75-1.26) and heart failure (HR = 0.94; 95% CI = 0.59-1.50). The results also showed a significant dose-dependent effect of higher risk of ischemic stroke with increasing dosage of rosiglitazone, while there was no increased risk at any level of pioglitazone dosage. Conclusions: This population-based cohort study shows that rosiglitazone imposes a higher risk of developing stroke or heart failure in this Asian patient population, suggesting the adverse side effects of rosiglitazone across ethnic boundaries. Pioglitazone, on the other hand, does not increase cardiovascular or stroke risk compared to the non-TZD group among diabetic patients without a history of macrovascular disease.
Pilot Study Using Proteomics to Identify Predictive Biomarkers of Necrotizing Enterocolitis from Buccal Swabs in Very Low Birth Weight Infants
Authors: Murgas Torrazza Roberto , Li Nan , Young Christopher , Kobeissy Firas , Chow Marjorie , Chen Sixue , Mai Volker , Sharma Renu , Hudak Mark , Shuster Jonathan , Neu Josef
Published: September 2013

Background: Necrotizing enterocolitis (NEC) is a major cause of death and morbidity in very low birth weight infants. Objective: To identify biomarker(s) that would predict NEC using buccal swab samples utilizing a proteomic approach. Methods: Cumulative buccal swab samples derived from very low birth weight preterm infants (<32 weeks' gestational age and <1,250 g) at 1, 2 and 3 weeks prior to the development of NEC and matched controls were subjected to two-dimensional difference gel electrophoresis and LC-MS/MS analysis for proteomic protein discovery. After identification of 21 altered proteins, we chose 3 candidate proteins using a broad systems biologic analysis approach that suggested several altered cellular processes that could be associated with NEC. Results: Preliminary validation studies using Western blots on these samples and 10 additional NEC and 10 matched control buccal samples collected within 2 or 3 weeks before NEC diagnosis analysis showed lower interleukin-1 receptor antagonist. Conclusion: Our results suggest that interleukin-1 receptor antagonist is worthy of further studies to determine its utility in helping predict NEC.
Comparative Study of the Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation from Human Leukocyte Antigen-Haploidentical Related and Unrelated Donors in the Treatment of Leukemia
Authors: Yang Kai , Si Yingjian , Chen Huiren , He Xuepeng , Lou JinXing , Bai Xue , Du Junfeng , Guo Zhi , Chen Peng
Published: September 2013

Aims: To compare the efficacy of hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA)-haploidentical related donors (RD) and unrelated donors (URD) in the treatment of leukemia. Methods: Ninety-three leukemia patients underwent allogeneic HSCT were divided into two groups: 51 cases of RD-HSCT and 42 cases of URD-HSCT. In the RD-HSCT group, a preconditioning regimen with fludarabine (Flu) + busulfan (Bu) + cytosine arabinoside (Ara-C) was used in 42 patients and total body irradiation (TBI) + Flu + Ara-C was used in the remaining 9. Results: In the URD-HSCT group, a modified preconditioning regimen with Bu + cyclophosphamide was used in 35 patients, while the other 7 patients underwent treatment with TBI + Flu. After transplantation, the occurrence rate of grade II-IV acute graft-versus-host disease (GVHD) was 46.0 and 51.2% in the two groups. Likewise, the rate of chronic GVHD was 46.0 and 63.4%, respectively. No significant differences in the occurrence of acute and chronic GVHD were detected between the two groups. The differences in early-stage infection rate after transplantation, recurrence rate, 3-year survival rate, and disease-free survival rate between the two groups were not significant. Conclusion: HLA-haploidentical RD-HSCT with enhanced preconditioning and administration of immunosuppressants showed a clinical efficacy similar to that of URD-HSCT against leukemia, without the risk of increased infection and GVHD.