bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermoanalytical Investigation of Some Sulfone-Containing Drugs
Authors: Salama Nahla N. , El Ries Mohammed A. , Toubar Safaa , Abd El Hamid Maha , Walash Mohammed I.
Published: June 2012

The thermal behavior of some sulfone-containing drugs, namely, dapsone (DDS), dimethylsulfone (MSM), and topiramate (TOP) in drug substances, and products were investigated using different thermal techniques. These include thermogravimetry (TGA), derivative thermogravimetry (DTG), differential thermal analysis (DTA), and differential scanning calorimetry (DSC). The thermogravimetric data allowed the determination of the kinetic parameters: activation energy (Ea), frequency factor (A), and reaction order (n). The thermal degradation of dapsone and topiramate was followed a first-order kinetic behavior. The calculated data evidenced a zero-order kinetic for dimethylsulfone. The relative thermal stabilities of the studied drugs have been evaluated and follow the order DDS > TOP > MSM. The purity was determined using DSC for the studied compounds, in drug substances and products. The results were in agreement with the recommended pharmacopoeia and manufacturer methods. DSC curves obtained from the tablets suggest compatibility between the drugs, excipients and/or coformulated drugs. The fragmentation pathway of dapsone with mass spectrometry was taken as example, to correlate the thermal decomposition with the resulted MS-EI. The decomposition modes were investigated, and the possible fragmentation pathways were suggested by mass spectrometry.
Dose-Escalated Hypofractionated Intensity-Modulated Radiotherapy in High-Risk Carcinoma of the Prostate: Outcome and Late Toxicity
Authors: Thomson David , Merrick Sophie , Swindell Ric , Coote Joanna , Kelly Kay , Stratford Julie , Wylie James , Cowan Richard , Elliott Tony , Logue John , Choudhury Ananya , Livsey Jacqueline
Published: June 2012

Background. The benefit of dose-escalated hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) in prostate cancer is not established. We report 5-year outcome and long-term toxicity data within a phase II clinical trial.Materials and Methods. 60 men with predominantly high-risk prostate cancer were treated. All patients received neoadjuvant hormone therapy, completing up to 6 months in total. Thirty patients were treated with 57 Gy in 19 fractions and 30 patients with 60 Gy in 20 fractions. Acute and 2-year toxicities were reported and patients followed longitudinally to assess 5 year outcomes and long-term toxicity. Toxicity was measured using RTOG criteria and LENT/SOMA questionnaire.Results. Median followup was 84 months. Five-year overall survival (OS) was 83% and biochemical progression-free survival (bPFS) was 50% for 57 Gy. Five-year OS was 75% and bPFS 58% for 60 Gy. At 7 years, toxicity by RTOG criteria was acceptable with no grade 3 or above toxicity. Compared with baseline, there was no significant change in urinary symptoms at 2 or 7 years. Bowel symptoms were stable between 2 and 7 years. All patients continued to have significant sexual dysfunction.Conclusion. In high-risk prostate cancer, dose-escalated hypofractionated radiotherapy using IMRT results in encouraging outcomes and acceptable late toxicity.
Resilience and Its Association with Depression, Emotional and Behavioural Problems, and Mental Health Service Utilisation among Refugee Adolescents Living in South Australia
Authors: Ziaian Tahereh , de Anstiss Helena , Antoniou Georgia , Baghurst Peter , Sawyer Michael
Published: June 2012

Background. Despite the frequency of traumatic or stressful events experienced by refugee children and adolescents prior to migration and following resettlement, the majority do not experience mental health problems emphasising the critical nature of resilience. While a host of factors deemed to be protective of mental health in young refugees have been identified, there has been little research exploring the role of resilience as a distinct psychological construct. This study aimed to explore the nature of psychological resilience in refugee adolescents and the relationship between resilience and depression, other emotional and behavioural problems, and mental health service uptake. Method. One hundred and seventy multiethnic refugee adolescents aged 13–17 from South Australia were administered a survey comprising the Connor-Davidson Resilience Scale (CD-RISC), Children’s Depression Inventory (CDI), and Strengths and Difficulties Questionnaire (SDQ). Results. Females tended to have higher resilience, as did those adolescents who had been living in Australia longer. Adolescents suffering from depressive symptoms or other emotional or behavioural problems had lower resilience. There was little evidence of an association between resilience scores and exposure to trauma or service utilisation. Discussion. Fostering resilience may be critical to efforts to prevent or reduce mental health problems in refugee adolescents.
A New Bottle Design Decreases Hypoxemic Episodes during Feeding in Preterm Infants
Authors: Jenik Alejandro , Fustiñana Carlos , Marquez Maritza , Mage David , Fernandez Gloria , Mariani Gonzalo
Published: June 2012

Oxygen saturation is lower during bottle feeding than during breastfeeding in preterm infants. Our objective was to compare two different bottle systems in healthy preterm infants before discharge in terms of SpO2and oral feeding efficiency (rate of milk intake). Infants without supplement oxygen needs were evaluated twice on the same day during two consecutive feeds, by the same nurse. Infants served as their own controls for comparison of two systems of bottles, the order of which was randomized. The new bottle's nipple design mimics mom's breast in shape and feel, and the bottle vents to air when the child sucks on the nipple. The other system was the hospital's standard plastic bottle with silicone nipple. The rate of milk intake was calculated as the total volume transferred minus volume lost divided by time of feeding, mL/min. Thirty-four infants (BW:1,163±479.1 g) were studied at35.4±1.3weeks after-conception. SpO2was significantly higher in infants fed with the new bottle design. Milk intake rate was significantly higher with the new bottle than with the standard bottle design. The new bottle design improves oral feeding performance in preterm infants near to discharge when compared to that of a standard bottle.
Association of Indoor Smoke-Free Air Laws with Hospital Admissions for Acute Myocardial Infarction and Stroke in Three States
Authors: Loomis Brett R. , Juster Harlan R.
Published: June 2012

Objective. To examine whether comprehensive smoke-free air laws enacted in Florida, New York, and Oregon are associated with reductions in hospital admissions for acute myocardial infarction (AMI) and stroke.Methods. Analyzed trends in county-level, age-adjusted, hospital admission rates for AMI and stroke from 1990 to 2006 (quarterly) for Florida, 1995 to 2006 (monthly) for New York, and 1998 to 2006 (monthly) for Oregon to identify any association between admission rates and passage of comprehensive smoke-free air laws. Interrupted time series analysis was used to adjust for the effects of preexisting moderate local-level laws, seasonal variation in hospital admissions, differences across counties, and a secular time trend.Results. More than 3 years after passage of statewide comprehensive smoke-free air laws, rates of hospitalization for AMI were reduced by 18.4% (95% CI: 8.8–28.0%) in Florida and 15.5% (95% CI: 11.0–20.1%) in New York. Rates of hospitalization for stroke were reduced by 18.1% (95% CI: 9.3–30.0%) in Florida. The few local comprehensive laws in Oregon were not associated with reductions in AMI or stroke statewide.Conclusion. Comprehensive smoke-free air laws are an effective policy tool for reducing the burden of AMI and stroke.
Statistical Complexity of Low- and High-Dimensional Systems
Authors: Ryabov Vladimir , Nerukh Dmitry
Published: June 2012

We suggest a new method for the analysis of experimental time series that can distinguish high-dimensional dynamics from stochastic motion. It is based on the idea of statistical complexity, that is, the Shannon entropy of the so-called ϵ-machine (a Markov-type model of the observed time series). This approach has been recently demonstrated to be efficient for making a distinction between a molecular trajectory in water and noise. In this paper, we analyse the difference between chaos and noise using the Chirikov-Taylor standard map as an example in order to elucidate the basic mechanism that makes the value of complexity in deterministic systems high. In particular, we show that the value of statistical complexity is high for the case of chaos and attains zero value for the case of stochastic noise. We further study the Markov property of the data generated by the standard map to clarify the role of long-time memory in differentiating the cases of deterministic systems and stochastic motion.
First Trimester Abortion: A Rare Cause of Intrauterine Bony Spicules
Authors: Singla Anshuja , Gupta Bindiya , Guleria Kiran
Published: June 2012

Bony fragments in the uterus occur after second trimester termination of pregnancy following retained fetal bones. Very rarely, they can form following first trimester loss. Clinical symptoms range from pain, menstrual symptoms, and infertility. Ultrasound shows a hyperechoic shadow, and treatment is by curettage or hysteroscopic removal.
Increased BOLD Variability in the Parietal Cortex and Enhanced Parieto-Occipital Connectivity during Tactile Perception in Congenitally Blind Individuals
Authors: Leo Andrea , Bernardi Giulio , Handjaras Giacomo , Bonino Daniela , Ricciardi Emiliano , Pietrini Pietro
Published: June 2012

Previous studies in early blind individuals posited a possible role of parieto-occipital connections in conveying nonvisual information to the visual occipital cortex. As a consequence of blindness, parietal areas would thus become able to integrate a greater amount of multimodal information than in sighted individuals. To verify this hypothesis, we compared fMRI-measured BOLD signal temporal variability, an index of efficiency in functional information integration, in congenitally blind and sighted individuals during tactile spatial discrimination and motion perception tasks. In both tasks, the BOLD variability analysis revealed many cortical regions with a significantly greater variability in the blind as compared to sighted individuals, with an overlapping cluster located in the left inferior parietal/anterior intraparietal cortex. A functional connectivity analysis using this region as seed showed stronger correlations in both tasks with occipital areas in the blind as compared to sighted individuals. As BOLD variability reflects neural integration and processing efficiency, these cross-modal plastic changes in the parietal cortex, even if described in a limited sample, reinforce the hypothesis that this region may play an important role in processing nonvisual information in blind subjects and act as a hub in the cortico-cortical pathway from somatosensory cortex to the reorganized occipital areas.
Simulating Evacuations with Obstacles Using a Modified Dynamic Cellular Automata Model
Authors: Eng Aik Lim , Wee Choon Tan
Published: June 2012

A modified dynamic cellular automata model is proposed to simulate the evacuation of occupants from a room with obstacles. The model takes into account some factors that play an important role in an evacuation process, such as human emotions and crowd density around the exits. It also incorporates people’s ability to select a less congested exit route, a factor that is rarely investigated. The simulation and experimental results show that modifications to the exits provide reasonable improvement to evacuation time, after taking into account the fact that people will tend to select exit routes based on the distance to the exits and the crowd density around the exits. In addition, the model is applied to simulations of classroom and restaurant evacuation. Results obtained with the proposed model are compared with those of several existing models. The outcome of the comparison demonstrates that it performs better than existing models.
Generalizations of Wendroff Integral Inequalities and Their Discrete Analogues
Authors: Ashyraliyev Maksat
Published: June 2012

Generalizations of Wendroff type integral inequalities with four dependent limits and their discrete analogues are obtained. In applications, these results are used to establish the stability estimates for the solution of the Goursat problem.
Mixed Nanostructured Ti‐W Oxides Films for Efficient Electrochromic Windows
Authors: Dinh Nguyen Nang , Ninh Dang Hai , Thao Tran Thi , Vo-Van Truong
Published: June 2012

With the aim to enhance the electrochromic (EC) efficiency and electrochemical stability of electrochromic devices (ECD), mixed nanostructured TiO2/WO3 films were prepared by an electrochemical deposition method with the purpose of adding WO3 nanoparticles to porous nanocrystalline doctor‐blade TiO2 (nc‐TiO2) films. The results of the characterization of electrochromic properties in 1 M LiClO4 + propylene carbonate (LiClO4 + PC) of both the nc‐TiO2/F‐doped tin oxide (FTO) and WO3/TiO2/FTO configurations showed the reversible coloration and bleaching of the ECDs. The response time of the ECD coloration of WO3/TiO2/FTO was found to be as small as 2 sec, and its coloration efficiency (CE) as high as 35.7 cm2 × C−1. By inserting WO3 nanoparticles into the porous TiO2 structures, WO3/TiO2 heterojunctions were formed in the films, consequently enabling both the CE and electrochemical stability of the working electrodes to be considerably enhanced. Since a large‐area WO3/TiO2 can be prepared by the doctor‐blade technique followed by the electrochemical deposition process, mixed nanostructured Ti‐W oxides electrodes constitute a good candidate for smart window applications, taking advantage of the excellent coloration and stability properties as well as the simple and economical fabrication process involved.
The Projection Pressure for Asymptotically Weak Separation Condition and Bowen′s Equation
Authors: Wang Chenwei , Chen Ercai
Published: June 2012

Let be a weakly conformal iterated function system on ℝd with attractor K. Let π be the canonical projection. In this paper we define a new concept called “projection pressure” Pπ(φ) for φ ∈ C(Σ) and show the variational principle about the projection pressure under AWSC. Furthermore, we check that the zero of “projection pressure” still satisfies Bowen′s equation. Using the root of Bowen′s equation, we can get the Hausdorff dimension of the attractor K.
Where Do Phosphosites Come from and Where Do They Go after Gene Duplication?
Authors: Diss Guillaume , Freschi Luca , Landry Christian R.
Published: June 2012

Gene duplication followed by divergence is an important mechanism that leads to molecular innovation. Divergence of paralogous genes can be achieved at functional and regulatory levels. Whereas regulatory divergence at the transcriptional level is well documented, little is known about divergence of posttranslational modifications (PTMs). Protein phosphorylation, one of the most important PTMs, has recently been shown to be an important determinant of the retention of paralogous genes. Here we test whether gains and losses of phosphorylated amino acids after gene duplication may specifically modify the regulation of these duplicated proteins. We show that when phosphosites are lost in one paralog, transitions from phosphorylated serines and threonines are significantly biased toward negatively charged amino acids, which can mimic their phosphorylated status in a constitutive manner. Our analyses support the hypothesis that divergence between paralogs can be generated by a loss of the posttranslational regulatory control on a function rather than by the complete loss of the function itself. Surprisingly, these favoured transitions cannot be reached by single mutational steps, which suggests that the function of a phosphosite needs to be completely abolished before it is restored through substitution by these phosphomimetic residues. We conclude by discussing how gene duplication could facilitate the transitions between phosphorylated and phosphomimetic amino acids.
Nutraceuticals as Ligands of PPARγ
Authors: Penumetcha Meera , Santanam Nalini
Published: June 2012

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors that respond to several exogenous and endogenous ligands by modulating genes related to lipid, glucose, and insulin homeostasis. PPARγ, expressed in adipose tissue and liver, regulates lipid storage and glucose metabolism and is the target of type 2 diabetes drugs, thiazolidinediones (TZDs). Due to high levels of toxicity associated with the first generation TZDs, troglitazone (Rezulin), rosiglitazone (Avandia), and pioglitazone (Actos), there is a renewed search for newer PPAR drugs that exhibit better efficacy but lesser toxicity. In recent years, there has been a definite increase in the consumption of dietary supplements among diabetics, due to the possible health benefits associated with these nutraceutical components. With this impetus, investigations into alternative natural ligands of PPARs has also risen. This review highlights some of the dietary compounds (dietary lipids, isoflavones, and other flavanoids) that bind and transactivate PPARγ. A better understanding of the physiological effects of this PPAR activation by nutraceuticals and the availability of high-throughput technologies should lead to the discovery of less toxic alternatives to the PPAR drugs currently on the market.
Transcriptional Mechanisms Controlling miR-375 Gene Expression in the Pancreas
Authors: Avnit-Sagi Tali , Vana Tal , Walker Michael D.
Published: June 2012

MicroRNAs (miRNAs) are a class of small non-coding RNAs that play an important role in mediating a broad and expanding range of biological activities. miR-375 is expressed selectively in the pancreas. We have previously shown that selective expression of miR-375 in pancreatic beta cells is controlled by transcriptional mechanisms operating through a TATA box-containing promoter. Expression of miR-375 has been reported in non-beta cells within the endocrine pancreas, and indeed inactivation of miR-375 leads to perturbation in cell mass and number of both alpha and beta cells. Consistent with its expression throughout the endocrine pancreas, we now show that the promoter of the miR-375 gene shows selective activity in pancreatic endocrine alpha cells, comparable to that observed in beta cells. We previously identified a novel negative regulatory element located downstream of the miR-375 gene transcription start site. By generating luciferase reporter genes, we now show that the sequence is functional also when positioned upstream of a heterologous promoter, thus proving that the repressor effect is mediated at least in part at the level of transcription. Further characterization of the transcriptional control mechanism regulating expression of miR-375 and other pancreatic miRNAs will contribute to a better understanding of pancreas development and function.
Comparing Years of Healthy Life, Measured in 16 Ways, for Normal Weight and Overweight Older Adults
Authors: Diehr Paula , Thielke Stephen , O’Meara Ellen , Fitzpatrick Annette L. , Newman Anne
Published: June 2012

Introduction. The traditional definitions of overweight and obesity are not age specific, even though the relationship of weight to mortality is different for older adults. Effects of adiposity on aspects of health beside mortality have not been well investigated.Methods. We calculated the number of years of healthy life (YHL) in the 10 years after baseline, for 5,747 older adults. YHL was defined in 16 different ways. We compared Normal and Overweight persons, classified either by body mass index (BMI) or by waist circumference (WC).Findings. YHL for Normal and Overweight persons differed significantly in 25% of the comparisons, of which half favored the Overweight. Measures of physical health favored Normal weight, while measures of mental health and quality of life favored Overweight. Overweight was less favorable when defined by WC than by BMI. Obese persons usually had worse outcomes.Discussion. Overweight older adults averaged as many years of life and years of healthy life as those of Normal weight. There may be no outcome based reason to distinguish Normal from Overweight for older adults.Conclusion. The “Overweight paradox” appears to hold for nonmortality outcomes. New adiposity standards are needed for older adults, possibly different by race and sex.
Roles of p53 in Various Biological Aspects of Hematopoietic Stem Cells
Authors: Nii Takenobu , Marumoto Tomotoshi , Tani Kenzaburo
Published: June 2012

Hematopoietic stem cells (HSCs) have the capacity to self-renew as well as to differentiate into all blood cell types, and they can reconstitute hematopoiesis in recipients with bone marrow ablation. In addition, transplantation therapy using HSCs is widely performed for the treatment of various incurable diseases such as hematopoietic malignancies and congenital immunodeficiency disorders. For the safe and successful transplantation of HSCs, their genetic and epigenetic integrities need to be maintained properly. Therefore, understanding the molecular mechanisms that respond to various cellular stresses in HSCs is important. The tumor suppressor protein, p53, has been shown to play critical roles in maintenance of “cell integrity” under stress conditions by controlling its target genes that regulate cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. In this paper, we summarize recent reports that describe various biological functions of HSCs and discuss the roles of p53 associated with them.
Photochemical Impact on Ozone Fluxes in Coastal Waters
Authors: Coleman L. , McVeigh P. , Berresheim H. , Martino M. , O'Dowd C. D.
Published: June 2012

Ozone fluxes, derived from gradient measurements in Northeast Atlantic coastal waters, were observed to depend on both tide height and solar radiation. Peak ozone fluxes of−0.26±0.04 μg m-2 s-1occurred during low-tide conditions when exposed microalgae fields contributed to the flux footprint. Additionally, at mid-to-high tide, when water surfaces contribute predominantly to the flux footprint, fluxes of the order of−0.12±0.03 μg m-2 s-1were observed. Considering only fluxes over water covered surfaces, and using an advanced ozone deposition model that accounts for surface-water chemistry enhancing the deposition sink, it is demonstrated that a photochemical enhancement reaction with dissolved organic carbon (DOC) is required to explain the enhanced ozone deposition during daylight hours. This sink amounts to an ozone loss rate of up to 0.6 ppb per hour under peak solar irradiance and points to a missing sink in the marine boundary layer ozone budget.
Pseudolaric Acid B Induces Caspase-Dependent and Caspase-Independent Apoptosis in U87 Glioblastoma Cells
Authors: Khan Muhammad , Zheng Bin , Yi Fei , Rasul Azhar , Gu Zhuyi , Li Ting , Gao Hongwen , Qazi Javed Iqbal , Yang Hong , Ma Tonghui
Published: June 2012

Pseudolaric acid B (PLAB) is one of the major bioactive components ofPseudolarix kaempferi. It has been reported to exhibit inhibitory effect on cell proliferation in several types of cancer cells. However, there is no report elucidating its effect on glioma cells and organ toxicityin vivo. In the present study, we found that PLAB inhibited growth of U87 glioblastoma cells in a dose-dependent manner with IC50~10 μM. Flow cytometry analysis showed that apoptotic cell death mediated by PLAB was accompanied with cell cycle arrest at G2/M phase. Using Western blot, we found that PLAB induced G2/M phase arrest by inhibiting tubulin polymerization in U87 cells. Apoptotic cell death was only partially inhibited by pancaspase inhibitor, z-VAD-fmk, which suggested that PLAB-induced apoptosis in U87 cells is partially caspase-independent. Further mechanistic study demonstrated that PLAB induced caspase-dependent apoptosis via upregulation of p53, increased level of proapoptotic protein Bax, decreased level of antiapoptotic protein Bcl-2, release of cytochrome c from mitochondria, activation of caspase-3 and proteolytic cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-independent apoptosis through apoptosis inducing factor (AIF). Furthermore,in vivotoxicity study demonstrated that PLAB did not induce significant structural and biochemical changes in mouse liver and kidneys at a dose of 25 mg/kg. Therefore, PLAB may become a potential lead compound for future development of antiglioma therapy.
S100P-Derived RAGE Antagonistic Peptide Reduces Tumor Growth and Metastasis
Authors: Arumugam Thiruvengadam , Ramachandran Vijaya , Gomez Sobeyda B. , Schmidt Ann M. , Logsdon Craig D.
Published: June 2012

Purpose: The receptor for advanced glycation end products (RAGE) contributes to multiple pathologies, including diabetes, arthritis, neurodegenerative diseases, and cancer. Despite the obvious need, no RAGE inhibitors are in common clinical use. Therefore, we developed a novel small RAGE antagonist peptide (RAP) that blocks activation by multiple ligands.

Experimental Design: RAGE and its ligands were visualized by immunohistochemical analysis of human pancreatic tissues, and siRNA was used to analyze their functions. Interactions between RAGE and S100P, S100A4, and HMGB-1 were measured by ELISA. Three S100P-derived small antagonistic peptides were designed, synthesized, and tested for inhibition of RAGE binding. The effects of the peptide blockers on NFκB-luciferase reporter activity was used to assess effects on RAGE-mediated signaling. The most effective peptide was tested on glioma and pancreatic ductal adenocarcinoma (PDAC) models.

Results: Immunohistochemical analysis confirmed the expression of RAGE and its ligands S100P, S100A4, and HMGB-1 in human PDAC. siRNA silencing of RAGE or its ligands reduced the growth and migration of PDAC cells in vitro. The most effective RAP inhibited the interaction of S100P, S100A4, and HMGB-1 with RAGE at micromolar concentrations. RAP also reduced the ability of the ligands to stimulate RAGE activation of NFκB in cancer cells in vitro and in vivo. Importantly, systemic in vivo administration of RAP reduced the growth and metastasis of pancreatic tumors and also inhibited glioma tumor growth.

Conclusion: RAP shows promise as a tool for the investigation of RAGE function and as an in vivo treatment for RAGE-related disorders. Clin Cancer Res; 18(16); 4356–64. ©2012 AACR.
Rare Cancer Trial Design: Lessons from FDA Approvals
Authors: Gaddipati Himabindu , Liu Ke , Pariser Anne , Pazdur Richard
Published: June 2012

A systematic analysis of clinical trials supporting rare cancer drug approvals may identify concepts and terms that can inform the effective design of prospective clinical trials for rare cancers. In this article, using annual incidence ≤6 of 100,000 individuals to define “rare cancer,” we identified clinical trials for rare cancers, supporting U.S. Food and Drug Administration (FDA) drug approvals for rare cancer indications between December 1987 and May 2011. We characterized each selected trial for study design, sample size, primary efficacy endpoints, and statistical comparisons. We also profiled trials with regard to type of submission, review designation, and approval type. Our results indicated that, of 99 trials that supported the approvals of 45 drugs for 68 rare cancer indications, one third of these trials were randomized; 69% of approvals relied on objective response rate as the primary efficacy endpoint; and 63% were based on a single trial. Drugs granted accelerated approval appeared more likely to be associated with postmarketing safety findings, relative to drugs approved under the regular approval. Data collected across clinical trials were robust: Use of different lower incidence rates in analyzing these trials did not have effects on trial characteristics. The absolute number of drug approvals for rare cancer indications increased markedly over time. We concluded that one third of clinical trials supporting drug approvals for rare cancer indications were randomized, affirming the feasibility and value of randomized trial design to evaluate drugs for rare cancers. Postmarketing safety data may relate to trial design and approval type. An operational definition of “rare cancer” can be useful for the analysis of trial data and for the path toward harmonizing the terminology in the area of clinical research on rare cancers. Clin Cancer Res; 18(19); 5172–8. ©2012 AACR.
Screening of Elderly for Chronic Kidney Disease
Authors: Ležaić Višnja , Bajčetić Sanja , Peruničić-Peković Gordana , Bukvić Danica , Dimković Nada , Djukanović Ljubica
Published: June 2012

Background and Aims: The frequency of chronic kidney disease (CKD) markers was assessed in two groups of patients over 60 years – one without and the other with hypertension. Methods: The cross-sectional study involved 585 asymptomatic elderly patients (227 males), 93 without and 492 with hypertension. Data on patients were obtained by interview, analysis of medical records and physical examinations. Serum and urine creatinine, proteinuria, microalbuminuria (MAU, turbidimetry), and urinary sediment were analyzed. Results: Among the 585 patients, there were 54.5% with a positive family history for hypertension and 14% for kidney diseases. MAU was significantly more frequent (30 vs. 11%) and the mean estimated glomerular filtration rate (eGFR) higher (71 ± 14 vs. 64 ± 14 ml/min/1.73 m) in patients without hypertension than in those with hypertension. The majority of patients with stage 3 CKD had eGFR >45 ml/min/1.73 m2 with normal urinary findings. Multivariate logistic regression analysis found age and treatment with angiotensin-converting enzyme inhibitors to be associated with reduced eGFR, MAU and proteinuria. In addition, smoking was associated with eGFR, but a family history for kidney disease and belonging to the group without hypertension were associated with MAU. Conclusion: The high prevalence of markers for CKD in symptomless elderly without hypertension confirmed that the elderly, as a high-risk population, should be screened based on increased age alone.
A Paleoneurohistological Study of 3,000-Year-Old Mummified Brain Tissue from the Mediterranean Bronze Age
Authors: Prats-Muñoz Gemma , Malgosa Assumpció , Armentano Nuria , Galtés Ignasi , Esteban Jordi , Bombi Josep A. , Tortosa Montserrat , Fernández Eva , Jordana Xavier , Isidro Albert , Fullola Josep M. , Petit M. Àngels , Guerrero Victor M. , Calvo Manuel , Fernández Pedro L.
Published: June 2012

Objectives: Mummified nervous tissue is very rarely found in ancient remains and usually corresponds to corpses which were frozen or preserved in bogs, conditions which limit tissue autolysis and bacterial degradation. Here, we show the unusual finding of spontaneously mummified brain tissue from several individuals from the little known megalithic talaiotic culture of the island of Minorca, dating approximately 3,000 years before present and corresponding to the late Mediterranean Bronze Age. Methods: These individuals were part of an intact burial site containing 66 subjects. Intracraneal samples were carefully rehydrated with Sandison’s solution. We used classical histochemical as well as 2D and 3D (scanning) electron-microscopic techniques. Results: We provide evidence of the nervous nature of the samples as well as a detailed description of the morphological features of these ancient tissues. The intracranial material consisted of well-preserved eosinophilic reticular tissue and, although mostly absent, some exceptional pigment-containing neurons were identified. Conclusions: We present a detailed morphological analysis which can provide valuable information and guidelines for the interpretation of this scarce type of mummified samples and provide explanations for this surprising preservation.
Genetic Identification of Missing Persons: DNA Analysis of Human Remains and Compromised Samples
Authors: Alvarez-Cubero M.J. , Saiz M. , Martinez-Gonzalez L.J. , Alvarez J.C. , Eisenberg A.J. , Budowle B. , Lorente J.A.
Published: June 2012

Human identification has made great strides over the past 2 decades due to the advent of DNA typing. Forensic DNA typing provides genetic data from a variety of materials and individuals, and is applied to many important issues that confront society. Part of the success of DNA typing is the generation of DNA databases to help identify missing persons and to develop investigative leads to assist law enforcement. DNA databases house DNA profiles from convicted felons (and in some jurisdictions arrestees), forensic evidence, human remains, and direct and family reference samples of missing persons. These databases are essential tools, which are becoming quite large (for example the US Database contains 10 million profiles). The scientific, governmental and private communities continue to work together to standardize genetic markers for more effective worldwide data sharing, to develop and validate robust DNA typing kits that contain the reagents necessary to type core identity genetic markers, to develop technologies that facilitate a number of analytical processes and to develop policies to make human identity testing more effective. Indeed, DNA typing is integral to resolving a number of serious criminal and civil concerns, such as solving missing person cases and identifying victims of mass disasters and children who may have been victims of human trafficking, and provides information for historical studies. As more refined capabilities are still required, novel approaches are being sought, such as genetic testing by next-generation sequencing, mass spectrometry, chip arrays and pyrosequencing. Single nucleotide polymorphisms offer the potential to analyze severely compromised biological samples, to determine the facial phenotype of decomposed human remains and to predict the bioancestry of individuals, a new focus in analyzing this type of markers.
Palaeopathology: The Study of Disease in the Past
Authors: Fernández Pedro L.
Published: June 2012

Palaeopathology studies ancient human or animal remains from a pathological point of view, for which techniques and tools such as inspection and light and electron microscopy after adequate rehydration, immunohistochemistry and molecular biology are used. Despite the degradation of tissues, partial preservation of their structure and content after a natural or artificial mummification process often allows the extraction of valuable biological data, which sometimes provides interesting historical information.
Epidemic Trends of Obesity with Impact on Metabolism and Digestive Diseases
Authors: Feneberg Anja , Malfertheiner Peter
Published: June 2012

Currently, more than 14% of the world’s population is pre-obese or obese. The percentage is even higher in developed countries. Obesity is an important risk factor for a vast number of nonmalignant and malignant digestive diseases. Some of the more important examples are cholelithiasis, nonalcoholic fatty liver disease, and gastroesophageal reflux disease on the one hand and esophageal adenocarcinoma, gastric cardia adenocarcinoma, pancreatic cancer, liver cancer, gallbladder cancer, and colorectal cancer on the other hand. Their epidemic trends as reported in recent studies are reviewed here. Knowledge of their dependencies on obesity will yield a deeper understanding which is necessary to improve prevention and treatment concepts of this epidemic.
The Role of Obesity in Gastroesophageal Reflux Disease and Barrett’s Esophagus
Authors: Eusebi Leonardo Henry , Fuccio Lorenzo , Bazzoli Franco
Published: June 2012

The prevalence of gastroesophageal reflux disease (GERD) and related disorders has been increasing worldwide, particularly in Western populations where a parallel rise in obesity prevalence has been reported. As weight gain often overlaps with the GERD-related symptoms, several recent studies investigated the significance of this correlation, mainly using meta-analyses. Here, we discuss the large amount of evidence linking obesity and GERD-related symptoms, providing potential mechanisms for their co-occurrence. Particular attention is given also to the association between obesity, Barrett’s esophagus and esophageal adenocarcinoma development.
Nutritional and Behavioral Modification Therapies of Obesity: Facts and Fiction
Authors: Vranešić Bender Darija , Krznarić Željko
Published: June 2012

Current practice guidelines for management of overweight and obesity recommend a tripartite treatment – lifestyle modification program of diet, exercise, and behavior therapy for all persons with a body mass index of at least 30 (and those with body mass index 25 plus two weight-related comorbidities). Behavior therapy provides the structure that facilitates meeting goals for energy intake and expenditure. Lately, there has been a shift in focus from behavior change to cognitive change because it improves long-term results of lifestyle modification programs. Weight loss diets based on the amounts of individual macronutrients (high-protein diets, low-fat diets and low-carbohydrate diets, etc.) in the diet are not more effective than ‘classical’ low-calorie and balanced diets. An exception has been detected only in short-term diets with a low glycemic load. Also, epidemiological studies show that there is an inversely proportional relationship between body weight and Mediterranean diet. Cognitive behavioral therapy based on the Mediterranean diet has proven to be effective in clinical practice with regard to weight loss, body fat distribution, biochemical parameters, blood pressure and simplicity of following the diet.
Principles and Results of Bariatric Surgery
Authors: Lundell Lars
Published: June 2012

Bariatric surgery is followed by substantial and durable weight loss and associated with it favorable metabolic effects far beyond those achieved by lifestyle modifications and pharmacological treatments. The perioperative and postoperative morbidity and mortality have decreased significantly over the years to the level that bariatric surgery now can compare with other frequently recommended and well-accepted procedures such as cholecystectomy and hysterectomy. In fact, the postoperative mortality risk of bariatric surgery is far lower than that of coronary artery bypass surgery but with significantly greater improvement in long-term mortality. Much of the improvement in perioperative morbidity and mortality can be attributed to advances in many components of the care chain such as the introduction of laparoscopic surgery, as well as establishment of a nationwide center of excellence network and required outcome reporting. Extensive evidence on safety and efficacy supports bariatric surgery as the standard of care for treatment of severe obesity. Bariatric surgery reduces the risk of global mortality, all-cause mortality and cardiovascular mortality when compared to obese control patients. Both gastric banding and gastric bypass seem to reduce mortality risk.
Medical Complications of Bariatric Surgery: Focus on Malabsorption and Dumping Syndrome
Authors: Hammer Heinz F.
Published: June 2012

Gastroenterologists increasingly see patients with symptoms after bariatric surgery. A number of gastrointestinal or extra-gastrointestinal symptoms should raise the suspicion of malabsorption or dumping syndrome. Little is known about long-term consequences of disordered intestinal anatomy and physiology resulting from bariatric surgical procedures. The latency phase of clinical problems is unknown, but may potentially be long, and postoperative courses over many decades have to be considered regarding the consequences of surgical alterations of gastrointestinal structure and function. Long-term nutritional requirements in patients with bariatric procedures are incompletely understood. This review focuses on the pathophysiology of long-limb Roux-en-Y gastric bypass (RYGB) because it has become the most common bariatric procedure in many parts of the world. Although several potential mechanisms for nutritional deficiencies after RYGB like deficiency of dietary intake, lack of gastric secretions, exclusion of proximal duodenum and jejunum, or asynergia between food bolus and biliopancreatic secretions have been postulated, it was only very recently that in-depth studies have been carried out to measure the extent to which the long-limb RYGB causes malabsorption. In order to improve care for these patients, specialists who are trained in understanding pathophysiological changes in digestion and absorption after bariatric surgery and who recognize and treat clinical symptoms and nutritional deficits after bariatric surgery are needed. In addition, clinical researchers should take advantage of the experimental setups provided by standardized surgical procedures, and scientific societies should design courses and scientific meetings which combine the expertise in gastroenterology, surgery and nutrition.
Extraintestinal Manifestations of Autoimmune Pancreatitis
Authors: Milosavljevic Tomica , Kostic-Milosavljevic Mirjana , Jovanovic Ivan , Krstic Miodrag
Published: June 2012

The term autoimmune pancreatitis (AIP) was first used in Japan in 1995 to describe a newly recognized form of chronic pancreatitis, after the description of Yoshida and colleagues. But Sarles in 1961, first described a form of idiopathic chronic inflammatory sclerosis of the pancreas, suspected to be due to an autoimmune process. AIP has become a widely accepted term because clinical, serologic, histologic, and immunohistochemical findings suggest an autoimmune mechanism. Most affected patients have hypergammaglobulinemia and increased serum levels of IgG, particularly IgG4. Recently published International Consensus Diagnostic Criteria for Autoimmune Pancreatitis include Guidelines of the International Association of Pancreatology, classifying AIP into types 1 and 2, using five cardinal features of AIP, namely imaging of pancreatic parenchyma and duct, serology, other organ involvement, pancreatic histology, and an optional criterion of response to steroid therapy. Extrapancreatic presentations can include sclerosing cholangitis, retroperitoneal fibrosis, sclerosing sialadenitis (Küttner tumor), lymphadenopathy, nephritis, and interstitial pneumonia. Increased IgG4+ plasma cell infiltrate has been reported in sclerosing lesions from other organ sites, including inflammatory pseudotumors of the liver, breast, mediastinum, orbit, and aorta, and it has been observed with hypophysitis and IgG4-associated prostatitis. Abundant IgG4+ plasma cells were also confirmed in Riedel thyroiditis, sclerosing mesenteritis, and inflammatory pseudotumor of the orbit and stomach. Extrapancreatic lesions could be synchronously or metachronously diagnosed with AIP, sharing the same pathological conditions, showing also a favorable result to corticosteroid therapy and distinct differentiation between IgG4-related diseases from the inherent lesions of the corresponding organs.
A Case of Postpartum Eosinophilic Gastroenteritis and Review of the Literature
Authors: Milić Sandra , Poropat Goran , Malić Danijela , Štimac Davor
Published: June 2012

Eosinophilic gastroenteritis (EG) is a rare disease of unknown etiology that can involve any area of the gastrointestinal (GI) tract. It can be classified into three major types: predominantly mucosal, muscularis, or subserosal form. Diagnosis of EG is confirmed after the exclusion of other disorders having similar features, such as parasitic infection, carcinoma, allergy, and autoimmune conditions such as Churg-Strauss disease. Correct diagnosis hinges on the presence of eosinophilic infiltration of one or more areas of the GI tract, without extraintestinal involvement. We present the case of a 30-year-old female with symptoms of EG 26 days after delivery. After corticosteroid and montelukast treatment for 2 weeks, all symptoms and objective clinical findings disappeared. Although numerous cases of this disorder have been described, to our knowledge this is the first case of postpartum EG. This case highlights the need to include this entity in the differential diagnosis of postpartum GI disorders.
Molecular Hepatic Carcinogenesis: Impact of Inflammation
Authors: Szabo Gyongyi , Lippai Dora
Published: June 2012

Hepatocellular cancer (HCC) represents one of the most rapidly spreading cancers in the world. Most HCC develops in cirrhotic livers after prolonged inflammation, supporting the hypothesis that inflammation contributes to cancer development. Increasing evidence suggests that inflammatory cell recruitment and activation is an important contributor to promoting cancerous malformation in hepatocytes. Intracellular signaling pathways involved in classical inflammatory pathway activation can be altered in parenchymal cells, hepatocytes, in the liver to promote HCC development. Inflammation is triggered by pathogen-derived or endogenous danger-associated molecular patterns via pattern recognition receptors. Activation of the pattern recognition receptors triggers downstream signaling cascades to induce proinflammatory cytokine production, release of reactive oxygen species and modulate cellular responses. Many of these inflammatory mediators have adverse effects on DNA repair and induce DNA methylation, both of which are important elements in HCC development. This review summarizes the key points and discusses recent findings related to the role of inflammation in cancer and HCC development.
The Role of Inflammation and Proteinases in Tumor Progression
Authors: Herszényi László , Lakatos Gábor , Hritz István , Varga Mária Zsófia , Cierny Gabriel , Tulassay Zsolt
Published: June 2012

Chronic inflammation is an important risk factor for the development of cancers. The link between chronic inflammation and the risk of developing cancer is now well established. At least 20% of all cancers arise in association with infection and chronic inflammation. Inflammation and cancer are linked both along intrinsic (driven by genetic events causing malignancy) and extrinsic (driven by inflammatory conditions predisposing to tumor) pathways. Proteinases are key contributors to the breakdown and reconstitution of extracellular matrix components in physiological processes and pathological conditions, including destructive diseases and tumor progression. Matrix metalloproteinases are especially essential in the complex process of coregulation between cellular components of the tumor environment, and they are considered as potential diagnostic and prognostic biomarkers in many types and stages of cancer. Although the link between chronic inflammation, proteinases and risk of developing cancer is now well established, several open questions remain. The most exciting challenge is to find the best approach to target cancer-associated inflammation in patients with cancer. With respect to matrix metalloproteinases, the development of a new generation of selective inhibitors is a promising area of research.
Macro-Role of MicroRNA in Gastric Cancer
Authors: Link Alexander , Kupcinskas Juozas , Wex Thomas , Malfertheiner Peter
Published: June 2012

Gastric cancer is a heterogeneous disease with currently still unknown mechanisms of development. Besides genetic and epigenetic mechanisms, microRNAs (miRNAs) have recently been discovered as one of the crucial players in gastric carcinogenesis through posttranscriptional regulation of tumor suppressor and oncogenes. A substantial number of deregulated miRNAs have been revealed in gastric cancer and the biological significance of those miRNAs has been confirmed in multiple functional experiments. A growing number of studies suggest involvement of miRNAs in various steps of gastric carcinogenesis: from gastritis toward metastatic disease. Great biological stability of miRNAs opens novel fields in biomarker research with potential clinical implementation in screening, diagnosis, prediction of prognosis and therapeutic management. In this review, we provide the basic knowledge of miRNA biogenesis and discuss extensively the role of miRNAs in gastric carcinogenesis, including Helicobacter pylori-related miRNA alterations and potential translational clinical implementations.