A fish-based multi-metric assessment index in the Karun River basin, Iran.
Large river systems are one of the most important water resources for human societies. However, the ecological integrity of large rivers has been altered greatly by human activities. To monitor and manage these ecosystems, multimetric indices (MMI) are considered as efficient tools. This study aimed to develop and validate a fish-based multimetric index for the Karun River basin, Iran (Karun fish-based multi-metric index [KFMMI]). Eighteen rivers and 54 sites in the basin were sampled in July-August 2019, and physico-chemical and habitat characteristics were used to identify reference sites based on principal components analysis (PCA). Of the 54 sites, 14, 26, and 14 sites were classified as least, moderate, and most disturbed sites, respectively. Fifty-four candidate metrics were evaluated for range, responsiveness, and redundancy with other metrics. This resulted in the identification of eight metrics (relative abundance of native and endemic taxa, relative richness of migratory taxa, relative richness of Leuciscidae taxa, relative richness of herbivorous taxa, relative abundance of cyprinid taxa, relative richness of vegetative inhabitant taxa, relative abundance of slow water flow, and relative richness of edge inhabitant taxa) that informed on species richness and composition, migratory status, functional feeding groups, and habitat preferences. The KFMMI showed excellent performance in separating least, moderate, and most disturbed sites in our study area. Regarding water quality, the KFMMI was classified 16, 5, and 29 sites as good, moderate, and bad, respectively. The discrimination efficiency of KFMMI was 81.6%, which makes it an effective management tool for directing restoration actions at most disturbed sites and intensifying protection of least disturbed sites.


Study on Performance Tests and the Application of Construction Waste as Subgrade Backfill.
The application of construction waste as an aggregate in subgrade backfilling is an important recycling option. This study analyzed a subgrade backfill material consisting of lime-fly ash construction waste mixture (LFCWM). Compaction and California bearing ratio (CBR) tests were performed on LFCWM under different cement-aggregate ratios (CARs, 3:7, 4:6, 5:5, 8:2). Different normal stresses (100, 200, and 300 kPa) and aggregate sizes (20%, 40%, 60%, 80% of P4.75) were also evaluated. The experimental results indicated that: (1) when the CAR was 4:6, the optimum water content and the maximum dry density reached their maximum values of 10.1% and 2.03 g/cm3, respectively, the maximum CBR value was 42.5%, and the shear strength reached its maximum value. (2) With an increase in shear displacement, the shear stress showed a rapid initial increase, then a slow decrease, and finally tended to stabilize. (3) Normal stress had a positive effect on the shear strength of the mixture. (4) When P4.75 was 40%, the shear strength of LFCWM was the maximum. The research results have been successfully applied to road engineering, providing an important reference for the application of construction waste aggregate in roadbed engineering.


Disease-Specific Expression of Conjunctiva Associated Lymphoid Tissue (CALT) in Mouse Models of Dry Eye Disease and Ocular Allergy.
Conjunctiva-associated tissue (CALT) is assumed to play a crucial role in the immune system of the ocular surface. Its function in several ocular surface diseases (OSD) is still not fully understood. This study investigates the function of CALT in mouse models of dry-eye disease and ocular allergy. Since antigen-presentation is the central similarity in the pathologies, this study focuses on antigen-presentation in CALT Morphology and the expression of CALT, which was investigated in mice after induction of dry-eye, ocular allergy, topical antigen-stimulation, and after local depletion of phagocytic cells. Antigen uptake was investigated after the application of fluorescent ovalbumin (OVA). OSD influences the appearance and morphology of CALT in a disease-dependent manner. Ocular allergy leads to an increase and dry-eye disease to a decrease in number and size of CALT. The development of CALT is dependent on the presence of APCs. Professional APCs are present in CALT, and soluble antigen is transported into the follicle. CALT appearance is disease-specific and indicative of differing functions. Although the specific involvement of CALT in OSD needs further study, the existence of functional APCS and antigen-uptake supports the hypothesis that CALT is an immunological key player at the ocular surface.


[Integrity of multilayer of human periodontal ligament fibroblasts and human gingival fibroblasts grown on filter membrane of Transwell].
To investigate the integrity of multilayer of human periodontal ligament fibroblasts (HPDLF) and human gingival fibroblasts (HGF) on filter membrane of Transwell and to provide basis for the drug transcellular transport by the HPDLF and HGF in the hypothesis of delivering medicine to the periodontium and whole body through the root canal. HPDLF and HGF derived from the primary culture were seeded on polycarbonate filter membrane of transwell respectively. After 1, 2, 3 and 4 weeks of culture, transepithelial electrical resistance (TEER) was detected and the growth of HPDLF and HGF observed by light microscope. After 2 weeks of culture, section of filter membrane where HPDLF and HGF lived was observed with light microscope and transmission electron microscope (TEM), and the permeability of the drug transport cell models was measured with fluorescein sodium. HPDLF and HGF converged 1 week after inoculation, and the cells connected each other tightly and completely 2 weeks later. Observation of section of filter membrane by light microscope and TEM revealed a stratified cell growth of HPDLF and HGF 2 weeks after inoculation, and TEER of HPDLF and HGF were (56.14 +/- 7.43) and (57.34 +/- 7.62) ohm.cm(-2) respectively. The values of TEER remained the same level until 4 weeks later. Two weeks after inoculation, the paracellular transport of fluorescein sodium was less than 1% after the cell models were incubated for 30 min. Stratified cell layers of HPDLF and HGF grown on filter membrane of Transwell are analogous to periodontal membrane and gingiva 2 weeks after inoculation, the test results of permeability and TEER were consistent with the demands of development of cell models. HPDLF and HGF grown on filter membrane of Transwell could be used to study drug transcellular transport by HPDLF and HGF in vitro.


Layered patterning of hepatocytes in co-culture systems using microfabricated stencils.
Microfabrication and micropatterning techniques in tissue engineering offer great potential for creating and controlling microenvironments in which cell behavior can be observed. Here we present a novel approach to generate layered patterning of hepatocytes on micropatterned fibroblast feeder layers using microfabricated polydimethylsiloxane (PDMS) stencils. We fabricated PDMS stencils to pattern circular holes with diameters of 500 microm. Hepatocytes were co-cultured with 3T3-J2 fibroblasts in two types of patterns to evaluate and characterize the cellular interactions in the co-culture systems. Results of this study demonstrated uniform intracellular albumin staining and E-cadherin expression, increased liver-specific functions, and active glycogen synthesis in the hepatocytes when the heterotypic interface between hepatocytes and fibroblasts was increased by the layered patterning technique. This patterning technique can be a useful experimental tool for applications in basic science, drug screening, and tissue engineering, as well as in the design of bioartificial liver devices.


[Bioptic investigations of the nervous system (author's transl)].
Bioptic investigation of nervous tissue can be made by taking tissue samples of nerves, skin, muscle, rectum, dental pulp and brain. The choice of site for the biopsy depends on the results of previous clinical neurological, neurophysiological and biochemical investigations. Indications are: unexplained peripheral neuropathies, progressive degenerative diseases of the central nervous system and enzymopathies which are principally manifest in the nervous system (neurometabolic diseases). The result of a nerve tissue biopsy usually only leads to classification in a disease group (pathogenic unit) which only becomes diagnostically relevant in conjunction with the clinical data. In biopsies of the brain a virological examination should always be performed in addition to the morphological (light and electron microscopic) and biochemical investigation.


Disposition of acetone, methyl ethyl ketone and cyclohexanone in acute poisoning.
A case of coma due to the drinking of a liquid cement for polyvinyl chloride resin, containing acetone, methyl ethyl ketone, cyclohexanone and polyvinyl chloride is described. The patient also simultaneously ingested the alcoholic beverage, sake. After gastric lavage, plasma exchanges and direct hemoperfusions, the patient recovered. The concentrations of these chemicals in plasma and urine were analyzed at various time intervals to estimate the clearance. The elimination half lives for acetone and methyl ethyl ketone were 18 hours and 10 hours, respectively. Although cyclohexanone made up the largest component in the solvents, the blood level was extremely low and a large amount of cyclohexanol, a metabolite of cyclohexanone was detected in the blood and urine. The glucuronide metabolite of cyclohexanol was also estimated after the hydrolysis with beta-glucuronidase. Since the conversion of cyclohexanone to cyclohexanol is known to be catalyzed by alcohol dehydrogenase, possible interactions between sake ingestion and cyclohexanone metabolism is proposed.


Differential expression of neurotrophins in penises of streptozotocin-induced diabetic rats.
To explore the mechanism of diabetic erectile dysfunction, we studied the distribution of neurotrophins in the penises of diabetic rats, including nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). Male Sprague-Dawley rats were injected with 65 mg/kg streptozotocin to induce diabetes mellitus (DM). The control rats were raised as age-matched control. Eight weeks later, the intercavernous pressure (ICP) of the rats was measured after electrostimulation and before sacrifice. Each peeled penis was divided into 2 parts, one for immunohistochemistry and the other for Western blot analysis. The ICP of the DM group rats was significantly decreased as compared to the vehicle control rats. There were significantly more NGF-positive neurons in the penises of the diabetic rats than in those of the control rats, while the opposite results were observed for BDNF-positive neurons. In the Western blot analysis, the proteins of NGF, NT-3, and NT-4 were all increased, while that of BDNF was decreased in diabetic rats. This is the first study revealing the expression of NT-4 protein in cavernous tissue. The abnormal level of these 4 neurotrophins in cavernous tissue may be one of the factors of the pathogenesis of diabetic ED. The increase of neurotrophins may reflect the degree of cavernous tissue denervation and may represent a compensatory mechanism. The lesion of the retrograde axonal transport of the nerves caused by hyperglycemia may be related to this phenomenon.


Scaling behaviors of the voltage distribution in dielectric breakdown networks.
We study the distribution of voltage drops across bonds in dielectric breakdown networks and its qth moments in the two-dimensional Euclidean space. Performing numerical simulations, we find that the distribution is composed of three different power-law regimes which are distinguished by two crossover voltages V(1) and V(2). The scaling behaviors of these crossover voltages with respect to the system size govern those of the qth moments of the voltage distribution. This feature differs from the multifractal behavior of the qth moment in random resistor networks. We discuss the implications of these scaling behaviors in relation to the application of the dielectric breakdown network to memory devices.


Cyclin-dependent kinase 4/6 inhibitors in breast cancer therapy.
To review the latest preclinical and clinical findings on the role of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors in breast cancer and update on the studies investigating the predictive biomarkers of response to CDK4/6 inhibitors. The retinoblastoma tumor suppressor (Rb) pathway is frequently deregulated in breast cancer and strategies to target this pathway have recently been proven to be effective in breast cancer patients. Preclinical and clinical data suggest that CDK4/6 inhibitors might be particularly useful in patients with hormone-receptor-positive or HER2-positive tumors, whereas the role of such inhibitors in triple-negative breast cancer is still controversial. Clinical trials are now investigating the safety and efficacy of different CDK4/6 inhibitors, mostly in breast cancer patients with hormone-receptor-positive tumors. Recent studies demonstrated that alterations in the cyclin D-CDK4-Rb pathway may have a role in primary resistance to CDK4/6 inhibitors. Target therapies have brought great improvements in the management of breast cancer patients. CDK4/6 inhibitors look promising in the treatment of patients with hormone-receptor-positive breast cancer, but it is of pivotal importance to identify which subgroup of patients would mostly benefit from CDK4/6 inhibition with biomarker-driven clinical trials.


Disease concepts and treatment by tribal healers of an Amazonian forest culture.
The extensive medicinal plant knowledge of Amazonian tribal peoples is widely recognized in the scientific literature and celebrated in popular lore. Despite this broad interest, the ethnomedical systems and knowledge of disease which guide indigenous utilization of botanical diversity for healing remain poorly characterized and understood. No study, to our knowledge, has attempted to directly examine patterns of actual disease recognition and treatment by healers of an Amazonian indigenous culture. The establishment of traditional medicine clinics, operated and directed by elder tribal shamans in two remote Trio villages of the Suriname rainforest, presented a unique investigational opportunity. Quantitative analysis of clinic records from both villages permitted examination of diseases treated over a continuous period of four years. Cross-cultural comparative translations were articulated of recorded disease conditions through ethnographic interviews of elder Trio shamans and a comprehensive atlas of indigenous anatomical nomenclature was developed. 20,337 patient visits within the period 2000 to 2004 were analyzed. 75 disease conditions and 127 anatomical terms are presented. Trio concepts of disease and medical practices are broadly examined within the present and historical state of their culture. The findings of this investigation support the presence of a comprehensive and highly formalized ethnomedical institution within Trio culture with attendant health policy and conservation implications.


Gut microbial shifts by synbiotic combination of Pediococcus acidilactici and lactulose in weaned piglets challenged with Shiga toxin-producing Escherichia coli.
Development of alternatives to in-feed antibiotics in the swine industry have been the focused of many pig gut microbiota studies to improve animal health. In this study, we evaluated the effects of probiotic Pediococcus acidilactici (PRO), prebiotic lactulose (PRE), and their synbiotic combination (SYN) on gut microbiota using 16S rRNA gene sequencing in weaned piglets challenged with Shiga-toxin producing Escherichia coli (STEC). Our data showed that prebiotics, probiotics and synbiotics improved the intestinal health in weaned piglets. No significant differences were observed in species richness and species diversity in weaned piglets fed prebiotics, probiotics and their synbiotic combination. However, beta diversity analysis revealed distinct clustering of the microbiota of according to dietary treatment and by oral challenge of STEC. At the phylum level, Firmicutes to Bacteroidetes ratio was lower in the dietary treatment groups than the control group. Oral supplementation of prebiotics, probiotics and synbiotics enriched the abundance of Prevotella and Roseburia. Succinivibrio was elevated in PRO group; however, Phascolarctobacterium was depleted with STEC challenge regardless of dietary treatment. Overall, our data showed that administration of synbiotics in piglets improved intestinal health through gut microbiota modulation. Our data indicated that prebiotics, probiotics and their synbiotic combination could promote intestinal health through gut microbiota modulation in weaned piglets.


Nephron formation adopts a novel spatial topology at cessation of nephrogenesis.
Nephron number in the mammalian kidney is known to vary dramatically, with postnatal renal function directly influenced by nephron complement. What determines final nephron number is poorly understood but nephron formation in the mouse kidney ceases within the first few days after birth, presumably due to the loss of all remaining nephron progenitors via epithelial differentiation. What initiates this event is not known. Indeed, whether nephron formation occurs in the same way at this time as during embryonic development has also not been examined. In this study, we investigate the key cellular compartments involved in nephron formation; the ureteric tip, cap mesenchyme and early nephrons; from postnatal day (P) 0 to 6 in the mouse. High resolution analyses of gene and protein expression indicate that loss of nephron progenitors precedes loss of ureteric tip identity, but show spatial shifts in the expression of cap mesenchyme genes during this time. In addition, cap mesenchymal volume and rate of proliferation decline prior to birth. Section-based 3D modeling and Optical Projection Tomography revealed a burst of ectopic nephron induction, with the formation of multiple (up to 5) nephrons per ureteric tip evident from P2. While the distal-proximal patterning of these nephrons occurred normally, their spatial relationship with the ureteric compartment was altered. We propose that this phase of nephron formation represents an acceleration of differentiation within the cap mesenchyme due to a displacement of signals within the nephrogenic niche.


Inhibition of the P2X7/NLRP3 Inflammasome Signaling Pathway by Deacetylgedunin from Toona sinensis.
Limonoids are considered the effective part in Meliaceae plants that exert anti-inflammatory effects. Gedunin-type limonoids specifically have anti-inflammatory effects. However, the role of gedunin-type limonoids in the inflammatory diseases mediated by NLRP3 inflammasome remains to be explored. We found that deacetylgudunin (DAG), a gedunin-type limonoid from Toona sinensis, had similar anti-inflammatory effects and lower toxicity than gedunin. Further studies showed that DAG down-regulated the NF-κB pathway, inhibited K+ efflux and ROS release, inhibited ASC oligomerization, and significantly weakened the interaction of NLRP3 with ASC and NEK7. Furthermore, DAG could not further inhibit IL-1β secretion and K+ efflux when combined with the P2X7 inhibitor A438079. In conclusion, our research revealed that DAG exerted an anti-inflammatory effect by inhibiting the P2X7/NLRP3 signaling pathway and enriched the application of gedunin-type limonoids in inflammatory diseases driven by the NLRP3 inflammasome.


The effect of ochratoxin A on the concentration of protein carbonyls in rats.
The mechanism of ochratoxin A (OTA) toxicity has been found to involve the production of free radicals and consequent oxidative stress. Until now, the only studied pathway of OTA-caused oxidative damage was peroxidation of lipids. The aim of this study was to check whether OTA induced the production of protein carbonyls, markers of protein oxidation. Exposed rats (5 per group) were given daily OTA (0.5 mg kg(-1) b. w., i. p.) for 7 days, 14 days, or 21 days, and control rats solvent only (TRIS). All animals were killed 24 hours after the last treatment. The levels of OTA in plasma, kidney and liver homogenates increased gradually during the whole length of the experiment. The levels of protein carbonyls in kidney homogenates of OTA-treated rats was significantly higher after days 14 and 21 than in controls (P < 0.05). The levels of protein carbonyls in the liver was significantly higher in OTA-treated animals only after day 21 (P < 0.05). These results confirm that oxidative stress is involved in the mechanism of OTA toxicity, and that it causes the oxidation of proteins.


Bone mineral density, its predictors, and outcomes in peritoneal dialysis patients.
The objective of the present work was to assess bone mineral density (BMD) and its predictors in peritoneal dialysis (PD) patients, to check the history of those patients 4 years after the assessment, and to relate thoses outcome to BMD. We used dual-energy X-ray absorptiometry to measure BMD in 26 patients at the femoral neck (FN), and we related those measurements to demographic, nutrition, and laboratory data. Four years after the assessments, the outcomes of those patients were checked and related to BMD. In the study patients, the mean FN BMD was 0.842 +/- 0.137 g/cm2. Serum albumin, lean body mass, alkaline phosphatase (ALP), and treatment with acetylsalicylic acid were significant predictors for BMD in the first multivariate model. A second model included blood pH, serum phosphorus, serum creatinine, and age as significant BMD predictors. Hemoglobin or hematocrit could have replaced phosphorus as a BMD predictor The prevalences of abnormal values for BMD predictors in the study patients were phosphorus > 4.5 mg/dL, 69.2%; pH < 7.36, 53.8%; albumin < 3.5 g/dL, 46.1%; ALP > 104 IU/L, 23.1%; and hemoglobin < 11.0 g/ dL, 23.1%. In 8 patients, a successful renal transplantation occurred at 8.5 +/- 9.3 months; 9 patients died at 25.9 +/- 12.5 months; and 9 patients continued dialysis for a further 50.4 +/- 1.7 months. The highest BMD was found in the patients who underwent renal transplantation (0.962 +/- 0.110 g/cm2); the lowest BMD was found in the patients who died (0.737 +/- 0.100 g/ cm2, p = 0.001). In PD patients, low BMD indicates worse outcome. High prevalences of predictors for low BMD (age, poor nutrition status, metabolic acidosis, high phosphorus, anemia) also contribute to worse outcome in PD patients.


[Stroke--risk factors and primary prevention].
The five major risk factors for stroke are hypertension, smoking, diabetes, atrial fibrillation and physical inactivity. All of these are amenable. In addition, although hypercholesterolemia is not strongly associated with stroke in epidemiological studies, primary prevention with statins provides a modest reduction of stroke risk. Unchanged population levels of blood pressure in Sweden over the last two decades are accompanied by constant stroke incidence rates. The single most cost-effective preventive action is detection and treatment of hypertension in the elderly. Antismoking advice and anticoagulants in patients with atrial fibrillation and other cardiac sources of embolism also have favourable effects relative to costs. There is a dearth of successful population-based programs to prevent stroke.


Depression in the wives of nuclear submarine personnel.
The authors compared levels of depression among 24 wives of nuclear submarine personnel under conditions of husband-presence and husband-absence in a crossover research design. The wives had significantly higher depression scores under conditions of husband-absence on both the Zung Depression Scale and the Multiple Affect Adjective Checklist. The results are discussed in terms of the tremendous stresses imposed on the wives as a result of the nuclear submarine deployment schedule and the failure of the Navy and the spouses to recognize and reward the wives for their efforts.


Telescopic esophageal anastomosis: operative technique, clinical experiences.
The authors reconstructed the continuity of the alimentary tract by performing telescopic esophagogastrostoma in 208 patients who underwent either esophageal resection or total gastrectomy. The substance of the telescopic technique is to invaginate the distal section of any oral tubular organ to the lumen of an aboral tubular one and to fix it there. In case of telescopic esophageal anastomosis a 10-15 mm long esophageal segment is invaginated into the gastric tube or jejunum. A 3-4 mm wide serosal surface of the wall of the distal anastomosing organ straps the esophagus circularly. Ninety-six transthoracic and 12 transhiatal esophagectomies, 19 partial esophageal resections, four esophageal bypasses, and 77 total or extended total gastrectomies were reconstructed using telescopic anastomosis. Undisturbed healing could be observed in 67 patients after esophageal operations and in 46 patients of total gastrectomies. Anastomosis leakage occurred in 12 of 108 patients (11.1%) after cervical esophagogastrostomy. Leakage could be observed in 7 of 44 patients (15.9%) after end to side and in 5 of 64 patients (7.8%) in case of end to end esophago gastrostoma. There were no failures after two cases of cervical esophago-ileocolostoma and 21 of esophagogastrostomas in the thoracic position. All of the 59 intra-abdominal anastomoses healed without complication. Thirteen of 131 patients (9.9%) died after esophageal operations and four of 77 (5.2%) after gastrectomies. There were no mortal complications due to anastomotic leakage. The telescopic anastomosis is a safe alternative method in cases of total gastrectomy or esophageal operation.


3D volumes constructed from pixel-based images by digitally clearing plant and animal tissue.
Construction of three-dimensional volumes from a series of two-dimensional images has been restricted by the limited capacity to decrease the opacity of tissue. The use of commercial software that allows colour-keying and manipulation of two-dimensional images in true three-dimensional space allowed us to construct three-dimensional volumes from pixel-based images of stained plant and animal tissue without generating vector information. We present three-dimensional volumes of (1) the crown of an oat plant showing internal responses to a freezing treatment, (2) a sample of a hepatocellular carcinoma from a woodchuck liver that had been heat-treated with computer-guided radiofrequency ablation to induce necrosis in the central portion of the tumour, and (3) several features of a sample of mouse lung. The technique is well suited to images from large sections (greater than 1 mm) generated from paraffin-embedded tissues. It is widely applicable, having potential to recover three-dimensional information at virtually any resolution inherent in images generated by light microscopy, computer tomography, magnetic resonance imaging or electron microscopy.


Standards for Deriving Nonhuman Primate-Induced Pluripotent Stem Cells, Neural Stem Cells and Dopaminergic Lineage.
Humans and nonhuman primates (NHP) are similar in behavior and in physiology, specifically the structure, function, and complexity of the immune system. Thus, NHP models are desirable for pathophysiology and pharmacology/toxicology studies. Furthermore, NHP-derived induced pluripotent stem cells (iPSCs) may enable transformative developmental, translational, or evolutionary studies in a field of inquiry currently hampered by the limited availability of research specimens. NHP-iPSCs may address specific questions that can be studied back and forth between in vitro cellular assays and in vivo experimentations, an investigational process that in most cases cannot be performed on humans because of safety and ethical issues. The use of NHP model systems and cell specific in vitro models is evolving with iPSC-based three-dimensional (3D) cell culture systems and organoids, which may offer reliable in vitro models and reduce the number of animals used in experimental research. IPSCs have the potential to give rise to defined cell types of any organ of the body. However, standards for deriving defined and validated NHP iPSCs are missing. Standards for deriving high-quality iPSC cell lines promote rigorous and replicable scientific research and likewise, validated cell lines reduce variability and discrepancies in results between laboratories. We have derived and validated NHP iPSC lines by confirming their pluripotency and propensity to differentiate into all three germ layers (ectoderm, mesoderm, and endoderm) according to standards and measurable limits for a set of marker genes. The iPSC lines were characterized for their potential to generate neural stem cells and to differentiate into dopaminergic neurons. These iPSC lines are available to the scientific community. NHP-iPSCs fulfill a unique niche in comparative genomics to understand gene regulatory principles underlying emergence of human traits, in infectious disease pathogenesis, in vaccine development, and in immunological barriers in regenerative medicine.


Objective Response to First-Line Treatment as a Predictor of Overall Survival in Metastatic Breast Cancer: A Retrospective Analysis from Two Centers over a 25-Year Period.
The purpose of this study was to study the efficacy of subsequent treatment lines for metastatic breast cancer (MBC), as well as the association between radiologic objective response rate (ORR) and overall survival (OS). In this retrospective study, consecutive patients treated for MBC in two centers in Greece from January 1, 1992, to December 31, 2016, were identified and clinicopathologic data regarding tumor characteristics and administered treatments were collected. The efficacy per treatment line in terms of ORR, progression-free survival (PFS) and OS, as well as the prognostic value of ORR at first line were investigated. A total of 977 patients with MBC were identified; 950 received any treatment. At first line, ORR was 43.5%, PFS 11.4 months (95% CI 10.4-12.4), and median OS 52.4 months (95% CI 47.7-57.1). Lower ORR and shorter PFS were observed with each subsequent line. Median OS was significantly longer for patients that had an objective response at first line, 61.9 months (95% CI 51.1-69.7) for responders versus 41.3 months (95% CI 44.1-63.3) for nonresponders (p < 0.001). In multivariable analysis, failure to achieve an objective response was an independent predictor of poor survival (hazard ratio 1.70, 95% CI 1.34-2.15, p < 0.001). Late treatment lines for MBC seem to have limited efficacy, while response to first-line therapy is associated with long-term survival. The latter should be considered in the treatment strategy of patients with MBC.


The chromatin fingerprint of gene enhancer elements.
Different cell types within a single organism are generally distinguished by strikingly different patterns of gene expression, which are dynamic throughout development and adult life. Distal enhancer elements are key drivers of spatiotemporal specificity in gene regulation. Often located tens of kilobases from their target promoters and functioning in an orientation-independent manner, the identification of bona fide enhancers has proved a formidable challenge. With the development of ChIP-seq, global cataloging of putative enhancers has become feasible. Here, we review the current understanding of the chromatin landscape at enhancers and how these chromatin features enable robust identification of tissue-specific enhancers.


Adjustable Magnetic Phase Transition Inducing Unusual Zero Thermal Expansion in Cubic RCo2-Based Intermetallic Compounds (R = Rare Earth).
Metallic materials that exhibit negligible thermal expansion or zero thermal expansion (ZTE) have great merit for practical applications, but these materials are rare and their thermal expansions are difficult to control. Here, we successfully tailored the thermal expansion behaviors from strongly but abruptly negative to zero over wide temperature ranges in a series of (Gd,R)(Co,Fe)2 (R = Dy, Ho, Er) intermetallic compounds by tuning the composition to bring the first-order magnetic phase transition to second-order. Interestingly, an unusual isotropic ZTE property with a coefficient of thermal expansion of α l = 0.16(0) × 10-6 K-1 was achieved in cubic Gd0.25Dy0.75Co1.93Fe0.07 (GDCF) in the temperature range of 10-275 K. The short-wavelength neutron powder diffraction, synchrotron X-ray diffraction, and magnetic measurement studies evidence that this ZTE behavior was ascribed to the rare-earth-moment-dominated spontaneous volume magnetostriction, which can be controlled by an adjustable magnetic phase transition. The present work extends the scope of the ZTE family and provides an effective approach to exploring ZTE materials, such as by adjusting the magnetism or ferroelectricity-related phase transition in the family of functional materials.


Effectiveness of maximal safe resection for glioblastoma including elderly and low Karnofsky performance status patients: retrospective review at a single institute.
Elderly and low Karnofsky performance status (KPS) patients have been excluded from most prospective trials. This retrospective study investigated glioblastoma treatment outcomes, including those of elderly and low KPS patients, and analyzed the prognostic factors using the medical records of 107 consecutive patients, 59 men and 48 women aged from 21 to 85 years (median 65 years), with newly diagnosed glioblastoma treated at our institute. There were 71 high-risk patients with age >70 years and/or KPS <70%. Based on the extent of resection, the patients were classified into 3 groups: more than subtotal resection (subtotal, n = 44), partial resection (partial, n = 29), and biopsy only (biopsy, n = 34). Median overall survival (OS) of all 107 patients was 13.5 months. Median OS was 13.2 months in the high-risk group. Median OSs were 15.8, 12.8, and 12.1 months in the subtotal, partial, and biopsy groups, respectively. Multivariate analysis of 73 patients in the subtotal and partial groups found age ≤65 years (p = 0.047), 60 Gy irradiation (p = 0.009), O(6)-methylguanine-deoxyribonucleic acid methyltransferase-negative (p = 0.027), and more than subtotal removal (p = 0.003) were significant prognostic factors. The median postoperative KPS score tended to be better than the preoperative score, even in the high-risk group. We recommend maximal safe resection for glioblastoma patients, even those with advanced age and/or with low KPS scores.


Thermal transport in phononic Cayley-tree networks.
We analytically investigate the heat current I and its thermal fluctuations Δ in a branching network without loops (Cayley tree). The network consists of two types of harmonic masses: vertex masses M placed at the branching points where phononic scattering occurs and masses m at the bonds between branching points where phonon propagation takes place. The network is coupled to thermal reservoirs consisting of one-dimensional harmonic chains of coupled masses m. Due to impedance mismatch phenomena, both I and Δ are non-monotonic functions of the mass ratio μ=M/m. Furthermore, we find that in the low-temperature limit the thermal conductance approaches zero faster than linearly due to the small transmittance of the long-wavelength modes.


Cloning and Molecular Characterization of Hsp Genes from Anoplophora glabripennis and Their Responses to Cold Stress.
Anoplophora glabripennis (Agla) is an important global quarantine pest due to its highly destructive impacts on forests. It is widely distributed in many countries in Asia, Europe, and North America. The survival of A. glabripennis larvae has been facilitated by its high adaptability to low temperature. When insects are subjected to temperature stress, heat shock proteins (Hsps) limit cell damage and improve cell tolerance via their protein folding, localization, and degradation activities. However, the temperature adaptation mechanisms of A. glabripennis Hsps remain unclear. In this study, four A. glabripennis Hsp genes, AglaHsp20.43, AglaHsp71.18, AglaHsp82.09, and AglaHsp89.76, were cloned. Sequence analysis showed that all four Hsps had specific conserved domains. Phylogenetic analysis revealed that Hsps from different subfamilies were evolutionarily conserved, and that AglaHsps were highly similar to those of Coleoptera species. Protein expression vectors (pET30a-AglaHsps) were constructed and used to express AglaHsps in E. coli, where all four proteins were expressed in inclusion bodies. Western blot analysis showed that AglaHsps were expressed at a range of temperatures, from -10 °C to 25 °C. AglaHsp82.09 and AglaHsp89.76 showed high expressions with treatment at 0 °C. Our results will facilitate clarification of the molecular mechanisms underlying A. glabripennis responses to environmental stress.


Selection of strains of Epicoccum purpurascens for tolerance to fungicides and improved biocontrol of Sclerotinia sclerotiorum.
A wild-type isolate of Epicoccum purpurascens was exposed to shortwave ultraviolet light. One of the resulting cultures (M-20-A) was grown on media amended with the fungicides iprodione or vinclozolin and fungicide-tolerant strains were obtained. Several comparisons were made between new strains and the wild type. Sporulation was improved compared with the wild type. Strains varied in their tolerance to iprodione and vinclozolin but were not tolerant to the fungicide benomyl. Strains R4000, 16-B, and 7-A inhibited Sclerotinia sclerotiorum in vitro more than either the wild type or M-20-A, and exhibited improved control of white mold of bean in the greenhouse compared with M-20-A. Key words: biological control, fungicide resistance, white mold, iprodione, vinclozolin.


Human macrovascular endothelial cells: optimization of culture conditions.
The purpose of this study is to identify optimal culture conditions to support the proliferation of human macrovascular endothelial cells. Two cell lines were employed: human saphenous vein endothelial cells (HSVEC) and human umbilical vein endothelial cells (HUVEC). The influence of basal nutrient media (14 types), fetal bovine serum (FBS), and mitogens (three types) were investigated in relation to cell proliferation. Additionally, a variety of extracellular matrix (ECM) substrate-coated culture dishes were also tested. The most effective nutrient medium in augmenting cell proliferation was MCDB 131. Compared to the more commonly used M199 medium, MCDB 131 resulted in a 2.3-fold increase in cell proliferation. Media containing 20% FBS increased cell proliferation 7.5-fold compared to serum-free media. Among the mitogens tested, heparin (50 microg/ml) and endothelial cell growth supplement (ECGS) (50 microg/ml) significantly improved cell proliferation. Epithelial growth factor (EGF) provided no improvement in cell proliferation. There were no statistical differences in cell proliferation or morphology when endothelial cells were grown on uncoated culture plates compared to plates coated with ECM proteins: fibronectin, laminin, gelatin, or collagen types I and IV. The culture environment yielding maximal HSVEC and HUVEC proliferation is MCDB 131 nutrient medium supplemented with 2 mM glutamine, 20% FBS, 50 microg/ml heparin, and 50 microg/ml ECGS. The ECM substrate-coated culture dishes offer no advantage.


Staged bone grafting following placement of an antibiotic spacer block for the management of segmental long bone defects.
Segmental long bone defects resulting from injury or surgical intervention are difficult problems to manage. Amputation, external fixators, vascularized fibular grafts, acute limb shortening, and various quantities of allograft and autograft have historically been the mainstays of treatment. Recently, the use of osteoinductive substances such as recombinant bone morphogenic proteins, and osteoconductive scaffolds such as calcium phosphate have found use in the treatment of these clinical situations. More recently, Masquelet described the use of a cement spacer placed within the osseous void followed by staged bone grafting within the induced biomembrane formed around the spacer as a potential treatment strategy to manage these large defects.This article describes a series of 11 patients for which we used this technique of staged bone grafting following placement of an antibiotic spacer to successfully manage osseous long bone defects ranging from 4 to 15 cm. The limbs were stabilized and aligned at the time of initial spacer placement with a plate and screw construct, intramedullary nail, or fine wire fixator. Osteoinductive substances including bone morphogenic protein-2 and platelet rich concentrate were used in addition to allograft to improve bony healing. In our series, osseous consolidation and full weight bearing was achieved in 10 of 11 patients. Two patients developed heterotopic ossification. There was 1 non-union and 1 infection, which occurred in the same patient. Staged bone grafting within an induced biomembrane created after the use of a cement spacer is a reasonable option in the management of both acute and delayed segmental long bone defects.


The effects of depression, health status, and stressful life-events on self-reported memory problems among aged blacks.
A sample of 1,250 Black elderly individuals was examined to assess the prevalence and correlates of self-reported memory problems. More than 48.3 percent of the sample reported poor memory and forgetfulness as either a very (17.9%) or somewhat (30.4%) serious problem. Multivariate logistic regression was employed to detect the significant predictors of self-reported memory problems. According to our data, those Black elderly individuals who have hearing problems, who report a higher number of stressful life-events, who experience a higher level of depression, and who suffer from poorer health are more likely to complain of memory problems.


Knowledge and Attitude Toward Human Papillomavirus and HPV Vaccination in Iranian Population: A Systematic Review.
Background and objective: Human papillomavirus (HPV) is the main cause of cervical cancer. This systematic review was performed to provide an overview of knowledge and attitude about HPV infection and HPV vaccine in Iranian population. Materials and Methods: The information was identified by searching international and national databases; pubmed/MEDLINE (NCBI), Embase (Elsevier), Google Scholar, Scientific Information Database, MagIran, and IranDoc. The current research was performed using the terms of medical subject headings (MeSH) and combinations of the keywords including: "human papillomavirus" or "human papillomavirus vaccine" with the words "knowledge," "awareness," "attitude" and "Iran." Studies were evaluated according to the checklist of STrengthening the Reporting of OBservational Studies in Epidemiology (STROBE). Results: A total of 10 observational studies that met the inclusion criteria were included in this review. The overall knowledge and awareness of the Iranian population (parents, women, university students, medical students, nurses and hospital staff) about HPV and HPV vaccination was low; however, the attitude toward this issue was positive and strong. Conclusion: Due to the low levels of knowledge about HPV infection and its methods of prevention, efforts should be increased to enhance the knowledge of the general population about HPV infection and vaccination in order to prevent its incidence and complications.


Erythrocyte death in vitro induced by starvation in the absence of Ca(2+).
Human erythrocytes (RBCs), stored at 4 degrees C under nominal absence of external energy sources and calcium ions, show a gradual decrease in membrane roughness (R(rms)) at the end of which the appearance of morphological phenomena (spicules, vesicles and spherocytes) is observed on the cell membrane, phenomena that can mainly be ascribed to the ATP-dependent disconnection of the cortical cytoskeleton from the lipid bilayer. After depletion of the intracellular energy sources obtained under the extreme conditions chosen, treatment with a minimal rejuvenation solution makes the following remarks possible: (i) RBCs are able to regenerate adenosine triphosphate (ATP) and 2,3-bisphosphoglycerate only up to 4 days of storage at 4 degrees C, whereas from the eighth day energy stocks cannot be replenished because of a disorder in the transmembrane mechanisms of transport; (ii) the RBCs' roughness may be restored to the initial value (i.e. that observed in fresh RBCs) only in samples stored up to 4-5 days, whereas after the eighth day of storage the rejuvenation procedure appears to be inefficient; (iii) membrane physical properties - as measured by R(rms) - are actually controlled by the metabolic production of ATP, necessary to perform the RBCs' basic functions; (iv) once energy stores cannot be replenished, a regulated sequence of the morphological events (represented by local buckles that lead to formation of spicules and vesicles of the lipid bilayer with generation of spherocytes) is reminiscent of the RBCs' apoptotic final stages; (v) the morphological phenomenology of the final apoptotic stages is passive (i.e. determined by simple mechanical forces) and encoded in the mechanical properties of the membrane-skeleton; and (vi) necrotic aspects (e.g. disruption of cell membrane integrity, so that intracellular protein content is easily released) ensue when RBCs are almost totally (> or =90%) depleted in an irreversible way of the energetic stores.


Evidence for an oncogenic role of HOXC6 in human non-small cell lung cancer.
Identification of specific biomarkers is important for the diagnosis and treatment of non-small cell lung cancer (NSCLC). HOXC6 is a homeodomain-containing transcription factor that is highly expressed in several human cancers; however, its role in NSCLC remains unknown. The expression and protein levels of HOXC6 were assessed in NSCLC tissue samples by Quantitative real-time PCR (qRT-PCR) and immunohistochemistry, respectively. HOXC6 was transfected into the NSCLC cell lines A549 and PC9, and used to investigate its effect on proliferation, migration, and invasion using CFSE, wound healing, and Matrigel invasion assays. Next-generation sequencing was also used to identify downstream targets of HOXC6 and to gain insights into the molecular mechanisms underlying its biological function. HOXC6 expression was significantly increased in 66.6% (20/30) of NSCLC tumor samples in comparison to normal controls. HOXC6 promoted proliferation, migration, and invasion of NSCLC cells in vitro. RNA-seq analysis demonstrated the upregulation of 310 and 112 genes in A549-HOXC6 and PC9-HOXC6 cells, respectively, and the downregulation of 665 and 385 genes in A549-HOXC6 and PC9-HOXC6 cells, respectively. HOXC6 was also found to regulate the expression of genes such as CEACAM6, SPARC, WNT6, CST1, MMP2, and KRT13, which have documented pro-tumorigenic functions. HOXC6 is highly expressed in NSCLC, and it may enhance lung cancer progression by regulating the expression of pro-tumorigenic genes involved in proliferation, migration, and invasion. Our study highlighted the oncogenic potential of HOXC6, and suggests that it may be a novel biomarker for the diagnosis and treatment of NSCLC.


Kallikarein-related peptidase 3 common genetic variant and the risk of prostate cancer.
Kallikarein-related peptidase 3 (KLK3) gene polymorphisms seem to play a role in susceptibility to prostate cancer (PC). The purpose of this study was to investigate the association between rs2735839 polymorphism of KLK3 gene and risk of PC in an Iranian population. In this case-control study, rs2735839 was genotyped in 532 patients with PC and 602 controls with benign prostate hyperplasia (BPH) using polymerase chain reaction-restriction fragment length polymorphism assay. The frequency of GG, AG, and AA genotypes of KLK3 polymorphism was 24.6% and 76.2%, 46.6% and 21.7%, and 28.8% and 2.1%, in patients with BPH and PC, respectively (P < 0.001). The frequency of G allele in patients with BPH and PC was 47.9% and 87%, respectively (odds ratio: 7.31; confidence interval: 5.88-9.10; P < 0.001). Patients with AG and GG genotypes had a higher total serum level of prostate-specific antigen (PSA) compared to those with AA genotype (P < 0.001). Patients with this polymorphism had higher risk of tumor with higher grade (P = 0.23), advanced stage (P = 0.11), perineural invasion (P = 0.07), and vascular invasion (P = 0.07) compared to those without it but this difference was not statistically significant. Based on our results, KLK3 gene polymorphism was associated with the risk of PC. Higher levels of PSA in the presence of KLK3 polymorphism in patients with PC indicated that rs2735839 polymorphism could be a risk factor for increased levels of PSA.


[Experimental animal model of airborne influenza infection].
Experiments were performed for analysing the responses of the host to influenza respiratory tract infections. NMRI and Balb/c mice were infected with various doses of mouse adapted influenza virus (A/PR8/34) by aerosol. Clinical symptoms, rate of survival, total cell yield and total protein content in the lung lavage fluid as well as the course of virus titres showed typical changes depending on time and infection dose. Histologically, after moderate infection doses mice developed mononuclear infiltrations as bronchitis and peribronchitis whereas oedema and severe pneumonitis occurred in highly infected animals. The mouse model seems to be a useful basis for analysing the effects of immunization procedure against influenza.


Different inhibitory effects in the early and late phase of treatment with KAT-681, a liver-selective thyromimetic, on rat hepatocarcinogenesis induced by 2-acetylaminofluorene and partial hepatectomy after diethylnitrosamine initiation.
We recently reported that short-term treatment with KAT-681 (KAT), a liver-selective thyromimetic, inhibits the development of preneoplastic lesions in rat livers and may be a candidate chemopreventive agent for hepatocarcinogenesis. In this study, time-course observations of hepatocellular proliferative lesions were carried out during short-term and long-term treatment with KAT to investigate its anti-hepatocarcinogenic effects. The hepatocellular proliferative lesions in male F344 rats were induced by the initiation treatment of diethylnitrosamine (DEN), followed by treatment with 2-acetylaminofluorene (2-AAF) and partial hepatectomy (PH). The rats were administered KAT orally at a dose of 0.25 mg/kg/day for 3 weeks (experiment 1) or 0.1 mg/kg/day for 20 weeks (experiment 2). In experiment 1, a serial reduction in the number of altered hepatocellular foci (AHF) with positive expression of glutathione S-transferase placental form (GST-P) was observed until day 14 of the treatment period. The proliferative index (PI) of hepatocytes in the AHF significantly increased in the KAT group throughout the treatment period, with a peak on day 2. KAT treatment showed no obvious effects on GST-P-positive hepatocellular adenomas (HCAs) at any time point. In contrast, long-term KAT treatment in experiment 2 revealed a reduction in the mean size of HCAs in addition to reductions in the number and mean size of AHF. The PIs within the lesions in KAT-treated rats were significantly lower than those in controls. The present study indicates that KAT has different inhibitory effects on hepatocarcinogenesis in the early and late phases of KAT treatment; there is a reduction in AHF with enhanced cell proliferation in the early phase and the inhibition of development of AHF and HCAs with suppression of cell proliferation in the late phase. These results may suggest further potential of KAT as a promising chemopreventive agent for hepatocarcinogenesis.


Use of annexin V antibody to identify apoptotic cells during pregnancy.
In a previous study, we demonstrated that apoptosis increased according to gestational age, accounting partly for the presence of free fetal DNA in maternal plasma and serum. Using simultaneous TUNEL assay and FISH analysis, we identified the fetal origin of part of the apoptotic cell population, but very few TUNEL-positive cells showed hybridization signals since they were in a late apoptosis stage and nuclei were destroyed. In the present study, the apoptotic cell population was identified immunocytochemically using Annexin V, a marker of cells in an early stage of apoptosis. The mean apoptosis rate in mononuclear cells isolated from the peripheral blood of 20 pregnant women in the 16th to 19th week of pregnancy with Annexin V was 6.8 +/- 0.5% (range: 4.2-8.1%) compared to 6.14 +/- 0.5% (range: 3.7-6.9%) obtained with ethidium bromide staining. FISH using X and Y chromosome-specific probes was applied in 11 cases known to be carrying male fetuses. Eighty percent of Annexin V+ cells showed hybridization signals, while the proportion of apoptotic cells showing X/Y signals was 7.8% (range: 5-12%). Although our results are still preliminary, it seems that use of Annexin V antibody to detect the apoptotic cell population improves FISH analysis and allows a more accurate estimate of the proportion of fetal cells among the apoptotic cell population.


AS1411 Aptamer-Anionic Linear Globular Dendrimer G2-Iohexol Selective Nano-Theranostics.
Molecular theranostics is of the utmost interest for diagnosis as well as treatment of different malignancies. In the present study, anionic linear globular dendrimer G2 is employed as a suitable carrier for delivery and AS1411 aptamer is exploited as the targeting agent to carry Iohexol specifically to the human breast cancer cells (MCF-7). Dendrimer G2 was prepared and conjugation of dendrimer and aptamer was carried out thereafter. Based on the data yielded by AFM, morphology of smooth and spherical non-targeted dendrimer changed to the rough aspherical shape when it conjugated. Then, conjugation was confirmed using DLS, ELS and SLS methods. Toxicity on nucleolin positive MCF-7 cells and nucleolin negative HEK-293 cells was assessed by XTT and apoptosis/necrosis assays. In vitro uptake was determined using DAPI-FITC staining and ICP-MS methods. In vivo studies including in vivo CT imaging, pathology and blood tests were done to confirm the imaging ability, bio-safety and targeted nature of the Nano-Theranostics in vivo. In a nutshell, the prepared construction showed promising effects upon decreasing the toxicity of Iohexol on normal cells and accumulation of it in the cancer tumors as well as reducing the number of cancer cells.


Incidence of lumbar spondylolysis in the general population in Japan based on multidetector computed tomography scans from two thousand subjects.
Epidemiological analysis using CTs. To investigate the true incidence of lumbar spondylolysis in the general population in Japan. Although there have been several reports on the incidence of lumbar spondylolysis, they had some weakness. One of them concerns the subjects investigated, because the incidence of lumbar spondylolysis varies considerably, and some patients are asymptomatic. In addition, most of the past studies used plain radiograph films or skeletal investigation. Therefore, the past reported incidence may not correspond to that of the general population. We reviewed the computed tomography (CT) scans of 2000 subjects (age: 20-92 years) who had undergone abdominal and pelvic CT on a single multidetector CT scanner for reasons unrelated to low back pain. We reviewed them for spondylolysis, spondylolytic spondylolisthesis, and spina bifida occulta (SBO) in the lumbosacral region. The grade (I-IV) of spondylolisthesis was measured using midsagittal reconstructions. Lumbar spondylolysis was found in 117 subjects (5.9%). Their male-female ratio was 2:1. Multiple-level spondylolysis was found in 5 subjects (0.3%). Among these 117 subjects, there were 124 vertebrae with spondylolysis. Of them, 112 (90.3%) corresponded to L5, and 26 (21.0%) had unilateral spondylolysis.SBO was found in 154 subjects. Of them, 25 had spondylolysis (16.2%), whereas, in 1846 subjects without SBO, 92 had spondylolysis (5.0%). The incidence of spondylolysis among the patients with SBO was significantly higher than that in subjects without SBO (Odd ratio was 3.7-fold).Of 124 vertebrae with spondylolysis, 75 (60.5%) showed low-grade (Meyerding grade I or II) spondylolisthesis, and no subject presented high-grade spondylolisthesis. Spondylolisthesis was found in 74.5% of the subjects with bilateral spondylolysis, and in 7.7% of those with unilateral spondylolysis. The incidence of lumbar spondylolysis in the Japanese general population was 5.9% (males: 7.9%, females: 3.9%).


Impact of MYC on malignant behavior.
MYC, a member of the helix-loop-helix leucine zipper family of nuclear transcription factors, is a potent proto-oncogene primarily identified as the target of the t(8;14)(q24;q32) chromosome translocation in Burkitt lymphoma. Activation of the MYC gene in normal cells both results in enhanced cellular proliferation and up-regulation of pro-apoptotic pathways, reflecting the tight regulation of the molecule in the normal cellular system. In the process of transformation, these secondary inhibitory functions of the MYC molecule have to be overcome through secondary mutations of the MYC gene itself and/or by abrogating the inhibitory effects of physiological regulators and/or repressors of proliferation such as BCL2, BCL6, BLIMP1, or others. Most aggressive lymphomas, therefore, harbor additional oncogenic alterations that cooperate with MYC deregulation, with different alterations identified in human solid or hematological tumors. These alterations are likely to counteract the pro-apoptotic function of MYC. MYC gene alterations in diffuse large B-cell lymphomas and in B-cell lymphomas, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma are frequently associated with BCL2 or/and BCL6 translocations conferring a very aggressive behavior. This review summarizes inherent factors of the biology and function of MYC important in the process of transformation, especially taking account the interdependence of MYC on various cellular networks that have to be co-deregulated to achieve the full malignant phenotype.


Effects of 18 days of bed rest on leg and arm venous properties.
Venous function may be altered by bed rest deconditioning. Yet the contribution of altered venous compliance to the orthostatic intolerance observed after bed rest is uncertain. The purpose of this study was to assess the effect of 18 days of bed rest on leg and arm (respectively large and small change in gravitational gradients and use patterns) venous properties. We hypothesized that the magnitude of these venous changes would be related to orthostatic intolerance. Eleven healthy subjects (10 men, 1 woman) participated in the study. Before (pre) and after (post) 18 days of 6 degrees head-down tilt bed rest, strain gauge venous occlusion plethysmography was used to assess limb venous vascular characteristics. Leg venous compliance was significantly decreased after bed rest (pre: 0.048 +/- 0.007 ml x 100 ml(-1) x mmHg(-1), post: 0.033 +/- 0.007 ml x 100 ml(-1) x mmHg(-1); P < 0.01), whereas arm compliance did not change. Leg venous flow resistance increased significantly after bed rest (pre: 1.73 +/- 1.08 mmHg x ml(-1) x 100 ml x min, post: 3.10 +/- 1.00 mmHg x ml(-1) x 100 ml x min; P < 0.05). Maximal lower body negative pressure tolerance, which was expressed as cumulative stress index (pressure x time), decreased in all subjects after bed rest (pre: 932 mmHg x min, post: 747 mmHg x min). The decrease in orthostatic tolerance was not related to changes in leg venous compliance. In conclusion, this study demonstrates that after bed rest, leg venous compliance is reduced and leg venous outflow resistance is enhanced. However, these changes are not related to measures of orthostatic tolerance; therefore, alterations in venous compliance do not to play a major role in orthostatic intolerance after 18 days of head-down tilt bed rest.


Frontal affinity chromatography combined on-line with mass spectrometry: a tool for the binding study of different epidermal growth factor receptor inhibitors.
Frontal affinity chromatography (FAC) is a simple but powerful method to analyze molecular interactions between an analyte and an immobilized ligand by calculating the extent of retardation of the elution front. By combination of FAC with a PE-Mariner electrospray ionization mass spectrometry, a very efficient and straightforward procedure was developed herein for analyzing the binding properties of different inhibitors of the epidermal growth factor receptor (EGFR). In this study, a polyclonal antibody prepared with a known anti-EGFR inhibitor coupled with bovine serum albumin was adopted as the stationary phase in the FAC system. Using the antibody to mimic the receptor, other different anti-EGFR inhibitors as well as the small-molecule half-antigen itself were recognized directly from the crude extract of herb, which afforded us a novel promising approach for the efficient screening of lead compounds or drug candidates from natural resources.


Integrating sphere for measuring scattering loss in optical fiber waveguides.
An integrating sphere for light scattered from fused silica optical fiber waveguides that is relatively simple to construct and easy to use is described. The novel feature is the use of a solid sphere of fused silica to facilitate coupling the scattered light out of the fiber cladding into the detector. The fiber is inserted into a slot in the sphere, and glycerine is used to index match between the fiber and sphere. The sphere is coated with high reflectivity barium sulfate, and a silicon photodiode detects the radiation in the sphere. The construction, operation, and performance tests on the sphere are described.


Genetic factors underlying insomnia and ovarian insufficiency.
Premature ovarian insufficiency (POI) is characterized by a loss of regular hormone production and egg release in women below the age of 40 years, which often leads to infertility, vaginal dryness and dysfunctional sleep. Acknowledging the common co-occurrence of insomnia and POI, we tested the overlap between POI and insomnia-associated genes, which were implicated in previous large-scale populational genetics efforts. Among the 27 overlapping genes, three pathways were found as enriched: DNA replication, homologous recombination and Fanconi anemia. We then describe biological mechanisms, which link these pathways to a dysfunctional regulation and response to oxidative stress. We propose that oxidative stress may correspond to one of the convergent cellular processes between ovarian malfunction and insomnia pathogenic etiology. This overlap might also be driven by cortisol release associated with dysregulated DNA repair mechanisms. Benefiting from the enormous advances in populational genetics studies, this study provides a novel outlook on the relationship between insomnia and POI. The shared genetic factors and critical biological nodes between these two comorbidities may lead to identification of putative pharmacological and therapeutical targets, which can leverage novel approaches to treat or alleviate their symptoms.


alphaB-crystallin is mutant B-RAF regulated and contributes to cyclin D1 turnover in melanocytic cells.
The serine/threonine kinase, B-RAF, is frequently mutated in melanoma and is required for cell proliferation. Proteasomal turnover of cyclins and cyclin-dependent kinase inhibitors via E3 ubiquitin ligases regulates cell cycle progression. We previously showed that B-RAF regulates Cks1, a co-factor for the F-box protein Skp2. Recently, a second F-box protein cofactor was identified, alphaB-crystallin, that binds Fbx4 and promotes cyclin D1 degradation. Here, we demonstrate that alphaB-crystallin is down-regulated in mutant B-RAF melanoma cells compared to melanocytes in a B-RAF and MEK-dependent manner. In a subset of lines, MEK inhibition was sufficient to up-regulate alphaB-crystallin protein levels; whereas in other lines combined MEK and proteasome inhibition was required. alphaB-crystallin knockdown partially stabilized cyclin D1 in melanocytes. Expression of alphaB-crystallin in mutant B-RAF melanoma cells did not promote cyclin D1 turnover under normal conditions, but did enhance turnover following etoposide-induced DNA damage. Together, these data show that alphaB-crystallin is highly expressed in melanocytes contributing, in part, to cyclin D1 turnover. Furthermore, alphaB-crystallin is down-regulated in a B-RAF-dependent manner in melanoma cells and its re-expression regulates cyclin D1 turnover after DNA damage.


New hominids from the Lake Turkana Basin, Kenya.
New hominid fossils from the Lake Turkana Basin range in age from ca. 3.35 to ca. 1.0 Ma. Those recovered from sediments stratigraphically just above the Tulu Bor Tuff in the Lomekwi Member of the Nachukui Formation are best attributed to Australopithecus afarensis. This species is rare in Kenya, probably because of the scarcity of sediments deposited during its time span. Younger specimens are referable either to the megadont A. boisei or early Homo. Collectively the new fossils promote further understanding of morphological variation in East African Plio-Pleistocene hominids.


Characterization of Borrelia burgdorferi sensu lato strains isolated from human material in Slovenia.
The aim of the study was to assess genotypic and phenotypic diversity among a large number of clinical isolates of Borrelia burgdorferi sensu lato obtained from patients in Slovenia. Plasmid profiles and species identification were determined by PFGE, protein profiles by SDS-PAGE. Of 706 B. burgdorferi sensu lato human isolates 599 (85%) were found to be B. afzelii, 101 (14%) B. garinii and six (1%) B. burgdorferi sensu stricto. The vast majority of strains (605; 86%) were isolated from skin, 58 (8%) from blood, and 43 (6%) from CSF. When analysed by RFLP, B. afzelii strains were unique, while heterogeneity was found within B. garinii and B. burgdorferi sensu stricto species. An unusual plasmid content was found in 52/706 (7%) isolated strains, more often in B. garinii than in B. afzelii strains. A plasmid dimer was found in B. afzelii and B. garinii strains, whereas multiple copies of the large plasmid were associated nearly exclusively with B. garinii strains. Analysis of protein profiles revealed that OspA and OspB are expressed more often by B. afzelii strains, and OspC by B. garinii strains. Heterogeneity of Borrelia strains may play a significant role in the virulence and pathogenesis of the infection. Differences in antigenic components have an important impact on serological testing and vaccine development.


Useful histological findings in incisional biopsies of oral squamous cell carcinoma.
Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers. The aim of this study was to investigate the histopathological features of OSCC specimens obtained from incisional biopsies and to alert clinicians to the importance of more representative biopsies. Forty-eight OSCC samples were obtained from incisional biopsies and classified by Bryne's score. The following morphological features were analyzed: invasive front, invasiveness, apoptotic cells, atypical mitosis, giant cells, acantholysis, ulceration, necrosis, calcification, surface epithelium, granulation tissue, desmoplasia, tissue invasions, inflammatory infiltrate and tumor thickness. Ten (21%) cases were classified as high grade malignancies and 38 (79%) as low grade. Apoptotic cells (n = 26), atypical mitosis (1–2/20×; n = 38), giant cells (n = 8), acantholysis (n = 5), necrosis (n = 5), calcification (n = 1), granulation tissue (n = 32), desmoplasia (n = 4), perineural invasion (n = 2), muscular invasion (n = 8), invasion of salivary gland tissue (n = 3), vascular invasion (n = 10), and chronic inflammation (n = 33) were observed. Vascular invasion (p = 0.04, Pearson's χ2 test) and necrosis (p = 0.04, Pearson's χ2 test) were significantly associated with cases of high-grade malignant tumors. Atypical mitosis was associated with a greatest tumor thickness (p = 0.04, Fischer's exact test). This study suggests that incisional biopsies may be useful and significant as they can show histopathological variables that are important to classify oral squamous cell carcinomas into low grade and high grade according to Bryne's score, which was used in this study. Thus, more representative biopsies might be useful to achieve this and allow a more accurate planning.


Pulmonary Nodular Lymphoid Hyperplasia in a 33-Year-Old Woman.
Pulmonary nodular lymphoid hyperplasia is a reactive lymphoproliferative disease. It is very rare, which means that many aspects of the disease are unknown or have not been proven. Pulmonary nodular lymphoid hyperplasia can be symptomatic or asymptomatic, progressive or not, and solitary or multiple, and a surgical approach is the current treatment of choice. We present a case of pulmonary nodular lymphoid hyperplasia that was visualized as multiple ground glass opacities on a computed tomography (CT) scan, and observed for 1 year because the patient was pregnant. Over this period, the number and extent of the opacities progressed, but no symptoms were reported. A surgical biopsy was done and some remaining lesions regressed on follow-up CT scans, while others progressed, without any appearance of symptoms.


Isokinetic strength benefits after 24 weeks of multicomponent exercise training and combined exercise training in older adults.
Studies that have attempted to address the influence of exercise programs on muscle strength have usually analyzed single exercise training types. They have not often addressed multicomponent exercise interventions that combine strength, flexibility, balance and aerobic training. The aim of the present study was to assess and compare improvements in muscle strength induced by 24 weeks of two training regimens in elderly adults aged 65-82 years. Participants underwent a multicomponent exercise program (ME, n=25, 69.4+/-4.1 yrs) or combined ME plus resistance training (CE, n=24, 68.7+/-4.2 yrs). Maximum strength of knee extensors (KE) and flexors (KF) was measured at 60 masculine/s and 180 masculine/s with an isokinetic dynamometer before and 12 and 24 weeks after the training programs. The CE group showed a significant increase in maximum voluntary knee extensors (22.3%, p<0.001) and knee flexors (29.6%, p<0.001) at 180 masculine/s in the non-dominant leg, in knee extensor torque at 60 masculine/s in the dominant (6.7%, p=0.023) and non-dominant leg (17.3%, p<0.001) and in knee flexor torque at 60 masculine/s in dominant (16.4%, p=0.020) and non-dominant leg (24.2%, p<0.001). No significant changes were observed in the ME group after 24 weeks of training. The present study indicates that twice-weekly ME has a limited effect on isokinetic muscle strength. Our results also emphasize that adding moderate intensity resistance exercise twice a week to a ME protocol is sufficient to induce higher and significant strength improvements in healthy older subjects.


PERSONALITY TRAITS, ANGER AND PSYCHIATRIC SYMPTOMS RELATED TO QUALITY OF LIFE IN PATIENTS WITH NEWLY DIAGNOSED DIGESTIVE SYSTEM CANCER.
The presence of psychiatric symptoms, anger, and personality characteristics are factors that affect the quality of life of newly diagnosed digestive system cancer patients. This study aims to identify which stable characteristics of the individual's personality interfere with quality of life, even when reactive emotional characteristics of falling ill are controlled. A cross-sectional study was performed at the Oncology Clinic ( Hospital das Clínicas ), Marília/SP, Brazil, in which 50 adult patients with digestive system cancer and diagnosed less than 6 months answered the State-Trait Anger Expression Inventory, Temperament and Character Inventory, Hospital Anxiety and Depression Scale and WHOQOL-BREF. Multiple regression was performed to verify if quality of life was related to stable characteristics of the subject's personality (anger trait, temperament and character) after controlling to the transient emotional aspects (anger state, psychiatric symptoms). The quality of life psychological health score was higher in presence of self-directedness character and reward dependence temperament and quality of life environment score was higher in presence of self-directedness character and lower in presence of harm avoidance temperament. The psychological well-being and the adaptive needs to the environment that favoring a better quality of life were reinforced mainly by the self-directedness character; which means that patients more autonomous cope better with the disease. On the other hand, the harm avoidance temperament (meaning the patient has fear of aversive situations) impaired the adaptive capacity to deal with the changes of the day-to-day imposed by the disease. Understanding these personality traits is important to the health professionals drive the patient to more successful treatment.


Cervical spine injury in patients with facial skeletal trauma.
The records of 2,555 patients admitted to hospital with facial fractures were reviewed for concomitant neck injury. Cervical spine injury occurred in 1.3% of all patients with facial fractures, the incidence rising to 5.5% with facial fractures resulting only from MVA's. Neck injuries occurred most frequently in the setting of MVA's (85%) and multisystem trauma (70%) and tended to involve two main levels of the cervical spine: C2 (31%) and the two lower cervical vertebrae C6 and C7 (50%). Examination of the pattern of cervical spine injury with respect to the pattern of facial skeletal injury does not support the premise of a direct causal relation between them.


Analysis of detergent-insoluble and whole cell lysate fractions of resting neutrophils using high-resolution mass spectrometry.
Neutrophilic granulocytes play a major role in the initiation and resolution of the inflammatory response, and demonstrate significant transcriptional and translational activity. Although much was known about neutrophils prior to the introduction of proteomics, the use of MS-based methodologies has provided an unprecedented tool to confirm and extend previous findings. In the present study, we performed a Gel-LC-MS/MS analysis of neutrophil detergent insoluble and whole cell lysate fractions of resting neutrophils. We achieved a set of identifications through the use of high-resolution mass spectrometry and validation of its data. We identified a total of 1249 proteins with a wide range of intensities from both detergent-insoluble and whole cell lysate fractions, allowing a mapping of proteins such as those involved in intracellular transport (Rab and Sec family proteins) and cell signaling (S100 proteins). These results represent the most comprehensive proteomic characterization of resting human neutrophils to date, and provide important information relevant for further studies of the immune system in health and disease. The methods applied here can be employed to help us understand how neutrophils respond to various physiologic and pathophysiologic conditions and could be extended to protein quantitation after cell activation.


Alignment and use of microbeam with full-field x-ray microscopes.
Demonstration tests of the alignment of Fresnel zone plate focusing optics using a full-field x-ray microscope and microbeam x-ray diffraction measurements combined with the full-field x-ray microscope were performed. It was confirmed that the full-field x-ray microscope enables direct two-dimensional observation of a microbeam with sub-micrometer spatial resolution. This allowed visualization of the misalignment of the focusing optics, resulting in accurate alignment of the optics within a short time. In addition, the microscope could be used to observe the sample as well as the microbeam, which enabled clarification of the position and two-dimensional shape of the microbeam on the sample. This realized a measurement procedure that a 100-μm-size sample was imaged with sub-micrometer spatial resolution, and then, microbeam-use measurements were performed for only the region of interest determined by the microscope, which has been difficult with conventional microbeam applications. The combination of observations by a full-field x-ray microscope and measurements using a microbeam is expected to open a new style of measurement.


[Clinical usefulness of combination treatment with thiazolidinedione and insulin].
Because most type-2 Diabetes Mellitus(DM) is a consequence of both impaired insulin secretion and insulin resistance, it should be treated most efficiently using insulin and thiazolidinedione(TZD), a novel insulin-sensitizer, in combination. In our study, patients with non-obese type-2 DM treated with insulin alone were further administered with TZD. In 80% of patients, addition of TZD caused not only the decrease in insulin dosage and/or HbA1c but also the decrease in hypoglycemic events presumably through improvement in insulin profile, i.e. endogenous:exogenous ratio. More importantly, TZD did not cause unfavorable increase in BMI and patients positively accepted these changes. We conclude that combination of TZD and insulin is a good regimen for non-obese type-2 DM.


CH...anion interaction in BF2 complexes of C3-bridged oligopyrroles.
Alkyl-substituted derivatives of 1,3-dipyrrolyl-1,3-propanedione BF2 complexes, the efficient receptors for halide and oxoanions with use of bridging CH as well as pyrrole NH, are reported. BF2 complexes with only one pyrrole NH interaction site (2d,e), which exhibit smaller affinities than the basic structure (2b), bind anions tightly, which is inferred by UV/vis absorption spectral changes, compared to the derivatives with an alkyl group at the bridging carbon (2f) or two pyrrole nitrogen sites (2c). With use of 1H NMR and theoretical studies for anion complexes of 2d and 2e, bridging CH (and one beta-CH in 2d) as well as pyrrole NH is found to interact with anions.


The association of parturition scars and pelvic shape: A geometric morphometric study.
Pelvic features, mostly known as parturition scars, have been extensively studied in the last decades and are frequently investigated in archaeological and forensic contexts. It is still unclear, however, whether they really relate to pregnancy and birth, or whether these features are caused by other biomechanical factors. Because the length and difficulty of labor correlates with the form of the birth canal, we studied the association between the expression of pelvic features and pelvic shape using geometric morphometrics. We scored the expression of the preauricular sulcus, margo auricularis groove, sacral preauricular extension, dorsal and ventral pubic pitting for 54 individuals from a 19th century collection and 19 individuals from the Bronze Age cemetery of Hainburg-Teichtal, Austria. Based on photogrammetric surface models, pelvic shape was captured by 331 landmarks and semilandmarks. The multivariate association between pelvic features and pelvic shape was explored by partial least squares analysis. Within the female subsample, we detected a significant association of a constrained birth canal with a strong expression of the preauricular sulcus, the margo auricularis groove, and a retroverted position of the acetabulum. No significant association was found among males. This suggests that difficult or prolonged labor may indeed cause more strongly expressed pelvic features, presumably because of increased strain of the pelvic ligaments during birth. Furthermore, the retroversion of the acetabulum, which is known to cause sacroiliac joint dysfunction, changes the strain on pelvic ligaments and can thus also result in the development of pronounced pelvic features.


The Effects of Ultrasound on the Electro-Oxidation of Sulfate Solutions at Low pH.
The electro-oxidation of sulfate solutions is a well-established route for the generation of powerful oxidants such as persulfate. Despite this, the effects of simultaneous ultrasound irradiation during this process has attracted little attention. Herein, we investigate the effects of a low-intensity ultrasonic field on the generation of solution-phase oxidants during the electro-oxidation of sulfate solutions. Our results show that at high current densities and high sulfate concentrations, ultrasound has little effect on the Faradaic and absolute yields of solution-phase oxidants. However, at lower current densities and sulfate concentrations, the amount of these oxidants in solution appears to decrease under ultrasonic irradiation. A mechanism explaining these results is proposed (and validated), whereby anodically-generated sulfate and hydroxyl radicals are more effectively transported into bulk solution (where they are quenched) during sonication, whereas in the absence of an ultrasonic field these radicals combine with one another to form more persistent species (such as persulfate) that can be detected by iodometry.


Cadmium, lead, copper and zinc in blue mussels (Mytilus edulis) sampled in the Hardangerfjord, Norway.
Cadmium, lead, copper and zinc were determined in the soft tissues of blue mussels (Mytilus edulis) sampled from four locations along the Hardangerfjord in western Norway. A source of pollution is located at the head of the fjord and the sampling was performed at various distances from this source. The results obtained in this study (1998) were compared with results from similar studies carried out in 1983 and 1992. The mean cadmium concentrations in blue mussels sampled at Måge (13 km from the source of pollution) were approximately 18 mg kg-1 fresh weight in 1983, 2.4 mg kg-1 fresh weight in 1992 and 1.1 mg kg-1 fresh weight in 1998. The mean cadmium concentrations in blue mussels sampled at Varaldsøy (105 km from the source of pollution) were approximately 5 mg kg-1 fresh weight in 1983, 0.5 mg kg-1 fresh weight in 1992 and 0.4 mg kg-1 fresh weight in 1998. The mean lead concentration in blue mussels sampled at Måge was 140 mg kg-1 fresh weight in 1983. The mean lead concentrations in 1992 and 1998 had decreased to 6 and 3 mg kg-1 fresh weight, respectively. The mean lead concentrations in blue mussels from Gravdal were 15 mg kg-1 fresh weight in 1982, 1 mg kg-1 in 1992 and less than 1 mg kg-1 fresh weight in 1998. The mean copper concentrations in blue mussels were relatively constant over this period at all locations, with a variation between 0.6 and 1.2 mg kg-1 fresh weight. The mean zinc concentration in blue mussels sampled at Måge decreased from 120 to 30 mg kg-1 fresh weight in the period between 1983 and 1998.


Trait-Based Emotional Intelligence, Body Image Dissatisfaction, and HRQoL in Children.
Body image dissatisfaction (BID) is related to an increased risk for various health issues including descreased health-related quality of life (HRQoL), the development of problematic eating behaviors and obesity. Previous research indicates that emotional intelligence is one important factor related to BID in adults. Whether this is the case in children, remains yet unknown. Taking this into consideration, the aim of this study was to explore the relationship between BID and trait-based emotion intelligence (TEI) as well as HRQoL in female and male primary school children. TEI and BID were assessed via self-reports as well as HRQoL via parental reports in a large sample of 991 primary school children (429 girls) within the "Baden Württemberg Study", which evaluated the effectiveness of the health prevention programm "Join the Healthy Boat" in Southwestern Germany. Our findings demonstrated the interrelation between higher levels of TEI and lower levels of BID among girls and boys. Positive associations were found between better HRQoL, better intrapersonal and stress management abilites (subscales of TEI) and lower BID, as reflected by parental and self-reports. Our results reveal an interconnectivity between TEI, BID, and better HRQoL in female and male primary school children. Although the observed correlations were rather small, they nervertheless support the idea that TEI consists a key-factor for the self-regulation of health-related behavior. Prevention programs could benefit from including processes, that sough to improve aspects of emotional intelligence such as intrapersonal, interpersonal abilities, and adaptability, as an effort of preventing problematic habits or lifestyles that could lead to disordered eating behaviors as well as to obesity in middle childhood.


[Strategies for the detection of DNA polymorphism in human populations].
We develop here several models concerning strategies for detection of restriction polymorphisms in humans. These different strategies concern the numbers of individuals to test in a DNA collection, the nature of restriction enzyme to utilize, and the length of the probes. For enzyme utilization different strategies are based on (i) the nature of the restriction site; (ii) the mean length of restriction fragments obtained; (iii) the methylated cytosine characteristics in the CG doublets. Each of these approaches are tested in experimental situations.


An approach to the research on ion and water properties in the interphase between the plasma membrane and bulk extracellular solution.
In vivo, cells are immersed in an extracellular solution that contains a variety of bioactive substances including ions and water. Classical electrophysiological analyses of epithelial cells in the stomach and small intestine have revealed that within a distance of several hundred micrometers above their apical plasma membrane, lies an extracellular layer that shows ion concentration gradients undetectable in the bulk phase. This "unstirred layer", which contains stagnant solutes, may also exist between the bulk extracellular solution and membranes of other cells in an organism and may show different properties. On the other hand, an earlier study using a bacterial planar membrane indicated that H+ released from a transporter migrates in the horizontal direction along the membrane surface much faster than it diffuses vertically toward the extracellular space. This result implies that between the membrane surface and unstirred layer, there is a "nanointerface" that has unique ionic dynamics. Advanced technologies have revealed that the nanointerface on artificial membranes possibly harbors a highly ordered assembly of water molecules. In general, hydrogen bonds are involved in formation of the ordered water structure and can mediate rapid transfer of H+ between neighboring molecules. This description may match the phenomenon on the bacterial membrane. A recent study has suggested that water molecules in the nanointerface regulate the gating of K+ channels. Here, the region comprising the unstirred layer and nanointerface is defined as the interphase between the plasma membrane and bulk extracellular solution (iMES). This article briefly describes the physicochemical properties of ions and water in the iMES and their physiological significance. We also describe the methodologies that are currently used or will be applicable to the interphase research.


Fluorometric determination of magnesium in serum with 2-hydroxy-1-naphthaldehyde salicyloylhydrazone.
This simple, rapid, sensitive fluorometric method for determining magnesium is based on formation of a fluorescent complex of magnesium with 2-hydroxy-1-naphthaldehyde salicyloyl-hydrazone in alkaline ethanolic medium (lambda ex = 420 nm, lambda em = 460 nm). The detection limit of the method is 0.05 microgram/L (2 nmol/L) and the relative standard deviations (CVs) are 0.8%, 1.1%, and 2.5% at magnesium concentrations of 50, 5.0, and 0.50 microgram/L, respectively. The standard curve is linear from 0 to 250 micrograms/L (0-10 mumol/L). We investigated the chemistry of the reaction, and have applied the method to determine magnesium in 100-fold-diluted, otherwise untreated serum samples. Within-run CVs for the method were 1.7%, 1.1%, and 1.3% at mean magnesium concentrations of 15.7, 26.4, and 36.2 mg/L, respectively. Day-to-day CVs were 2.7%, and 3.6% at mean magnesium concentrations of 10.1 and 25.5 mg/L, respectively. Samples from 96 hospitalized patients in intensive-care units were analyzed by the proposed method (y) and by an automated colorimetric method involving Magon sulfonate reagent (x). Linear regression analysis of the results yielded: y = 1.01x - 0.04 (r = 0.982, Sxy = 0.90).


Results of transthoracic esophagotomy retrieval of esophageal foreign body obstructions in dogs: 14 cases (2000-2004).
The records of 14 consecutive cases of esophageal foreign body obstruction in dogs that had undergone transthoracic esophagotomy for foreign body retrieval were reviewed. Clinical results were considered successful in 13 of 14 dogs. One dog was euthanized at surgery because of the severity of associated thoracic lesions. Clinical signs resolved in the remaining 13 dogs. Two dogs had postoperative complications. One dog developed a pyothorax, and one dog developed a subcutaneous seroma. The overall recovery rate was 93%.


Prognostic biological factors in severe acute pancreatitis.
Acute pancreatitis is a serious disease. Many clinical and laboratory prognostic scores for the severity of acute pancreatitis have been proposed over the years. The aim was to identify the biological factors of prognostic severity. The study was prospective, including a four-year period between 2007 and 2010. 103 patients were diagnosed with severe acute pancreatitis and treated in a surgical clinic in Bucharest. 58 were males, accounting for 56.31%, and 45 were women, 43.69% respectively. Numerous biochemical analyses of blood, especially the number of leukocytes, glucose, urea and bilirubin were monitored. They proposed generic profiles for patients with severe acute pancreatitis. There is no single biological prognostic factor, but a combination of different markers may contribute to a more precise prediction of severity, as confirmed by international literature.


Brain Effects of SC-Nanophytosomes on a Rotenone-Induced Rat Model of Parkinson's Disease-A Proof of Concept for a Mitochondria-Targeted Therapy.
Mitochondria are an attractive target to fight neurodegenerative diseases due to their important functions for cells and the particularly close relationship between the functional connectivity among brain regions and mitochondrial performance. This work presents a mitochondria-targeted therapy designed to modulate the functionality of the mitochondrial respiratory chain and lipidome, parameters that are affected in neurodegeneration, including in Parkinson's disease (PD). This therapy is supported by SC-Nanophytosomes constructed with membrane polar lipids, from Codium tomentosum, and elderberry anthocyanin-enriched extract, from Sambucus nigra L. SC-Nanophytosomes are nanosized vesicles with a high negative surface charge that preserve their properties, including anthocyanins in the flavylium cation form, under conditions that mimic the gastrointestinal tract pH changes. SC-Nanophytosomes, 3 µM in phospholipid, and 2.5 mg/L of EAE-extract, delivered by drinking water to a rotenone-induced PD rat model, showed significant positive outcomes on disabling motor symptoms associated with the disease. Ex vivo assays were performed with two brain portions, one comprising the basal ganglia and cerebellum (BG-Cereb) and the other with the cerebral cortex (C-Cortex) regions. Results showed that rotenone-induced neurodegeneration increases the α-synuclein levels in the BG-Cereb portion and compromises mitochondrial respiratory chain functionality in both brain portions, well-evidenced by a 50% decrease in the respiratory control rate and up to 40% in complex I activity. Rotenone-induced PD phenotype is also associated with changes in superoxide dismutase and catalase activities that are dependent on the brain portion. Treatment with SC-Nanophytosomes reverted the α-synuclein levels and antioxidant enzymes activity to the values detected in control animals. Moreover, it mitigated mitochondrial dysfunction, with positive outcomes on the respiratory control rate, the activity of individual respiratory complexes, and the fatty acid profile of the membrane phospholipids. Therefore, SC-Nanophytosomes are a promising tool to support mitochondria-targeted therapy for neurodegenerative diseases.


Inhibitory effects of Inula britannica extract fermented by Lactobacillus plantarum KCCM 11613P on coagulase activity and growth of Staphylococcus aureus including methicillin-resistant strains.
The aim of this study was to evaluate the antimicrobial efficacy of fermented Inula britannica extract (FIBE) against Staphylococcus aureus strains including methicillin-resistant S. aureus (MRSA). I. britannica extract was fermented by Lactobacillus plantarum KCCM 11613P, and the pathogenicity of S. aureus strains was determined via assessment of coagulase, DNase, and hemolytic activities. Epicatechin concentration increased from 4.38 to 6.05 μg/mg during fermentation (p < 0.01). FIBE treatment inhibited coagulase release from S. aureus to levels below the inhibitory concentration. FIBE promoted the release of intracellular nucleic acids and N-phenyl-1-naphthylamine absorption. In three S. aureus strains, damaged cells exhibited 21.58, 16.79, and 17.65% decreases in membrane potential induced by cell membrane depolarization, respectively (p < 0.05). Upon FIBE treatment in culture, the minimum inhibitory concentration of FIBE exerted a bacteriostatic effect. In conclusion, FIBE possesses antimicrobial properties, including inhibition of virulence factors, damage to cell membranes, and inhibition of bacterial growth. PRACTICAL APPLICATIONS: Methicillin-resistant Staphylococcus aureus (MRSA) is a serious concern in hospitals because of its known antibiotic resistance. Vancomycin and tigecycline are used for treating MRSA, but the appearance of vancomycin-intermediate and multidrug-resistant strains of these bacteria has created a demand for new antimicrobial agents. This study demonstrates the effective application of Inula britannica and fermentation technology for developing natural antimicrobial agents against methicillin-resistant Staphylococcus aureus.


An Assessment of Waveform Processing for a Single-Beam Bathymetric LiDAR System (SBLS-1).
The single-beam bathymetric light detection and ranging (LiDAR) system 1 (SBLS-1), which is equipped with a 532-nm-band laser projector and two concentric-circle receivers for shallow- and deep-water echo signals, is a lightweight and convenient prototype instrument with low energy consumption. In this study, a novel LiDAR bathymetric method is utilized to achieve single-beam and dual-channel bathymetric characteristics, and an adaptive extraction method is proposed based on the cumulative standard deviation of the peak and trough, which is mainly used to extract the signal segment and eliminate system and random noise. To adapt the dual-channel bathymetric mechanism, an automatic channel-selection method was used at various water depths. A minimum half-wavelength Gaussian iterative decomposition is proposed to improve the detection accuracy of the surface- and bottom-water waveform components and ensure bathymetric accuracy and reliability. Based on a comparison between the experimental results and in situ data, it was found that the SBLS-1 obtained a bathymetric accuracy and RMSE of 0.27 m and 0.23 m at the Weifang and Qingdao test fields. This indicates that the SBLS-1 was bathymetrically capable of acquiring a reliable, high-efficiency waveform dataset. Hence, the novel LiDAR bathymetric method can effectively achieve high-accuracy near-shore bathymetry.


Use of ribosome-inactivating proteins from Sambucus for the construction of immunotoxins and conjugates for cancer therapy.
The type 2 ribosome-inactivating proteins (RIPs) isolated from some species belonging to the Sambucus genus, have the characteristic that although being even more active than ricin inhibiting protein synthesis in cell-free extracts, they lack the high toxicity of ricin and related type 2 RIPs to intact cells and animals. This is due to the fact that after internalization, they follow a different intracellular pathway that does not allow them to reach the cytosolic ribosomes. The lack of toxicity of type 2 RIPs from Sambucus make them good candidates as toxic moieties in the construction of immunotoxins and conjugates directed against specific targets. Up to now they have been conjugated with either transferrin or anti-CD105 to target either transferrin receptor- or endoglin-overexpressing cells, respectively.


Tungsten Hydride Phosphorus- and Arsenic-Bearing Molecules with Double and Triple W-P and W-As Bonds.
Laser ablation of tungsten metal provides W atoms which react with phosphine and arsine during condensation in excess argon and neon, leading to major new infrared (IR) absorptions. Annealing, UV irradiation, and deuterium substitution experiments coupled with electronic structure calculations at the density functional theory level led to the assignment of the observed IR absorptions to the E≡WH3 and HE═WH2 molecules for E = P and As. The potential energy surfaces for hydrogen transfer from PH3 to the W were calculated at the coupled-cluster CCSD(T)/complete basis set level. Additional weak bands in the phosphide and arsenide W-H stretching region are assigned to the molecules with loss of H from W, E≡WH2. The electronic structure calculations show that the E≡WH3 molecules have a W-E triple bond, the HE═WH2 molecules have a W-E double bond, and the H2E-WH molecules have a W-E single bond. The formation of multiple E-W bonds leads to increasing stability for the isomers.


Influence of cefotaxime on Staphylococcus aureus with respect to their interaction with macrophages.
Many antibiotics in addition to their direct effect on bacteria can modulate host defence in different ways. The influence of cefotaxime on the phagocytic and bactericidal activity of mouse peritoneal macrophages was investigated. At concentrations of half the MIC the antibiotic caused macrophages to kill intracellular Staphylococcus aureus at a higher level than did macrophages without drug. Bacteria pretreated with cefotaxime became more sensitive to macrophage phagocytic and bactericidal activity. Macrophages taken from mice receiving intravenous cefotaxime showed greater phagocytic capacity than those from control mice.