Relationships between cheese-processing conditions and curd and cheese properties to improve the yield of Idiazabal cheese made in small artisan dairies: A multivariate approach.
Very diverse cutting and cooking intensity processes are currently used in small artisan dairies to manufacture Idiazabal cheese. The combination of the technical settings used during cheese manufacturing is known to affect cheese composition and yield, as well as whey losses. However, the information regarding the effect on microstructure and texture of cheese is scarce, especially in commercial productions. Therefore, the effect of moderate- and high-intensity cutting and cooking processes on whey losses, curd-grain characteristics, microstructure and cheese properties, and yield were analyzed. Three trials were monitored in each of 2 different small dairies during the cheesemaking of Idiazabal cheese, which is a semihard cheese made from raw sheep milk. The role and know-how of the cheesemakers are crucial in these productions because they determine the cutting point and handle semi-automatic vats. The 2 dairies studied used the following settings: dairy A used moderate-intensity cutting and cooking conditions, and dairy B used high-intensity cutting and cooking settings. Multiple relationships between cheese-processing conditions and curd, whey, and cheese properties as well as yield were obtained from a partial least square regression analysis. An increased amount of fat and casein losses were generated due to a combination of an excessively firm gel at cutting point together with high-intensity cutting and cooking processes. The microstructural analysis revealed that the porosity of the protein matrix of curd grains after cooking and cheese after pressing was the main feature affected, developing a less porous structure with a more intense process. Moderate-intensity cutting and cooking processes were associated with a higher cheese yield, regardless of the longer pressing process applied. No significant differences were observed in cheese composition. After 1 mo of ripening, however, the cheese was more brittle and adhesive when the high-intensity cutting and cooking process was applied. This could be associated with the composition, characteristics, and size distribution of curd grains due to differences in the compaction degree during pressing. These results could help to modify specific conditions used in cheesemaking, especially improving the process in those small dairies where the role of the cheesemaker is crucial.


Modified Pereyra procedure for female stress incontinence.
28 patients were treated with the modified Pereyra procedure for female stress urinary incontinence. In 12 patients this was the primary operative correction of the complaints and resulted in total continence in 10 patients (83%). The other patients had a recurrent stress incontinence which might have contributed to lower success rate of 54% in the total series. Due to less extensive surgery than in suprapubic urethropexy and due to low complication rate we feel that the modified Pereyra procedure is a good alternative as a primary operation for stress urinary incontinence.


Overexpression of platelet-derived growth factor receptor alpha promotes tumor progression and indicates poor prognosis in hepatocellular carcinoma.
Dysregulation of platelet-derived growth factor receptor alpha (PDGFRα) has been documented in various cancers. However, its role in hepatocellular carcinoma (HCC) remains unknown. We and others have examined that upregulation of PDGFRα might be involved in hepatocarcinogenesis. Here, we report that PDGFRα plays a critical role in HCC progression and prognosis. The expression of PDGFRα was markedly higher in human HCC compared to adjacent liver tissues. Although PDGFRA mRNA was decreased in HCC, PDGF-A mRNA was dramatically increased in HCC. Overexpression of PDGFRα was strongly correlated with microvessel density (MVD) of HCC (p<0.05), as well as macroscopic vascular invasion of the tumors (p<0.05). HCC patients with high PDGFRα expression displayed a shorter overall survival and a higher recurrence rate than those with low PDGFRα expression (p<0.05, respectively). Additionally, stable overexpression of PDGFRα in hepatoma cells promoted cell proliferation, migration, invasion and epithelial-mesenchymal transition in vitro. Similarly, an in vivo assay showed that PDGFRα overexpression in hepatoma cells exhibited remarkably tumorigenic potential in tumor size and weight in vivo, which displayed markedly elevated MVD than controls. Thus, our study provided the evidence that PDGFRα may serve as a candidate prognostic marker and a novel therapeutic target for HCC.


Alcohol surveys with high and low coverage rate: a comparative analysis of survey strategies in the alcohol field.
Two Swedish alcohol surveys were compared in a search for a reasonable explanation of the large difference in their coverage rates, namely 75% and 28%. In many respects both surveys conducted in the late 1980s by large, well-known institutes, are of a similar type with rather large samples of Swedes. The technique used in the survey with a very high coverage rate (Survey A) takes into consideration the actual drinking pattern of the population studied (i.e., the concentration of drinking on weekends). By dividing a "normal week's consumption" into four units (Monday-Thursday, Friday, Saturday and Sunday), the technique allows one to average periods with varying drinking habits. In the survey with a low coverage rate (Survey B) a "normal week's consumption" was not so divided. A test of internal validity within Survey A underlined the general finding that its higher coverage rate was due to this division. A test of the external validity at aggregate level did not support assumptions about "telescoping" effects in A. Both A and B had a normal week as a basis of measurement for investigating typical drinking habits. The literature concerning differences in coverage rates focuses on the measurement of modal habits versus mean habits. The main explanation of differences is that methods that focus on modal habits (i.e., the Quantity-Frequency Scale) generate a lower coverage rate than do methods that elicit the arithmetic mean (i.e., the last-week recall). Since A and B both belong to the former type of scale, this does not explain our results.


LncACTdb 3.0: an updated database of experimentally supported ceRNA interactions and personalized networks contributing to precision medicine.
LncACTdb 3.0 is a comprehensive database of experimentally supported interactions among competing endogenous RNA (ceRNA) and the corresponding personalized networks contributing to precision medicine. LncACTdb 3.0 is freely available at http://bio-bigdata.hrbmu.edu.cn/LncACTdb or http://www.bio-bigdata.net/LncACTdb. We have updated the LncACTdb 3.0 database with several new features, including (i) 5669 experimentally validated ceRNA interactions across 25 species and 537 diseases/phenotypes through manual curation of published literature, (ii) personalized ceRNA interactions and networks for 16 228 patients from 62 datasets in TCGA and GEO, (iii) sub-cellular and extracellular vesicle locations of ceRNA manually curated from literature and data sources, (iv) more than 10 000 experimentally supported long noncoding RNA (lncRNA) biomarkers associated with tumor diagnosis and therapy, and (v) lncRNA/mRNA/miRNA expression profiles with clinical and pathological information of thousands of cancer patients. A panel of improved tools has been developed to explore the effects of ceRNA on individuals with specific pathological backgrounds. For example, a network tool provides a comprehensive view of lncRNA-related, patient-specific, and custom-designed ceRNA networks. LncACTdb 3.0 will provide novel insights for further studies of complex diseases at the individual level and will facilitate the development of precision medicine to treat such diseases.


Effects of Acid and Salt Solutions on the Pasting, Rheology and Texture of Lotus Root Starch⁻Konjac Glucomannan Mixture.
To explore the functional properties of mixed biopolymer systems affected by acid and salts. The effects of acid and salt solutions (i.e., NaCl, KCl and CaCl₂) on the pasting, rheology, texture and microstructure of lotus root starch⁻konjac glucomannan (LRS/KGM) mixtures were assessed. Acid (citric acid buffer) treatment worsened the pasting (except for breakdown viscosity), rheological (except for fluid index), and textural properties, thereby inhibiting retrogradation, weakening pseudoplasticity and thickening, and reducing mixture viscoelasticity. Furthermore, it led to destructive ruptures and large pores in the internal microstructure. Salt treatment worsened the pasting properties (except for setback viscosity), thus inhibiting retrogradation and weakening pseudoplasticity, but enhanced the rheological properties, improving thickening and fluctuating viscoelasticity of the mixture. Moreover, salt addition decreased the hardness while increasing mixture cohesiveness, and modified the elasticity, adhesiveness and internal microstructure in a salt type- and concentration-dependent manner. A salt solution concentration of 0.5 mol/L NaCl, 0.1 mol/L KCl, and 0.5 mol/L CaCl₂ led to the mixture with the best texture and gel network.


Evidence-based medicine and hypertension.
Evidence-based medicine (EBM) has been propagated as a revolutionary development which will improve the quality of clinical decision-making and guideline development Historically it follows an early 19th-century French attempt to introduce mathematical analysis into clinical practice. This met with resistance from both clinicians and scientists and was only accepted in more recent times with the development of clinical epidemiology and clinical trials. EMB claims to utilize the best available evidence to reach scientific conclusions, rejecting the appeal to expert authority. This involves a hierarchy of sources which places large controlled trials at the apex. Less value is attributed to arguments from clinical observation or pathophysiology. Systematic reviews and meta-analyses of trials therefore provide the strongest evidence for clinical decisions. The approach advocated in EBM is an over-simplification of the process of clinical thinking which involves interpretation and synthesis of relevant evidence from all sources and extrapolation to the clinical situation. In this process, there is no hierarchy of evidence. The relative value given to any particular evidence depends more upon its relevance and persuasiveness than the category to which it belongs. Discussion and debate amongst informed 'experts' is an integral feature of this process at each stage. Although advocates of EBM acknowledge the contribution of all forms of evidence, the differential value attached to different sources has led to naïve and simplistic attempts to omit the traditional processes of interpretation, synthesis and extrapolation and to draw wide-ranging conclusions from trial data without adequate scientific discussion.


Enhanced TAG-72 expression and tumor uptake of radiolabeled monoclonal antibody CC49 in metastatic breast cancer patients following alpha-interferon treatment.
The IFNs, alpha and gamma, have been shown to enhance the tumor-associated glycoprotein (TAG-72) on adenocarcinoma cells in vitro and in mice with human breast cancer xenografts, resulting in improved targeting of monoclonal antibody CC49. To determine the effect of IFN-alpha on biodistribution and tumor uptake of 131I-labeled CC49, patients with metastatic breast cancer were randomized to either receive or not receive IFN-alpha (3 million units daily for 14 days) by s.c. injection. Three days after beginning IFN-alpha, all patients received 10-20 mCi of 131I-CC49 (specific activity, 16.7 mCi/mg) i.v. Total-body Anger camera scans, along with total-body blood and plasma pharmacokinetics, were performed. Tumor biopsies were taken in all patients before and 48 h after IFN-alpha treatment. There were no significant differences in number of metastases imaged or whole-body, blood and plasma pharmacokinetics between IFN-alpha-treated and untreated patients. Quantitative immunohistochemistry on biopsy specimens from IFN-alpha-treated patients demonstrated a significant increase in mean +/- SEM TAG-72 expression (45.7 +/- 19.4%) compared to patients that were not given IFN-alpha (1.3 +/- 0.95%; P < 0.05). Although slight increases in the percent injected dose of 131I-CC49 in tumor occurred after IFN-alpha-treatment, the changes were not significant at the P < 0.05 level. These data suggest that IFN-alpha may be useful in enhancing TAG-72 antigen expression in vivo in humans, despite modest improvement in tumor uptake of CC49, possibly because of limited tumor access or other unknown factors.


Experimental stretch neuropathy. Changes in nerve conduction under tension.
We developed an animal model of stretch injury to nerve in order to study in vivo conduction changes as a function of nerve strain. In 24 rabbits, the tibial nerve was exposed and stretched by 0%, 6% or 12% of its length. The strain was maintained for one hour. Nerve conduction was monitored during the period of stretch and for a one-hour recovery period. At 6% strain, the amplitude of the action potential had decreased by 70% at one hour and returned to normal during the recovery period. At 12% strain, conduction was completely blocked by one hour, and showed minimal recovery. These findings have clinical implications in nerve repair, limb trauma, and limb lengthening.


Reproducibility and reliability of the anatomic axis of the lower extremity.
Two observers measured the tibiofemoral angle of 60 knees on hip-knee-ankle and anteroposterior (AP) knee radiographs and repeated the measurements 6 months later. Intraobserver reproducibility was moderate. Interobserver reliability was poor. These findings were the same irrespective of which radiograph was used during the measurement. Hence, although an AP knee radiograph was as reliable and reproducible as the hip-knee-ankle view, the radiographic tibiofemoral angle should not be considered a precise measurement.


Brucellosis-induced avascular necrosis of the hip in a middle-aged person.
Brucellosis is a zoonotic disease mostly transmitted to humans through consumption of unpasteurized dairy products and can lead to a systemic disease with any organ involvement. In this report, we describe a case of brucellosis-induced avascular necrosis of the hip. Brucellosis was diagnosed through serological tests, and avascular necrosis of the femoral head was confirmed by pelvic MRI. The patient was treated with a combination of antimicrobial treatments and referred to the orthopedic service for total hip arthroplasty. Brucellosis may present with unusual manifestations and should be always taken into consideration, particularly in endemic areas.


Preliminary study on the osseointegration effects of contactless automated implant cavity preparation via femtosecond laser ablation.
Microrobots were used to control the femtosecond laser ablation of bone tissues to prepare implant cavities for dental implant surgery. The method was optimized through depth-of-cut experiments of ex vivo rabbit femurs, and the optimized method was used to prepare implant cavities on the left femurs of eight live rabbits. A power of 10 W and a scanning rate of 4000 mm/s were found to be optimal. After seven days of osteoinduction, the expression of collagen type I was significantly higher in the experimental group than in the control group (manually drilled implant cavities). The bone-implant contacts of the experimental group at 4 and 8 weeks were 9.65% and 23.08%, respectively.


Excitons and Biexciton Dynamics in Single CsPbBr3 Perovskite Quantum Dots.
Colloidal lead halide perovskite quantum dots, due to their optical versatility and facile solution processability, have been recently recognized as components of various optoelectronic devices. Detailed understanding of their exciton recombination dynamics at the single-particle level is necessary for utilizing their full potential. We conducted spectroscopic studies of the excitons and biexciton dynamics in single CsPbBr3 perovskite quantum dots. It was found that while the rates of radiative recombination remain essentially constant, the overall relaxation process is dominated by nonradiative recombination of single excitons and biexcitons. The radiative lifetime scaling is determined to be ∼1.0 for single exciton and ∼4.4 for biexcitons. A linear dependence of fluorescence lifetime vs intensity distribution agrees well with the prediction of the model of multiple recombination centers. The blinking mechanism of CsPbBr3 quantum dots is addressed by considering the trion states under higher excitation powers.


Suplatast tosilate protects the lung against hyperoxic lung injury by scavenging hydroxyl radicals.
Prolonged exposure to hyperoxia produces extraordinary amounts of reactive oxygen species (ROS) in the lung and causes hyperoxic lung injury. Although supraphysiological oxygen is routinely administered for the management of respiratory failure, there is no effective strategy to prevent hyperoxic lung injury. In our previous study, we showed that suplatast tosilate, an asthma drug that inhibits T helper 2 (Th2) cytokines, ameliorated bleomycin-induced lung injury and fibrosis through Th2-independent mechanisms. Because bleomycin also generates ROS, we hypothesized that suplatast tosilate might have antioxidant activity and protect the lung against hyperoxic lung injury. To test this hypothesis, mice exposed to hyperoxia were given suplatast tosilate through drinking water. Treatment with suplatast tosilate significantly prolonged mouse survival, reduced the increases in the numbers of inflammatory cells, levels of the pro-inflammatory cytokines/chemokines IL-6 and MCP-1, and protein in bronchoalveolar lavage fluid, and ameliorated lung injury in histological assessment. Suplatast tosilate treatment also significantly inhibited hyperoxia-induced elevations in the levels of 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage, in bronchoalveolar lavage fluid and 8-isoprostane, a marker of lipid peroxidation, in lung tissue. This finding suggests that suplatast tosilate exerts an antioxidant activity in vivo. In addition, we investigated whether suplatast tosilate has a scavenging effect on hydroxyl radical, the most reactive and harmful ROS, using electron paramagnetic resonance spin-trapping. Suplatast tosilate was shown to scavenge hydroxyl radicals in a dose-dependent manner, and its reaction rate constant with hydroxyl radical was calculated as 2.6×1011M-1S-1, which is faster than that of several well-established antioxidants, such as ascorbate, glutathione, and cysteine. These results suggest that suplatast tosilate protects the lung against hyperoxic lung injury by decreasing the degree of oxidative stress induced by ROS, particularly by scavenging hydroxyl radicals. Suplatast tosilate might become a potential therapeutic for hyperoxic lung injury.


Epidermal-like architecture obtained from equine keratinocytes in three-dimensional cultures.
Despite the high prevalence of skin conditions in the horse, there is a dearth of literature on the culture and biology of equine skin cells, and this is partially attributable to the lack of suitable in vitro skin models. The objective of this study was to develop a three-dimensional (3D) culture system that would support the proliferation and differentiation of equine keratinocytes, similar to that observed in natural epidermis. Cell monolayers were obtained from explants of equine skin and serially passaged as highly pure keratinocyte populations (> 95% of cells), based on their expression of cytokeratins, including CK-5 and CK-14, which are associated in vivo with proliferating keratinocyte populations. Explant-derived keratinocytes were seeded into Alvetex™ 3D tissue scaffolds for 30 days under conditions that promote cell differentiation. Ultrastructural, immunohistochemical and biochemical analyses revealed that keratinocytes within scaffolds were able to proliferate and attain tissue polarity, including differentiation into basal and suprabasal layers. The basal layer contained distinct cuboidal cells with large nuclei and stained for proliferative markers such as CK-5 and CK-14. In contrast, the suprabasal layers consisted of cells with distinct polyhedral morphology, abundant cytoplasmic processes and desmosomes indicative of stratum spinosum and distinct flattened cornified cells that expressed involucrin, a marker of terminal differentiation. Thus, keratinocytes derived from primary equine skin explants were able to attain epidermal-like architecture in culture. This novel system could provide a very useful tool for modelling skin diseases, drug testing/toxicity studies and, potentially, equine regenerative medicine. Copyright © 2016 John Wiley & Sons, Ltd.


Sexual Trauma and Combat During Deployment: Associations With Suicidal Ideation Among OEF/OIF/OND Veterans.
Compelling evidence has emerged on the association between military sexual trauma and suicide attempt; however, research investigating how sexual trauma during deployment relates to suicidal ideation has received considerably less attention and has yielded mixed findings. Furthermore, such research has not accounted for other types of trauma that may occur during deployment. Our objectives were to examine whether sexual trauma during deployment was associated with recent suicidal ideation, adjusting for exposure to combat. Our sample included 199 Operation Enduring Freedom/Iraqi Freedom/New Dawn (OEF/OIF/OND) veterans entering inpatient trauma-focused treatment who completed the Beck Scale for Suicide Ideation (Beck & Steer, ) and the Deployment Risk and Resilience Inventory Sexual Harassment and Combat Experiences Scales (King, King, Vogt, Knight, & Samper, ). Deployment-related sexual trauma was significantly associated with recent suicidal ideation, adjusting for age and gender (β = .18, ηp (2) = .03) and additionally for combat (β = .17, ηp (2) = .02). These findings underscore the importance of assessing for deployment-related sexual trauma when assessing suicide risk in OEF/OIF/OND veterans in inpatient settings.


Ziprasidone versus olanzapine, risperidone or quetiapine in patients with chronic schizophrenia: a 12-week open-label, multicentre clinical trial.
The efficacy, safety and tolerability of ziprasidone versus the comparators olanzapine, risperidone or quetiapine were investigated in adult patients with chronic schizophrenia, schizoaffective and schizophreniform disorders, with lack of efficacy or intolerance to their previous antipsychotic treatment based on clinical judgement of the investigator. A total of 293 patients were randomized to 12 weeks treatment with either ziprasidone 80-160 mg/day (n=147) or with one of the comparator drugs (n=146). In the latter group the investigator could choose between olanzapine 10-20 mg/day (n=24), risperidone 4-8 mg/day (n=22) or quetiapine 300-750 mg/day (n=97). The study comprised four visits including a baseline examination prior to randomization and further examinations at the end of weeks 1, 4 and 12. Ziprasidone was non-inferior (defined as a difference of 7 units or less on the PANSS scale to the disadvantage of ziprasidone) to the composite group (olanzapine, risperidone or quetiapine) on the total PANSS score as well as on all subscores (P<0.0001); there were no significant between-group differences in the CGI-S and I and UKU scores. Ziprasidone-treated patients lost an average of 2.1 kg in the 12 weeks of the study, the mean weight for risperidone and quetiapine remained unchanged, and patients receiving olanzapine gained 3.1 kg on average.


Annona muricata as Possible Alternative in the Treatment of Hyperglycemia: A Systematic Review.
The study of the bioactive compounds present in Annona muricata extracts has won popularity due to the growing evidence of its medicinal properties, including anticancer and antidiabetic effects. The aim of this study was to systematically analyze the scientific evidence regarding A. muricata's hypoglycemic effect and the factors affecting the composition of bioactive compounds in different extracts. In vivo, in vitro, and in silico studies were analyzed in the PubMed database following the strategies proposed by the PRISMA guidelines. It was identified that the methodology and results of the articles were heterogeneous. The hypoglycemic function was found to be mediated by multiple effects at the molecular level, including enzymatic inhibition, pancreatic β cells proliferation stimulation, and food intake-related genes regulation. These effects depend on several factors such as plant bioactive compounds content, extraction method, and characteristics of the organism that consumes it. Therefore, this review exhibits the necessity of further research, using established doses according to the bioactive compounds content in A. muricata.


The development and testing of information system for community nursing.
The paper presents the development and testing of information system (IS) for community nursing (CN). The goal of IS is to support CN practice and to encourage research and development in the field. The development was based on analysis of CN process. Principal functions of CN were analysed. The logical data model and corresponding user interface were designed. A special emphasis in the development process was put on testing in practice and users' training. The developed IS will: increase work efficiency, introduce process-oriented nursing doctrine, support integrated treatment of the subjects and enable data comparison and exchange. An important subsidary goal of the IS development and usage is the harmonisation of concepts and terminology used in Slovenia with those used in the EU. In this framework International Classification of Nursing Practice (ICNP) which was translated into Slovene was introduced and tested.


Comparison of color removal from reactive dye contaminated water by systems containing fungal biosorbent, active carbon and their mixture.
The adsorption of Everzol Black (EB) from synthetic aqueous solution onto active carbon (AC) and dried fungal biosorbent (Rhizopus arrhizus) was studied under the same experimental conditions. The effects of initial dye concentration, adsorbent dosage and contact time were examined at a batch-scale level. As an alternative to AC, fungus was investigated as a low-cost adsorbent for dye removal. The amount of EB adsorbed onto AC was lower compared with fungal biosorbent; dye adsorption capacity of AC and fungal biosorbent were 94.48 and 106.61 mg/g, respectively. The adsorbent dosage experiments showed that 4 g/L biosorbent removed 100% of EB (Co: 114.39 mg/L) after 2 hours. The results obtained from this study showed that biosorbent effectively removed reactive dye from dye-containing water in a short time period. Langmuir and Freundlich adsorption isotherm models were used for mathematical description of the biosorption equilibrium data; the Freundlich model was found to exhibit good fits to the experimental data. According to the Freundlich isotherm, the maximum dye adsorption capacities of AC and biosorbent were calculated as 344.82 and 357.14 mg/g, respectively. The Fourier transform infrared spectroscopy spectral analysis showed the involvement of functional groups for dye bindings.


The mechanosensory protein MEC-6 is a subunit of the C. elegans touch-cell degenerin channel.
Mechanosensory transduction in touch receptor neurons is believed to be mediated by DEG/ENaC (degenerin/epithelial Na+ channel) proteins in nematodes and mammals. In the nematode Caenorhabditis elegans, gain-of-function mutations in the degenerin genes mec-4 and mec-10 (denoted mec-4(d) and mec-10(d), respectively) cause degeneration of the touch cells. This phenotype is completely suppressed by mutation in a third gene, mec-6 (refs 3, 4), that is needed for touch sensitivity. This last gene is also required for the function of other degenerins. Here we show that mec-6 encodes a single-pass membrane-spanning protein with limited similarity to paraoxonases, which are implicated in human coronary heart disease. This gene is expressed in muscle cells and in many neurons, including the six touch receptor neurons. MEC-6 increases amiloride-sensitive Na+ currents produced by MEC-4(d)/MEC-10(d) by approximately 30-fold, and functions synergistically with MEC-2 (a stomatin-like protein that regulates MEC-4(d)/MEC-10(d) channel activity) to increase the currents by 200-fold. MEC-6 physically interacts with all three channel proteins. In vivo, MEC-6 co-localizes with MEC-4, and is required for punctate MEC-4 expression along touch-neuron processes. We propose that MEC-6 is a part of the degenerin channel complex that may mediate mechanotransduction in touch cells.


Effects of air pollution resulting from wire reclamation incineration on pulmonary function in children.
This study evaluated the effect of long-term air pollution resulting from wire reclamation incineration on pulmonary function in children. General physical examination and the determination of spirometric parameters, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and forced mid-expiratory flow (FEF25-75%) were conducted in 400 primary school children between ages 9 and 11 years who reside in one control and three polluted areas. A survey using ATS-DLD-78-C questionnaire indicated that there were no significant differences in their demographic characteristics among children in the four areas under study. Those who had nonrespiratory diseases that might affect pulmonary function and those who failed to perform spirometric measurements were excluded from the study; therefore, 382 children were included in data analysis. The results revealed that (1) the mean values of FVC and FEV1 (expressed as percentage of predicted values calculated from Polgar's equations) in the polluted areas were significantly lower than the nonpolluted area (p less than 0.05), and (2) the incidence of pulmonary function abnormality in the polluted areas was greater than that of the nonpolluted area (p less than 0.05). The results indicated that air pollution produced by wire reclamation incineration can impair children's pulmonary function.


Use of Molecular Diagnostic Tools for the Identification of Species Responsible for Snakebite in Nepal: A Pilot Study.
Snakebite is an important medical emergency in rural Nepal. Correct identification of the biting species is crucial for clinicians to choose appropriate treatment and anticipate complications. This is particularly important for neurotoxic envenoming which, depending on the snake species involved, may not respond to available antivenoms. Adequate species identification tools are lacking. This study used a combination of morphological and molecular approaches (PCR-aided DNA sequencing from swabs of bite sites) to determine the contribution of venomous and non-venomous species to the snakebite burden in southern Nepal. Out of 749 patients admitted with a history of snakebite to one of three study centres, the biting species could be identified in 194 (25.9%). Out of these, 87 had been bitten by a venomous snake, most commonly the Indian spectacled cobra (Naja naja; n = 42) and the common krait (Bungarus caeruleus; n = 22). When both morphological identification and PCR/sequencing results were available, a 100% agreement was noted. The probability of a positive PCR result was significantly lower among patients who had used inadequate "first aid" measures (e.g. tourniquets or local application of remedies). This study is the first to report the use of forensic genetics methods for snake species identification in a prospective clinical study. If high diagnostic accuracy is confirmed in larger cohorts, this method will be a very useful reference diagnostic tool for epidemiological investigations and clinical studies.


[Combined therapy with tricyclic and MAOI antidepressants in the treatment of resistant major depression].
This paper shows the results of associating tricyclic and MAOI antidepressants in the treatment of resistant major depression. Forty five patients from private practice with diagnosis of major depression according to DSM III R criteria, with negative response to separate tricyclic or MAOI treatment, were given both types associated. They improved without dangerous side effects.


Mandibular Canines with Two Roots and Two Root Canals: Case Report and Literature Review.
Usually, the mandibular canine only has one root and one root canal. However, there has been a noticeable increment in evidence showing variations in its morphology, such as the presence of two roots and two root canals. The aim of this article was to present a case of a mandibular canine with two roots and two root canals and to review the available literature on this anatomic variation. Root canal treatment of tooth #43 with such morphology was performed in a 47-year-old woman. Careful inspection of the preoperative radiograph indicated the presence of more than one canal. The 12-month follow-up showed normal periapical tissues, with no pain or tenderness. Literature review revealed that the overall prevalence of such root canal configuration is 5.7%, with a strong preference for female sex (87.5%). Although mandibular canines with two roots and two root canals are not common, clinicians should always anticipate the presence of possible variations. Therefore, timely diagnosis and meticulous exploration of such mandibular canines allow for planning of an individualized treatment protocol, tailored to their peculiar morphology, focused on avoiding excessive weakening or even perforation of the roots.


Research note: adolescents' perception of psychosis risk following cannabis consumption.
Cannabis consumption during adolescence has been associated with the onset of psychosis. In 2010, we examined adolescents' perception of this association. Adolescents (N = 583) from four Romanian urban high schools filled in psychosis proneness scales according to the risk they assigned to hypothetical adolescents described in vignettes. Target adolescent's frequency and age of first consumption were manipulated. Analysis of variance indicated a main effect of target's consumption frequency, but no effect of age of first consumption on psychosis risk perception. Participants' own consumption status acted as moderator. Results highlight the discrepancy between clinical research results and adolescents' perception of psychosis risk. The study's limitations are noted.


[Occurrence and detection of viruses in drinking water].
Viruses can pass disinfection steps of water treatment plants without being inactivated. Investigations during the last 15 years revealed repeatedly the presence of enteric viruses in finished water meeting standards for coliform bacteria. Methods for the detection of viruses in water which implicate their growth on specific cell cultures are very time consuming and do not cover many viral species. Molecular detection methods including PCR techniques may help in the development of alternate methods for virus detection particularly in drinking water which usually does not contain PCR inhibiting factors.


In vitro evaluation of a newly developed implantable artificial lung.
A prototype of an implantable artificial lung without a pump (Prototype II) has been tested. A commercially available membrane oxygenator, MENOX AL6000alpha (Dainippon Ink and Chemicals, Inc., Tokyo, Japan), was used as a basic model. The packing density of the hollow fiber was decreased in order to achieve low resistance through the blood pathway. The configuration of its housing was also re-designed using computational fluid dynamics (CFD). The first prototype, known as Prototype I, was already tested in a 15 kg pig, which showed excellent gas exchange with normal hemodynamics. A second prototype, Prototype II, has a larger membrane surface area than Prototype I. The device was evaluated for resistance through the blood path and gas transfer rate in an in vitro setting by the single pass method using fresh bovine blood. The resistance through the blood path of Prototype II was 2.7+- 0.7 mmHg/(L/min) at Q = 5L/min. The oxygen (O2) transfer rate was 178 +- 5.3 ml/min at Q = 5 L/min, V/Q = 3, and the carbon dioxide (CO2) transfer rate was 149 +- 28 ml/min at Q = 5 L/min, V/Q = 2 (Q: blood flow rate, V: sweep oxygen flow rate through the artificial lung). For the purpose of implantation, this prototype showed sufficiently low resistance in the pulmonary circulation with reasonable gas exchange.


Spectral stability of periodic waves in the generalized reduced Ostrovsky equation.
We consider stability of periodic travelling waves in the generalized reduced Ostrovsky equation with respect to co-periodic perturbations. Compared to the recent literature, we give a simple argument that proves spectral stability of all smooth periodic travelling waves independent of the nonlinearity power. The argument is based on the energy convexity and does not use coordinate transformations of the reduced Ostrovsky equations to the semi-linear equations of the Klein-Gordon type.


Airway management by physicians wearing anti-chemical warfare gear: comparison between laryngeal mask airway and endotracheal intubation.
To evaluate the ease with which successful insertion of a laryngeal mask airway can be performed in comparison with endotracheal intubation by medical personnel wearing chemical protective equipment. Anaesthetists and non-anaesthetists (each n = 20) participated in the prospective comparative trial in an animal laboratory. The time and success rates of laryngeal mask airway vs. endotracheal tube insertions were measured as performed on anaesthetized monkeys. The results showed that the laryngeal mask airway was inserted more rapidly than the endotracheal tube by both groups (3.6 s and 28.6 s, P < 0.0001). Failed intubation occurred in 35% (anaesthetists) vs. 55% (non-anaesthetists) (P = 0.17). In view of the 100% success rate of insertion even in unfavourable conditions, the possible role of the laryngeal mask airway in the scenario of a toxic mass casualty event should be considered.


Biobanked human foreskin epithelial cell sheets reduce inflammation and promote wound healing in a nude mouse model.
Human epithelial cell sheets (ECSs) are used to clinically treat epithelial conditions such as burns, corneal blindness, middle ear cholesteatoma and vitiligo. As a widely used material in clinic, there is little information on the biobanking of ECSs and its repair effect after storage. Two methods for biobanking foreskin ECSs were compared in a short term (7 days): 4-degree storage and programmed cryopreservation. Cell sheet integrity, viability, apoptosis, immunogenicity, mechanical properties and function were evaluated. In vivo, ECSs were directly transplanted to skin defect models and histological examination was performed at 1 week postoperatively. We successfully extracted human foreskin-derived primary epithelial cells and fabricated them into ECSs. Compared with 4-degree storage, programmed cryopreservation preserved the ECS structural integrity, enhanced the mechanical properties, decreased HLA-I expression, and increased cell viability and survival. An increased proportion of melanocytes with proliferative capacity remained in the cryopreserved sheets, and the undifferentiated epithelial cells were comparable to those of the fresh sheets. In vivo, cryopreserved ECSs could reduce inflammatory cell infiltration and promote connective tissue remodeling, epithelial cell proliferation and vascular regeneration. Programmed cryopreservation of ECSs was superior and more feasible than 4-degree storage and the cryopreserved ECSs achieved satisfying skin wound healing in vivo. We anticipate that the off-the-shelf ECSs could be quickly used, such as, to repair human epithelial defect in future.


Diabetes, Cardiovascular Disorders and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Body Burden in Czech Patients 50 Years After the Intoxication.
The correlation between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication and the parameters of metabolic impairment was examined in the last eight male survivors of 80 workers exposed to TCDD during the production of herbicides in a chemical factory in 1965-1967. Their median TCDD blood level was 112 (46-390) pg/g lipids, and the median TCDD body deposit was 3.9 (0.8-11.7) μg. This puts these patients into the most severely intoxicated group of subjects, according to back-calculated levels of TCDD. The median TCDD blood level in eight controls was 12 pg/g (<0.10 to 22.2 pg/g). Markers of metabolic impairment - diabetes, dyslipidaemia, arterial hypertension, carotid artery plaque, skin microvascular reactivity, eye fundus hypertensive angiopathy and history of coronary heart disease - were assessed and compared to a general male population of comparable age. Measured parameters compared with a population of comparable age were as follows: prevalence of diabetes (62.5% versus 17.6%), arterial hypertension (87.5% versus 71.8%), dyslipidaemia (87.5% versus 88.8%), history of coronary heart disease (62.5% versus 26.0%) and eye fundus hypertension angiopathy (50% versus 14%). All eight patients (100% versus 43%) developed plaques in carotid arteries, six had stenosis >50% and two had a carotid intervention (stenting or endarterectomy). Total cholesterol levels decreased compared to the earlier study this patient group in 2008, most likely due to a more intensive use of lipid-lowering drugs. Several metabolic parameters were higher (diabetes as much as 3.5-fold) in the group of severely TCDD-intoxicated subjects than in a general population of comparable age. This suggests that TCDD plays a role in the development of metabolic impairment and vascular changes.


Immortalization of human uterine leiomyoma and myometrial cell lines after induction of telomerase activity: molecular and phenotypic characteristics.
In vitro model systems for studying uterine leiomyomas are limited in that human-derived leiomyoma cells grow poorly in culture compared with normal myometrial cells and begin to senesce early, at approximately passage 10 in our studies. To our knowledge, a good in vitro human-derived cell culturing system for leiomyomas does not exist. In an attempt to fill this void, we have immortalized a uterine leiomyoma cell line by inducing telomerase activity, which allows cells to bypass their normal programmed senescence. Telomerase activity was induced by infecting the target (uterine leiomyoma and normal myometrial) cells with a retroviral vector containing hTERT, the gene for the catalytic subunit of telomerase. Subsequent analysis by RT-PCR and the telomeric repeat amplification protocol assay confirmed expression of the inserted gene and induction of telomerase activity in leiomyoma and myometrial cells. Analysis of cells for estrogen receptor-alpha and progesterone receptor proteins by Western blotting showed no change in expression of these proteins between the immortalized and parental leiomyoma and myometrial cells. Both immortalized and parental myometrial and leiomyoma cells expressed the smooth muscle-specific cytoskeletal protein alpha-actin and were negative for mutant p53 protein as evidenced by immunocytochemical staining. The immortalized leiomyoma and myometrial cells showed no anchorage-independent growth, with the exception of a small subpopulation of immortalized leiomyoma cells at a higher passage that did form two to three small colonies (per 50,000 cells) in soft agar. None of the immortalized cells were tumorigenic in nude mice. In conclusion, our data show the successful insertion of the hTERT gene into leiomyoma and myometrial cells and the immortalization of these cell lines without phenotypic alteration from the parental cell types (up to 200 population doublings). These cells should help to advance research in understanding the molecular pathways involved in the conversion of a normal myometrial cell to a leiomyoma cell and the mechanisms responsible for the growth of uterine leiomyomas. Answers to these questions will undoubtedly lead to the development of more effective treatment and intervention regimens for clinical cases of uterine leiomyoma.


A retrospective multi-center study of treatment, outcome, and prognostic factors in 34 dogs with disseminated aspergillosis in Australia.
Disseminated aspergillosis (DA) in dogs has a guarded prognosis and there is a lack of a gold standard treatment protocol. To retrospectively assess survival times and factors influencing survival times. Dogs diagnosed with DA from January 2007 to June 2017. Disseminated aspergillosis case data were retrieved from 13 Australian veterinary referral centers, with a diagnosis confirmed with culture or PCR. Factors influencing survival time after diagnosis were quantified using a Cox proportional hazards regression model. Thirty-four dogs met the study inclusion criteria. Twenty-two dogs were treated with antifungal treatment and 12 dogs received no antifungal treatment. Accounting for censoring of dogs that were either still alive on the date of data collection or were loss to follow-up, dogs treated with itraconazole alone (n = 8) had a median survival time (MST) of 63 (95% CI: 20-272) days compared to 830 (95% CI: 267-1259) days for the n = 14 dogs that received multimodal antifungal therapy ( χ 2 test statistic 8.6; df = 1; P < .01). The daily hazard of death (DHOD) for dogs with abnormally high serum creatinine concentration at the time of diagnosis was 7.4 (95% CI: 1.9-29) times that of dogs with serum creatinine within the reference interval. Serum creatinine concentration at the time of diagnosis is a useful prognostic indicator for survival after a diagnosis of DA. The MST for dogs treated with multimodal antifungal therapy is longer than itraconazole alone and warrant further investigation (P < .01).


The quest for culturally sensitive health-care systems in Scotland: insights for a multi-ethnic Europe.
Health systems are serving increasingly ethnically diverse populations. This requires cultural sensitivity/competence. Sharing insights from multi-ethnic countries is important. Insights from Scotland, discussed in this paper, include that the creation of culturally sensitive health systems requires reduction of stigma associated with immigration and immigrants; the wider use of ethnicity alongside, or instead of, race, country of birth, nationality and immigrant status; prioritization of actions using the concept of inequity; understanding that meeting the needs of minorities improves health systems for everyone; more use of anti-discriminatory laws to drive national policy and locality planning; research to assess needs and effectiveness; evaluation of processes and outcomes; institutional and professional sincerity and confidence, and monitoring that policies are implemented and working. Even when conditions are favourable, as in Scotland, the challenges are many, implementation is tough and timescales long. Scotland's record is, nonetheless, comparatively strong in Europe. Sharing experience across national boundaries should spur on progress globally.


AIDS and drug rationing.
Financial shortage in resource-limited and poor countries restricts treatment in HIV-infected patients especially in poor countries. Higher HIV prevalence in poorer countries makes drug rationing a real concern. Different countries solve the problem with different methods regarding WHO guidelines, but fairness and equity should be a major consideration in drug rationing. This paper is aimed at reviewing different strategic approaches to drug rationing in AIDS treatment and then discusses pharmacists' role. In conclusion, there is no fair and equitable strategy, and in each society, cultural, ethical and socioeconomic issues along with considering a critical role for pharmacists must be taken into account.


Prevalence of medication adherence and its associated factors among patients with noncommunicable disease in rural Puducherry, South India - A facility-based cross-sectional study.
Trends in morbidity and mortality due to noncommunicable diseases (NCDs) are rising because of poor control status. Medication nonadherence is one of the most common and modifiable causes of inadequate control status. To determine the prevalence of drug adherence among patients with NCD in rural Puducherry. A facility-based cross-sectional study was done among 260 patients with NCD receiving treatment from rural primary health center in Puducherry during February and March 2018. Information regarding sociodemographic profile and household was collected using pretested semi-structured questionnaire. Morisky Medication Adherence Scale was done to assess the adherence. We calculated adjusted prevalence ratios (aPRs) to identify the factors associated with medication adherence. Among the 260 participants, 42.7% belonged to elderly age group; 66.2% were females; 44% did not have any formal education; 70% were unemployed. The majority were suffering from hypertension (71.2%) followed by diabetes (56.2%). This study found that almost one-third (32.7%) of the study participants were not properly adherent to medications. Elderly [aPR 2.51 95% confidence interval (CI): 1.70-3.70] and female participants (aPR 1.64 95% CI: 1.04-2.58) were found to have more chance being nonadherent to medications after adjusting for possible confounding variables. This study reported that almost one-third of the study participants were nonadherent to medications. Elderly age group and female gender were found to be the determinants of nonadherence. Corrective measures need to be started at patient level first by motivating and educating them regarding the importance of drug intake.


Oxidation of NAD(P)H in a Reconstituted Spinach Chloroplast Preparation Using Ascorbate and Hydrogen Peroxide.
The conversion of fructose-1,6-bisphosphate to glycerate-3-phosphate (PGA) was studied in a reconstituted spinach (Spinacia oleracea L.) chloroplast preparation to determine whether a chloroplast-localized NAB(P)H-oxidizing system (Kow, Smyth, Gibbs 1982 Plant Physiol 69: 72-76 with substrates of ascorbate, NAD(P)H, and H(2)O(2) could serve as a coupling enzyme in the recycling of NAD(P)H. The rate of PGA formation was monitored as an indicator of NAD(P) generation. With NAD as a cofactor, ascorbate enhanced PGA formation, and an additional increase resulted upon addition of glucose-glucose oxidase, a H(2)O(2)-generating enzyme. This increase in PGA formation due to H(2)O(2) was eliminated by the addition of catalase. With NADP and ferredoxin as cofactors, the recycling of NADP apparently was catalyzed both by ferredoxin-NADP reductase coupled to O(2) and by the NAD(P)H-oxidizing system.It was concluded that the oxidation of NAD(P)H by a system using ascorbate and H(2)O(2) can serve as a means of recycling NAD(P)H but that another reaction involving ascorbate and NAD(P)H may also function in the spinach chloroplast.


Consecutive exotropia after correction of hyperopia.
A study was done of 22 children in whom exotropia developed following correction of hyperopia because of accommodative esotropia that had not been corrected surgically. The early onset of esotropia and high degree of hyperopia seemed to predispose to the spontaneous development of exotropia. Reduction of the hyperopia by 50% to 60% resulted in satisfactory realignment of the eyes and some form of binocularity.


[Left-sided gallbladder].
Transposition of the gallbladder to the left side without situs inversus viscerum is rare. These gallbladders are almost always situated under the left lobe of the liver between the IV and III segments or on the III segment to the left of the falciform ligament. One left positioned gallbladder was found in a consecutive series of 2536 patients undergoing microlaparotomy cholecystectomy for symptomatic gallstone disease in the "Moritz Kaposi" Teaching Hospital between 1990 and 2000, a prevalence of 0.04 per cent. Despite of the abnormal position of the gallbladder, the biliary pain experienced by the patient was on the right side. Preoperative diagnosis of this anomaly was not made in this patient despite preoperative sonography. The cystic duct may open in the common hepatic duct either side. In this anomaly safe microlaparotomy cholecystectomy or laparoscopic cholecystectomy can be performed.


Otolaryngology Program Director, House-Staff, and Student Opinions: Step 1 Pass/Fail Score Reporting.
To compare otolaryngology program director, house-staff, and medical student perspectives on the score reporting change of USMLE Step 1 to pass/fail. Separate electronic surveys were sent to program directors of ACGME-accredited otolaryngology programs (Cronbach's alpha = .87), otolaryngology house-staff (Cronbach's alpha = .91), and medical students interested in otolaryngology (Cronbach's alpha = .76). Among the 51 otolaryngology program directors that completed the survey (response rate of 46.8%), 17.6% favored reporting USMLE Step 1 as pass/fail. A majority believed the reporting change would make it more difficult to screen (74.5%) and objectively compare applicants (82.4%). Step 2 CK scores will be more important to most program directors due to the reporting change (83.7%). Of the 93 house-staff that completed surveys, most did not favor the reporting change (61.3%). Over half (54.0%) of the 87 medical students that completed surveys did not support the scoring change, and most (65.5%) did not feel that it would decrease anxiety around residency applications (65.5%). Most house-staff and medical students felt that the scoring change would put non-U.S. MD students at a disadvantage (65.6% of house-staff, 69.8% of medical students). Most survey respondents do not agree with the decision to report Step 1 as pass/fail. Despite its intended goals, most do not believe pass/fail Step 1 reporting will improve medical student well-being and believe it will put certain student populations at a greater disadvantage.


Depression alters "top-down" visual attention: a dynamic causal modeling comparison between depressed and healthy subjects.
Using functional magnetic resonance imaging (fMRI), we recently demonstrated that nonmedicated patients with a first episode of unipolar major depression (MDD) compared to matched controls exhibited an abnormal neural filtering of irrelevant visual information (Desseilles et al., 2009). During scanning, subjects performed a visual attention task imposing two different levels of attentional load at fixation (low or high), while task-irrelevant colored stimuli were presented in the periphery. In the present study, we focused on the visuo-attentional system and used "Dynamic Causal Modeling" (DCM) on the same dataset to assess how attention influences a network of three dynamically-interconnected brain regions (visual areas V1 and V4, and intraparietal sulcus (P), differentially in MDD patients and healthy controls. Bayesian model selection (BMS) and model space partitioning (MSP) were used to determine the best model in each population. The best model for the controls revealed that the increase of parietal activity by high attention load was selectively associated with a negative modulation of P on V4, consistent with high attention reducing the processing of irrelevant colored peripheral stimuli. The best model accounting for the data from the MDD patients showed that both low and high attention levels exerted modulatory effects on P. The present results document abnormal effective connectivity across visuo-attentional networks in MDD, which likely contributes to deficient attentional filtering of information.


Lack of adaptation to severe malnutrition in elderly patients.
Sarcopenia is a common feature in the healthy elderly. However, little is known on age-related modifications of body composition in malnourished patients. The aims of this cross-sectional study were to evaluate the effects of aging per se on body composition and resting energy expenditure (REE) in malnourished patients. Ninety-seven non-stressed patients referred for chronic malnutrition (C-reactive protein <5 mg/l) were separated into two groups: middle-aged (26 female, 19 male, 48+/-15 yr), and elderly (26 female, 26 male, 79+/-6 yr). Body composition was assessed by bioelectrical impedance analysis and REE by indirect calorimetry. In middle-aged patients, body composition remained stable between moderate (body-mass index [BMI; in kg/m(2)] 16-18.5) and severe (BMI < 16) malnutrition, with similar values of fat-free mass (FFM), body cell mass (BCM) and fat mass (FM) as percentages of body weight, whereas in elderly patients malnutrition occurred at the expense of FFM and BCM, with unchanged FM absolute values. REE/FFM values remained stable in middle-aged patients at every stage of malnutrition, whereas they increased in elderly patients along with their degree of malnutrition. In multivariate analysis, both body composition and REE/FFM were influenced by sex, age, BMI and mid-arm circumference. Compared to younger patients, weight loss in the elderly leads to cachexia, with a preferential loss of FFM and BCM that may participate in the more severe outcomes observed in these patients. They also show elevated REE/FFM values that induce higher energy needs.


Adsorption and separation of organic six-membered ring analogues on neutral Cd(II)-MOF generated from asymmetric schiff-base ligand.
A new CdL(2)-MOF was synthesized based on an asymmetric Schiff-base ligand LH, which is obtained by condensation of 5-formyl-8-hydroxyquinoline and 3-pyridinecarboxylic acid hydrazide. A series of organic six-membered ring analogues, namely, 1,4-dioxane, cyclohexane, cyclohexene, benzene, cyclohexanone, and cyclohexanol, can be absorbed by the CdL(2) porous framework in liquid-phase to generate G(n)⊂CdL(2) (n = 1 and 2) host-guest complexes. In addition, the CdL(2) host framework displays different affinity for these six-membered ring substrates and can effectively separate them under mild conditions (i.e., 1, 4-dioxane > cyclohexane > cyclohexene and benzene > cyclohexanone > cyclohexanol). The empty CdL(2) displays strong green-yellow emission. Furthermore, these host-guest systems show an interesting guest-driven luminescent emission, and the emission intensities of these guest-loaded complexes are effectively reduced.


Clinical use of a rapid collagen binding assay for von Willebrand factor cleaving protease in patients with thrombotic thrombocytopenic purpura.
A simple collagen binding assay (CBA) for measuring activity of the von Willebrand factor cleaving protease in clinical samples is described, and results of fifty masked plasmapheresis samples rom patients with TTP/HUS and other diseases are presented. There was 97.5% concordance between the CBA and a multimer gel assay. The CBA identified low protease activity in 78% of patients who had a clinical syndrome consistent with TTP/HUS and in 2 of 10 sick controls, giving it a positive predictive value of 0.94. The heterogeneity regarding the presence or absence of vWF protease activity in patients with TTP/HUS was confirmed by finding a low negative predictive value of 0.50 with the CBA. The CBA detected inhibitors of the protease in 26 of 29 patients (90%) with TTP/HUS and low protease activity levels. The CBA is a useful clinical assay for examining von Willebrand factor protease activity and detecting inhibitors against the protease.


Fish-oil supplementation alters numbers of circulating endothelial progenitor cells and microparticles independently of eNOS genotype.
Emerging cellular markers of endothelial damage and repair include endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs), respectively. Effects of long-chain (LC) n-3 (omega-3) polyunsaturated fatty acids (PUFAs) and the influence of genetic background on these markers are not known. We investigated effects of fish-oil supplementation on both classical and novel markers of endothelial function in subjects prospectively genotyped for the Asp298 endothelial nitric oxide synthase (eNOS) polymorphism and at moderate risk of cardiovascular disease (CVD). A total of 84 subjects with moderate risk of CVD (GG: n = 40; GT/TT: n = 44) completed a randomized, double-blind, placebo-controlled, 8-wk crossover trial of fish-oil supplementation that provided 1.5 g LC n-3 PUFAs/d. Effects of genotype and fish-oil supplementation on the blood lipid profile, inflammatory markers, vascular function (by using peripheral artery tonometry), and numbers of circulating EPCs and EMPs (by using flow cytometry) were assessed. There was no significant effect of fish-oil supplementation on blood pressure, plasma lipids, or plasma glucose, although there was a trend (P = 0.069) toward a decrease in the plasma triglyceride concentration after fish-oil supplementation compared with placebo treatment. GT/TT subjects tended to have higher concentrations of total cholesterol and low-density lipoprotein cholesterol, but vascular function was not affected by either treatment or eNOS genotype. Biochemical markers of endothelial function were also unaffected by treatment and eNOS genotype. In contrast, there was a significant effect of fish-oil supplementation on cellular markers of endothelial function. Fish-oil supplementation increased numbers of EPCs and reduced numbers of EMPs relative to those with placebo treatment, which potentially favored the maintenance of endothelial integrity. There was no influence of genotype for any cellular markers of endothelial function, which indicated that effects of fish-oil supplementation were independent of eNOS genotype. Emerging cellular markers of endothelial damage, integrity, and repair appear to be sensitive to potentially beneficial modification by dietary n-3 PUFAs. This trial was registered at www.controlled-trials.com/isrctn as ISRCTN76272133.


A serine hydroxymethyltransferase from marine bacterium Shewanella algae: Isolation, purification, characterization and l-serine production.
Currently, l-serine is mainly produced by enzymatic conversion, in which serine hydroxymethyltransferase (SHMT) is the key enzyme, suggesting the importance of searching for a SHMT with high activity. Shewanella algae, a methanol-utilizing marine bacterium showing high SHMT activity, was selected based on screening bacterial strains and comparison of the activities of SHMTs. A glyA was isolated from the S. algae through thermal asymmetric interlaced PCR (TAIL-PCR) and it encoded a 417 amino acid polypeptide. The SaSHMT, encoded by the glyA, showed the optimal activity at 50°C and pH 7.0, and retained over 45% of its maximal activity after incubation at 40°C for 3h. The enzyme showed better stability under alkaline environment (pH 6.5-9.0) than Hyphomicrobium methylovorum GM2's SHMT (pH 6.0-7.5). The SaSHMT can produce 77.76mM of l-serine by enzymatic conversion, with the molecular conversion rate in catalyzing glycine to l-serine being 1.41-fold higher than that of Escherichia coli. Therefore, the SaSHMT has the potential for industrial applications due to its tolerance of alkaline environment and a relatively high enzymatic conversion rate.


Effects of antimicrobial drugs on the cytotoxicity of epirubicin, bleomycin, estramustine and cisplatin.
The effect of concomitant treatment with different antibiotics on the cytotoxicity of epirubicin, bleomycin, estramustine and cisplatin was studied in vitro on fibroblasts (V79) and two cancer cell lines (colon cancer HT29 and lung cancer P31). The cell lines were propagated under standard tissue culture conditions and evaluated as the number of surviving cell clones in comparison to untreated controls. Fifteen commonly used antibiotics were tested and thirteen of these were found to modify the cytotoxic effect in one or several of the combinations tested. One antibiotic agent could affect the toxicity of different cytostatics in opposite directions and there were marked differences between the cell lines tested. Only in one of the situations, the combination of bleomycin and ceftazidim, did the antibiotic cause opposite effects on the toxicity of a cytostatic when comparing fibroblasts and carcinoma cells. A most impressive observation was the pronounced increase in cisplatin-induced cytotoxicity by amphotericin B. In conclusion, the results suggest that antibiotics can interact with the cytotoxicity of antitumoral drugs but that the feature of this interaction is seemingly an erratic phenomenon. Further studies are certainly justified, especially regarding the effects of amphotericin B and its mechanisms in enhancing the cytotoxicity of cisplatin.


Electron micrography and x-ray study of dip-lacquered LiF (220).
It has been proposed to use the 220 reflection of LiF with a multilayer deposited upon the top for simultaneous spectroscopy near Fe-k and O-k and below the C-k absorption edge (284 eV) in x-ray astronomy. We demonstrate that a substantial reduction of surface roughness is obtained by dip lacquering state-of-the-art polished LiF(220) surfaces. Using a microdensitometer analysis of electron micrographs of surface replicas and x-ray reflection, we have measured approximately 10-A rms roughness of Au-coated dip-lacquered LiF(220) crystals, as opposed to approximately 60 A measured on the bare LiF(220) crystal surface.


Noninvasive imaging of dendritic cell migration into lymph nodes using near-infrared fluorescent semiconductor nanocrystals.
Effective tracking of immunotherapeutic cells is essential for monitoring the migration of injected cells to the target tissue. Here we report the use of near-infrared (NIR) -emitting fluorescent semiconductor nanocrystals, called quantum dots (QDs), for noninvasive in vivo tracking of dendritic cell (DC) migration into lymph nodes. The effect of QDs on DC viability and maturation was systematically investigated using MTT assays and FACS analysis. We found that the labeling of DCs with QDs had no effect on DC phenotype or maturation potential. Cytokine and migration assays revealed that there were no significant changes in either cytokine production or chemokine-dependent migration of QD-labeled DCs relative to unlabeled cells; in both labeled and unlabeled cells, cytokine production and migratory capacity was increased by stimulation with lipopolysaccharide. Furthermore, QDs did not influence allogenic naive T cell activation or uptake of exogenous antigens. Notably, we also demonstrated that it was possible to track QD-labeled DCs injected into the footpad into popliteal and inguinal lymph nodes using NIR fluorescence. Taken together, our protocols establish the potential of noninvasive in vivo imaging of NIR-emitting QDs for tracking immunotherapeutic cells.


Animal model for the absorption of lipophilic substances from tear fluid by the epithelium of the nasolacrimal ducts.
To compare the nasolacrimal tissues of several species to see how closely they resemble the human and to measure nasolacrimal absorption of a substance, to show that an absorption pathway exists for substances placed in the external eye, other than directly through the cornea or conjunctiva. The nasolacrimal systems of six different vertebrates were investigated by light microscopy to find a species with a nasolacrimal system comparable to that of humans, for use in absorption experiments. In addition to primates, rabbits were revealed by histology to have a lacrimal system closely comparable to that of humans. The rabbit lacrimal system had a stratified epithelium consisting of two layers. Subepithelially, the lamina propria was composed of two strata: loose connective tissue containing elastic fibers and lymphatic cells and a rich venous plexus comparable to a cavernous body. Rabbits were therefore chosen for the absorption experiments. (3)H-cortisol was dropped into the eyes of female rabbits. After 21, 43, or 146 minutes, the rabbits were killed, the blood collected, and the nasolacrimal systems prepared and embedded for histologic examination. Serum was obtained from the clotted blood, and radioactivity was counted. Autoradiographs of sections of rabbit nasolacrimal duct were also prepared. Uptake of radioactivity into the serum was high and increased with time. After 21 minutes, maximum incorporation of the applied radioactivity into the blood the level was 7.1%; after 43 minutes, 12.4%; and after 146 minutes, 15.5%. Transport of radioactivity was visualized in autoradiographs of rabbit nasolacrimal systems. (3)H-cortisol is incorporated from the nasolacrimal ducts into the blood of rabbits. The comparable morphology of rabbits and humans suggests that absorption of cortisol would also take place in humans. Future investigations of the nasolacrimal passage are needed to understand whether absorption of normal tear fluid components in the nasolacrimal ducts is a physiological function that also plays a role in pathologic conditions such as dry eye. The similarities between rabbit and human nasolacrimal ducts support the use of the rabbit for such studies.


DIX domain containing 1 (DIXDC1) modulates VEGFR2 level in vasculatures to regulate embryonic and postnatal retina angiogenesis.
In sprouting angiogenesis, VEGFR2 level is regulated via a fine-tuned process involving various signaling pathways. Other than VEGF/VEGFR2 signaling pathway, Wnt/ β-catenin signaling is also important in vascular development. However, the crosstalk between these two signaling pathways is still unknown to date. In this study, we aimed to investigate the role of DIX domain containing 1 (DIXDC1) in vasculature, facilitating the crosstalk between VEGF/VEGFR2 and Wnt/ β-catenin signaling pathways. In mice, DIXDC1 deficiency delayed angiogenesis at the embryonic stage and suppressed neovascularization at the neonatal stage. DIXDC1 knockdown inhibited VEGF-induced angiogenesis in endothelial cells in vitro by downregulating VEGFR2 expression. DIXDC1 bound Dishevelled Segment Polarity Protein 2 (Dvl2) and polymerized Dvl2 stabilizing VEGFR2 protein via its direct interaction. The complex formation and stability of VEGFR2 was potentiated by Wnt signaling. Moreover, hypoxia elevated DIXDC1 expression and likely modulated both canonical Wnt/β-catenin signaling and VEGFR2 stability in vasculatures. Pathological angiogenesis in DIXDC1 knockout mice was decreased significantly in oxygen-induced retinopathy (OIR) and in wound healing models. These results suggest that DIXDC1 is an important factor in developmental and pathological angiogenesis. We have identified DIXDC1 as an important factor in early vascular development. These results suggest that DIXDC1 represents a novel regulator of sprouting angiogenesis that links Wnt signaling and VEGFR2 stability and may have a potential role in pathological neovascularization.


ABO and Rh(D) blood group frequencies in the Ards Peninsula, northeastern Ireland: evidence for the continuing existence of a major politico-religious boundary.
Data are presented on the ABO and Rh(D) frequencies of 1685 individuals living in the Ards Peninsula, northeastern Ireland. Previous investigations based on surname analysis and linguistic studies showed a basic north-south population divide that could be traced back at least to the early seventeenth century. The current survey indicates the continuation of this divide, which is coincident with known patterns of religious persuasion.


Multicenter evaluation of a nonweekend reading schedule for radiometric pyrazinamide susceptibility testing of Mycobacterium tuberculosis.
Pyrazinamide (PZA) is an integral component of the short-course chemotherapy regimen for tuberculosis. The BACTEC 460TB PZA susceptibility test for Mycobacterium tuberculosis with a daily (D) reading schedule has been available for more than 10 years, but weekend laboratory staffing is necessary. A nonweekend (NW) reading schedule has not been validated in a multicenter study. This prospective multicenter study compares the interlaboratory reproducibility of PZA susceptibility results by following both the D and NW schedules. A total of 181 cultures were shared among four laboratories. Isolates were selected based on resistance or borderline resistance to at least one streptomycin-isoniazid-rifampin-ethambutol drug or PZA. One laboratory used a D reading schedule, and three laboratories used a NW schedule. Both reading schedules are based on the standard BACTEC 460TB PZA protocol. With the NW schedule, the growth index (GI) is not available for test interpretation on Saturday, Sunday, and Monday. Of the 181 shared cultures, 154 were found to be susceptible by all laboratories, 19 were found to be resistant, and 8 had discordant results. The overall pairwise interlaboratory agreement was 97.7%. The discrepancies were not associated with the type of reading schedule used. However, the median control GI was significantly higher for the NW schedule (321) than for the D schedule (259) (P < 0.0001) although results were available on average in about 7 days from setup for both schedules. These results show that the NW schedule is a suitable alternative for laboratories that do not read and interpret PZA susceptibility tests on weekends.


Characterization of the enzyme responsible for nopaline and ornaline synthesis in sunflower crown gall tissues.
Extracts prepared from sunflower (Helianthus annuus L.) crown gall tissues induced by Agrobacterium tumefaciens strains C58 and T37 (nopaline utilizers) catalyze the synthesis of nopaline and ornaline. These compounds are not synthesized in extracts of crown gall tissues induced by strains B6, 15955 (octopine utilizers), and AT1 (utilizes neither octopine nor nopaline) or in extracts of habituated sunflower callus. Both synthetic activities require NADPH, alpha-ketoglutarate, and either arginine or ornithine; histidine and lysine will not substitute. Incorporation of arginine or ornithine into product is inhibited by the other substrate but not by histidine or lysine. On the basis of inhibition and K(m) data, both activities appear to be catalyzed by one enzyme and the same enzyme is apparently present in crown gall tissues induced by strains C58 and T37.


[Chronic hypercapnia at rest or exercise-induced and ventilatory patterns in patients suffering from chronic obstructive bronchopulmonary disease].
The authors review the recent literature on hypercapnia at rest and on exertion in patients suffering from chronic airflow obstruction. At rest, the data in the literature has shown that for varying degrees of airflow obstruction, chronic hypercapnic patients show similar occlusion pressures to normocapnic patients. (The occlusion pressure is an index of the amplitude of neuro-muscular signals coming from the respiratory centre). However, their respiratory profile is characterised by a smaller tidal volume due to a reduction of the inspiratory time and often of a more rapid respiratory rate at a lower minute ventilation (VE). This pattern alone could explain CO2 retention by alveolar hypoventilation. On effort, various authors have shown that hypercapnic patients, or those becoming so during exercise, differ from normals by adopting a ventilatory pattern characterised by a reduction in ventilation linked to their airflow obstruction and a smaller tidal volume. The limited increase in tidal volume on effort is dependent on the duration of inspiration and the reduction of vital capacity and inspiratory capacity. As at rest, the two populations cannot be distinguished in terms of occlusion pressure.


Feasibility and Acceptability of a Dietary Intervention to Reduce Salt Intake and Increase High-Nitrate Vegetable Consumption in Malaysian Middle-Aged and Older Adults with Elevated Blood Pressure: Findings from the DePEC-Nutrition Trial.
The DePEC-Nutrition trial is a complex dietary and behavioural intervention of salt intake reduction combined with increased high-nitrate vegetable consumption among Malaysian middle-aged and older adults with elevated blood pressure. This study aimed to assess the feasibility and acceptability of the trial. Participants were recruited from the South East Asia Community Observatory (SEACO) database and randomised into one of four groups: (1) low salt; (2) high-nitrate vegetable; (3) combined high-nitrate vegetable and low salt; and (4) control. The intervention included a combination of group counselling sessions, information booklets, reinforcement videos and text messages to modify dietary behaviour. The primary outcomes evaluated were the measures of feasibility and acceptability of (1) recruitment, follow-up attendance and retention; (2) data collection procedures and clinical outcome measures; and (3) individual and combined multi-modal dietary interventions. A total of 74 participants were recruited, and the 10-month retention rate was 73%. Data collection procedures were acceptable with minimal missing data. All intervention strategies were feasible and acceptable, with group counselling being the most acceptable strategy. This study provides important insights into improving the screening process of participants, facilitating their access to the research facilities and refining the measurement protocols and dietary recommendations, which are instrumental in formulating the design of a full-scale definitive DePEC-Nutrition trial.


[Madreporic hydroxyapatite granulates for filling bone defects].
Two macrocrystalline madreporic granular hydroxyapatite implants of different size range (single crystal size within both implants 1-3 microns) were implanted for 7, 28, 84 and 168 days into the trabecular bone of the distal femur epiphysis of rabbits. Both materials were investigated histologically. For testing of granular materials a new animal model has been developed. The drill hole was closed by reimplantation of an autologeous chondrocortical tissue slice to prevent loss of particles into the knee-joint. Both of the granular materials tested developed increasing bone bonding from the 7th day on to outer surfaces and pore surfaces. The degradation of both of the materials affected the superficial implant layers in soft-tissue interfaces exclusively and was mainly due to passive processes, e.g. leaching, fragmentation of granules after crack-production, particulate degradation and subsequent phagocytosis of liberated implant particles by macrophages and foreign body giant cells. Zones of superficial implant degradation were bonded partially to bone a second time. A possible low-degree, active superficial degradation by foreign body giant cells is discussed. Osteoclasts of typical morphology as being observed on other hydroxyapatite implant surfaces were not demonstrated. This was related to the low degradation rate of the implants. Both of the granular materials tested are useful in filling bone defects. A guided tissue regeneration due to partial implant degradation and subsequent bone formation seems to be impossible since the degradation rate of the materials is too low.


Risk Factors of Vitamin D Deficiency in Chinese Ischemic Stroke Patients: A Cross-Sectional Study.
Lower serum vitamin D has been reported to be associated with stroke. This study aimed to analyze the risk factors of vitamin deficiency in Chinese stroke patients, and further analyze its impact in different gender and their clinical variables. 982 stroke patients were enrolled. Laboratory parameters such as serum vitamin D, apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB), ApoA-I/ApoB, cholesterol (CH), fibrinogen (FIB), blood glucose (Glu), high-density lipoprotein (HDL), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were collected and recorded. The severity of stroke was assessed by National Institute of Health Stroke Scale (NIHSS) score. Based on their serum vitamin D level, patients were divided into three groups: Vitamin D deficiency (<50 nmol/L), vitamin D insufficiency (≥50-75 nmol/L) and vitamin D sufficiency (≥75 nmol/L) and differences were compared among the three groups. Statistical analyses were done to assess the risk factors for serum vitamin D deficiency in our ischemic stroke patients. Gender, NIHSS, and FIB showed significant differences among the vitamin D groups (P < 0.001 ∼ P = 0.002). The female gender (OR = 2.422, P < 0.001), severity of stroke using NIHSS (OR = 1.055, P = 0.008) and FIB (OR = 1.256, P = 0.005) were risk factors of vitamin D deficiency in ischemic stroke patients. In subgroup analysis, NIHSS was significantly associated with vitamin D deficiency in the male group (OR = 1.087, P = 0.002) and higher FIB group (OR = 1.078, P = 0.001). The female gender, severity of stroke using NIHSS and FIB were risk factors for vitamin D deficiency in our incident stroke patients. NIHSS was more sensitive to vitamin D deficiency in male ischemic stroke patients. Besides, under higher FIB circumstance, the increasing NIHSS score was more related to the vitamin D deficiency. Levels of vitamin D in patients with ischemic stroke should be well monitored during the disease cascade.


Conjunctiva philophthalmosis: a case report in Thailand.
A 31-year-old Thai woman, a resident of Mapthaphut, Rayong Province, eastern Thailand, attended Rayong Provincial Hospital after suffering from consistent irritation of the eye for 5 days. Examination conducted by an ophthalmologist revealed a small worm moving on the conjunctiva of the right eye. The worm was removed and sent for identification. It was 2.9 mm in length, elongated oval, pharynx very large, ceca end close to the excretory pore, genital pore opens in front of the ventral sucker at the cecal bifurcation; it was identified as Philophthalmus sp., a trematode that parasitizes the eyes of birds. This is the first human case of Philophthalmus infection in Thailand.


Three-dimensional kinematics at the ankle joint complex in rheumatoid arthritis patients with painful valgus deformity of the rearfoot.
To evaluate the three-dimensional (3D) kinematics of the ankle joint complex (AJC) in rheumatoid arthritis (RA) patients with painful valgus deformity of the rearfoot. Fifty patients with RA underwent gait analysis using electromagnetic tracking techniques to measure 3D kinematics at the AJC under barefoot and shod walking conditions. Three axial rotations (dorsiflexion/plantarflexion, inversion/eversion and internal/external rotation) were measured during the gait cycle, and the angular positions at key gait events, range of motion and the motion: time integral were measured. Descriptive and analytical comparisons were made with normative data derived from a sex- and age-matched population (n=45). AJC dysfunction in RA was characterized by excessive eversion motion (within an eversion range) and no inversion motion through the neutral joint position for the subtalar component of the joint complex, in both barefoot and shod walking conditions. Motion was coupled such that internal rotation of the leg relative to the rearfoot was greater than normal. AJC motion was different for all rotations between barefoot and shod conditions, but in both situations there were statistically significant between-group differences in the motion:time integral for inversion/eversion (barefoot, P<0.0001; shod, P<0.0001) and external/internal rotation (barefoot, P<0.0001; shod, P<0.0001). There were no statistically significant differences between RA and normative data for dorsiflexion/plantarflexion motion under barefoot (P=0.16) and shod (P=0.50) walking conditions. Painful valgus deformity of the rearfoot is associated with changes in the 3D kinematics affecting eversion at the AJC and internal rotation of the leg, both when walking barefoot and in shoes.


Intracranial Hypotension Syndrome: The Importance of Neurointensive Care.
Surgical procedures involving the spine can result in various complications, including vascular, nerve root and dura mater injury, surgical wound infection, and hematoma formation. Unintentional durotomy is a frequent complication of these procedures (up to 17%). Two clinical cases are reported in which the occurrence of epileptiform activity in the form of generalized tonic-clonic seizures after instrumentation of the dorsal and lumbar spine raised suspicion of cerebrospinal fluid (CSF) fistula. In both cases, the diagnostic suspicion and early approach allowed for the adoption of a timely medical and surgical plan, with the aim of reducing the volume of lost CSF as well as the potential neurological dysfunction resulting from this surgical complication.


[Multiple primary cancers associated with gynecologic malignancies].
Seventeen multiple primary cancers including 16 double cancers and one triple cancer were found in 316 patients with gynecologic malignancies who were treated in our department from 1984 to 1988. All pathologic slides but one were reviewed, and cases with possible metastasis or recurrence were not included in this study. The incidence of multiple primary cancers in gynecologic malignancies was 5.4%. Multiple primary cancers were encountered in 4.4% of 205 cervical cancers (including carcinoma in situ), 15.2% of 33 endometrial cancers, and 8.6% of 58 ovarian cancers (including low potential malignancy), respectively. The most frequent sites of other cancers were seen in the large intestine and rectum (5/17), breast (4/17), and gynecologic organs (3/17). Higher incidences were seen in our study that in those in domestic literature. This is probably because detailed anamnesis and gastrointestinal series were obtained in most gynecologic malignancies (especially in endometrial or ovarian cancer).


Establishing a composite neonatal adverse outcome indicator using English hospital administrative data.
We adapted a composite neonatal adverse outcome indicator (NAOI), originally derived in Australia, and assessed its feasibility and validity as an outcome indicator in English administrative hospital data. We used Hospital Episode Statistics (HES) data containing information infants born in the English National Health Service (NHS) between 1 April 2014 and 31 March 2015. The Australian NAOI was mapped to diagnoses and procedure codes used within HES and modified to reflect data quality and neonatal health concerns in England. To investigate the concurrent validity of the English NAOI (E-NAOI), rates of NAOI components were compared with population-based studies. To investigate the predictive validity of the E-NAOI, rates of readmission and death in the first year of life were calculated for infants with and without E-NAOI components. The analysis included 484 007 (81%) of the 600 963 eligible babies born during the timeframe. 114/148 NHS trusts passed data quality checks and were included in the analysis. The modified E-NAOI included 23 components (16 diagnoses and 7 procedures). Among liveborn infants, 5.4% had at least one E-NAOI component recorded before discharge. Among newborns discharged alive, the E-NAOI was associated with a significantly higher risk of death (0.81% vs 0.05%; p<0.001) and overnight hospital readmission (15.7% vs 7.1%; p<0.001) in the first year of life. A composite NAOI can be derived from English hospital administrative data. This E-NAOI demonstrates good concurrent and predictive validity in the first year of life. It is a cost-effective way to monitor neonatal outcomes.


Materials management's role in product line development.
Product line management and product line cost accounting are terms that are appearing more frequently in the literature, and on hospital management and board meeting agendas. As regulatory and competitive pressures continue to shape the health care market, health provider organizations will put increasing emphasis on defining, developing and managing their product lines. (Product lines are much more than DRGs.) Product line management and cost accounting present the materials manager with an opportunity to become more involved with the


Concurrent expression of Oct4 and Nanog maintains mesenchymal stem-like property of human dental pulp cells.
Human dental pulp stem cells (DPSCs), unique mesenchymal stem cells (MSCs) type, exhibit the characteristics of self-renewal and multi-lineage differentiation capacity. Oct4 and Nanog are pluripotent genes. The aim of this study was to determine the physiological functions of Oct4 and Nanog expression in DPSCs. Herein, we determined the critical role of an Oct4/Nanog axis modulating MSCs properties of DPSCs by lentiviral-mediated co-overexpression or co-knockdown of Oct4/Nanog in DPSCs. MSCs properties including osteogenic/chondrogenic/adipogenic induction differentiation was assayed for expression of osteogenic/chondrogenic/adipogenic markers by quantitative real-time RT-PCR analysis. Initially, we observed that the expression profile of Oct4 and Nanog in dental pulp cells, which exerted properties of MSCs, was significantly up-regulated compared to that of STRO-1-CD146- dental pulp cells. Down-regulation of Oct4 and Nanog co-expression significantly reduced the cell proliferation, osteogenic differentiation capability, STRO-1, CD146, and Alkaline phosphatase (ALP) activity of DPSCs. In contrast, co-overexpression of Oct4 and Nanog enhanced the expression level of STRO-1 and CD146, proliferation rate and osteogenic/chondrogenic/adipogenic induction differentiation capability, and expression of osteogenic/chondrogenic/adipogenic induction differentiation markers. Our results suggest that Oct4-Nanog signaling is a regulatory switch to maintain properties in DPSCs.


Lentivirus-mediated expression of cDNA and shRNA slows degeneration in retinitis pigmentosa.
Mutations in Pde6b lead to high levels of signaling molecules cyclic guanosine monophosphate (cGMP) and Ca(2+), which ultimately result in photoreceptor cell death in certain forms of retinitis pigmentosa (RP). The level of cGMP, which is controlled by opposing activities of guanylate cyclase (GUCY) and photoreceptor phosphodiesterase-6 (PDE6), regulates the opening of cyclic nucleotide-gated ion channels [CNG] and thereby controls Ca(2+) influx into the outer segments. Using a lentiviral gene therapy approach, we have previously shown that degeneration can be temporarily slowed either by introducing wild-type PDE6β or knocking down expression of GUCY2E and CNGA1 in photoreceptors of Pde6b(H620Q), a mouse model for RP. Rescue was transient with either approach. Therefore, we tested a novel combination therapy using bipartite lentiviral vectors designed to both introduce wild-type PDE6β expression and knockdown GUCY2E or CNGA1. Immunoblot analysis shows simultaneous increases in PDE6β and decreases in GUCY2E or CNGA1 in retinas transduced by the vectors, indicating successful transduction. In Pde6b(H620Q) mutants, we observe rescue of photoreceptor function and an increase in photoreceptor rows as compared with untreated controls. However, no evidence of prolonged rescue beyond the limit of the previously tested single therapy was observed.


Crystal structure of pyruvate decarboxylase from Zymobacter palmae.
Pyruvate decarboxylase (PDC; EC 22.214.171.124) is a thiamine pyrophosphate- and Mg(2+) ion-dependent enzyme that catalyses the non-oxidative decarboxylation of pyruvate to acetaldehyde and carbon dioxide. It is rare in bacteria, but is a key enzyme in homofermentative metabolism, where ethanol is the major product. Here, the previously unreported crystal structure of the bacterial pyruvate decarboxylase from Zymobacter palmae is presented. The crystals were shown to diffract to 2.15 Å resolution. They belonged to space group P21, with unit-cell parameters a = 204.56, b = 177.39, c = 244.55 Å and Rr.i.m. = 0.175 (0.714 in the highest resolution bin). The structure was solved by molecular replacement using PDB entry 2vbi as a model and the final R values were Rwork = 0.186 (0.271 in the highest resolution bin) and Rfree = 0.220 (0.300 in the highest resolution bin). Each of the six tetramers is a dimer of dimers, with each monomer sharing its thiamine pyrophosphate across the dimer interface, and some contain ethylene glycol mimicking the substrate pyruvate in the active site. Comparison with other bacterial PDCs shows a correlation of higher thermostability with greater tetramer interface area and number of interactions.


Zamamidine D, a Manzamine Alkaloid from an Okinawan Amphimedon sp. Marine Sponge.
A new manzamine alkaloid, zamamidine D (1), was isolated from an Okinawan Amphimedon sp. marine sponge. The structure of zamamidine D (1) including the relative configuration was elucidated on the basis of spectroscopic data. Zamamidine D (1) is the first manzamine alkaloid possessing a 2,2'-methylenebistryptamine unit as the aromatic moiety instead of a β-carboline unit. Zamamidine D (1) showed antimicrobial activity against several bacteria and fungi.


Nuclear DNA pattern of the gallbladder cancer.
Nuclear DNA of the gallbladder cancer was stained by the Feulgen method and analyzed using a new concept of DNA score. DNA score was determined by the peak ploidy unit and decided numbers of frequency in each ploidy unit. As the result, a significant correlation between DNA score and the depth of cancer invasion was demonstrated. The depth of cancer invasion, as reported already, has close correlation to the prognosis of the patients of gallbladder cancer. These results indicate that the nuclear DNA analysis is useful for the determination of malignancy and the prediction of the prognosis of the patients.


Bacteriophages: potential treatment for bacterial infections.
Bacteriophages (phages) are viruses of bacteria that can kill and lyse the bacteria they infect. After their discovery early in the 20th century, phages were widely used to treat various bacterial diseases in people and animals. After this enthusiastic beginning to phage therapy, problems with inappropriate use and uncontrolled studies and ultimately the development of antibacterials caused a cessation of phage therapy research in the West. However, a few institutions in Eastern Europe continued to study and use phages as therapeutic agents for human infections. The alarming rise in antibacterial resistance among bacteria has led to a review of the Eastern European studies and to the initiation of controlled experiments in animal models. These recent studies have confirmed that phages can be highly effective in treating many different types of bacterial infections. The lethality and specificity of phages for particular bacteria, the ability of phages to replicate within infected animal hosts, and the safety of phages make them efficacious antibacterial agents. Although there are still several hurdles to be overcome, it appears likely that phage therapy will regain a role in both medical and veterinary treatment of infectious diseases, especially in the scenario of emerging antibacterial resistance.


Effects of a combined aerobic and strength training program in youth patients with acute lymphoblastic leukemia.
Cure rates of youth with Acute Lymphoblastic Leukemia (ALL) have increased in the past decades, but survivor's quality of life and physical fitness has become a growing concern. Although previous reports showed that resistance training is feasible and effective, we hypothesized that a more intense exercise program would also be feasible, but more beneficial than low- to moderate-intensity training programs. We aimed to examine the effects of an exercise program combining high-intensity resistance exercises and moderate-intensity aerobic exercises in young patients undergoing treatment for ALL. A quasi-experimental study was conducted. The patients (n = 6; 5-16 years of age) underwent a 12-week intra-hospital training program involving high-intensity strength exercises and aerobic exercise at 70% of the peak oxygen consumption. At baseline and after 12 weeks, we assessed sub-maximal strength (10 repetition-maximum), quality of life and possible adverse effects. A significant improvement was observed in the sub maximal strength for bench press (71%), lat pull down (50%), leg press (73%) and leg extension (64%) as a result of the training (p < 0.01). The parents' evaluations of their children's quality of life revealed an improvement in fatigue and general quality of life, but the children's self-reported quality of life was not changed. No adverse effects occurred. A 12-week in-hospital training program including high-intensity resistance exercises promotes marked strength improvements in patients during the maintenance phase of the treatment for Acute Lymphoblastic Leukemia without side-effects. Parents' evaluations of their children revealed an improvement in the quality of life. Key pointsPatients with ALL present low muscle strength and poor quality of life.High-intensity resistance exercises combined with moderate-intensity aerobic exercise improved muscle strength and quality of life during the maintenance phase of ALL treatment.The exercise training program seemed to be tolerable and safe in ALL patients.


Testicular intravascular volume and microvessel mitotic activity: effect of experimental varicocele.
Testicular blood flow increases bilaterally in animals with experimental left varicocele (ELV). The present experiments were undertaken to determine if increases in testicular intravascular volume and capillary growth were potential contributors to this increase in flow. Testicular intravascular volume (microliters/g) was estimated by determining testicular vascular 125I-albumin space. Microvessel mitotic activity was estimated by examining 3H-thymidine incorporation into endothelial nuclei, as assayed by silver grain localization over microvessel endothelial nuclei after exposure of testes to 3H-thymidine in vivo. Testicular intravascular volume was 25-30 microliters/g testis in control testes and in ELV animals was increased an average of 9% and 28% in right and left testes, respectively. This increase was statistically significant (P < 0.05) on the left side only. Approximately 1.5-2.0% of testicular microvessel endothelial nuclei exhibited silver grain localization, and ELV was not associated with a change in these values in either right or left testis. Ancillarily, there was a modest but significant association between microvessel mitotic activity and mitotic activity in adjacent seminiferous tubules. It was concluded that bilateral increases in testicular blood flow after ELV are not uniquely the result of bilateral expansion of intravascular volume and growth of the testicular capillaries. It is speculated, however, that mitogenic factors from the seminiferous tubules potentially affect mitotic activity of the adjacent microvasculature.