Cascading failures in interdependent systems under a flow redistribution model.
Robustness and cascading failures in interdependent systems has been an active research field in the past decade. However, most existing works use percolation-based models where only the largest component of each network remains functional throughout the cascade. Although suitable for communication networks, this assumption fails to capture the dependencies in systems carrying a flow (e.g., power systems, road transportation networks), where cascading failures are often triggered by redistribution of flows leading to overloading of lines. Here, we consider a model consisting of systems A and B with initial line loads and capacities given by {L_{A,i},C_{A,i}}_{i=1}^{n} and {L_{B,i},C_{B,i}}_{i=1}^{n}, respectively. When a line fails in system A, a fraction of its load is redistributed to alive lines in B, while remaining (1-a) fraction is redistributed equally among all functional lines in A; a line failure in B is treated similarly with b giving the fraction to be redistributed to A. We give a thorough analysis of cascading failures of this model initiated by a random attack targeting p_{1} fraction of lines in A and p_{2} fraction in B. We show that (i) the model captures the real-world phenomenon of unexpected large scale cascades and exhibits interesting transition behavior: the final collapse is always first order, but it can be preceded by a sequence of first- and second-order transitions; (ii) network robustness tightly depends on the coupling coefficients a and b, and robustness is maximized at non-trivial a,b values in general; (iii) unlike most existing models, interdependence has a multifaceted impact on system robustness in that interdependency can lead to an improved robustness for each individual network.


Mechanism of the Photochemical Isomerization and Oxidation of 2-Butenedial: A Theoretical Study.
Under tropospheric conditions, 2-butenedial is photochemically removed to produce secondary organic aerosol. Upon solar irradiation in the lower troposphere, the main photochemical products are ketene-enol (a key intermediate product), furanones, and maleic anhydride. The oxidative reaction mechanism was studied using the multireference method CASSCF to explore the hypersurface of the two most accessible singlet excited states, and by DFT for the ground state. Photoisomerization of 2-butenedial in the first excited state directly produces ground state ketene-enol upon nonradiative relaxation. From this intermediate, furan-2-ol and successively 3H-furan-2-one and 5H-furan-2-one are formed. The cooperative effect of two water molecules is essential to catalyze the cyclization of ketene-enol to furan-2-ol, followed by hydrogen transfers to furanones. Two water molecules are also necessary to form maleic anhydride from furan-2-ol. For this last reaction, in which one extra oxygen must be acquired, we hypothesize a mechanism with singlet oxygen as the oxidant.


Cytochrome P450 CYP3A in human renal cell cancer.
Renal cell cancer is the main malignant tumour of the kidney and has an increasing incidence. This type of tumour has a poor prognosis and shows intrinsic resistance to several anti-cancer drugs. The CYP3A P450 family, which consists of three closely related forms, is involved in the oxidative activation and deactivation of a variety of carcinogens and several anti-cancer drugs. In this study the presence and cellular localization of CYP3A has been investigated using a combination of immunohistochemistry, immunoblotting and reverse transcriptase polymerase chain reaction (RT-PCR) in renal cell cancer and corresponding normal kidney. CYP3A was consistently expressed in both renal call cancer and in normal kidney. In renal cell cancer, CYP3A was localized to tumour cells and in normal kidney the predominant cellular localization of CYP3A was to proximal tubular epithelial cells. RT-PCR showed that both CYP3A5 mRNA and CYP3A7 mRNA were consistently present in both tumour and normal samples, while CYP3A4 mRNA was present in 65% of tumours and 90% of normal samples. This study indicates that individual members of the CYP3A family are expressed in renal cell cancer. The presence of CYP3A in renal cell cancer might be important in the metabolic potentiation as well as the detoxification of chemotherapeutic agents used to renal cancer.


Multilevel and urban health modeling of risk factors for diabetes mellitus: a new insight into public health and preventive medicine.
This study aimed to apply multidisciplinary analysis approaches and test two hypotheses that (1) there was a significant increase in the prevalence of diabetes mellitus (DM) from 2002 to 2010 in the city of Philadelphia and that (2) there were significant variations in the prevalence of DM across neighborhoods, and these variations were significantly related to the variations in the neighborhood physical and social environment (PSE). Data from the Southeastern Pennsylvania Household Health Surveys in 2002-2004 (period 1, n = 8,567) and in 2008-2010 (period 2, n = 8,747) were analyzed using a cross-sectional comparison approach. An index of neighborhood PSE was constructed from 8 specific measures. The results show that age-adjusted prevalence of DM increased from period 1 (10.20%) to period 2 (11.91%) (P < 0.001). After adjusting age, sex, and survey years, an estimate of 12.14%, 18.33%, and 11.89% of the odds ratios for DM was related to the differences in the neighborhood PSE disadvantage, the prevalence of overweight/obesity, and those with lower education attendance, respectively. In conclusion, prevalence of DM significantly increased from 2002 to 2010 in the city of Philadelphia. In addition to risk factors for DM at personal level, neighborhood PSE disadvantage may play a critical role in the risk of DM.


Recombinant Adeno-Associated Virus Expressing Truncated IK Cytokine Diminishes the Symptoms of Inflammatory Arthritis.
IK can downregulate interferon-gamma-induced major histocompatibility complex (MHC) class II expression through the MHC class II transactivator, which suggests that IK can inhibit the interactions between immune cells. We delivered adeno-associated virus serotype 2 (AAV2) encoding the genes for truncated IK (tIK) or green fluorescent protein (GFP) to DBA1/J mice via intravenous injection. Seven weeks after injection, collagen-induced arthritis was induced in the AAV2-treated mice. AAV2-tIK injection reduced the severity of arthritis and the percentage of pathogenic Th17 cells compared with AAV2-GFP injection. These results suggest a novel gene therapy strategy for treatment of inflammatory arthritis.


Miniature Spectroscopes with Two-Dimensional Guided-Mode Resonant Metal Grating Filters Integrated on a Photodiode Array.
A small spectroscope with 25 color sensors was fabricated by combining metamaterial color filters and Si photodiodes. The metamaterial color filters consisted of guided-mode resonant metal gratings with subwavelength two-dimensional periodic structures. Transmittance characteristics of the color filters were designed to obtain peak wavelengths proportional to grating periods. For each color sensor, a peak wavelength of the spectral sensitivity could be tuned in the range of visible wavelengths by adjusting each grating period. By performing spectrum reconstruction using Tikhonov regularization, the spectrum of an incident light was obtained from the signal of photodiodes. Several monochromatic lights were made incident on the fabricated device and the spectral characteristics of the incident light were reconstructed from the output signals obtained from the respective color sensors. The peak wavelengths of the reconstructed spectra were in good agreement with the center wavelengths of the monochromatic lights.


Decreased Streptococcus pneumoniae susceptibility to oral antibiotics among children in rural Vietnam: a community study.
Streptococcus pneumoniae is the most significant bacterial cause of community-acquired pneumonia among children under five years worldwide. Updated resistance information of S. pneumoniae among children is essential to adjust the recommendations for empirical treatment of community-acquired pneumonia, which will have immense implications for local and global health. This study investigated the prevalence of antibiotic resistance in isolated strains of S. pneumoniae and relationship with antibiotic use and demographic factors of children under five in rural Vietnam in 2007. In Bavi district, 847 children 6 to 60 months were selected from 847 households. The main child-caregivers in the households were interviewed weekly using structured questionnaires to collect information of daily illness symptoms and drug use for the selected child over a four-week period (from March through June 2007). In the 3rd week, the children were invited for a clinical examination and to collect nasopharyngeal samples for S. pneumoniae identification. Etest and disk diffusion were used to test antibiotic susceptibility. Of 818 participating children, 258 (32%) had ongoing respiratory infections, 421 (52%) carried S. pneumoniae, and 477 (58%) had used antibiotics within the previous three weeks. Of the 421 isolates, 95% were resistant to at least one antibiotic (401/421). Resistance to co-trimoxazole, tetracycline, phenoxymethylpenicillin, erythromycin and ciprofloxacin was 78%, 75%, 75%, 70% and 28%, respectively. Low resistance was noted for amoxicillin (4%), benzylpenicillin (4%), and cefotaxime (2%). The intermediate resistance to amoxicillin was 32%. Multidrug-resistance was seen in 60%. The most common pattern was co-resistance to co-trimoxazole, tetracycline and erythromycin. The proportion of children carrying resistant bacteria was higher among the children who had used antibiotics in the previous three weeks. Resistance to commonly used antibiotics and multidrug-resistance of S. pneumoniae in the area is remarkably high. High-dose amoxicillin is the only investigated oral antibiotic that can possibly be used for treatment of community-acquired pneumococcal infections. Strategies to promote appropriate prescribing and dispensing of effective antibiotics should be immediately implemented for the benefit of local and global health.


Antibiotic Resistome Alteration by Different Disinfection Strategies in a Full-Scale Drinking Water Treatment Plant Deciphered by Metagenomic Assembly.
Disinfection regimes are considered the most solid strategy to reduce microbial risks in drinking water, but their roles in shaping the antibiotic resistome are poorly understood. This study revealed the alteration of antibiotic resistance genes (ARGs) profiles, their co-occurrence with mobile genetic elements (MGEs), and potential hosts during drinking water disinfection based on metagenomic assembly. We found the ozone/chlorine (O3/Cl2) coupled disinfection significantly increased the relative abundance of ARGs and MGE-carrying antibiotic resistance contigs (ARCs) through the enrichment of ARGs within the resistance-nodulation-cell division and ATP-binding cassette antibiotic efflux families that are primarily carried by Pseudomonas, Acinetobacter, Mycobacterium, and Methylocystis, whereas the antimicrobial resin/chlorine coupled disinfection posed unremarkable changes to the ARG and MGE abundances. Moreover, the co-occurrence patterns of antibiotic efflux and beta-lactam ARGs and MGEs were widely identified, and ARCs carrying the recR and mexH genes were detected in all the samples, with the highest abundance of 2.25 × 10-2 copies per cell after O3/Cl2 disinfection. Sequence-independent binning analysis successfully retrieved two draft ARG-carrying genomes of Acidovorax sp. MR-S7 and Hydrogenophaga sp. IBVHS2, further revealing the host-ARG relationship during O3/Cl2 disinfection. Overall, this study provides novel insights into the antibiotic resistome alteration during drinking water disinfection.


Abandoning the concept of 'schizophrenia': some implications of validity arguments for psychological research into psychotic phenomena.
After more than 90 years of research in which the presence or absence of a diagnosis of schizophrenia has been used as an independent variable, little of certainty has been found out about the aetiology of the hypothesized schizophrenia disease process. One possible reason for this lack of progress is that schizophrenia is not a valid object of scientific inquiry. Data from published research (mainly carried out by distinguished psychiatrists) are reviewed casting doubt on: (i) the reliability, (ii) the construct validity, (iii) the predictive validity, and (iv) the aetiological specificity of the schizophrenia diagnosis. It is argued that continued research into the aetiology of schizophrenia is likely to prove fruitless and that psychologists should adopt alternative methods of studying psychosis. Two alternative strategies--the development of empirical methods of psychiatric classification and the study of individual symptoms--are discussed.


[No advantage to referring patients with acute myocardial infarction from a general hospital to an intervention clinic for percutaneous coronary intervention; comparison of mortality rates in 2000 and 2003 in the Meander Medical Centre, Amersfoort].
To evaluate whether implementation of the 2000 Netherlands Society of Cardiology guideline 'ST-elevation acute coronary syndromes', which recommends the use ofpercutaneous coronary intervention (PCI), has reduced mortality and complication rates in a general hospital, and whether patient characteristics and outcomes are comparable to those reported in the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT) 2 and 3 trials. Retrospective outcomes study. Data from 2003 were compared with data from 2000 regarding patients with acute myocardial infarction who received thrombolysis at the Meander Medical Centre in Amersfoort, the Netherlands, or percutaneous transluminal coronary angioplasty (PTCA) after referral to an intervention clinic. Data included baseline characteristics, type of treatment, outcomes and complications. Age, sex and mortality ofall patients were compared to data from the ASSENT 2 and 3 trials. Data were included from 130/132 patients treated in 2003 and 145/145 patients treated in 2000. Baseline characteristics were comparable, except age: there were significant more elderly patients in 2003 (p = 0.006). After implementation of the guideline, significantly more patients underwent PTCA (odds ratio (OR) 4.41 (95% CI: 2.51-7.75)). After adjusting for confounding factors there was no significant difference in in-hospital mortality (adjusted OR 1.11 (95% CI: 0.48-2.60)), 30-day mortality and 1-year mortality. Significantly more minor complications were reported (OR 2.58 (95% CI: 1.07-6.19)). Significantly more women and patients older than 75 years were treated compared with the ASSENT 2 and 3 trials. The 30-day mortality rate was significantly higher compared with ASSENT 2 (OR 1.60 (95% CI: 1.07-2.41)) and ASSENT 3 (OR1.74 (95% CI: 1.14-2.66)). The implementation of new guidelines 'ST-elevation acute coronary syndromes' did not result in lower mortality or fewer complications.


Modern restorative dentistry: a new approach.
An analysis of the role of restorative dentistry within oral health care shows that it has broadened its scope over its long history. It started with the replacement of lost teeth and, later, lesions and structural defects of tooth tissue were treated. Progress has been achieved through the development of new materials and procedures, specifically those that ensure microscopic and/or chemical adhesion and those that allow for the removal of infection tissue and its restoration, while protecting the remaining healthy structure of the tooth. Teeth can also be protected even before the initiation of an infected lesion by sealing morphologic features such as pits and fissures. All of these procedures are components of modern restorative dentistry which now contributes to the disappearance of the totally edentulous patient. Dentistry has the responsibility of helping in the generation of sufficient social and economic resource to make this modern restorative dentistry available to the community as a whole.


Variational calculation of specific, highly excited vibrational states in DFCO: comparison with experimental data.
A stimulated emission pumping spectra of jet-cooled DFCO performed by Crane et al. (J. Mol. Spectrosc. 1997, 183, 273) has provided a great number of ro-vibrational lines up to 9000 cm(-1) of excitation energy. By combining a Jacobi-Wilson (JW) approach with a Davidson scheme, we calculate the lines provided by the experiment up to 9000 cm(-1) using an ab initio global potential energy surface (PES) developed by Kato et al. (J. Chem. Phys. 1997, 107, 6114). Comparisons between experimental and calculated data provide a critical test of the quality of the PES used. We show that the variational calculated energies can be efficiently corrected by taking into account the error observed for the A' fundamental transitions nu(i) (i = 1, ..., 5) and the first overtone 2nu(6). A detailed analysis of the eigenstates obtained by the calculation allows one to quantify the coupling between the different modes. Such an information is essential to understand and predict the energy flow through a DFCO molecule that is initially excited.


Effect of hormone therapy on the enteroinsular axis.
Menopause is associated with a decline in insulin response to glucose and with insulin resistance. It has been proven that hormone therapy (HT) improves carbohydrate metabolism in postmenopausal women. However, it is known that gastrointestinal hormones play a key role in the coordination of digestion and absorption of ingested nutrients and in the regulation of pancreatic endocrine function. Therefore, the aim of this study was to investigate the effect of HT on gastrointestinal hormones and carbohydrate metabolism in postmenopausal women. The prospective study was performed in 90 healthy postmenopausal women (mean age 54.5 years, standard deviation 3.34 years), of whom 49 completed the study. They were randomized and treated either with continuous transdermal HT (0.05 mg 17[beta]-estradiol every 24 hours) combined with 5 mg oral dydrogesterone daily (group A, n = 25), or with oral HT (2 mg 17[beta]-estradiol semihydrate every 24 hours) combined with 10 mg dydrogesterone as a continuous therapy (group B, n = 8). The control group (group C, n = 16) received no HT. Both basal and meal-stimulated plasma concentrations of glucose, insulin, glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), and cholecystokinin (CCK), as well as basal estrogen levels, were measured before HT and after 6 and 12 months of treatment. At the same time intervals, all the studied parameters were measured for group C. After 12 months of the transdermal HT, a decrease in both fasting (P < 0.002) and postprandial (P < 0.05) plasma glucose levels was observed. Oral HT reduced only the fasting plasma glucose level in the 12th month of treatment (P < 0.05). Regardless of the route of administration, HT reduced postprandial plasma levels of insulin (oral HT: P < 0.05; transdermal HT: P < 0.02). Fasting plasma levels of GIP were reduced after 6 and 12 months of transdermal HT (P < 0.002 and P < 0.001, respectively). Moreover, levels of postprandial GIP were reduced after 6 and 12 months of transdermal HT (P < 0.002 in both cases). Fasting and postprandial GLP-1 levels were reduced by transdermal HT after 12 months of supplementation. Oral HT also decreased these levels, but not significantly. The observed differences may, however, be related not only to the route of administration, but also to the difference in the dose of estradiol. Regardless of the route of administration, HT did not influence plasma levels of CCK. Hormone therapy significantly influences the enteroinsular axis in postmenopausal women and contributes to the normalization of plasma glucose levels.


ATP-induced focal adhesion kinase activity is negatively modulated by phospholipase D2 in PC12 cells.
Extracellular ATP has been known to modulate various cellular responses including mitogenesis, secretion and morphogenic activity in neuronal cells. In the ATP-induced morphogenic activity, focal adhesion kinase(s) such as Fak have been suggested to play a critical role. Binding of ATP to its specific cell surface receptor in PC12 cells induces phospholipase D (PLD) activity. However, the role of PLD on ATP-induced Fak activation in PC12 cells remains unclear. In this study, we investigated the role of PLD on the ATP-induced Fak activation and paxillin phosphorylation using two established cell lines: wild type PLD2- and lipase-inactive mutant PLD2-inducible PC12 cells. Stimulation of cells with ATP caused PLD2 activation via classical protein kinase C activation. ATP also induced Fak activation, and paxillin phosphorylation, and were dramatically reduced by wild type PLD2 overexpression but not by lipase-inactive mutant PLD2 overexpression. When the PC12 cells were pretreated with propranolol, a specific inhibitor for phosphatidic acid phosphohydrolase resulting in the accumulation of PA, ATP-induced Fak activation and paxillin phosphorylation were also reduced. We found that inhibition of tyrosine phosphatases by pervanadate completely blocked PLD2-dependent Fak and paxillin dephosphorylation. Taken together, we suggest that PLD2 activity might play a negative role in ATP-induced Fak and paxillin phosphorylation possibly through tyrosine phosphatases.


Regional Hyperthermic Perfusion for Cancer.
Regional perfusion of cancer resulted from studies that infused nitrogen mustard into arteries supplying tumours while at the same time blocking the venous return to maximise exposure of the tumour to the chemotherapeutic agent.


Gradient Hydrogen Migration Modulated with Self-Adapting S Vacancy in Copper-Doped ZnIn2S4 Nanosheet for Photocatalytic Hydrogen Evolution.
It is a challenge to regulate charge flow synergistically at the atomic level to modulate gradient hydrogen migration (H migration) for boosting photocatalytic hydrogen evolution. Herein, a self-adapting S vacancy (Vs) induced with atomic Cu introduction into ZnIn2S4 nanosheets was fabricated elaborately, which can tune charge separation and construct a gradient channel for H migration. Detailed experimental results and theoretical simulations uncover the behavior mechanism of Vs generation with Cu introduction after substituting a Zn atom tendentiously. Cu-S bond shrinkage and Zn-S bond distortion are presented around Vs areas. Besides, Vs induced by Cu introduction lowers the internal electric field to restrain electron transmission between layers, which are enriched on the Vs area because of the lower surface electrostatic potential. Atomic Cu and Vs show a synergistic effect for regulating regional charge separation due to the Cu dopant being a hole trap and Vs being an electron trap. The channels for H migration with gradient ΔGH0 are constructed by different S atom sites, which are modulated by Vs. Gradient H migration driven by a photothermal effect occurs on an identical surface without striding across a heterogeneous interface, which is a valid pathway with lower resistance for boosting H2 release. Ultimately, 5 mol % Cu confined in ZnIn2S4 nanosheets achieves an optimum photocatalytic hydrogen evolution activity of 9.8647 mmol g-1 h-1, which is 14.8 times higher than 0.6640 mmol g-1 h-1 for ZnIn2S4, and apparent quantum efficiency reaches 37.11% at 420 nm. This work demonstrates the behavior mechanism of atomic substitution and provides cognition for hydrogen evolution mechanism deeply.


Key architectural changes in tumor-negative lymph nodes from metastatic-free oral cancer patients are valuable prognostic factors.
Regional lymph node (LN) metastasis in oral cancer patients is the most significant grave prognostic factor. We evaluated the relationship between clinical outcomes and different histopathological changes in tumor-negative LNs (LN0) selected from neck dissections without metastatic disease (pN0). A total of 435 LN0 selected from pN0 neck dissections (up to three nodes in each level) were scored for histopathological parameters of LN areas, capsule thickness, subcapsular and medullary sinus ectasia, lobular architecture and percent of cortical reactive follicles. These were compared to 328 LN0 selected from neck dissections with metastases (pN+) after exclusion of metastatic LNs. Data were presented by maximum scores of each parameter in I-III (close) and in IV-V (distant) levels. Limited data from level V and regression analyses inferred that the values in level IV represented the worst changes for most patients. Cox proportional hazard regression on each parameter in close and distant levels demonstrated that capsule thickness, number of lobules and percent of reactive follicles were significantly associated with time to death from disease. The higher the change in distant levels, the shorter the time to death, while the higher the change in close levels (given a stable change in distant levels), the longer the time to death. After adjustment for gender, age and location, only the effect of the percent of reactive follicles retained their significant effect. Logistic regression of metastases demonstrated that all parameters except for percent of reactive follicles were significantly associated with risk of metastases, with differences between close and distant levels similar to those found for time to death. After adjustment for gender, age and location, only the area and number of lobes retained their significance. The findings of this study suggested that selective histopathological changes in tumor-negative LNs in metastatic-free patients provide new valuable prognostic parameters.


[Interaction between HIV-1 and GB virus type-C during coinfection status].
The human immunodeficiency virus (HIV) infection is one of the most important problems in public health. It is estimated that 3 3 million people are infected around the world. HIV and GBV-C share the same transmission route, being frequent the co-infection. Since both viruses replicate in CD4+ lymphocytes, recent studies have described an interaction. Decreasing of HIV viral load and higher CD4 counts have been observed in co-infected patients, leading a better clinical outcome. Nevertheless, some epidemiological studies have shown contradictory results. Additionally, in vitro models report inhibition of HIV by E1, E2, NS3 and NS5A GBV-C proteins, resulting in a decreasing of p24 antigen. This review summarizes the principal findings about co-infection and mechanisms that have been proposed for HIV-1 inhibition.


Effect of insulin on myocardial contractility during canine endotoxin shock.
During endotoxin shock the heart becomes less responsive to the stimulatory effect of insulin on glucose uptake. In the present study we sought to determine if the heart was also less responsive to the positive inotropic effect of insulin during non-cardiogenic endotoxin shock. Responses of the heart to insulin were assessed under conditions of hyperinsulinaemic (4U.min-1), euglycaemic clamp (INS). Adult mongrel dogs, weighing 20-25 kg, were anaesthetised and instrumented to measure differences in substrate concentrations between arterial and coronary sinus blood, circumflex artery blood flow (using electromagnetic flow probe), haemodynamic variables, and left ventricular posterior wall thickness (using sonomicrometry). The first derivative of left ventricular pressure with respect to time was measured and its maximal value (LV dP/dtmax) used as an index of cardiac performance. Myocardial contractility was measured using the end systolic pressure-dimension relationship. Endotoxin shock was induced by Salmonella typhimurium (1 mg.kg-1 intravenously), and resulted in depression of myocardial performance but increased contractility. INS caused a twofold elevation in myocardial glucose uptake in control animals while in endotoxin shocked dogs it was unable to elevate glucose uptake above the pre-endotoxin level. In control animals INS caused both increased cardiac contractility and performance. In the endotoxin shock group INS was unable to increase LVdP/dtmax above the basal, pre-endotoxin level and did not cause any significant change in myocardial contractility. We suggest that the heart becomes less responsive to the positive inotropic as well as metabolic effects of insulin during endotoxin shock. Changes in LV dP/dtmax can be attributed to the changing loading conditions that occur during endotoxin shock.


Single-tube analysis of DNA methylation with silica superparamagnetic beads.
DNA promoter methylation is a signature for the silencing of tumor suppressor genes. Most widely used methods to detect DNA methylation involve 3 separate, independent processes: DNA extraction, bisulfite conversion, and methylation detection via a PCR method, such as methylation-specific PCR (MSP). This method includes many disconnected steps with associated losses of material, potentially reducing the analytical sensitivity required for analysis of challenging clinical samples. Methylation on beads (MOB) is a new technique that integrates DNA extraction, bisulfite conversion, and PCR in a single tube via the use of silica superparamagnetic beads (SSBs) as a common DNA carrier for facilitating cell debris removal and buffer exchange throughout the entire process. In addition, PCR buffer is used to directly elute bisulfite-treated DNA from SSBs for subsequent target amplifications. The diagnostic sensitivity of MOB was evaluated by methylation analysis of the CDKN2A [cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4); also known as p16(INK4a)] promoter in serum DNA of lung cancer patients and compared with that of conventional methods. Methylation analysis consisting of DNA extraction followed by bisulfite conversion and MSP was successfully carried out within 9 h in a single tube. The median pre-PCR DNA yield was 6.61-fold higher with the MOB technique than with conventional techniques. Furthermore, MOB increased the diagnostic sensitivity in our analysis of the CDKN2A promoter in patient serum by successfully detecting methylation in 74% of cancer patients, vs the 45% detection rate obtained with conventional techniques. The MOB technique successfully combined 3 processes into a single tube, thereby allowing ease in handling and an increased detection throughput. The increased pre-PCR yield in MOB allowed efficient, diagnostically sensitive methylation detection.


A micro-computed tomographic evaluation of dentinal microcrack alterations during root canal preparation using single-file Ni-Ti systems.
The aim of the present study was to evaluate the length of dentinal microcracks observed prior to and following root canal preparation with different single-file nickel-titanium (Ni-Ti) systems using micro-computed tomography (micro-CT) analysis. A total of 80 mesial roots of mandibular first molars presenting with type II Vertucci canal configurations were scanned at an isotropic resolution of 7.4 µm. The samples were randomly assigned into four groups (n=20 per group) according to the system used for root canal preparation, including the WaveOne (WO), OneShape (OS), Reciproc (RE) and control groups. A second micro-CT scan was conducted after the root canals were prepared with size 25 instruments. Pre- and postoperative cross-section images of the roots (n=237,760) were then screened to identify the lengths of the microcracks. The results indicated that the microcrack lengths were notably increased following root canal preparation (P<0.05). The alterations in microcrack length in the OS group were more significant compared with those in the WO, RE and control groups (P<0.05). In conclusion, the formation and development of dentinal microcracks may be associated with the movement caused by preparation rather than the taper of the files. Among the single-file Ni-Ti systems, WO and RE were not observed to cause notable microcracks, while the OS system resulted in evident microcracks.


Divergent effects of adrenaline in human induced pluripotent stem cell-derived cardiomyocytes obtained from hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease that affects the heart muscle with diverse clinical outcomes. HCM can cause sudden cardiac death (SCD) during or immediately after mild to rigorous physical activity in young patients. However, the mechanism causing SCD as a result of exercise remains unknown, but exercise-induced ventricular arrhythmias are thought to be responsible for this fatal consequence. To understand the disease mechanism behind HCM in a better way, we generated patient-specific induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from HCM patients carrying either the MYBPC3-Gln1061X or TPM1-Asp175Asn mutation. We extensively investigated the effects of low to high concentrations of adrenaline on action potential characteristics, and the occurrence of arrhythmias in the presence of various concentrations of adrenaline and in wash-out condition. We classified and quantified different types of arrhythmias observed in hiPSC-CMs, and found that the occurrence of arrhythmias was dependent on concentrations of adrenaline and positions of mutations in genes causing HCM. In addition, we observed ventricular tachycardia types of arrhythmias in hiPSC-CMs carrying the TPM1-Asp175Asn mutation. We additionally examined the antiarrhythmic potency of bisoprolol in HCM-specific hiPSC-CMs. However, bisoprolol could not reduce the occurrence of arrhythmias during administration or during the wash-out condition of adrenaline in HCM-specific hiPSC-CMs. Our study demonstrates hiPSC-CMs as a promising tool for studying HCM. The experimental design used in this study could be suitable and beneficial for studying other components and drugs related to cardiac disease in general.


Postoperative Portomesenteric Venous Thrombosis After Colorectal Cancer Surgery.
Portomesenteric venous thrombosis (PMVT) can occur after colorectal surgery. Most previous studies included patients with various diseases, especially inflammatory bowel disease. The prevalence and clinical significance of PMVT developing after surgery for colorectal cancer (CRC) remain unclear. Consecutive patients who underwent resection for CRC between June 2003 and April 2016 were retrospectively analyzed. Postoperative PMVT was diagnosed based on pre- and postoperative computed tomography (CT). Postoperative PMVT developed in 10 (0.24%) of 4232 patients who underwent resection for CRC. One patient had alcoholic liver cirrhosis, whereas nine did not have prior or current liver disease. PMVT in eight patients was detected within 2 weeks after surgery by CT, performed to evaluate non-specific symptoms such as mild fever and abdominal pain, or performed postoperatively after deep pelvic dissection. PMVT in the remaining two asymptomatic patients was diagnosed following surveillance CT 3 and 7 months after surgery, respectively. PMVT in the patient with liver cirrhosis was detected 13 days after surgery and found to involve the main portal vein, causing hyperbilirubinemia and requiring emergency thrombectomy with thrombolysis. PMVT in the nine patients without liver disease was resolved by anticoagulation therapy or conservative care without long-term complications. PMVT after CRC surgery is likely an early postoperative event in most patients. The incidence of clinically significant PMVT in patients with CRC may be lower than previously reported. CT was reliable in the diagnosis and follow-up of these patients. Most patients with PMVT can be managed conservatively without serious long-term morbidity.


[Short-term evaluation of Altis® single-incision sling in women stress urinary incontinence].
Midurethral slings are the main surgical treatment of stress urinary incontinence. Altis is a minimally invasive single-incision sling system. The aim of this study is to report the safety and efficacity results during a year of follow up. This single-centre and retrospective study has been performed in a university hospital, between February 2015 and May 2018. We included women aged more than 18, complaining a stress urinary incontinence with a urethral hypermobility and positive support maneuvers, who had failed from non surgical treatment. A prospective data collection has been done at the moment of inclusion, peroperative time, at 6 weeks, 6 months and a year after the procedure. The main evaluation criteria was the cure rate at twelve months. Thirty patients were included in our study. The mean age was 45,4±12,9 years old, the mean ICIQ-UI score was 13,5±4,06 and the median pad test was at 12g. Ninety three percent of the procedures were done as ambulatory surgery. The average operating time was at 22,2minutes. Overall, 75% of our patients were objectively cured and 14,2% were in fail of this treatment. The short term results show a good efficacity and safety of this procedure. But its place remains to be defined in relation to other techniques, TVT, TOT and non-prosthetic techniques. 3.


The Times, They are a-Changing: HOPE for HIV-to-HIV Organ Transplantation.
HIV-infected persons who achieve undetectable viral loads on antiretroviral therapy currently have near-normal lifespans. Liver disease is a major cause of non-AIDS-related deaths, and as a result of longer survival, the prevalence of end-stage renal disease in HIV is increasing. HIV-infected persons undergoing organ transplantation generally achieve comparable patient and graft survival rates compared to their HIV-uninfected counterparts, despite a nearly threefold increased risk of acute rejection. However, the ongoing shortage of suitable organs can limit transplantation as an option, and patients with HIV have higher waitlist mortality than others. One way to solve this problem would be to expand the donor pool to include HIV-infected individuals. The results of a South Africa study involving 27 HIV-to-HIV kidney transplants showed promise, with 3- and 5-year patient and graft survival rates similar to those of their HIV-uninfected counterparts. Similarly, individual cases of HIV-to-HIV liver transplantation from the United Kingdom and Switzerland have also shown good results. In the United States, HIV-to-HIV kidney and liver transplants are currently permitted only under a research protocol. Nevertheless, areas of ambiguity exist, including streamlining organ allocation practices, optimizing HIV-infected donor and recipient selection, managing donor-derived transmission of a resistant HIV strain, determining optimal immunosuppressive and antiretroviral regimens, and elucidating the incidence of rejection in HIV-to-HIV solid organ transplant recipients.


Avian pneumovirus and its survival in poultry litter.
The survival of avian pneumovirus (APV) in turkey litter was studied at different temperature (room temperature, [approximately 22-25 C], 8 C, and -12 C) conditions. Built-up turkey litter from a turkey breeder farm known to be free of APV was obtained and was divided into two portions. One portion was sterilized by autoclaving and the other portion was kept nonautoclaved. Both samples were inoculated with a Vero cell-propagated Minnesota isolate of APV subtype C (APV/MN2A) with a titer of 10(5) 50% tissue culture infective dose at 1% level. These samples were then stored at three different temperatures: -12 C, 8 C, and room temperature (20-25 C). The samples were tested for the presence of viral RNA by reverse transcriptase-polymerase chain reaction and for the presence of live virus by virus isolation in Vero cells at the intervals of 1, 2, 3, 7, 14, 30, 60, and 90 days. Our studies revealed the presence of APV RNA even after 90 days in the autoclaved litter samples kept at -12 C and at 8 C. The virus was isolated from the autoclaved litter kept at -12 C up to 60 days. From the nonautoclaved litter, viral RNA was detected up to 60 days and virus was isolated up to 14days. The present study indicated that APV could survive in built-up turkey litter up to 60 days postinoculation at a temperature of-12 C.


Imaging samples in silica aerogel using an experimental point spread function.
Light microscopy is a powerful tool that allows for many types of samples to be examined in a rapid, easy, and nondestructive manner. Subsequent image analysis, however, is compromised by distortion of signal by instrument optics. Deconvolution of images prior to analysis allows for the recovery of lost information by procedures that utilize either a theoretically or experimentally calculated point spread function (PSF). Using a laser scanning confocal microscope (LSCM), we have imaged whole impact tracks of comet particles captured in silica aerogel, a low density, porous SiO2 solid, by the NASA Stardust mission. In order to understand the dynamical interactions between the particles and the aerogel, precise grain location and track volume measurement are required. We report a method for measuring an experimental PSF suitable for three-dimensional deconvolution of imaged particles in aerogel. Using fluorescent beads manufactured into Stardust flight-grade aerogel, we have applied a deconvolution technique standard in the biological sciences to confocal images of whole Stardust tracks. The incorporation of an experimentally measured PSF allows for better quantitative measurements of the size and location of single grains in aerogel and more accurate measurements of track morphology.


On parallel and antiparallel topology of a homodimeric multidrug transporter.
The recently suggested antiparallel topology of EmrE has intriguing implications for many aspects of the biology of ion-coupled transporters. However, it is at odds with biochemical data that demonstrated the same topology for all protomers in the intact cell and with extensive cross-linking studies. To examine this apparent contradiction we chemically cross-linked dimers with a rigid bifunctional maleimide using Cys replacements at positions not permissible by an antiparallel topology. A purified cross-linked dimer binds substrate and transports it in proteoliposomes with kinetic constants similar to those of the non-cross-linked dimer. The cross-linked dimers do not interact with non-cross-linked dimers as judged from the fact that inactive mutants do not affect their activity (negative dominance). The results support the contention that EmrE with parallel topology is fully functional. We show that the detergents used in crystallization increase the fraction of monomers in solution. We suggest that the antiparallel orientation observed is a result of the arrangement of the monomers in the crystal. Functionality of EmrE with the suggested antiparallel orientation of the monomers remains to be characterized.


Failure Modes during Low-Voltage Electrowetting.
Low-voltage electrowetting devices allow significant contact angle changes below a 50 V bias; however, operation under prolonged cycling and failure modes have not yet been sufficiently elucidated. In this work, the failure modes and performance degradation of Cytop (23-210 nm)/aluminum oxide (15-44 nm) bilayers have been investigated. Contact angle and leakage current were measured during stepped voltage measurements up to failure, showing three electrowetting response regimes: ideal Young-Lippmann behavior, contact angle saturation, and dielectric breakdown. The onset of ionic conduction in aluminum oxide and the resulting breakdown control when the layer would ultimately fail, but the thickness of the Cytop layer determined the achievable contact angle versus voltage characteristics. Cyclic electrowetting measurements studied the repeatability of contact angle change using an applied voltage above or below the voltage drop needed for polymer breakdown (VT). Results show repeatable electrowetting below VT and a rapidly diminishing contact angle response above VT. The leakage current and injected charge cannot be used to comprehensively assess the stability of the system during operation. The contact potential difference measured with a Kelvin probe provides an alternative means of assessing the extent of the damage.


Comparative metabolism of N-tert-butyl-N-[1-(1-oxy-pyridin-4-yl)-ethyl]- and N-tert-butyl-N-(1-phenyl-ethyl)-nitroxide by the cytochrome P450 monooxygenase system.
The use of spin-trapping agents for a direct ESR detection of *OH in biological systems is limited by the low stability of the hydroxyl radical-derived nitroxides. Among the various probes used for trapping of *OH, DMSO has proven to be highly efficient. The reaction between *OH and DMSO yields methyl radical (CH(3)*), which can react with N-tert-butyl-alpha-phenylnitrone (PBN) and alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) to form stable, ESR-detectable nitroxides. The latter approach has been successfully used in in vivo experiments for analysis of *OH; in these experiments, POBN/*CH(3) and PBN/*CH(3) were detected in the bile duct and the urine of the treated animals. However, the sites of generation of *OH produced in vivo are unknown. Currently, no ESR data is available for the formation of *OH in liver of animals subjected to oxidative stress. Since nitroxides containing aromatic rings are likely to be substrates of cytochrome P450, experiments were carried out for assessing the ability of the cytochrome P450 monooxygenase system to metabolize PBN/*CH(3) and POBN/*CH(3), respectively. In the presence of NADPH, rat liver microsomes catalyzed the reduction of POBN/*CH(3) to the corresponding hydroxylamine (POBN/CH(3)), while PBN/*CH(3) was metabolized without accumulation of its hydroxylamine form (PBN/CH(3)). The metabolism of PBN/.CH(3) was inhibited by 4-methylpyrazole and ketoconasole, suggesting that cytochrome P450-catalysis was required for the consumption of this nitroxide. Under anaerobic conditions, both the nitroxide and hydroxylamine forms of PBN/CH(3) were metabolized, implying that these adducts may undergo reductive cytochrome P450-catalyzed biotransformation. On the basis of the susceptibility of PBN/*CH(3) to undergo irreversible metabolic transformation, it is discussed that POBN may prove to be a more efficient spin-trapping agent for the in vivo detection of *OH.


[Percutaneous renal artery angioplasty--review of current indicators].
The most frequent cause of secondary arterial hypertension is renal artery stenosis. The aetiology of renal artery stenosis is mainly atherosclerotic (75-80%), in the remaining cases fibromuscular dysplasia is the causative factor. Renovascular hypertension has a poorer prognosis than spontaneous because it is more resistant to antihypertensive treatment, signifies an increased risk for the development and progression of malignant hypertension and may lead to irreversible renal dysfunction due to ischaemia. Renal revascularisation has been proved an effective treatment modality in patients with arterial hypertension or renal failure due to renal artery stenosis. However, surgical treatment is associated with the mortality rate of 6-9% due to the concomitant presence of ischaemic heart disease, cerebral and peripheral arteriosclerosis. Percutaneous transluminal renal angioplasty is equally effective in the treatment of arterial hypertension as surgical operation, leading to the improvement or stabilisation of renal function. The advent of renal stenting has markedly changed the efficacy and safety of procedures with PTRA becoming an alternative to surgery. The high efficacy of PTRA is associated with low mortality and relatively few complications as compared with surgical treatment. However, there is continuous discussion concerning the efficacy of percutaneous and surgical renal revascularisation in arterial hypertension. PTRA is currently increasingly frequently recommended in patients with renovascular hypertension not only to control blood pressure but also to protect renal function.


Microvascular reperfusion injury: rapid expansion of anatomic no reflow during reperfusion in the rabbit.
The aim was to define the degree and time course of reperfusion-related expansion of no reflow. In five groups of anesthetized, open-chest rabbits (30-min coronary occlusion and different durations of reperfusion), anatomic no reflow was determined by injection of thioflavin S at the end of reperfusion and compared with regional myocardial blood flow (RMBF; radioactive microspheres) and infarct size (triphenyltetrazolium). The area of no reflow progressively increased from 12.2 +/- 4.2% of the risk area after 2 min of reperfusion to 30.8 +/- 3.1% after 2 h and 34.9 +/- 3.3% after 8 h and significantly correlated with infarct size after 1 h of reperfusion (r = 0.88-0.97). This rapid expansion of no reflow predominantly occurred during the first 2 h, finally encompassing approximately 80% of the infarct size, and was accompanied by a decrease of RMBF within the risk area, being hyperemic after 2 min of reperfusion (3.78 +/- 0.75 ml x min(-1) x g(-1)) and plateauing at a level of approximately 0.9 ml x min(-1) x g(-1) by 2 and 8 h of reperfusion (preischemic RMBF: 2.06 +/- 0.01 ml x min(-1) x g(-1)). The development of macroscopic hemorrhage lagged behind no reflow, was closely correlated with it, and may be the consequence of microvascular damage.


Postpartum substance use and depressive symptoms: a review.
National survey data suggest that new mothers have high prevalences of alcohol and illicit drug use. Depression correlates with substance use, and new mothers with postpartum depression may be at high risk for substance use. Understanding postpartum substance use and its relationship to postpartum depression can inform future research and intervention. A literature search was conducted resulting in 12 studies published from 1999-2012 examining postpartum alcohol use, drug use, or combined postpartum depression and substance use. Postpartum alcohol (prevalence range 30.1%-49%) and drug use (4.5%-8.5%) were lower than use among not pregnant, not postpartum women (41.5%-57.5%, 7.6%-10.6%, respectively) but higher than use among pregnant women (5.4%-11.6%, 3.7%-4.3%, respectively). Correlates of postpartum problem drinking were being unemployed, unmarried, and a cigarette smoker. Prevalence of drug use was highest among white new mothers, followed by blacks and Hispanics, but black new mothers appeared at greater risk of drug use. No identified studies examined correlates of postpartum drug use beyond race/ethnicity. Postpartum depressive symptoms were prevalent among postpartum substance users and those with a substance use history (19.7%-46%). The postpartum period is a critical time. Prevalent substance use and the scarcity of studies warrant research to identify means to reduce maternal substance use.


Life Outcomes and Higher Education: The Need for Longitudinal Research Using a Broad Range of Quality of Life Indicators.
Higher education is increasingly becoming an option for young adults with intellectual disability (ID). Although initial evaluations of postsecondary education for this population have been promising, a broader "quality of life" framework needs to be adopted in order to truly understand the impact of these programs. Moreover, researchers and program evaluators must collect longitudinal data that follows former students for multiple years and uses multiple measures. We conducted a pilot evaluation of the life outcomes of students who had attended at least two semesters in Kentucky's supported higher education program for students with ID, collecting data on life status and experiences using measures from the National Core Indicators-Adult Consumer Survey. The findings from this pilot study show better outcomes for young adults who participated in a postsecondary education program compared to young adults who did not, but these findings need to be considered in light of several limitations. In many respects, our data provided more new questions than answers. Recommendations for collecting and evaluating broad-based, longitudinal data to gain insight into the potential benefits of postsecondary education for people with intellectual disability are discussed.


Heat conduction in driven Frenkel-Kontorova lattices: thermal pumping and resonance.
Heat conduction through the Frenkel-Kontorova chain under the influence of an ac driving force applied locally at one boundary is studied by nonequilibrium molecular dynamics simulations. We observe the occurrence of thermal resonance, namely, there exists a value of the driving frequency at which the heat flux takes its maximum value. The resonance frequency is determined by the dynamical parameters of the model, which has been numerically explored. Remarkably, the heat can be pumped from the low-temperature heat bath to the high temperature one by suitably adjusting the frequency of the ac driving force. By examining effects of the driving amplitude on heat conduction, we show that the amplitude threshold for nonlinear supratransmission is absent when the system is in contact with heat baths, namely, the heat flux smoothly increases with the increasing of amplitude.


MRI-compatible bone phantom for evaluating ultrasonic thermal exposures.
The goal of the proposed study was the development of a magnetic resonance imaging (MRI) compatible bone phantom suitable for evaluating focused ultrasound protocols. High resolution CT images were used to segment femur bone. The segmented model was manufactured with (Acrylonitrile Butadiene Styrene) ABS plastic using a 3-D printer. The surrounding skeletal muscle tissue was mimicked using an agar-silica-evaporated milk gel (2% w/v-2% w/v-40% v/v). MR thermometry was used to evaluate the exposures of the bone phantom to focused ultrasound. The estimated agar-silica-evaporated milk gel's T1 and T2 relaxation times in a 1.5T magnetic field were 776ms and 66ms respectively. MR thermometry maps indicated increased temperature adjacent to the bone, which was also shown in situations of real bone/tissue interfaces. Due to growing interest of using MRI guided Focused Ultrasound Surgery (MRgFUS) in palliating bone cancer patients at terminal stages of the disease, the proposed bone phantom can be utilized as a very useful tool for evaluating ultrasonic protocols, thus minimizing the need for animal models. The estimated temperature measured and its distribution near the bone phantom/agar interface which was similar to temperatures recorded in real bone ablation with FUS, confirmed the phantom's functionality.


Simplified PCR detection method for nasal Mycobacterium leprae.
We report here a simplified method for the detection of nasal carriage of Mycobacterium leprae. DNA extracted from nasal swabs was analyzed by PCR, and M. leprae specific amplicons detected by means of a novel peptide-nucleic-acid-ELISA (PNA-ELISA) method. Parameters for the method were established using swabs taken from untreated lepromatous leprosy patients. We have developed this method to study nasal carriage in endemic populations. However, due to the sensitivity of PCR based techniques, we wished to assess the possibility of false positive samples arising in our method. We therefore examined samples taken from individuals in Norway, a country non-endemic for leprosy, using our technique. A total of 219 nasal swabs were collected and tested in our laboratory in London. All of these were found to be negative by our criteria. In order to corroborate our results, and also to assess the specificity of the method, a small number of these samples were randomly selected, and a known amount of M. leprae DNA added to them. All 219 samples were then retested using the same techniques under "double blind" conditions in our laboratory in India. All of the samples to which M. leprae DNA had been added were successfully identified by this method whereas all other swabs were negative. Taken together, these results suggest that the technique described here is simple, sensitive, and specific for use in large-scale epidemiological studies. This study, part of the larger MILEP 2 study, represents the first use of a PNA-PCR method for an epidemiological study of infection. The method using PNA-ELISA is significantly simpler and more rapid than gel based detection methods. The supply of laboratory consumables and overall detection procedure were simplified and standardized by use of PCR Ready-to-Go beads.


A Reconfigurable Readout Integrated Circuit for Heterogeneous Display-Based Multi-Sensor Systems.
This paper presents a reconfigurable multi-sensor interface and its readout integrated circuit (ROIC) for display-based multi-sensor systems, which builds up multi-sensor functions by utilizing touch screen panels. In addition to inherent touch detection, physiological and environmental sensor interfaces are incorporated. The reconfigurable feature is effectively implemented by proposing two basis readout topologies of amplifier-based and oscillator-based circuits. For noise-immune design against various noises from inherent human-touch operations, an alternate-sampling error-correction scheme is proposed and integrated inside the ROIC, achieving a 12-bit resolution of successive approximation register (SAR) of analog-to-digital conversion without additional calibrations. A ROIC prototype that includes the whole proposed functions and data converters was fabricated in a 0.18 μm complementary metal oxide semiconductor (CMOS) process, and its feasibility was experimentally verified to support multiple heterogeneous sensing functions of touch, electrocardiogram, body impedance, and environmental sensors.


Beta-lactam-resistant Staphylococcus aureus in spinal osteomyelitis and spondylodiscitis: current landscape in antibiotic resistance, treatment, and complications.
Spinal osteomyelitis and spondylodiscitis (SD) are infections of the vertebral body and disc, respectively, with more than 50% associated with Staphylococcus aureus. Methicillin-resistant S. aureus (MRSA) has become a pathogen of interest in cases of SD due to increasing prevalence. The purpose of this investigation was to characterize the current epidemiological and microbiological landscape in SD cases, in addition to medical and surgical challenges in treating these infections. The PearlDiver Mariner database was queried for ICD-10 codes to identify cases of SD from 2015 to 2021. The initial cohort was stratified by offending pathogens, including methicillin-sensitive S. aureus (MSSA) and MRSA. Primary outcome measures included epidemiological trends, demographics, and rates of surgical management. Secondary outcomes included length of hospital stay, rate of reoperation, and complications associated with surgical cases. Multivariable logistic regression was used to control for age, gender, region, and Charlson Comorbidity Index (CCI). Nine thousand nine hundred eighty-three patients met the inclusion criteria and were retained for this study. Approximately half (45.5%) of SD cases resulting from S. aureus infections each year were resistant to beta-lactam antibiotics. The proportion of cases that were managed surgically was 31.02%. Among the cases that involved surgical intervention, 21.83% underwent revision operations within 30 days of the original procedure and 37.29% of cases returned to the operating room within 1 year. Substance abuse, specifically alcohol, tobacco, and drug use, were strong predictors for surgical intervention in cases of SD (all p < 0.001), in addition to obesity (p = 0.002), liver disease (p < 0.001), and valvular disease (p = 0.025). After adjusting for age, gender, region, and CCI, cases of MRSA were more likely to undergo surgical management (OR 1.19, p = 0.003). MRSA SD also exhibited higher rates of reoperation within 6 months (OR 1.29, p = 0.001) and 1 year (OR 1.36, p < 0.001). Surgical cases resulting from MRSA infections also exhibited higher morbidity and significant rates of transfusion (OR 1.47, p = 0.030), acute kidney injury (OR 1.35, p = 0.001), pulmonary embolism (OR 1.44, p = 0.030), pneumonia (OR 1.49, p = 0.002), and urinary tract infection (OR 1.45, p = 0.002) compared with MSSA SD infections. More than 45% of cases of S. aureus SD in the US are resistant to beta-lactam antibiotics, presenting obstacles in treatment. Cases of MRSA SD are more likely to be managed surgically and have higher rates of complications and reoperations. Early detection and prompt operative management are imperative to reduce the risk of complications.


Congenital-infantile fibrosarcoma presenting as a hemangioma: a case report.
Congenital-infantile fibrosarcoma (CIFS) is a rare pediatric soft tissue tumor that on initial clinical presentation can mimic an infantile hemangioma. Management of these conditions differs drastically, and delay in diagnosis and treatment may affect prognosis. A 6-month-old male infant originally presented to dermatology for evaluation of a suspected right buttock hemangioma, present at birth as a small red mass just lateral to the gluteal cleft. The lesion rapidly grew over 2 weeks to a size of 4×4.5×4.5 cm, with violaceous color change and central ulceration. The patient received a course of cephalexin; however, the mass became painful with several episodes of bleeding and did not show clinical improvement. Magnetic resonance imaging and ultrasound supported the diagnosis of atypical hemangioma. Plastic Surgery was consulted for excision due to recurrent bleeding. An excisional biopsy was undertaken and pathologic finding showed CIFS. The case was discussed with Hematology/Oncology and Pediatric Surgery, and the patient underwent re-excision and obtained clear margins. Initial metastatic workup was negative; however, patient had evidence of recurrent disease as well as pulmonary metastasis on his most recent surveillance imaging. He underwent re-excision of the gluteal mass and is currently receiving adjuvant chemotherapy. This case demonstrates a rare malignancy initially misdiagnosed as a hemangioma. Consideration of CIFS is crucial in cases of complicated hemangiomas not responding to standard treatment. Treatment calls for excision with wide margins and/or adjuvant chemotherapy if excision is not possible. Classic pathologic findings, immunohistochemistry, and/or reverse transcription-polymerase chain reaction can confirm the diagnosis. A correct and rapid diagnosis of CIFS is critical to optimizing treatment and subsequent prognosis.


Fabrication of Low Noise Borosilicate Glass Nanopores for Single Molecule Sensing.
We show low-cost fabrication and characterization of borosilicate glass nanopores for single molecule sensing. Nanopores with diameters of ~100 nm were fabricated in borosilicate glass capillaries using laser assisted glass puller. We further achieve controlled reduction and nanometer-size control in pore diameter by sculpting them under constant electron beam exposure. We successfully fabricate pore diameters down to 6 nm. We next show electrical characterization and low-noise behavior of these borosilicate nanopores and compare their taper geometries. We show, for the first time, a comprehensive characterization of glass nanopore conductance across six-orders of magnitude (1M-1μM) of salt conditions, highlighting the role of buffer conditions. Finally, we demonstrate single molecule sensing capabilities of these devices with real-time translocation experiments of individual λ-DNA molecules. We observe distinct current blockage signatures of linear as well as folded DNA molecules as they undergo voltage-driven translocation through the glass nanopores. We find increased signal to noise for single molecule detection for higher trans-nanopore driving voltages. We propose these nanopores will expand the realm of applications for nanopore platform.


[A Case of Ascending Colon Cancer with Lynch Syndrome Who Underwent XELOX Adjuvant Chemotherapy].
Lynch syndrome is an inherited syndrome with the development of the colorectal and various other cancers. Lynch syndrome is caused by mutations in the mismatch repair genes. A 33 year-old male underwent XELOX adjuvant chemotherapy for ascending colon cancer with Lynch syndrome. Although efficacy of 5-FU is not demonstrated in Lynch syndrome, MOSAIC trial had suggested a benefit from FOLFOX compared with 5-FU in patients who have colorectal cancer with Lynch syndrome. Oxaliplatin-based adjuvant chemotherapy can be a therapeutic option for colorectal cancer in lynch syndrome patients.


First observation of homozygote Hb Q-Iran (alpha 75 (EF4) Asp-His).
The first observation of homozygote Hb Q-Iran (α1 75(EF4) Asp-His) is presented in this report. The clinical and hematological data of the index case, his father and mother showed that homozygous or heterozygous Hb Q-Iran has no clinical importance.


Centroid position estimating method for observational analysis.
[Purpose] This study aimed to develop a clinical observation method to evaluate the position of the mass center. From the human visual capability, we considered it would be practical to divide the body into two parts: the upper and the lower body mass. If we could identify their optimal position, we could observe the middle point in between as the center of mass. [Participants and Methods] Twenty healthy males performed forward bending, backward bending, squatting, and walking. The three-dimensional coordinates were analyzed using a conventional model. In addition, five "virtual" markers were assigned as upper and lower mass, respectively. The midpoints of each five virtual marker combinations defined the mass centers, providing 25 coordinates. We calculated the difference in the coordinates between mass centers from virtual markers and mass centers using a conventional model. The combination with the slightest error was evaluated to determine the 95% confidence interval of the observed points and whether the value was clinically beneficial. [Results] The optimal combination of the upper and lower mass was Th8 and in the middle of both hip and knee centers. [Conclusion] The overall magnitude of error was about 30 mm and enough to evaluate the center of mass with macroscopy.


Symptoms in advanced cancer: relationship to endogenous cortisol levels.
We investigated a possible relationship between levels of endogenous cortisol and severity of different symptoms in patients with advanced cancer. Twenty-three patients with predominantly gastrointestinal cancer, recruited in a palliative care unit, entered the study. Urinary free cortisol (UFC) was measured together with demographic data, blood parameters, tumour burden, concurrent illness, medication, nutritional status and quality of life. Significant positive correlations were found between levels of endogenous cortisol and appetite loss, fatigue and nausea/vomiting. The findings support the view of a chronic stress condition in advanced cancer. Interaction between cytokines and the hypothalamic-pituitary-adrenal (HPA) axis may also be important in the interpretation of the results.


A plant Bcl-2-associated athanogene is proteolytically activated to confer fungal resistance.
The Bcl-2-associated athanogene (BAG) family is a multifunctional group of proteins involved in numerous cellular functions ranging from apoptosis to tumorigenesis. These proteins are evolutionarily conserved and encode a characteristic region known as the BAG domain. BAGs function as adapter proteins forming complexes with signaling molecules and molecular chaperones. In humans, a role for BAG proteins has been suggested in tumor growth, HIV infection, and neurodegenerative diseases; as a result, the BAGs are attractive targets for therapeutic interventions, and their expression in cells may serve as a predictive tool for disease development. The Arabidopsis genome contains seven homologs of BAG family proteins (Figure 1), including four with a domain organization similar to animal BAGs (BAG1-4). The remaining three members (BAG5-7) contain a predicted calmodulin-binding motif near the BAG domain, a feature unique to plant BAG proteins that possibly reflects divergent mechanisms associated with plant-specific functions. As reported for animal BAGs, plant BAGs also regulate several stress and developmental processes (Figure 2). The recent article by Li et al. focuses on the role of BAG6 in plant innate immunity. This study shows that BAG6 plays a key role in basal plant defense against fungal pathogens. Importantly, this work further shows that BAG6 is proteolytically activated to induce autophagic cell death and resistance in plants. This finding underscores the importance of proteases in the execution of plant cell death, yet little is known about proteases and their substrates in plants.


Bladder neck obstruction in the female.
Bladder neck dysfunction is a rare cause of obstruction in women. The symptoms are nonspecific and diagnosis relies on video-urodynamic evaluation. In this case study, a woman presented with urinary retention, recurring urinary tract infections, and bilateral hydronephrosis, in whom video-urodynamics revealed bladder neck obstruction. Her clinical presentation, as well as the pertinent literature on the diagnosis and treatment of bladder neck obstruction in women, are reviewed.


Configurational temperature in active matter. I. Lines of invariant physics in the phase diagram of the Ornstein-Uhlenbeck model.
This paper shows that the configurational temperature of liquid-state theory, T_{conf}, defines an energy scale, which can be used for adjusting model parameters of active Ornstein-Uhlenbeck particle (AOUP) models in order to achieve approximately invariant structure and dynamics upon a density change. The required parameter changes are calculated from the variation of a single configuration's T_{conf} for a uniform scaling of all particle coordinates. The resulting equations are justified theoretically for models involving a potential-energy function with hidden scale invariance. The validity of the procedure is illustrated by computer simulations of the Kob-Andersen binary Lennard-Jones AOUP model, showing the existence of lines of approximate invariance of the reduced-unit radial distribution function and time-dependent mean-square displacement.


Perceived determinants to alcohol consumption and misuse: a survey of university students.
Before an attempt is made to develop any population-specific behavioural change programme, it is important to know what the factors that influence behaviours are. The aim of this study was to identify what are the perceived determinants that attribute to young people's choices to both consume and misuse alcohol. Using a descriptive survey design, a web-based questionnaire based on the Theory of Triadic Influence was administered to students aged 18-29 years at one university in Northern Ireland. Out of the total respondents ( n = 595), knowledge scores on alcohol consumption and the health risks associated with heavy episodic drinking were high (92.4%, n = 550). Over half (54.1%, n = 322) cited the Internet as their main source for alcohol-related information. The three most perceived influential factors of inclination to misuse alcohol were strains/conflict within the family home ( M = 2.98, standard deviation ( SD) = 0.18, 98.7%, n = 587), risk taking/curiosity behaviour ( M = 2.97, SD = 0.27, 97.3%, n = 579) and the desire not to be socially alienated ( M = 2.94, SD = 0.33, 96%, n = 571). Females were statistically significantly more likely to be influenced by desire not to be socially alienated than males ( p = .029). Religion and personal reasons were the most commonly cited reasons for not drinking. Future initiatives to reduce alcohol misuse and alcohol-related harms need to focus on changing social normative beliefs and attitudes around alcohol consumption and the family and environmental factors that influence the choice of young adult's alcohol drinking behaviour. Investment in multi-component interventions may be a useful approach.


A survey of Heterophyes nocens and Pygidiopsis summa metacercariae in mullets and gobies along the coastal areas of the Republic of Korea.
The infection status of mullets Mugil cephalus (n = 139) and gobies (n = 35) Acanthogobius flavimanus with metacercariae of Heterophyes nocens and Pygidiopsis summa was examined in 11 western, southern, and eastern coastal areas of the Republic of Korea, using a digestion technique. Heterophyid metacercariae were highly prevalent in mullets from western and southern coastal areas; Shinan-gun (100% for H. nocens and 100% for P. summa), Muan-gun (93% and 100%), Buan-gun (42% and 75%), Seocheon-gun (73% and 53%), Ganghwa-gun (47% and 100%), Sacheon-shi (47% and 77%), and Gangjin-gun (50% and 70%, respectively). Only 1 (10%) of 10 mullets from an eastern coastal area, i.e., Donghae-shi, was positive for P. summa metacercariae. Metacercarial densities were the highest in the trunk of mullets for H. nocens and the gill for P. summa. Gobies from Muan-gun were positive for H. nocens (40%) and P. summa metacercariae (40%), and gobies from Seocheon-gun revealed H. nocens metacercariae (20%). The metacercarial density was remarkably higher in mullets than in gobies. The results revealed that H. nocens and P. summa metacercariae are prevalent in mullets and gobies from coastal areas of the Republic of Korea, and the prevalence and intensity of infection vary according to geographical locality.


Inhibited and aggressive preschool children at 23 years of age: personality and social transitions into adulthood.
In a 19-year longitudinal study, the 15% most inhibited and the 15% most aggressive children at ages 4-6 years were followed up until age 23 years and were compared with controls who were below average in preschool inhibition or aggressiveness. As adults, inhibited boys and girls were judged as inhibited by their parents and showed a delay in establishing a first stable partnership and finding a first full-time job. However, only the upper 8% in terms of inhibition tended to show internalizing problems, including self-rated inhibition. Aggressive boys showed an externalizing personality profile in the parental and self-judgments, were educational and occupational underachievers, and showed a higher adult delinquency rate than the controls, even after sex and socioeconomic status were controlled. The results suggest delayed social transitions without internalizing problems for most male and female inhibited children and a significant long-term risk of an externalizing profile for aggressive children.


Stability of Ar(H2)2 to 358 GPa.
"Chemical precompression" through introducing impurity atoms into hydrogen has been proposed as a method to facilitate metallization of hydrogen under external pressure. Here we selected Ar(H2)2, a hydrogen-rich compound with molecular hydrogen, to explore the effect of "doping" on the intermolecular interaction of H2 molecules and metallization at ultrahigh pressure. Ar(H2)2 was studied experimentally by synchrotron X-ray diffraction to 265 GPa, by Raman and optical absorption spectroscopy to 358 GPa, and theoretically using the density-functional theory. Our measurements of the optical bandgap and the vibron frequency show that Ar(H2)2 retains 2-eV bandgap and H2 molecular units up to 358 GPa. This is attributed to reduced intermolecular interactions between H2 molecules in Ar(H2)2 compared with that in solid H2 A splitting of the molecular vibron mode above 216 GPa suggests an orientational ordering transition, which is not accompanied by a change in lattice symmetry. The experimental and theoretical equations of state of Ar(H2)2 provide direct insight into the structure and bonding of this hydrogen-rich system, suggesting a negative chemical pressure on H2 molecules brought about by doping of Ar.


[Graft versus host reaction and hybrid resistance in experimental models and clinical practice].
The "F1 hybrid transplantation law" states that F1 hybrids of two unrelated inbred strains of mice accept grafts from either parent strain while neither parent accept grafts from the F1 hybrid. However, there are two notable exceptions to this law. Indeed, parent grafts containing immunologically competent cells (spleen cells, bone marrow etc.) react against the F1 normal hosts in which they are placed. In the absence of a host-versus-graft reaction, the graft-versus-host reaction (GvH) may dominate the field and cause untoward reactions which not only negate any benefit derived from the graft, but also cause significant, and often fatal morbidity of the host, that is, a GvH Disease (GvHD). Furthermore, irradiated F1 mice are refractory to the grafting of parental bone marrow, lymphoma cells and normal lymphocytes because of a restriction by non-co-dominant, besides that of codominant MHC-H2 genes. These non-co-dominant genes have been designated Hh genes for Hybrid histocompatibility and the phenomenon itself, hybrid resistance. The cellular, humoral and genetic mechanisms involved in the GvH and hybrid resistance production are explained and discussed in the first, while in the second section of the present review, their equivalent in three human pathological situations are taken into consideration. We focus in detail on two principal immunologic aspects of human bone marrow transplantation: GvH and hematopoietic engraftment; each one of these immunologic aspects has considerable impact on the course and outcome of marrow transplantation in humans. The allograft implantation between HLA-genetically-identical siblings, HLA-aploidentical family members or HLA-phenotypically identical donor-recipient couples are herewith examined, while the autologous bone marrow rescue approach is not taken into consideration. The outcome of bone marrow transplantation depends not only on the degree of genetic disparity between the donor and the recipient, but also on the underlying disease. Bone marrow transplantation is the therapy of choice for patients with aplastic anemia, severe combined immunodeficiency (SCID) and other genetic and acquired immunodeficiency, some leukemias and a few other diseases, mainly if HLA-genetically-identical siblings are available. However, in many cases such siblings are not available. Therefore, the probability of acute or chronic GvHD or graft rejection increases significantly. The clinical and pathologic manifestations, the prognostic factors, and the treatment and prevention of acute and chronic GvHD are illustrated in detail.(ABSTRACT TRUNCATED AT 400 WORDS)


A reply to Joseph Bernstein.
Dr. Bernstein suggests that anti-vivisectionists should be able to fill in a directive requesting that they receive no medical treatment developed through work on animals. It is replied that this would only be reasonable if research not using animals had long been funded as adequately and its results were currently available.


Development of a mitoxantrone-resistant P 388 in vivo: approaches to overcome resistance.
A normally, relatively sensitive P 388 developed resistance within few passages (P 388/Mitox) by in vivo treatment with suboptimal doses (1 mg/kg i.v.) of mitoxantrone. This resistance remained stable over 50 generations without further drug treatment. Immunization with irradiated cells (30 Gy) 7 days before tumor challenge led to partial rejection, proving that there was a higher immunogenicity of the resistant line in comparison to the parenteral P 388 line. The P 388/Mitox showed cross-resistance towards doxorubicin, daunorubicin and vincristine. Cis-DDP and bleomycin had in the resistant line significantly better antineoplastic efficacy than in the source P 388 and should be taken into consideration as second-line therapy following development of clinical mitoxantrone resistance. Nifedipine, a calcium channel blocker, and the immunosuppressive agent ciclosporin A were able to overcome resistance partially, but the mechanisms are still unclear. The P 388/Mitox can be considered as an interesting in vivo model for further research concerning resistance mechanisms and reversal of resistance.


Body Composition and S-Klotho Plasma Levels in Middle-Aged Adults: A Cross-Sectional Study.
The α-Klotho gene was identified as a possible "aging-suppressor" agent that extends life span when overexpressed. However, little is known about the association of the body composition with the secreted protein form of the α-Klotho gene (S-Klotho). Therefore, the aim of this study was to analyze the association of body composition, including lean and fat mass as well as bone mineral density (BMD), with S-Klotho plasma levels in middle-aged sedentary adults. A total of 74 (39 women) middle-aged sedentary adults (53.7 ± 5.1 years old; 75.7 ± 14.0 kg; 167.8 ± 9.8 cm) participated in the study. We measured weight and height, and we used dual-energy X-ray absorptiometry to measure fat mass and lean mass. We calculated the body mass index (BMI), fat mass index (FMI), and lean mass index (LMI). The S-Klotho plasma levels were measured in the ethylenediaminetetraacetic acid plasma using a solid-phase sandwich enzyme-linked immunosorbent assay. There was a strong positive association between LMI and S-Klotho plasma levels (β = 74.794, R2 = 0.346, p < 0.001), which persisted after controlling for age and gender as well as after additionally controlling for FMI. Significantly positive associations of BMI and BMD were also found with S-Klotho plasma levels (β = 33.981, R2 = 0.125, p = 0.002 and β = 858.194, R2 = 0.058, p = 0.041, respectively), which disappeared after controlling for LMI (β = 0.183, R2 = 0.611, p = 0.984 and β = -379.426, R2 = 0.617, p = 0.290, respectively). FMI was not significantly associated with S-Klotho plasma levels. Our study shows that LMI is strongly associated with S-Klotho plasma levels and explains the associations of BMI and BMD with S-Klotho plasma levels in middle-aged sedentary adults.


Electron attachment to C(2)Cl(4) and Trojan horse ionization.
In a recent study of tetrachloroethylene, the anion yield curves were analyzed using three published negative-ion Morse potentials. Unexpected ions at zero electron energy were explained by the "Trojan horse" mechanism. This communication also attributes formation of Cl(2)(-) at higher energies to a Trojan horse mechanism. Six new Morse potentials are calculated to account for the observed anion states. These combine all extant electron impact and attachment data. The electron affinity of the C(2)Cl(3) radical, 3.1(1) eV, and the C-Cl bond dissociation energy 4.0(1) eV are reported.


Paroxysmal Dyskinesia in Border Terriers: Clinical, Epidemiological, and Genetic Investigations.
In the last decade, a disorder characterized by episodes of involuntary movements and dystonia has been recognized in Border Terriers. To define clinical features of paroxysmal dyskinesia (PD) in a large number of Border Terriers and to study the genetics of the disease. 110 affected and 128 unaffected client-owned Border Terriers. A questionnaire regarding clinical characteristics of PD was designed at Utrecht University and the University of Helsinki. Thirty-five affected Border Terriers underwent physical examination and blood testing (hematology and clinical biochemistry). Diagnostic imaging of the brain was performed in 17 affected dogs and electroencephalograms (EEG) between episodes were obtained in 10 affected dogs. A genomewide association study (GWAS) was performed with DNA of 110 affected and 128 unaffected dogs. One hundred forty-seven questionnaires were included in the study. The most characteristic signs during episodes were dystonia, muscle fasciculations, and falling over. The majority of owners believed that their dogs remained conscious during the episodes. A beneficial effect of anti-epileptic therapy was observed in 29 of 43 dogs. Fifteen owners changed their dogs' diet to a hypoallergenic, gluten-free diet, and all reported reasonable to good improvement of signs. Clinical examinations and diagnostic test results were unremarkable. The GWAS did not identify significantly associated chromosome regions. The survey results and EEG studies provided further evidence that the observed syndrome is a PD rather than epilepsy. Failure to achieve conclusive results by GWAS indicates that inheritance of PD in Border Terriers probably is complex.


Risk-based containment and air monitoring criteria for work with dispersible radioactive materials.
This paper presents readily understood, technically defensible, risk-based containment and air monitoring criteria, which are developed from fundamental physical principles. The key for the development of each criterion was the use of a calculational de minimis level, in this case chosen to be 100 mrem (or 40 DAC-h). Examples are provided that demonstrate the effective use of each criterion. Comparison to other often used criteria is provided.


Treatment decisions and discontinuation of palliative chemotherapy near the end-of-life, in relation to socioeconomic variables.
During the last decades, the possibilities to prolong survival with chemotherapy even in metastatic disease have increased. Our aim was to study treatment decisions and treatment discontinuation decisions in the proximity of death. The medical records of 346 patients with disseminated cancer and a recorded death during 2009 were assessed in relation to demographic and clinical variables and documented treatment decisions were recorded. Palliative chemotherapy was offered in 54% or these cases and generally one or two regimens were administered, before ending treatment. During the last month of life, 32% received treatment and much more often as an oral (instead of intravenous) treatment than in earlier stages (p < 0.001). Younger patients (p = 0.02) and those with young children (p < 0.001) were treated to a higher degree and also closer to death (p = 0.03). Other variables associated with a higher probability of treatment were high education level (p = 0.001), living with a partner (p = 0.001), female gender (p = 0.023) and ethnicity of non-European origin (p = 0.031). In a multivariate analysis, young age and high education remained as independent factors. In 57% of the cases there was no formal documentation of treatment discontinuation or end-of-life discussions with the patient. Socioeconomic status (SES) is of importance for the treatment decisions. About half of the patients with disseminated disease receive palliative chemotherapy and of these, about one third are treated even during the last month of life. In a majority of cases, there is no formal documentation of treatment discontinuation or end-of-life discussions.


Stability analysis of a delayed Hopfield neural network.
In this paper, we study a class of neural networks, which includes bidirectional associative memory networks and cellular neural networks as its special cases. By Brouwer's fixed point theorem, a continuation theorem based on Gains and Mawhin's coincidence degree, matrix theory, and inequality analysis, we not only obtain some different sufficient conditions ensuring the existence, uniqueness, and global exponential stability of the equilibrium but also estimate the exponentially convergent rate. Our results are less restrictive than previously known criteria and can be applied to neural networks with a broad range of activation functions assuming neither differentiability nor strict monotonicity.


The role of follicular and interdigitating dendritic cells in HIV-related lymphoid hyperplasia: localization of fascin.
Fascin is a 55-kDa, actin-bundling protein expressed in follicular and interdigitating dendritic cells (DCs). Because these cells play a pivotal role in the pathogenesis of human immunodeficiency virus-related lymphoid hyperplasias (HLP), we evaluated them in 49 cases by immunohistochemical localization of fascin, and we related the findings to the histologic stage of disease. Fifteen cases of early HLP revealed strong localization of fascin within DCs of hyperplastic follicles and intense staining in interdigitating DCs and their processes in the interfollicular zones. Some follicles revealed focal disruption of the fascin-positive dendritic framework. DCs were also aligned beneath the peripheral sinuses of the node. In 15 cases of progressive HLP with partial follicular involution, 3 cases revealed findings similar to those described above. Twelve cases revealed loss of follicular dendritic staining, which was moderate in five cases and marked in seven. Residual clusters of DCs remained after partial dissolution. Interfollicular dendritic staining was reduced in 13 cases, and perisinusoidal staining was reduced in 7. In late-stage HLP, staining of both follicular and interdigitating DCs was reduced or absent. Nine cases of diffuse immunoblastic or angioimmunoblastic lymphadenopathy-like proliferation had markedly reduced or absent follicular DCs, but prominent staining was present in interfollicular DCs, which formed a meshwork throughout the node in eight cases. Two cases of hyaline-vascular lymphoid hyperplasia had increased follicular DCs forming a tight syncytial network. In most cases, there was reduction of dendritic fascin-expressing cells with advanced disease and destruction of the dendritic framework of the node. Diffuse hyperplasia of fascin-positive interdigitating cells occurred in cases with angioimmunoblastic morphologic features, and cases of hyaline-vascular lymphoid hyperplasia had increased follicular dendritic histiocytes forming a tight syncytial network. Destruction of DCs and, in some cases, interdigitating cell hyperplasia might be associated with the variable clinical course of HLP.


Air Pollution, Neighbourhood Socioeconomic Factors, and Neural Tube Defects in the San Joaquin Valley of California.
Environmental pollutants and neighbourhood socioeconomic factors have been associated with neural tube defects, but the potential impact of interaction between ambient air pollution and neighbourhood socioeconomic factors on the risks of neural tube defects is not well understood. We used data from the California Center of the National Birth Defects Study and the Children's Health and Air Pollution Study to investigate whether associations between air pollutant exposure in early gestation and neural tube defects were modified by neighbourhood socioeconomic factors in the San Joaquin Valley of California, 1997-2006. There were 5 pollutant exposures, 3 outcomes, and 9 neighbourhood socioeconomic factors included for a total of 135 investigated associations. Estimates were adjusted for maternal race-ethnicity, education, and multivitamin use. We present below odds ratios (ORs) that exclude 1 and a chi-square test of homogeneity P-value of <0.05. We observed increased odds of spina bifida comparing the highest to lowest quartile of particulate matter <10 μm (PM10 ) among those living in a neighbourhood with: (i) median household income of less than $30 000 per year [OR 5.1, 95% confidence interval (CI) 1.7, 15.3]; (ii) more than 20% living below the federal poverty level (OR 2.6, 95% CI 1.1, 6.0); and (iii) more than 30% with less than or equal to a high school education (OR 3.2, 95% CI 1.4, 7.4). The ORs were not statistically significant among those higher socioeconomic status (SES) neighbourhoods. Our results demonstrate effect modification by neighbourhood socioeconomic factors in the association of particulate matter and neural tube defects in California.


Bis(imidazolium)-calix[4]arene receptors for anion binding.
Efficient access to the bis(imidazolyl)calixarene 2 and dicationic bis(imidazolium) salts 1a,b x 2X directly bonded to the upper rim of calixarene structure has been reported. Anion binding properties of the new receptors were studied by 1H NMR spectroscopic methods. Bis(N-butylimidazolium) dication 1a exhibited the best recognition properties toward carboxylate anions with a 1:1 receptor-anion binding stoichiometry, whereas the presence of a bulky group such as isopropyl (1b) increased the difficulty of both imidazolium moieties to be able to support the association with the same single anion.


Development of an integrated energetic neutral particle measurement system on experimental advanced full superconducting tokamak.
Full function integrated, compact silicon photodiode based solid state neutral particle analyzers (ssNPA) have been developed for energetic particle (EP) relevant studies on the Experimental Advanced Superconducting Tokamak (EAST). The ssNPAs will be mostly operated in advanced current mode with a few channels to be operated in conventional pulse-counting mode, aiming to simultaneously achieve individually proved ultra-fast temporal, spatial, and spectral resolution capabilities. The design details together with considerations on EAST specific engineering realities and physics requirements are presented. The system, including a group of single detectors on two vertical ports and two 16-channel arrays on a horizontal port, can provide both active and passive charge exchange measurements. ssNPA detectors, with variable thickness of ultra thin tungsten dominated foils directly deposited on the front surface, are specially fabricated and utilized to achieve about 22 keV energy resolution for deuterium particle detection.


Mitochondrial Ca2+ removal amplifies TRAIL cytotoxicity toward apoptosis-resistant tumor cells via promotion of multiple cell death modalities.
Ca2+ has emerged as a new target for cancer treatment since tumor-specific traits in Ca2+ dynamics contributes to tumorigenesis, malignant phenotypes, drug resistance, and survival in different tumor types. However, Ca2+ has a dual (pro-death and pro-survival) function in tumor cells depending on the experimental conditions. Therefore, it is necessary to minimize the onset of the pro-survival Ca2+ signals caused by the therapy. For this purpose, a better understanding of pro-survival Ca2+ pathways in cancer cells is critical. Here we report that Ca2+ protects malignant melanoma (MM) and osteosarcoma (OS) cells from tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) cytotoxicity. Simultaneous measurements using the site-specific Ca2+ probes showed that acute TRAIL treatment rapidly and dose-dependently increased the cytosolic Ca2+ concentration ([Ca2+]cyt) and mitochondrial Ca2+ concentration ([Ca2+]mit) Pharmacological analyses revealed that the [Ca2+]mit remodeling was under control of mitochondrial Ca2+ uniporter (MCU), mitochondrial permeability transition pore (MPTP), and a Ca2+ transport pathway sensitive to capsazepine and AMG9810. Ca2+ chelators and the MCU inhibitor ruthenium 360, an MPTP opener atractyloside, capsazepine, and AMG9810 all decreased [Ca2+]mit and sensitized these tumor cells to TRAIL cytotoxicity. The Ca2+ modulation enhanced both apoptotic and non-apoptotic cell death. Although the [Ca2+]mit reduction potentiated TRAIL-induced caspase-3/7 activation and cell membrane damage within 24 h, this potentiation of cell death became pronounced at 72 h, and not blocked by caspase inhibition. Our findings suggest that in MM and OS cells mitochondrial Ca2+ removal can promote apoptosis and non-apoptotic cell death induction by TRAIL. Therefore, mitochondrial Ca2+ removal can be exploited to overcome the resistance of these cancers to TRAIL.


Immune Recognition of the Epidemic Cystic Fibrosis Pathogen Burkholderia dolosa.
Burkholderia dolosa caused an outbreak in the cystic fibrosis (CF) clinic at Boston Children's Hospital from 1998 to 2005 and led to the infection of over 40 patients, many of whom died due to complications from infection by this organism. To assess whether B. dolosa significantly contributes to disease or is recognized by the host immune response, mice were infected with a sequenced outbreak B. dolosa strain, AU0158, and responses were compared to those to the well-studied CF pathogen Pseudomonas aeruginosa In parallel, mice were also infected with a polar flagellin mutant of B. dolosa to examine the role of flagella in B. dolosa lung colonization. The results showed a higher persistence in the host by B. dolosa strains, and yet, neutrophil recruitment and cytokine production were lower than those with P. aeruginosa The ability of host immune cells to recognize B. dolosa was then assessed, B. dolosa induced a robust cytokine response in cultured cells, and this effect was dependent on the flagella only when bacteria were dead. Together, these results suggest that B. dolosa can be recognized by host cells in vitro but may avoid or suppress the host immune response in vivo through unknown mechanisms. B. dolosa was then compared to other Burkholderia species and found to induce similar levels of cytokine production despite being internalized by macrophages more than Burkholderia cenocepacia strains. These data suggest that B. dolosa AU0158 may act differently with host cells and is recognized differently by immune systems than are other Burkholderia strains or species.


Relationship of biomarkers of extracellular matrix with myocardial function in Type 2 diabetes mellitus.
The study evaluated the relationship of extracellular matrix and renin angiotensin system with myocardial dysfunction in Type 2 diabetes mellitus. All patients underwent resting and exercise echocardiography, including conventional parameters, E/E' ratio, global longitudinal strain and diastolic function reserve index. Plasma matrix metalloproteinase-1, TIMP-1, amino-terminal propeptide of type I and type III procollagen and renin angiotensin system activity were measured. As patients with diastolic dysfunction had a higher plasma level of TIMP-1 and propeptide of type III procollagen than those with no diastolic dysfunction. After multivariate adjustment, TIMP-1 associated with E/E' (both at rest and stress) and diastolic function reserve index. TIMP-1 is independently associated with myocardial diastolic dysfunction in patients with Type 2 diabetes mellitus.