Effects of weak, low-frequency pulsed electromagnetic fields (BEMER type) on gene expression of human mesenchymal stem cells and chondrocytes: an in vitro study.
In vitro effects of electromagnetic fields appear to be related to the type of electromagnetic field applied. Previously, we showed that human osteoblasts display effects of BEMER type electromagnetic field (BTEMF) on gene regulation. Here, we analyze effects of BTEMF on gene expression in human mesenchymal stem cells and chondrocytes. Primary mesenchymal stem cells from bone marrow and the chondrocyte cell line C28I2 were stimulated 5 times at 12-h intervals for 8 min each with BTEMF. RNA from treated and control cells was analyzed for gene expression using the affymetrix chip HG-U133A. A limited number of regulated gene products from both cell types mainly affect cell metabolism and cell matrix structure. There was no increased expression of cancer-related genes. RT-PCR analysis of selected transcripts partly confirmed array data. Results indicate that BTEMF in human mesenchymal stem cells and chondrocytes provide the first indications to understanding therapeutic effects achieved with BTEMF stimulation.


Intergenerational continuity in alcohol misuse: Maternal alcohol use disorder and the sequelae of maternal and family functioning.
Early onset of alcohol use is associated with a host of detrimental outcomes. As such, understanding the complex etiology of early onset alcohol use for prevention purposes is an important goal. Specific environmental stressors within the family (i.e., financial stress, negative parental well-being and negative family climate) heighten the risk of early onset alcohol use; however, the extent to which these factors are set in motion by prior maternal history of alcohol misuse has yet to be investigated. We used prospective, longitudinal data from 385 mother-child dyads to examine the link between a maternal alcohol use disorder and her child's early onset of alcohol use through the sequelae of maternal financial strain, maternal depressive symptoms, maternal excessive alcohol use, and negative family climate. Results indicate that a maternal alcohol use disorder itself, and the confluence of a maternal alcohol use disorder, subsequent financial strain, and depressive symptoms produce a negative family climate. In turn, a negative family climate increases the likelihood of alcohol use by the age of 15 among offspring. Moreover, we demonstrate that the cascade of consequences on maternal and family functioning linking a maternal alcohol use disorder to her child's early onset of alcohol use is proximal in nature, unfolding concurrently rather than in yearly spans of time. We discuss the implications of these findings with respect to the etiology of early onset alcohol use (and extant theoretical models) and prevention programming. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Evidence of metachronous development of ovarian teratomas: a case report of bilateral mature cystic teratomas of the ovaries and systematic literature review.
Mature cystic teratomas are usually found in the ovaries. They are bilateral in 10 to 15% of cases and multiple cystic teratomas may be present in one ovary. The aim of this study is to clarify if development of mature cystic teratomas of the ovaries in a single host is metachronous or due to autoimplant or recurrence. We report a woman with bilateral mature cystic teratomas of the ovaries. DNA profiles of these teratomas were investigated via short tandem repeat (STR) analysis and methylation statuses were determined via methylation sensitive multiplex ligation-dependent probe amplification methods. The results showed that the cystic teratomas originated from different stages of oogonia or primary oocyte before germinal vesicle stage failure of meiosis I in female gametogenesis. Potentially relevant literature was searched in PubMed database. Cases of bilateral or multiple mature cystic teratomas of the ovaries were analyzed. To date, there has been no reported case of multiple mature cystic teratomas in which clarification of the origin was achieved using molecular genetic methods. The results of this case study provide evidence of metachronous development of mature cystic teratomas of the ovaries and may serve as a reference in the management of patients following laparoscopic cystectomy.


High performance liquid chromatographic determination of Picumast and two active metabolites in plasma using on-line sample preparation.
A method for determining Picumast, an antiallergic drug, in plasma by HPLC and column switching has been developed. The system consisted of two precolumns, an analytical column, three pumps, an autosampler and a fluorescence detector. The precolumns (17 x 4.6 mm i.d.) were packed with LiChroprep RPR (a moderately polar reversed phase) and the analytical column with Nucleosil ODS (RP 18, 5 microns). The columns were connected according to the alternating precolumn technique. The mobile phase consisted of 30% CH3CN/70% 0.05 M KH2PO4, pH 2.5, with a flow gradient. Detection wavelengths were 333 nm for excitation and 383 nm for emission. The retention times of Picumast, M1 and M2 were 12, 3.6 and 4.0 min, respectively. Total run time was 15 min. The limit of detection was 3 ng/mL for M1 and 1 ng/mL for M2 and Picumast using an injection volume of 150 microL. The recoveries vary between 89% and 97% with standard deviations between 2.4 and 3.3%.


Occupational formaldehyde and amyotrophic lateral sclerosis.
Prior studies have yielded inconsistent evidence regarding the association between formaldehyde exposure and amyotrophic lateral sclerosis (ALS). We conducted a population case-control study in the Danish National Registries on the relationship between occupationally-derived formaldehyde exposure and ALS. Occupational history was obtained from a comprehensive and prospectively recorded pension database of all paid work in Denmark since 1964, and was linked to a job-exposure matrix to derive individual exposure estimates. Each case was matched to 4 age- and sex-matched population controls alive on the date of the case diagnosis via risk set sampling, and odds ratios and confidence intervals (CI) were calculated via conditional logistic regression, adjusting for potential confounders. There were 3650 incident cases of ALS in the Danish National Patient Register from 1982 to 2009. Among controls, 25% were ever employed in jobs with a positive prevalence of formaldehyde exposure. Exposure to formaldehyde was associated with a 1.3-fold increased rate of ALS (95% CI 1.2-1.4). This study suggests that formaldehyde exposure, or employment in formaldehyde-exposed occupations, is related to the risk of ALS.


Building and Implementing an Operational Plan.
Radiology practices engage in planning processes with varying frequency. Organizational planning can occur on three levels. Strategic planning is an infrequent event occurring every 5-7 years. It is aspirational and is guided by the mission and the vision of the organization. Operational planning is a yearly process in which businesses articulate their goals for the year. Creating a yearly operational plan provides departmental employees with a road map for the upcoming year and helps to tie their daily activities to the larger strategic plan of the organization. Finally, a project plan provides details describing how a specific goal will be met. The differences among these three types of plans (strategic plan, operational plan, and project plan) are described. The article then focuses on operational planning, providing a rationale for building an operational plan and then a description of the method used in the authors' division to build an operational plan. ©RSNA, 2018.


Quantifying the decanalizing effects of spontaneous mutations in rhabditid nematodes.
The evolution of canalization, the robustness of the phenotype to environmental or genetic perturbation, has attracted considerable recent interest. A key step toward understanding the evolution of any phenotype is characterizing the rate at which mutation introduces genetic variation for the trait (the mutational variance, V(M)) and the average directional effects of mutations on the trait mean (DeltaM). In this study, the mutational parameters for canalization of productivity and body volume are quantified in two sets of mutation accumulation lines of nematodes in the genus Caenorhabditis and are compared with the mutational parameters for the traits themselves. Four results emerge: (1) spontaneous mutations consistently decanalize the phenotype; (2) the mutational parameters for decanalization, V(M) (quantified as mutational heritability) and DeltaM, are of the same order of magnitude as the same parameters for the traits themselves; (3) the mutational parameters for canalization are roughly correlated with the parameters for the traits themselves across taxa; and (4) there is no evidence that residual segregating overdominant loci contribute to the decay of canalization. These results suggest that canalization is readily evolvable and that any evolutionary factor that causes mutations to accumulate will, on average, decanalize the phenotype.


Longitudinal in vivo maturational changes of metabolites in the prefrontal cortex of rats exposed to polyinosinic-polycytidylic acid in utero.
Proton magnetic resonance spectroscopy ((1)H MRS) studies in schizophrenia patients generally report decreased levels of N-acetyl-aspartate (NAA), glutamate and glutathione, particularly in frontal cortex. However, these data are inconsistent in part due to confounds associated with clinical samples. The lack of validated diagnostic biomarkers also hampers analysis of the neurodevelopmental trajectory of neurochemical abnormalities. Rodent models are powerful tools to address these issues, particularly when combined with (1)H MRS (clinically comparable technology). We investigated the trajectory of metabolic changes in the prefrontal cortex during brain maturation from adolescence to adulthood in vivo using (1)H MRS in rats exposed prenatally to polyinosinic-polycytidylic acid (POL), a rodent model of maternal immune activation (MIA), an epidemiological risk factor for several psychiatric disorders with a neurodevelopmental origin. Longitudinal in vivo (1)H MRS revealed a significant decrease in PFC levels of GSH and taurine in adult, but not adolescent rats. Significant age×MIA interactions for PFC levels of NAA were also observed. These data replicate some deficits observed in the PFC of patients with schizophrenia. There were no significant changes in the levels of glutamate or any other metabolite. These data suggest prenatal exposure to POL leads to subtle metabolic perturbations of the normal maturing PFC, which may be related to subsequent behavioural abnormalities. Further work is however required to examine any potential confound of shipping stress on the presumed imbalances in PFC metabolites in POL-exposed offspring. Testing the interactions between MIA with stress or genetic risk variants will also be an important advance.


Lead poisoning risk assessment of radiology workers using lead shields.
Purpose: Lead containing dust may be present on the exterior surfaces of shields used to prevent radiation exposure. We determined whether use of lead shields poses an exposure risk for radiology personnel.Methods: We collected hand dustwipe and blood samples from 58 Radiology Department employees of an academic hospital. Samples were analyzed for lead content by atomic absorption spectroscopy. Results were compared between lead apron users (46) and nonusers (12).Results: Hand dustwipe lead was undetectable (<3 µg/sample) in all cases. Blood lead levels ranged from 0-3 µg/dL.Conclusions: In this study of Radiology Department workers, we did not find an increased risk of lead contamination on their hands or in their blood. Although our sample size is small, we conclude that lead poisoning is unlikely to occur with high frequency in lead shield users.


Are marital relationships a barrier to health care utilization in Southern Appalachia?: A dyadic examination of the link between marital quality and individual health care usage.
There are substantial health disparities in Appalachia partially due to the poor access and utilization of health care. Social support, especially in Appalachia, is consistently linked to the utilization of available health care. The present study aims to identify how on aspect of social support, relationship functioning, are associated with health care utilization for couples in Southern Appalachian. Individual and couple data (N = 147, individuals; n = 76, couples) were collected from participants interested in a brief couple interventions. Individuals and Dyadic Path analyses were conducted in Mplus using methods to account for the dependence in the data. Relational aggression was the only marital factor linked to health care utilization in multivariate analyses while constructive communication was only linked to health care utilization in bivariate correlations, r = .24, p < .05. Dyadic results indicate that men's health care utilization may benefit from partner's relational aggression while women's utilization may be negatively influenced by her own self-reported relational aggression. An individual's social context must be considered in order to completely understand barriers to health care utilization. Further, the inclusion of couple/dyadic level interventions should be considered in order to improve health care utilization in the Appalachian region and similarly rural regions. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Charge-swapping Q balls.
Q balls are nontopological solitonic solutions to a wide class of field theories that possess global symmetries. Here we show that in these same theories there also exists a tower of novel composite Q-ball solutions where, within one composite Q ball, positive and negative charges coexist and swap at a frequency lower than the natural frequency of an individual Q ball. These charge-swapping Q balls are constructed by assembling Q balls and anti-Q balls tightly such that their nonlinear cores overlap. We explain why charge-swapping Q balls can form and why they swap charges.


Chemotherapeutic drug delivery to cancer cells using a combination of folate targeting and tumor microenvironment-sensitive polypeptides.
Chemotherapeutic agents often cause severe side effects because they produce a similar cytotoxicity in both cancerous and healthy cells. In this study, a rational strategy was implemented to take advantage of a combination of both tumor microenvironment-sensitive polypeptides (TMSP) and folate to create a more selective and efficient drug delivery system to target cancer cells. TMSP and folate were conjugated to the distal ends of DSPE-PEG2000-maleimide and DSPE-PEG5000-amine to create DSPE-PEG2000-TMSP and DSPE-PEG5000-folate, respectively, which were incorporated onto the surface of a docetaxel-loaded nanostructured lipid carrier (F/TMSP-DTX-NLC). TMSP are comprised of polycationic cell-penetrating peptides (CPP) and polyanionic inhibitory peptides, which are coupled via a proteinase-sensitive cleavable linker. The linker can be cleaved in the presence of matrix metalloprotease-2 and -9 (MMP-2/9). TMSP provides the ability to enhance specific cancer cellular uptake after selectively unmasking polyanionic inhibitory peptides in MMP-2/9 protease-oversecretion tumor tissue, whereas in circulation, the penetration is shielded. The folate moiety binds selectively to folate receptor-positive tumors. The cleaved dual-modified nanocarriers are then taken up by the tumor cells via both receptor-mediated endocytosis and CPP penetrating action to overcome the higher interstitial pressure in the tumor. The nanocarrier system demonstrated a small size, high encapsulation efficiency (>95%), sustained release and targeted delivery. The strong cellular uptake and cytotoxic activity of dual-modified F/TMSP-DTX-NLC in KB, HT-1080, MCF-7 and A549 cells verified the correlation with folate receptor expression and MMP-2/9 secretion. The remarkable penetration into KB and HT-1080 multicellular tumor spheroids confirmed that the temporary mask of the polyanionic inhibitory peptide in TMSP does not disturb the penetration ability of CPP in the tumor microenvironment with abundant proteases. Furthermore, the active targeting and triggered activation exhibited higher antitumor efficacy and lower systemic toxicity with the KB tumor model in nude mice compared to the nonmodified DTX-NLC and Taxotere(®). These results suggested that the application of combined TMSP and folate modifications may be an approach in the selectively targeted delivery of anticancer drugs with low systemic toxicity.


Severe 2009 pandemic influenza A (H1N1) infection and increased mortality in patients with late and advanced HIV disease.
To describe the clinical course of infection by 2009 (H1N1) influenza virus in different stages of HIV disease. Prospective, observational study. During the pandemic period, HIV-infected patients presenting respiratory symptoms at a third level referral hospital in Mexico City were tested for 2009 influenza A (H1N1) viral RNA. Clinical files were prospectively analyzed. Infection by H1N1 was confirmed in 30 (23.8%) of the total 126 HIV-infected patients studied. In the group of patients with 2009 H1N1 virus infection, 16 (53.3%) were hospitalized, 12 (40%) had active opportunistic infections and six (20%) died. In the group of 96 patients not infected with 2009 H1N1 virus, 54 (56.25%) were hospitalized with opportunistic infections and 12 (12.5%) died. For all hospitalized patients, being on HAART and having undetectable HIV viral loads at hospitalization was associated with higher survival (P = 0.019). Patients with 2009 H1N1 virus infection had a higher mortality rate, even after adjusting for HAART (P = 0.043). Coinfection by HIV and H1N1 2009 virus was more severe in patients with opportunistic infections, as shown by longer hospital stays (P = 0.0013), higher rates of hospitalization (P < 0.0001), use of mechanical ventilation (P = 0.0086) and death (P = 0.026). Delayed administration of oseltamivir in hospitalized patients was significantly associated with mortality (P = 0.0022). Our data suggest that infection by 2009 H1N1 is more severe in HIV-infected patients with late and advanced HIV disease than in well controlled patients under HAART.


Systematic evaluation of the conformational properties of aliphatic omega-methoxy methyl esters.
[structure: see text] A systematic conformational study of omega-methoxy methyl esters, CH(3)O-(CH2)n-COO-CH3 with n = 3 and 4, has been performed using quantum mechanical calculations at the MP2 level. Calculations have been carried out in both gas phase and chloroform solution, a polarizable continuum solvation model being used to represent the latter. Results have been compared with those recently obtained for the analogues omega-hydroxy acids, HO-(CH2)n-COOH with n = 3 and 4. The compounds with n = 3 clearly favor coiled conformations, the population expected for extended and semiextended conformations being very low. However, for compounds with n = 4 the minimum energy extended and semiextended structures become considerably more stable. The overall results indicate that the conformational preferences of the central aliphatic segment of omega-methoxy methyl esters and omega-hydroxy acids are not influenced by the formation of intramolecular O-H...O hydrogen bonds.


The Proteins Interacting with Prmt5 in Medaka (Oryzias latipes) Identified by Yeast Two-Hybridization.
Prmt5 plays major role in regulation of gene expression, RNA processing, cell growth and differentiation, signal transduction, germ cell development, etc., in mammals. Prmt5 is also related to cancer. Knowing the proteins interacting with Prmt5 is important to understand Prmt5's function in cells. Although there have been reports on proteins binding with Prmt5 in mammals, the partner proteins of Prmt5 in fish are still unclear. The objective was to obtain proteins that bind with Prmt5 in medaka, a model fish. Yeast two hybridization was adopted to achieve the objective. Medaka Prmt5 was used as a bait to fish the prey, binding proteins in a cDNA library of medaka. Co-immunoprecipitation and in silicon analysis were performed to study the interaction of medaka Mep50 and Prmt5. Eight proteins were identified to bind with Prmt5 from 69 preliminary positive colonies. The binding proteins are methylosome protein 50 (Mep50), apolipoprotein A-I-like (Apo-AI), PR domain containing protein 1a with zinc fingers (Prdm1a), Prdm1b, T-cell immunoglobulin mucin family member 3 (Tim-3), phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase (Paics), NADH dehydrogenase subunit 4 (ND4) and sciellin (Scl). Co-immunoprecipitation confirmed the interaction of medaka Prmt5 and Mep50. Predicted structures of medaka Prtm5 and Mep50 are similar to that of human PRMT5 and MEP50. Medaka Mep50, Prdm1a, Prdm1b, Apo-AI, Tim-3, Paics, ND4, and Scl bind with Prmt5.


Reconstruction of an amputated glans penis with a buccal mucosal graft: case report of a novel technique.
Penile amputation is a rare catastrophe and a serious complication of circumcision. Reconstruction of the glans penis may be indicated following amputation. Our report discusses a novel technique for reconfiguration of an amputated glans penis 1 year after a complicated circumcision. A 2-year-old male infant presented to us with glans penis amputation that had occurred during circumcision 1 year previously. The parents complained of severe meatal stenosis with disfigurement of the penis. Penis length was 3 cm. Complete penile degloving was performed. The distal part of the remaining penis was prepared by removing fibrous tissue. A buccal mucosal graft was applied to the distal part of the penis associated with meatotomy. The use of a buccal mucosal graft is a successful and simple procedure with acceptable cosmetic and functional results for late reconfiguration of the glans penis after amputation when penile size is suitable.


Telemedicine supported by Augmented Reality: an interactive guide for untrained people in performing an ECG test.
In many telemedicine applications, the correct use of medical device at the point of need is essential to provide an appropriate service. Some applications may require untrained people to interact with medical devices and patients: care delivery in transportation, military actions, home care and telemedicine training.Appropriate operation of medical device and correct connection with patient's body are crucial. In these scenarios, tailored applications of Augmented Reality can offer a valid support by guiding untrained people at the point of need. This study aims to explore the feasibility of using Augmented Reality in telemedicine applications, by facilitating an acceptable use of biomedical equipment by any unskilled person. In particular, a prototype system was built in order to estimate how untrained users, with limited or no knowledge, can effectively interact with an ECG device and properly placing ECG electrodes on patient's chest. An Augmented Reality application was built to support untrained users in performing an ECG test. Simple markers attached to the ECG device and onto patient's thorax allow camera calibration. Once objects and their pose in the space are recognized, the video of the current scene is enriched, in real-time, with additional pointers, text boxes and audio that help the untrained operator to perform the appropriate sequence of operations. All the buttons, switches, ports of the ECG device together with the location of precordial leads were coded and indicated. Some user's voice commands were also included to improve usability. Ten untrained volunteers, supported by the augmented reality, were able to carry out a complete ECG test first on a mannequin and then on a real patient in a reasonable time (about 8 minutes on average). Average positioning errors of precordial electrodes resulted less than 3 mm for the mannequin and less than 7 mm for the real patient. These preliminary findings suggest the effectiveness of the developed application and the validity of clinical ECG recordings. This application can be adapted to support the use of other medical equipment as well as other telemedicine tasks and it could be performed with a Tablet or a Smartphone.


A novel PDE2A reporter cell line: characterization of the cellular activity of PDE inhibitors.
We report here the generation and pharmacological characterization of a phosphodiesterase 2A (PDE2A) reporter cell line. Human PDE2A was stably transfected in a parental cell line expressing the atrial natriuretic peptide (ANP) receptor and the cyclic nucleotide-gated (CNG) cation channel CNGA2, acting as the biosensor for intracellular cGMP. In this reporter cell line, cGMP levels can be monitored in real-time via aequorin luminescence stimulated by calcium influx through the CNG channel. By using different PDE inhibitors, we could show that our PDE2A reporter assay specifically monitors PDE2A inhibition with high sensitivity. In the absence of ANP stimulation, the PDE2A selective inhibitors EHNA, BAY 60-7550 and PDP did not increase basal luminescence levels in this experimental setting. However, in combination with ANP, these inhibitors stimulated luminescence signals and induced leftward shifts of ANP concentration-response curves. Similar results were obtained when using IBMX, trequinsin and dipyridamole, which inhibit PDE2A nonselectively with lower potency. PDP, the most potent PDE2A inhibitor known to date, was found to exhibit much lower cellular activity as anticipated from its biochemical PDE2A inhibitory activity. By cellular uptake and transport studies we could show that PDP's cell permeability is low and that the compound is a substrate for an efflux transporter. Other PDE inhibitors including vinpocetine, milrinone, rolipram, sildenafil, zaprinast, BRL 50481 and BAY 73-6691 did not stimulate luminescence signals on our PDE2A reporter cell line. The results imply that this novel PDE2A reporter assay provides an efficient, high throughput means for the identification and characterization of PDE2A inhibitors.


Alpha-fetoprotein in malignant germ cell tumors of the ovary.
To investigate the clinical significance of alpha-Fetoprotein (AFP) in malignant germ cell tumors of the ovary, we studied 46 patients who were treated by the Tokai Ovarian Tumor Study Group. The 46 patients had the following tumors: immature teratoma (IT), 17 cases; endodermal sinus tumor (EST), 16 cases; mixed germ cell tumor containing EST, 11 cases; embryonal carcinoma, 1 case; polyembryoma, 1 case. In all 29 non-IT cases, AFP was positive, and in 27 cases (93%) the level was above 1000 ng/ml. In 11 of 17 cases of IT (64.7%), AFP levels were elevated and in 1 case the level was above 1000 ng/ml. Elevation of the AFP level above 1000 ng/ml suggested the presence of EST. AFP levels were monitored in 27 of 29 cases without IT during treatment and follow-up. It was found that AFP levels should be monitored closely for at least 1 year after induction of remission. No recurrence was observed when AFP continued to be negative longer than 1 year. The mean interval to clinical recurrence from the reelevation of AFP was 4 months (1.4-9 months). An increase in the AFP to a positive level, even without clinical signs of recurrence, should be regarded as a recurrence. AFP was found to be a useful tumor marker for the diagnosis and management of malignant germ cell tumors of the ovary.


Nutrient Intake Prior to Exercise Is Necessary for Increased Osteogenic Marker Response in Diabetic Postmenopausal Women.
Type 2 diabetes increases bone fracture risk in postmenopausal women. Usual treatment with anti-resorptive bisphosphonate drugs has some undesirable side effects, which justified our interest in the osteogenic potential of nutrition and exercise. Since meal eating reduces bone resorption, downhill locomotion increases mechanical stress, and brief osteogenic responsiveness to mechanical stress is followed by several hours of refractoriness, we designed a study where 40-min of mechanical stress was manipulated by treadmill walking uphill or downhill. Exercise preceded or followed two daily meals by one hour, and the meals and exercise bouts were 7 hours apart. Fifteen subjects each performed two of five trials: No exercise (SED), uphill exercise before (UBM) or after meals (UAM), and downhill exercise before (DBM) or after meals (DAM). Relative to SED trial, osteogenic response, defined as the ratio of osteogenic C-terminal propeptide of type I collagen (CICP) over bone-resorptive C-terminal telopeptide of type-I collagen (CTX) markers, increased in exercise-after-meal trials, but not in exercise-before-meal trials. CICP/CTX response rose significantly after the first exercise-after-meal bout in DAM, and after the second one in UAM, due to a greater CICP rise, and not a decline in CTX. Post-meal exercise, but not the pre-meal exercise, also significantly lowered serum insulin response and homeostatic model (HOMA-IR) assessment of insulin resistance.


New method for atomistic modeling of the microstructure of activated carbons using hybrid reverse Monte Carlo simulation.
We propose a new hybrid reverse Monte Carlo (HRMC) procedure for atomistic modeling of the microstructure of activated carbons whereby the guessed configuration for the HRMC construction simulation is generated using the characterization results (pore size and pore wall thickness distributions) obtained by the interpretation of argon adsorption at 87 K using our improved version of the slit-pore model, termed the finite wall thickness (FWT) model (Nguyen, T. X.; Bhatia, S. K. Langmuir 2004, 20, 3532) . This procedure overcomes limitations arising from the use of short-range potentials in the conventional HRMC method, which make the latter unsuitable for carbons such as activated carbon fibers that are anisotropic with medium-range ordering induced by their complex pore structure. The newly proposed approach is applied specifically for the atomistic construction of an activated carbon fiber ACF15, provided by Kynol Corporation (Nguyen, T. X.; Bhatia, S. K. Carbon 2005, 43, 775) . It is found that the PSD of the ACF15's constructed microstructure is in good agreement with that determined using argon adsorption at 87 K. Furthermore, we have also found that the use of the Lennard-Jones (LJ) carbon-fluid interaction well depth obtained from scaling the flat graphite surface-fluid interaction well depth taken from Steele (Steele, W. A. Surf. Sci. 1973, 36, 317) provides an excellent prediction of experimental adsorption data including the differential heat of adsorption of simple gases (Ar, N(2), CH(4), CO(2)) over a wide range of temperatures and pressures. This finding is in agreement with the enhancement of the LJ carbon-fluid well depth due to the curvature of the carbon surface, found by the use of ab initio calculations (Klauda, J. B.; Jiang, J.; Sandler, S. I. J. Phys. Chem. B 2004, 108, 9842) .


A regression technique to analyze the second-order nonlinear optical response of thin films.
We present a new technique, based on regression analysis, to determine the second-order nonlinear optical susceptibility tensor of thin films. The technique does not require the absolute levels or phases of measured signals to be mutually calibrated. In addition it yields indicators that address the quality of theoretical models describing the sample. We use the technique to determine the susceptibility tensor of samples of a nonracemic chiral material which have very low symmetry (both chiral and anisotropic) and have many independent tensor components. The results show the importance of using detailed theoretical models that account for the linear optical properties of the sample.


Modeling and characterization of a cantilever-based near-field scanning microwave impedance microscope.
This paper presents a detailed modeling and characterization of a microfabricated cantilever-based scanning microwave probe with separated excitation and sensing electrodes. Using finite-element analysis, we model the tip-sample interaction as small impedance changes between the tip electrode and the ground at our working frequencies near 1 GHz. The equivalent lumped elements of the cantilever can be determined by transmission line simulation of the matching network, which routes the cantilever signals to 50 Omega feed lines. In the microwave electronics, the background common-mode signal is canceled before the amplifier stage so that high sensitivity (below 1 aF capacitance changes) is obtained. Experimental characterization of the microwave microscope was performed on ion-implanted Si wafers and patterned semiconductor samples. Pure electrical or topographical signals can be obtained from different reflection modes of the probe.


Forskolin Delays the Ethanol-Induced Desensitization of Hypothalamic β-Endorphin Neurons in Primary Cultures.
Ethanol and its metabolite acetaldehyde have been shown to stimulate immunoreactive β-endorphin (IR-β-EP) secretion from hypothalamic neurons in primary cultures. Also, chronic ethanol and acetaldehyde have been shown to cause the development of tolerance and desensitization of these neurons. In this study, we determined some of the cellular events leading to desensitization of the function of β-endorphin (p-EP) Secretory neurons. The fetal hypothalamic cells were treated with various doses of ethanol (W and 50 mM) or acetaldehyde (6.25,12.5, and 25 mM) for 6 hr or treated with these drugs at 12 hr intervals for 72 hr. Determination of IR-β-EP concentrations in the media revealed that ethanol increased IR-β-EP secretion from these cultures for 12 hr; after this period, the cultured cells did not respond to ethanol. Acetaldehyde stimulated IR-β-EP secretion from this culture for a period of 48 hr, but the IR-β-EP secretory response to acetaldehyde reduced gradually with time during the first 48-hr period and reached the basal level at 72 hr. The desensitization of β-EP neurons 12 hr after treatment with alcohol did not seem to be related to the loss of viable cells, because chronic ethanol exposures did not produce any effect on cell viability. However, reduced IR- β-EP secretory response to acetaldehyde with time was associated with the time-dependent increase in cell death. Pretreatment of cultures with a cAMP analog, forskolin, increased the activity of functional β-EP neurons and delayed the ethanol desensitization effects on these neurons. Pretreatment of forskolin did not delay the acetaldehyde desensitization of β-EP neurons, but protected these cells from acetaldehyde toxicity. These results suggest that (i) chronic treatment with ethanol desensitizes β-EP-secreting neurons due to reduced cellular functions and (ii) chronic acetaldehyde reduces β-EP neurotransmission due to cell death. Furthermore, data suggest for the first time that cAMP pretreatments delay the ethanolinduced desensitization of opioid neurons and partly protect against the neurotoxic action of acetaldehyde on opioid neurons.


CCM111, the water extract of Antrodia cinnamomea, regulates immune-related activity through STAT3 and NF-κB pathways.
Antrodia cinnamomea (AC) exhibits many bioactivities, including anti-inflammatory, anti-cancer, and hepatoprotection activities. Many researchers have studied the functions of the components or fractions of AC, but the functions of the original extractions of AC have not been studied. In addition, the detailed relationship between AC and immune-related signaling pathways is unclear. In this study, we screened the effects of CCM111, which is the extract of AC, on seven immune-related signaling pathways and further investigated whether CCM111 can influence inflammation. Interestingly, our results showed that CCM111 significantly inhibited the IL-6-stimulated STAT3 pathway and the LPS-stimulated NF-κB pathway in macrophages. CCM111 also decreased the phosphorylation of STAT3, Tyk2 and the nuclear translocation of p65. Moreover, CCM111 and F4, a fraction of CCM111, down-regulated nitric oxide (NO) production, the protein levels of iNOS and COX-2, and inflammatory cytokines in macrophage cells. Therefore, our study suggested that CCM111 has the potential to be developed as an effective anti-inflammatory agent.


Supramolecular structure of the Salmonella typhimurium type III protein secretion system.
The type III secretion system of Salmonella typhimurium directs the translocation of proteins into host cells. Evolutionarily related to the flagellar assembly machinery, this system is also present in other pathogenic bacteria, but its organization is unknown. Electron microscopy revealed supramolecular structures spanning the inner and outer membranes of flagellated and nonflagellated strains; such structures were not detected in strains carrying null mutations in components of the type III apparatus. Isolated structures were found to contain at least three proteins of this secretion system. Thus, the type III apparatus of S. typhimurium, and presumably other bacteria, exists as a supramolecular structure in the bacterial envelope.


Metabolomics approach to chemical diversity of the Mediterranean marine sponge Agelas oroides.
The Mediterranean marine sponge Agelas oroides is known to contain a large quantity of oroidin, a deterrent, antifouling and antibiofilm pyrrole-2-aminoimidazole. In contrast with other tropical specimens, the chemical composition of Mediterranean Agelas oroides is surprisingly relatively poor in other related metabolites. In the course of finding novel marine natural products, LC-MS based metabolomics study of the Mediterranean Agelas oroides, however, revealed that next to the major compound oroidin, the sponge contains in fact a great diversity of known pyrrole-imidazole alkaloids in minute amounts. Here, we describe identification of 13 known oroidin class alkaloids along with one new monobromoagelaspongin (24). Five betaines and one amine were also identified from the aqueous fraction. One of those compounds (-)-equinobetaine B (30) was found to be an enantiomer of the known natural product (+)-equinobetaine B.


Enterococcus thailandicus sp. nov., isolated from fermented sausage ('mum') in Thailand.
A Gram-positive and catalase-negative coccus that formed chains, designated strain FP48-3(T), isolated from fermented sausage ('mum'), was studied systematically. Strain FP48-3(T) was facultatively anaerobic and produced l-lactic acid from glucose. Straight-chain fatty acids C(18 : 1) and C(16 : 0) were the dominant components. The DNA G+C content of strain FP48-3(T) was 37.9 mol%. On the basis of 16S rRNA and RNA polymerase alpha-subunit (rpoA) gene sequence analysis, strain FP48-3(T) was closely related to Enterococcus hirae LMG 6399(T), Enterococcus durans LMG 10746(T) and Enterococcus faecium LMG 11423(T), with 99.3-99.6 and 95.1-96.9 % sequence similarities, respectively. Strain FP48-3(T) could be clearly distinguished from E. hirae LMG 6399(T), E. durans LMG 10746(T) and E. faecium LMG 11423(T) by low DNA-DNA relatedness (< or =14 %) and phenotypic characteristics. Therefore, this strain represents a novel species of the genus Enterococcus, for which the name Enterococcus thailandicus sp. nov. is proposed. The type strain is FP48-3(T) (=KCTC 13134(T)=NBRC 101867(T)=NRIC 0107(T)=TISTR 933(T)=PCU 282(T)).


Adrenocorticotropic hormone and 1,25-dihydroxyvitamin D3 enhance human osteogenesis in vitro by synergistically accelerating the expression of bone-specific genes.
To improve definition of the physical and hormonal support of bone formation, we studied differentiation of human osteoblasts in vitro at varying combinations of ACTH, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D), and extracellular calcium, with and without added cortisol. Bone mineralization, alkaline phosphatase activity, and osteoblast-specific markers RunX2, osterix, and collagen I increased with 10 pM ACTH, 10 nM 1,25(OH)2D, or at 2 mM calcium with important synergistic activity of combinations of any of these stimuli. Signals induced by ACTH at 10-30 min included cAMP, TGF-β, and Erk1/2 phosphorylation. Affymetrix gene expression analysis showed that 2 h treatment of ACTH or 1,25(OH)2D increased the expression of bone regulating and structural mRNAs, including collagen I, biglycan, the vitamin D receptor, and TGF-β. Accelerating expression of these bone-specific genes was confirmed by quantitative PCR. Expression of 1,25(OH)2D 1α-hydroxylase (1α-hydroxylase) increased with 1,25(OH)2D, ACTH, and extracellular calcium from 0.5 to 2 mM. Unlike renal 1α-hydroxylase, in osteoblasts, 1α-hydroxylase activity is independent of parathyroid hormone. In keeping with calcium responsivity, calcium-sensing receptor RNA and protein increased with 10 nM ACTH or 1,25(OH)2D. Inclusion of 200 nM cortisol or 10 nM ACTH in differentiation media blunted osteoblasts alkaline phosphatase response to 1,25(OH)2D and calcium. Our results point to the importance of ACTH in bone maintenance and that extra skeletal (renal) 1,25(OH)2D is required for bone mineralization despite 1α-hydroxylase expression by osteoblasts.


Utility of prognostic genomic tests in breast cancer practice: The IMPAKT 2012 Working Group Consensus Statement.
We critically evaluated the available evidence on genomic tests in breast cancer to define their prognostic ability and likelihood to determine treatment benefit. Independent evaluation of six genomic tests [Oncotype Dx™, MammaPrint(®), Genomic Grade Index, PAM50 (ROR-S), Breast Cancer Index, and EndoPredict] was carried out by a panel of experts in three parameters: analytical validity, clinical validity, and clinical utility based on the principles of the EGAPP criteria. PANEL STATEMENTS: The majority of the working group members found the available evidence on the analytical and clinical validity of Oncotype Dx™ and MammaPrint(®) to be convincing. None of the genomic tests demonstrated robust evidence of clinical utility: it was not clear from the current evidence that modifying treatment decisions based on the results of a given genomic test could result in improving clinical outcome. The IMPAKT 2012 Working Group proposed the following recommendations: (i) a need to develop models that integrate clinicopathologic factors along with genomic tests; (ii) demonstration of clinical utility should be made in the context of a prospective randomized trial; and (iii) the creation of registries for patients who are subjected to genomic testing in the daily practice.


Synthesis of Manganese ZIF-8 from [Mn(BH4)2·3THF]·NaBH4.
Cubic and highly porous [Mn(2-methylimidazolate)2] (Mn-ZIF-8) was synthesized from [Mn(BH4)2·3THF]·NaBH4 under an Ar atmosphere. The structure contains rare Mn2+-4N tetrahedral geometry and has larger cell parameters, resulting in 20% larger amounts of gas uptake compared with [Zn(2-methylimidazolate)2]. A kinetically favored reaction using a reactive metal borohydride precursor is key for the construction of new metal-organic framework systems.


Isolated electrodeless high-frequency quartz crystal microbalance for immunosensors.
This paper presents a contactless technique to measure shear bulk wave resonance frequencies of an isolated quartz crystal in a flow cell. The line antenna placed outside the cell generates and detects the resonance frequencies in a wireless-electrodeless manner. It is revealed that this mechanism relies on the quasistatic electric field. A 0.3-mm-thick AT-cut quartz was used, and its overtone resonance frequencies up to 80 MHz were measured in liquids. Exact vibrational analysis was carried out for a triple-layered resonator system consisting of the adsorbed material layer, the electrode film, and the quartz plate. It predicts higher frequency sensitivity to the adsorbed material at higher modes when the electrode layer is removed. The 13th overtone (72-MHz resonance frequency) was used to detect human immunoglobulin G with concentrations between 0.1 and 20 microg/mL captured by protein A immobilized on one side of the crystal. The real-time measurement of the frequency response yielded the equilibrium constant KA=5.21 x 10(7) M(-1).


[Operative approach to the retromaxillary space].
From 1977-1982 we observed 59 tumours involving the retromaxillary fossa. The primary site, direction of spread and histology are described. In selecting one of the various approaches to this anatomical region it is necessary to distinguish between tumours which have invaded the retromaxillary fossa secondarily and those which have developed primarily within it. The importance of the transfacial premaxillary approach for the latter group is shown.


Wide surgical margins improve prognosis for HCC with microvascular invasion.
Hepatocellular carcinoma (HCC) is the sixth leading cause of malignant tumors worldwide. Liver resection is a pivotal treatment modality for HCC. Surgical margin plays an important role in decreasing recurrence and improving prognosis for HCC patients. This paper aimed to perform a systematic review of the literature in regard to surgical margin in HCC patients with microvascular invasion (MVI). Residual MVI due to insufficient surgical margins is the main origin of postoperative recurrence and metastasis in HCC patients. A wide surgical margin (WSM) significantly improves oncological outcomes and long-term survival in HCC patients with MVI. Progress in the preoperative prediction of MVI may contribute to precise surgical decision-making in the future. WSM was associated with better outcomes in HCC patients with MVI. WSM is recommended for well-preserved liver function HCC patients who are predicted to have a high risk of MVI preoperatively.


Influence of initial use of serotonergic antidepressants on antiparkinsonian drug use in levodopa-using patients.
To assess whether there is an association between initial use of serotonergic antidepressants and changes in antiparkinsonian drug treatment. A retrospective cohort study was performed with the PHARMO record linkage system. All patients from 1994 until 2004 of 40 years or older who were first time users of an antidepressant and who had used a levodopa-containing drug at least 180 days before initiation of the antidepressant were included. The maximum follow-up time was 180 days. The first change in antiparkinsonian drug treatment, defined as an increase in the daily dosage of any antiparkinsonian drug, the start of a new antiparkinsonian drug or a change in the dosage form during the follow-up period, was taken as an endpoint. Antidepressants were classified in two ways: according to their class [selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (TCA) or other antidepressants] or by the extent of their inhibition of serotonin reuptake (high, intermediate or low). A total of 221 patients was included in our study. The adjusted hazard ratio for a change in antiparkinsonian drug treatment was 0.7 (95% CI 0.3-1.5) comparing SSRI with TCA users, and it was 0.9 (95% CI 0.4-2.1) comparing users of other antidepressants with TCA users. The adjusted hazard ratio for a change in antiparkinsonian drug treatment was 0.6 (95% CI 0.3-1.4) comparing users of antidepressants with high versus low extent of inhibition of serotonin reuptake, and it was 0.7 (95% CI 0.3-1.4) comparing users of antidepressants with intermediate versus low extent of inhibition of serotonin reuptake. Based on these observations, we found no evidence to be more cautious using SSRIs or serotonergic antidepressants compared to other antidepressants in patients with Parkinson's disease.


Prognostic impact of the inclusion of uPA/PAI-1 for adjuvant treatment decision-making in ER+/Her2- pN0 early breast cancers.
Intermediate-risk early breast cancer (EBC) is a heterogeneous group in which adjuvant chemotherapy decision proves to be difficult. Clinical and pathological criteria are sometimes insufficient to determine the best therapeutic options, and validated biomarkers such as uPA/PAI-1, are needed to contribute to the decision-making. The objective of this study was to evaluate the clinical outcome of an unselected ER+/HER2- pN0 EBC cohort of patients in whom the routine clinical decision process included a prospective uPA/PAI-1 determination. This monocentric retrospective study included 520 patients who underwent curative surgery in our institute between 2006 and 2011. Adjuvant therapeutic strategy was decided based on clinical-pathological data, altogether with a routine prospective determination of uPA/PAI-1 tumor levels using fresh, extemporaneously sampled tissue. We evaluated the correlation between uPA/PAI-1 levels, clinical-pathological variables, and the patient's outcome (relapse-free survival, RFS, and overall survival, OS). Median follow-up was 5.4 years. The 5- and 10-year RFS rates were ,respectively, 95 and 89%, and the five-year OS rate was 96.3%. Forty percent of tumors had low uPA/PAI-1 levels. Seventy-five percent of patients with low uPA/PAI-1 levels did not receive chemotherapy, when 25% did. Sixty percent of patients with high uPA and/or PAI-1 levels received chemotherapy, while 40% did not. No statistical significant correlation was found between the uPA/PAI-1 levels and RFS or OS. The personalization of the patients' treatment using uPA/PAI-1 tumor levels allows the reversion of the well-known poor prognostic impact of high uPA/PAI-1 levels and strongly supports the use of this biomarker in clinical practice.


Fractionation of poly(methacrylic acid) and poly(vinyl pyridine) in aqueous and organic mobile phases by multidetector thermal field-flow fractionation.
Multidetector thermal field-flow fractionation (ThFFF) is shown to be a versatile characterisation platform that can be used to characterise hydrophilic polymers in a variety of organic and aqueous solutions with various ionic strengths. It is demonstrated that ThFFF fractionates isotactic and syndiotactic poly(methacrylic acid) (PMAA) as well as poly(2-vinyl pyridine) (P2VP) and poly(4-vinyl pyridine) (P4VP) according to microstructure in organic solvents and that the ionic strength of the mobile phase has no influence on the retention behaviour of the polymers. With regard to aqueous solutions, it is shown that, despite the weak retention, isotactic and syndiotactic PMAA show different retention behaviours which can qualitatively be attributed to microstructure. Additionally, it is shown that the ionic strength of the mobile phase has a significant influence on the thermal diffusion of polyelectrolytes in aqueous solutions and that the addition of an electrolyte is essential to achieve a microstructure-based separation of P2VP and P4VP in aqueous solutions.


[Ozone therapy in gastroduodenal pathology associated with Helicobacter pylori].
Three methods of ozone therapy (intravenous injection of ozonized physiologic saline, oral intake of ozonized low-mineral water and combination of the two treatments) were compared by efficacy in 215 patients with gastroduodenal pathology associated with Helicobacter pilori. All the techniques of ozone therapy proved effective in relation to regress of clinical symptoms, regeneration processes, eradication of Helicobacter pylori, but the combined regimen was the best.


Evolution of Nucleic-Acid-Based Constitutional Dynamic Networks Revealing Adaptive and Emergent Functions.
The evolution of networks is a fundamental unresolved issue in developing the area of systems chemistry. We introduce a versatile rewiring mechanism that leads to the emergence of nucleic-acid-based constitutional dynamic networks (CDNs). A two-component constituent AA' functionalized with a Mg2+ -ion-dependent DNAzyme activator unit forms a complex with an intact hairpin HBB' composed of B and B' sequences. Cleavage of HBB' leads to the two-component constituent BB', and its rewiring with AA' yields CDN X composed of the equilibrated constituents AA', AB', BA', and BB'. In analogy, subjecting AA' to an intact hairpin HCC' leads to the formation of CDN Y consisting of AA', AC', CA', and CC'. Subjecting AA' to the mixture of HBB' and HCC' evolves the [3×3] CDN Z, composed of nine constituents, thus demonstrating hierarchical adaptive properties. Furthermore, the DNAzyme units associated with the constituents are applied to tailor emerging catalytic functions from the different CDNs.


A new strategy for browning regulation: Flos Sophorae Immaturus extract and thermal treatment modulates nitric oxide and reactive oxygen species network in fresh-cut potatoes.
Browning discoloration is a critical issue that negatively affects the quality of fresh-cut products and their industrial growth. Although many individual anti-browning technologies have been adopted, very few reports on the combination use of natural product extracts and physical methods exist. This study investigated the use of Flos Sophorae Immaturus extract in conjunction with thermal treatment and discovered that the combination effectively retarded browning in fresh-cut potatoes. Accordingly, the activities of polyphenol oxidase, peroxidase, and phenylalanine ammonia-lyase, as well as phenol accumulation, were effectively regulated. Meanwhile, this combination treatment also allowed for the modulation of nitric oxide synthase, superoxide dismutase, and catalase activities, while also regulating the concentrations of nitric oxide, superoxide anion, and hydrogen peroxide. Furthermore, the duplex treatment also regulated the antioxidant capacity and malondialdehyde concentrations. In addition, 39 phytoactive compounds, including protocatechuic acid, quercetin, (-)-alpha-pinene, and matrine, were identified in the extract, which may function as the anti-browning composition. These findings suggest that the combination technology modulated the dynamic equilibrium of production and clearance of nitric oxide and reactive oxygen species, thereby reducing browning deterioration. This is, to our knowledge, the first report of the combined application of Flos Sophorae Immaturus and thermal treatment, which may offer a novel option for fresh-cut preservation. PRACTICAL APPLICATION: The feasibility of integrating a novel highly efficient, safe, environmentally friendly, and easy-to-operate anti-browning alternative, with the ability to integrate into the existing processing line was investigated. The color of sliced potato chips was significantly improved (73.4%) by dipping them in a 0.01% Flos Sophorae Immaturus solution for 5 min and then in 55°C water for 2 min. In this regard, superior browning alleviation may depend on the regulation of the browning reaction and the NO-ROS network. This method has a promising future for making fresh-cut products more appealing to consumers and may provide guidance for fresh-cut producers and related industries.


PCR and DNA sequencing in establishing the aetiology of bacterial infections in children.
The results of partial polymerase chain reaction (PCR) amplification of the bacterial 16S rRNA gene and subsequent DNA sequencing of clinical samples from children are described. In 13 out of 62 samples, DNA from bacteria likely to be the cause of infection was identified. In the vast majority (11/13) of samples with significant pathogen culture the specimen had been negative. Antibiotics had been given in all cases except for three prior to sampling. PCR and subsequent DNA sequencing is a valuable supplementary tool for establishing the cause of bacterial infections in children when culture is negative.


Understanding mixed sequence DNA recognition by novel designed compounds: the kinetic and thermodynamic behavior of azabenzimidazole diamidines.
Sequence-specific recognition of DNA by small organic molecules offers a potentially effective approach for the external regulation of gene expression and is an important goal in cell biochemistry. Rational design of compounds from established modules can potentially yield compounds that bind strongly and selectively with specific DNA sequences. An initial approach is to start with common A·T bp recognition molecules and build in G·C recognition units. Here we report on the DNA interaction of a synthetic compound that specifically binds to a G·C bp in the minor groove of DNA by using an azabenzimidazole moiety. The detailed interactions were evaluated with biosensor-surface plasmon resonance (SPR), isothermal calorimetric (ITC), and mass spectrometry (ESI-MS) methods. The compound, DB2277, binds with single G·C bp containing sequences with sub-nanomolar potency and displays slow dissociation kinetics and high selectivity. A detailed thermodynamic and kinetic study at different experimental salt concentrations and temperatures shows that the binding free energy is salt concentration dependent but essentially temperature independent under our experimental conditions, and binding enthalpy is temperature dependent but salt concentration independent. The results show that in the proper compound structural context novel heterocyclic cations can be designed to strongly recognize complex DNA sequences.


The data management of a phase III efficacy trial of an 11-valent pneumococcal conjugate vaccine and related satellite studies conducted in the Philippines.
A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted. We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently. There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff. Current Controlled Trials ISRCTN62323832.


Adrenocortical adenoma with primary aldosteronism in culture.
Four adrenocortical adenomata with primary aldosteronism (Conn's adenomata) were examined by light and electron microscopy employing cell culture methods. Unstimulated cells existed as a unit of the clusters, but Conn's adenoma cells reacted to ACTH. The cultured cells produced mostly cortisol under ACTH-stimulation as time passed. Lipid droplets in their cytoplasm decreased in number and the smooth endoplasmic reticulum (sER) was well-developed with dilated, anastomosing tubule. Moreover, mitochondria sometimes had tubulovesicular cristae. It is assumed that Conn's adenoma cells are hybrid type cells, which are intrinsically capable of producing cortisol as well as aldosterone.


(-)-Epigallocatechin-3-gallate inhibits Met signaling, proliferation, and invasiveness in human colon cancer cells.
The Met receptor tyrosine kinase is deregulated in a variety of cancers and is correlated with advanced stage and poor prognosis. Thus, Met has been identified as an attractive candidate for targeted therapy. We compared the tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) and a specific Met inhibitor, SU11274, as suppressing agents of Met signaling in HCT116 human colon cancer cells. Treatment with hepatocyte growth factor increased phospho-Met levels, and this was inhibited in a concentration-dependent manner by EGCG and SU11274 (IC(50) 3.0 vs. 0.05muM, respectively). Downstream activation of Erk and Akt signaling pathways also was suppressed. Both compounds at a concentration of 5muM lowered cell viability and proliferation, with EGCG being more effective than SU11274, and the invasion of colon cancer cells in Matrigel assays was strongly inhibited. These findings are discussed in the context of the pleiotropic effects of tea catechins, their tissue metabolite levels, and the potential to inhibit colon cancer metastasis and invasion.


Application of the health belief model in promotion of self-care in heart failure patients.
Heart failure (HF) is a condition due to a problem with the structure or function of the heart impairs its ability to supply sufficient blood flow to meet the body's needs. In developing countries, around 2% of adults suffer from heart failure, but in people over the age of 65, this rate increases to 6-10%. In Iran, around 3.3% of adults suffer from heart failure. The Health Belief Model (HBM) is one of the most widely used models in public health theoretical framework. This was a cohort experimental study, in which education as intervention factor was presented to case group. 180 Heart failure patients were randomly selected from patients who were referred to the Shahid Rajaee center of Heart Research in Tehran and allocated to two groups (90 patients in the case group and 90 in the control group). HBM was used to compare health behaviors. The questionnaire included 69 questions. All data were collected before and 2 months after intervention. About 38% of participants don't know what, the heart failure is and 43% don't know that using the salt is not suitable for them. More than 40% of participants didn't weigh any time their selves. There was significant differences between the mean grades score of variables (perceived susceptibility, perceived threat, knowledge, Perceived benefits, Perceived severity, self-efficacy Perceived barriers, cues to action, self- behavior) in the case and control groups after intervention that was not significant before it. Based on our study and also many other studies, HBM has the potential to be used as a tool to establish educational programs for individuals and communities. Therefore, this model can be used effectively to prevent different diseases and their complications including heart failure.


Transcortical Sensory Aphasia after Left Frontal Lobe Infarction: Loss of Functional Connectivity.
The underlying mechanism of transcortical sensory aphasia (TSA) caused by lesions occurring in the left frontal lobe remains unclear. We attempted to investigate the mechanism with the use of functional MRI (fMRI). We studied 2 patients with TSA after a left frontal infarction identified by diffusion-weighted MRI. As control subjects, a patient with transcortical motor aphasia and a healthy normal adult were chosen. The Korean version of Western Aphasia Battery was performed initially and at 3 months post stroke. We performed fMRI using verb generation and sentence completion tasks. Resting-state fMRI (rs-fMRI) was also obtained for network-level analysis initially and at 3 months post stroke. The results of diffusion- and perfusion-weighted MRI revealed no diffusion-perfusion mismatch. Initial fMRI in patients with TSA showed no reversed inter-/intrahemispheric activation patterns. rs-fMRI showed significantly decreased resting-state functional connectivity in the language network in patients with TSA compared with the control subjects. Follow-up rs-fMRI studies showed improvement in functional connectivity along with the recovery of patients' language function. Our data showed that the auditory comprehension deficits in patients with frontal lobe infarcts is attributed to difficulty accessing the posterior language area due to functional disconnection between language centers in the acute stage of stroke.


Can we modify the intrauterine environment to halt the intergenerational cycle of obesity?
Child obesity is a global epidemic whose development is rooted in complex and multi-factorial interactions. Once established, obesity is difficult to reverse and epidemiological, animal model, and experimental studies have provided strong evidence implicating the intrauterine environment in downstream obesity. This review focuses on the interplay between maternal obesity, gestational weight gain and lifestyle behaviours, which may act independently or in combination, to perpetuate the intergenerational cycle of obesity. The gestational period, is a crucial time of growth, development and physiological change in mother and child. This provides a window of opportunity for intervention via maternal nutrition and/or physical activity that may induce beneficial physiological alternations in the fetus that are mediated through favourable adaptations to in utero environmental stimuli. Evidence in the emerging field of epigenetics suggests that chronic, sub-clinical perturbations during pregnancy may affect fetal phenotype and long-term human data from ongoing randomized controlled trials will further aid in establishing the science behind ones predisposition to positive energy balance.


Duplex ultrasound evaluation of lower extremity venous insufficiency.
Physicians unfamiliar with venous insufficiency, particularly disorders of the superficial venous system, often underestimate the complexity of the problem and the importance of proper evaluation before initiating treatment. In addition to a directed history evaluation and physical examination, additional evaluation with use of a variety of noninvasive diagnostic instruments, including duplex ultrasound, may be necessary when determining the cause, severity, and best treatment options available for a particular patient. After such evaluation, the treating physician should have a precise map of the patient's pathways of venous insufficiency, including sources of reflux (eg, saphenofemoral junction, saphenopopliteal junction, perforators), tributaries, vein size, and vein morphology.


Injectable hyaluronic acid-tyramine hydrogels incorporating interferon-α2a for liver cancer therapy.
We report an injectable hydrogel system that incorporates interferon-α2a (IFN-α2a) for liver cancer therapy. IFN-α2a was incorporated in hydrogels composed of hyaluronic acid-tyramine (HA-Tyr) conjugates through the oxidative coupling of Tyr moieties with hydrogen peroxide (H2O2) and horseradish peroxidase (HRP). IFN-α2a-incorporated HA-Tyr hydrogels of varying stiffness were formed by changing the H2O2 concentration. The incorporation of IFN-α2a did not affect the rheological properties of the hydrogels. The activity of IFN-α2a was furthermore well-maintained in the hydrogels with lower stiffness. Through the caspase-3/7 pathway in vitro, IFN-α2a released from HA-Tyr hydrogels inhibited the proliferation of liver cancer cells and induced apoptosis. In the study of the pharmacokinetics, a higher concentration of IFN-α2a was shown in the plasma of mice treated with IFN-α2a-incorporated hydrogels after 4h post injection, with a much higher amount of IFN-α2a delivered at the tumor tissue comparing to that of injecting an IFN-α2a solution. The tumor regression study revealed that IFN-α2a-incorporated HA-Tyr hydrogels effectively inhibited tumor growth, while the injection of an IFN-α2a solution did not demonstrate antitumor efficacy. Histological studies confirmed that tumor tissues in mice treated with IFN-α2a-incorporated HA-Tyr hydrogels showed lower cell density, with more apoptotic and less proliferating cells compared with tissues treated with an IFN-α2a solution. In addition, the IFN-α2a-incorporated hydrogel treatment greatly inhibited the angiogenesis of tumor tissues.


Medical Informatics Operating Room Vitals and Events Repository (MOVER): a public-access operating room database.
Artificial intelligence (AI) holds great promise for transforming the healthcare industry. However, despite its potential, AI is yet to see widespread deployment in clinical settings in significant part due to the lack of publicly available clinical data and the lack of transparency in the published AI algorithms. There are few clinical data repositories publicly accessible to researchers to train and test AI algorithms, and even fewer that contain specialized data from the perioperative setting. To address this gap, we present and release the Medical Informatics Operating Room Vitals and Events Repository (MOVER). This first release of MOVER includes adult patients who underwent surgery at the University of California, Irvine Medical Center from 2015 to 2022. Data for patients who underwent surgery were captured from 2 different sources: High-fidelity physiological waveforms from all of the operating rooms were captured in real time and matched with electronic medical record data. MOVER includes data from 58 799 unique patients and 83 468 surgeries. MOVER is available for download at https://doi.org/10.24432/C5VS5G, it can be downloaded by anyone who signs a data usage agreement (DUA), to restrict traffic to legitimate researchers. To the best of our knowledge MOVER is the only freely available public data repository that contains electronic health record and high-fidelity physiological waveforms data for patients undergoing surgery. MOVER is freely available to all researchers who sign a DUA, and we hope that it will accelerate the integration of AI into healthcare settings, ultimately leading to improved patient outcomes.


Intracellular recording from neurones of the guinea-pig gall-bladder.
1. Intracellular recordings were made from neurones of the guinea-pig gall-bladder in vitro. Intracellular injection of horseradish peroxidase revealed a simple structure, consisting of a soma and a single process, but no discernible dendritic arborization. 2. The resting membrane potential was -50.5 +/- 0.4 mV and the input resistance was 80 M omega. 3. Gall-bladder neurones spiked only once at the onset of depolarizing current pulses. Action potentials were blocked by tetrodotoxin, but a Ca2(+)-dependent spike could be elicited in the presence of tetrodotoxin and tetraethylammonium. 4. Action potential after-hyperpolarizations had a duration of 172 +/- 3.7 ms and reversed at a membrane potential of -93 mV; this reversal potential was linearly related to the logarithm of the external potassium concentration. The initial phase of the after-hyperpolarization was inhibited by tetraethylammonium (1-10 mM) and was not affected by 3,4-diaminopyridine. The late phase of the after-hyperpolarization was blocked by apamin (10 nM) or curare (500 microM). Both the early and late phases of the after-hyperpolarization were inhibited when the preparation was perfused with a calcium-free, high-magnesium solution. The calcium-free, high-magnesium solution had no effect on the membrane potential or input resistance of these cells. 5. Fast excitatory synaptic responses and antidromic responses were elicited in gall-bladder neurones by focal stimulation of fibre tracts. High-frequency fibre tract stimulation often resulted in prolonged, calcium-dependent, depolarizations that were associated with a decrease in input resistance. 6. 5-Hydroxytryptamine and substance P caused depolarizations that were associated with a decrease in input resistance. Bethanechol caused hyperpolarizations that were associated with a decrease in input resistance and which were blocked by atropine.


The effects of time-restricted eating versus habitual diet on inflammatory cytokines and adipokines in the general adult population: a systematic review with meta-analysis.
Time-restricted eating (TRE) may facilitate weight loss, but its impact on inflammation remains unclear. Chronic inflammation can detrimentally increase risk of obesity-associated comorbidities. The aim of this systematic review was to synthesize and determine the effects of TRE on cytokine and adipokines (C-reactive protein [CRP], TNF alpha [TNF-α], interleukin-6 [IL-6], leptin, and adiponectin) in adults. PubMed, Scopus, Cochrane CENTRAL, and Web of Science were systematically searched for randomized controlled trials (RCTs) and non-RCTs to determine the effects of TRE on cytokines and adipokines in adults up to 23 June, 2023. Risk of bias was assessed using risk of Bias 2 tool for RCTs and the ROBINS-I for non-RCTs. The standardized mean differences (SMDs) and their 95% confidence intervals (CIs) were estimated with the DerSimonian-Laird method through random-effect models. The PRISMA recommendations were followed. A total of 25 studies (13 RCTs, 12 non-RCTs) involving 936 participants were included. The pooled SMD for the effect of TRE compared with the control group on cytokines and adipokines was -0.11 (95% CI: -0.33, 0.12; I2 = 19.7%; n = 10 comparisons) for CRP; -0.25 (95% CI: -0.47, -0.03; I2 = 0%; n = 11 comparisons) for TNF-α; -0.09 (95% CI: -0.39, 0.21; I2 = 16.4%; n = 8 comparisons) for IL-6; -0.81 (95% CI: -1.37, -0.24; I2 = 65.3%; n = 5 comparisons) for leptin; and 0.07 (95% CI: -0.40, 0.54; I2 = 56.9%; n = 6 comparisons) for adiponectin. Time-restricted eating may be an effective approach to reduce TNF-α and leptin levels in the general adult population. This review was registered at PROSPERO as CRD42022358162.


Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome.
We report 2 families with undiagnosed recessive presynaptic congenital myasthenic syndrome (CMS). Whole exome or genome sequencing identified segregating homozygous variants in VAMP1: c.51_64delAGGTGGGGGTCCCC in a Kuwaiti family and c.146G>C in an Israeli family. VAMP1 is crucial for vesicle fusion at presynaptic neuromuscular junction (NMJ). Electrodiagnostic examination showed severely low compound muscle action potentials and presynaptic impairment. We assessed the effect of the nonsense mutation on mRNA levels and evaluated the NMJ transmission in VAMP1lew/lew mice, observing neurophysiological features of presynaptic impairment, similar to the patients. Taken together, our findings highlight VAMP1 homozygous mutations as a cause of presynaptic CMS. Ann Neurol 2017;81:597-603.


Posterior chamber intraocular lens implantation in pediatric cataract with microcornea and/or microphthalmos.
To report the results of secondary posterior chamber intraocular lens (PC-IOL) implantation in pediatric cataract eyes with microcornea and/or microphthalmos. Retrospective studies were conducted by reviewing the charts of 26 eyes of 15 patients with secondary PC-IOL implantations for microcornea and/or microphthalmos associated with cataract in children between 1999 and 2002. The corneal diameter was 9.5 mm or less at the time of secondary PC-IOL implantation. Preoperative examinations were conducted for bilaterality, corneal diameter, eye abnormalities and systemic abnormalities. Postoperative results were evaluated in terms of visual developments, refractive changes, axial length measurements and the occurrence of complications. The follow-up period was at least one year after secondary PC-IOL implantation. Age at the first diagnosis for cataract with microcornea and/or microphthalmos was 2.7 months on average. Among 15 patients, 8 (53.3%) had a family history. All patients received an initial irrigation and aspiration, posterior capsulectomy, and anterior vitrectomy at 0.8 years (0.1-3.3 years) of age and a secondary PC-IOL implantation surgery at 6.7 years (1.6-17.2 years) of age on average. The postoperative follow-up period was 2.1 years (1.1-4.3 years) on average. The average power of the implanted PC-IOL was +21.2D. Postoperative complications were secondary glaucoma in two eyes, secondary pupillary membrane formation in two eyes. Best corrected visual acuities in 20 eyes in children capable of the vision test at the last follow-up were 20/60 or better in 11 eyes, 20/80 to 20/150 in eight eyes, and 20/200 or worse in one eye. The secondary PC-IOL implantation in pediatric cataract with microcornea and/or microphthalmos is recommended as a means of improving vision, but must be conducted carefully to avoid possible complications.


MUS81 Inhibition Increases the Sensitivity to Therapy Effect in Epithelial Ovarian Cancer via Regulating CyclinB Pathway.
MUS81 is a key endonuclease involved in homologous recombination (HR) repair after DNA double-strand damage. Structure-specific endonucleases (SSEs) plays a crucial role in DNA replication, repair and transcription, and SSEs are also important for maintaining the secondary structure of DNA; therefore, their activity must be precisely controlled to ensure genome stability. We previously described that MUS81 expression was significantly correlated with CyclinB expression based on protein microarray analysis. CyclinB is a cell-cycle regulatory protein that has been shown to be involved in the activation of DNA damage repair checkpoints by inducing G2/M phase arrest, promoting apoptosis, and participating in the regulation of chemotherapeutic drug sensitivity by inducing nuclear degradation, as shown by immunofluorescence assays. In this study, MUS81-downregulated cells were generated using lentivirus-mediated RNAi. Our results demonstrated that the inhibition of MUS81 expression activated the CHK1 and CyclinB signaling pathways and sensitized ovarian cancer cells to X-ray and Olaparib treatment both in vitro and in vivo. MUS81 may be a potential therapeutic target for epithelial ovarian cancer (EOC).


Usefulness of chemotherapy for the treatment of very elderly dogs with multicentric lymphoma.
OBJECTIVE To evaluate factors for associations with duration of first remission and survival time in dogs ≥ 14 years of age with stage III to V multicentric lymphoma. DESIGN Retrospective cohort study. ANIMALS 29 dogs ≥ 14 years of age with multicentric lymphoma treated with a chemotherapy protocol at dosages used for younger dogs (n = 22) or with prednisolone alone (7). PROCEDURES Various data were collected from the medical records, including treatment response and related adverse events. Survival analysis was performed to determine duration of first remission and survival time (from start of chemotherapy), and these outcomes were compared between various groupings. RESULTS The 7 (24%) dogs that received prednisolone alone had a median survival time of 27 days and were excluded from further analysis. Complete clinical remission was achieved in 21 of the 22 (95%) remaining dogs; 1 (5%) achieved partial remission. Median duration of first remission was 181 days. Anemic dogs had a briefer remission period (median, 110 days) than nonanemic dogs (median, 228 days). Median survival time for all 22 dogs was 202 days, with estimated 1- and 2-year survival rates of 31% and 5%, respectively. Six (27%) dogs had adverse events of chemotherapy classified as grade 3 or worse. CONCLUSIONS AND CLINICAL RELEVANCE Survival time was substantially longer in dogs treated with a chemotherapy protocol versus prednisolone alone. Findings suggested that the evaluated chemotherapy protocols for lymphoma were beneficial for and tolerated by very elderly dogs, just as by younger dogs, and need not be withheld, or dosages adjusted, because of age alone.


Comparison of speckle reduction diversity tools for active millimeter-wave imaging.
Imaging concealed objects with millimeter-wave coherent radiation is accompanied by speckle. Like all interference phenomena, speckle depends on three light parameters of the millimeter-wave laser beam--phase, wavelength, and angle of incidence--and can be reduced by the diversity of these three parameters. Diversity tools to improve images of concealed objects have been compared. We report measurements, simulations, and image reconstruction results over the whole W-band (75-110 GHz) and demonstrate where each tool works the best. Multiphase diversity is successful in reducing speckle contrast: multiangle to improve the image quality, and multispectral to recognize a small object's features. A simple postprocessing eliminates the areas still covered by interference.


Skeletal type III abnormalities--a simplified treatment.
There are various forms of skeletal Type III abnormalities. The most common occurs when the maxilla is underdeveloped and the mandible grows ahead of it. In severe cases, skeletal Type III abnormalities are considered the most unattractive as well as being one of the most difficult to treat in orthodontics. A simplified approach is presented for using the Frankel III appliance to treat skeletal Type III abnormalities in young children.


Plasma concentration, urinary excretion and renal clearance of L-carnitine during pregnancy: a reversible secondary L-carnitine deficiency.
Plasma concentration, urinary excretion and renal clearance of free, total and esterified L-carnitine were monitored monthly in 14 women during the last 6 months of pregnancy and 1 month after delivery. Plasma concentration and renal clearance measured 1 month after delivery overlapped with normal values for females of comparable age, and were considered the reference values for further comparisons. Plasma concentration of free, total and esterified L-carnitine decreased during pregnancy, reaching values as low as half of those measured 1 month after delivery, whereas urinary excretion and renal clearance, mainly of L-carnitine esters, increased, with renal clearance reaching a peak at the 16th week of pregnancy. Pregnancy thus leads to a reversible secondary deficiency of L-carnitine. The involvement of L-carnitine in the excretion of an excess of acyl-S-coenzyme A groups to prevent a possible systemic acidosis, as well as hormonal changes and a reduction of L-carnitine biosynthesis, could play a significant role in the variations in L-carnitine metabolism encountered in pregnancy. As physiological components of L-carnitine are excreted via a saturable tubular reabsorption, their threshold seems to follow plasma concentration, even when they decrease markedly, as in pregnancy.


[Aspects of low anterior rectum resection].
Results analysis of 162 low anterior rectum resections, carried out in the hospital during 1999-2006 years on account of upper and medial rectal ampulla adenocarcinoma is presented in the article. Method of marking rectum resection distal border with use of optical coherent tomography was worked out and put into practice. Comparative evaluation of operation results with total and partial mesorectal cellular tissue removal was carried out. It is established that local recurrence has been indexed in 14.28% of patients undergoing anterior resection with maintenance of mesorectum part in 7.89% of patients undergoing mesorectumectomy. Indications for mobilization of left bend colon and one or another type of discharge ostomy were formulated. Measures for prediction and prophylaxis of anal incontinence after rectum resection and also the new method of small pelvis cavity intraoperative drainage were offered.


Serum profiles of oxytocin during oral contraceptive treatment.
Serum profiles of oxytocin were studied by means of a continuous blood sampling system in five young healthy women before and during treatment with a combined oral contraceptive. Oxytocin levels were determined by a specific radioimmunoassay in blood samples collected in 10-min fractions from 22.00 to 06.00. The values were further analyzed by the pulse detection program PULSAR. Great individual differences in oxytocin profiles were observed, and in some of the women these differences were also pronounced between the two sampling occasions. All 10 profiles demonstrated irregular peaks which occurred with varying frequency. Although the baseline level of oxytocin increased in all women and the average concentration increased in four of the women during treatment, there was no clear-cut effect on the peak frequency. Based on results from animal experiments, it is suggested that the increase in oxytocin levels may be related to an excitatory effect exerted by estrogen on oxytocin secreting neurons.


Silver(I) diaqua-magnesium catena-borodiphosphate(V) monohydrate, AgMg(H(2)O)(2)[BP(2)O(8)]·H(2)O.
The title compound contains infinite one-dimensional [BP(2)O(8)](3-) borophosphate helical ribbons, built up from alternate BO(4) and PO(4) tetra-hedra arranged around the 6(5) screw axes. The vertex-sharing BO(4) and PO(4) tetra-hedra form a spiral ribbon of four-membered rings in which BO(4) and PO(4) groups alternate. The ribbons are connected through slightly distorted MgO(4)(H(2)O)(2) octa-hedra, in which the four O atoms belong to the phosphate groups. The free threads of the helices are occupied by silver ions, which are in an irregular environment surrounded by six O atoms. The central channels of the helices, running along the c axis, are filled with the water mol-ecules. The structure is stabilized by O-H⋯O hydrogen bonds between the water mol-ecules and O atoms that are part of the helices. The crystal structure of the title compound is isotopic with other analogous borophosphates such as A(I)M(II)(H(2)O)(2)[BP(2)O(8)]·H(2)O, where A(I) = Li, Na, K or NH(4) (+) and M(II) = Mg, Mn, Fe, Co, Ni, Cu, Zn or Cd.


Improving Psychological Health Outcomes in Children with Atopic Dermatitis.
Atopic dermatitis (AD) is a chronic inflammatory skin disease that usually develops in early childhood. AD has a significant impact on quality of life and psychological health outcomes in both adults and children. There are increased reported rates of psychiatric comorbidities including anxiety, depression, ADHD and suicidal ideation compared to the general population. Primary caregivers of children with pediatric eczema and their families may also have derangements in psychological health and quality of life. A number of interventions exist for AD and address wellbeing outcomes as an important aspect of effective treatment. A comprehensive literature search was conducted using PubMed/Medline, Embase, the Cochrane Central Register of Controlled Trials in February 2023. Published studies up to April 2023 were included related to interventions for childhood AD that included psychological health or quality of life outcomes. These interventions were stratified according to type and evidence quality. Search strategy revealed a wide variety of interventions with demonstrated improvements in quality of life or wellbeing of patients with pediatric AD or their families. Both pharmacological and non-pharmacological interventions demonstrated effectiveness in improving disease outcomes. A variety of both pharmacological and non-pharmacological interventions may be employed to improve psychological health outcomes in children with AD.


Graphic representation of skeletal maturity determinations.
Skeletal maturation determinations are usually reported as numeric data indicating accordance with chronologic age. However, significant changes in skeletal maturation can occur without falling outside two SDs. The purpose of our study was to design simple computer-generated sex-based charts to enhance the evaluation of skeletal maturation, especially when frequent assessments are made. The graphic representation of successive reports clearly depicts whether values retain their position in relation to the mean. In addition, the report includes computation of the exact SD score.


Elevated levels of urinary 8-hydroxy-2'-deoxyguanosine in male electrical and electronic equipment dismantling workers exposed to high concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans, polybrominated diphenyl ethers, and polychlorinated biphenyls.
To investigate the occupational exposure levels to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs), indoor dust (n = 3) in workshops and hair samples from male workers (n = 64) were collected at two electrical and electronic equipmentwaste (E-waste) dismantling factories located in the LQ area in east China in July 11--13, 2006. Pre- and postworkshift urines (64 of each) were also collected from the workers to study oxidative damage to DNA using 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a biomarker. The concentrations of PCDD/Fs, PCDD/F-WHO-TEQs, PBDEs, PCBs and PCB-WHO-TEQs were (50.0 +/- 8.1) x 10(3), 724.1 +/- 249.6, (27.5 +/- 5.8) x 10(6), (1.6 +/- 0.4) x 10(9), (26.2 +/- 3.0) x 10(3) pg/g dry weight (dw) in dust, and (2.6 +/- 0.6) x 10(3),42.4 +/- 9.3, (870.8 +/- 205.4) x 10(3), (1.6 +/- 0.2) x 10(6), 41.5 +/- 5.5 pg/g dw in hair, respectively. The homologue and congener profiles in the samples demonstrated that high concentrations of PCDD/Fs, PBDEs, and PCBs were originated from open burning of E-waste. The 8-OHdG levels were detected at 6.40 +/- 1.64 micromol/mol creatinine in preworkshift urines. However, the levels significantly increased to 24.55 +/- 5.96 micromol/mol creatinine in postworkshift urines (p < 0.05). Then, it is concluded that there is a high cancer risk originated from oxidative stress indicated by the elevated 8-OHdG levels in the E-waste dismantling workers exposed to high concentrations of PCDD/Fs, PBDEs, and PCBs.


[Histopathologic representation of a tumoral EEG focus by spectral analysis].
This work is intended for those: (1) wishing to use spectral analysis for clinical purposes and who have ony limited computer facility possibilities at their disposal; (2) who are looking for a simple and, above all, easily and immediately interpretable graphic representation of the spectral data developed by a cerebral focal lesion, which can be interpreted even by an inexperienced clinician. Finally this paper emphasized the value of a particularly interesting clinical sign from quantitative analysis, namely the EEG supervision of cerebral tumours, either evolving or recovering.


Abdominal hernias: imaging review and historical perspectives.
Many eminent anatomists originally described abdominal hernias, some of which are still named after the original authors. In this article, the radiologic features of abdominal hernias are reviewed as imaged on x-ray, ultrasound, multidetector computed tomography, and magnetic resonance imaging. Recognition of the typical appearance of various types of abdominal hernias and associated adverse features such as bowel obstruction, perforation, strangulation, or volvulus formation can help in formulating an accurate diagnosis. A short biography of the scientists associated with eponymous hernias and their other important scientific contributions are also described.


Direct production of functional matrix metalloproteinase--14 without refolding or activation and its application for in vitro inhibition assays.
Human matrix metalloproteinase (MMP)-14, a membrane-bound zinc endopeptidase, is one of the most important cancer targets because it plays central roles in tumor growth and invasion. Large amounts of active MMP-14 are required for cancer research and the development of chemical or biological MMP-14 inhibitors. Current methods of MMP-14 production through refolding and activation are labor-intensive, time-consuming, and often associated with low recovery rates, lot-to-lot variation and heterogeneous products. Here, we report direct production of the catalytic domain of MMP-14 in the periplasmic space of Escherichia coli. 0.5 mg/L of functional MMP-14 was produced without tedious refolding or problematic activation process. MMP-14 prepared by simple periplasmic treatment can be readily utilized to evaluate the potencies of chemical and antibody-based inhibitors. Furthermore, co-expression of both MMP-14 and antibody Fab fragments in the periplasm facilitated inhibitory antibody screening by avoiding purification of MMP-14 or Fabs. We expect this MMP-14 expression strategy can expedite the development of therapeutic drugs targeting MMPs with biological significance.


Near infrared overtone (vOH = 2 ← 0) spectroscopy of Ne-H2O clusters.
Vibrationally state selective overtone spectroscopy and dynamics of weakly bound Ne-H2O complexes (D0(para) = 31.67 cm-1, D0(ortho) = 34.66 cm-1) are reported for the first time, based on near infrared excitation of van der Waals cluster bands correlating with vOH = 2 ← 0 overtone transitions (|02-⟩←|00+⟩ and |02+⟩←|00+⟩) out of the ortho (101) and para (000) internal rotor states of the H2O moiety. Quantum theoretical calculations for nuclear motion on a high level ab initio potential energy surface (CCSD(T)/VnZ-f12 (n = 3,4), corrected for basis set superposition error and extrapolated to the complete basis set limit) are employed for assignment of Σ←Σ,Π←Σ, and Σ←Π infrared bands in the overtone spectra, where Σ(K = 0) and Π (K = 1) represent approximate projections (K) of the body angular momentum along the Ne-H2O internuclear axis. End-over-end tumbling of the ortho Ne-H2O cluster is evident via rotational band contours observed, with band origins and rotational progressions in excellent agreement with ab initio frequency and intensity predictions. A clear Q branch in the corresponding |02+⟩fΠ(111)←eΣ(000) para Ne-H2O spectrum provides evidence for a novel e/f parity-dependent metastability in these weakly bound clusters, in agreement with ab initio bound state calculations and attributable to the symmetry blocking of an energetically allowed channel for internal rotor predissociation. Finally, Boltzmann analysis of the rotational spectra reveals anomalously low jet temperatures (Trot ≈ 4(1) K), which are attributed to "evaporative cooling" of weakly bound Ne-H2O clusters and provide support for similar cooling dynamics in rare gas-tagging studies.


Validity of Postmortem Glycated Hemoglobin to Determine Status of Diabetes Mellitus in Corneal Donors.
To examine the stability of postmortem glycated hemoglobin (HbA1c) measurement and its relationship to premortem glycemia. Postmortem blood samples were obtained from 32 donors (8 known diabetic) and shipped on ice to a central laboratory to examine the stability of HbA1c measurements during the first 9 postmortem days. Thirty-nine other suspected diabetic donors underwent comparison of premortem and postmortem HbA1c measurements. Postmortem HbA1c measurements remained stable after 9 postmortem days (all measurements within ±0.2% from baseline with a mean difference of 0.02% ± 0.10%). Of the premortem measurements obtained within 90 days before death, 79% were within ±1.0% of the postmortem measurements compared with 40% for measurements more than 90 days apart. Three of the postmortem HbA1c measurements exceeded 6.5% (considered a threshold for diabetes diagnosis), although the medical histories did not indicate any previous diabetes diagnosis. Postmortem HbA1c testing is feasible with current eye bank procedures and is reflective of glycemic control of donors during 90 days before death. HbA1c testing could potentially be a useful adjunct to review of the medical history and records for donor assessment for endothelial keratoplasty suitability and long-term graft success.


[Evaluation of the Effects of Remifentanil Doses on Hemodynamics and Perfusion Index at the Onset of Pneumoperitoneum during Laparoscopic Surgery].
The aim of this study was to investigate whether changes in perfusion index (PI) correlate with non-invasive haemodynamic parameters (HR, BP) following the onset of pneumoperitoneum under two doses (moderate-dose (MD) and high-dose (HD)) of remifentanil and to compare its reliability. We divided 33 patients who were scheduled for laparoscopic surgery under general anesthesia into two groups according to the dose of continuously infused remifentanil: moderate dose 0.5 μg x kg(-1) x min(1) (MD group, n = 16) and high dose 1.0 μg x kg(-1) x min(-1) (HD group, n = 17). Non-invasive blood pressure (NIBP), HR, and PI were measured before the start of surgery (time 1), after the start of surgery (time 2), before the start of pneumoperitoneum (time 3), and 1 min after the stable state of pneumoperitoneum (time 4). PI decreased from the baseline after pneumoperitoneum in MD group, on the other hand PI did not change in HD group. Between the two groups, the magnitude of the PI changes was statistically different although MBP and HR were not statistically different PI may be a reliable and easier alternative to conventional haemodynamic parameters for detection of stress response to pneumoperitoneum during remifentanil anaesthesia in adult patients.


Genomic analysis of HPV-positive versus HPV-negative oesophageal adenocarcinoma identifies a differential mutational landscape.
High-risk human papillomavirus (hr-HPV) has been implicated in a subset of patients with oesophageal adenocarcinoma (OAC). We therefore hypothesised that HPV associated OAC may have distinct genomic aberrations compared with viral negative oesophageal cancer. Whole exome sequencing was performed to explore the mutational landscape and potential molecular signature of HPV-positive versus HPV-negative OAC. Four hr-HPV-positive and 8 HPV-negative treatment-naive fresh-frozen OAC tissue specimens and matched normal tissue were analysed to identify somatic genomic mutations. Data were subjected to cancer driver gene identification and pathway analysis. The HPV-positive cohort harboured approximately 50% less non-silent somatic mutations than the virus-negative patients with oesophageal cancer (1.31 mutations/Mb vs 2.56 mutations/Mb, p=0.048). TP53 aberrations were absent in the HPV-positive OAC group whereas 50% of the HPV-negative patients with OAC exhibited TP53 mutations. HPV-negative cancers were enriched with non-silent mutations in cancer driver genes, but not HPV-positive tumours. Enriched A>C transversions at adenine-adenine (AA) dinucleotide was observed in 5/7 Siewert class I OAC samples but none (0/5) in Siewert class II tumours (p=0.027). These findings demonstrate distinct genomic differences between HPV-positive and HPV-negative OACs indicating different biological mechanisms of tumour formation.