Determination of optical properties of turbid medium from relative interstitial CW radiance measurements using the incomplete P3 approximation.
Interstitial determination of the tissue optical properties is important in biomedicine, especially for interstitial laser therapies. Continuous wave (CW) radiance techniques which examine light from multiple directions have been proposed as minimally invasive methods for determining the optical properties under an interstitial probe arrangement. However, both the fitting algorithm based on the P3 approximation and the analytical method based on the diffusion approximation (DA), which are currently used recovery algorithms, cannot extract the optical properties of tissue with low transport albedos accurately from radiance measurements. In this paper, we proposed an incomplete P3 approximation for the radiance, the P3in for short, which is the asymptotic part of the solution for the P3 approximation. The relative differences between the P3in and the P3 were within 0.48% over a wide range of clinically relevant optical properties for measurements at source detector separations (SDS) from 5 mm to 10 mm and angles from 0° to 160°. Based on the P3in, we developed an analytical method for extracting the optical properties directly using simple expressions constructed from the radiance measurements at only two SDSs and four angles. The developed recovery algorithm was verified by simulated and experimental radiance data. The results show that both the absorption and reduced scattering coefficients were recovered accurately with relative errors within 5.28% and 3.86%, respectively, from the simulated data and with relative errors within 10.82% and 10.67%, respectively, from the experimental data over a wide range of albedos from 0.5 to 0.99. Since the developed P3in-based radiance technique can obtain the optical properties rapidly from the measurements at only two SDSs and four angles, it is expected to be used for in vivo and in situ determination of the optical properties in online treatment planning during laser therapies.


Determination of cytosine-beta-D-arabinoside in plasma using capillary electrophoresis.
An assay for the antileukaemic agent cytosine-beta-D-arabinoside (ara-C) has been developed using capillary zone electrophoresis. Solid-phase extraction and on-capillary peak concentration are used to improve the detection limit. The electrophoretic separation time is less than 5 min. The limit of detection for ara-C in plasma is 0.5 microM (signal-to-noise ratio = 3). The assay has been validated for the determination of ara-C in human plasma over the concentration range 1-10 microM. The calibration curve was linear with a correlation coefficient r2 = 0.996. At an ara-C concentration of 8 microM the intra-day coefficient of variation was 9.1% and the inter-day coefficient of variation was 12.3%. At an ara-C concentration of 2 microM the coefficients of variation were 15.2 and 12.0%, respectively.


Oxidative DNA base damage by the antitumor agent 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine).
Tirapazamine is a bioreductively activated DNA-damaging agent that selectively kills the hypoxic cells found in solid tumors. In this work, base excision repair enzymes were used to provide evidence that tirapazamine causes significant amounts of damage to both purine and pyrimidine residues in double-stranded DNA.


A premenopausal woman with virilization secondary to an ovarian Leydig cell tumor.
A 33-year-old woman presented to an endocrinology clinic with a 5-year history of secondary amenorrhea. 2 years before presentation, she had noticed progressively worsening signs of virilization. Measurement of levels of serum free and total testosterone, androstenedione, dehydroepiandrosterone sulfate and gonadotropins; transvaginal ultrasonography, abdominal and pelvic MRI and (18)F-fluorodeoxyglucose PET imaging. Virilization secondary to an ovarian Leydig cell tumor. The patient underwent a left salpingo-oophorectomy that confirmed the diagnosis of a unilateral Leydig cell tumor. Complete normalization of androgens and gonadotropin levels was achieved after surgery.


Abdominal compartment syndrome after open biopsy in a child with bilateral Wilms' tumour.
Although Wilms' tumour is one of the most common solid malignancies in children, bilateral disease is rare. We report a child with bilateral Wilms' tumour who developed abdominal compartment syndrome after an open biopsy.


Altered host immune responses to membrane vesicles from Salmonella and Gram-negative pathogens.
Membrane vesicles (MVs), discrete nano-structures produced from the outer membrane of Gram-negative bacteria such as Salmonella enterica Typhimurium (S. Typhimurium), strongly activate dendritic cells (DCs), contain major antigens (Ags) recognized by Salmonella-specific B-cells and CD4+ T-cells, and provide protection against S. Typhimurium challenge in a mouse model. With this in mind, we hypothesized that alterations to the gene expression profile of bacteria will be reflected in the immunologic response to MVs. To test this, we assessed the ability of MVs from wild-type (WT) S. Typhimurium or a strain with a phenotype mimicking the intracellular-phase of S. Typhimurium (PhoP(c)) to activate dendritic cells and initiate a strong inflammatory response. MVs, isolated from wild-type and PhoP(c)S. Typhimurium (WTMVs and PhoPcMVs, respectively) had pro-inflammatory properties consistent with the parental bacterial strains: PhoPcMVs were less stimulatory for DC activation in vitro and were impaired for subsequent inflammatory responses compared to WTMVs. Interestingly, the reduced pro-inflammatory properties of PhoPcMVs did not completely rely on signals through TLR4, the receptor for LPS. Nonetheless, both WTMVs and PhoPcMVs contained abundant immunogenic antigens capable of being recognized by memory-immune CD4+ T-cells from mice previously infected with S. Typhimurium. Furthermore, we analyzed a suite of pathogenic Gram-negative bacteria and their purified MVs for their ability to activate DCs and stimulate inflammation in a manner consistent with the known inflammatory properties of the parental strains, as shown for S. Typhimurium. Finally, analysis of the potential vaccine utility of S. Typhimurium MVs revealed their capacity to encapsulate an exogenous model antigen and stimulate antigen-specific CD4+ and CD8+ T-cell responses. Taken together, our results demonstrate the dependence of bacterial cell gene expression for MV immunogenicity and subsequent in vitro immunologic response, as well as their potential utility as a vaccine platform.


RpoN of the fish pathogen Vibrio (Listonella) anguillarum is essential for flagellum production and virulence by the water-borne but not intraperitoneal route of inoculation.
To investigate the involvement of RpoN in flagellum production and pathogenicity of Vibrio (Listonella) anguillarum, the rpoN gene was cloned and sequenced. The deduced product of the rpoN gene displayed strong homology to the alternative sigma 54 factor (RpoN) of numerous species of bacteria. In addition, partial sequencing of rpoN-linked ORFs revealed a marked resemblance to similarly located ORFs in other bacterial species. A polar insertion or an in-frame deletion in the coding region of rpoN abolished expression of the flagellin subunits and resulted in loss of motility. Introduction of the rpoN gene of V. anguillarum or Pseudomonas putida into the rpoN mutants restored flagellation and motility. The rpoN mutants were proficient in the expression of other proposed virulence determinants of V. anguillarum, such as ability to grow under low available iron conditions, and expression of the LPS O-antigen and of haemolytic and proteolytic extracellular products. The infectivity of the rpoN mutants with respect to the wild-type strain was unaffected following intraperitoneal injection of fish but was reduced significantly when fish were immersed in bacteria-containing water. Thus, RpoN does not appear to regulate any factors required for virulence subsequent to penetration of the fish epithelium, but is important in the infection of fish by water-borne V. anguillarum.


Screening conditions for rationally engineered electrodeposition of nanostructures (SCREEN): electrodeposition and applications of polypyrrole nanofibers using microfluidic gradients.
A rapid screening method for optimizing electrochemical deposition conditions of polypyrrole (PPy) nanostructures is reported. An electrochemical cell is integrated within a low-cost microfluidic system, in which electrochemical deposition is carried out across a linear concentration gradient of a reaction parameter. The protocol, refered to as the screening of conditions for rationally engineered electrodeposition of nanostructures (SCREEN), allows rapid screening of conditions for the production of specific morphologies by characterizing the electrodeposited samples produced within a chemical gradient. To demonstrate the utility of the SCREEN method, applications in tunable optical coatings and superhydrophobic surfaces are presented.


CT for the evaluation of flank pain.
Unenhanced helical CT allows rapid and accurate determination of whether a stone is present anywhere in the urinary tract. There is a learning curve for both radiologist and urologist, but a number of signs are highly predictive of stone. Helical CT scans should always be accompanied by a "scoutogram" to convey an idea of what the stone might look like. The scan requires no contrast medium and takes only 5 to 10 minutes of imaging time, making it cost effective. It behooves both urologists and radiologists to familiarize themselves with the techniques for reading these scans.


FDG Uptake on Positron Emission Tomography Correlates with Survival and Time to Recurrence in Patients with Stage I Non-Small-Cell Lung Cancer.
Patients with stage I non-small-cell lung cancer (NSCLC) have a wide variation in outcomes, most likely because there are undetected metastases at presentation. We retrospectively reviewed patients with early stage lung cancer to determine if FDG uptake of the primary tumor as measured on positron emission tomography (PET) at the time of diagnosis was associated with overall survival (OS) or time to recurrence (TTR). We reviewed the Tumor Registry at our institution and identified 336 consecutive patients diagnosed with stage I NSCLC over a 5-year period who underwent an FDG-PET/computed tomography within 90 days before surgery. Kaplan-Meier curves were used to describe the survival and TTR experience within subgroups defined by PET maximum standardized uptake value (SUVmax). Cox proportional hazards model was used to assess the impact of PET SUVmax as a continuous variable on OS and TTR. Logistic regression was used to analyze the effect of SUVmax on dichotomized outcomes. Three hundred thirty-six consecutive patients (176 women and 160 men) with stage I NSCLC were retrospectively reviewed. Mean SUVmax was 9.2 ± 6.9 (range 0.6-30.3). The hazard or risk of dying and recurrence increased significantly as SUVmax increased (p = 0.0008 and 0.024, respectively). Preoperative FDG uptake in the primary tumor in patients with stage I disease is associated with OS and TTR. This may be useful in identifying early stage patients who may benefit from more aggressive therapy after surgical resection.


Characterization of high-yield pulp (HYP) by the solute exclusion technique.
By following the solute exclusion technique, we determined the pore characteristics of 3 hardwood high-yield pulps (aspen, birch, maple). The fiber saturation point (FSP) was 1.40, 1.36 and 1.19 g water/g pulp, for aspen, birch, maple, respectively, which is lower than that of chemical pulps. Different fractions obtained from the Bauer-McNett classifier showed that the HYP fines have much more pore volume than their long fiber counterparts. The effects of beating, drying and re-wetting on the pore characteristics of HYP were also studied. Beating led to increased total pore volumes. Upon drying and re-wetting, much of the small pores from the HYP underwent permanent closure while the big pores were only slightly affected. Finally, the relationship between the water retention value (WRV) and FSP for HYP was examined.


Role of adenosine in regulation of regional cerebral blood flow in sensory cortex.
We have previously demonstrated that rat pial arterioles located on the somatosensory cortex dilated in response to contralateral sciatic nerve stimulation (SNS). We hypothesized that the vasodilation was mediated by adenosine, released as a result of somatosensory cortex activation. To test this hypothesis, we examined the effects of SNS (0.15-0.2 V, 5 ms, 5 Hz for 20 s) on pial arterioles under conditions of altered adenosine availability. Cerebrospinal fluid (CSF) adenosine was altered by perfusing mock CSF, under a cranial window in anesthetized rats, containing either an adenosine uptake competitor (dipyridamole or inosine) or an adenosine receptor blocker (theophylline). With CSF only, SNS caused pial arterioles (resting diam, 29 +/- 1 micron) to dilate by 38 +/- 10% (peak magnitude) for 32 +/- 2 s. Dipyridamole (10(-6) M) significantly (P less than 0.02) enhanced both the magnitude (to 62 +/- 12%) and duration (to 68 +/- 10 s) of the response. Similarly, inosine (10(-3) M) significantly (P less than 0.02) potentiated the vasodilative response from resting values of 27 +/- 5% and 34.8 +/- 4.1 s to 37 +/- 6% and 89.6 +/- 14.1 s. In contrast, theophylline (5 x 10(-5) M) significantly (P less than 0.001) attenuated arteriolar vasodilation from resting values of 38 +/- 5% and 29.3 +/- 1.2 s to 18 +/- 3% and 22.0 +/- 0.9 s. Neither dipyridamole nor theophylline had a significant effect on neuronal response (sensory-evoked response) recorded from the somatosensory cortex. These results suggest that adenosine is involved in the regulation of pial vasodilation during cerebral cortical activation.


Effects of pentoxifylline on human polymorphonuclear neutrophil responses to TNF in whole blood.
We used flow cytometry to study the effects of pentoxifylline (PTX) on the expression of adhesion molecules and fMLP receptors on whole-blood polymorphonuclear neutrophils (PMN) in response to TNF, together with the oxidative burst and actin polymerisation. This technique analyses cells individually and avoids PMN activation related to isolation procedures. PTX reduced CD11b upregulation induced by TNF. Moreover, PTX reduced both TNF-induced binding of bacterial formyl peptides (fMLP) by human PMN and TNF priming of the PMN oxidative burst in response to these peptides. PTX also reduced TNF-induced actin polymerisation, which has been reported to participate in receptor cycling. This phenomenon could account in part for the ability of PTX to reduce fMLP binding to the PMN surface and subsequently to inhibit the PMN oxidative burst in response to fMLP. In addition to the PTX-induced decrease of TNF production, these effects on PMN could be beneficial in pathological conditions where high TNF production may induce excessive PMN activation, leading to vascular damage and tissue injury.


[Overall biostatistical approach to the 24-h behavior of arterial blood pressure in chronic uremic normotensive patients].
The present study discusses the 24-h patterns of blood pressure in chronic uremic patients classified as normotensives by means of casual sphygmomanometric measurements. Data obtained enabled us to affirm that the blood pressure of normotensive chronic uremic patients is not normal due to a wider distribution, the occurrence of supraphysiologic values during day-night time and the absence of a circadian rhythm. The lack of a nocturnal decrease in blood pressure causes a hyperbaric impact on the arterial wall for "normotensive" chronic uremic patients.


All-fiber polarization beam splitting and rotating based on vector-mode-assisted coupling.
We propose and design a new kind of all-fiber polarization beam splitter and rotator (PBS and PBR) based on vector-mode-assisted coupling. By embedding a high-contrast-index ring-core between two cores of the conventional fiber couplers, being a three-core coupling structure, the state of polarization (SOP) of fiber-guided modes can be availably controlled, such as polarization splitting and rotating, by transitional coupling through TM01 or TE01 vector mode. Furthermore, the SOP of coupled mode can be rotated with arbitrary angle under different three-core layouts. In particular, by exploiting HE21-assisted coupling case, we can realize full-dimensional SOP rotation for arbitrary polarization input. We give the numerical simulation for the proposed all-fiber PBS and PBR, and investigate the corresponding polarization extinction ratio and polarization rotating purity in detail. The calculation results manifest a favorable performance on SOP management of fiber-guided modes. This vector-mode-assisted coupling might be expected to find potential applications in the polarization-based optical signal processing, multiplexing, and sensing system.


Eastern equine encephalomyelitis. Histopathologic and ultrastructural changes with isolation of the virus in a human case.
Enveloped Toga virus particles were demonstrated by means of an electron microscopy in the brain tissues of a 3-year-old girl with acute encephalitis. Areas of demyelinization and necrosis throughout the white matter and brainstem were revealed by light microscopy. These viral particles were identified as eastern equine encephalomyelitis virus in postmortem isolation of the virus utilizing young mice and complement-fixation studies. To the authors' knowledge, this is the first demonstration of eastern equine encephalomyelitis virus particles in human tissues by electron microscopy.


Computed tomography of unusual calcified pancreatic tumors.
Two unusual pancreatic tumors, a pancreatic fibroma and a solid and papillary neoplasm of the pancreas, are described. Both appeared to be heavily calcified on CT examination, a feature that has not been reported.


Serum alkaline phosphatase for screening of hypovitaminosis D.
This study assessed the utility of serum alkaline phosphatase as a screening test to identify vitamin D deficiency and documented that it was not a useful screening tool.


Molecular characterization of inhibiting biochar water-extractable substances using electrospray ionization fourier transform ion cyclotron resonance mass spectrometry.
Biochar has gained significant interest worldwide for its potential use as both a carbon sequestration technique and soil amendment. Recently, research has shown that pinewood-derived biochar water extracts inhibited the growth of aquatic photosynthetic microorganisms, both prokaryotic and eukaryotic algae, while chicken litter- and peanut shell-derived biochar water extracts showed no growth inhibition. With the use of electrodialysis, the pinewood-derived biochar water extract is separated into 3 fractions (anode-isolated, center chamber retained, and cathode-isolated substances) all with varying toxic effects. Because of its ultrahigh resolution and mass precision, electrospray ionization (ESI) coupled to Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) is utilized in this study to analyze biochar water extracts at a molecular level to enhance our understanding of the toxic nature of pinewood-derived biochar water extracts as compared to benign peanut shell-derived biochar water extracts. The molecular composition of pinewood-derived biochar water extracts shows unique carbohydrate ligneous components and sulfur containing condensed ligneous components that are both absent from the peanut shell water extracts and more prevalent in the anode-isolated substances. Using Kendrick mass defect analysis, we also determine that the most likely inhibitor species contain carboxyl and hydroxyl homologous series, both of which are characteristic functional groups hypothesized in our previous research for the inhibitor species. We have suggested that inhibition of aquatic photosynthetic microorganism growth is most likely due to degraded lignin-like species rich in oxygen containing functionalities. From the study conducted here, we show the potential of ultrahigh resolution FTICR-MS as a valuable analytical technique for determining whether certain biochars are safe and benign for use as carbon sequestration and soil amendment.


Potentially toxic metals in ombrotrophic peat along a 400 km English-Scottish transect.
Four samples of ombrotrophic peat were collected from each of 10 upland locations in a transect from the southern Pennines to the Highland Boundary Fault, a total distance of ca. 400 km. Bulk compositions and other properties were determined. Total contents of Al and heavy metals (Ni, Cu, Zn, Cd, Pb) were determined following digestion with hydrofluoric acid, and concentrations of metals extractable with dilute nitric acid were also measured. Supernatants obtained from aqueous extractions of the peat samples were analysed for pH, major cations and anions, dissolved organic carbon and dissolved metals, and concentrations of free metal ions (Al(3+), Ni(2+), etc.) were estimated by applying a chemical speciation model. Both total and HNO(3)-extractable metal concentrations varied along the transect, the highest values being found at locations close to industrial and former mining areas. The HNO(3)-extractable soil metal contents of Ni, Cu and Cd were appreciably lower than lowest-observed-effect-concentrations (LOEC) for toxicity towards microorganisms in acid, organic rich soils. However, the contents of Zn at two locations, and of Pb at five locations exceeded LOECs, suggesting that they may be exerting toxic effects in the peats. Soil solution concentrations of free heavy metal ions (Cu(2+), Zn(2+), Cd(2+), Pb(2+)) were substantially lower than LOECs for toxicity towards vascular plants, whereas concentrations of Al(3+) were near to toxic levels at two locations.


Native and non-native structure in a protein-folding intermediate: spectroscopic studies of partially reduced IGF-I and an engineered alanine model.
The structure of a metastable folding intermediate of human insulin-like growth factor I (IGF-I) and an engineered model are investigated by circular dichroism and two-dimensional 1H NMR spectroscopy. The intermediate, which contains two of three native disulfide bonds, was trapped by acid quenching and isolated by reverse-phase HPLC. The reduced cysteine residues were mapped to residues 47 and 52 (corresponding to A6-A11 in insulin). In the native state this disulfide bridge anchors an adjoining amphipathic alpha-helix (helix 2; residues 42 to 49) against the hydrophobic core. Comparison of CD and 1H-NMR spectra demonstrates that the acid-quenched intermediate is partially folded and contains elements of native secondary and tertiary structure. Spectra are similar to those of an equilibrium model in which the reduced cysteine residues are replaced by alanine. Complete 1H-NMR sequential assignment of the alanine model has been obtained and demonstrates that removal of the disulfide bond is associated with local unfolding of the adjoining alpha-helix. Native secondary structure (including helices 1 and 3) is otherwise retained and defines a folded subdomain. Long-range nuclear Overhauser effects (NOE) within this subdomain are similar to those of native IGF-I; no non-native NOE is observed. Our results support the hypothesis that folding of the insulin motif is directed by a subset of native structural elements and that these elements form at an early step in the pathway. Formation of helix 2, despite its prominence in the native state, is likely to represent a late step. Hydrophobic collapse of this segment appears to precede helix formation.


Radiation dose of interventional radiology system using a flat-panel detector.
Currently, cardiac interventional radiology equipment has tended toward using flat-panel detectors (FPDs) instead of image intensifiers (IIs) because FPDs offer better imaging performance. However, the radiation dose from an FPD in cardiac interventional radiology is not clear. The purpose of our study was to measure the radiation doses during cineangiography and fluoroscopy of many cardiac radiology systems that use FPDs or IIs, in clinical settings. This study examined 20 radiology systems in 15 cardiac catheterization laboratories (11 used FPD and nine used II). The entrance surface doses with digital cineangiography and fluoroscopy were compared for the 20 systems using acrylic plates (20-cm thick) and a skin dose monitor. For fluoroscopy, the average entrance surface doses of the 20-cm-thick acrylic plates were identical for FPD (average +/- SD, 16.63 +/- 7.89 mGy/min; range, 5.7-26.4 mGy/min; maximum/minimum, 4.63) and II (17.81 +/- 12.52 mGy/min; range, 6.5-42.2 mGy/min; maximum/minimum, 6.49) (p = 0.799). For digital cineangiography, the average entrance surface dose of the 20-cm-thick acrylic plate was slightly lower with FPD (29.68 +/- 16.40 mGy/10 s; range, 8.9-58.5 mGy/10 s; maximum/minimum, 6.57) than with II (38.50 +/- 33.71 mGy/10 s; range, 15.2-117.1 mGy/10 s; maximum/minimum, 7.70), although the difference was not significant (p = 0.487). We found that the average entrance doses of cineangiography and fluoroscopy in FPD systems were not significantly different from those in II systems. Hence, FPDs did not inherently reduce the radiation dose, although FPDs possess good detective quantum efficiency. Therefore, to reduce the radiation dose of cardiac interventional radiology systems, even FPD systems, practical measures are necessary.


Interactive videodisc: its place in today's nursing curricula.
The need for nurse educators to realistically assess interactive videodisc technology is readily apparent when one considers the analyzed educational benefits of that medium. Skills of discrimination, generalization, and sequencing are particularly targeted for the population of nursing students because these abilities are necessary for problem solving, analysis, nursing diagnosis, and conceptual learning. However, in these times of limited resources one must carefully evaluate the necessary expenditures versus the perceived advantages of the technology. This article reviews the literature on educational applications of videodisc technology and reports on a survey of videodisc use at 504 National League of Nursing (NLN) accredited baccalaureate programs. Results of this study validate the current cautious approach to implementing interactive videodisc technology in nursing programs.


Modern Total Knee Arthroplasty (TKA): With Or Without a Tourniquet?
Since arthritis of the knee is one of the most common pathologies in industrialized nations, there has been a growing interest in fast-track total knee arthroplasty (TKA). However, while one of the main concerns is the role of a tourniquet, the available data are inconclusive. This study sought to assess the link between postoperative outcomes and use of a tourniquet in TKA. Our goal was to determine whether it is justified to forego tourniquet use as indicated by the fast-track concept. The participants (n = 108) in this retrospective, non-randomized study were assigned into two groups after they satisfied the inclusion criteria: primary gonarthrosis or secondary gonarthrosis without previous arthrotomy. TKA was performed without (Group I, n = 55) or with (Group II, n = 53) a tourniquet. The postoperative outcome was evaluated in terms of postoperative pain, based on a numeric rating scale (NRS) and the need for pain medication, and postoperative function, based on range of motion (ROM) and walking tests. Overall, no significant correlations were observed between tourniquet use and postoperative pain according to the NRS. Group I required less oxycodone, but more non-opioids. There was no significant difference in the improvement in pre- to postoperative ROM with regard to tourniquet use. The final walking distance was significantly longer in Group I. These results suggest that there is no strongly significant link between the postoperative outcome and the use of a tourniquet. However, further studies will be needed to determine whether a tourniquet may have some other impact on TKA.


Summation of symbols by pigeons (Columba livia): the importance of number and mass of reward items.
In each of 3 experiments, different sets of 4 pigeons (Columba livia) were trained to discriminate between 2 visual symbols that covered wells containing food items that varied in number, mass, or both. In Experiment 1, the symbols were associated with 0, 1, 3, 5, 7, or 9 pieces of grain reward. The pigeons learned to choose the symbol corresponding to the larger reward, and on summation tests, they chose the pair of symbols that summed to the larger total reward. When number of food pellets was varied but mass of reward was held constant in Experiment 2, preference for the larger number symbols failed to appear. When number was held constant and mass was varied in Experiment 3, the pigeons showed a clear preference for the larger mass symbols on single-symbol and summation tests. These findings show that pigeons summate the value of symbols and are more likely to represent symbols by mass of food reward than by number of food items.


The efficacy of wearable activity tracking technology as part of a weight loss program: a systematic review.
The world obesity rate has increased over the past two decades. This problem has been linked to inactivity and lack of exercise among individuals which prompted the development of wearable activity tracking technology. This technology is commonly offered as a bracelet, watch, or pendent that provides feedback of daily activity such as total step count, heart rate, and energy expenditure. Despite the popularity of these devices, their efficacy to assist in behavior change and weight loss is still being studied. The purpose of this systematic review was to appraise the current evidence on the efficacy of wearable activity devices when used in a comprehensive weigh loss program. A systematic review was conducted according the PRISMA guidelines. A search of electronic databases was conducted through December 2016 using the following keywords: activity monitor, consumer, wearable, technology, Fitbit®, Garmin®, Jawbone®, physical, activity, tracker, weight loss, walking, pedometer, accelerometer, step count, calories, obesity, digital, self-monitoring, and mobile health (mHealth). The grading of studies was conducted using the PEDro scale. We identified 7184 citations, 25 met the inclusion criteria. Twenty-one studies scored a 6 or higher and four studies scored a 5 on the PEDro scale. All subjects had a Body Mass Index (BMI) of ≥25 kg/m2 and were mostly women. The results suggests that short-term (<6 months) weight loss interventions using activity trackers may be a better option than a standard weight loss program in middle age or older adults. Younger adults may not benefit from such technology.


Sarcomeric myosin heavy chain gene family: organization and pattern of expression.
The sarcomeric myosin heavy chains (MHCs), which exhibit different levels of ATPase activity, are encoded by a closely related multigene family from which seven members have been identified and characterized in the rat. The MHC genes appear to map to a single chromosome, and at least two of them, alpha- and beta-cardiac, are closely linked in the genome. Each of these genes is approximately 25 kilobases long, and their coding sequences are interrupted by 40 introns. Each MHC gene displays a pattern of expression that is tissue-specific and developmentally regulated, with more than one MHC gene expressed in each muscle and developmental stage. Moreover, with the exception of the extra-ocular muscle MHC gene that has a very specific pattern of expression, the other genes are all expressed in more than one tissue. The expression of all MHC genes can be modulated by thyroid hormone. Surprisingly, however, the same myosin heavy chain gene can be regulated by thyroid hormone in highly different modes, even in opposite directions, depending on the tissue in which it is expressed. Furthermore, the skeletal embryonic and neonatal myosin heavy chain genes, so far considered specific to these two developmental stages, can be re-induced by hypothyroidism in specific adult muscles.


Celecoxib is a substrate of CYP2D6: Impact on celecoxib metabolism in individuals with CYP2C9*3 variants.
Celecoxib was characterized as a substrate of human cytochrome P450 (CYP) 2D6 in vitro. In recombinant CYP2D6, celecoxib hydroxylation showed atypical substrate inhibition kinetics with apparent Km, Ki, and Vmax of 67.2 μM, 12.6 μM, and 1.33 μM/min, respectively. In human liver microsomes (HLMs), a concentration-dependent inhibition of celecoxib hydroxylation by quinidine was observed after CYP2C9 and CYP3A4 were inhibited. In individual HLMs with variable CYP2D6 activities, a significant correlation was observed between celecoxib hydroxylation and CYP2D6-selective dextromethorphan O-demethylation when CYP2C9 and CYP3A4 activities were suppressed (r = 0.97, P < 0.0001). Molecular modeling showed two predominant docking modes of celecoxib with CYP2D6, resulting in either a substrate or an inhibitor. A second allosteric binding antechamber, which stabilized the inhibition mode, was revealed. Modeling results were consistent with the observed substrate inhibition kinetics. Using HLMs from individual donors, the relative contribution of CYP2D6 to celecoxib metabolism was found to be highly variable and dependent on CYP2C9 genotypes, ranging from no contribution in extensive metabolizers with CYP2C9*1*1 genotype to approximately 30% in slow metabolizers with allelic variants CYP2C9*1*3 and CYP2C9*3*3. These results demonstrate that celecoxib may become a potential victim of CYP2D6-associated drug-drug interactions, particularly in individuals with reduced CYP2C9 activity.


The Effect of a Polyvalent Antivenom on the Serum Venom Antigen Levels of Naja sputatrix (Javan Spitting Cobra) Venom in Experimentally Envenomed Rabbits.
The treatment protocol of antivenom in snake envenomation remains largely empirical, partly due to the insufficient knowledge of the pharmacokinetics of snake venoms and the effects of antivenoms on the blood venom levels in victims. In this study, we investigated the effect of a polyvalent antivenom on the serum venom antigen levels of Naja sputatrix (Javan spitting cobra) venom in experimentally envenomed rabbits. Intravenous infusion of 4 ml of Neuro Polyvalent Snake Antivenom [NPAV, F(ab')2 ] at 1 hr after envenomation caused a sharp decline of the serum venom antigen levels, followed by transient resurgence an hour later. The venom antigen resurgence was unlikely to be due to the mismatch of pharmacokinetics between the F(ab')2 and venom antigens, as the terminal half-life and volume of distribution of the F(ab')2 in serum were comparable to that of venom antigens (p > 0.05). Infusion of an additional 2 ml of NPAV was able to prevent resurgence of the serum venom antigen level, resulting in a substantial decrease (67.1%) of the total amount of circulating venom antigens over time course of envenomation. Our results showed that the neutralization potency of NPAV determined by neutralization assay in mice may not be an adequate indicator of its capability to modulate venom kinetics in relation to its in vivo efficacy to neutralize venom toxicity. The findings also support the recommendation of giving high initial dose of NPAV in cobra envenomation, with repeated doses as clinically indicated in the presence of rebound antigenemia and symptom recurrence.


Acne and obesity: A nationwide study of 600,404 adolescents.
The association between body mass index (BMI) and acne is unclear. To determine the association between BMI and acne in youths. A nationwide, population-based, cross-sectional study was conducted in 2002-2015 by using medical data on 600,404 youths during compulsory military service. BMI was measured at age 17 years. Acne was diagnosed by dermatologists. Unadjusted and adjusted odds ratios (aORs) of acne in relation to BMI (stratified into 8 groups) were calculated, with the low-normal group (18.5≤ BMI ≤21.99 kg/m2) serving as the reference. The study included 299,163 males (49.9%) and 301,241 females (50.1%) with a mean age of 18.9 years (standard deviation, 0.6) and 18.7 years (standard deviation, 0.5), respectively, at recruitment. Acne was diagnosed in 55,842 males (18.7%) and 48,969 females (16.3%). The proportion of participants with acne decreased gradually from the underweight to the severely obese group (males, from 19.9% to 13.9%; females, from 16.9% to 11.3%). The findings on multivariable analysis were similar to the unadjusted analysis results, showing the lowest odds of acne in severely obese participants (aOR for males, 0.53; 95% confidence interval, 0.42-0.64; aOR for females, 0.5; 95% confidence interval, 0.37-0.62). The findings persisted in the sensitivity analyses. Information was lacking on potential confounders and acne severity. In youths, overweight and obesity are inversely associated with acne in a dose-dependent manner.


Crypt abscesses in the caeca of feral rabbits in a rabbit haemorrhagic disease endemic region of New Zealand.
To describe the pathology of crypt abscesses in the caeca of feral rabbits in the Manawatu region of New Zealand, and to examine the possible relationship between their prevalence and rabbit haemorrhagic disease (RHD) virus (RHDV) infection. During the course of a 3-year study of RHD, 173 wild rabbits (Oryctolagus cuniculus) were shot on three pastoral livestock farms in the Manawatu region of New Zealand. All rabbits were necropsied, and tissue samples of the caeca were examined histologically. The age of each animal was determined, and blood samples collected for the detection of RHDV antibodies. Logistic regression was used to model the odds of rabbits having crypt abscesses. At necropsy, 63/173 (36.4%) rabbits were found to have small circular black nodules on the mucosal surface of their appendix caecum and/or sacculus rotundus. Microscopically, these were identified as small crypt abscesses composed of dilated sacs at the base of the mucosa that were often lined by a thin layer of attenuated epithelial cells. They usually contained large amounts of concentrically-laminated mucopolysaccharide material that was sometimes pigmented, inflammatory debris, and were often the site of a moderate multifocal appendicitis. Although RHDV was active in the study area, no association was found between RHDV antibodies in serum and the presence of lesions. The lesions were more common in older individuals and those born in summer or autumn. This is the first report of crypt abscesses with inflammation and necrotic debris in the caeca of rabbits. No association between the occurrence of crypt abscesses and RHDV infection was identified. Wild rabbits born in a particular season were presumably exposed very early in life to conditions that caused the crypt abscesses to develop. Alternatively, association with season of birth may represent rabbits that were of similar age in a later stage of their lives, when they became exposed to the cause of the lesions, which remains unidentified.


The physiological and pathophysiological modulation of the endocrine function of the heart.
Under physiological conditions, the endocrine heart contributes to the maintenance of cardiovascular homeostasis through the polypeptide hormones ANF and BNP, which are members of the natriuretic peptide (NP) family. Given that NPs are of interest from the basic and clinical points of view, the genetic expression and secretion of ANF and BNP as well as the nature of the interaction of these hormones with their receptors has been the subject of extensive studies since the discovery of ANF in 1980. Following hemodynamic overload, increased secretion of NPs by the heart can be seen. This change may occur without an increase in gene expression as observed for atrial NPs following acute volume expansion, or it can occur with an increase in both ANF and BNP gene expression in atria only as seen in mineralocorticoid escape during which it is obvious that a critical decrease in hormone stores must be reached before transcriptional activation occurs. Chronic hemodynamic pressure or volume overload results in increased expression of NPs in atria and ventricles. Under these circumstances, the increased production of BNP by hypertrophic ventricles changes the normal plasma concentration ratio of ANF to BNP, a fact that has clinical diagnostic and prognostic implications. There are exceptions to this rule: chronic, severe L-NAME hypertension, which may occur without left ventricular hypertrophy, does not cause this effect and increased ventricular NP gene expression can occur in mineralocorticoid hypertension before detectable ventricular hypertrophy. Atrial and ventricular NP gene expression appears to be under different transcriptional control because pharmacological treatments such as chronic ACE inhibition or ET(A) receptor blockade can reverse the increased ventricular NP expression but has no detectable effect on atrial NP gene expression. This is not unlike the myosin heavy chain switch that is observed in certain pathologies, and can be pharmacologically reversed in a manner similar to NPs in the ventricles but it does not occur in atrial muscle. These observations made in vivo or using isolated adult atria often differ strikingly from results obtained using the mixed phenotype afforded by cardiocytes in culture, indicating that the kinds of questions addressed by each approach must be judiciously chosen. G-protein coupled receptor-mediated actions of neurohumors such as endothelin and phenylephrine are normally used to stimulate NP gene expression and release in different in vitro models. The main physiological stimulus for increased ANF release, atrial muscle stretch, also appears to rely on G-protein-coupled mechanisms. Alternative agonists and receptor types at play are suggested by the finding that circulating levels of BNP are selectively increased before and during overt cardiac allograft rejection episodes in human patients. The data suggest that enhanced BNP plasma levels could form a basis for a noninvasive test for cardiac allograft rejection. However, the molecular mechanism by which expression of NPs are regulated in the transplanted heart is not well understood. Conditioned medium from mixed lymphocyte reaction cultures, considered an in vitro model of transplantation immunity, induces specific upregulation of BNP as do individual pro-inflammatory cytokines. Findings such as these suggest that the study of NPs will continue to produce a wealth of information relevant to basic and clinical scientists.


Extreme power law in a driven many-particle system without threshold dynamics.
We study a one-dimensional system of spatially extended particles, which are attached to regularly spaced locations by means of elastic springs. The particles are assumed to be driven by Gaussian noise and to have dissipative, energy-conserving, or antidissipative (pinball-like) interactions, when the particle density exceeds a critical threshold. While each particle in separation shows a well-behaved behavior characterized by a Gaussian velocity distribution, the interaction of particles at high densities can cause an avalanchelike momentum and energy transfer, which can generate extreme (steep) power laws without a well-defined variance and mean value. Specifically, the velocity variance increases dramatically towards the free boundaries of the driven many-particle system. The model might also have some relevance for better understanding of crowd disasters. Our results suggest that these are most likely caused by passive momentum transfers, not by active pushing.


Inter-task transfer of meaningful, functional skills following a cognitive-based treatment: Results of three multiple baseline design experiments in adults with chronic stroke.
The transfer of skills learned in rehabilitation to new skills in the home has hitherto been notoriously difficult to achieve. The Cognitive Orientation to daily Occupational Performance (CO-OP) treatment approach has been associated with improved performance in people living with stroke, but the specific impact on transfer to untrained skills has not been investigated. The objective of the study was to investigate the capacity of CO-OP treatment to improve performance in both trained and untrained self-selected skills in adults living with stroke. A single case experiment with multiple baselines across skills was conducted, with two replications. The participants self-selected four skills; three were trained using CO-OP; the fourth was not. Using video recording, data points were collected at multiple baselines, during intervention, post-intervention, and at follow-up. The Performance Quality Rating Scale (PQRS) was used by an independent rater to score performances. The two-standard deviation band method was used to determine the significance of improvements. At follow-up, significant performance improvements were seen in all three single case experiments in all trained and untrained skills. A cognitive-based approach was associated with improved performance in trained and untrained skills in three adults with chronic stroke; further controlled research is warranted.


Making the Most of Mealtimes (M3): effect of eating occasions and other covariates on energy and protein intake among Canadian older adult residents in long-term care.
Food intake varies among long-term care (LTC) residents and, as a result, some residents are at risk for protein-energy malnutrition and its consequences, such as sarcopenia. The present study aimed to determine whether eating occasions, as well as other factors that may vary with eating occasions (e.g. family/volunteer presence), were associated with energy and protein intake at meals and snacks. The present study comprised a secondary analysis of the cross-sectional Making the Most of Mealtimes study, including 630 residents (median age 88.00 years, range 62-107 years; 197 males) from 32 Canadian LTC homes. An analysis of variance compared protein and energy intake at meals and snacks. Mixed repeated measures linear regression testing for meal and relevant covariates (e.g. family/volunteer presence) was also conducted. Energy and protein intake was significantly associated with eating occasions (F = 44.31, P < 0.001; F = 12.72, P < 0.001), with the greatest energy intake at breakfast, and the greatest protein intake at dinner. Regression analysis confirmed these findings when considering other factors. Covariates associated with higher intake included: being male (+79 kcal; +3.4 g protein), living on a dementia care unit (+39 kcal; +2.1 g protein) and family/volunteer presence at meals (+58 kcal; +2.5 g protein). Intake was lowest in the oldest age group (-59 kcal; -3.6 g protein) and for those sometimes requiring eating assistance (-36 kcal; -2.0 g protein). Energy and protein intake appears to be associated with eating occasions. Based on these exploratory findings, LTC homes may consider providing more protein-dense foods at breakfast. Protein and energy dense snacks could also be used more extensively to support intake.


Cardiopulmonary adaptation to exercise in coal miners.
Twenty-six coal miners, without associated functional chronic obstructive lung disease (COLD), assessed by normal airway resistance, were divided into three groups: (1) Group C, normal X-ray; (2) Group S1, micronodular silicosis; and (3) Group S2, complicated silicosis. All subjects were evaluated while at rest and during exercise. Significant lung volume reduction was observed in the S2 Group only. Blood gases, pulmonary pressure, and cardiac output were found to be within the normal range for all three groups when at rest. The pulmonary pressure and pulmonary vascular resistance were higher, however, for the S1 and S2 Groups when compared to the C Group. During exercise, pulmonary hypertension was observed in 50% of teh patients with complicated silicosis. When all data (N = 26) were included, the high values for pulmonary pressure and pulmonary vascular resistance correlated well with the loss in vital capacity (VC) and the decrease in forced expiratory volume in 1 sec (FEV 1.0). From the initial 26 patients, 19 were selected on the basis of their normal airway resistance and FEV 1.0/VC ratio. This selection did not alter the differences noted for the pulmonary pressure and total pulmonary vascular resistance, which previously existed between the groups, even though the correlations were not statistically significant. We conclude that silicosis without associated COLD leads to mineral hemodynamic impairment at rest and during exercise, and that airway resistance does not detect impairment of flow as effectively as FEV 1.0 reduction. The increased pulmonary vascular resistance observed, especially in complicated silicosis, may be best explained by the loss of lung parenchyma and possible impairment of small airways.


[Vaccination status in very and extremely preterm infants at the age of 2 years--a nationwide pilot analysis].
Preterm infants are at increased risk of suffering from vaccine preventable diseases. Therefore it is recommended to vaccinate them in time at the same chronological age as full term infants. Several reports have shown that vaccinations of very and extreme low birth weight infants are often delayed but till now there are no data for Germany. Our study analysed the vaccination rates and suffered complications of 318 preterm infants with birth weights under 1 500 g at the age of 2 years from all over the country copying their vaccination-record and asking the parents to answer a questionnaire. The preterm infants received the first 3 doses of the pentavalent or hexavalent vaccines consequently (1st dose: 100%, 2nd dose: 100%, 3rd dose: 97.5%), whereas the booster dose was accomplished to a lesser extent (89.0%) during their second year of life. The majority of the vaccinations were administered delayed. Moreover, the preterm infants received the first doses of the pneumococcal conjugate vaccine and the measles-mumps-rubella vaccine quite consequently, but the booster dose was again injected less frequent. According to their parents 17.8% of these preterm infants suffered from non-severe adverse reactions and none of them had an episode of apnoea following the immunisation. In conclusion preterm infants in Germany receive their basic immunisations consequently, but often too late. There is still the need to improve the frequency of the booster dose application especially in the second year of life and to prevent delays of vaccinations.


The spread of pathogens through trade in pig meat: overview and recent developments.
A number of animal diseases can be transmitted to pigs via meat if the animals are fed scraps of meat imported from infected countries. For this reason, garbage feeding of pigs is regulated in many countries. The major porcine diseases recognised as being significant for this transmission pathway are foot and mouth disease, African swine fever, classical swine fever and swine vesicular disease. The World Organisation for Animal Health Terrestrial Animal Health Code (the Terrestrial Code) offers risk management recommendations for meat from countries where these diseases are present. However, there is no Terrestrial Code chapter on porcine reproductive and respiratory syndrome (PRRS), a relatively new viral disease of pigs which, since its recognition in the 1990s, has become endemic in most pig-producing countries. This paper assesses the risk of spread of PRRS virus through trade in pig meat, and concludes that the likelihood of its transmission by this pathway is negligible.


Two paradigms of bistable plaid motion reveal independent mutual inhibition processes.
Perception is sometimes bistable, switching between two possible interpretations. Levelt developed several propositions to explain bistable perception in binocular rivalry, based on a model of competing neural populations connected through reciprocal inhibition. Here we test Levelt's laws with bistable plaid motion. Plaids are typically tristable, either a coherent pattern, transparent with one component in front, or transparent with the opposite depth order. In Experiment 1, we use a large angle between component directions to prevent plaid coherence, limiting the ambiguity to alternations of grating depth order. Similar to increasing contrast in binocular rivalry, increasing component speed led to higher switch rates (analogous to Levelt's fourth proposition). In Experiment 2, we used occlusion cues to prevent one depth order and limit bistability to one transparent depth order alternating with coherence. Increasing grating speed shortened coherent motion periods but left transparent periods largely unchanged (analogous to Levelt's second proposition). Switch dynamics showed no correlation between the experiments. These data suggest that plaid component speed acts like contrast in binocular rivalry to vary switch dynamics through a mutual inhibition model. The lack of correlation between both experiments suggests reciprocal inhibition mediates bistability between a variety of neural populations across the visual system.


Quercetagetin-Loaded Composite Nanoparticles Based on Zein and Hyaluronic Acid: Formation, Characterization, and Physicochemical Stability.
Zein and hyaluronic acid (HA) composite nanoparticles were self-assembly fabricated using antisolvent coprecipitation (ASCP) method to deliver quercetagetin (Que). FTIR, CD, and FS results revealed that electrostatic attraction, hydrogen bonding, and hydrophobic effect were the dominant driving forces among zein, Que, and HA. With the increasing of HA level, the morphological structure of zein-Que-HA complex was changed from nanoparticle (from 100:5:5 to 100:5:20) to microgel (from 100:5:25 to 100:5:30). The encapsulation efficiency of Que has significantly increased from 55.66% (zein-Que, 100:5) to 93.22% (zein-Que-HA, 100:5:20), and Que in the zein-Que-HA composite nanoparticles exhibited obviously enhanced photochemical, thermal, and physical stability. After 8 months of storage (4 °C), the retention rate of Que also up to 77.93%. These findings interpreted that zein-HA composite nanoparticle would be an efficient delivery system for encapsulating and protecting bioactive compounds.


The role of histidines 26 and 33 in the structural stabilization of cytochrome c.
Comparative studies of the importance of the two histidines of rat cytochrome c that are not ligands of the heme iron, for the stability of the protein, were carried out by site-directed mutagenesis. Histidine 26 was substituted by valine and the resulting effects on the stability of the Met-80-sulfur to heme iron bond to changes in pH and temperature, and of the global stability of the protein to unfolding in urea solutions, were measured. It is suggested that the loss of the hydrogen bond between the His-26 imidazole and the backbone amide of Asn-31 caused the observed decreases in local stability; and that, in addition, the elimination of the hydrogen bond between this imidazole and the carbonyl of Pro-44 resulted in an increase of the mobility of the lower loop (residues 41-47) on the right side of the protein and of its distance from the middle loop (residues 26-31), probably leading to greater hydration of the interior right side of the molecule. These changes resulted in a decrease in the global stability of the protein. Further mutation of Asn-52 to Ile led to a total recovery of the wild-type stability of the sulfur-iron bond, and a partial restoration of the global stability of the protein. Substitution of Phe for His-33 did not alter the sulfur-iron bond but caused a pronounced increase in the global stability of the protein. It is suggested that this effect results from hydrophobic interaction of the Phe-33 side chain with the lower loop on the right side of the protein. Such an interaction also explains the observation that the same mutation reversed the loss of global stability caused by substitution of Val to His-26, but did not restore the strength of the sulfur-iron bond that this mutation had brought about.


Cocaine babies: a result of multiple teratogenic influences.
The history of cocaine use is reviewed. Cocaine teratogenesis has only recently been studied, and initial human studies had serious methodological flaws. These flaws included ascertainment bias, publication bias (studies finding cocaine effects have been more likely to be presented or published), and overemphasis on the perinatal period. Comparison with alcohol teratogenesis shows that alcohol is a more potent teratogen, which, however, produces major and specific effects (fetal alcohol syndrome) in less than 10% of offspring with heavy alcohol exposure during pregnancy. Nonspecific minor congenital anomalies or fetal alcohol effects are seen in a larger number. Personal experience with two groups of children exposed to cocaine in utero is reviewed. Insurance patients gained weight, took vitamins, and generally, their children did well in spite of cocaine use. Indigent patients were usually unmarried and often "street people," probably used more cocaine, generally used other drugs as well, often did not gain weight during pregnancy, and were much more likely to have children with problems. Surveys show that most cocaine users also use alcohol, often simultaneously. Those who use both agents are more likely to have troubled backgrounds and antisocial behavior and to drop out of treatment programs than those who use only alcohol. Cocaethylene or ethylbenzoylecgonine is formed in the liver when cocaine and alcohol are simultaneously ingested. It is a potent stimulant and dopamine uptake blocker that is more toxic to myocardial cells than is cocaine. Good nutrition is now known to be very important in preventing congenital anomalies and fetal death. A multihit model of neurologic handicap, which stresses the importance of a good postnatal environment, is briefly outlined.(ABSTRACT TRUNCATED AT 250 WORDS)


New 19-acetoxyingol diterpenes from the latex of Euphorbia poisonii (Euphorbiaceae).
The poisonous latex of Euphorbia poisonii gave bioactive 3,12-diacetyl-8-nicotinyl-7-phenylacetyl 19-acetoxyingol (1) together with its less active congeners, 3,12-diacetyl-7-phenylacetyl 19-acetoxyingol (2) and 3-acetyl-7-phenylacetyl 19-acetoxyingol (3). The chemical structures of 1-3 were determined by spectroscopic methods including HRMS, DEPT, HETCOR, COSY, NOESY, HMQC and HMBC. The absolute configurations of the hydroxylated carbons in 2 and 3 were provisionally suggested by the Mosher ester method. Bioactivity-guided isolation, structure determination and cytotoxic activity of the new ingols are described.


Clinical evaluation of a single antibody RIA assay for alpha-fetoprotein.
Open neural tube defects have been associated with elevated levels of alpha-fetoprotein in maternal serum and amniotic fluid. In the present study, specimens were collected during 14 to 20 weeks of gestation in five laboratories. Dates were confirmed by ultrasound. Among 1,049 subjects included in total serum alpha-fetoprotein determinations, 25 infants were born with neural tube defects, one patient had intrauterine fetal demise, and 1,023 delivered normal infants. The false-negative rate for serum alpha-fetoprotein was 0.38%, and the false-positive rate was 0.29%. For the total 1,211 amniotic fluid specimens, 23 infants were born with neural tube defects. The false-negative rate for amniotic fluid alpha-fetoprotein was 0.25%. All were closed lesions. There were no false-positive values. This study reaffirms the value of screening for neural tube defects by means of serum alpha-fetoprotein RIA. It also negates the argument that serum screening would promote excessive amniocentesis.


Absorption spectroscopy of three-dimensional bacteriorhodopsin crystals at cryogenic temperatures: effects of altered hydration.
A comparative study of absorption spectroscopy at 100 K has been performed on three-dimensional crystals of bacteriorhodopsin extracted from a lipidic cubic phase and on native purple membrane. A modified microspectrophotometer has been designed which yields absorption data with a high signal-to-noise ratio and remarkable reproducibility. Excellent agreement of the absorption spectra of the three-dimensional crystals and the purple membrane is observed provided that a rigorous crystal-handling procedure is followed. This result supports the equivalence of the protein structure in both the cubic phase crystals and the native purple membrane. On the other hand, it is shown that dramatic deviations of the crystal spectrum can be induced by minor changes in the extraction method. Exposure to air at room temperature can lead within a short time to an irreversible dehydration manifested by a distinct species with an absorption maximum at 500 nm. Exposure of the crystals to a buffer with lower ionic strength than the crystallization solution produces a different spectral form with an absorption maximum at 477 nm, which was assigned to a distorted protein conformation induced by osmotic stress. The extreme sensitivity of these crystals to experimental conditions is relevant for X-ray structural studies, in particular as different experimental treatments are implemented to trap the intermediates of the protein's photocycle.


Determination of adhesive bond strength to dentine. A new method.
Specimens for the determination of adhesive bond strength to dentine were prepared using suitable surfaces of freshly extracted teeth from 15 patients who were having immediate dentures fitted. As soon as possible after extraction, shallow cavities were cut into the dentine to a depth of 1 mm using a high-speed round bur (diameter 4.2 mm) under water coolant. The cavities were restored using dentine bonding agents and single increments of light activated composite resin. The restored teeth were cut down to approximately 5 mm in diameter and 3 mm thick and were either placed in previously prepared sites in the buccal or occlusal surfaces of their respective dentures or in containers of tap water. Patients were instructed to remove their dentures only for cleaning with a soft nylon brush and toilet soap, while the laboratory specimens were stored at ambient temperature. After one week, the tensile force needed to dislodge each restoration from its cavity was determined using a universal testing machine. Previously reported laboratory methods for bond strength determination have usually employed a flat dentine surface. However, this study more closely resembled the clinical situation in that the smear layer was produced by a rotary cutting instrument, and the effects of polymerization shrinkage when curing the composite resin were simulated. Furthermore, it was easier to confine the bonding agent to the desired dentine surface.


[Brushing teeth: how to promote this habit in children].
To teach how to correctly brush teeth to elementary students in their own school is a method widely used by health educators. This article analyses the results of an educational project promoted by the Burela, Lugo mayor's office which instructed 58 six-year-old students in oral hygiene. After receiving instructions how to brush their teeth using a rotational technique, those students had problems with their right side half arches, lower dental arch in general, and the molar tongue faces.


Hypersensitivity to acid is associated with impaired esophageal mucosal integrity in patients with gastroesophageal reflux disease with and without esophagitis.
Increased esophageal sensitivity and impaired mucosal integrity have both been described in patients with gastroesophageal reflux disease, but the relationship between hypersensitivity and mucosal integrity is unclear. The aim of the present study was to investigate acid sensitivity in patients with erosive and nonerosive reflux disease and control subjects to determine the relation with functional esophageal mucosal integrity changes as well as to investigate cellular mechanisms of impaired mucosal integrity in these patients. In this prospective experimental study, 12 patients with nonerosive reflux disease, 12 patients with esophagitis grade A or B, and 11 healthy control subjects underwent an acid perfusion test and upper endoscopy. Mucosal integrity was measured during endoscopy by electrical tissue impedance spectroscopy and biopsy specimens were analyzed in Ussing chambers for transepithelial electrical resistance, transepithelial permeability and gene expression of tight junction proteins and filaggrin. Patients with nonerosive reflux disease and esophagitis were more sensitive to acid perfusion compared with control subjects, having a shorter time to perception of heartburn and higher perceived intensity of heartburn. In reflux patients, enhanced acid sensitivity was associated with impairment of in vivo and vitro esophageal mucosal integrity. Mucosal integrity was significantly impaired in patients with esophagitis, displaying higher transepithelial permeability and lower extracellular impedance. Although no significant differences in the expression of tight junction proteins were found in biopsies among patient groups, mucosal integrity parameters in reflux patients correlated negatively with the expression of filaggrin. In conclusion, sensitivity to acid is enhanced in patients with gastroesophageal reflux disease, irrespective of the presence of erosions, and is associated with impaired esophageal mucosal integrity. Mucosal integrity of the esophagus is associated with the expression of filaggrin.


The effect of major depression on sexual function in women.
Eleven hundred eighty-four depressed women were entered into five short-term (8 weeks) studies of gepirone-extended release (ER) vs. placebo for treatment of major depressive disorder (MDD) (134001, 134002, and 134017), or atypical depressive disorder (ADD) (134004 and 134006). The effect of depression on sexual function was examined prior to treatment. To determine the effect of depression on the prevalence of Diagnostic and Statistical Manual Fourth Edition (DSM-IV) sexual dysfunction diagnoses and the Derogatis Inventory of Sexual Function (DISF) total score and domain scores and to measure the effect of severity of depression. Hamilton Depression Rating Scale (HAMD-17), DSM-IV diagnoses, and DISF total and domain scores. DSM-IV diagnoses--hypoactive sexual desire disorder (HSDD), sexual aversion disorder (SAD), female arousal disorder (FAD), and female orgasmic disorder (FOD)--were made by a trained psychiatrist. The HAMD-17 measured antidepressant efficacy. The DISF or its self-report version measured sexual function. To access the effect of severity of depression, baseline HAMD-17 scores were stratified as mild (<18), moderate (19-22), severe (23-25), or extreme (26-33). All measures were taken at baseline. In this depressed female population, prevalence rates were HSDD 17.7%, SAD 3.4%, FAD 5.8%, and FOD 7.7%. These rates for females are within the reported normal (nondepressed) values. However, DISF scores are one or more standard deviations below population norms for total score. DISF domains are not equally affected: orgasm is most impaired, while sexual desire and sexual arousal are somewhat preserved. Higher HAMD scores result in lower DISF scores (greater sexual dysfunction). In women, depression affects DISF scores more than DSM-IV diagnoses for sexual dysfunction. With increasing severity of depression (increased HAMD scores), sexual dysfunction becomes greater (lower DISF scores). For equal HAMD scores, DISF scores for MDD and ADD are the same.


Anterior communicating artery aneurysms: an overview.
AComA aneurysms are most commonly found at the A1-A2 junction on the dominant side. The angle of the arteries at the bifurcation and the direction of blood flow are factors of hemodynamic stress in the apical region where these aneurysms often develop. They exist at the bifurcation of dominant A1, A2 and AComA and usually point in the direction away from the dominant A1. They are more prone to rupture and demonstrate the highest incidence of post-operative morbidity among anterior circulation aneurysms. Consideration of aneurysm morphology may be used to guide approaches in AComA aneurysms. Resection of the gyrus rectus in combination with a pterional approach was popularized by Yasargil and it became the standard for treatment or exposure of AComA aneurysms, although other skull base approaches are also widely used. Clip selection is of extreme importance and the preservation of blood flow to the perforators should be emphasized. Adequate dissection and exposure of the entire "H" complex prior to clipping is the key to a successful outcome. Separating the perforators from the neck or dome of the artery and preserving the parent vessel presents a substantial challenge to the surgeon when the aneurysm is behind the parent artery, making it difficult to achieve a good outcome.


Contextual cueing in naturalistic scenes: Global and local contexts.
In contextual cueing, the position of a target within a group of distractors is learned over repeated exposure to a display with reference to a few nearby items rather than to the global pattern created by the elements. The authors contrasted the role of global and local contexts for contextual cueing in naturalistic scenes. Experiment 1 showed that learned target positions transfer when local information is altered but not when global information is changed. Experiment 2 showed that scene-target covariation is learned more slowly when local, but not global, information is repeated across trials than when global but not local information is repeated. Thus, in naturalistic scenes, observers are biased to associate target locations with global contexts.


The macroecology of infectious diseases: a new perspective on global-scale drivers of pathogen distributions and impacts.
Identifying drivers of infectious disease patterns and impacts at the broadest scales of organisation is one of the most crucial challenges for modern science, yet answers to many fundamental questions remain elusive. These include what factors commonly facilitate transmission of pathogens to novel host species, what drives variation in immune investment among host species, and more generally what drives global patterns of parasite diversity and distribution? Here we consider how the perspectives and tools of macroecology, a field that investigates patterns and processes at broad spatial, temporal and taxonomic scales, are expanding scientific understanding of global infectious disease ecology. In particular, emerging approaches are providing new insights about scaling properties across all living taxa, and new strategies for mapping pathogen biodiversity and infection risk. Ultimately, macroecology is establishing a framework to more accurately predict global patterns of infectious disease distribution and emergence.


Dual-Signal Luminescent Detection of Dopamine by a Single Type of Lanthanide-Doped Nanoparticles.
Detection of dopamine, an important neurotransmitter, is vital for understanding its roles in mammals and disease diagnosis. However, commonly available methods for dopamine detection typically rely on a single signal readout, which can be susceptible to interference by internal or external factors. Here, we report a dual-signal detection of dopamine based on label-free luminescent NaGdF4:Tb nanoparticles. In the presence of dopamine, the NaGdF4:Tb nanoparticles exhibit luminescence quenching under the excitation of 272 nm, while they give enhanced luminescence under 297 nm excitation, realizing both turn off and turn on detection of dopamine. The nanoparticle-based dual-signal sensors exhibit high sensitivity, with a detection limit of ∼30 nM, and good selectivity, which offers the possibility to identify potential interferents in the samples. We further demonstrate that the dual-signal response results from different energy-transfer processes within the nanoparticles under the excitation of different light. The new strategy demonstrated here should pave the way for the development of multiresponse nanosensors based on lanthanide-doped luminescent nanomaterials.


Protection against ischemic brain damage by GDNF affecting cell survival and death signals.
Neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF) on cell survival and death signals were investigated after 90 min of transient middle cerebral artery occlusion (MCAO) in rats. Immunoreactivities of phosphorylated Akt (p-Akt), cleaved caspase-9 (c-cas9), and -3 (c-cas3) increased after the reperfusion in the penumbra in vehicle group with peaks at 3 h, 8 h, and 1 day, respectively. Topical application of GDNF (6.8 micrograms/9 microliters) on brain surface potentiated and prolonged p-Akt activation, but suppressed activation of the caspases, and reduced the number of terminal deoxynucleotidyl transferase-mediated dUDP-biotin in situ nick labeling (TUNEL) positive cells. These results suggest that GDNF plays a protective role against ischemic injury by controlling the balance between Akt pathway and caspase cascades.


Neuropeptide-Y innervation of estrogen-induced progesterone receptor-containing dopamine cells in the monkey hypothalamus: a triple labeling light and electron microscopic study.
Light and electron microscopic triple immunostaining was performed on coronal vibratome sections prepared from the hypothalamus of ovariectomized (OVX) and OVX plus estrogen-treated African green monkeys (Cercopithecus aethiops). Immunoreactivity for progesterone receptors (PRs) and neuropeptide-Y (NPY) was visualized by a dark blue to black nickel diaminobenzidine reaction, while the tyrosine hydroxylase-containing perikarya were labeled with a light brown diaminobenzidine reaction. In the OVX plus estrogen-treated material, 30% of the tyrosine hydroxylase-immunoreactive neurons contained PR-immunopositive nuclei. The majority of these cells were found in the central portion of the periventricular area, and a few could be observed in the anterior hypothalamus and the arcuate and dorsomedial hypothalamic nuclei. These tyrosine hydroxylase-immunoreactive PR-containing cells were surrounded with NPY-immunoreactive axon terminals. A correlated electron microscopic analysis of the same sections revealed synaptic contacts between these NPY-immunoreactive boutons and the PR-containing tyrosine hydroxylase-immunoreactive neurons. In contrast, in the OVX animals, no PR-containing tyrosine hydroxylase-immunoreactive neurons could be detected. In these monkeys, the frequency of synaptic contacts between the NPY-immunoreactive axon terminals and tyrosine hydroxylase-immunopositive cells was similar to that in the OVX plus estrogen-treated monkeys. These observations indicate that in a population of hypothalamic dopamine cells, the presence of nuclear PRs is estrogen dependent, show that these cells are innervated by NPY axons, and suggest that these estrogen-induced PR-containing dopamine neurons are involved in mediation of the effect of NPY on hypophyseal hormone secretion, including ovarian steroid hormone-dependent LH and PRL release.


Metallothionein-I/II null mice are sensitive to chronic oral cadmium-induced nephrotoxicity.
Chronic exposure to cadmium (Cd) via food and drinking water is a major human health concern. We have previously shown that metallothionein (MT), a metal-binding protein, plays an important role in protecting against Cd toxicity produced by repeated sc injections. However, it is unclear whether MT protects against Cd-induced nephrotoxicity following chronic oral exposure, a route with obvious human relevance. To clarify this issue, MT-I/II knockout (MT-null) and background-matched wild-type (WT) mice were allowed free access to drinking water containing CdCl(2) (30, 100, and 300 ppm Cd), or feed containing CdCl(2) (100 ppm Cd) for 6 months, and the resultant nephrotoxicity was examined. Chronic oral Cd exposure produced a dose-dependent accumulation of Cd in liver and kidney of WT mice, reaching levels up to 50 microg Cd/g tissue. Immunohistological localization of renal MT indicated that chronic oral Cd exposure in WT mice greatly increased MT in the proximal tubules and the medulla, with cellular localization in both the cytoplasm and nuclei. As expected, no MT was detected in kidneys of MT-null mice. After 6 months of Cd exposure, tissue Cd concentrations in MT-null mice were only about one-fifth of that in WT mice. Even though the renal Cd concentrations were much lower in the MT-null mice, they were more sensitive than WT mice to Cd-induced renal injury, as evidenced by more severe nephropathic lesions, increased urinary excretion of gamma-glutamyl-transferase and glucose, and elevated blood urea nitrogen. Six months of Cd exposure to MT-null animals resulted in greater increases in renal caspase-3 activity, an indicator of apoptosis, than to WT mice. In conclusion, this study demonstrates that lack of MT renders MT-null mice vulnerable to Cd-induced nephrotoxicity after chronic oral exposure, the primary route of human Cd exposure.


Proteomic analysis for the early detection and rational treatment of cancer--realistic hope?
Proteomics is an emerging field in medical science focused on the library of proteins specific to a given biosystem, the proteome, and understanding relationships therein. This field incorporates technologies that can be applied to serum and tissue in order to extract important biological information to aid clinicians and scientists in understanding the dynamic biology of their system of interest, such as a patient with cancer. These tools include laser capture microdissection, tissue lysate arrays and mass spectrometry approaches. These new technologies are more potent coupled with advanced bioinformatics analysis. They are used to characterize the content of, and changes in, the proteome induced by physiological changes, benign and pathologic. The application of these tools has assisted in the discovery of new biomarkers and may lead to new diagnostic tests and improvements in therapeutics. These tools additionally can provide a molecular characterization of cancers, which may allow for individualized molecular therapy. Understanding the basic concepts and tools used will illustrate how best to apply these technologies for patient benefit for the early detection of cancer and improved patient care.


Significant substituent effect on the anomerization of pyranosides: mechanism of anomerization and synthesis of a 1,2-cis glucosamine oligomer from the 1,2-trans anomer.
Aminoglycosides containing a 2,3-trans carbamate group easily undergo anomerization from the 1,2-trans glycoside to the 1,2-cis isomer under mild acidic conditions. The N-substituent of the carbamate has a significant effect on the anomerization reaction; in particular, an N-acetyl group facilitated rapid and complete α-anomerization. The differences in reactivity due to the various N-substituents were supported by the results of DFT calculations; the orientation of the acetyl carbonyl group close to the anomeric position was found to contribute significantly to the directing of the anomerization reaction. By exploiting this reaction, oligoaminoglycosides with multiple 1,2-cis glycosidic bonds were generated from 1,2-trans glycosides in a one-step process.


Effect of long-term piceatannol treatment on eNOS levels in cultured endothelial cells.
Piceatannol (3, 3', 4, 5'-tetrahydroxy-trans-stilbene) is a naturally occurring phytochemical found in passion fruit (Passiflora edulis) seeds. Previously, we demonstrated that piceatannol has acute vasorelaxant effects in rat thoracic aorta. It was suggested that endothelial NO synthase (eNOS) might be involved in piceatannol-induced acute vasorelaxation. Here, we investigated the expression of eNOS in EA.hy926 human umbilical vein cells after long-term treatment with piceatannol, and compared this effect with that of resveratrol, an analog of piceatannol. Long-term treatment with piceatannol up-regulated eNOS mRNA expression and increased eNOS protein expression in a dose-dependent manner. Moreover, piceatannol increased the levels of phosphorylated eNOS. Treatment with resveratrol also increased eNOS expression, but to a lesser degree than piceatannol. These findings indicate that piceatannol may improve vascular function by up-regulating eNOS expression.


Detection of changes in global genome methylation using the cytosine-extension assay.
Methylation is a reversible covalent chemical modification of DNA intended to regulate gene expression, genome stability, and chromatin structure. Although there are various methods of methylation analysis, most of them are either laborious or expensive, or both. Here, we describe a quick, inexpensive method for analysis of global genome methylation using a cytosine extension assay. The assay can be used for analysis of the total level of CpG, CNpG, and asymmetrical methylation in a given cell culture or in a plant tissue sample.


XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity.
XPA, a DNA binding protein in the nucleotide excision repair (NER) pathway, modulates damage recognition. Recently, a common single-nucleotide polymorphism (A --> G) of unknown function was identified in the 5' non-coding region of the XPA gene. Because a deficiency in NER is associated with an increased risk of lung cancer, we evaluated the role of this polymorphism in 695 lung cancer case patients and 695 age-, sex-, ethnicity- and smoking-matched control subjects. We also studied the effect of this polymorphism on NER capacity in a subset sample for whom the host cell reactivation data were available. The presence of one or two copies of the G allele was associated with a reduced lung cancer risk for Caucasians [adjusted odds ratio (ORadj) = 0.69 [95% confidence interval (CI) = 0.53-0.90]], Mexican-Americans [ORadj = 0.32 (95% CI = 0.12-0.83)] and African-Americans [ORadj = 0.45 (95% CI = 0.16-1.22)]. In Caucasians, ever smokers with one or more copies of the G allele were observed to have a significantly reduced risk of lung cancer. Control subjects with one or two copies of the G allele demonstrated more efficient DRC than did those with the homozygous A allele. Our data suggest that the XPA 5' non-coding region polymorphism modulates NER capacity and is associated with decreased lung cancer risk, especially in the presence of exposure to tobacco carcinogens.


[Arterial switch: aortocoronary bypass with interposition of polytetrafluoroethylene (Gore-tex) vascular graft].
We report a case of an infant with transposition of the great arteries accompanied by an unusual coronary artery pattern, in whom an expanded polytetrafluorethylene (Gore-tex) graft to the right coronary artery was used during surgical correction (switch arterial), with a postsurgical follow-up time of 8 months.


lnterleukin-8 gene polymorphism and susceptibility to gastric cancer in a Brazilian population.
Studies have demonstrated that some polymorphisms in different interleukin genes may increase the risk of cancer. The aim of this study was to investigate the association between the IL-8 (rs4073) -251A/T gene polymorphism and the risk of gastric cancer (GC). A case-control study was conducted on patients with noncardia gastric cancer. DNA was extracted from leukocytes and the IL-8 (rs4073) -251A/T polymorphism was analyzed by PCR-RFLP. Infection with Helicobacter pylori was investigated in the serum by ELISA. The sample consisted of 104 patients with GC and 196 controls. Cigarette smoking (P=0.007) and high fat intake (P=0.01) were more frequent in patients with GC. The proportion of patients infected with H. pylori was similar in the two groups (P=0.101). The frequency of the genotype A/T was higher in the cancer group (P=0.008). An increased risk of GC was found in subjects carrying the genotype A/T (OR=2.50, CI: 1.27-4.90), subjects with high fat intake (OR=1.92, CI: 1.17-3.15), and smokers (OR=2.00, CI: 1.203.31). Subjects with the heterozygous A/T genotype, high fat intake and smokers or ex-smokers presented an increased risk of GC. Individuals with A/A genotype may have protective effect for GC.


Metabolic risk factors in drug-naive patients with first-episode psychosis.
Metabolic risk factors, such as obesity, as well as abnormalities in glucose and lipid metabolism, have been shown to have an increased prevalence in patients with schizophrenia, especially in those treated with antipsychotic medication. However, studies looking at these abnormalities in drug-naive patients have been few in number and have yielded mixed results. The aim of our study was to look at the prevalence of some of the cardiovascular risk factors, such as obesity and lipid and glucose abnormalities, in drug-naive patients with first-episode psychosis compared to healthy controls matched for age, gender, and ethnicity. One hundred sixty patients aged between 18 and 40 years who presented to the Early Psychosis Intervention Programme in Singapore with a diagnosis of first-episode psychosis according to the Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition were assessed for their body mass index (BMI) and plasma levels of fasting glucose and lipids. The results of this assessment were compared to similar data from 200 controls matched for age, gender, and ethnicity, collected as part of an annual workplace health screening. The study was conducted from June 2002 to March 2005. There were significant differences in the mean baseline weight, BMI, and plasma levels of total and LDL cholesterol; all of these values were significantly higher in the controls compared to patients (p < .005 for all). Controls were significantly more likely to have high BMI (>or= 23 kg/m(2)) and high LDL cholesterol level (> 3.4 mmol/L) as compared to patients (p < .005 and p = .01, respectively). However, patients compared to controls were significantly more likely to have diabetes (p = .007). The link between diabetes and psychotic illness previously reported in relatives of patients with schizophrenia and in medication-naive patients implies a possible genetic link between schizophrenia and abnormal glucose metabolism. However, the finding of low prevalence of obesity and dyslipidemia at the onset of illness suggests that the increased frequency of these abnormalities in patients is an effect of their antipsychotic medication.


Understanding protein evolution: from protein physics to Darwinian selection.
Efforts in whole-genome sequencing and structural proteomics start to provide a global view of the protein universe, the set of existing protein structures and sequences. However, approaches based on the selection of individual sequences have not been entirely successful at the quantitative description of the distribution of structures and sequences in the protein universe because evolutionary pressure acts on the entire organism, rather than on a particular molecule. In parallel to this line of study, studies in population genetics and phenomenological molecular evolution established a mathematical framework to describe the changes in genome sequences in populations of organisms over time. Here, we review both microscopic (physics-based) and macroscopic (organism-level) models of protein-sequence evolution and demonstrate that bridging the two scales provides the most complete description of the protein universe starting from clearly defined, testable, and physiologically relevant assumptions.


Adoptive T cell therapy: An overview of obstacles and opportunities.
The therapeutic potential of adoptive cell therapy (ACT) in cancer patients was first acknowledged 3 decades ago, but it was an esoteric approach at the time. In recent years, technological advancements have transformed ACT into a viable therapeutic option that can be curative in some patients. In fact, current ACT response rates are 80% to 90% for hematological malignancies and 30% for metastatic melanoma refractory to multiple lines of therapy. Although these results are encouraging, there is still much to be done to fulfill ACT's potential, specifically with regard to improving clinical efficacy, expanding clinical indications, reducing toxicity, and increasing production and cost-effectiveness. This review addresses the current major obstacles to ACT and presents potential solutions. Cancer 2017;123:2154-62. © 2017 American Cancer Society.


Improved image contrast of calcifications in breast tissue specimens using diffraction enhanced imaging.
The contrast of calcifications in images of breast tissue specimens using a synchrotron-based diffraction enhanced imaging (DEI) apparatus has been measured and is compared to the contrast in images acquired using a conventional synchrotron-based radiographic imaging modality. DEI is an imaging modality which derives image contrast from x-ray absorption, refraction and small-angle scatter-rejection (extinction), unlike conventional radiographic techniques, which can only derive contrast from absorption. DEI is accomplished by inserting an analyser crystal in the beam path between the sample and the detector. Two of the three breast tissue specimens contained calcifications associated with cancer, while a third contained benign calcifications. Results of the image analysis indicate that the DEI contrast of images taken with the analyser crystal tuned to the peak of its rocking curve, was as much as 19 times that of the conventional radiograph, with an average of 5.5 for all calcifications. This improved image contrast for even near-pixel-size calcifications suggests potential utility for DEI in breast imaging.


[A case of xanthogranuloma of the urinary bladder following herniorrhaphy].
We report a case of xanthogranuloma of the bladder following herniorrhaphy. The patient complained of urinary frequency, residual feeling, and presented with a solid mass located on the dome of the bladder. He had undergone previous inguinal herniorrhaphy. Transurethral biopsy revealed an inflammatory change. Partial cystectomy was carried out for en bloc removal of the tumor. The histological diagnosis was xanthogranuloma of the bladder. Postoperatively, the symptoms disappeared. This is the sixth case report of xanthogranuloma of the urinary bladder and the first case following herniorrhaphy in the Japanese literature.


Drinking style of parents of alcoholic and control probands.
One aspect of the familial component of alcoholism is the use of alcohol among the parents of affected individuals. Both the individual and concordant drinking styles of the parents of 291 inpatient alcoholic probands and 71 non-alcoholic control subjects were measured using family history methods. Social drinking was almost twice as prevalent among fathers of controls compared to fathers of alcoholics. Problem drinking was more than twice as prevalent among the fathers of alcoholics compared to fathers of controls. The abstinence rate for fathers of both groups was similar. Mothers' drinking styles were similar to the fathers' pattern for both groups. Concordance of drinking style in the parental pair was examined. Similarity in drinking style for the parents of control probands was greatest for social drinking. For parents of alcoholic probands high concordance was also found by problem drinking. Overall a great similarity in drinking style was found for the parents of control probands compared to the parents of alcoholic probands.


Dementia, pain, depression, behavioral disturbances, and ADLs: toward a comprehensive conceptualization of quality of life in long-term care.
Quality of life in long-term care settings is a multidimensional construct that includes functional, cognitive, behavioral, and psychological variables. Quality of life variables have been found to be related to one another, but directional influences have not been tested. The purpose of this study was to develop and compare two competing path models composed of quality of life variables, including dementia, pain, behavioral disturbances, and ADLs. Path analytic results revealed that cognitive, emotional, and behavioral variables interact with one another to predict patients' activities of daily living. Pain levels did not influence activities of daily living directly, but rather influenced behavioral disturbances and depression, which in turn influenced activities of daily living. These preliminary findings suggest that in order to assist long-term care residents in improving their activities of daily living, decreasing pain is likely to yield the greatest overall improvements. Future research on the relationships between quality of life variables is recommended to further develop multidimensional treatment models for healthcare providers in long-term care.


Resveratrol activation of AMPK-dependent pathways is neuroprotective in human neural stem cells against amyloid-beta-induced inflammation and oxidative stress.
Alzheimer's disease (AD) is a neurodegenerative disorder with progressive memory loss resulting in dementia. Amyloid-beta (Aβ) peptides play a critical role in the pathogenesis of this disease, and are thought to promote inflammation and oxidative stress leading to neurodegeneration in the neocortex and hippocampus of the AD brains. AMP-activated protein kinase (AMPK) is a master regulator of cellular energy homeostasis, and cell survival in response to inflammation and oxidative stress. However, the neuroprotective mechanisms by which AMPK achieves these beneficial effects in human neural stem cells (hNSCs) exposed to Aβ is still not well understood. Resveratrol is a potent activator of AMPK suggesting it may have therapeutic potential against AD. Therefore, we will test the hypothesis that the AMPK activator resveratrol protects against Aβ mediated neuronal impairment (inflammation and oxidative stress) in hNSCs. Here, Aβ-treated hNSCs had significantly decreased cell viability that correlated with increased TNF-α and IL-1β inflammatory cytokine expression. Co-treatment with resveratrol significantly abrogated the Aβ-mediated effects in hNSCs, and was effectively blocked by the addition of the AMPK-specific antagonist (Compound C). These results suggest the neuroprotective effects of resveratrol are mediated by an AMPK-dependent pathway. In addition, resveratrol rescued the transcript expression levels of inhibitory kappa B kinase (IKK) in Aβ-treated hNSCs. NF-κB is a transcription factor with a key role in the expression of a variety of genes involved in inflammatory responses. Resveratrol prevented the Aβ-mediated increases in NF-κB mRNA and protein levels, and its nuclear translocation in hNSCs. Co-treatment with resveratrol also significantly restored iNOS and COX-2 levels in Aβ-treated hNSCs. Furthermore, hNSCs co-treated with resveratrol were significantly rescued from Aβ-induced oxidative stress, which correlated with reversal of the Aβ-induced mRNA decrease in oxidative defense genes (SOD-1, NRF2, Gpx1, Catalase, GSH and HO-1). Taken together, these novel findings show that activation of AMPK-dependent signaling by resveratrol rescues Aβ-mediated neurotoxicity in hNSCs, and provides evidence supporting a neuroprotective role for AMPK activating drugs in Aβ-related diseases such as AD.


The effect of cisapride in maintaining symptomatic remission in patients with gastro-oesophageal reflux disease.
Successful treatment of gastro-oesophageal reflux disease (GORD) has traditionally been assessed as healing of reflux oesophagitis, which may not be relevant in patients with moderate disease. In these patients symptom relief and patient satisfaction with therapy are of fundamental importance. Cisapride has well-documented prokinetic effects and may be well suited for long-term therapy of GORD, but its effectiveness in purely symptomatic treatment is unknown. We therefore compared two dosage regimens of cisapride with placebo over a period of 6 months in patients with evidence of gastrooesophageal reflux, initially treated with antisecretory medication, with regard to maintaining symptom relief and satisfaction with treatment. Five hundred and thirty-five patients with reflux oesophagitis grade 1 (n = 293) or 2 (n = 124) or with no reflux oesophagitis but pathologic 24-h pH-metry (n = 118) achieved satisfactory symptom relief with an H2-receptor antagonist or proton pump inhibitor within 4-8 weeks. In a double-blind randomized, parallel-group study, they were then treated with cisapride, 20 mg at night or 20 mg twice daily, or placebo and followed up for a maximum period of 6 months. Relapse was defined as dissatisfaction with therapy or an average consumption of more than two antacid tablets a day. Median time to relapse was 63 days for cisapride, 20 mg twice daily; 59 days for cisapride, 20 mg at night; and 49 days for placebo. Time to relapse was not significantly different (P = 0.09). Presence and grade of oesophagitis at base line, type of therapy before randomization, and pattern of non-reflux symptoms at base line did not influence these findings significantly. The study indicates that cisapride is of limited value in maintenance therapy of GORD in patients in whom symptom relief has been accomplished with potent antisecretory medication. This 'step-down' approach to therapy seems disadvantageous in the long-term therapy of GORD.


Photochromism and molecular logic gate operation of a water-compatible bis-glycosyl diarylethene.
We report the synthesis of a water-compatible bis-glycosyl diarylethene using click chemistry that undergoes photochromism and functions as a molecular logic gate.


Supplemental Nutrition Assistance Program Data: Why Disclosure Is Needed.
The Supplemental Nutrition Assistance Program (SNAP) provides funding to low-income households to purchase food at participating stores. The goals of the program include reducing hunger, improving nutrition, and strengthening the US food system. These are interrelated, as food access and choice depend on availability.SNAP generates data that could be useful for program evaluation and evidence-based policymaking to reach public health goals. However, the US Department of Agriculture (USDA) does not collect or disclose all SNAP-related data. In particular, the USDA does not systematically collect food expenditure data, and although it does collect transaction (sales) and redemption data (the amount retailers are reimbursed through SNAP), it does not release these data at the store level.In 2018, Congress quietly changed the law to prohibit the USDA from disclosing store-level transaction and redemption data, and in 2019, the US Supreme Court blocked disclosure of these data. These federal proceedings can inform the outcome of additional efforts to disclose SNAP-related data, as well as future research and policy evaluation to support improved public health outcomes for SNAP beneficiaries.