RELATION OF PROTEIN SYNTHESIS TO THE DIVISION CYCLE IN MAMMALIAN CELL CULTURES.
Protein synthesis in suspension cultures of human cells in logarithmic growth was inhibited with puromycin or chloramphenicol, and the growth rate and mitotic index were measured as a function of time. The mitotic index remained constant for about 1 hour after addition of inhibitor; this indicates that any protein synthesis necessary for mitosis is completed before the beginning of prophase. For rates of protein synthesis equal to or greater than 0.3 that of untreated cells, the index decreased over a 5- to-7-hour period and then remained constant. The final value of the index relative to that of the uninhibited control was approximately equal to the relative rate of protein synthesis. The period from the end of DNA synthesis to mitosis (G(2)) was increased by partial inhibition of protein synthesis. A mathematical model of the inhibition process has been formulated which predicts the shape of the mitotic index curves and the increase in the G(2) period. An interpretation of the model is that the rate-limiting step is the synthesis of an enzyme which catalyzes the formation of a compound necessary to initiate mitosis.


Entry of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into the rat brain.
We studied blood-to-brain entry of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridinium (MPP+) and butanol in anesthetized rats using the indicator-fractionation method with right atrial bolus injection. Minimal amounts of MPP+, which has low octanol/water partition coefficient, crossed the blood-brain barrier. MPTP and butanol, both of which have high octanol/water partition coefficients, were almost completely extracted by all regions of the brain on the first pass. The main difference between the MPTP and butanol tracers is that butanol rapidly left the brain with an exponential rate constant of 1.24 min-1, whereas MPTP was avidly retained by the brain with a washout rate constant of 0.10 min-1 (mean values for the four brain regions that we studied). Early retention of MPTP by the brain was not due to its rapid metabolism by monoamine oxidase because pargyline pretreatment did not affect this rate constant. However, 30 min after [3H]MPTP injection, brain retention of the 3H tracer was reduced significantly by pargyline treatment, and the ratio of brain MPTP/MPP+ was increased markedly.


[Short-term outcomes of laparoscopic-assisted procedures for chronic complications of diverticular disease].
To estimate efficacy of laparoscopic-assisted procedures for chronic complications of diverticular disease (DD). It was made a prospective comparative study within 2007-2015. Inclusion criteria were verified chronic DD (>6 weeks after the first attack) and bowel resection followed by primary anastomosis. contraindications for pneumoperitoneum, BMI ≥35 kg/m2, infiltrate dimension >10 cm, preoperatively non-excluded neoplasm. 233 patients with chronic DD underwent elective surgery, 136 (58.4%) of them were included in the study. There were 80 (58.8%) females aged 57.2±6.2 (24-83) years. Main group consisted of 75 patients after laparoscopic-assisted procedures, 61 were in control group (open ones). Both groups were homogeneous in age, gender, BMI, type of chronic complications, extent of inflammation, extent of bowel resection, surgery time (211.1 vs 206.3 min; p=0.16), incidence of preventive stoma (12.9 vs 19.7%; p=0.32) and complications rate (10.7 vs 14.7%; p=0.47). Maximal time of surgery was noted in case of chronic abdominal mass with statistically significance for main group (240.0±12.2 min vs 207.6±13.7 min; р=0.01). Conversion rate was 12.0% in main group. Main group showed significant higher rate of stapler anastomoses (66.7 vs 22.9%; р<0.0001), less intraoperative blood loss (100 ml vs 350 ml; р=0.001). Early postoperative period was significantly shorter in main group (9.5±0.4 days vs 12.9±1.2 days, р=0.02). Laparoscopic-assisted procedures for diverticular disease are associated with more favorable early postoperative period with the same complication rate. Technical complexity and operative time depend on the extent of pelvic inflammatory changes.


Extraction environment enhancement: critical evaluation of early socket healing in long-term barrier-protected extraction sockets.
Resorption and remodeling of the alveolar bone occurs after periodontal disease, trauma, or tooth extraction. Loss of the functional apparatus can have a deleterious effect on the ability to place endosseous root-form implants into prosthetically ideal locations. As a result, there has been a trend toward socket preservation at the time of extraction. However, there has been limited investigation with histologic verification of results on types of materials used to preserve or augment extraction sockets. Minimizing bone loss after extractions enables an implant to be placed in an ideal orientation surrounded by bone, thereby increasing the longevity of the implant and associated prosthesis. The case reports presented detail clinical and histological results during the 3 to 6 months after a bone maintenance procedure that used a nonexpanded polytetrafluoroethylene barrier placed over an extraction socket with no graft material at the time of tooth extraction.


Mycophenolate mofetil as a treatment for presumed idiopathic chronic hepatitis in dogs: Six cases (2010-2022).
The objectives of this study were to describe the clinical findings, treatment and outcomes of six dogs with presumed idiopathic chronic hepatitis treated with mycophenolate mofetil (MMF). Medical records were retrospectively searched to identify dogs in which idiopathic chronic hepatitis was diagnosed on histopathology between January 2010 and June 2022 that were treated with MMF for at least two weeks with >2 follow-up examinations. Data recorded from each dog included signalment, clinical signs, diagnostic test results and treatment. Six dogs were treated with MMF at a median initial dosage of 9.6 mg/kg PO q 12 h. Reported adverse effects from MMF included decreased appetite, vomiting and diarrhoea. In all six dogs, MMF was used successfully long term for the treatment of idiopathic chronic hepatitis as determined by 46% or greater improvement of alanine aminotransferase (ALT) between 4 and 18 weeks of starting MMF. Three dogs were also temporarily treated for 4-6 months on a tapering dose of prednisone. In two dogs, ALT remained within the reference interval, and in one dog, it was very mildly elevated when on MMF alone. In all six dogs, owners reported that the medication was well tolerated. To the authors' knowledge, this is the first report describing the use of MMF with and without a tapering dose of prednisone for the treatment of idiopathic chronic hepatitis in six dogs. Based on the outcomes of the dogs in this report, MMF can be effective for the long-term treatment of idiopathic chronic hepatitis as measured by reduction in ALT and improvement of clinical signs.


Expression of CENPE and its Prognostic Role in Non-small Cell Lung Cancer.
Non-small cell lung cancer (NSCLC) is one of the most important causes of death worldwide. Most patients are diagnosed in the advanced stage and have a poor prognosis. This study was to investigate the expression and significance of CENPE in NSCLC. Collecting information about CENPE in the Oncoming database, and perform a further analysis of the data in the current database to conduct a meta-analysis for its functional role in NSCLC. Patient life cycle analysis using Kaplan-Meier Plotter and GEPIA databases are used to perform patient survival analysis. A total of 12 studies involved the expression of CENPE in NSCLC cancer tissues and normal tissues, including 1195 samples. CENPE was highly expressed in NSCLC cell carcinoma compared with the control group (P < 0.05). Moreover, the expression of CENPE was correlated with the overall survival rate of CENPE. The overall survival rate of patients with high expression of CENPE was poor, and the prognosis of patients with low expression of CENPE was better (P<0.05). We propose high expression of CENPE in NSLCL tissue is related to the prognosis of NSCLC, which may provide important basis for the development of tumor drugs.


The emotion word fluency test as an embedded performance validity indicator - Alone and in a multivariate validity composite.
This project was designed to cross-validate existing performance validity cutoffs embedded within measures of verbal fluency (FAS and animals) and develop new ones for the Emotion Word Fluency Test (EWFT), a novel measure of category fluency. The classification accuracy of the verbal fluency tests was examined in two samples (70 cognitively healthy university students and 52 clinical patients) against psychometrically defined criterion measures. A demographically adjusted T-score of ≤31 on the FAS was specific (.88-.97) to noncredible responding in both samples. Animals T ≤ 29 achieved high specificity (.90-.93) among students at .27-.38 sensitivity. A more conservative cutoff (T ≤ 27) was needed in the patient sample for a similar combination of sensitivity (.24-.45) and specificity (.87-.93). An EWFT raw score ≤5 was highly specific (.94-.97) but insensitive (.10-.18) to invalid performance. Failing multiple cutoffs improved specificity (.90-1.00) at variable sensitivity (.19-.45). Results help resolve the inconsistency in previous reports, and confirm the overall utility of existing verbal fluency tests as embedded validity indicators. Multivariate models of performance validity assessment are superior to single indicators. The clinical utility and limitations of the EWFT as a novel measure are discussed.


Prevalence of comorbid substance use disorders with anxiety disorders or post-traumatic stress disorder in people seeking treatment for substance abuse: a systematic review protocol.
This systematic review will aim to assess evidence of the prevalence of comorbid substance use disorders with anxiety disorders or post-traumatic stress disorder in people seeking treatment for substance use. Research shows that anxiety disorders and post-traumatic stress disorder are highly prevalent in people with substance use disorders and can worsen the treatment outcomes, increasing the risk of relapse and poor adherence. However, evidence from systematic reviews on the prevalence of these comorbidities in substance use treatment settings is limited. Participants will be people seeking treatment for substance use. Studies will be included if they have investigated the prevalence of the comorbid substance use disorders with anxiety disorders or post-traumatic stress disorder in treatment settings. Primary studies will be screened from the databases MEDLINE, PsycINFO, CINAHL, and Embase, and from searches to source gray literature. Eligible cross-sectional and cohort studies published after 1994 with no language limits will be retrieved, and their methodological quality will be assessed. Data extraction will include study details, methods, and outcomes. Results will be described by narrative summary or, if studies are sufficiently similar, a meta-analysis will be performed. Prevalence data will be pooled for meta-analysis by a random effects model. The results will be presented graphically in a forest plot. Data heterogeneity will be statistically tested using χ2 and I2 tests. If substantial heterogeneity is detected, sources of heterogeneity will be explored by subgroup analysis and meta-regression, and results will be presented by a narrative summary. PROSPERO CRD42020149956.


Generation and analysis of soybean plastid transformants expressing Bacillus thuringiensis Cry1Ab protoxin.
We describe the generation of fertile and homoplasmic soybean plastid transformants, expressing the Bacillus thuringiensis insecticidal protoxin Cry1Ab. Transgenes were targeted in the intergenic region of Glycine max plastome, between the rps12/7 and trnV genes and selection was carried out using the aadA gene encoding spectinomycin resistance. Molecular analysis confirmed the integration of the cry1Ab and aadA expression cassettes at the expected location in the soybean plastome, and the transmission of the transgenes to the next generation. Western blot analyses showed that the Cry1Ab protoxin is highly expressed in leaves, stems and seeds, but not in roots. Its expression confers strong insecticidal activity to the generated transgenic soybean, as exemplified with velvetbean caterpillar (Anticarsia gemmatalis).


Pneumatic fractures in confined granular media.
We perform experiments where air is injected at a constant overpressure P_{in}, ranging from 5 to 250 kPa, into a dry granular medium confined within a horizontal linear Hele-Shaw cell. The setup allows us to explore compacted configurations by preventing decompaction at the outer boundary, i.e., the cell outlet has a semipermeable filter such that beads are stopped while air can pass. We study the emerging patterns and dynamic growth of channels in the granular media due to fluid flow, by analyzing images captured with a high speed camera (1000 images/s). We identify four qualitatively different flow regimes, depending on the imposed overpressure, ranging from no channel formation for P_{in} below 10 kPa, to large thick channels formed by erosion and fingers merging for high P_{in} around 200 kPa. The flow regimes where channels form are characterized by typical finger thickness, final depth into the medium, and growth dynamics. The shape of the finger tips during growth is studied by looking at the finger width w as function of distance d from the tip. The tip profile is found to follow w(d)∝d^{β}, where β=0.68 is a typical value for all experiments, also over time. This indicates a singularity in the curvature d^{2}d/dw^{2}∼κ∼d^{1-2β}, but not of the slope dw/dd∼d^{β-1}, i.e., more rounded tips rather than pointy cusps, as they would be for the case β>1. For increasing P_{in}, the channels generally grow faster and deeper into the medium. We show that the channel length along the flow direction has a linear growth with time initially, followed by a power-law decay of growth velocity with time as the channel approaches its final length. A closer look reveals that the initial growth velocity v_{0} is found to scale with injection pressure as v_{0}∝P_{in}^{3/2}, while at a critical time t_{c} there is a cross-over to the behavior v(t)∝t^{-α}, where α is close to 2.5 for all experiments. Finally, we explore the fractal dimension of the fully developed patterns. For example, for patterns resulting from intermediate P_{in} around 100-150 kPa, we find that the box-counting dimensions lie within the range D_{B}∈[1.53,1.62], similar to viscous fingering fractals in porous media.


Prevalence, prenatal diagnosis and survival of gastroschisis.
To describe the prevalence, associated anomalies, prenatal diagnosis and survival of cases of gastroschisis. Data were extracted from the Northern Congenital Abnormality Survey (NorCAS) for cases delivered during 1997 to 2006. A total of 143 cases of gastroschisis were notified from 310 410 registered births. Ten (7%) gastroschisis cases were associated with other structural anomalies. The male to female ratio among isolated gastroschisis cases was 1:1.1 and 4:1 among non-isolated cases. The total prevalence for isolated cases was 4.28 per 10,000 births (95% CI 3.56-5.01), and the overall live birth prevalence was 4.21 per 10,000 live births (95% CI 3.49-4.93). There was an increase in total prevalence during the ten years, although this increase did not reach statistical significance (chi(2) test for trend = 0.996, p = 0.318). The maternal age-specific prevalence was highest in the less than 20 years age group (18.6 per 10 000 births (95% CI 14.0-23.3)). 130 (97.7%) isolated cases resulted in a live birth; 122 (91.7%) infants were alive at age one year. The accuracy of prenatal diagnosis was high, with gastroschisis being detected in 130 (97.7%) isolated cases. This population-based study demonstrates a continued increase in gastroschisis, especially in young mothers. The accuracy of prenatal diagnosis was very high. Just over 90% of children born with gastroschisis survived.


Divergence of annual and perennial species in the Brassicaceae and the contribution of cis-acting variation at FLC orthologues.
Variation in life history contributes to reproductive success in different environments. Divergence of annual and perennial angiosperm species is an extreme example that has occurred frequently. Perennials survive for several years and restrict the duration of reproduction by cycling between vegetative growth and flowering, whereas annuals live for 1 year and flower once. We used the tribe Arabideae (Brassicaceae) to study the divergence of seasonal flowering behaviour among annual and perennial species. In perennial Brassicaceae, orthologues of FLOWERING LOCUS C (FLC), a floral inhibitor in Arabidopsis thaliana, are repressed by winter cold and reactivated in spring conferring seasonal flowering patterns, whereas in annuals, they are stably repressed by cold. We isolated FLC orthologues from three annual and two perennial Arabis species and found that the duplicated structure of the A. alpina locus is not required for perenniality. The expression patterns of the genes differed between annuals and perennials, as observed among Arabidopsis species, suggesting a broad relevance of these patterns within the Brassicaceae. Also analysis of plants derived from an interspecies cross of A. alpina and annual A. montbretiana demonstrated that cis-regulatory changes in FLC orthologues contribute to their different transcriptional patterns. Sequence comparisons of FLC orthologues from annuals and perennials in the tribes Arabideae and Camelineae identified two regulatory regions in the first intron whose sequence variation correlates with divergence of the annual and perennial expression patterns. Thus, we propose that related cis-acting changes in FLC orthologues occur independently in different tribes of the Brassicaceae during life history evolution.


PA32540 for the secondary prevention of cardiovascular disease in patients at risk for aspirin-associated gastric ulcers.
Prescribed in patients with a history of myocardial infarction, stroke, transient ischemic attack, coronary intervention or bypass surgery, aspirin is one of the medications most commonly used in the secondary prevention of cardiovascular diseases. It has become a mainstay of therapy after years of solid evidence supporting its efficacy in clinical trials. However, a number of risks and side effects accompany its benefits, including the notable risk of bleeding and gastrointestinal side effects. Numerous mechanisms have been proposed to attenuate these effects to promote adherence and to expand the population for which aspirin is a reasonable treatment option. A polypill or combination formulation that includes a proton pump inhibitor, a drug commonly prescribed alongside aspirin, is one potential avenue of therapy. One such combination pill, PA32540, has undergone Phase I and Phase III trials and shows promising safety and efficacy results in these preliminary trials.


Necrotic changes in prolactinomas after long term administration of bromocriptine.
Six prolactinoma patients were studied endocrinologically and their tumors were examined histologically after long term bromocriptine therapy. In patient 1 with a large prolactinoma, a marked reduction in size and a remarkable decrease in elevated serum PRL levels occurred after bromocriptine treatment for 8 months. The histological findings consisted of two components, i.e. shrunken island-like cell nests and acellular spaces. Some degenerative and necrotic tumor cells, hyaline substance, and fibrosis were observed with light and electron microscopy in these acellular spaces. Island-like cell nests consisted of atrophic cells having disproportionally scanty cytoplasm. The same histological findings were observed in four other patients. However, in another patient whose tumor decreased in size only slightly during bromocriptine therapy, the specimen had few acellular spaces. Thus, long term bromocriptine treatment of patients with prolactinomas may result in necrosis of some adenoma cells in some patients.


[Determination of kidney circulation with radioxenon].
On 23 investigations in dogs the 133xenon eluation method was compared with the bloody measurement of the renal blood supply. The most favourable correlation presents the measurement of the initial decrease of the curves with r = 0.827 and y = 0.889x + 53.3, besides the modified hight-surface-method. Possibilities of error exist especially by the recirculation of xenon and the influence on the blood supply by the xenon-injection.


The first experience with sodium-glucose cotransporter 2 inhibitor for the treatment of systemic right ventricular failure.
In congenitally corrected transposition of the great arteries, the morphological right ventricle supports the systemic circulation. This chronic exposure to pressure overload ultimately leads to systemic right ventricular (sRV) dysfunction and heart failure. Pharmacological options for the treatment of sRV failure are poorly defined and no solid recommendations are made in the most recent guidelines. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a new class of antihyperglycaemic drugs that have been demonstrated to significantly reduce the risk of worsening heart failure and death from cardiovascular causes in patients with chronic heart failure with reduced left ventricular ejection fraction, yet no data are available in sRV patients. We report on the treatment and clinical follow-up of a patient with advanced heart failure and poor sRV function in the context of congenitally corrected transposition of the great arteries, who did not tolerate sacubitril/valsartan and had a high burden of heart-failure-related hospitalizations. Treatment with dapagliflozin was well tolerated and resulted in (small) subjective and objective functional and echocardiographic improvement and a reduction in heart-failure-related hospitalizations.


Effect of dipeptidyl peptidase 4 inhibitors on acute and subacute models of inflammation in male Wistar rats: An experimental study.
The prevalence of Type 2 diabetes mellitus (T2DM) has reached alarming proportions due to the rapidly increasing rates of this disease worldwide. Preclinical and clinical studies have revealed elevated levels of inflammatory markers in a vast number of illnesses such as T2DM, obesity, and atherothrombosis collectively called metabolic syndrome leading to adverse cardiovascular events. Dipeptidyl peptidase 4 (DPP-4) inhibitors which are the enhancers of glucagon-like peptide 1 (GLP -1), could have anti-inflammatory potential which could help in reducing cardiovascular complications of diabetes and benefit patients suffering from the metabolic syndrome. The objective of this study was to analyze the effect of DPP-4 inhibitors, namely vildagliptin and saxagliptin on acute and subacute models of inflammation. Male Wistar rats were randomly divided into control, standard, and two treatment groups (6 animals in each group, total 24 animals). The animals received the drugs orally. The effects of vildagliptin and saxagliptin on inflammation were tested in acute (carrageenan-induced paw edema method) and subacute (grass pith and cotton pellet implantation method) models of inflammation. Vildagliptin and saxagliptin used in the present study showed a significant anti-inflammatory activity in acute and subacute models of inflammation. The present study suggests that vildagliptin and saxagliptin have significant anti-inflammatory potential. Based on the findings of the present study and the available literature, it can be concluded that the anti-inflammatory potential of DPP-4 inhibitors could help to reduce the cardiovascular complications of Type 2 diabetes and the related cluster of metabolic disorders collectively called the metabolic syndrome.


N-linked glycosylation of west nile virus envelope proteins influences particle assembly and infectivity.
West Nile virus (WNV) encodes two envelope proteins, premembrane (prM) and envelope (E). While the prM protein of all WNV strains contains a single N-linked glycosylation site, not all strains contain an N-linked site in the E protein. The presence of N-linked glycosylation on flavivirus E proteins has been linked to virus production, pH sensitivity, and neuroinvasiveness. Therefore, we examined the impact of prM and E glycosylation on WNV assembly and infectivity. Similar to other flaviviruses, expression of WNV prM and E resulted in the release of subviral particles (SVPs). Removing the prM glycosylation site in a lineage I or II strain decreased SVP release, as did removal of the glycosylation site in a lineage I E protein. Addition of the E protein glycosylation site in a lineage II strain that lacked this site increased SVP production. Similar results were obtained in the context of either reporter virus particles (RVPs) or infectious lineage II WNV. RVPs or virions bearing combinations of glycosylated and nonglycosylated forms of prM and E could infect mammalian, avian, and mosquito cells (BHK-21, QT6, and C6/36, respectively). Those particles lacking glycosylation on the E protein were modestly more infectious per genome copy on BHK-21 and QT6 cells, while this absence greatly enhanced the infection of C6/36 cells. Thus, glycosylation of WNV prM and E proteins can affect the efficiency of virus release and infection in a manner that is cell type and perhaps species dependent. This suggests a multifaceted role for envelope N-linked glycosylation in WNV biology and tropism.


Electromechanical characteristics of ZnO:Al nanorods.
In this study, we explore the effect of aluminum doping on the mechanical, piezoelectric, and semiconductive properties of zinc oxide (ZnO) nanorods using scanning probe microscopy. The results show that the size of ZnO:Al nanorods can be changed by tuning the dopant concentrations during nanorod growth. The average surface potentials of the samples were -42.2-34.4 mV. Single nanorod bending generation output surface potentials were 0.05-0.08 V. The power density per unit substrate area was 0.72 nW/mm(-2) for a device outputting ultrasonic wavelengths.


Detection of mycoplasma infection of mammalian cells.
Mycoplasma infection was detected in cultures of COS cells with a novel, simple assay that detects the conversion of arginine to citrulline by the enzyme, arginine deiminase, specific to all species of mycoplasma. Transfection of COS cells was inhibited in mycoplasma-infected cells, a phenomenon that was readily reversed by treatment with a mycoplasma removal agent. Cultures of cells used for transfection should be regularly monitored for evidence of mycoplasma by assay of arginine deiminase activity or by other methods.


Paintable Silicone-Based Corrugated Soft Elastomeric Capacitor for Area Strain Sensing.
Recent advances in soft polymer materials have enabled the design of soft machines and devices at multiple scales. Their intrinsic compliance and robust mechanical properties and the potential for a rapid scaling of the production process make them ideal candidates for flexible and stretchable electronics and sensors. Large-area electronics (LAE) made from soft polymer materials that are capable of sustaining large deformations and covering large surfaces and are applicable to complex and irregular surfaces and transducing deformations into readable signals have been explored for structural health monitoring (SHM) applications. The authors have previously proposed and developed an LAE consisting of a corrugated soft elastomeric capacitor (cSEC). The corrugation is used to engineer the directional strain sensitivity by using a thermoplastic styrene-ethylene-butadiene-styrene (SEBS). A key limitation of the SEBS-cSEC technology is the need of an epoxy for reliable bonding of the sensor onto the monitored surface, mainly attributable to the sensor's fabrication process that comprises a solvent that limits its direct deployment through a painting process. Here, with the objective to produce a paintable cSEC, we study an improved solvent-free fabrication method by using a commercial room-temperature-vulcanizing silicone as the host matrix. The matrix is filled with titania particles to form the dielectric layer, yielding a permittivity of 4.05. Carbon black powder is brushed onto the dielectric and encapsulated with the same silicone to form the conductive stretchable electrodes. The sensor is deployed by directly painting a layer of the silicone onto the monitored surface and then depositing the parallel plate capacitor. The electromechanical behavior of the painted silicone-cSEC was characterized and exhibited good linearity, with an R2 value of 0.9901, a gauge factor of 1.58, and a resolution of 70 με. This resolution compared well with that of the epoxied SEBS-cSEC reported in previous work (25 με). Its performance was compared against that of its more mature version, the SEBS-cSEC, in a network configuration on a cantilever plate subjected to a step-deformation and to free vibrations. Results showed that the performance of the painted silicone-sCEC compared well with that of the SEBS-cSEC, but that the use of a silicone paint instead of an epoxy could be responsible for larger noise and the under-estimation of the dominating frequency by 6.7%, likely attributable to slippage.


Acute pulmonary embolism: diagnosis with MR angiography.
To prospectively evaluate pulmonary magnetic (MR) angiography as a diagnostic examination for acute pulmonary embolism (PE). Thirty-six consecutive patients (19 women, 17 men; age range, 28-84 years) underwent pulmonary digital subtraction angiography (DSA) and pulmonary MR angiography. MR angiograms were obtained during suspended respiration and the pulmonary arterial phase of gadolinium-based contrast medium injection. A steady-state gradient-recalled-echo sequence with free induction decay sampling was used. DSA studies were interpreted for the presence of acute PE by two independent radiologists; an adjudicator made the final decision on discordant interpretations. By using DSA, a total of 19 acute pulmonary emboli were depicted in 13 patients. Prospectively, 13 of these emboli were depicted by using MR angiography. MR angiography missed six emboli: Four required the DSA adjudicator to make the decision, and one was in a patient whose MR angiogram was acquired during breathing. Four of these six emboli were small subsegmental emboli, and two were segmental. Performed without pulmonary arterial catheterization, iodinated contrast media, or ionizing radiation, pulmonary MR angiography had a high accuracy for depicting lobar and segmental emboli, but was unable to depict four of five subsegmental emboli.


Levels of SCS7/FA2H-mediated fatty acid 2-hydroxylation determine the sensitivity of cells to antitumor PM02734.
PM02734 is a novel synthetic antitumor drug that is currently in phase I clinical trials. To gain some insight into its mode of action, we used the yeast Saccharomyces cerevisiae as a model system. Treatment of S. cerevisiae with PM02734 rapidly induced necrosis-like cell death, as also found for mammalian cells treated with its close analogue kahalalide F. We have screened the complete set of 4,848 viable S. cerevisiae haploid deletion mutants to identify genes involved in sensitivity or resistance to PM02734. Forty-five percent of the 40 most sensitive strains identified had a role in intracellular vesicle trafficking, indicating that the drug severely affects this process. A mutant strain lacking the sphingolipid fatty acyl 2-hydroxylase Scs7 was found to be the most resistant to PM02734, whereas overexpression of Scs7 rendered the cells hypersensitive to PM02734. To validate these findings in human cells, we did small interfering RNA experiments and also overexpressed the Scs7 human homologue FA2H in human cancer cell lines. As in yeast, FA2H silencing turned the cells resistant to the drug, whereas FA2H overexpression led to an increased sensitivity. Moreover, exogenous addition of the 2-hydroxylated fatty acid 2-hydroxy palmitic acid to different human cell lines increased their sensitivity to the cytotoxic compound. Taken together, these results suggest that the cell membrane and, in particular, 2-hydroxy fatty acid-containing ceramides are important for PM02734 activity. These findings may have important implications in the development of PM02734 because tumor cells with high FA2H expression are expected to be particularly sensitive to this drug.


Is body mass index the prognostic factor in breast cancer?: a meta-analysis.
This study was performed to integrate the results of previous studies that investigated the relationship between body mass index (BMI) and prognosis in breast cancer. We reviewed the English literatures using the MEDLINE database from 1966 to 1999. The materials included 12 published articles with a total of 8,029 cases of breast cancer. The effect size was obtained from hazard ratio in each study. Homogeneity test was conducted before the integration of each effect size and the result demonstrated that the studies were heterogeneous. A random effect model was used to integrate the overall effect size. The integrated effect size was 1.56 (95% confidence interval, 1.22-2.00). In addition, publication bias should be accounted for because each published study was asymmetric in shape revealed by funnel plot. These results suggest that BMI have a prognostic significance in breast cancer. We believe that well-designed longitudinal studies, involving a large number of samples are required to resolve these issues.


Simultaneous determination of 4-hydroxyphenyl lactic acid, 4-hydroxyphenyl acetic acid, and 3,4-hydroxyphenyl propionic acid in human urine by ultra-high performance liquid chromatography with fluorescence detection.
A simple and reliable method was established for simultaneous determination of 4-hydroxyphenyl acetic acid, 4-hydroxyphenyl lactic acid, and 3,4-hydroxyphenyl propionic acid in human urine by high-performance liquid chromatography with fluorescence detection. Solid-phase extraction was used to eliminate the interferences in urine. The separation of three analytes was achieved using a C18 column and a mobile phase formed by a 95:5 v/v mixture of 50 mmol/L ammonium acetate buffer at pH 6.8 that contained 5 mmol/L tetrabutyl ammonium bromide and acetonitrile. Under the optimized conditions, the detection limits of 4-hydroxyphenyl acetic acid, 4-hydroxyphenyl lactic acid, and 3,4-hydroxyphenyl propionic acid were 4.8 × 10-3 , 8.80 × 10-3 , and 9.00 × 10-3 mg/L, respectively, and the recoveries were in the range of 85.0-120.0% with relative standard deviations of 1.5-3.1%. This method was used to analyze urine samples from breast cancer patients, healthy people and post-surgery breast cancer patients. Significant differences in urinary levels of 4-hydroxyphenyl acetic acid and 4-hydroxyphenyl lactic acid could be found between the breast cancer patients group and other two groups. No effect of age and sex was observed on the urinary levels of 4-hydroxyphenyl acetic acid and 4-hydroxyphenyl lactic acid. This method might be helpful for cancer biomarkers discovery in urine.


On the scent of human olfactory orbitofrontal cortex: meta-analysis and comparison to non-human primates.
It is widely accepted that the orbitofrontal cortex (OFC) represents the main neocortical target of primary olfactory cortex. In non-human primates, the olfactory neocortex is situated along the basal surface of the caudal frontal lobes, encompassing agranular and dysgranular OFC medially and agranular insula laterally, where this latter structure wraps onto the posterior orbital surface. Direct afferent inputs arrive from most primary olfactory areas, including piriform cortex, amygdala, and entorhinal cortex, in the absence of an obligatory thalamic relay. While such findings are almost exclusively derived from animal data, recent cytoarchitectonic studies indicate a close anatomical correspondence between non-human primate and human OFC. Given this cross-species conservation of structure, it has generally been presumed that the olfactory projection area in human OFC occupies the same posterior portions of OFC as seen in non-human primates. This review questions this assumption by providing a critical survey of the localization of primate and human olfactory neocortex. Based on a meta-analysis of human functional neuroimaging studies, the region of human OFC showing the greatest olfactory responsivity appears substantially rostral and in a different cytoarchitectural area than the orbital olfactory regions as defined in the monkey. While this anatomical discrepancy may principally arise from methodological differences across species, these results have implications for the interpretation of prior human lesion and neuroimaging studies and suggest constraints upon functional extrapolations from animal data.


Postoperative analgesic and behavioral effects of intranasal fentanyl, intravenous morphine, and intramuscular morphine in pediatric patients undergoing bilateral myringotomy and placement of ventilating tubes.
Bilateral myringotomy and placement of ventilating tubes (BMT) is one of the most common pediatric surgical procedures in the United States. Many children who undergo BMT develop behavioral changes in the postanesthesia care unit (PACU) and require rescue pain medication. The incidence of these changes is lower in children receiving intraoperative opioids by the nasal, IM, or IV route compared with placebo. However, there are no data to indicate which route of administration is better. Our study was designed to compare the immediate postoperative analgesic and behavioral effects of 3 frequently used intraoperative techniques of postoperative pain control for patients undergoing BMT under general anesthesia. One hundred seventy-one ASA physical status I and II children scheduled for BMT were randomized into 1 of 3 groups: group 1-nasal fentanyl 2 μg/kg with IV and IM saline placebo; group 2-IV morphine 0.1 mg/kg with nasal and IM placebo; or group 3-IM morphine 0.1 mg/kg with nasal and IV placebo. All subjects received a standardized general anesthetic with sevoflurane, N(2)O, and O(2) and similar postoperative care. The primary end point of the study was the pain scores measured by the Faces, Legs, Activity, Cry, and Consolability (FLACC) scale in the PACU. There were no significant differences in peak FLACC pain among the 3 groups (mean [95% CI] 2.0 [1.2-2.8] for intranasal fentanyl, 2.7 [1.7-3.6] for IV morphine, and 2.9 [2.1-3.7] for IM morphine, respectively). There were no differences in the scores on the Pediatric Anesthesia Emergence Delirium (PAED) scale, incidence of postoperative emergence delirium (PAED score ≥ 12), emesis, perioperative hypoxemia, or need for airway intervention, and postoperative rescue analgesia. There were also no differences in the duration of PACU stay or parental satisfaction among the groups. In this double-blind, double-dummy study, there was no difference in the efficacy of intranasal fentanyl, IM and IV morphine in controlling postoperative pain and emergence delirium in children undergoing BMT placement. The IM route is the simplest and avoids the potential for delays to establish vascular access for IV therapy and the risks of laryngospasm if intranasal drugs pass through the posterior nasopharynx and irritate the vocal cords.


Scenemulator: an innovative tutor note to facilitate non-specialist tutor in PBL tutorial session.
The tutor notes are the principal learning material to assist the non-specialist tutors in facilitating the students in tutorial groups effectively. Objective: This research aimed to study which tutor notes (scenemulators = scene + simulator + tutor notes anda typical one) is best to ensure effectiveness amongst Thammasat University preclinical tutors to facilitate in tutorial sessions. Three of the scenemulators and one of typical tutor notes were formed based on the endocrinologist and endocrine block committees. After completion of each scenario over 3 consecutive years, twenty-two items with a five- rating scale questionnaire were co-operated to be completed by preclinical tutors at the Faculty ofMedicine, Thammasat University (n = 21-22/year). Thirteen and six were the topics efficiency and the comparative satisfaction, respectively. The last three were the tutor notes most needed by the tutors. Data were analyzed using descriptive statistics (mean + SD) andANOVA. From the 85%-response data, mean scores (M) on the topics efficiency on scenemulators and the regular tutor notes were above 4.5 and 3, respectively. Noticeably, the more preferable tutor notes were scenemulator (p-value <0.001). The present study demonstrated the potential ofscenemulators in filling up uncertain significant matters and its effective use as a tool to assist non-specialist PBL tutors.


SOM-based algorithms for qualitative variables.
It is well known that the SOM algorithm achieves a clustering of data which can be interpreted as an extension of Principal Component Analysis, because of its topology-preserving property. But the SOM algorithm can only process real-valued data. In previous papers, we have proposed several methods based on the SOM algorithm to analyze categorical data, which is the case in survey data. In this paper, we present these methods in a unified manner. The first one (Kohonen Multiple Correspondence Analysis, KMCA) deals only with the modalities, while the two others (Kohonen Multiple Correspondence Analysis with individuals, KMCA_ind, Kohonen algorithm on DISJonctive table, KDISJ) can take into account the individuals, and the modalities simultaneously.


Influence of normal forces on the frictional behavior in tribological systems made of different bracket types and wire dimensions.
The aim of the present work was measuring the effect of varying normal forces on frictional forces applied to different bracket types in combination with archwires made of NiTi and stainless steel of variable cross section. The measurements were carried out in artificial saliva. Three-way ANOVA and Bonferroni post-hoc tests (α=0.05) were applied. Except for one subgroup the combination of normal force, bracket system and wire dimension had significant effect on friction (p<0.001) as friction increased with increasing normal forces. Only moderately tied ligatures or passive self-ligating brackets generate low friction forces. There was a statistically significant order (0.016"×0.022"<0.018"×0.025"<0.019"×0.025") for stainless steel wire material. Finite element modeling simulation showed the increasing effect of active clip force on friction especially for 0.025" wire profiles. If compared to NiTi wires, stainless steel archwires delivered higher friction. Combinations between wire-type and ligation should be chosen carefully for the intended treatment step.


Amplification of noise in a cascade chemical reaction.
Networks of chemical reactions have been given much attention recently. However, dynamical aspects of such networks remain to be elucidated. In this paper, we study a cascade chemical reaction, consisting of a series of downstream-coupled Brusselators. Along the cascade of reaction, small fluctuations naturally existing in the concentration of chemical species are amplified. Such amplification of small noise leads to the formation of chemical oscillations in the downstream chemical species. The amplification rate of small noise in the concentration along the cascade is studied and the method to calculate the amplification rate analytically is developed. It is also shown that the nonlinear evolution of the chemical oscillation in the downstream reaction strongly depends on the frequency of the initial inlet chemical concentration.


Genetic Polymorphism of GSTM1 and GSTT1 and Risk of Prostatic Carcinoma - a Meta-analysis of 7,281 Prostate Cancer Cases and 9,082 Healthy Controls.
Genetic polymorphisms constitute one of the reasons behind the racial variation in prostate cancer occurrence. Published studies regarding genetic associations of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) null deletion polymorphisms with prostatic carcinoma have generated inconsistent results among different populations. To date, even a single meta-analysis is not available representing the association of these genes with prostate cancer in different ethnic groups. Therefore, the aim of the current study was to provide a clear picture of GSTM1 and GSTT1 null deletion and risk of prostate cancer among different ethnic groups (i.e. Asians, Europeans, Americans, Africans and Eurasians). A systematic search was performed with the help of various search engines to find out the all the recent studies (2004 to 2015) evaluating the role of GSTM1 and GSTT1 deletion in prostate cancer development. Odds ratios (ORs) with 95% confidence interval (CI) of a total of 34 studies with 7,281 cases and 9,082 controls was analyzed using STATA and MedCalc software. Overall, GSTM1 deletion (OR 3.67; CI 1.39-9.85; P= 0.001) was strongly associated with prostatic cancer. In the sub group analysis GSTM1 null deletion was also significantly associated with prostate cancer among Asians (OR 4.84; CI 1.08-21.5; P= 0.03), Eurasians (OR 17.69; CI 9.87-31.70; <0.001) and Americans (OR 0.11; CI 0.01-1.06; P= 0.05). No association was observed among Europeans (P=0.42) and Africans (P= 0.40). As a whole GSTT1 null deletion (OR 0.85; CI 0.28-2.58; P= 0.77) did not show anyt significant association with prostate cancer risk among different populations. When the data were stratified into different groups, however, Africans demonstrated a significant association of GSTT1 null deletion (OR 1.95; CI 1.57-2.39; <0.001) with prostate cancer, whereas no association was found among Asians (P= 0.90), Americans (P= 0.50), Europeans (P= 0.89) and Eurasians (P= 1.0). In conclusion, both GSTM1 and GSTT1 may contribute to prostate cancer development but GSTM1 may prove to be a stronger candidate risk factor.


Development of ion beam figuring system with electrostatic deflection for ultraprecise X-ray reflective optics.
We developed an ion beam figuring system that utilizes electrostatic deflection. The system can produce an arbitrary shape by deterministically scanning the ion beam. The scan of the ion beam, which can be precisely controlled using only an electrical signal, enables us to avoid degradation of the mirror shape caused by imperfect acceleration or deceleration of a mechanically scanning stage. Additionally, this surface figuring method can easily be combined with X-ray metrology because the workpiece remains fixed during the figuring. We evaluated the figuring accuracy of the system by fabricating a plano-elliptical mirror for X-ray focusing. A mirror with a shape error of 1.4 nm root mean square (RMS) with a maximum removal depth of 992 nm, which corresponds to figuring accuracy of 0.14% RMS, was achieved. After the second shape corrections, an elliptical shape with a shape error of approximately 1 nm peak-to-valley, 0.48 nm RMS could be fabricated. Then, the mirror surface was smoothed by a low-energy ion beam. Consequently, a micro-roughness of 0.117 nm RMS, measured by atomic force microscopy, was achieved over an area of 1 × 1 μm(2).


HRC promotes anoikis resistance and metastasis by suppressing endoplasmic reticulum stress in hepatocellular carcinoma.
Histidine-rich calcium binding protein (HRC) is markedly overexpressed in hepatocellular carcinoma (HCC) and is significantly correlated with metastasis. Anoikis resistance and endoplasmic reticulum (ER) stress may have a critical effect on survival before metastasis. However, the potential functions of HRC in anoikis resistance in HCC remain unknown. Here, we uncovered the clinical value of HRC and its functional significance on anoikis in HCC. The positive expression of HRC was observably correlated with tumor size, tumor encapsulation, and tumor-node-metastasis (TNM) stage. The expression of HRC increased in HCC cells cultured in suspension. HRC enhanced the anoikis resistance of HCC, and promoted the HCC metastasis in vivo. Mechanistically, the anoikis resistance was probably dependent on endoplasmic reticulum stress. Modulating HRC level changed the ERS to affect anoikis resistance by acting protein kinase RNA-like ER kinase (PERK)-eIF2a-ATF4-CHOP signaling axis. In conclusion, we define HRC as a novel candidate oncogene involved in anoikis resistance and HCC metastasis, and provide a new potential therapeutic target for HCC.


Human fibroblastoid interferon: immunosorbent column chromatography and N-terminal amino acid sequence.
Three mice and one rabbit were inoculated with purified human fibroblastoid interferon. Neutralizing activity to human fibroblastoid interferon was observed in the serum of these animals with the rabbit showing the highest anti-interferon titers (10(6) neutralizing units/mL). Rabbit antiserum was coupled to cyanogen bromide activated Sepharose, and the resulting material was tested for use in the purification of human fibroblastoid interferon. Pure interferon obtained by this procedure was analyzed, and we report the sequence of the first 13 N-terminal amino acid residues of this protein.


Infant Food Security in New Zealand: A Multidimensional Index Developed from Cohort Data.
Food security (FS) during infancy is associated with lifelong outcomes. New Zealand is a developed economy that reports poor childhood nutrition-related health statistics, particularly among minority children, yet has no measure of FS applicable to infancy. The objective was to develop an FS index for New Zealand infants and examine its association with demographic covariates and health outcomes. Within a large (n = 6853) nationally representative cohort, variables describing infant food consumption, breastfeeding, and maternal food-related coping methods were collected from mothers during late infancy. An FS index was derived using confirmatory factor analysis. Associations were assessed by logistic regressions and described using odds ratios (OR) and ≥95% confidence intervals (CI). Fifteen percent of the cohort was highly FS, 43% tenuously food insecure (FIS), and 16% highly food insecure (FIS). Infants from minority ethnic groups had lower odds of being food secure, as did those born to the youngest mothers, mothers who smoked, or those who lived in low-income households. FIS infants had higher odds of morbidity. Interventions to improve infant FS should focus on improving dietary quality, and should give particular consideration to minority infants. We identified that FIS shows wide ethnic and socioeconomic inequity, and is associated with poorer health. The most important driving factors of FIS included poor quality weaning diets, as well as poverty and its proxies. Any interventions to improve infant FS should focus on increasing fruit and vegetable consumption to recommended intake levels, and should give particular consideration to minority infants.


Immunohistochemical comparison of alpha- and beta-synuclein in adult rat central nervous system.
We investigated the immunohistochemical localization of alpha- and beta-synuclein (alphaS and betaS) in the adult rat CNS and compared the distribution of these proteins with that of synaptophysin (SYN), a well-established presynaptic marker. Anti-SYN, alphaS and betaS antibodies immunolabeled the neuropil in a punctate pattern. No SYN immunoreactivity was found in the neuronal cytoplasm. In contrast, both anti-alphaS and betaS immunostained the neuronal cytoplasm and nucleus to various extents depending on the brain region. alphaS-positive neurons were found in the olfactory bulb, deeper layers of the cerebral neocortex, substantia nigra and pontine nucleus. Immunoreactivity was most intense in neurons of the substantia nigra. betaS-positive neurons were more widely distributed throughout the CNS: more than 50% of neurons were positive for betaS in the granular cell layer of the olfactory bulb, layer IV of the cerebral cortex, CA3 of the hippocampus, basal ganglia and thalamic reticular nuclei. Moreover, there were differences among these proteins in the distribution pattern of immunoreactivity in the neuropil in some CNS regions. These findings suggest that although alphaS and betaS are concentrated in presynaptic terminals, significant amounts of these proteins are also present in the neuronal perikarya. Furthermore, the distribution of alphaS-positive neurons is similar to that of intraneuronal inclusions in alphaS transgenic animals as well as in human alpha-synucleinopathies.


Public perceptions of quality care and provider profiling in New York: implications for improving quality care and public health.
Despite a growing emphasis on providing health care consumers with more information about quality care, useful and valid provider-specific information often has not been available to the public or has been underutilized. To assess this issue in New York State, random telephone surveys were conducted in September 2002 and March 2003, respectively, of 1,001 and 500 English- or Spanish-speaking persons, 18 years or older. Results indicated that 33% of New Yorkers were very concerned about the quality of care, with African Americans being particularly concerned. Less than half of the respondents recalled hearing or seeing information about health care quality in the past year and less than 20% actually used this information in medical decision making. African Americans were the least likely to recall receiving or being exposed to quality-related information, whereas women and more educated adults were the most likely to report being exposed. Furthermore, New Yorkers received quality information from multiple sources, with about 20% saying that they obtained information about physician and hospital quality from media (eg, newspaper) and nonmedia (eg, recommendation by family member) sources. Evaluations of different kinds of information suggested that some types (eg, whether or not a doctor is board certified) carried more weight in health care decision making than other types (eg, government ratings). Unexpectedly, those who used information to make health care decisions were more likely to have reported experiencing a medical error in the household. Finally, in the 6-month follow-up survey, concerns about the quality of care in the state remained about the same, while fears of terrorism decreased and preparations for future terrorist attacks increased. In the survey, few major differences were found in results based on payer status (eg, private insurance versus Medicaid/no insurance). These findings have implications for both the private and public health care sectors. Specifically, they suggest that greater access to and use of provider-specific health care information by the public is a viable way to improve quality, particularly if health care professionals support the public use of these data.


Potential role of stress and sensitization in the development and expression of multiple chemical sensitivity.
Chemical sensitivity in humans may be an acquired disorder in which individuals become increasingly sensitive to chemicals in the environment. It is hypothesized that in individuals with multiple chemical sensitivity (MCS), a sensitization process has occurred that is akin to behavioral sensitization and kindling observed in rodents. In the rodent sensitization model, repeated exposure to stress or drugs of abuse enhances behavioral and neurochemical responses to subsequent stimuli (stress or drugs of abuse). Kindling is a form of sensitization in which repeated application of electrical stimuli applied to the brain at low levels culminates in the induction of full-blown seizures when the same stimulus is applied at a later time. A similar sensitization of specific limbic pathways in the brain may occur in individuals with MCS. The time-dependent nature of sensitization and kindling and the role of stress in the development of sensitization are discussed in the context of rodent models, with an emphasis on application of these models to human studies of MCS.


Cross-cultural comparison of Lp(a) profiles.
Lipoprotein(a) (Lp(a)) and apolipoprotein(a) (apo(a)) phenotypes as genetic markers for coronary heart disease (CHD) have been the focus of great interest in recent times. Included in this study were four Australian populations comprising 348 Anglo-Celtic Melburnians (157 men and 191 women), 339 Chinese Melburnians (169 men and 170 women), 402 South Asian Melburnians (216 men and 186 women) and 394 Aboriginal Australians from Western Australia (175 men and 219 women). Plasma Lp(a) concentrations were more highly skewed towards the lower range in the Chinese and Aboriginal groups than in the Anglo-Celtics and South Asians. Approximately 33% of Anglo-Celtics, 20% Aboriginals, 13% Chinese and 44% South Asians had plasma Lp(a) levels above the generally accepted risk threshold values of 300 mg/L. In Aboriginals and Chinese, the S4 apo(a) phenotype predominated while in Anglo-Celtics and South Asians, the highest frequency occurred in the S3 phenotype. In the S4 phenotype, Lp(a) values varied between the four populations but there was no significant difference in concentration between gender.


Nurses' Attitudes Toward Patients Who Use Cannabis: Does Legal Status or Care Setting Matter?
Cannabis has been cited as the most frequently used drug in this country, and intolerance toward substance use is a recognized concern in nursing. The twofold purpose of this descriptive study was to determine (a) what, if any, were the differences between nurses' attitudes of patient cannabis use in states in which cannabis was legal versus illegal and (b) how do nurses working in diverse care settings differ in their attitudes regarding patient cannabis use. A sample of 809 registered nurses from across the United States were recruited to take part in this study in October 2018. A previously validated 20-question survey was used to collect participants' perceptions of and attitudes toward patient cannabis use. Demographic information collected included age, gender, educational level, years in practice, primary area of practice, and legal status of cannabis in state of practice. An independent t test and analysis of variance were used to analyze group differences. Findings from this study indicated that there was no significant difference in attitudes of nurses in states in which cannabis use was legal (M = 28.76, SD = 7.83) and states in which it was illegal (M = 29.43, SD = 7.65), t(807) = 1.202, p = .230. In addition, no significant differences were found in attitudes across six areas of practice, F(5) = 1.531, p = .178. Furthermore, nursing attitudes were largely positive toward patient cannabis use (M = 29.04, SD = 7.762; range: 20-100). Findings from this study indicate that cannabis use may not carry the same perceived stigma as other illicit substances for nurses and unbiased care may be provided regardless of personal beliefs.


Immunocytologic dissection of the urine sediment using monoclonal antibodies.
A method to identify nucleated nonsquamous cells in urine using monoclonal antibodies and immunoperoxidase stain is described. Cells from washed deposits of midstream urine samples were transferred to gelatinized slides in a cytocentrifuge, air-dried, acetone fixed, and subjected to microwave irradiation. Slide preparations were then treated with monoclonal antibodies with the use of a four-layer peroxidase-antiperoxidase technique. It was possible to identify granulocytes, monocytes, lymphocytes, and renal epithelial and urothelial cells. This method was found to be helpful in determining the profiles of cells in urine in acute tubular necrosis, drug-related acute interstitial nephritis, and crescentic glomerulonephritis.


Investigation of Na+ and K+ Competitively Binding with a G-Quadruplex and Discovery of a Stable K+-Na+-Quadruplex.
DNA G-quadruplex (G4) could adopt multiple conformations, and the exact conformation is related to the presence of cations. However, the fact that cations with various concentrations could competitively bind with G4 is rarely investigated, which greatly limits the potential applications of G4-based sensors. Here, with PW17 (a G4-forming DNA sequence) as an example, Na+ and K+ with different concentrations competitively binding with PW17 are clarified by circular dichroism spectroscopy and electrospray ionization mass spectroscopy. Although Na+ could induce PW17 switching to unstable and antiparallel Na+-stabilized PW17 (2Na+-PW17) ( CNa+ = 5-70 mM) and further to stable and hybrid 2Na+-PW17 ( CNa+ = 70-800 mM), K+ ( CK+ = 0.1-10 mM) could replace Na+ in 2Na+-PW17 with 2Na+-PW17 transforming into K+-stabilized PW17 (2K+-PW17). Moreover, the replacing ability strictly relied on CK+ and CNa+. In the switching process, a stable intermediate including a K+ and an Na+ in one G4 (K+-Na+-PW17) is firstly detected. Importantly, the stable K+-Na+-PW17 is detected at 0.5 mM K+ and 140 mM Na+. Based on the facts, the interferences of Na+ with the performance of PW17-based K+ sensors are investigated. With the stable K+-Na+-PW17 as a sensing probe and protoporphyrin IX (PPIX) as a G4 fluorescent read-out probe, a linear relationship between CK+ (500 nM-10 mM) and PPIX fluorescence is observed, which provides a fluorescence assay for detecting K+ with the co-existing 140 mM Na+. This study exhibits clear evidence of Na+ and K+ competitively binding with G4 and finds a novel and stable K+-Na+-PW17, which provides a clue to further explore G4 functions in Na+-contained samples.


Distinguishing the Photothermal and Photoinjection Effects in Vanadium Dioxide Nanowires.
Vanadium dioxide (VO2) has drawn significant attention for its unique metal-to-insulator transition near the room temperature. The high electrical resistivity below the transition temperature (∼68 °C) is a result of the strong electron correlation with the assistance of lattice (Peierls) distortion. Theoretical calculations indicated that the strong interelectron interactions might induce intriguing optoelectronic phenomena, such as the multiple exciton generation (MEG), a process desirable for efficient optoelectronics and photovoltaics. However, the resistivity of VO2 is quite temperature sensitive, and therefore, the light-induced conductivity in VO2 has often been attributed to the photothermal effects. In this work, we distinguished the photothermal and photoinjection effects in VO2 nanowires by varying the chopping frequency of the optical illumination. We found that, in our VO2 nanowires, the relatively slow photothermal processes can be well suppressed when the chopping frequency is >2 kHz, whereas the fast photoinjection component (direct photoexcitation of charge carriers) remains constant at all chopping frequencies. By separating the photothermal and photoinjection processes, our work set the basis for further studies of carrier dynamics under optical excitations in strongly correlated materials.


Evaluation of the effects of photobiomodulation on vertebras in two rat models of experimental osteoporosis.
The aim of this study was to evaluate the effects of photobiomodulation (PBM) on cancellous bone in rat models of ovariectomized induced osteoporosis (OVX-D) and glucocorticoid-induced osteoporosis (GIOP). The experiment comprised of nine groups. A group of healthy rats was used for baseline evaluations. The OVX-D rats were further divided into groups as follows: control rats with osteoporosis, OVX-D rats that received alendronate (1 mg/kg 60 days), OVX-D rats treated with pulsed wave laser (890 nm, 80 Hz, 900 s, 0.0061 W/cm2, 5.5 J/cm2, three times a week, 60 days), and OVX-D rats treated with alendronate + pulsed laser. Dexamethasone was administered to the remaining rats that were split into four groups: control, alendronate-treated rats, laser-treated rats, and GIOP rats treated with alendronate + laser. T12, L1, L2, and L3 vertebrae were subjected to laser. Results of the current study demonstrated that OVX-D and GIOP significantly decreased some stereological parameters, and type 1 collagen gene expression compared to the healthy group. There was a significant increase in osteoclast number in both OVX-D and glucocorticoid administration compared to the healthy group. However, the detrimental effect of the OVX-D procedure on bone was more serious than glucocorticoid administration. Results showed that laser alone had a detrimental effect on trabecular bone volume, and cortical bone volume in groups GIOP and OVX-D compared to those in the healthy group. Alendronate significantly improved total vertebral bone volume, trabecular bone volume, and cortical bone volume, in GIOP and OVX-D groups compared to the laser-treated groups. Furthermore, the alendronate + laser in OVX-D rats and GIOP rats produced significantly increased osteoblast number and type 1 collagen gene expression and caused a significant decrease in osteoclast number compared to the controls.


Irritative spontaneous nystagmus following intratympanic gentamicin for Menière's disease.
Intratympanic aminoglycosides were first used to treat unilateral intractable Meniere's disease over 30 years ago. Gentamicin, the current drug of choice, provides excellent vertigo control with a low incidence of hearing loss. Its salutory effect results from direct damage to both the sensory neuroepithelium and the dark cells of the labyrinth. This latter effect may reverse the degree of endolymphatic hydrops. Twelve patients with unilateral Meniere's disease were treated and prospectively studied. Although further follow-up is necessary, 10 patients have complete vertigo control, while 2 remain significantly improved. Three patients developed a spontaneous "irritative" nystagmus during the early post-treatment period. This new unique finding may represent a recovery phenomenon resulting from a temporary reversible ototoxic effect in the treatment ear. Despite our patients having a somewhat higher incidence of hearing loss compared to the reported rate, the results of this treatment are encouraging.


A quasi-unidimensional granular chain to attenuate impact.
We study via numerical simulations a granular chain not only with decreasing radii (forward tapering) in geometric progression, but also decorated with grains positioned on the top and bottom of the chain, without altering its original length. The decorating grains act as an auxiliary chain which traps part of the energy and linear momentum, both propagating as a pulse due to disturbances produced at the end of the chain. Thus, this configuration optimizes the impact attenuation and aligns the chain naturally (by symmetry) which facilitates the construction of the experimental setup. Furtheremore, since the decorating grain radii increase along the chain, this new type of chain is necessarily short in order to avoid precompression. Nevertheless, even with short chains, it is possible to mitigate impacts almost completely.


Structure of acetylglutamate kinase, a key enzyme for arginine biosynthesis and a prototype for the amino acid kinase enzyme family, during catalysis.
N-Acetyl-L-glutamate kinase (NAGK), a member of the amino acid kinase family, catalyzes the second and frequently controlling step of arginine synthesis. The Escherichia coli NAGK crystal structure to 1.5 A resolution reveals a 258-residue subunit homodimer nucleated by a central 16-stranded molecular open beta sheet sandwiched between alpha helices. In each subunit, AMPPNP, as an alphabetagamma-phosphate-Mg2+ complex, binds along the sheet C edge, and N-acetyl-L-glutamate binds near the dyadic axis with its gamma-COO- aligned at short distance from the gamma-phosphoryl, indicating associative phosphoryl transfer assisted by: (1) Mg2+ complexation; (2) the positive charges on Lys8, Lys217, and on two helix dipoles; and (3) by hydrogen bonding with the y-phosphate. The structural resemblance with carbamate kinase and the alignment of the sequences suggest that NAGK is a structural and functional prototype for the amino acid kinase family, which differs from other acylphosphate-making devices represented by phosphoglycerate kinase, acetate kinase, and biotin carboxylase.


Complex Polarity: Building Multicellular Tissues Through Apical Membrane Traffic.
The formation of distinct subdomains of the cell surface is crucial for multicellular organism development. The most striking example of this is apical-basal polarization. What is much less appreciated is that underpinning an asymmetric cell surface is an equally dramatic intracellular endosome rearrangement. Here, we review the interplay between classical cell polarity proteins and membrane trafficking pathways, and discuss how this marriage gives rise to cell polarization. We focus on those mechanisms that regulate apical polarization, as this is providing a number of insights into how membrane traffic and polarity are regulated at the tissue level.


Use of Twitter at a major national pharmacy conference.
The results of a study of Twitter use by attendees of the 2013 ASHP Midyear Clinical Meeting (MCM) and other interested parties are presented. All messages posted on the social media platform Twitter under the official MCM "hashtag" (#ashpmidyear) during the five-day conference were archived and evaluated. Demographic data on authors of MCM-related tweets were collected by evaluating information provided by Twitter users in their public profiles. The archived messages were classified by content type. A total of 1539 messages originating from 400 unique U.S.- and foreign-based Twitter accounts were posted under the MCM hashtag, an average of 3.84 tweets per account. The estimated rate of conference-related Twitter use by MCM attendees was 1.7%. One third of Twitter users posting conference-related tweets were identified as pharmacists; 86 (21.5%) and 65 (16.25%) tweets originated from accounts held by pharmacy students and pharmaceutical industry representatives, respectively. The authors of MCM-related tweets represented a broad cross-section of pharmacy practice settings and specialties. About 39% of the evaluated Twitter postings were classified as social, with about 31% of postings pertaining to specific MCM educational sessions and nearly 25% classified as advertising. The majority of MCM-related tweets by onsite and remote Twitter users were social in nature or pertained to educational sessions held over the course of the conference.


Surgery for obstructive sleep apnoea.
Obstructive sleep apnoea/hypopnoea syndrome(OSAHS) is the periodic reduction or cessation of airflow during sleep. The syndrome is associated with loud snoring, disrupted sleep and observed apnoeas. Surgery for obstructive sleep apnoea/hypopnoea syndrome aims to alleviate symptoms of daytime sleepiness, improve quality of life, and reduce the signs of sleep apnoea recorded by polysomnography. The objective of this review was to assess the effects of any type of surgery for the treatment of the symptoms of obstructive sleep apnoea/hypopnoea syndrome in adults. We searched the Cochrane Airways Group Specialised Register and reference lists of articles. We contacted experts in the field, research dissemination bodies and other Cochrane Review Groups. Searches were current as of July 2005. Randomised trials comparing any surgical intervention for obstructive sleep apnoea/hypopnoea syndrome with other surgical or non-surgical interventions or no intervention. Two reviewers assessed electronic literature search results for possibly relevant studies. Characteristics and data from studies meeting the inclusion criteria were extracted and entered into RevMan 4.2. In the 2005 update for this review eight studies (412 participants) of mixed quality met the inclusion criteria. Data from seven studies were eligible for assessment in the review. No data could be pooled. Uvulopalatopharyngoplasty (UPPP) versus conservative management (one trial): An un validated symptom score showed intermittent significant differences over a 12-month follow-up period. No differences in Polysomnography (PSG) outcomes were reported. Laser-assisted uvulopalatoplasty (LAUP) versus conservative management/placebo (two trials): One study recruited mixed a population, and separate data could not be obtained for this trial. In the other study no significant differences in Epworth scores or quality of life reported. A significant difference in favour of LAUP was reported in terms of apnoea hypopnoea index (AHI) and frequency and intensity of snoring. UPPP versus oral appliance (OA) (one trial): AHI was significantly lower with OA therapy than with UPPP. No significant differences were observed in quality of life. UPPP versus lateral pharyngoplasty (lateral PP) (one trial): No significant difference in Epworth scores, but a greater reduction in AHI with lateral PP was reported. Tongue advancement (mandibular osteotomy) + PPP versus tongue suspension + PPP (one trial): There was a significant reduction in symptoms in both groups, but no significant difference between the two surgery types. Complications reported with all surgical techniques included nasal regurgitation, pain and bleeding. These did not persist in the long term. An additional study assessed the effects of four different techniques. No data were available on between group comparisons. Multilevel temperature-controlled radiofrequency tissue ablation (TCRFTA) versus sham placebo and CPAP (one trial): There was an improvement in primary and secondary outcomes of TCRFTA over sham placebo and but no difference in symptomatic improvement when compared with CPAP. There are now a small number of trials assessing different surgical techniques with inactive and active control treatments. The studies assembled in the review do not provide evidence to support the use of surgery in sleep apnoea/hypopnoea syndrome, as overall significant benefit has not been demonstrated. The participants recruited to the studies had mixed levels of AHI, but tended to suffer from moderate daytime sleepiness where this was measured. Short-term outcomes are unlikely to consistently identify suitable candidates for surgery. Long-term follow-up of patients who undergo surgical correction of upper airway obstruction is required. This would help to determine whether surgery is a curative intervention, or whether there is a tendency for the signs and symptoms of sleep apnoea to re-assert themselves, prompting patients to seek further treatment for sleep apnoea.


Low-velocity graded treadmill stress testing in hemiparetic stroke patients.
Coronary artery disease is prevalent in stroke patients and is an important factor affecting rehabilitation and health outcomes. However, the presence of neurological deficits in gait and balance has discouraged systematic application of exercise testing and prescription in the stroke population. We evaluated a novel graded treadmill stress test in paretic stroke patients and tested floor walking as a predictor of adequate neurological function to perform the treadmill test. Patients (n = 31) with residual paretic gait deficits after ischemic stroke were evaluated with graded treadmill at gait velocities individualized to functional mobility observed during an initial zero-incline treadmill tolerance test. Most patients (30/31) tolerated testing, achieving mean heart rates of 129 +/- 14 beats per minute (mean +/- SD), representing 84 +/- 10% of maximal age-predicted heart rate. Evidence for asymptomatic myocardial ischemia was found in 29% of those without known coronary artery disease. Exercise termination was more often due to generalized fatigue than cardiopulmonary intolerance (23/31 versus 4/31; P < .0001) or hemiparetic leg fatigue (1/31; P < .0001). Floor walking across a wide range of velocities (0.25 to 2.5 mph) demonstrated a strong linear relation with treadmill velocities (n = 24; r = 80; P < .0001); all patients floor walking at > or = 0.5 mph had adequate neuromotor function to perform the exercise test. These findings suggest that graded treadmill exercise testing, with proper safety precautions, can be used to assess cardiopulmonary function in paretic stroke patients. A simple floor-walking test predicts adequate neurological function to perform the exercise test. Exercise capacity is most limited by generalized fatigue and not by the paretic limb, supporting a rationale for endurance training in this population.


Multiplanar distraction osteogenesis of fibula free flaps used for secondary reconstruction of traumatic maxillary defects.
Traumatic maxillary bone loss, if not treated acutely, is accompanied by contracture of the overlying soft tissue envelope and loss of facial projection in three dimensions. Reconstruction aimed at replacing the bony architecture, expanding the soft tissue envelope and establishing a platform for dental rehabilitation can be accomplished in a staged approach. We present two patients who underwent replacement of missing maxillary segments with a free fibula flap, followed by distraction of the free fibula in three dimensions and eventual dental rehabilitation with osseo-integrated implants.


A Minimally Invasive Method for Intratracheal Instillation of Drugs in Neonatal Rodents to Treat Lung Disease.
Treatment of neonatal rodent with drugs instilled directly into the trachea could serve as a valuable tool to study the impact of a locally administered drug. This has direct translational impact because surfactant and drugs are administered locally into the lungs. Though the literature has many publications describing minimally invasive transoral intubation of adult mice and rats in therapeutic experiments, this approach in neonatal rat pups is lacking. The small size of orotracheal region/pharynx in the pups makes visualization of laryngeal lumen (vocal cords) difficult, contributing to the variable success rate of intratracheal drug delivery. We hereby demonstrate effective oral intubation of neonatal rat pup - a technique that is non-traumatic and minimally-invasive, so that it can be used for serial administration of drugs. We used an operating otoscope with an illumination system and a magnifying lens to visualize the tracheal opening of the rat neonates. The drug is then instilled using a 1 mL syringe connected to a pipette tip. The accuracy of the delivery method was demonstrated using Evans blue dye administration. This method is easy to get trained in and could serve as an effective way to instill drugs into trachea. This method could also be used for administration of inoculum or agents to simulate disease conditions in animals and, also, for cell-based treatment strategies for various lung diseases.


Direct and indirect vitamin A supplementation strategies result in different plasma and tissue retinol kinetics in neonatal rats.
Many questions remain regarding vitamin A (VA) supplementation of infants. Herein we compared direct oral VA supplementation of the neonate and indirect treatment through maternal dietary VA (M-VA) treatment on VA status and kinetics in neonatal rats. Treatments included direct VA combined with retinoic acid (RA) [D-VARA; VA (6 mg/kg) + 10% RA, given orally to neonates on postnatal day (P)2 and P3] and indirect VA supplementation through increased M-VA, compared with each other and oil-treated neonates. [(3)H]retinol was administered orally to all neonates on P4. Plasma and tissue [(3)H]retinol kinetics were determined from 1 h to 14 days post-dosing. D-VARA versus placebo dramatically increased liver and lung retinol, but only in the first 8-10 days. In M-VA neonates, liver and lung VA increased progressively throughout the study. Compartmental modeling of plasma [(3)H]retinol showed that both D-VARA and indirect M-VA reduced retinol recycling between plasma and tissues. Compartmental models of individual tissues predicted that D-VARA stimulated the uptake of VA in chylomicrons to extrahepatic tissues, especially intestine, while the uptake was not observed in M-VA neonates. In conclusion, indirect maternal supplementation had a greater sustained effect than D-VARA on neonatal VA status, while also differentially affecting plasma and tissue retinol kinetics.


Expression of the ubiquitin-proteasome pathway and muscle loss in experimental cancer cachexia.
Muscle protein degradation is thought to play a major role in muscle atrophy in cancer cachexia. To investigate the importance of the ubiquitin-proteasome pathway, which has been suggested to be the main degradative pathway mediating progressive protein loss in cachexia, the expression of mRNA for proteasome subunits C2 and C5 as well as the ubiquitin-conjugating enzyme, E2(14k), has been determined in gastrocnemius and pectoral muscles of mice bearing the MAC16 adenocarcinoma, using competitive quantitative reverse transcriptase polymerase chain reaction. Protein levels of proteasome subunits and E2(14k) were determined by immunoblotting, to ensure changes in mRNA were reflected in changes in protein expression. Muscle weights correlated linearly with weight loss during the course of the study. There was a good correlation between expression of C2 and E2(14k) mRNA and protein levels in gastrocnemius muscle with increases of 6-8-fold for C2 and two-fold for E2(14k) between 12 and 20% weight loss, followed by a decrease in expression at weight losses of 25-27%, although loss of muscle protein continued. In contrast, expression of C5 mRNA only increased two-fold and was elevated similarly at all weight losses between 7.5 and 27%. Both proteasome functional activity, and proteasome-specific tyrosine release as a measure of total protein degradation was also maximal at 18-20% weight loss and decreased at higher weight loss. Proteasome expression in pectoral muscle followed a different pattern with increases in C2 and C5 and E2(14k) mRNA only being seen at weight losses above 17%, although muscle loss increased progressively with increasing weight loss. These results suggest that activation of the ubiquitin-proteasome pathway plays a major role in protein loss in gastrocnemius muscle, up to 20% weight loss, but that other factors such as depression in protein synthesis may play a more important role at higher weight loss.


[Symptoms of anxiety and depression in atopic eczema/dermatitis syndrome].
The presence of chronic disease is a risk factor for the development of mood disturbances and panic disorders. They can influence the course of disease and effectiveness of therapy. Depression may be the cause of making light doctor's advice. Anxious patients often aggravate symptoms of the disease. To study symptoms of anxiety and depression in patients suffering from atopic eczema/dermatitis syndrome (ZAZS). Material. We studied 38 patients suffering from adequately controlled moderate ZAZS and 62 volunteers in the control group. Mental status of subjects was assessed by means of State and Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI) questionnaires. ZAZS patients demonstrated higher intensity of anxiety (as a trait and as a state) than healthy subjects. Intensity and prevalence of depression in the atopic eczema/ dermatitis syndrome group was higher than in the control group. Patients suffering from atopic/eczema dermatitis syndrome are pre-disposed to anxiety and depression manifestation. Even adequately controlled symptoms of atopic/eczema dermatitis syndrome may be the cause of those disturbances' occurrence.


Protective effect of the thromboxane A2 receptor antagonist ONO 3708 on ischemia-reperfusion injury in the dog liver.
Prostaglandins are widely known to have cytoprotective effects in a variety of conditions. Thromboxane A2 has the opposite effect of prostaglandins. In this study the effects of the thromboxane A2 receptor antagonist ONO 3708 on ischemia and subsequent reperfusion in the dog liver was evaluated. Mongrel dogs weighing from 10 to 15 kg were divided into three groups: a control group, a group with induced liver ischemia and subsequent reperfusion, and a group that received ONO 3708 and then underwent induced liver ischemia and subsequent reperfusion. Liver ischemia was induced by the Pringle procedure for 60 minutes. The concentrations of total free amino acids, aromatic amino acids, and branched-chain amino acids in blood taken from the portal and hepatic veins were examined before and after the Pringle procedure in the latter two groups and at the corresponding points in the control group. Disturbances in amino acid metabolism in the liver occurred 5 minutes after the declamping in the ischemic group, and prostaglandin I2 and thromboxane A2 levels and lipid peroxide production, were increased. In contrast, hepatic amino acid metabolism was unchanged, and prostaglandin I2 and thromboxane A2, and lipid peroxide production, were normalized in the group that was treated with ONO 3708. ONO 3708 appears to protects hepatic tissue from ischemia-reperfusion injury through free-radical scavenging, by increasing prostaglandin I2 levels, and by decreasing thromboxane A2 production.


Combination of commercially available molecular assays and culture based methods in diagnosis of tuberculosis and drug resistant tuberculosis.
Early diagnosis of tuberculosis is of major clinical importance. Among 4733 clinical specimens collected from 3363 patients and subjected to Ziehl-Neelsen microscopy, 4109 were inoculated onto Löwenstein-Jensen slants and 3139 in Bactec/9000MB. Polymerase Chain Reaction (PCR) was performed in 3139 specimens, whereas, a genotypic assay was directly applied in 93 Mycobacterium tuberculosis complex PCR-positive for isoniazid and rifampicin resistance detection specimens (GenoType MTBDRplus). Recovered M. tuberculosis isolates (64) as well as, 21 more sent from Regional Hospitals were tested for antimycobacterial resistance with a phenotypic (manual MGIT-SIRE) and a genotypic assay (GenoType MTBDRplus). PCR in the clinical specimens showed excellent specificity (97.4%) and accuracy (96.8%), good sensitivity (70.4%), but low positive predictive value (40.3%). MGIT-SIRE performed to M. tuberculosis did not confer a reliable result in 16 isolates. Of the remaining 69 isolates, 15 were resistant to streptomycin, seven to isoniazid, seven to ethambutol and five to rifampicin. GenoType MTBDRplus correctly detected isoniazid (seven) and rifampicin-resistant M. tuberculosis strains (five), showing an excellent performance overall (100%). Susceptibility results by the molecular assay applied directly to clinical specimens were identical to those obtained from recovered isolates of the corresponding patients. Combining molecular and conventional methods greatly contribute to early diagnosis and accurate susceptibility testing of tuberculosis.


Screening of Toxic Effects of Bisphenol A and Products of Its Degradation: Zebrafish (Danio rerio) Embryo Test and Molecular Docking.
Bisphenol A (BPA) acts as an endocrine-disrupting compound even at a low concentration. Degradation of BPA could lead to the formation of toxic products. In this study, we compare the toxicity of BPA and seven intermediate products of its degradation. The accuracy of three molecular docking programs (Surflex, Autodock, and Autodock Vina) in predicting the binding affinities of selected compounds to human (ERα, ERβ, and ERRγ) and zebrafish (ERα, ERRγA, and ERRγB) estrogen and estrogen-related receptors was evaluated. The docking experiments showed that 4-isopropylphenol could have similar toxicity to that of BPA due to its high affinity to ERRγ and ERRγB and high octanol-water partitioning coefficient. The least toxic compounds were hydroquinone and phenol. Those compounds as well as BPA were screened in the zebrafish (Danio rerio) embryo test. 4-isopropylphenol had the strongest toxic effect on zebrafish embryos and caused 100% lethality shortly after exposure. BPA caused the delay in development, multiple deformations, and low heartbeats (30 bps), whereas hydroquinone had no impact on the development of the zebrafish embryo. Thus, the results of zebrafish screening are in good agreement with our docking experiment. The molecular docking could be used to screen the toxicity of other xenoestrogens and their products of degradation.


Exercise training protects against aging-induced mitochondrial fragmentation in mouse skeletal muscle in a PGC-1α dependent manner.
Aging is associated with impaired mitochondrial function, whereas exercise training enhances mitochondrial content and function in part through activation of PGC-1α. Mitochondria form dynamic networks regulated by fission and fusion with profound effects on mitochondrial functions, yet the effects of aging and exercise training on mitochondrial network structure remain unclear. This study examined the effects of aging and exercise training on mitochondrial network structure using confocal microscopy on mitochondria-specific stains in single muscle fibers from PGC-1α KO and WT mice. Hyperfragmentation of mitochondrial networks was observed in aged relative to young animals while exercise training normalized mitochondrial network structure in WT, but not in PGC-1α KO. Mitochondrial fission protein content (FIS1 and DRP1) relative to mitochondrial content was increased with aging in both WT and PGC-1α KO mice, while exercise training lowered mitochondrial fission protein content relative to mitochondrial content only in WT. Mitochondrial fusion protein content (MFN1/2 and OPA1) was unaffected by aging and lifelong exercise training in both PGC-1α KO and WT mice. The present results provide evidence that exercise training rescues aging-induced mitochondrial fragmentation in skeletal muscle by suppressing mitochondrial fission protein expression in a PGC-1α dependent manner.


Nutrigenetics and nutrigenomics insights into diabetes etiopathogenesis.
Diabetes mellitus (DM) is considered a global pandemic, and the incidence of DM continues to grow worldwide. Nutrients and dietary patterns are central issues in the prevention, development and treatment of this disease. The pathogenesis of DM is not completely understood, but nutrient-gene interactions at different levels, genetic predisposition and dietary factors appear to be involved. Nutritional genomics studies generally focus on dietary patterns according to genetic variations, the role of gene-nutrient interactions, gene-diet-phenotype interactions and epigenetic modifications caused by nutrients; these studies will facilitate an understanding of the early molecular events that occur in DM and will contribute to the identification of better biomarkers and diagnostics tools. In particular, this approach will help to develop tailored diets that maximize the use of nutrients and other functional ingredients present in food, which will aid in the prevention and delay of DM and its complications. This review discusses the current state of nutrigenetics, nutrigenomics and epigenomics research on DM. Here, we provide an overview of the role of gene variants and nutrient interactions, the importance of nutrients and dietary patterns on gene expression, how epigenetic changes and micro RNAs (miRNAs) can alter cellular signaling in response to nutrients and the dietary interventions that may help to prevent the onset of DM.


Macroscopic and microscopic diversity of missplicing in the central nervous system of patients with myotonic dystrophy type 1.
Myotonic dystrophy type I (DM1) is a multiorgan disease caused by CTG-repeat expansion in the DMPK gene. Sequestration of the splicing factor MBNL1 results in aberrant splicing in many genes in DM1 skeletal muscle, whereas MBNL2 plays a leading role in missplicing in the central nervous system (CNS) of patients with DM1. Splicing misregulation of most MBNL2-regulated genes occurs in the temporal cortex but not in the cerebellum of autopsied patients with DM1. To understand the diversity at macroscopic and microscopic levels in CNS of patients with DM1. Using autopsied brain tissues, we examined alternative splicing ratios of MBNL2-regulated genes and expression levels of potential splicing factors. We found differences in splicing abnormalities among tested regions of the CNS from patients with DM1. In the frontal and temporal cortices and the hippocampus, many genes were aberrantly spliced, but severity differed among the brain regions. By contrast, there were no significant differences in the ratio of splicing variants for most of the genes in the cerebellar cortex and spinal cord between DM1 and control samples. We failed to find any change in the amount of potential factors (MBNL and CUGBP proteins and DMPK mRNA) which explain the modest missplicing in the cerebellum. LASER capture microdissection demonstrated splicing misregulation in the molecular layer of the cerebellum but not in the granular layer. This is the first study to reveal missplicing in a functional cell layer of DM1 and to compare splicing misregulation in a wide region of the CNS using statistical analysis.


Resilience and sexual health among menopausal women: a cross-sectional study.
Resilience can be defined as the capacity to overcome stressful situations, such as menopausal transition. Female sexual dysfunction is a problem that prevents women from experiencing satisfaction from sexual activity. In this study, we assessed resilience, sexual function, and quality of life among a sample of mid-aged Spanish menopausal women. This cross-sectional study was performed in 101 symptomatic menopausal women. Participants filled out the 14-item Wagnild and Young Resilience Scale, the 19-item Female Sexual Function Index (FSFI), the 16-item Cervantes-SF form, and a sociodemographic questionnaire. Resilience scores were significantly higher among women with high sexual function scores (FSFI > 26), with a 14-item Wagnild and Young Resilience Scale total valuation of 86 [80-94] versus 74 [66-79.50] (P<0.001). Sexual function was significantly worse in the low resilience subgroup of participants, with an FSFI total score of 18.90 [14.10-24] versus 29.40 [24.60-33] in the mid-high resilience one (P<0.001). Menopauserelated quality of life was significantly worse among low resilient women, with a Cervantes-SF total score of 42.50 [34.17-56.70] versus 30.80 [20.80-44.90] in the mid-high resilience one (P = 0.004). In our sample, resilience was related to sexual health. Higher resilience scores seem to be linked to a better quality of life during the menopausal transition.


Primer requirement and template specificity of a DNA polymerase of chick embryo.
A DNA polymerase purified from extracts of chick embryo catalyzes the synthesis of poly(dT) in the presence of poly(rA) or poly(dA) as template and poly(dT) or oligo(dT) as primer. Oligo- or polyribonucleotides are relatively ineffective initiators of polydeoxynucleotide polymerization. Using activated DNA as template, the enzyme catalyzes a repair-like reaction that resembles that catalyzed by RNA-directed DNA polymerase of RNA tumor viruses and Escherichia coli DNA polymerase II. With natural templates containing poly(rA) sequences, such as avian myeloblastosis virus RNA or rabbit globin mRNA, and oligo(dT) as initiator, principally poly(dT) is synthesized. Consequently, the enzyme differs from the RNA-directed DNA polymerase associated with RNA tumor viruses by its incapacity to transcribe heteropolymeric regions of RNA templates. The possible role of the enzyme in repair of DNA during transcription is discussed.


AMEE 2009 spotlight on educational research.
The AMEE meeting is unique among the medical education conferences in that it is truly international. Educational research presented at the 2009 AMEE Meeting was both diverse and robust. In this article, we will present an overview of educational research from the meeting. We will begin with outlining our methods for the selection and categorization of themes, discuss some highpoints from some of the respective themes, and finally from the conference overall.


Treatment of Pisotriquetral Arthritis by Pyrocarbon Interposition Arthroplasty.
Purpose Pisiformectomy is the baseline treatment for pisotriquetral arthritis when medical treatment fails to address the problem. This operation may lead to loss of mobility and strength in the wrist. This study reports the short-term outcomes of a new technique for treating pisotriquetral arthritis using a pisotriquetral interposition arthroplasty with a pyrocarbon implant. Patients and Methods We performed a clinical and radiographic study on a series of eight patients who received this treatment at a mean follow-up of 2.8 years. We also studied the mobility of the implant and did assessed articular instability using dynamic radiology and fluoroscopy. Results We observed one proximal dislocation of the implant in one hand which was reoperated to reposition the implant and strengthen the capsule. All patients were satisfied or very satisfied with their operation and had an average functional recovery period of 1.6 months. At the last follow-up, the Mayo Wrist Score (MWS), Quick Disability of Arm Shoulder and Hand (QDASH), and Patient-Rated Wrist Evaluation (PRWE) scores were 89, 18, and 20, respectively. Postoperatively, there was a 22% improvement in the grip strength of the wrists as well as improved mobility, mainly as regards the radioulnar deviation (47% improvement) and the Visual Analogue Scale (VAS) pain scores decreased from 8 preoperatively to 2 at the latest follow-up. The functional radiologic and fluoroscopic study reported good adaptive mobility of the implant in all the patients, without any indication of pisotriquetral joint instability. Conclusion The short-term results of pisotriquetral arthroplasty using the Pyrocardan implant are encouraging. This new surgical solution appears to be a valid alternative to pisiformectomy or pisotriquetral arthrodesis. Long-term studies are required to confirm these preliminary findings.