Antitumor activity of novel octalactin A analogs in murine leukemia cells in vitro.
Octalactin A and B (code names K1 and K2) are eight-membered-ring lactones from a marine bacterium. K1 is reportedly cytotoxic. Since access to this natural product is severely limited, the entire synthesis of K1 has been achieved in K. Buszek's laboratory, and several of its structural and stereochemical analogs (code names K3-K9) have been tested for their ability to prevent murine L1210 leukemic cells from synthesizing macromolecules and growing in vitro. At 50 microM, K1 is inactive and the eight-membered lactone K4, an oxocene, is the only compound found to inhibit tumor cell growth by about 90% in the L1210 system. The long-term inhibition of L1210 cell growth by K4 is concentration dependent (IC50 around 10 microM) and not reversible following drug removal. The delayed and weaker cytotoxic effects of K4 suggest that the inhibition of tumor cell proliferation observed 1-4 days after K4 treatment is not solely caused by drug cytotoxicity. When compared to a spectrum of representative anticancer drugs, higher concentrations of K4 must be used to maximally inhibit tumor cell growth. In contrast to its antiproliferative activity, 50 microM K4 fails to alter the rates of DNA, RNA and protein synthesis in L1210 cells. This discrepancy between the ability of K4 to inhibit macromolecule synthesis and leukemic cell growth suggests that other molecular targets are involved in the antitumor action of this drug. At 50 microM, K4 inhibits the polymerization of purified tubulin by about 45%, and therefore may be a novel microtubule de-stabilizing drug weaker than vincristine. Even though other mechanisms may be involved in its antitumor action, the ability of K4 to partially disrupt microtubule dynamics indirectly suggests that this synthetic oxocene may be a cell cycle-specific anticancer drug that blocks mammalian cells in M-phase.


Heatstroke during endurance exercise: is there evidence for excessive endothermy?
Five of 28,753 cyclists participating in an annual 109-km bicycle race died, four within 24 h of the race and the fifth 17 d later. All five deaths were reported to be the consequence of exertional heatstroke. One runner of 6874 participating in an annual 56-km ultramarathon developed heatstroke and required active cooling for 10 h to achieve normothermia. The purpose of this article was to postulate (i) why only 6 of 35,627 athletes were hospitalized for heatstroke in these races, (ii) if exercise alone could have elevated their body temperatures sufficiently to cause heatstroke, and (iii) why the runner required such prolonged cooling. Clinical and autopsy data are presented for three of the cyclists and the runner for whom access to this information was granted. Calculations were made to predict the work rates necessary to produce their measured rectal temperatures. The rectal temperatures of two of the cyclists were 42.0 and 41.2 degrees C on hospitalization, and that of the runner was 41.8 degrees C on collapse. Standard calculations showed that in the prevailing environmental conditions and with their exercise speeds, none should have developed exertional heatstroke. The third cyclist experienced a cardiac arrest to which his elevated (rectal) temperature may have contributed. The hyperthermic states experienced by the cases presented may have resulted from failure of their heat-losing mechanisms. Alternatively, they might have resulted from excessive endothermy, triggered by physical exertion and other unknown initiating factors. Excessive endothermy should be considered in cases of heatstroke that occur in mild to moderate environmental conditions. Furthermore, prompt initiation of cooling is crucial in all cases of suspected heatstroke.


Alcohol disrupts sleep homeostasis.
Alcohol is a potent somnogen and one of the most commonly used "over the counter" sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to unravel the mechanism of alcohol-induced sleep disruptions. We have conducted a series of experiments using two different species, rats and mice, as animal models. We performed microdialysis, immunohistochemical, pharmacological, sleep deprivation and lesion studies which suggest that the sleep-promoting effects of alcohol may be mediated via alcohol's action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Since binge alcohol consumption is a highly prevalent pattern of alcohol consumption and disrupts sleep, we examined the effects of binge drinking on sleep-wakefulness. Our results suggest that disrupted sleep homeostasis may be the primary cause of sleep disruption observed following binge drinking. Finally, we have also shown that sleep disruptions observed during acute withdrawal, are caused due to impaired sleep homeostasis. In conclusion, we suggest that alcohol may disrupt sleep homeostasis to cause sleep disruptions.


SEX ALLOCATION AND MALE FITNESS GAIN IN A COLONIAL, HERMAPHRODITIC MARINE INVERTEBRATE.
While simultaneous hermaphroditism occurs in most animal phyla, theories for its adaptive significance remain untested. Sex allocation theory predicts that combined sexes are favored in sedentary and sessile organisms because localized gamete dispersal and local mate competition (LMC) among gametes promote decelerating fitness "gain curves" that relate male investment to reproductive success. Under this LMC model, males fertilize all locally available eggs at low sperm output, additional output leads to proportionally fewer fertilizations, and combined sexes with female-biased sex allocation are favored. Decelerating male gain curves have been found in hermaphroditic flowering plants, but the present paper reports the first analysis in an animal. The colonial hermaphroditic bryozoan Celleporella hyalina forms unisexual male and female zooids that can be counted to estimate absolute and relative gender allocations. I placed "sperm donor" colonies-each with different numbers of male zooids, and each homozygous for diagnostic allozyme alleles-among target maternal colonies on field mating arrays, and estimated donor fertilization success by scoring allozyme markers in target-colony progeny. Fertilization success increased with numbers of donor male zooids, but linear and not decelerating curves fit the data best. Mean sex allocation was not female biased, consistent with nondecelerating male gain. Sperm donors, moreover, did not monopolize matings as expected under high LMC, but rather shared paternity with rival colonies. Hence localized water-borne gamete dispersal alone may not yield decelerating male gain and favor the maintenance of hermaphroditism; relaxed sperm competition in low density populations might also be required. In free-spawning marine organisms, males cannot control access to fertilizations, intense sperm competition may be commonplace, and high male sex allocation may be selected to enhance siring success under competition.


The number, speed, and impact of plastid endosymbioses in eukaryotic evolution.
Plastids (chloroplasts) have long been recognized to have originated by endosymbiosis of a cyanobacterium, but their subsequent evolutionary history has proved complex because they have also moved between eukaryotes during additional rounds of secondary and tertiary endosymbioses. Much of this history has been revealed by genomic analyses, but some debates remain unresolved, in particular those relating to secondary red plastids of the chromalveolates, especially cryptomonads. Here, I examine several fundamental questions and assumptions about endosymbiosis and plastid evolution, including the number of endosymbiotic events needed to explain plastid diversity, whether the genetic contribution of the endosymbionts to the host genome goes far beyond plastid-targeted genes, and whether organelle origins are best viewed as a singular transition involving one symbiont or as a gradual transition involving a long line of transient food/symbionts. I also discuss a possible link between transporters and the evolution of protein targeting in organelle integration.


Common systemic medications that every optometrist should know.
Healthcare in the twenty-first century has witnessed an increased use of prescription drugs. As a member of a patient's health care team, optometrists should be aware of the pharmaceuticals taken by patients and their potential ocular complications. This paper will discuss the most prescribed medications in Australia today and their effects on the visual system. The paper will review the agents used to treat six common systemic conditions, their frequency of use, mechanism of action, clinical indications, and potential ocular manifestations. Literature has documented both positive and negative associations of systemic medications on the eye's health. Many associations documented here have shown conflicting evidence, thus warranting further investigation. Based on the frequency and severity of the ocular manifestations in the literature, recommendations for clinical care are given. Being familiar with the most common ocular side effects associated with common systemic medications aids in the correct and timely diagnosis of ocular complications to prevent permanent sequelae.


Impact of Combined Theory-Based Intervention on Psychological Effects and Physical Activity among Chinese Adolescents.
The current study was intended to assess the effect of a facilitated behavioral intervention based on the extended theory of planned behavior (TPB) on psychological constructs and physical activity among adolescents over a period of eight weeks. Students (n = 51, 12 ± 0.3 years of age) in the seventh grade at a junior middle school in China were randomly assigned to two groups: the intervention group (n = 24) and the control group (n = 27). Both groups were pre- and post-tested with the related psychological constructs of the extended TPB, along with behavioral measures of the Physical Activity Scale and ActiGraph accelerometer (model wGT3X-BT). The intervention group took part in 45 min classes once per week for 8 weeks, including five indoor theoretical courses and three outdoor basketball matches. The control group was not required to make any change to their normal school day. Also, 2 × 2 repeated measures analysis of variance (ANOVA) was conducted to compare the differences between the two groups, and then t-test was employed to compare the independent and paired differences. Significant increases in pre-post subjective norms (SN) (p = 0.041, Cohen's d = 0.62), perceived behavior control (PBC) (p = 0.023, Cohen's d = 0.72), exercise intention (EI) (p = 0.043, Cohen's d = 0.61), and self-efficacy (SE) (p = 0.035, Cohen's d = 1.36) were observed in the intervention group. In addition, participants in the intervention group increased their exercise frequency (p < 0.001, Cohen's d = 1.25) and intensity (p = 0.028, Cohen's d = 0.68), especially their time spent on light intensity physical activity (light-PA%; p = 0.031, Cohen's d = 0.68), and their percentage of sedentary time (SB%) was also reduced (from 68% ± 10% to 58% ± 7%, p < 0.001, Cohen's d = 1.17). Furthermore, the intervention group showed significantly better performance in PBC (p = 0.032, Cohen's d = 0.62), EI (p < 0.001, Cohen's d = 1.32), SE (p < 0.001, Cohen's d = 1.15), SB% (p < 0.001, Cohen's d = 1.22), light-PA% (p < 0.001, Cohen's d = 1.12), and total physical activity (TPA) (p = 0.015, Cohen's d = 0.72) compared to the control group at the post-test. No significant pre post differences were observed for any psychological or behavioral variables in the control group, except for exercise frequency, but the values were still lower than those in the intervention group after the 8-week intervention (3.70 ± 0.72 versus 3.92 ± 0.83). The combined theory-based intervention was effective at improving psychological constructs and physical activity among seventh-grade adolescents in 8 weeks.


Constitution and Smoking.
Among 167 adult male factory workers of Neapolitan parentage but of American birth or upbringing, the lean men smoked significantly more than the fat ones. Smoking was positively correlated with serum cholesterol but was not associated with morphological masculinity, blood pressure, diet, or consumption of alcohol.


Treatment of large lumbar disc herniation with percutaneous ozone injection via the posterior-lateral route and inner margin of the facet joint.
To evaluate the effects of percutaneous ozone injection via the posterior-lateral route and inner margin of the facet joint in the treatment of large lumbar disc herniation. Fifty-eight patients with large lumbar disc herniation were treated with percutaneous injection of ozone via the posterior-lateral route and inner margin of the facet joint under digital subtraction angiography. Second injections were performed 5 d after the initial injection. All patients were followed up for 6-18 mo. A modified Macnab method was used for assessing clinical outcomes after oxygen-ozone therapy. Successful puncture was obtained in all patients. The overall efficacy was 91.4%; the outcome was the excellent in 37 cases (63.8%), good in 16 cases (27.6%) and fair/poor in 5 cases (8.6%) according to the Macnab criteria. No severe complications were found throughout this study. Percutaneous intradiscal ozone injection via the posterior-lateral route and inner margin of the facet joint is effective and safe for treatment of large lumbar disc herniation.


Lung Transplantation for COPD.
In appropriately selected patients with COPD and alpha1-antitrypsin deficiency emphysema, lung transplantation prolongs life, improves functional capacity, and enhances quality of life. However, rejection remains an obstacle to better medium-term results, and lung transplantation is a treatment, not a cure and not a panacea.


A Lifespan Developmental-Stage Approach to Tobacco and Other Drug Abuse Prevention.
At least by informal design, tobacco and other drug abuse prevention programs are tailored to human developmental stage. However, few papers have been written to examine how programming has been formulated as a function of developmental stage throughout the lifespan. In this paper, I briefly define lifespan development, how it pertains to etiology of tobacco and other drug use, and how prevention programming might be constructed by five developmental stages: (a) young child, (b) older child, (c) young teen, (d) older teen, and (e) adult (emerging, young-to-middle and older adult substages). A search of the literature on tobacco and other drug abuse prevention by developmental stage was conducted, and multiple examples of programs are provided for each stage. A total of 34 programs are described as examples of each stage (five-young children, 12-older children, eight-young teens, four-older teens, and five-adults). Implications for future program development research are stated. In particular, I suggest that programming continue to be developed for all stages in the lifespan, as opposed to focusing on a single stage and that developmentally appropriate features continues to be pursued to maximize program impact.


Portraits of people with mental disorders in English Canadian history.
This paper will discuss the ways in which academic and non-academic historians in English Canada have portrayed people with mental disorders. The phrase "people with mental disorders" refers to individuals who were considered mentally disturbed by their contemporaries and/or by historians. This includes discussion of people who were in mental institutions as well as people who were never confined. Citations are from both detailed studies and fleeting references on this topic. Areas considered include portraits of people with mental disorders as being anonymous, passive, active, named, dangerous, untrustworthy; they also include the problem of stereotypes in the writing of this history.


The effects of temperature and dissolved oxygen on antioxidant defences and oxidative damage in the fathead minnow Pimephales promelas.
Fathead minnows Pimephales promelas maintained at 25° C for 6 h had significantly higher superoxide dismutase (SOD) activity than fish maintained at 7 or 32° C, but hypoxic conditions (3 mg l(-1) O2 ) over the same time period did not affect SOD activity. Fish in better body condition (length-adjusted mass) had higher SOD activity. In a separate experiment, P. promelas maintained at three water temperatures (7, 23 and 32° C) for 31 days did not differ in liver acrolein, a biomarker of oxidative stress.


Atomic Force Microscopy Study of the Anti-inflammatory Effects of Triptolide on Rheumatoid Arthritis Fibroblast-like Synoviocytes.
High-resolution atomic force microscopy (AFM) was used for the in situ evaluation of the anti-inflammatory effects of triptolide on rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) to understand the anti-RA effects of triptolide, based on the morphological and biophysical changes observed in RA-FLS. RA-FLS have been reported to play a primary role in inflammatory bone destruction during the development of RA and thus are regarded as an important target for RA treatment. Triptolide pretreatment significantly inhibited tumor necrosis factor-α-induced expression of the interleukin (IL)-1β, IL-6, and IL-8 genes in MH7A cells. Using AFM, we showed that triptolide-induced morphological damage in MH7A cells by inducing significant ultrastructure changes in the membrane, which were closely related to triptolide-induced apoptosis in MH7A cells. Using force measurements determined with AFM, triptolide was shown to increase the stiffness of MH7A cells. These findings not only revealed the strong anti-inflammatory effects of triptolide on RA-FLS, highlighting triptolide as a potential anti-RA agent, but also revealed the possible use of AFM for studying anti-inflammatory responses in RA-FLS, which we expect to be developed into a potential tool for anti-RA drug studies in RA-FLS.


Magnetic Molecularly Imprinted Polymers: Synthesis and Applications in the Selective Extraction of Antibiotics.
Recently, magnetic molecularly imprinted polymers (MMIPs) have integrated molecular imprinting technology (MIT) and magnetic separation technology and become a novel material with specific recognition and effective separation of target molecules. Based on their special function, they can be widely used to detect contaminants such as antibiotics. The antibiotic residues in the environment not only cause harm to the balance of the ecosystem but also induce bacterial resistance to specific antibiotics. Given the above consideration, it is especially important to develop sensitive and selective methods for measuring antibiotics in the complex matrix. The combination of MMIPs and conventional analytical methods provides a rapid approach to separate and determine antibiotics residues. This article gives a systematic overview of synthetic approaches of the novel MMIPs materials, briefly introduces their use in sample pretreatment prior to antibiotic detection, and provides a perspective for future research.


RNAi: running interference for the cell.
RNA interference or RNAi is a recently characterized mechanism of eukaryotic gene regulation in which a short sequence of double-stranded RNA (dsRNA) specifically down-regulates expression of the associated gene. Preliminary characterization of this phenomenon has revealed a set of inter-related cellular pathways which appear to represent both a response to foreign RNA and a mechanism of endogenous gene regulation. Introduction of dsRNA into cells by a variety of means, including transfection of synthetic RNA duplexes, triggers the RNAi response resulting in specific suppression of target gene expression. Recent efforts on a genome wide scale have involved application of RNAi as an important new tool in cell biology to elucidate gene function in living cells.


Gender Differences in Attitudes Toward Death Among Chinese College Students and the Implications for Death Education Courses.
This study aims to explore the attitudes of college-age students to determine how they approach the idea of death by using a questionnaire that explores five separate dimensions of attitudes and beliefs. We received 1,206 completed surveys and found evidence of a substantial gender difference in attitudes toward death. These differences remain after adjustment for differences between males and females in other correlates of death attitudes and are not a function of gender differences in the dimensionality of the five scales used to characterize attitudes. We speculate that these differences originate in culturally defined expectations that are gender-related, as well as in substantial differences in individual family experiences of death. These speculations can take the form of testable hypotheses that should explain differences within genders as well as between genders. We believe that better education about death for college students can shape a healthier mental state among them.


Effect of bisphosphonates on local recurrence of giant cell tumor of bone: a meta-analysis.
Giant cell tumor of bone (GCTB) is a locally aggressive tumor, and its postoperative recurrence remains a problem. The present meta-analysis aimed to analyze the effect of bisphosphonates (BPs) on local recurrence of GCTB. Seven case-control studies were included by computerized searches of bibliographic databases (PubMed, AMED, EMBASE, the Cochrane library, ISI Web of Science, and China National Knowledge Infrastructure). The pooled adjusted ORs were calculated to evaluate the local recurrence of GCTB. The BP group presented significantly lower total local recurrence rate than the control group in GCTB (P<0.01). Subgroup analysis shows BP group presented significantly lower local recurrence than the control group in GCTB with different tumor grades (P<0.05). In patients who underwent intralesional curettage, a significantly lower local recurrence rate was found in the BP group compared with the control group (P<0.01), but no significance was found for patients who underwent wide resection (P=0.16). None of the included studies described severe adverse effects related to BPs. The results confirmed the effect of BPs on reducing the local recurrence of GCTB, and the effect is not influenced by the tumor grades. BPs are benefit for the patients who underwent intralesional curettage but not recommended for those who underwent wide resection.


Effectiveness of supplemental vibrational force in reducing pain associated with orthodontic treatment: a systematic review.
The aim of this review was to systematically appraise the current evidence of utilizing vibration to reduce orthodontic pain. A comprehensive search was performed in ten databases. Only randomized controlled trials (RCTs) with patients receiving orthodontic treatment accompanied by vibrational force application were included. Risk of bias was assessed using the Cochrane tool. The lack of reasonable homogeneity across studies prevented the quantitative synthesis of the data. Fifteen RCTs were included. Three out of four RCTs revealed lower pain levels in at least one time-point when aligners were enhanced by vibration. Three out of 11 RCTs found that vibration accompanying fixed appliances was effective in reducing orthodontic pain. All studies had different methodologic shortcomings including: performance bias due to lack of participants' blinding; inappropriate sample size calculation; nonuniform demographic characteristics of participants; high potential of retrospective documentation of pain perception; and attrition bias. It is difficult to answer the question of whether vibration alleviates orthodontic pain or not, especially with the multiple existing shortcomings. More precise research is needed. It is recommended to focus on comparing different vibrational variables in an attempt to find the optimal values that might contribute to pain reduction, including: vibrational frequency; magnitude; and number and duration of sessions per day. Based on the concept of stimulation-induced analgesia, it is suggested that future research highlights the number of vibration sessions/day.


Reproductive Health and Substance Use Education for Autistic Youth.
We provide an update on reproductive health education (RHE) and substance use prevention education (SUPE) participation for autistic youth compared with other youth with and without individualized education plans (IEPs) and 504 plans. The 800 000 autistic youth served by the US special education system need education to make informed decisions about reproductive health and substance use. Data were from the National Longitudinal Transition Study-2012, a survey designed to yield nationally representative estimates of the experiences of US youth. Autistic youth (n = 390) who received RHE and SUPE were compared with youth with all other IEP classifications (n = 4420), with a 504 plan (n = 350), and with no IEP or 504 plan (n = 980). All youth were ≥14 years old and able to self-report on a survey. Bivariate and multivariate regression analyses were performed for each group to identify characteristics associated with RHE and SUPE receipt. Autistic youth reported a significantly lower rate of RHE (47.4%) and SUPE (49.6%) inclusion versus students with no IEP or 504 plan (59.2% and 57.4%, respectively). Autistic girls were more than twice as likely to report RHE receipt than autistic boys (55.1% vs 45.9%). For autistic youth, no markers for receipt of SUPE were identified. Autistic youth are underserved when it comes to school-based RHE and SUPE, potentially undermining self-determination and leading to poorer lifespan health trajectories. Research and policy advocacy are needed to ensure that these youth have access to RHE and SUPE.


Oncogene expression in hepatic and biliary neoplasms of the fish Rivulus ocellatus marmoratus: correlation with histologic changes.
One day old mangrove rivulus (Rivulus ocellatus marmoratus) were exposed to 9 mg/l diethylnitrosamine (DEN) for 6 weeks, kept in water without DEN for an additional 18-20 months, then necropsied. Oncogene expression was detected by immunohistochemical staining of freeze-dried cryofixed livers. Positive controls for immunohistochemistry included tumors grown by injecting athymic nude mice with cell lines having known oncogene expression. Livers from 15 DEN-exposed fish contained 178 altered foci and neoplasms; 48% of these lesions over-expressed Ras, Myc, Fos, p53 or epidermal growth factor receptor (EGFR). Raf overexpression was not detected. Myc overexpression was positively correlated (P < 0.05) with smaller hepatocyte size in both hepatocellular neoplasms and in altered foci. Increased EGFR expression occurred primarily in inflamed lesions. Increased Ras expression in hepatocellular neoplasms was correlated with anaplasia, gamma-glutamyltranspeptidase activity and lesions that contained mixed acinar and trabecular profiles. Accumulation of p53 occurred more often in neoplasms than in altered foci and correlated with unusual cytoplasmic vacuoles. In hepatocellular neoplasms, Fos overexpression was correlated with increased cell diameter, nuclear pleomorphism, and enlarged nucleoli. Only 1/14 biliary neoplasms overexpressed an oncoprotein (Myc). None of the changes in oncoprotein expression were correlated with cell proliferation (bromodeoxyuridine staining). Although several of the correlations found in mangrove rivulus also occur in mammals, the general relevance of some of our findings can be determined only after they are confirmed in other species.


Development of primary central nervous system lymphoma associated with human immunodeficiency virus and JC virus infection.
We report here a case of a 37-year-old man with human immunodeficiency virus (HIV) infection followed by JC virus (JCV) infection and primary central nervous system lymphoma (PCNSL). The patient had been infected with HIV type 1 due to blood products for hemophilia A during infancy. He had progression of nervous symptoms and was diagnosed with progressive multifocal leukoencephalopathy (PML) clinically at the age of 36, when his CD4-positive lymphocyte counts ranged between 350 and 450/μl. Oral mefloquine, intravenous methylprednisolone pulse therapy, and intravenous immunoglobulin were not effective for the PML, and the patient entered a vegetative state. Brain biopsy revealed JCV infection without pathological findings of PML. Eight months after the clinical diagnosis of PML, he developed respiratory failure and brain magnetic resonance imaging revealed a mass lesion in the brain stem. The patient died 19 months after the diagnosis of PML. Autopsy findings were compatible with PCNSL. EBV-encoded small RNA-1-positive cells were not detected. We present a case of JCV-positive PCNSL with HIV infection complicated with clinical PML.


Reference interval estimation: Methodological comparison using extensive simulations and empirical data.
To statistically compare and evaluate commonly used methods of estimating reference intervals and to determine which method is best based on characteristics of the distribution of various data sets. Three approaches for estimating reference intervals, i.e. parametric, non-parametric, and robust, were compared with simulated Gaussian and non-Gaussian data. The hierarchy of the performances of each method was examined based on bias and measures of precision. The findings of the simulation study were illustrated through real data sets. In all Gaussian scenarios, the parametric approach provided the least biased and most precise estimates. In non-Gaussian scenarios, no single method provided the least biased and most precise estimates for both limits of a reference interval across all sample sizes, although the non-parametric approach performed the best for most scenarios. The hierarchy of the performances of the three methods was only impacted by sample size and skewness. Differences between reference interval estimates established by the three methods were inflated by variability. Whenever possible, laboratories should attempt to transform data to a Gaussian distribution and use the parametric approach to obtain the most optimal reference intervals. When this is not possible, laboratories should consider sample size and skewness as factors in their choice of reference interval estimation method. The consequences of false positives or false negatives may also serve as factors in this decision.


Bisphenol A triggers the malignancy of nasopharyngeal carcinoma cells via activation of Wnt/β-catenin pathway.
It is critical to understand the risk factors responsible for the tumorigenesis and progression of nasopharyngeal carcinoma (NPC). Bisphenol A (BPA) can regulate the estrogenic signals to modulate cancer progression, while its roles in NC were not investigated. Our present study revealed that the BPA can increase proliferation and migration of NPC cells while decrease the chemosensitivity to doxorubicin (Dox). The inhibitor of GSK-3β/β-catenin (LiCl) can restore BPA-induced cell proliferation of NPC cells, which is due to that BPA can decrease phosphorylation while increase expression and nucleus localization of β-catenin. Mechanistically, BPA can increase the mRNA stability of β-catenin (encoded by CTNNB1) via suppressing the expression of miR-214-3p, which can direct target the 3'UTR of β-catenin mRNA. Further, BPA can decrease phosphorylation of β-catenin via repressing the expression of CK1α. Collectively, our data showed that BPA can trigger the proliferation and malignancy of NPC cells via activation of Wnt/β-catenin pathway. It indicated that body accumulation and inhalation exposure of BPA might be a risk factor for NPC development.


Quantitative RT-PCR for inhibin/activin subunits: measurements of rat hypothalamic and ovarian inhibin/activin subunit mRNAs during the estrous cycle.
Inhibins (alpha-beta(A) and alpha-beta(B)) and activins (beta(A)-beta(A), beta(A)-beta(B) and beta(B)-beta(B)) were originally isolated from ovarian follicular fluids as FSH secretion modifiers. Inhibin/activin subunits, alpha, beta(A) and beta(B), are widely distributed in several tissues, including gonads and brain, and inhibins and activins have been reported to be involved in ovarian or hypothalamic functions. In this study, we established and employed a competitive RT-PCR assay system for rat inhibin/activin subunits by capillary electrophoresis to determine rat hypothalamic and ovarian inhibin/activin subunit mRNA levels during the estrous cycle. Linearity of standards for alpha, beta(A), and beta(B) subunit assays were between 0.01-0.3 amol, 0.003-0.09 amol and 0.002-0.02 amol of each fragment DNA as a standard, respectively. Hypothalamic beta(A) subunit mRNA during the estrous morning (1000 h) tended to be increased compared with that of the proestrous evening (1700 h), although they were not significantly different. Ovarian alpha subunit mRNA levels tended to be increased during the proestrous morning (1000 h) and were significantly increased in the proestrous evening (1700 h), compared with diestrus and estrus (P < 0.05). Ovarian beta(A) subunit mRNA was also significantly higher in the proestrous evening, compared with diestrus and estrus (P < 0.05), but in the case of beta(B) subunit mRNA there was no difference among diestrus, proestrus and estrus. We thus established a sensitive competitive RT-PCR system for the measurement of inhibin/activin alpha, beta(A) and beta(B) subunits, and this assay system would be helpful for the study of inhibin/activin action in brain and other tissues where these factors are expressed at low levels.


The Self and Its Prolonged Intrinsic Neural Timescale in Schizophrenia.
Schizophrenia (SCZ) can be characterized as a basic self-disorder that is featured by abnormal temporal integration on phenomenological (experience) and psychological (information processing) levels. Temporal integration on the neuronal level can be measured by the brain's intrinsic neural timescale using the autocorrelation window (ACW) and power-law exponent (PLE). Our goal was to relate intrinsic neural timescales (ACW, PLE), as a proxy of temporal integration on the neuronal level, to temporal integration related to self-disorder on psychological (Enfacement illusion task in electroencephalography) and phenomenological (Examination of Anomalous Self-Experience [EASE]) levels. SCZ participants exhibited prolonged ACW and higher PLE during the self-referential task (Enfacement illusion), but not during the non-self-referential task (auditory oddball). The degree of ACW/PLE change during task relative to rest was significantly reduced in self-referential task in SCZ. A moderation model showed that low and high ACW/PLE exerted differential impact on the relationship of self-disorder (EASE) and negative symptoms (PANSS). In sum, we demonstrate abnormal prolongation in intrinsic neural timescale during self-reference in SCZ including its relation to basic self-disorder and negative symptoms. Our results point to abnormal relation of self and temporal integration at the core of SCZ constituting a "common currency" of neuronal, psychological, and phenomenological levels.


Neonatal lupus erythematosus: studies on HLA class II genes and autoantibody profiles in Japanese mothers.
Neonatal lupus erythematosus (NLE) is a rare disorder of neonates characterized by two major clinical manifestations: congenital heart block and cutaneous lupus lesions. The disease is associated with placentally transferred maternal anti-Ro/SSA and/or La/SSB antibodies. To clarify possible class II HLA associations with maternal autoantibody responses, haplotypic and allelic distributions, along with the polymorphism of the MHC class II HLA alleles, were analyzed based on PCR-RFLP results in 25 Japanese mothers of two groups defined by precipitating autoantibody profiles. Among mothers with both anti-Ro/SSA and anti-La/SSB antibodies, but not those with anti-Ro/SSA alone, the class II haplotypes DRB1*1101-DQA1*0501-DQB1*0301 and DRB1*08032-DQA1*0103-DQB1*0601 as well as individual class II alleles DRB1*1101, DRB1*08032 and DQB1*0301 showed significantly increased frequencies compared to those in normal controls. All anti-Ro/SSA and anti-La/SSB positive mothers carried DRB1 alleles that shared the same amino acid residues at positions 14-31 and 71 of the DRB1 chain. These mothers also carried homozygous or heterozygous DQ6 and DQ3 alleles that shared the same amino acid residues at positions 27-36 and 71-77 of hypervariable regions of the DQB1 chain. Furthermore, all mothers with both anti-Ro/SSA and anti-La/SSB were homozygous for DPB1*0501. Nine of 10 anti-Ro/SSA and anti-La/SSB-positive mothers, but only 6 of 15 mothers with anti-Ro/SSA alone, had affected infants. Thus, our findings suggest that there may be immunogenetic differences among mothers according to their autoantibody profiles, and that mothers with both anti-Ro/SSA and anti-La/SSB are more likely to have infants with NLE than mothers with anti-Ro/SSA alone.


Spirometry in elderly laryngectomized patients: A feasibility study.
Laryngeal cancer is the second most common respiratory neoplasm after lung cancer. Laryngectomy is a well established treatment for larynx cancers which involve relevant anatomic alterations. Spirometry is an essential investigation tool for diagnosis and severity of respiratory diseases, difficult to perform in laryngectomees. 43 consecutive laryngectomized patients were enrolled from July 2014 to March 2015. Patients fulfilling inclusion criteria underwent spirometry at baseline assessment and after two days. During the examination, the spirometer was placed directly on the stoma of the patient, through mouthpiece "Spirometry Filter 74". At baseline, 26 eligible laryngectomees correctly performed the spirometry test with mouthpiece adhering to the stoma; 4 patients refused to perform the second spirometry after 2 days. The feasibility of spirometry examination in these patients was 100% despite difficulties in the execution of the test. The Pearson coefficient of reproducibility for FEV1, FVC and Tiffeneau Index was, respectively, 0.98, 0.94 and 0.77. Spirometry in laryngectomee patients is a feasible procedure for assessment of respiratory function; despite technical difficulties in the execution of the test, our results underline the reproducibility and repeatability of the spirometry. In conclusion, when performed within dedicated respiratory pathophysiology unit, spirometry is a reliable tool in the assessment and follow up of laryngectomees.


Therapeutic plasma exchange for Graves' disease in pregnancy.
Graves' disease in pregnancy may be associated with maternal, fetal and neonatal complications, which are proportionate to the severity of hyperthyroidism. Optimal management is detailed preconception counselling, achievement of an euthyroid state prior to conception, and close monitoring of thyroid function and thyroid-stimulating antibodies together with judicious use of anti-thyroid medications during pregnancy. A case of Graves' disease in pregnancy, complicated by pancytopenia, with a deterioration in thyroid function following cessation of thionamide therapy is described here. Therapeutic plasma exchange was subsequently used to achieve rapid control prior to thyroidectomy. Therapeutic plasma exchange is an effective treatment for hyperthyroidism where thionamides are ineffective or contraindicated, as a bridge to definitive management.


Ly antigens: markers of T cell function on mouse spleen cells.
By the use of Ly antisera and complement it is possible to remove subpopulations of mouse T cells from spleen cell suspension. It is shown that these Ly antisera are specific for the Ly alleles carried by the cells. Helper cells from primed or unprimed mice and cells which respond to Con A express Ly-1 antigen but little or no Ly-2 antigen (Ly-1+ phenotype) whereas cells which respond to PHA express both Ly-1 and Ly-2 antigens (Ly-1+2+ phenotype).


Ab initio random structure search for 13-atom clusters of fcc elements.
The 13-atom metal clusters of fcc elements (Al, Rh, Ir, Ni, Pd, Pt, Cu, Ag, Au) were studied by density functional theory calculations. The global minima were searched for by the ab initio random structure searching method. In addition to some new lowest-energy structures for Pd13 and Au13, we found that the effective coordination numbers of the lowest-energy clusters would increase with the ratio of the dimer-to-bulk bond length. This correlation, together with the electronic structures of the lowest-energy clusters, divides the 13-atom clusters of these fcc elements into two groups (except for Au13, which prefers a two-dimensional structure due to the relativistic effect). Compact-like clusters that are composed exclusively of triangular motifs are preferred for elements without d-electrons (Al) or with (nearly) filled d-band electrons (Ni, Pd, Cu, Ag). Non-compact clusters composed mainly of square motifs connected by some triangular motifs (Rh, Ir, Pt) are favored for elements with unfilled d-band electrons.


Retroperitoneal Kirschner wire migration after surgical treatment in a patient with cerebral palsy.
Although Kirschner (K)-wire is among the most commonly used implants in orthopedic surgeries, the migration of this material is a very rare complication. In this article, we present the case of a K-wire migration four years after the surgery detected during the routine control of a 10-year-old male patient who underwent surgical treatment due to the diagnosis of developmental hip dys-plasia on the cerebral palsy. The aim of this study was to raise the awareness regarding this complication particularly for the pediatric orthopedic surgeons, and to recommend the removal of the K-wire as soon as bone union occurs.


Comparative Analysis of Preoperative and Postoperative Muscle Mass around Hip Joint by Computed Tomography in Patients with Hip Fracture.
This study was conducted in order to assess changes in hip muscles by comparing results of preoperative and postoperative computed tomography (CT) in older patients who underwent surgery for treatment of hip fracture. A total of 50 patients (aged ≥65 years) who underwent surgery for treatment of intertrochanteric fractures (25 patients) and femoral neck fractures (25 patients) between February 2013 and February 2019 and underwent preoperative and postoperative pelvic CT were enrolled in the study. The cross-sectional area, attenuation and estimates of muscle mass of the gluteus medius, gluteus minimus, iliopsoas, and rectus femoris on the uninjured side were measured. Basic patient data (sex, age, height, weight, body mass index [BMI], bone mineral density [BMD], Harris hip score [HHS], and length of follow-up) were collected from medical records. No significant differences in sex, age, height, weight, BMI, BMD, HHS, and length of follow-up were observed between the two groups. No significant difference in the cross-sectional areas and attenuations of gluteus medius and gluteus minimus was observed after surgery; however, a statistically significant decrease was observed in those of iliopsoas and rectus femoris after surgery. Lower estimates with statistical significance of muscle mass of the iliopsoas and rectus femoris were observed on postoperative CT. Muscle mass of the hip flexor (iliopsoas, rectus femoris) showed significant decreases on postoperative CT compared with preoperative CT. Based on these findings, selective strengthening exercise for hip flexor should be beneficial in rehabilitation of hip fractures.


Thermoase-derived flaxseed protein hydrolysates and membrane ultrafiltration peptide fractions have systolic blood pressure-lowering effects in spontaneously hypertensive rats.
Thermoase-digested flaxseed protein hydrolysate (FPH) samples and ultrafiltration membrane-separated peptide fractions were initially evaluated for in vitro inhibition of angiotensin I-converting enzyme (ACE) and renin activities. The two most active FPH samples and their corresponding peptide fractions were subsequently tested for in vivo antihypertensive activity in spontaneously hypertensive rats (SHR). The FPH produced with 3% thermoase digestion showed the highest ACE- and renin-inhibitory activities. Whereas membrane ultrafiltration resulted in significant (p < 0.05) increases in ACE inhibition by the <1 and 1-3 kDa peptides, only a marginal improvement in renin-inhibitory activity was observed for virtually all the samples after membrane ultrafiltration. The FPH samples and membrane fractions were also effective in lowering systolic blood pressure (SBP) in SHR with the largest effect occurring after oral administration (200 mg/kg body weight) of the 1-3 kDa peptide fraction of the 2.5% FPH and the 3-5 kDa fraction of the 3% FPH. Such potent SBP-lowering capacity indicates the potential of flaxseed protein-derived bioactive peptides as ingredients for the formulation of antihypertensive functional foods and nutraceuticals.


Stress fiber dynamics as probed by antibodies against myosin.
The dynamics of microfilament bundles (stress fibers) in tissue culture cells were studied by microinjecting an affinity-purified polyclonal antibody against chicken gizzard myosin. This antibody cross-reacted exclusively with the light chains of nonmuscle myosin and should therefore bind to the head portion of myosin molecules. When injected in high concentrations (13-26 mg/ml), it disrupted stress fibers in a high proportion (60-80%) of rat and chicken embryo fibroblasts, as well as in PtK2 cells. Myosin was found collected in large aggregates probably comprising protein: antibody precipitates, while actin and alpha-actinin were not localized in any defined structures in stress fiber depleted cells. Fibroblasts rounded up, probably because of lack of tension-generating microfilament bundles. After several hours, stress fibers were seen to regrow again in the afflicted cells, even when myosin precipitates and excess antibody were still present. The extent of stress fiber disruption and the time point of their reappearance were dependent on the concentration of the injected antibody.


Evaluation of immature granulocyte counts by the XE-IG master: upgraded software for the XE-2100 automated hematology analyzer.
We evaluated an automated immature granulocyte (IG) count in the peripheral blood with the XE-IG Master (Sysmex Corporation). The XE-IG Master is the upgraded software package for the XE-2100 automated hematology analyzer. Reproducibility tests demonstrated a mean coefficient of variation of 7.02% for the IG percentage (IG%) and 6.93% for the absolute IG count. Correlations of the IG counts were assessed in two ways. A flow cytometric IG count using CD11b, CD16, and CD45 monoclonal antibodies and a manual differential count were used as reference methods. The regression equation and the correlation coefficient of the IG% for the flow cytometric reference count versus results with the XE-IG Master were: y = 0.91x + 0.10; r = 0.96. For the comparison with the manual differential count of promyelocytes, myelocytes, and metamyelocytes, the regression equation and correlation coefficient were: y = 0.81x + 1.27; r = 0.78. Samples were found to be stable up to 48 hours both at room temperature and when refrigerated. We investigated the clinical significance of the IG count as a new marker of acute inflammation. In this preliminary study, most samples with a high IG count had positive values for C-reactive protein and the erythrocyte sedimentation rate (positive sample rates were 84.0% and 95.0%, respectively) despite neutrophil counts within the normal range. Elevated IG counts correlated most closely with CD64 expression on polymorphonuclear cells and less so with the concentration of interleukin 6. Compared with other available inflammation markers, the IG count is rapidly generated with each full blood count at no extra cost and with no delay in sample analysis.


Retained placenta--a major cause of maternal morbidity.
Retained placenta is a condition when placenta is not delivered by 30 minutes after delivery of baby. It commonly occurs among those women who deliver at home and it is responsible for more of maternal morbidity and mortality. One reason behind this is it mostly occurs in home delivery where active management of third stage of labour is lacking and once it takes place it increases the chances of post partum haemorrhage (PPH) and sepsis irrespective of place of delivery. In this prospective study carried out in a Hospital which is located at a distance of 10-12 kilometers from the centre of the capital, we tried to find out the prevalence of retained placenta, its relation with the place of delivery, steps taken to manage the cases of retained placenta and morbidity in terms of blood loss and hospital stay. The frequency of retained placenta in this study is 3.96% with majority having home delivery (82.8%). Those women who had blood loss of more than 1 litre (4.0%) all were home deliveries. Among all 12.0% cases had severe anaemia and needed significant amount of blood transfusion. All cases with retained placenta were first tried with use of oxytocics and controlled cord traction followed by manual removal of placenta under general anaesthesia. All cases were successfully managed with control cord traction (CCT) except 18 cases who needed manual removal of placenta (MRP).


Quantification, characterisation and safety testing of foot-and-mouth disease virus antigens eluted from alhydrogel vaccines.
Different methods for the elution and the concentration of FMDV-antigen from formaldehyde-inactivated alhydrogel vaccines were compared. With locally produced vaccines the best results were obtained if the antigen was eluted with potassium phosphate buffer and the concentration was performed by ultrafiltration. Final recoveries of 50% of the 140-S antigen could be obtained. For innocuity control 1-3 mg of 140-S antigen was eluted from 21 vaccine. SDS-polyacrylamide gel electrophoresis and iso-electric focusing patterns of eluted antigen will be discussed.


Publicly available hospital comparison web sites: determination of useful, valid, and appropriate information for comparing surgical quality.
To explore hospital comparison Web sites for general surgery based on: (1) a systematic Internet search, (2) Web site quality evaluation, and (3) exploration of possible areas of improvement. A systematic Internet search was performed to identify hospital quality comparison Web sites in September 2006. Publicly available Web sites were rated on accessibility, data/statistical transparency, appropriateness, and timeliness. A sample search was performed to determine ranking consistency. Six national hospital comparison Web sites were identified: 1 government (Hospital Compare [Centers for Medicare and Medicaid Services]), 2 nonprofit (Quality Check [Joint Commission on Accreditation of Healthcare Organizations] and Hospital Quality and Safety Survey Results [Leapfrog Group]), and 3 proprietary sites (names withheld). For accessibility and data transparency, the government and nonprofit Web sites were best. For appropriateness, the proprietary Web sites were best, comparing multiple surgical procedures using a combination of process, structure, and outcome measures. However, none of these sites explicitly defined terms such as complications. Two proprietary sites allowed patients to choose ranking criteria. Most data on these sites were 2 years old or older. A sample search of 3 surgical procedures at 4 hospitals demonstrated significant inconsistencies. Patients undergoing surgery are increasingly using the Internet to compare hospital quality. However, a review of available hospital comparison Web sites shows suboptimal measures of quality and inconsistent results. This may be partially because of a lack of complete and timely data. Surgeons should be involved with quality comparison Web sites to ensure appropriate methods and criteria.


[The effect of mammographic screening on tumor size, axillary node status and the degree of histologic anaplasia].
Breast cancer is the most frequent malignant tumor in women in Hungary. Significant reduction of mortality has been brought about not only by the increasing efficiency of complex therapy but also by regular mammographic screening. Of the histopathological data of 633 patients operated with primary breast tumor at the 1st Surgical Clinic of the Debrecen Medical University between January 1st 2000 and December 31st 2004, the authors analyzed tumor diameter, axillary node status and the degree of histologic anaplasia and compared them with the data of mammographic screening. Of the "screened"patients, 70.7% were diagnosed with T1 size tumors, 28.5% with T2 size, and 0.8% with tumors bigger than that. In the "unscreened" patients, our findings were 44.3%, 45.9% and 9.8% respectively. Within T1 tumors, Tla tumors were found in 11%, TIb in 37.6% and T1c in 51.4% in the "screened" group of patients, while the "unscreened" group's results were 2.3%, 12.6% and 85% respectively. 72.7% of the "screened" patients and 56.2% of the "unscreened" patients were found to be axillary node-negative. A study of the degree of histologic anaplasia showed G-I tumors in 15.6%, G-IIs in 62.1% and G-IIIs in 22.3% of the "screened" patients. The corresponding values for the "unscreened" patients were 6.1%, 53.8% and 40.1%, respectively. The differences were highly significant (p < 0.001) in all the parameters investigated. The authors have found a significant increase in the proportion of node-negative patients and patients with smaller tumors even after the first round of mammographic screening and at less than 50% participation. It is to be hoped that a 20% reduction in mortality can be achieved by further increasing the rate of participation.


Quad-port multiservice integrated optically transparent automotive antenna for vehicular classification applications.
The demand for vehicular antennas increases in tandem with the need for multiple features in automobiles. The development of optically transparent antenna (OTA) has made it possible to deploy antennas on delicate surfaces such as glass. Earlier studies on OTA demonstrated its viability using materials such as transparent conducting oxides (TCO) and conductive polymers. A tri-band OTA is proposed in this paper for vehicular applications. The antenna operates at 1.8 GHz, 2.4 GHz and 3.39-12 GHz bands, covering automotive/wireless applications such as GSM, Bluetooth, Wi-Fi, vehicular communication and electronic toll collection. The proposed OTA is developed on soda lime glass, and the material TCO is used for the radiator and the ground plane. The antenna prototype is tested on windshield and in an anechoic chamber, the gain and efficiency are found to be greater than 1 dBi and 80%, respectively. Furthermore, a machine learning technique for vehicle classification is proposed, which could help in electronic toll collection, automatic vehicle identifier, and parking management applications. The presented algorithm achieves 80% classification accuracy with a minimum window size.


Antimutagenic activity of tea: role of polyphenols.
Tea is considered to be one of the most promising dietary chemopreventive agents and, consequently, it is being studied extensively worldwide. Despite the fact that tea has proved very efficient in affording protection against chemical-induced cancer in animal models of the disease, epidemiological studies do not always support the laboratory findings, so that the value of tea as a human anticarcinogen may be considered as 'not proven'. A major mechanism of the anticarcinogenic activity of tea in animals is impairment of the interaction of carcinogens with DNA leading to mutations. The antimutagenic activity of tea as well as the underlying mechanisms will be reviewed, and the role of polyphenols, the postulated bioactive components, and caffeine will be critically evaluated. In rats, exposure to tea modulated the disposition of heterocyclic amines, a major group of food-borne carcinogens, stimulating the pathways that lead to deactivation, and this is concordant with the established ability of tea to modulate the carcinogen-metabolizing enzyme systems. These observations provide a rational mechanism for the anticarcinogenic activity of tea in animals. The beneficial activities of tea have always been attributed to the polyphenols, as these are present in tea at substantial concentrations and are endowed with antioxidant activity. It is becoming increasingly evident, however, that the bioavailability of these compounds is poor as a result of limited absorption and presystemic metabolism by mammalian and microbial enzymes. We propose that the biological activity of tea may be mediated by caffeine and microbial metabolites of polyphenols.


Cognitive impairment and Alzheimer's disease: Links with oxidative stress and cholesterol metabolism.
Oxidative stress has been implicated in the progression of a number of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease and amyotrophic lateral sclerosis. We carried out an in-depth study of cognitive impairment and its relationships with oxidative stress markers such as ferric-reducing ability of plasma (FRAP), plasma malondialdehyde and total antioxidative capacity (TAC), as well as cholesterol parameters, in two subsets of subjects, AD patients (n = 59) and a control group of neurologically normal subjects (n = 29), attending the University Hospital Salvador in Santiago, Chile. Cognitive impairment was assessed by a set of neuropsychological tests (Mini-Mental State Examination, Boston Naming Test, Ideomotor Praxia by imitation, Semantic Verbal Fluency of animals or words with initial A, Test of Memory Alteration, Frontal Assessment Battery), while the levels of those oxidative stress markers and cholesterol metabolism parameters were determined according with standard bioassays in fresh plasma samples of the two subgroups of patients. No significant differences were observed when the cholesterol parameters (low-, high-density lipoprotein, total cholesterol) of the AD group were compared with normal controls. Interestingly, a correlation was evidenced when the levels of cognitive impairment were analyzed with respect to the plasma antioxidant capacity (AOC) of patients. In this context, the subset of subjects exhibiting cognitive impairment were divided into two subgroups according with their Global Dementia Scale performance: a subgroup with mild AD and a subgroup with moderate to severe AD. Significant differences in AOC were found between subgroups. The different correlations between cognitive impairment of subgroups of subjects with the oxidative stress profile are discussed in the context of AD pathogenesis.


Prenatal course of metaphyseal anadysplasia associated with homozygous mutation in MMP9 identified by exome sequencing.
Metaphyseal anadysplasia (MANDP) is a rare autosomal recessive form of skeletal dysplasia characterized by normal length at birth and transitory bowing of the legs. Although several families with MANDP have been reported, homozygous mutations in the matrix metalloproteinase type 9 (MMP9) gene have been described in only one consanguineous family, and thus the pre and postnatal phenotypic spectrum is still obscure. A clinically similar but more severe type is caused by autosomal-dominant inheritance and is caused by mutations in matrix metalloproteinase type 13 gene (MMP13). Here, we report the prenatal and early postnatal course of two affected sib fetuses with early sonographic evidence of long bone shortening and postnatally no metaphyseal changes. Whole-exome sequencing revealed homozygous mutation in MMP9 in both fetuses suggesting a diagnosis of MANDP. We propose that MANDP should be considered in pregnancies with early prenatal shortening of the long bones without associated finding of lethal skeletal dysplasias. In addition, the finding of homozygous mutation in non-consanguineous parents of Jewish-Caucasus ancestry may suggest unawareness of such relation or the occurrence of a founder mutation in this gene.


Late Cretaceous vicariance in Gondwanan amphibians.
Overseas dispersals are often invoked when Southern Hemisphere terrestrial and freshwater organism phylogenies do not fit the sequence or timing of Gondwana fragmentation. We used dispersal-vicariance analyses and molecular timetrees to show that two species-rich frog groups, Microhylidae and Natatanura, display congruent patterns of spatial and temporal diversification among Gondwanan plates in the Late Cretaceous, long after the presumed major tectonic break-up events. Because amphibians are notoriously salt-intolerant, these analogies are best explained by simultaneous vicariance, rather than by oceanic dispersal. Hence our results imply Late Cretaceous connections between most adjacent Gondwanan landmasses, an essential concept for biogeographic and palaeomap reconstructions.


Streptococcus mutans in plaque after mouth-rinsing with buffers of varying pH value.
After a period of mouthrinsing with a phosphoric buffer solution with low pH the proportional distribution of Streptococcus mutans in plaque from occlusal retention sites was significantly higher than after a control period. This indicates that colonization with S. mutans may be favored or that other microorganisms competing with S. mutans are inhibited under these circumstances.


ERP abnormalities of illusory contour perception in Williams syndrome.
Williams syndrome is a genetic disorder in which visuo-spatial performance is poor. Theorists have claimed that the deficit lies in high-level processing, leaving low-level visual processes intact. We investigated this claim by examining an aspect of low-level processing, perceptual completion, i.e. the ability of this clinical group to perceive illusory Kanizsa squares. We then used event-related potentials to examine neural correlates of perceptual completion. While participants were able to perceive illusory contours, the neural correlates of this apparently normal perception were different from controls. Such differences in low-level visual processes may significantly impact on the development of higher-level visual processes. We conclude that, contrary to earlier claims, there is atypical neural processing during low-level visual perception in Williams syndrome.


The nasopharyngoscope and camera examination of the primary carcinoma of nasopharynx.
The site of origin, the histology, the morphology, the extent, and the T category of the primary carcinoma of nasopharynx and their correlations, including incidence of cervical lymph node metastasis, of 159 consecutive cases seen in a period of four years are studied.


Oxygenic photosynthesis: history, status and perspective.
Cyanobacteria and plants carry out oxygenic photosynthesis. They use water to generate the atmospheric oxygen we breathe and carbon dioxide to produce the biomass serving as food, feed, fibre and fuel. This paper scans the emergence of structural and mechanistic understanding of oxygen evolution over the past 50 years. It reviews speculative concepts and the stepped insight provided by novel experimental and theoretical techniques. Driven by sunlight photosystem II oxidizes the catalyst of water oxidation, a hetero-metallic Mn4CaO5(H2O)4 cluster. Mn3Ca are arranged in cubanoid and one Mn dangles out. By accumulation of four oxidizing equivalents before initiating dioxygen formation it matches the four-electron chemistry from water to dioxygen to the one-electron chemistry of the photo-sensitizer. Potentially harmful intermediates are thereby occluded in space and time. Kinetic signatures of the catalytic cluster and its partners in the photo-reaction centre have been resolved, in the frequency domain ranging from acoustic waves via infra-red to X-ray radiation, and in the time domain from nano- to milli-seconds. X-ray structures to a resolution of 1.9 Å are available. Even time resolved X-ray structures have been obtained by clocking the reaction cycle by flashes of light and diffraction with femtosecond X-ray pulses. The terminal reaction cascade from two molecules of water to dioxygen involves the transfer of four electrons, two protons, one dioxygen and one water. A rigorous mechanistic analysis is challenging because of the kinetic enslaving at millisecond duration of six partial reactions (4e-, 1H+, 1O2). For the time being a peroxide-intermediate in the reaction cascade to dioxygen has been in focus, both experimentally and by quantum chemistry. Homo sapiens has relied on burning the products of oxygenic photosynthesis, recent and fossil. Mankind's total energy consumption amounts to almost one-fourth of the global photosynthetic productivity. If the average power consumption equalled one of those nations with the highest consumption per capita it was four times greater and matched the total productivity. It is obvious that biomass should be harvested for food, feed, fibre and platform chemicals rather than for fuel.


The dual-use dilemma for the life sciences: perspectives, conundrums, and global solutions.
The term "dual-use" traditionally has been used to describe technologies that could have both civilian and military usage, but this term has at least three different dimensions that pose a dilemma for modern biology and its possible misuse for hostile purposes: (1) ostensibly civilian facilities that are in fact intended for military or terrorist bioweapons development and production; (2) equipment and agents that could be misappropriated and misused for biological weapons development and production; and (3) the generation and dissemination of scientific knowledge that could be misapplied for biological weapons development and production. These three different aspects of the "dual-use dilemma" are frequently confused--each demands a distinct approach within a "web of prevention" in order to reduce the future risk of bioterrorism and biowarfare. This article discusses the nature of the different perspectives and divergent approaches as a contribution to finding a scientifically acceptable global solution to the problem posed by the dual-use dilemma. We propose that: (1) facilities that are intended for bioweapons development and production should be primarily prevented by a strengthened Biological and Toxin Weapons Convention (BTWC) effectively implemented in all nation states, one that includes provisions for adequate transparency to improve confidence and a mechanism for thorough inspections when there is sufficient cause, and enhanced law enforcement activities involving international cooperation and sharing of critical intelligence information; (2) potentially dual-use equipment and agents should be available to legitimate users for peaceful purposes, but strengthened national biosafety and physical and personnel biosecurity controls in all nations together with effective export controls should be implemented to limit the potential for the misappropriation of such equipment and materials; and (3) information should be openly accessible by the global scientific community, but a culture of responsible conduct involving the breadth of the international life sciences communities should be adopted to protect the ongoing revolution in the life sciences from being hijacked for hostile misuse of the knowledge generated and communicated by life scientists.


Biglycan- and Sphingosine Kinase-1 Signaling Crosstalk Regulates the Synthesis of Macrophage Chemoattractants.
In its soluble form, the extracellular matrix proteoglycan biglycan triggers the synthesis of the macrophage chemoattractants, chemokine (C-C motif) ligand CCL2 and CCL5 through selective utilization of Toll-like receptors (TLRs) and their adaptor molecules. However, the respective downstream signaling events resulting in biglycan-induced CCL2 and CCL5 production have not yet been defined. Here, we show that biglycan stimulates the production and activation of sphingosine kinase 1 (SphK1) in a TLR4- and Toll/interleukin (IL)-1R domain-containing adaptor inducing interferon (IFN)-β (TRIF)-dependent manner in murine primary macrophages. We provide genetic and pharmacological proof that SphK1 is a crucial downstream mediator of biglycan-triggered CCL2 and CCL5 mRNA and protein expression. This is selectively driven by biglycan/SphK1-dependent phosphorylation of the nuclear factor NF-κB p65 subunit, extracellular signal-regulated kinase (Erk)1/2 and p38 mitogen-activated protein kinases. Importantly, in vivo overexpression of soluble biglycan causes Sphk1-dependent enhancement of renal CCL2 and CCL5 and macrophage recruitment into the kidney. Our findings describe the crosstalk between biglycan- and SphK1-driven extracellular matrix- and lipid-signaling. Thus, SphK1 may represent a new target for therapeutic intervention in biglycan-evoked inflammatory conditions.


Chemical synthesis of a human fibroblast interferon gene and its expression in Escherichia coli.
Using the solid phase phosphotriester method, a gene coding for human fibroblast interferon consisting of 166 amino acid residues was chemically synthesized. The gene obtained by ligation of 61 synthesized oligodeoxyribonucleotide fragments was inserted into the downstream of tryptophan promoter, and expressed in E. coli. Lysate of this E. coli showed the antiviral activity which was specifically neutralized by anti-fibroblast interferon antibody. No particular advantage was observed in the expression efficiency by the synthetic gene over that by the native gene.


Self-Assembled Asperities for Pressure-Tunable Adhesion.
Control of adhesion is important in a host of applications including soft robotics, pick-and-place manufacturing, wearable devices, and transfer printing. While there are adhesive systems with discrete switchability between states of high and low adhesion, achieving continuously variable adhesion strength remains a challenge. In this work, a pressure-tunable adhesive (PTA) that is based on the self-assembly of stiff microscale asperities on an elastomeric substrate is presented. It is demonstrated that the adhesion strength of the PTA increases with the applied compressive preload due to the unique contact formation mechanism caused by the asperities. Additionally, a contact mechanics model is developed to explain the resulting trends. For a specific PTA design, the critical pull-off force can be increased from 0.4 to 30 mN by increasing the applied preload from 1 to 30 mN. Finally, the applicability of precision control of adhesion strength is demonstrated by utilizing the PTA for pick-and-place material handling. The approach in pressure-tunable adhesive design based on self-assembly of asperities presents a scalable and versatile approach that is applicable to a variety of material systems having different mechanical or surface properties.


Impacts of the 2003 and 2015 summer heatwaves on permafrost-affected rock-walls in the Mont Blanc massif.
Rockfall is one of the main geomorphological processes that affects the evolution and stability of rock-walls. At high elevations, rockfall is largely climate-driven, very probably because of the warming of rock-wall permafrost. So with the ongoing global warming that drives the degradation of permafrost, the related hazards for people and infrastructure could continue to increase. The heatwave of summer 2015, which affected Western Europe from the end of June to August, had a serious impact on the stability of high-altitude rock-walls, including those in the Mont Blanc massif. A network of observers allowed us to survey the frequency and intensity of rock-wall morphodynamics in 2015, and to verify its relationship with permafrost. These observations were compared with those of the 2003 summer heatwave, identified and quantified by remote sensing. A comparison between the two years shows a fairly similar rockfall pattern in respect of total volumes and high frequencies (about 160 rockfalls >100m3) but the total volume for 2003 is higher than the 2015 one (about 300,000m3 and 170,000m3 respectively). In both cases, rockfalls were numerous but with a low magnitude and occurred in permafrost-affected areas. This suggests a sudden and remarkable deepening of the active layer during these two summers, rather than a longer-term warming of the permafrost body.


Sirolimus on Gorham-Stout disease. Case report.
Gorham-Stout disease (GSD) is a rare disease of unknown etiology characterized by vascular proliferation that produces destruction of bone matrix. This case is about 43 year old woman who begins with pain in sternum, dyspnea, abdominal mass and, serous-hematic pleural effusion. Imaging tests were performed showing lesions on 6th and 10th left ribs archs. Later, a thoracotomy was performed observed absence of the end of the 6th and lung, pleural and costal biopsy was token. The histologic features described lymphatic vascular proliferation in bone tissue of chest wall. Other pathologies were excluded and in view of the findings, GSD diagnosis was made. treatment was initiated with sirolimus achieving remission of the disease after the first month; however, because the presence of metrorrhagia the treatment was discontinued, reappearing symptoms afterwards. For that reason the treatment was restarted getting disappearance of the symptoms again, 4 weeks later. we present the first clinical cases of EGS with pleural effusion with response to sirolimus treatment that could be an alternative to the current therapy.


The central representation of an aversive event maintains the opioid and nonopioid forms of analgesia.
Exposure to an aversive event, such as shock, can elicit either an opioid or nonopioid analgesia in rats. We suggest that the central representation of an aversive event in working memory activates both forms of analgesia. We formalize this basic hypothesis by coupling it with a current model of animal learning and memory, SOP (Wagner, 1981). SOP is designed to capture the standard operating procedures that govern memory systems. Our application of SOP suggests that manipulations which disrupt the maintenance of information in working memory should alter the magnitude and time course of analgesia. Three experiments are reported that support our proposal. Experiment 1 showed that analgesia decays more rapidly if the representation of the aversive event is displaced from working memory by presenting a postshock distractor. Experiment 2 demonstrated that the postshock distractor alters the magnitude and time course of both the opioid and nonopioid forms of analgesia. Experiment 3 demonstrated that pharmacologically disrupting working memory, by administering a high dose of pentobarbital, prevents mild shock from inducing a strong change in pain reactivity. Implications of the results are discussed.


Overexpression of a putative maize calcineurin B-like protein in Arabidopsis confers salt tolerance.
The calcineurin B-like proteins (CBLs) represent a unique family of calcium sensors in plants. Although extensive studies and remarkable progress have been made in Arabidopsis (Arabidopsis thaliana) CBLs, their functions in other plant species are still quite limited. Here, we report the cloning and functional characterization of ZmCBL4, a novel CBL gene from maize (Zea mays). ZmCBL4 encodes a putative homolog of the Arabidopsis CBL4/SOS3 protein, with novel properties. ZmCBL4 has one copy in maize genome and harbors seven introns in its coding region. ZmCBL4 expressed differentially in various organs of the maize plants at a low level under normal condition, and its expression was regulated by NaCl, LiCl, ABA and PEG treatments. Expression of 35S::ZmCBL4 not only complemented the salt hypersensitivity in Arabidopsis sos3 mutant, but also enhanced the salt tolerance in Arabidopsis wild type at the germination and seedling stages. Moreover, the LiCl tolerance in all of the ZmCBL4-expressing lines increased more significantly as compared with the NaCl tolerance, and in consistent with this, it was found that the expression of Arabidopsis AtNHX8, a putative plasma membrane Li+/H+ antiporter gene identified recently, was induced in these transgenic lines under LiCl stress. The ZmCBL4-expressing Arabidopsis lines accumulated less Na+ and Li+ as compared with the control plants. This study has identified a putative maize CBL gene which functions in the salt stress-elicited calcium signaling and thus in the tolerance to salinity.


Penetrating Traumas to the Parotid Region.
Penetrating trauma to the parotid gland is a rare condition. Mostly, gunshot wounds to the parotid area are seen. Facial paralysis and sialocele formation are particular concerns and may cause significant morbidities. Early diagnosis and early exploration are crucial in the setting of facial paralysis following penetrating trauma. Sialocele formation and fistulas can be managed conservatively or surgically.


[Results of morphologic epidemiologic study of coronary arteries in Kaunas population aged 20-69 years: atherosclerotic lesions and their interrelationship].
The object of study was the type, frequency and extent, as well as correlation of atherosclerotic lesions in Kaunas population aged 20-69 years. The frequency and intimal area of raised atherosclerotic lesions (fibrous and complicated plaque and calcinosis) are age-dependent. The increase of raised lesions area seems to alter at different decades of life. In men the most substantial progression in left anterior descending artery was observed at the fourth-fifth, in right coronary artery--at the fifth, and in both arteries of women - at the sixth decade of life. The area of fatty streaks is not dependent on age and comprises approximately 4-5% of intimal surface. We observed weak negative correlation between area of raised lesions and fatty streaks, and strong correlation between the area of all type of raised lesions in all three coronary arteries. The coronary artery atherosclerosis is progressing with age. Age decades, when increase of raised lesion area is observed, correspond to age periods, in which mortality due to ischemic heart disease increases significantly.


[Oral complications in patients with anorexia nervosa and bulimia nervosa].
This article presents the oral situation of 11 anorectic and 41 bulimic patients and compares it with 50 healthy control persons. While patients with an eating disorder showed less signs of gingival inflammation (SBI: anorexia: 14.6%; bulimia: 12.5%; controls: 44.7%), they had clearly more enamel erosions than healthy control persons. In 27 of 41 bulimic patients a bilateral swelling of the parotid gland was found. A significant correlation between the parotid enlargement and enamel erosion exists in bulimic patients with an anorectic prephase. Patients with an eating disorder had higher levels of serum amylase than healthy control persons. A significant correlation between serum amylase activity and dental characteristics was found in bulimic patients.


Plastic-embedded human marrow biopsy specimens: improved histochemical methods.
Improved methods for processing, sectioning, and staining plastic (glycol methacrylate)-embedded human marrow biopsy specimens were studied. Special stains, including naphthol AS-D-chloro-acetate esterase, PAS, reticulin, and iron, have been modified so that they are suitable for undecalcified, 2-microns-thick, plastic-embedded human marrow biopsy specimens. These adaptations permit plastic-embedded marrow specimens to be used for clinical diagnosis. Marrow biopsy specimens embedded in plastic were compared with biopsy specimens preserved by the conventional paraffin method. The plastic-embedded marrows provide better results from morphologic examination (enhancing diagnostic accuracy), permit assessment of bone as well as of marrow, and allow histochemical analysis to be performed.


Customized morphologies of self-condensed multisegment polymer nanowires.
The direct formation of multisegment nanowires consisting of polymer domains by ion beam irradiation is investigated. Cross-linking reactions in the ion tracks result in localized gelation, giving isolated nanowires on substrates. It is demonstrated that the morphology of the final nanostructure is customized by appropriate selection of the ion fluence, combination of polymers, and the solvent employed for development. Octopus-like nanostructures consisting of a tangled hydrophilic polymer core and splayed hydrophobic polymer segments are successfully produced as an example of the process. The present technique provides universal feasibility for the formation of nanostructures based on "any" polymer materials in which radiation induces cross-linking reactions.


Effects of adenine-nucleotides on the sequence-specificity of origin recognition complex-binding to DNA.
We examined effects of adenine-nucleotides on the sequence-specificity of origin recognition complex (ORC)-binding to DNA, using a gel electrophoretic mobility shift assay. The sequence-specific DNA binding of ORC was observed in the presence of ATP or ATP-gamma-S but not in the presence of adenosine 5'-diphosphate (ADP) or in the absence of any adenine-nucleotides. In contrast, the sequence-independent DNA binding of ORC was observed under any one of these conditions. These results suggest that ATP increases the sequence-specificity of ORC-binding to DNA. In relation to the requirement for incubation at high temperature and inhibition by cardiolipin, there was no significant difference between the sequence-specific and the sequence-independent DNA binding activities of ORC.


A population-based, postlicensure evaluation of the safety of a combination diphtheria, tetanus, acellular pertussis, hepatitis B, and inactivated poliovirus vaccine in a large managed care organization.
Prelicensure studies of diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio virus vaccine suggested that there were higher rates of fever after its administration than when its component antigens were given separately. We conducted an open, controlled, cohort study to evaluate selected potential adverse events after receipt of diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus vaccine in the Southern California Kaiser Permanente Health Care Plan. From April 2003 through June 2005, we identified 61,004 infants who received >or=1 dose of vaccine (120000 total doses). This group was compared with a previous cohort of 58,251 age-, gender-, and medical center-matched infants (116,637 doses) who received diphtheria, tetanus, acellular pertussis vaccine and separate doses of hepatitis B and inactivated poliovirus vaccines from January 2002 through March 2003. We compared the incidence of seizures, medically attended events that were associated with fever, and other selected adverse outcomes. We identified 16 infants (8 with fever) who had a seizure in the diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus cohort and 15 infants (6 with fever) among control subjects in the 8-day period after receipt of any dose of vaccine. The incidence of all seizures or seizures associated with fever was not significantly different between cohorts. The incidence of medically attended events that were associated with fever in the 4-day period after any dose of vaccine was also similar in both cohorts. As well, no significant differences between the diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and control cohorts, were noted in the incidence of allergic reactions within 48 hours of any dose of vaccine, outpatient visits within 21 days, hospitalizations within 21 days, or death within 1 year. We did not observe a statistically significant increase in any of several clinically important safety events after diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus vaccination compared with a historical cohort who received separate component vaccines.


Functional connectivity within and between intrinsic brain networks correlates with trait mind wandering.
Individual differences across a variety of cognitive processes are functionally associated with individual differences in intrinsic networks such as the default mode network (DMN). The extent to which these networks correlate or anticorrelate has been associated with performance in a variety of circumstances. Despite the established role of the DMN in mind wandering processes, little research has investigated how large-scale brain networks at rest relate to mind wandering tendencies outside the laboratory. Here we examine the extent to which the DMN, along with the dorsal attention network (DAN) and frontoparietal control network (FPCN) correlate with the tendency to mind wander in daily life. Participants completed the Mind Wandering Questionnaire and a 5-min resting state fMRI scan. In addition, participants completed measures of executive function, fluid intelligence, and creativity. We observed significant positive correlations between trait mind wandering and 1) increased DMN connectivity at rest and 2) increased connectivity between the DMN and FPCN at rest. Lastly, we found significant positive correlations between trait mind wandering and fluid intelligence (Ravens) and creativity (Remote Associates Task). We interpret these findings within the context of current theories of mind wandering and executive function and discuss the possibility that certain instances of mind wandering may not be inherently harmful. Due to the controversial nature of global signal regression (GSReg) in functional connectivity analyses, we performed our analyses with and without GSReg and contrast the results from each set of analyses.


Scope of practice review: providers for triage and assessment of spine-related disorders.
This study explored which health care providers could be involved in centralized intake for patients with nonspecific low back pain to enhance access, continuity, and appropriateness of care. We reviewed the scope of practice regulations for a range of health care providers. We also conducted telephone interviews with 17 individuals representing ten provincial colleges and regulatory bodies to further understand providers' legislated scopes of practice. Activities relevant to triaging and assessing patients with low back pain were mapped against professionals' scope of practice. Family physicians and nurse practitioners have the most comprehensive scopes and can complete all restricted activities for spine assessment and triage, while the scope of registered nurses and licensed practical nurses are progressively narrower. Chiropractors, occupational therapists, physiotherapists, and athletic therapists are considered experts in musculoskeletal assessments and appear best suited for musculoskeletal specific assessment and triage. Other providers may play a complementary role depending on the individual patient needs. These findings indicate that an interprofessional assessment and triage team that includes allied health professionals would be a feasible option to create a centralized intake model. Implementation of such teams would require removing barriers that currently prevent providers from delivering on their full scope of practice.


Transcatheter arterial chemoembolization therapy for patients with hepatocellular carcinoma: a case-controlled study.
Transcatheter arterial chemoembolization (TACE) currently is used as a palliative treatment for patients with unresectable hepatocellular carcinoma (HCC), but its efficacy still is debated. Our aim was to assess the impact of TACE on patient survival and to identify prognostic factors for survival. Fifty-six cirrhotic patients with unresectable HCC undergoing at least 1 course of TACE were matched 1:1 for sex, age (in 5-year periods), parameters of Child-Pugh score, Okuda stage, and tumor type with a control group who had received only supportive care. The 2 groups were comparable for cause of cirrhosis, alpha-fetoprotein serum levels, and Cancer of the Liver Italian Program (CLIP) score. The 56 patients in the TACE group received a total of 123 treatment courses. The median follow-up period was 16 months (range, 1-67 mo) in the TACE group and 5 months (range, 1-77 mo) in the supportive care group. Survival rates at 12, 24, and 30 months in patients receiving TACE were 74.3%, 52.1%, and 38.8%, respectively, with a median survival time of 25 months, whereas in supportive care patients the rates were 39.4%, 25.4%, and 19%, respectively, with a median survival time of 7 months (P = .0004). At univariate analysis, TACE, tumor type, presence of ascites, alpha-fetoprotein serum level, CLIP score, and Okuda stage were associated significantly with survival. Only TACE and CLIP score proved to be independent predictors of survival at multivariate analysis. TACE is an effective therapeutic option for cirrhotic patients with unresectable HCC and a CLIP score of 3 or less.


Lumbosacral magnetic root stimulation in lumbar plexopathy.
We report a 76-yr-old man with left femoral nerve distribution weakness resulting from a nontraumatic retroperitoneal hematoma associated with coumadin anticoagulation. Although electric root stimulation was relatively contraindicated, magnetic lumbosacral root stimulation identified a proximal conduction block allowing more extensive assessment of the nerve damage. To our knowledge, this is the first report of magnetic root stimulation in assessment of lumbosacral plexus dysfunction in retroperitoneal hematoma.


Expression and significance of transforming growth factor-β1 in epithelial ovarian cancer and its extracellular matrix.
The aim of the present study was to investigate the expression and significance of transforming growth factor-β1 (TGF-β1) in the cytoplasm and extracellular matrix (ECM) of epithelial ovarian cancer cells. The expression of TGF-β1 protein was detected in paraffin-embedded sections of 25 normal ovarian epithelial tissues, 10 benign epithelial cysts and 72 epithelial ovarian cancer specimens, using the Strept Avidin Biotin Peroxidase Complex immunohistochemistry method. In addition, the expression of TGF-β1 mRNA in normal fibroblasts (NFs) and ovarian cancer-associated fibroblasts (CAFs) was assessed using semi-quantitative polymerase chain reaction (PCR). TGF-β1 protein was expressed in the cytoplasm and ECM, and no significant difference was identified between normal and benign ovarian tissues (P>0.05). However, the cytosolic expression of TGF-β1 declined gradually between the benign ovarian tumor and epithelial ovarian cancer, while its expression in the ECM significantly increased (P<0.05). The expression of TGF-β1 in the cytoplasm and ECM in epithelial ovarian cancer was found to negatively correlate with tumor differentiation, however, it was positively associated with the clinical stages. The positive rates of TGF-β1 in the cytoplasm and ECM between ovarian cancers in clinical stages I-II and III-IV were significantly different (P<0.05). Furthermore, the PCR data indicated that the relative expression of TGF-β1 mRNA in ovarian CAFs (1.0270±0.0539) was significantly higher than that in NFs (0.7131±0.0186). Therefore, the expression of TGF-β1 was identified to be associated with the development and progression of epithelial ovarian cancer, and the high expression of TGF-β1 in the ECM may be associated with the invasion and metastasis of ovarian cancer.


REPRODUCTIVE CHARACTERISTICS OF THE FLOWER BREEDING DROSOPHILA HIBISCI BOCK (DROSOPHILIDAE) IN EASTERN AUSTRALIA: GENETIC AND ENVIRONMENTAL DETERMINANTS OF OVARIOLE NUMBER.
Quantitative genetic analysis of the ovariole number of the Australian Hibiscus flower-breeding Drosophila hibisci Bock was conducted on populations from two localities along a latitudinal cline in ovariole number previously observed in the species (Starmer et al., in press). Parental strains, F1 , F1r (reciprocal), F2 , backcross, and backcross reciprocal generations were used in a line-cross (generation means) analysis. This analysis revealed both additive and epistatic effects as important determinants of variation in ovariole number when larvae were reared at 25°C. Maternal effects and maternal-by-progeny genetic interactions were not significant. These results are comparable to previous studies that document epistatic components as genetic determinants of ovariole number in D. melanogaster. Parallel studies on ovariole number in D. hibisci parental and hybrid generations (F1 and F1r ) reared as larvae at three temperatures (18°, 21.5°, and 25°C) showed environmental effects and genotype-by-environment interactions as significant influences on the phenotype. Maternal effects were present when temperature of larval development was considered and significant, nonlinear environmental effects were detected. Field collections of D. hibisci females showed that field conditions result in significant departure of ovariole number from comparable laboratory reared females. The significant epistatic genetic effects, genotype-by-environment interactions, and maternal effects indicate that the genetic architecture of traits, such as ovariole number, may be more complex than often acknowledged and thus may be compatible with Wright's view of a netlike relationship between the genome and complex characters (Wright 1968).


Attention in natural scenes: Affective-motivational factors guide gaze independently of visual salience.
In addition to low-level stimulus characteristics and current goals, our previous experience with stimuli can also guide attentional deployment. It remains unclear, however, if such effects act independently or whether they interact in guiding attention. In the current study, we presented natural scenes including every-day objects that differed in affective-motivational impact. In the first free-viewing experiment, we presented visually-matched triads of scenes in which one critical object was replaced that varied mainly in terms of motivational value, but also in terms of valence and arousal, as confirmed by ratings by a large set of observers. Treating motivation as a categorical factor, we found that it affected gaze. A linear-effect model showed that arousal, valence, and motivation predicted fixations above and beyond visual characteristics, like object size, eccentricity, or visual salience. In a second experiment, we experimentally investigated whether the effects of emotion and motivation could be modulated by visual salience. In a medium-salience condition, we presented the same unmodified scenes as in the first experiment. In a high-salience condition, we retained the saturation of the critical object in the scene, and decreased the saturation of the background, and in a low-salience condition, we desaturated the critical object while retaining the original saturation of the background. We found that highly salient objects guided gaze, but still found additional additive effects of arousal, valence and motivation, confirming that higher-level factors can also guide attention, as measured by fixations towards objects in natural scenes.


The effect of fish bodies on the source level and beam pattern of acoustic transmitters in juvenile Chinook salmon.
The effect of the fish body on the source level and beam pattern of an acoustic fish tag signal was investigated through laboratory experiments and an analytical method. In laboratory experiments, the source level and beam pattern were measured in both a tag-only group and a tag-in-fish group. In the analytical method, both forward and backward scattering were calculated by assuming the acoustic tag was a point source and the swimbladder was an air-filled prolate spheroid. The mean source level of five tested tags decreased by ∼4 dB after implantation in fish bodies, which is important for designing fish migration studies using acoustic telemetry.


Incidence and progress of middle ear effusion in allergy practice as detected by acoustic otoscope reflectometry.
The incidence and progress of middle ear effusion (MEE) in allergy practice is not well established in prospective studies. A total of 393 patients were screened for MEE by history and physical including pneumatic otoscopy, prick and intradermal skin tests, acoustic otoscope reflectometry (AOR), impedance tympanometry (IT), and audiometry for those with established MEE. The primary diagnosis of the screened patients was intrinsic asthma in 70 or 18%, allergic rhinitis in 134 or 34%, allergic rhinitis and asthma in 80 or 21%, miscellaneous in 103 or 26%. Twenty patients were receiving immunotherapy (5%), and 89 (23%) had middle ear effusion (MEE). Among the MEE group were 52 males (58%), 37 females (42%), with an average age of 13 years, median of 8 years, and range of 6 months to 13 years. The MEE group was statistically different demographically from the initial group (P < .05) for age and history of recurrent otitis. The MEE group's primary diagnosis was similar to that of the initial group, except that there was a statistically significant difference in the number of patients on immunotherapy (P < .05) and those in the MEE group, with 11 (12%) versus 20 or 5% in the initial group. MEE resolved in 91% of cases which could be followed to resolution, with average duration of nasal steroid of 4 weeks, average duration of effusion 8 weeks, median 4 weeks, range 1 week to 6 months. Effusions in 8 patients (9%) were intractable with duration greater than 3 months.(ABSTRACT TRUNCATED AT 250 WORDS)