Nursery epidemic due to multiply-resistant Klebsiella pneumoniae: epidemiologic setting and impact on perinatal health care delivery.
Gram-negative bacilli frequently cause epidemics in high-risk newborn intensive care units. Recently, an epidemic caused by a multiply-resistant K. pneumoniae, serotype 21, occurred in the Vanderbilt University intensive care nursery. The background of this outbreak included an increasing endemic nosocomial sepsis rate, operation of the facility in excess of rated capacity, and increasingly inadequate nurse-to-patient staffing ratios. The epidemic lasted 11 weeks; 26 (12%) of the 232 infants at risk in the unit became colonized. Five infants developed systemic illness and one died. Cohorting, reinforcement of strict handwashing and isolation procedures, and closure of the unit to outborn admissions resulted in rapid termination of the outbreak. Followup studies performed on infants colonized with the epidemic bacterium demonstrated persistent fecal shedding up to 13 months following discharge from the hospital. This epidemic had a detrimental influence on high-risk newborn and obstetric health care delivery in an area encompassing portions of three states. Under a system of progressively more sophisticated referral units, nosocomial infections occurring at a tertiary center can have an impact on other hospitals within the network.


The influence of cyclosporin a on experimental autoimmune thyroid disease in the rat.
Female PVG/c rats, thymectomized on weaning and given 4 courses of whole body irradiation to a total dose of 1000 rads, developed experimental autoimmune thyroid disease (EAITD) as assessed by histological evidence of thyroiditis and circulating levels of antithyroglobulin antibodies. Hypothyroidism resulted. Induction of the disease was associated with a highly significant fall in T lymphocyte numbers. Eight weeks after their last dose of irradiation the animals commenced treatment with Cyclosporin A (10 mg/kg rat/day, intragastrically) and were treated for varying time intervals thereafter. The reversal of the T lymphocyte helper: suppressor ratio on Cyclosporin A therapy was associated with a significant improvement in the disease process. The alterations in the T cell subsets and in the disease lasted only as long as the drug was administered and thereafter reverted towards that seen in the control groups of animals receiving no treatment.


Transcriptional regulation of mouse delta-opioid receptor gene. Role of Ikaros in the stimulated transcription of mouse delta-opioid receptor gene in activated T cells.
Delta-opioid receptors (DOR) present on T cells have been shown to mediate the immunomodulatory effects of endogenous and synthetic DOR agonists on T cells. Considerable evidence indicates that there is stimulated transcription of DOR gene in activated T cells, which is correlated with augmented expression of DOR and enhanced capacity of DOR agonists to affect the T-cell's functions. However, the molecular mechanism underlying the stimulated transcription of the DOR gene in activated T cells is still unclear. In the present study, we analyzed a 1.3-kb DNA fragment immediately upstream of the translation start site (-1300 to +1 bp, with the translation start site designated as +1) of the mouse DOR gene in EL-4 cells, a mouse lymphoma T cell line that exhibits enhanced expression of DOR transcripts when activated by phytohemagglutinin. Through both in vivo and in vitro experiments, we have demonstrated that increased binding activity of Ikaros at the Ikaros-binding site (-378 to -374) in the DOR promoter is required for the stimulated transcription of DOR gene in phytohemagglutinin-activated T cells.


[Extracorporeal lithotripsy in urinary calculi using the LT 01 EDAP].
Three hundred and sixty nine extracorporeal lithotripsies for renal stones have been performed using the EDAP apparatus (ultrasound detection, piezoelectric destruction). In 7.1% of cases, the stone could not be located. By using low frequencies (1.25 to 5 cycles per second), extracorporeal lithotripsy was able to be performed in 82% of cases without anaesthesia and without premedication. 96.5% of patients treated have been followed and reviewed at one and three months: 169 (61%) cases were successful, 59 (21.3%) were partial results and 49 (17.7%) were failures. The best results were obtained in stones less than 20 mm in diameter. A poor result can only be improved by a second session of extracorporeal lithotripsy. The scintigraphic scars observed after high frequency extracorporeal lithotripsy were not observed when low frequencies were used. This new outpatient extracorporeal lithotripsy procedure without anaesthesia currently represents 79% of our primary indications in renal stones.


Limited drug-drug interaction of elbasvir/grazoprevir for chronic hepatitis C.
The assessment of drug-drug interaction (DDI) is important not only for safety but also for maintaining the efficacy of direct acting antivirals in chronic hepatitis C (CHC). This study aims to evaluate DDI before and during elbasvir/grazoprevir (EBR/GZR) treatment. CHC patients who treated with EBR/GZR in five hospitals were enrolled. The patients' demographic data, comorbidities, concomitant medications taken before and during EBR/GZR were recorded. DDI was evaluated using a tool from the HEP Drug Interactions (www.hep-druginteractions.org) website. In addition to the evaluation of DDI for EBR/GZR, the virtual DDI of ledipasvir/sofosbuvir (LDV/SOF), sofosbuvir/velpatasvir (SOF/VEL) and glecaprevir/pibrentasvir (GLE/PIB) were evaluated. Degrees of DDI were classified as "do not co-administer", "potential interaction", and "potentially weak interaction". A total of 460 patients were enrolled. At baseline, 80.1% of patients had one or more comorbidities and 72.8% took one or more medications. Cardiovascular diseases (43.9%), gastrointestinal diseases (37.4%), and metabolic diseases (36.7%) were the three most common comorbidities. The prevalence of DDI before EBR/GZR treatment was 12.8% (59 patients). Among the same population, the prevalence of virtual DDI of SOF/VEL, GLE/PIB, and LDV/SOF were 38.5% (179 patients), 48.8% (220 patients), and 57.0% (262 patients), respectively. During EBR/GZR treatment, 167 patients (36.3%) took newly prescribed medications. One patient (0.2%) and seven patients (1/5%) exhibited do-not-co-administer and potential interaction with EBR/GZR, respectively. DDI was limited in treatment with EBR/GZR. DDI can occur upon the administering of a new medication during antiviral treatment and attention should be paid to it. NCT03706222.


[Craniomandibular disorders management (1) Treatment planning].
Various treatment modalities have been reported in the management of the craniomandibular disorders in the half century after Costen reported his hypothesis on the temporomandibular disorders. Recent advances in the basic sciences such as anatomy, histology, pathology, physiology and clinical trials have brought us to this new era. We have been trying to establish our diagnosis and treatment modalities in the management of the craniomandibular disorders over the past fifteen years. In this series of articles we will describe our present concept. We will first discuss diagnosis and treatment planning. After the diagnosis and initial treatment planning craniomandibular management is usually divided into two phases. Phase I is the treatment of the stomatognathic system especially the temporomandibular joint. Behavioral modification and physical therapy and splint therapy are the most common forms of treatment. Sometimes, surgical treatment is required. Phase II is the compensatory phase of the occlusion consisting of occlusal equilibration, occlusal restorations, orthodontic treatment and gnathic surgery if needed. Another phase we like to add is maintenance. In this phase, home therapy, corrective follow-up and long term observation should be emphasized. The motivation of the patient throughout the management of the craniomandibular disorder (phase I, phase II and the maintenance phase) is essential to reach to a successful result.


Clinical profiles of four large pedigrees with familial dilated cardiomyopathy: preliminary recommendations for clinical practice.
This study aimed to characterize the clinical profile of familial dilated cardiomyopathy (FDC) in the families of four index patients initially diagnosed with idiopathic dilated cardiomyopathy (IDC) and to provide clinical practice recommendations for physicians dealing with these diseases. Recent evidence indicates that approximately one-half of patients diagnosed with IDC will have FDC, a genetically transmissible disease, but the clinical profile of families screened for FDC in the U.S. has not been well documented. Additionally, recent ethical guidelines suggest increased responsibilities in caring for patients with newly found genetic cardiovascular disease. After identification of four families with FDC, we undertook clinical screening including medical history, physical examination, electrocardiogram and echocardiogram. Diagnostic criteria for FDC-affected status of asymptomatic family members was based on left ventricular enlargement (LVE). Subjects with confounding cardiovascular diagnoses or body mass indices >35 were excluded. We identified 798 living members from the four FDC pedigrees, and screened 216 adults and 129 children (age <16 years). Twenty percent of family members were found to be affected with FDC; 82.8% of those affected were asymptomatic. All four pedigrees demonstrated autosomal dominant patterns of inheritance. The average left ventricular end-diastolic dimension was 61.4 mm for affected and 48.4 mm for unaffected subjects, with an average age of 38.3 years (+/- 14.6 years) for affected and 32.1 years for unaffected subjects. The age of onset for FDC varied considerably between and within families. Presenting symptoms when present were decompensated heart failure or sudden death. We propose that with a new diagnosis of IDC, a thorough family history for FDC should be obtained, followed by echocardiographic-based screening of first-degree relatives for LVE, assuming their voluntary participation. If a diagnosis of FDC is established, we suggest further screening of first-degree relatives, and all subjects with FDC undergo medical treatment following established guidelines. Counseling of family members should emphasize the heritable nature of the disease, the age-dependent penetrance and the unpredictable clinical course.


"Young ladies are delicate plants": Jane Austen and Greenhouse Romanticism.
By annotating how in Mansfield Park and Northanger Abbey Jane Austen tracks between the novelist's domain and the naturalist's, this essay seeks to unsettle some entrenched assumptions about her relationship to realism—and the ideological work of naturalization that realism is said to sponsor—as well as to romanticism. Austen's era, which we customarily identify as the time of a romantic return to nature, was marked by conflicts over what nature did and did not include—conflicts between, in the parlance of the period, "the botanist" and "the florist," between an account of nature as that which was given and an account of nature as that which (as with the modern nurseryman's new hybrids and luxuriants) might be manufactured. In arranging for her young heroines' stories of growing up to unfold in the "artificial climates" of modern fashionable gardening and amidst "florists' flowers," Austen deliberately works through those conflicts. She inhabits the plot of "natural development" to which she is often linked in elusively oppositional ways.


Effects of long-term chloroquine exposure on the phospholipid metabolism in retina and pigment epithelium of the mouse.
The influence of 6 month's treatment of normal mice with chloroquine on neuroretina and retinal pigment epithelium has been investigated biochemically and morphologically. All classes of neuroretinal phospholipids, except lysophosphatidylcholine, showed increased 14C-glucose incorporation after chloroquine treatment. No metabolic changes were observed in the pigment epithelium after the chloroquine treatment. Morphological signs of phospholipidosis were only evident in the ganglion cells of the neuroretina. It is concluded that long-term treatment with chloroquine does not affect pigment epithelium phospholipid metabolism but leads to morphological and biochemical signs of phospholipidosis in the neuroretina.


Pain Experience and Perception in the Obese Subject Systematic Review (Revised Version).
Pain is an integral part of life and has an important protective function. Pain perception has been shown to differ between subjects and changes with gender, race, and culture. In addition, it has been suggested that obesity influences pain perception and that obesity can be a risk factor for increased pain thresholds. The aim of this systematic review was to examine pain thresholds in obese subjects compared to non-obese subjects. The electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and EMBASE were searched using combinations of terms for obese, pain measurement, visual analog scale, quantitative sensory testing, and pain perception. Studies without comparison as well as cross-sectional studies, case series, and case reports were excluded. The search was conducted without restrictions on language or date of publication. From a total of 1818 identified studies, seven studies fulfilled the inclusion criteria, whereby only one study tested the pain threshold difference between obese and non-obese and also before and after body weight loss surgery. Two studies showed a lower pain threshold and four studies a higher pain threshold in obese subjects compared to non-obese subjects. Two studies showed no difference in pain threshold before and after substantial body weight loss due to surgery. Weight loss after surgery was not identified as a factor for higher pain thresholds in obese subjects. In view of the heterogeneity of the studies, the variability of the subjects and differences in methodological quality, a meta-analysis could not be performed. From the available literature, there is a tendency towards higher pain thresholds in obese subjects. Neither substantial weight loss, nor gender, were factors explaining difference in threshold. Future randomized, controlled trials should explore demographic variables that could influence pain perception or pain thresholds in obese individuals, and multimodal pain testing is necessary for better understanding of the apparent differences in pain thresholds in obese individuals.


[Evolution and characteristics of system,assessing quality by distinguishing features of traditional Chinese medicinal materials, of Dao-di herbs of Astragali Radix].
"Assessing the quality by distinguishing features of traditional Chinese medicinal materials" is a characteristic quality evaluation system of traditional Chinese medicine, and it is also the basis of "Rating according to characters and setting the price by the grade" on the market. Astragali Radix was regarded as a famous traditional Chinese medicine (TCM), and this paper has carried out herbal textual research on the development and formation of the concept, "assessing the quality by distinguishing features of traditional Chinese medicinal materials", of Astragali Radix. The authentic medicine producing areas of Astragalus in China have experienced a great change, Gansu , Sichuan and adjacent areas before the Tang Dynasty; Shanxi during the Tang and Song Dynasty. The concept, "assessing the quality by distinguishing features of traditional Chinese medicinal materials", of Astragali Radix was formed in the Song and Ming Dynasty and still used today, which described as that the shape is "straight as an arrow"; the texture is "soft as cotton"; the section looks like" gold well and jade hurdle"; it was sweet in taste and has beany flavor. The system, "assessing the quality by distinguishing features of traditional Chinese medicinal materials", of Astragali Radix has undergone the adjustments from "true or false" to "good or bad", advance with the times, pick out the advantages from others and absorb the experience of traditional identification actively. Besides, it always returns to laconism from erudition and was summarized highly. Assessing the quality by distinguishing features of traditional Chinese medicinal materials and commodity specifications have the same root, so the former has reference meaning to revise the latter.


Effects of impending ovarian failure induced by 4-vinylcyclohexene diepoxide on fertility in C57BL/6 female mice.
Repeated daily dosing of mice with 4-vinylcyclohexene diepoxide (VCD) causes a gradual onset of ovarian failure, providing a model for perimenopause. Because increasing numbers of women are delaying starting a family, infertility in aging women is of concern. This study was designed to determine the effects of impending ovarian failure on fertility in VCD-treated mice. Female C57BL/6J mice were dosed daily (17 d) with vehicle control or VCD (160 mg/kg, intraperitoneally) to deplete primordial follicles and then were divided into 2 groups. Group 1 was mated soon after dosing; group 2 was mated on day 20 after dosing, during impending ovarian failure. Fertility was evaluated on gestational day 16. In group 1, cycle length, pregnancy rate, and number of live fetuses did not differ between VCD-treated animals and controls, but VCD-treated mice required more matings to become pregnant and had more resorptions. In group 2, VCD-treated mice demonstrated proestrus and copulatory plugs, but only 1 animal became pregnant, and she had no viable fetuses. Ovaries from pregnant and nonpregnant controls contained similar numbers of follicles and corpora lutea. Ovaries from VCD-treated animals contained no follicles, and corpora lutea were seen only in pregnant animals. In VCD-treated mice mated soon after dosing, conception was more difficult and more resorbed fetuses were seen, whereas in those mated closer to impending ovarian failure, no successful pregnancies were achieved. These results demonstrate that VCD-treated mice can be used to model infertility in perimenopausal women.


An increase in the sympathoadrenal medullary function in stroke-prone spontaneously hypertensive rats under anesthetized and resting conditions.
Sympathoadrenal medullary functions were investigated in stroke-prone spontaneously hypertensive rats (SHR-SP) and in control normotensive Wistar-Kyoto rats (WKY) under halothane-anesthetized and resting conditions. The mean frequency of the spontaneous efferent activity of a single adrenal sympathetic nerve fiber was 1.08 +/- 0.11 impulses/s in WKY and 2.82 +/- 0.24 imp/s in SHR-SP, indicating a much higher level in SHR-SP than in WKY. The secretion rates of both adrenaline and noradrenaline from the adrenal gland were higher in SHR-SP than in WKY. The secretion rates of adrenaline and noradrenaline in WKY were 16.8 +/- 3.0 and 1.70 +/- 0.09 ng/kg X min, respectively, while those in SHR-SP were 36.7 +/- 3.9 and 2.56 +/- 0.18 ng/kg X min, respectively.


Spatial modeling of geographic inequalities in infant and child mortality across Nepal.
A survival regression model that allows for spatially correlated random effects is used to predict the hazard of dying among 12,714 children born between 1996 and 2006 in Nepal. The maps of fitted hazard rates show that even after accounting for individual and community-level covariates, a residual spatial pattern in infant mortality remains, with higher mortality concentrated in parts of Nepal's Far-Western and Mid-Western development regions. Results suggest a need to consider health policies and programs that reach children in spatially concentrated high-mortality areas.


Guidelines for radical reactions: some thirty years on.
In this viewpoint article we reflect on the state of play of organic free radical chemistry before the contributions of Beckwith et al. to our understanding of the factors that control intramolecular homolytic addition chemistry, and the rapid rise in the use of this chemistry once the impact of the "guidelines for radical reactions" became fully appreciated.


[Development of the main indicators of perinatal health in metropolitan France between 1995 and 1998. Results of the national perinatal survey].
To study trends in the main indicators of health, medical practice and risk factors. We compared two samples; both included all stillbirths and live births during one week in France: 13,318 in 1995 and 13,718 in 1998. Between 1995 and 1998, there was an increase in maternal age, a development of some characteristics of care (antenatal care by maternity unit staff, HIV screening procedure, antenatal classes) and an increase in the proportion of caesarean sections and epidurals. The proportion of live births before 37 weeks of gestation increased from 5.4% to 6.2%. This trend is explained by an increase in preterm deliveries among twins. Specific questions in the 1998 questionnaire showed that 6.3% of women had received fertility treatment before this pregnancy, 11.1% had an amniocentesis, and 1.1% had an intrauterine transfer. This type of survey carried out every three years can show major changes in health, risk factors and medical practices and can yield quick answers to specific questions.


Characterization and regeneration of wheat (Triticum aestivum L.) embryogenic cell suspension cultures.
Stable cell suspension cultures were established from two types of calli (one compact, nodular and embryogenic, the other friable and embryogenic) derived from cultured immature embryos of wheat (cv FLA302). Only aged calli, which had been subcultured for at least 5-8 months, formed suspensions comprised mainly of groups of small, round, densely cytoplasmic, starch-containing cells. Only the embryogenic suspension derived from the aged, compact and nodular callus formed distinct somatic embryos when plated on regeneration media containing IAA and zeatin. Upon subsequent transfer to fresh regeneration medium more than 200 green rooted plants were obtained.


Changes in public attitudes toward epilepsy in Hungary: results of surveys conducted in 1994 and 2000.
Our study investigated public attitudes toward epilepsy, and knowledge and understanding of epilepsy in Hungary. We compared changes of public attitudes in the last six years, hypothesizing a trend of positive changes because of recent national initiatives for acceptance and integration of people with epilepsy (e.g., participation of Hungary in the "Out of the Shadows" world campaign). We also studied how the demographic background of the respondents affects awareness, understanding, and attitudes toward epilepsy. Using a questionnaire design, we conducted a public opinion poll with a representative sample of 1,000 people in 1994 and 6 years later, in 2000. Hungarian respondents were most prejudiced regarding employment of people with epilepsy. In recent years, significant decreases in prejudice rates were found regarding all attitude aspects (marriage, children associating, work). Significant background effects of demographic variables were also apparent: differences by age, education, residence, and family status were found. Some culture-specific characteristics of understanding epilepsy could be observed. Significant positive attitude changes from 1994 to 2000 confirm the need for and potentialities of education of the public and informational initiatives. Demographic influences and culture-specific characteristics could be of relevance in designing public education for different target groups.


The use of a chemistry-based profiler for covalent DNA binding in the development of chemical categories for read-across for genotoxicity.
An important molecular initiating event for genotoxicity is the ability of a compound to bind covalently with DNA. However, not all compounds that can undergo covalent binding mechanisms will result in genotoxicity. One approach to solving this problem, when in silico prediction techniques are being used, is to develop tools that allow chemicals to be grouped into categories based on their ability to bind covalently to DNA. For this analysis to take place, compounds need to be placed within categories where the trend in toxicity can be explained by simple descriptors, such as hydrophobicity. However, this can occur only when the compounds within a category are structurally and mechanistically similar. Chemistry-based profilers have the ability to screen compounds and highlight those with similar structures to a target compound, and are thus likely to act via a similar mechanism of action. Here, examples are reported to highlight how structure-based profilers can be used to form categories and hence fill data gaps. The importance of developing a well-defined and robust category is discussed in terms of both mechanisms of action and structural similarity.


High Incidence of Diabetes Mellitus Among a Middle-Aged Population in Iran: A Longitudinal Study.
There are few data concerning the incidence rates of diabetes in Iran. This study aimed to determine the incidence of diabetes and its risk factors in a middle-aged population in Iran. All of the people who participated in the first phase of the Shahroud eye cohort study were invited to the study in 2014; after signing informed consent forms, a total of 4737 people 45 to 69 years of age were enrolled in the second phase of the study (participation rate: 91.3%). The 5-year incidence rate of diabetes was determined by age and sex, and we used the binomial logistic regression model to calculate the risk ratio. The prevalence of diabetes in the second phase was 20.19% in men, 26.45% in women and 23.89% in the total group. The 5-year incidence of diabetes was 11.19% in men, 15.55% in women and 13.73% in both sexes. With increases in age, the incidence of diabetes rose in both sexes. Age (risk ratio [RR]: 1.02; CI 95%: 1.01 to 1.03) hypertension (RR: 1.41; CI 95%: 1.15 to 1.74), being overweight (RR: 2.17; CI 95%: 1.64 to 2.88) and obesity (RR: 3.4; CI 95%: 2.53 to 4.41) were associated with increased risks for the incidence of diabetes. This study is 1 of the few studies in Iran that has reported the incidence of diabetes. Because the incidence of diabetes was high in the studied population, it is necessary for the health system to design and implement emergency intervention to prevent further spread of diabetes and its complications.


Chronotherapeutic effect of orexin antagonists on glucose metabolism in diabetic mice.
Disrupted sleep is associated with increased risk of type 2 diabetes. Central actions of orexin, mediated by orexin-1 and orexin-2 receptors, play a crucial role in the maintenance of wakefulness; accordingly, excessive activation of the orexin system causes insomnia. Resting-phase administration of dual orexin receptor antagonist (DORA) has been shown to improve sleep abnormalities and glucose intolerance in type 2 diabetic db/db mice, although the mechanism remains unknown. In the present study, to investigate the presence of functional link between sleep and glucose metabolism, the influences of orexin antagonists with or without sleep-promoting effects were compared on glucose metabolism in diabetic mice. In db/db mice, 2-SORA-MK1064 (an orexin-2 receptor antagonist) and DORA-12 (a DORA) acutely improved non-rapid eye movement sleep, whereas 1-SORA-1 (an orexin-1 receptor antagonist) had no effect. Chronic resting-phase administration of these drugs improved glucose intolerance, without affecting body weight, food intake, locomotor activity, and energy expenditure calculated from O2 consumption and CO2 production. The expression levels of pro-inflammatory factors in the liver were reduced by 2-SORA-MK1064 and DORA-12, but not 1-SORA-1, whereas those in the white adipose tissue were reduced by 1-SORA-1 and DORA-12 more efficiently than 2-SORA-MK1064. When administered chronically at awake phase, these drugs caused no effect. In streptozotocin-induced type 1-like diabetic mice, neither abnormality in sleep-wake behavior nor improvement of glucose intolerance by these drugs were observed. These results suggest that both 1-SORA-type (sleep-independent) and 2-SORA-type (possibly sleep-dependent) mechanisms can provide chronotherapeutic effects against type 2 diabetes associated with sleep disturbances in db/db mice.


Increased stimulatory effect by the combined administration of cocaine and alcohol in mice.
Locomotor activity was recorded after 5-30 mg/kg of cocaine in mice pretreated or not with a stimulant dose of ethanol (2.0 g/kg). The increase in locomotion induced by the association of cocaine plus ethanol was significantly larger when compared to either the group injected with only cocaine or only ethanol.


Desensitization of the thyroid cyclic AMP response to thyroid stimulating immunoglobulin: comparison with TSH.
Studies were conducted to examine the characteristics of thyroid cell cAMP stimulation by thyroid stimulating immunoglobulins (TSI) and to compare the cAMP response to TSI and TSH in desensitized human thyroid cells. In terms of cAMP production, preexposure (eight hours) of the cells to TSI induced a desensitization very similar to TSH-induced desensitization: both TSH- and TSI-desensitized cells showed a normal response to cholera toxin and forskolin stimulation; TSH and TSI desensitization was interchangeable in that desensitization by either stimulator affected the action of the other; the time of recovery from either TSH and TSH desensitization was identical; the cycloheximide (10(-4) mol/L) prevented both TSI- and TSH-induced desensitization; preexposure of the cells to iodine, which affects mainly the adenylate cyclase catalytic unit, or to epinephrine, which activate the inhibitory regulatory protein Ni by the alpha 2-adrenergic stimulation, induced a similar inhibition of the subsequent stimulation by both TSH or TSI. The remarkable similarities between TSH and TSI in stimulating and desensitizing thyroid cells strongly support the concept that TSI activates thyroid adenylate cyclase by interacting with the TSH receptor and not through an allosteric mechanism.


Value of the new Doppler-derived myocardial performance index for the evaluation of right and left ventricular function following repair of tetralogy of fallot.
The systolic and diastolic function in both ventricles may be altered even after successful corrective surgery of tetralogy of Fallot. The aim of this study was to assess the combined diastolic and systolic function of both ventricles using the Doppler-derived myocardial performance index (MPI) in patients with operated tetralogy of Fallot (TOF). We performed a prospective analysis of 51 patients following corrective surgery of TOF: 21 had a subannular patch, 20 had a homograft implantation at initial operation, and 10 were reoperated with secondary homograft implantation. Patients were examined with Doppler echocardiography, and the MPI, which incorporates ejection and isovolumetric relaxation and contraction times and is an index of global ventricular function, was calculated 10.2 +/- 8.0 (0.89-36) years after surgery. In 86.4% of the examined patients the right ventricular isovolumetric relaxation time was shortened compared to the normal published range or even did not exist (negative value) (p <0.01). The right ventricular MPI was paradoxically below the normal published range in 76.5% of the examined patients. The left ventricle global function was impaired in 23.5% of the examined patients, mainly due to altered systolic function with a prolonged left ventricular isovolumetric contraction time. The z score of the comparison between patients' left ventricular isovolumetric contraction time and the normal published values was 3.03. Patients with severe pulmonary regurgitation also had a prolongation of the isovolumetric relaxation time compared to patients with mild to moderate pulmonary regurgitation. The noncompliant right ventricle may shorten the right ventricular isovolumetric relaxation time, resulting in a paradoxically low right MPI. This may reduce the sensitivity of the index in recognizing patients with right ventricular dysfunction following corrective surgery of TOF. Additional diastolic impairment occurs in patients with right ventricular volume overload.


Ankle fracture is associated with prolonged venous dysfunction.
Leg swelling is a significant problem following ankle fracture. Venous pump function and femoral and popliteal venous patency were assessed prospectively in 26 patients with ankle fractures requiring open reduction, internal fixation and immobilization in plaster. Functional venous volume, venous filling index (VFI), ejection volume fraction (EVF) and residual volume fraction (RVF) were measured using air plethysmography at 5 days and at 6, 12 and 18 weeks after fracture. The uninjured leg was used as a control. Popliteal and femoral venous patency was determined using duplex ultrasonography. No patient developed deep vein thrombosis during the study. At 5 days after fracture there was a significant reduction in mean(s.d.) EVF, 18.2(12.1) versus 55.9(19.5) per cent, and increase in RVF, 87.0(14.3) versus 42.5(22.2) per cent (both P < 0.001). Analogous values were similar at 6 weeks, EVF 28.5(21.2) versus 55.6(21.9) per cent, RVF 82.2(16.8) versus 48.5(23.8) per cent (both P < 0.001), and at 12 weeks, EVF 39.1(16.0) versus 60.3(14.9) per cent, RVF 64.7(18.8) versus 38.8(13.2) per cent (both P < 0.001). However, by 18 weeks there was no significant difference in venous function between fractured and control limbs. It is concluded that there is a significant and prolonged impairment in venous pump function following ankle fracture.


Function of the medial olivocochlear system in children with phonological disorders.
To verify whether children with phonological disorders present alterations in the medial olivocochlear system. This is a prospective cross-sectional study in which 19 normal hearing children of both genders, with ages between 4 and 7 years, were divided into two groups: 11 children without phonological disorders (control group) and eight with phonological disorders (study group). The auditory condition was verified by visual examination of the external ear canal, pure tone audiometry, and tympanometry. The study included only children with hearing thresholds below or equal to 15 dB, type A tympanometry, and presence of acoustic reflexes. To evaluate the function of the medial olivocochlear system, it was carried out the evaluation of transient evoked otoacoustic emissions (TEOAE) with and without contralateral white noise at 60 dBHL. Data were statistically analyzed. The occurrence and average values of TEOAE suppression in right and left ears did not present differences in the frequencies of 1, 2, 3 and 4 kHz within groups. In the comparison of the mean and the occurrence of the suppressive effect of TEOAE between control and study groups, there was also no difference in the frequencies analyzed. Children with phonological disorders do not present alterations in the medial olivocochlear system, as evidenced by the occurrence of the suppressive effect of transient evoked otoacoustic emissions.


Magnetic Resonance Diffusion Kurtosis Imaging for Evaluating Stage of Liver Fibrosis in a Rabbit Model.
As an extension of the conventional diffusion weighted imaging, diffusion kurtosis imaging (DKI) is based on the non-Gaussian diffusion model that can inherently account for restricted water diffusion within the complex microstructure of most tissues. This study aimed to investigate association of liver DKI derived parameter with stage of liver fibrosis. Fifty-six healthy New Zealand white rabbits were enrolled into this study, among which 48 rabbits were randomly given carbon tetrachloride to model liver fibrosis, and 8 rabbits treated with normal saline served as control subjects. All rabbits underwent liver DKI followed by biopsy to stage fibrosis (stages F0-F4) on 6th, 8th, 10th, and 12th weekends after initiation of modeling fibrosis. Mean kurtosis (MK), fractional anisotropy (FA), and mean diffusion (MD) were derived from DKI data. Statistical analysis was to evaluate association of DKI derived parameter with stage of fibrosis. FA (r = 0.512) and MK (r = 0.567) increased, and MD (r = -0.574) decreased with increasing stage of fibrosis from F0 to F4 (all p values < 0.05). Significant differences were found in all parameters between F0 and F3 or F4, F1 and F4, F0 and F1-4, and F0-1 and F2-4 (all p values < 0.05). FA and MD could distinguish between F0 from F2, MD, and MK could distinguish F1 from F3, F0-2 from F3-4, and F1-2 from F3-4, and MK and FA could distinguish F2 from F4, and F0-3 from F4 (all p values < 0.05). According to receiver operating characteristic analysis, MK could best predict stage ≥F1, ≥F2, ≥F3, and F4, and discriminate F1-2 from F3-4 with areas under receiver operating characteristic curve of 0.766-0.930. DKI derived parameters can help stage fibrosis.


Application of the POSSUM system in bariatric surgery.
The POSSUM system has been devised for physiologic and operative scoring. The scoring system produced assessment for morbidity and mortality rates, which did not significantly differ from observed rates. The authors have applied this system to bariatric surgery. 20 patients were scored by the POSSUM system. All underwent elective bariatric surgery during 1997. All patients were scored at the time of surgery with the physiologic score (FIS) and at discharge with the operative severity score (IQ). The FIS score included age; cardiac signs; chest radiograph; respiratory history; blood pressure; pulse; Glasgow coma score; determinations of hemoglobin, leukocyte, urea, sodium, and potassium levels; and electrocardiogram. The IQ score included multiple procedures, total blood loss, peritoneal soiling, presence of malignancy, and mode of surgery. The mean POSSUM score was 23.9. The mean FIS was 13.95 (12-22), and the mean IQ was 9.4 (7-16). The distribution of patients was performed for BMI. The group with BMI 35-45 (n = 4 patients) had a mean POSSUM score of 22.75, a mean FIS of 13.75, and a mean IQ of 9.0. The group with BMI >45 (n = 16 patients) had a mean POSSUM score of 24.18, a mean FIS of 14.62, and a mean IQ of 9.5. The morbidities were gastric fistula with peritonitis and deep venous thrombosis. The two complications had similar POSSUM scores with different BMIs. No mortality was observed. According to this experience, the POSSUM scoring system appears to provide an indicator of minor risk of morbidity and mortality in bariatric surgery with vertical banded gastroplasty.


Frequency Modulated Parametric Oscillation for Antenna Powered Wireless Transmission of Voltage Sensing Signals.
Wireless transmission of voltage signals are particularly useful for sensors embedded inside a closed environment where long-term operation without internal batteries is desirable. For this purpose, voltage tuning resonators can be used, because their voltage-dependent frequency responses can be contactlessly characterized by loop antennas connected to the output and input ports of a network analyzer. However, such passive sensors have limited remote detectability and temporal resolution, especially for smaller frequency shifts that would require repetitive averaging for acceptable measurement accuracy. To overcome these limitations, a double frequency parametric resonator is inductively coupled with a voltage tuning resonator to convert resonance frequency shifts of the passive sensor into frequency encoded oscillation signals that can be instantaneously detected over larger distance separations. This antenna powered FM transmitter has a compact design to achieve good voltage sensitivity and linearity, making it potentially useful for multiple applications from PH sensing to electrophysiological recording.


Preoperative neuroimaging findings as a predictor of the surgical plane of cleavage: prospective study of 100 consecutive cases of intracranial meningioma.
To understand the cause and prevention of postoperative ischemic and/or venous parenchymal infarcts after intracranial meningioma resection, the authors describe the value of neuroimaging in predicting the surgical plane of cleavage. A prospective study of 100 meningiomas was performed, in which tumor size, absence or presence of peritumoral edema, tumor-parenchyma interface, and types of arterial vascularization (that is, dural-meningeal, pial-cortical, or mixed) were correlated with the type of dissection plane (extrapial, subpial, or mixed) encountered at surgery. A direct correlation was found between the tumor size identified on T1-weighted magnetic resonance (MR) imaging sequences and the degree of subpial (nonextrapial) surgical plane of cleavage (p < 0.00001). A similar correlation was found with the grade of peritumoral edema identified on preoperative computerized tomography (CT) scanning (p < 0.0001) or T2-weighted MR imaging sequences (p < 0.00001) and tumor pial vascularization as seen on angiography (p < 0.0001). Nevertheless, the tumor-parenchyma interface on preoperative T2-weighted MR imaging sequences was not predictive of the surgical plane (p > 0.5). The worst clinical outcome was found in the tumors located in eloquent areas and in which a subpial plane was encountered at surgery (p = 0.03). Peritumoral edema on preoperative CT and MR studies and tumor pial vascularization as seen on selective angiography can be used to predict the surgical plane of cleavage in meningiomas. The association between tumor size and a subpial surgical plane may be explained by a more pial vascularization seen on angiography. Meningiomas with a location in eloquent cortex and a subpial dissection plane should be considered a high-risk group.


Radial forearm free flap for reconstruction of the oral cavity: clinical experience in 55 cases.
Since the advent of modern microvascular techniques, the radial forearm free flap (RFFF) has become a reliable method for reconstruction of defects within the oral cavity. The purpose of the present study was to evaluate our experience with the use of the RFFF for the reconstruction of oral cavity defects after tumor resection. During a 9-year period, 103 consecutive patients were treated in our department for the reconstruction of oral defects after tumoral ablation by means of microvascularized free flaps. Fifty-five patients were reconstructed by means of the RFFF. Patients were treated for benign (n = 1) and malignant (n = 54) entities. All the patients underwent an abdominal split-thickness skin graft for the closure of the donor site. Fifty-five patients underwent reconstruction by means of the RFFF after resection of the oral cavity. Squamous cell carcinoma was present in 54 patients. A mean age of 55.5 years was observed (range 16-78). Thirty-nine patients (70.9%) were men and 16 (29.1%) women. Primary reconstruction was achieved in 52 patients (96.3%). A fasciocutaneous graft was used in all of the cases, with a mean size of 7.39 x 5.17 cm. The mean flap ischemic time was 56.02 minutes. During the immediate follow-up period, revision of the vascular anastomosis was necessary in 18.9% of the cases owing to flap ischemia. Our results revealed that the RFFF is a reliable method for reconstructing a wide range of oral cavity defects with an acceptable low morbidity rate. It provides adequate bulkiness and pliability, resulting in adequate reconstruction of a wide variety of defects within the oral cavity.


Use of the harmonic scalpel for nephron sparing surgery in renal cell carcinoma.
The harmonic scalpel is a new tool for excising and coagulating tissue with ultrasound using higher frequencies than an ultrasonic aspirator. We evaluated the usefulness of the harmonic scalpel in nephron sparing surgery. We used the harmonic scalpel to incise the renal parenchyma during nephron sparing surgery in 10 patients with renal cell carcinoma. Bleeding from the renal parenchyma was minimal but hemostasis of the larger vessels was not obtained even when the harmonic scalpel was used at maximal coagulation power. The cut surface of the kidneys, especially the vessels, were more clearly recognized than if an ultrasonic aspirator had been used, enabling hemostasis by figure-of-8 suture. The harmonic scalpel is useful for obtaining a clear parenchymal stump and hemostasis during nephron sparing surgery, although complete hemostasis of the arcuate or larger vessels cannot be achieved.


Peak expiratory flow rate of Nepalese children and young adults.
In diagnosis and treatment of respiratory diseases, the assessment of lung functions is of considerable importance. So, normal reference values for pulmonary function tests of any population need to be assessed. An attempt has been made in the present study to measure the peak expiratory flow rate (PEFR) in healthy Nepalese children and young adults. One hundred ninety six (196) students were selected by inclusion criteria from different schools and colleges in Pokhara Sub-Metropolitan City, Nepal. The anthropometric measurements and peak expiratory flow rate (PEFR) were measured by standard procedures. The mean PEFR values of males and females are found to have 350.3 (+/-135.0) l.min-1 and 280.2 (+/-98.77) l. min-1 respectively. The PEFR values of Nepalese males of the present study are found to be higher as compared to their females' counterparts. It is interestingly noted that at preadolescence time, PEFR is almost comparable in both sexes but after puberty males attained significantly higher values than females. The trend of PEFR values with development of the age is also been noted. It is interestingly pointed out that PEFR values of Nepalese males in the present study increases significantly with the advancement of age up to 20 years of age and then after PEFR do not change. On the other hand, females showed significant PEFR increment with the advancement of age up to 15 years of age only and then after PEFR do not improve significantly. PEFR was found to be influenced significantly by height not by the weight. Finally, a prediction equation was established by which PEFR of Nepalese population of 5 to 25 years of age can be estimated from age or height.


Nicotine inhibits voltage-dependent sodium channels and sensitizes vanilloid receptors.
Nicotine is an alkaloid that is used by large numbers of people. When taken into the body, it produces a myriad of physiological actions that occur primarily through the activation of neuronal nicotinic acetylcholine receptors (nAChRs). We have explored its ability to modulate TRPV1 receptors and voltage-gated sodium channels. The reason for investigating nicotine's effect on sodium channels is to obtain a better understanding of its anti-nociceptive properties. The reasons for investigating its effects on capsaicin-activated TRPV1 channels are to understand how it may modulate this channel that is involved in pain, inflammation, and gustatory physiology. Whole cell patch-clamp recordings from rat trigeminal ganglion (TG) nociceptors revealed that nicotine exhibited anesthetic properties by decreasing the number of evoked action potentials and by inhibiting tetrodotoxin-resistant sodium currents. This anesthetic property can be produced without the necessity of activating nAChRs. Nicotine also modulates TRPV1 receptors inducing a several-fold increase in capsaicin-activated currents in both TG neurons and in cells with heterologously expressed TRPV1 receptors. This sensitizing effect does not require the activation of nAChRs. Nicotine did not alter the threshold temperature (approximately 41 degrees C) of heat-activated currents in TG neurons that were attributed to arise from the activation of TRPV1 receptors. In this regard, its effect on TRPV1 receptors differs from those of ethanol that has been shown to increase the capsaicin-activated current but decrease the threshold temperature. These studies document several new effects of nicotine on channels involved in nociception and indicate how they may impact physiological processes involving pain and gustation.


Molecular epidemiology of bat lyssaviruses in Europe.
Bat rabies cases in Europe are principally attributed to two lyssaviruses, namely European bat lyssavirus type 1 (EBLV-1) and European bat lyssavirus type 2 (EBLV-2). Between 1977 and 2011, 961 cases of bat rabies were reported to Rabies Bulletin Europe, with the vast majority (>97%) being attributed to EBLV-1. There have been 25 suspected cases of EBLV-2, of which 22 have been confirmed. In addition, two single isolations of unique lyssaviruses from European insectivorous bats were reported in south-west Russia in 2002 (West Caucasian bat virus) and in Germany in 2010 (Bokeloh bat lyssavirus). In this review, we present phylogenetic analyses of the EBLV-1 and EBLV-2 using partial nucleoprotein (N) gene sequences. In particular, we have analysed all EBLV-2 cases for which viral sequences (N gene, 400 nucleotides) are available (n = 21). Oropharyngeal swabs collected from two healthy Myotis daubentonii during active surveillance programmes in Scotland and Switzerland also yielded viral RNA (EBLV-2). Despite the relatively low number of EBLV-2 cases, a surprisingly large amount of anomalous data has been published in the scientific literature and Genbank, which we have collated and clarified. For both viruses, geographical relationships are clearly defined on the phylogenetic analysis. Whilst there is no clear chronological clustering for either virus, there is some evidence for host specific relationships, particularly for EBLV-1 where more host variation has been observed. Further genomic regions must be studied, in particular for EBLV-1 isolates from Spain and the EBLV-2 isolates to provide support for the existence of sublineages.


Resuspension of coal and coal/municipal sewage sludge combustion generated fine particles for inhalation health effects studies.
Airborne particulate matter (PM) is an important environmental issue because of its association with acute respiratory distress in humans, although the specific particle characteristics that cause lung damage have yet to be identified. Particle size, acid aerosols, water-soluble transition metals (e.g. Cu, Fe, V, Ni and Zn), polyaromatic hydrocarbons, and particle composition are the focus of several popular hypotheses addressing respiratory distress. All of the above mentioned characteristics are contained in PM generated from the combustion of both pulverized coal, and biomass, including dried municipal sewage sludge (MSS). In this investigation, we report results from collaborative interdisciplinary research on the inhalation health risks caused by particles emitted from the co-combustion of municipal sewage sludge (MSS) and coal. A solid particle resuspension system was implemented to resuspend ash particles. Mice were exposed to resuspended coal and MSS/coal ash particles. Mice exposed to MSS/coal ash particulate demonstrated significant increases in lung permeability, a marker of the early stages of pathological lung injury, while the mice exposed to coal-only ash did not. These results show that the composition of particles actually inhaled is important in determining lung damage. Zinc was significantly more concentrated in the MSS/coal ash than coal ash particles and the pH of these particles did not differ significantly. Specifically, an MSS/coal mixture, when burned, emits particles that may cause significantly more lung damage than coal alone, and that consequently, the use of MSS as a 'green', CO2-neutral replacement fuel should be carefully considered.


Prediction of vascular complications following free tissue transfer.
Thirty-five consecutive free tissue transfers were evaluated prospectively. A prediction of postoperative vascular complications was made at the time of wound closure. Two vascular complications occurred, each predicted intraoperatively. Conversely, the 33 flaps that did not develop vascular complications were correctly identified intraoperatively. Intraoperative findings that correlated with postoperative vascular complications were clinically recognizable changes in flap perfusion.


Nonconscious emotional processing involves distinct neural pathways for pictures and videos.
Facial expressions are known to impact observers' behavior, even when they are not consciously identifiable. Relying on visual crowding, a perceptual phenomenon whereby peripheral faces become undiscriminable, we show that participants exposed to happy vs. neutral crowded faces rated the pleasantness of subsequent neutral targets accordingly to the facial expression's valence. Using functional magnetic resonance imaging (fMRI) along with psychophysiological interaction analysis, we investigated the neural determinants of this nonconscious preference bias, either induced by static (i.e., pictures) or dynamic (i.e., videos) facial expressions. We found that while static expressions activated primarily the ventral visual pathway (including task-related functional connectivity between the fusiform face area and the amygdala), dynamic expressions triggered the dorsal visual pathway (i.e., posterior partietal cortex) and the substantia innominata, a structure that is contiguous with the dorsal amygdala. As temporal cues are known to improve the processing of visible facial expressions, the absence of ventral activation we observed with crowded videos questions the capacity to integrate facial features and facial motions without awareness. Nevertheless, both static and dynamic facial expressions activated the hippocampus and the orbitofrontal cortex, suggesting that nonconscious preference judgments may arise from the evaluation of emotional context and the computation of aesthetic evaluation.


Reductive metabolism of 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) and the induction of unscheduled DNA synthesis in rat and human derived cell lines.
The cellular and microsomal reductive metabolism of 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) was studied aerobically and anaerobically in rat (JB1, BL8, Walker) mouse (3T3) and human (HepG2) derived cell lines. In all cases rates or reduction to the mono-N-oxide (SR 4317) were greater under anaerobic than aerobic conditions when determined using HPLC with UV and fluorescence detection. Of the rat derived cells, a transformed liver epithelial line (JB1) showed the greatest cellular and microsomal rates of reduction while Walker 256 carcinoma cells showed the lowest. Microsomal reduction of SR 4233 was the highest in preparations from rat liver but carbon monoxide did not inhibit the reaction, suggesting cytochrome P450 was not involved. Purified cytochrome P450 reductase could carry out the reduction of SR4233. Rates of reduction of SR4233 in microsomal preparations from the cell lines and in rat liver nuclei correlated with activities of cytochrome P450 reductase. Activation of SR 4233 to cause cellular DNA damage was measured using unscheduled DNA synthesis as an index. Under anaerobic conditions, SR 4233 caused a dose-dependent increase in unscheduled DNA synthesis. Only a slight increase occurred following aerobic incubation. No increase was seen using the reduced metabolites SR 4317 or SR 4330. Of the cell lines studied, Walker cells showed the highest induction of unscheduled DNA synthesis. It was concluded that rates of reduction of SR 4233 did not necessarily reflect the potential DNA-damaging effects of this compound.


[Chronic pain in children: a largely unknown or forgotten fact?].
It is described the experience of the first 130 patients specifically treated by the first Spanish Unit of Chronic Pain in Children. The mean age of the patients was 7.6 years (SD 5.1). Sex distribution was 6:4 for male:female. The more frequents causes of pain were: Hematologic cancer (35%), neuropathic pain (15%) and juvenile chronic arthritis (12%). The mean duration of pain prior to pain treatment was 295 days. The main therapeutic option was treatment with opiate agents (79%) during a mean period of time of 111 days and mean decrease of 88.1% in pain intensity.


Determination of the median effective dose (ED50 ) of spinal chloroprocaine in labour analgesia.
The primary goal of this study was to determine the median effective dose (ED50 ) of spinal chloroprocaine for labour analgesia. Thirty-eight parturients requesting neuraxial analgesia were enrolled. Doses of 1% chloroprocaine were determined by the technique of up-down sequential allocation, with an initial dose of 20 mg and steps of 2 mg. The chloroprocaine spinal dose was given as the spinal component of a combined spinal-epidural, which was then supplemented with an epidural dose of 7.5 μg sufentanil in 7 ml saline. Effective analgesia was defined as a score ≤ 10 mm within 15 min on a 100-mm visual analogue pain scale. Using the isotonic regression estimator method, the ED50 of chloroprocaine for the spinal component of a combined spinal-epidural for labour was calculated to be median (95%CI) 12.0 (9.3-17.0) mg.


Development of ramified microglia from early macrophages in the zebrafish optic tectum.
Microglia, the resident macrophage precursors of the brain, are necessary for the maintenance of tissue homeostasis and activated by a wide range of pathological stimuli. They have a key role in immune and inflammatory responses. Early microglia stem from primitive macrophages, however the transition from early motile forms to the ramified mature resident microglia has not been assayed in real time. In order to provide such an assay, we used zebrafish transgenic lines in which fluorescent reporter expression is driven by the promoter of macrophage expressed gene 1 (mpeg1; Ellet et al. [2011]: Blood 117(4): e49-e56,). This enabled the investigation of the development of these cells in live, intact larvae. We show that microglia develop from highly motile amoeboid cells that are engaged in phagocytosis of apoptotic cell bodies into a microglial cell type that rapidly morphs back and forth between amoeboid and ramified morphologies. These morphing microglia eventually settle into a typical mature ramified morphology. Developing microglia frequently come into contact with blood capillaries in the brain, and also frequently contact each other. Up to 10 days postfertilization, microglia were observed to undergo symmetric division. In the adult optic tectum, the microglia are highly branched, resembling mammalian microglia. In addition, the mpeg1 transgene also labeled highly branched cells in the skin overlying the optic tectum from 8-9 days postfertilization, which likely represent Langerhans cells. Thus, the development of zebrafish microglia and their cellular interactions was studied in the intact developing brain in real time and at cellular resolution.


Towards a fuller assessment of benefits to children's health of reducing air pollution and mitigating climate change due to fossil fuel combustion.
Fossil fuel combustion by-products, including particulate matter (PM2.5), polycyclic aromatic hydrocarbons (PAH), nitrogen dioxide (NO2) and carbon dioxide (CO2), are a significant threat to children's health and equality. Various policies to reduce emissions have been implemented to reduce air pollution and mitigate climate change, with sizeable estimated health and economic benefits. However, only a few adverse outcomes in children have been considered, resulting in an undercounting of the benefits to this vulnerable population. Our goal was to expand the suite of child health outcomes addressed by programs to assess health and economic benefits, such as the Environmental Protection Agency (EPA) Benefits Mapping and Analysis Program (BenMAP), by identifying concentration-response (C-R) functions for six outcomes related to PM2.5, NO2, PAH, and/or PM10: preterm birth (PTB), low birthweight (LBW), autism, attention deficit hyperactivity disorder, IQ reduction, and the development of childhood asthma. We conducted a systematic review of the literature published between January 1, 2000 and April 30, 2018 to identify relevant peer-reviewed case-control and cohort studies and meta-analyses. In some cases meta-analyses were available that provided reliable C-R functions and we assessed their consistency with subsequent studies. Otherwise, we reviewed all eligible studies published between our search dates. For each pollutant and health outcome, we present the characteristics of each selected study. We distinguish between C-R functions for endpoints having a causal or likely relationship (PTB, LBW, autism, asthma development) with the pollutants for incorporation into primary analyses and endpoints having a suggestive causal relationship with the pollutants (IQ reduction, ADHD) for secondary analyses. We have identified C-R functions for a number of adverse health outcomes in children associated with air pollutants largely from fossil fuel combustion. Their incorporation into expanded assessments of health benefits of clean air and climate mitigation policies will provide an important incentive for preventive action.


Cardiovascular changes associated with obstructive sleep apnea syndrome.
Five men free of lung or cardiovascular diseases and with severe obstructive sleep apnea participated in a study on the impact of sleep states on cardiovascular variables during sleep apneas. A total of 128 obstructive apneas [72 from stage 2 non-rapid-eye-movement (NREM) sleep and 56 from rapid-eye-movement (REM) sleep] were analyzed. Each apnea was comprised of an obstructive period (OP) followed by a hyperventilation period, which was normally associated with an arousal. Heart rate (HR), stroke volume (SV), cardiac output (CO) (determined with an electrical impedance system), radial artery blood pressures (BP), esophageal pressure nadir, and arterial O2 saturation during each OP and hyperventilation period were calculated for NREM and REM sleep. During stage 2 NREM sleep, the lowest HR always occurred during the first third of the OP, and the highest was always seen during the last third. In contrast, during REM sleep the lowest HR was always noted during the last third of the OP. There was an inverse correlation when the percentage of change in HR over the percentage of change in SV during an OP was considered. The HR and SV changes during NREM sleep allowed maintenance of a near-stable CO during OPs. During REM sleep, absence of a compensatory change in SV led to a significant drop in CO. Systolic, diastolic, and mean BP always increased during the studied OPs.(ABSTRACT TRUNCATED AT 250 WORDS)


Apatinib exerts anti-tumour effects on ovarian cancer cells.
Apatinib, a small molecule inhibitor of VEGFR-2 tyrosine kinase, shows strong anti-tumour activity against various tumours. The function of apatinib in ovarian cancer, however, remains unclear. This study was conducted to investigate the effects and potential mechanisms by which apatinib modulates the biological function of ovarian cancer cells in vitro and in vivo. The effects of apatinib on ovarian cancer cells were determined by assessing cell viability, migration and invasion. The cell cycle distribution and apoptosis of ovarian cancer cells were analysed using flow cytometry. Western blotting was performed to determine the levels of signalling pathway markers. A mouse xenograft model was used to evaluate the efficacy of apatinib in preventing tumour growth. Apatinib did not appreciably affect ovarian cancer cell proliferation and vitality, but did inhibit ovarian cancer cell migration. Apatinib suppressed the epithelial-mesenchymal transition in ovarian cancer cells by inhibiting the JAK/STAT3, PI3K/AKT and Notch signalling pathways. Apatinib effectively inhibited tumour growth in vivo. Based on our findings, apatinib is a highly potent, orally active anti-angiogenic and anti-ovarian cancer agent.


Cerebrospinal fluid lactate as a marker to differentiate between community-acquired acute bacterial meningitis and aseptic meningitis/encephalitis in adults: a Danish prospective observational cohort study.
The ability of cerebrospinal fluid (CSF) lactate to distinguish between acute bacterial meningitis (ABM) and aseptic meningitis/encephalitis (AME) is debated. We assessed the diagnostic value of CSF lactate to discriminate between ABM and AME. We included 176 patients from a prospective adult cohort with neuroinfections. In total, 51 ABM and 125 AME patients with clinically and/or microbiologically diagnosed acute meningitis were examined with CSF-lactate and traditional markers for infection. Receiver operating characteristic (ROC) curves were used to assess diagnostic performance. In CSF, lactate, leukocytes, fraction of neutrophils, protein and glucose ratio, were significantly different between the ABM and AME groups. CSF lactate had the best diagnostic value, with an area under the curve (AUC) of 0.976 (95%CI 0.966-0.997) and using a cut-off of 3.5 mmol/L a sensitivity of 96% and specificity of 85%. Antibiotic treatment before lumbar puncture had no significant effect on the AUC of CSF lactate. Compared to traditional CSF-markers, CSF lactate is more accurate to distinguish between ABM and AME.


Corynebacterium diphtheriae endocarditis.
Two patients with Corynebacterium diphtheriae endocarditis have been observed in the past ten years. Both cases occurred sporadically. In one case toxigenic C. diphtheriae caused endocarditis in an immunized child with congenital heart disease. The second patient developed rapidly progressive valve destruction caused by a nontoxigenic strain of C. diphtheriae. These cases illustrate that C. diphtheriae may produce endocarditis in addition to its previously described diseases spectrum.


Buckling of stiff polymer rings in weak spherical confinement.
Confinement is a versatile and well-established tool to study the properties of polymers either to understand biological processes or to develop new nanobiomaterials. We investigate the conformations of a semiflexible polymer ring in weak spherical confinement imposed by an impenetrable shell. We develop an analytic argument for the dominating polymer trajectory depending on polymer flexibility considering elastic and entropic contributions. Monte Carlo simulations are performed to assess polymer ring conformations in probability densities and by the shape measures asphericity and nature of asphericity. Comparison of the analytic argument with the mean asphericity and the mean nature of asphericity confirm our reasoning to explain polymer ring conformations in the stiff regime, where elastic response prevails.


[Effects of hydrogen sulfide on the K ATP current in isolated rat ventricular myocytes].
To investigate the effects of endogenous and exogenous hydrogen sulfide (H(2)S) on the K(ATP) current in isolated rat ventricular myocytes. Ventricular myocytes were isolated from rat heart by modified Langendorff perfusion with collagenase. K(ATP) current of single rat ventricular myocytes was recorded by whole-cell patch-clamp technique. The density of K(ATP) current was significantly reduced by 200 micromol/L DL-propargylglycine (PPG, an irreversible inhibitor of the H(2)S) [(5.3258 +/- 0.7556) pA/pF vs. (3.7856 +/- 0.4312) pA/pF, P < 0.01] in a time-dependent way. The density of K(ATP) current could be significantly increased by NaHS (a H(2)S donor, 9.375, 18.75, 37.5, 75, 150 micromol/L) in a concentration-dependent manner [(6.6310 +/- 0.6092) pA/pF vs. (9.0949 +/- 1.0259) pA/pF at 150 micromol/L, P < 0.01]. Both endogenous and exogenous H(2)S could open K(ATP) channels and enhance the K(ATP) current in rat ventricular myocytes.


Molecular identification of combined homozygous and compound heterozygous mutations in the CYP21 gene in simple virilizing congenital adrenal hyperplasia in Taiwan.
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder mainly caused by defects in the steroid 21-hydroxylase (CYP21) gene. We have experience of molecular analysis of in the CYP21 gene in 85 unrelated CAH families, in Taiwan for ten years. All ten exons of were analyzed by differential polymerase chain reactions (PCR) followed by single-strand conformation polymorphism (SSCP) analysis and the amplification-created restriction site (ACRS) method. More than 90% of the mutations were due to conversion of DNA sequences into its neighboring homologous pseudogene CYP21P. The most frequent mutation found in CAH patients in Taiwan was intron 2 mutation; the others were exons 8, 4 and 3, respectively, decreasing by frequency. Those were single homozygous mutations. In this report, we present two kinds of special mutations in our molecular research. Four families had their babies coming from combined homozygous mutation of both parents, that is due to both intron 2 (nt656) and 8-bp mutation. Eleven families had their babies coming from paternal codon 172 and maternal intron 2 (nt656) compound heterozygous mutations, that is codon 172 pat/int 2 (nt656) mat mutation. These two mutations had clinical manifestation of virilization, that is, enlarged clitoris only, but neither clinical nor laboratory finding of salt-losing. From our study, we found that autosomal recessive disorders such as simple virilizing CAH in our series could result from either combined homozygous mutations or compound heterozygous mutations. Further molecular study will focus on the salt-losing type in order to correlate the genotype/phenotype with this study.


Heredity of interocular similarities in components of refraction: a population-based twin study among 66- to 79-year-old female twins.
To examine genetic influences on interocular similarities in ocular refraction and components of refraction among elderly female twins. Refraction was assessed in 94 monozygotic (MZ) and 74 dizygotic (DZ) female twins aged 66-78 years. Absolute values of interocular differences (Aniso variables) in spherical refraction (SR), refractive astigmatism (AST), spherical equivalent (SE), corneal refractive power (CR), corneal astigmatism (CAST), anterior chamber depth (ACD) and axial length (AL) were calculated. The differences between sisters in each of the Aniso variables were calculated and graded into two categories, best differentiating the groups, here isometropic and anisometropic values. The cut-offs for grading as isometropic were AnisoSR < 0.75 D, AnisoAST < 0.5 D, AnisoSE < 1.0 D, AnisoCR < 0.5 D, AnisoCAST < 0.50 D, AnisoACD < 0.1 mm and AniosAL < 0.1 mm. Genetic influences on these traits were investigated by comparing the prevalence of isometropic and anisometropic differences between the MZ and DZ pairs in the Aniso variables and the interrelationships between the Aniso variables. When the Aniso variables were treated as continuous, no significant differences were found between the MZ and DZ subjects. When the proportions of isometropic intratwinpair interocular differences in the Aniso variables in the MZ and DZ cotwins were compared, the prevalences (MZ/DZ) were AnisoSR: 68%/60%; AnisoAST: 66%/57%; AnisoSE: 87%/68%; AnisoCR: 83%/78%; AnisoCAST: 69%/35%; AnisoACD: 77%/63%; and AnisoAL: 76%/60%. The differences were statistically significant for Aniso SE (p = 0.035, Fisher's exact test) and CAST (p = 0.007). The greater homogeneity in the interocular differences between the MZ sisters supports the assumption that isometropia of different elements of refraction is genetically influenced and tending to continue up to older ages. In cases where AnisoSE was <1.0 D, higher CR in one eye was associated with shorter AL (r = -0.398, p < 0.001), thereby contributing to emmetropization, irrespective of zygosity. In the cases of AnisoSE ≥1 D, no similar influence on emmetropization was observed. The difference between sisters in AnisoSE was associated with the intratwinpair difference in Aniso AL, but not with the intratwinpair differences in AnisoCR, irrespective of zygosity. The higher prevalence of similarities in isometropia of the spherical equivalent and corneal astigmatism between the MZ pairs compared to DZ pairs is consistent with the view that genetic influences on the refractive elements of the eye, tending to isometropia, continue into older age. The interrelation between CR and AL tends to maintain isometropia of SE irrespective of zygosity.


E-Model for Online Learning Communities.
The purpose of this study was to explore the students' perspectives on the phenomenon of online learning communities while enrolled in a graduate dental hygiene program. A qualitative case study method was designed to investigate the learners' experiences with communities in an online environment. A cross-sectional purposive sampling method was used. Interviews were the data collection method. As the original data were being analyzed, the researchers noted a pattern evolved indicating the phenomenon developed in stages. The data were re-analyzed and validated by 2 member checks. The participants' experiences revealed an e-model consisting of 3 stages of formal learning community development as core courses in the curriculum were completed and 1 stage related to transmuting the community to an informal entity as students experienced the independent coursework in the program. The development of the formal learning communities followed 3 stages: Building a Foundation for the Learning Community, Building a Supportive Network within the Learning Community and Investing in the Community to Enhance Learning. The last stage, Transforming the Learning Community, signaled a transition to an informal network of learners. The e-model was represented by 3 key elements: metamorphosis of relationships, metamorphosis through the affective domain and metamorphosis through the cognitive domain, with the most influential element being the affective development. The e-model describes a 4 stage process through which learners experience a metamorphosis in their affective, relationship and cognitive development. Synergistic learning was possible based on the interaction between synergistic relationships and affective actions.


Somatosensory evoked potentials and headache: a further examination of the central theory.
The central theory of headache was investigated by examining the amplitude of the somatosensory evoked potential (SSEP) in headache sufferers and headache-free controls. The P1-N1 amplitude was found to be greater, and to increase more rapidly with increasing stimulus intensity, for headache subjects than for controls. The N1-P2 amplitude was also found to be larger for headache subjects than for controls, but there was no significant difference between groups on the rate at which this component increased with stimulus intensity. When the P1-N1 and N1-P2 amplitudes were assessed in headache subjects, during and between attacks, no significant differences between conditions were observed. No significant differences between tension and migraine sufferers were observed on either component. It was concluded that the central nervous systems of headache sufferers may be more reactive to somatosensory input than those of headache-free persons and that this might be an important factor in the pathophysiology of headache.


Textured domains on tense surfaces and membranes: Effect of tilt and chirality.
We study the shape and texture of finite domains comprising chiral or achiral molecules carrying tilt, embedded in a two-dimensional surface or membrane, using a combination of simulations and exact variational calculations. We find a variety of shapes and textures including rectangular-shaped domains and a spontaneously broken chiral texture, when the molecules are achiral. We show that chiral tilt domains nucleating in a region of two-phase coexistence repel each other, thereby preventing coalescence and further growth. Our work principally addresses observations of domains in multicomponent giant unilamellar vesicles. It may also be relevant in the study of domains in phospholipid monolayers, nucleating domains of Sm-C* in Sm-A films, and chiral emulsions in Sm-A films, in situations where we can ignore dipolar interactions.


Accidental potassium dichromate poisoning. Toxicokinetics of chromium by ICP-MS-CRC in biological fluids and in hair.
Intoxications by chromium (Cr) compounds are very life threatening and often lethal. After oral ingestion of 2 or 3g of hexavalent Cr (Cr(VI)), gastrointestinal injury, but also hepatic and renal failure, often occurs which each leads to a fatal outcome in most patients. Cellular toxicity is associated with mitochondrial and lysosomal injury by biologically Cr(VI) reactive intermediates and reactive oxygen species. After Cr(VI) has been absorbed, there is not much that can be done except to control the main complications as the treatment is only symptomatic. The biotransformation of Cr(VI) to Cr(III) reduces the toxicity because the trivalent form does not cross cellular membranes as rapidly. In fact, more than 80% of Cr(VI) is cleared in urine as Cr(III). We report the case of a 58-year-old male patient who was admitted to hospital after accidental oral ingestion of a 30 g/L potassium dichromate (the estimated amount of ingested Cr is about 3g). ICP-MS equipped with a collision/reaction cell (CRC) and validated methods were used to monitor plasma (P), red blood cells (RBCs), urine (U) and hair chromium. For urine the results were expressed per gram of creatinine. After 7 days in the intensive care unit, the patient was discharged without renal or liver failure. P, RBC and U were monitored during 49 days. During this period Cr decreased respectively from 2088 μg/L to 5 μg/L, 631 μg/L to 129 μg/L and 3512 μg/g to 10 μg/g. The half-life was much shorter in P than in RBC as the poison was more quickly cleared from the P than from the RBC, suggesting a cellular trapping of the metal. Hair was collected 2 months after the intoxication. We report a very rare case of survival after accidental Cr poisoning which has an extremely poor prognosis and usually leads to rapid death. For the first time, this toxicokinetic study highlights a sequestration of chromium in the RBC and probably in all the cells.


Chemical modification of cytochrome P-450 LM2. Characterization of tyrosine as axial heme iron ligand trans to thiolate.
Phenobarbital-inducible isozyme cytochrome P-450 LM2 (RH, reduced-flavoprotein:oxygen oxidoreductase (RH-hydroxylating), EC 1.14.14.1) from rabbit liver microsomes has been modified with N-acetylimidazole and tetranitromethane. Up to four tyrosine residues of cytochrome P-450 LM2 are accessible to O-acetylation and to nitration. N-Demethylase activity, spectral dissociation constants and substrate binding kinetics of differently acetylated enzyme indicate the existence of two groups of accessible tyrosines also differing in their reactivity towards N-acetylimidazole. The fast-reacting tyrosine residue representing the first group is involved in the binding of the type II substrate aniline and appears to be located near the heme as shown by the protecting effect of the inhibitor metyrapone against modification, but obviously is not necessary for N-demethylation. Acetylation of one further tyrosine residue, however, caused an almost complete inhibition of the enzyme, indicating its involvement in the catalytic mechanism at the active center. Nitration of two tyrosine residues inactivates to about 20%. Obviously the third and fourth tyrosine residue are without functional importance. The experiments evidencing two functionally linked tyrosines are in line with HPLC analyses of tryptic peptides of cytochrome P-450 LM2 nitrated in the presence of metyrapone which gave evidence for the location of two distinct tyrosine residues in the active center. Nitration of tyrosine residues results in the partial formation of a hyperporphyrin spectrum of cytochrome P-450 LM2. Its appearance is prevented in the presence of metyrapone and can be reversed by reduction of the nitrotyrosinate .


Cardiac rhabdomyoma presenting as fetal hydrops.
Fetal hydrops and possible congenital heart disease with atrioventricular block was diagnosed one day before birth in a male infant of 35 weeks' gestation. Echocardiography and angiocardiography soon after birth revealed a cardiac tumor. The child died three days after birth. Necropsy showed tuberous sclerosis involving the heart (type-I rhabdomyoma), kidneys, retina, and central nervous system.


Regional deposition of inhaled 11C-nicotine vapor in the human airway as visualized by positron emission tomography.
The deposition of 11C-nicotine in the respiratory tract from a nicotine vapor inhaler was studied by means of positron emission tomography (PET) in an intrasubject comparison of six healthy smokers using two modes of inhalation: one with shallow, frequent inhalations ("buccal mode") and one with deep inhalations ("pulmonary mode"). An average of 15% of the radioactivity was released from the vapor inhaler after 5 minutes of inhalation. Approximately 45% of the dose released was found in the oral cavity. A significant amount of radioactivity, 10%, was observed in the esophagus, suggesting transfer of a major fraction of the dose to the stomach. Only a minor fraction, 5%, was found in the lungs, followed by 2% in the bronchi and 1% in the trachea. The deposition in the oral cavity closely followed a linear pattern during the 5 minutes of inhalation and was followed by a rapid elimination from the oral cavity, with an average half-life of 18 minutes. Only 8% of the dose released remained in the oral cavity 45 minutes after the end of inhalation. On the other hand, the dose fraction of about 14% distributed into the body tissue compartment at the end of inhalation had risen to 60% at that late time point. No statistically or clinically important differences were observed between the buccal and the pulmonary mode of inhalation in either deposition pattern or elimination rates.


Basal follicle-stimulating hormone and peak gonadotropin levels after gonadotropin-releasing hormone infusion show high diagnostic accuracy in boys with suspicion of hypogonadotropic hypogonadism.
Differential diagnosis between hypogonadotropic hypogonadism (HH) and constitutional delay of puberty in boys is challenging. Most tests use an acute GnRH stimulus, allowing only the release of previously synthesized gonadotropins. A constant GnRH infusion, inducing de novo gonadotropin synthesis, may allow a better discrimination. We evaluated the diagnostic accuracy of basal and peak gonadotropins after GnRH infusion, measured by ultrasensitive assays, to confirm the diagnosis in boys with suspected HH. We conducted a validation study following Standards for Reporting of Diagnostic Accuracy criteria at a tertiary public hospital. A GnRH i.v. infusion test was performed in 32 boys. LH and FSH were determined by immunofluorometric assay at 0-120 min. DIAGNOSIS ASCERTAINMENT: The following diagnoses were ascertained: complete HH (n = 19; testes < 4 ml at 18 yr), partial HH (n = 6; testes enlargement remained arrested for > or = 1 yr or did not reach 15 ml), and constitutional delay of puberty (n = 7; testes > or = 15 ml at 18 yr). Sensitivity, specificity, positive and negative predictive values, and diagnostic efficiency were assessed. Basal FSH less than 1.2 IU/liter confirmed HH with specificity of 1.00 (95% confidence interval = 0.59-1.00), rendering GnRH infusion unnecessary. In patients with basal FSH of at least 1.2 IU/liter, the coexistence of peak FSH less than 4.6 IU/liter and peak LH less than 5.8 IU/liter after GnRH infusion had high specificity (1.00; 95% confidence interval = 0.59-1.00) and diagnostic efficiency (76.9%) for HH. Basal FSH less than 1.2 IU/liter confirms HH, which precludes from further testing, reducing patient discomfort and healthcare system costs. In patients with basal FSH of at least 1.2 IU/liter, a GnRH infusion test has a high diagnostic efficiency.


Unlocking the doors to Canadian older inmate mental health data: Rates and potential legal responses.
This article is based on a quantitative study investigating the quality of life of older Canadian prisoners. For this study, social science methodology was used to answer certain legal questions, such as: what are the mental health issues of older male offenders and how are these needs influencing the exercise of their legal rights? Are institutions prepared to deal with the increased needs of older offenders? If no, is this an infringement of this group's rights? In this article, the mental health problems of older offenders are first outlined. Second, the legal, policy, and institutional limitations in responding to these problems are described. Based on these findings, it is maintained that a change in the treatment of older offenders is needed. Third, statutory and constitutional challenges are explored. If change does not come voluntarily, it is the duty of the courts to have a flexible and open-minded approach toward different actions that challenge the current prison regime.


Quality: walk the walk.
The College of American Pathologists (CAP) is dedicated to pathology and laboratory medicine quality. The CAP's Laboratory Accreditation Program, Proficiency Testing Program, Q-Probes and Q-Tracks, site-specific cancer checklists, webinars, annual meetings, and Advanced Practical Pathology series are all focused on providing superior patient quality. The CAP is synonymous with quality in pathology and laboratory medicine. As pathology practice becomes more sophisticated, the CAP's many programs will increasingly help pathologists provide appropriate, personalized care.


[Philosophy within the context of neurosciences].
Based on the interrelation between science and philosophy, this article addresses the impact of neurosciences on the philosophical issues posed by today's society, especially those related with epistemology and the philosophy of science. To do so, the different approaches in the cognitive sciences are taken into account, with special attention paid to those that have to do with social, embodied and situated cognition versus a more individual, rational and abstract cognition. This initial framework is taken as the starting point with which to analyse the ways of representing knowledge and the characteristics of the cognoscente agent.


Humoral and cell-mediated immune responses to epidermal growth factor in the rabbit.
Epidermal growth factor (EGF), which has been shown to stimulate epidermal proliferation and keratinization and to induce regeneration of rabbit corneal epithelium, was studied for its immunogenic potential in rabbits. Mouse-derived EGF was administered topically, subconjunctivally, intrastromally, and systemically. Systemic immunization was done both with and without complete Freund's adjuvant (CFA). EGF-stimulated cultures of lymphocytes from peripheral blood, spleen, and lymph nodes of all immunized animals were tested for cell-mediated immunity (CMI) to EGF. All experimental animals demonstrated CMI as determined by either classic positive delayed skin tests or by in vitro production of migration inhibitory factors, regardless of the route of sensitization. Only animals immunized systemically with EGF and CFA produced high-titered specific anti-EGF antibody, and only this group showed ocular reactions after subsequent topical challenge of EGF. These results suggest that antibody to EGF is the major cause for ocular inflammatory reactions observed subsequent to topical EGF challenge of a sensitized animal.


Prodrug of green tea epigallocatechin-3-gallate (Pro-EGCG) as a potent anti-angiogenesis agent for endometriosis in mice.
Green tea epigallocatechin-3-gallate (EGCG) can inhibit angiogenesis and development of an experimental endometriosis model in mice, but it suffers from poor bioavailability. A prodrug of EGCG (pro-EGCG, EGCG octaacetate) is utilized to enhance the stability and bioavailability of EGCG in vivo. In this study, the potential of pro-EGCG as a potent anti-angiogenesis agent for endometriosis in mice was investigated. Homologous endometrium was subcutaneously transplanted into mice to receive either saline, vitamin E, EGCG or pro-EGCG treatment for 4 weeks. The growth of the endometrial implants were monitored by IVIS(®) non-invasive in vivo imaging during the interventions. Angiogenesis of the endometriotic lesions was determined by Cellvizio(®) in vivo imaging and SCANCO(®) Microfil microtomography. The bioavailability, anti-oxidation and anti-angiogenesis capacities of the treatments were measured in plasma and lesions. The implants with adjacent outer subcutaneous and inner abdominal muscle layers were collected for histological, microvessel and apoptosis examinations. The result showed that EGCG and pro-EGCG significantly decreased the growth of endometrial implants from the 2nd week to the 4th week of intervention. EGCG and pro-EGCG significantly reduced the lesion size and weight, inhibited functional and structural microvessels in the lesions, and enhanced lesion apoptosis at the end of interventions. The inhibition by pro-EGCG in all the angiogenesis parameters was significantly greater than that by EGCG, and pro-EGCG also had better bioavailability and greater anti-oxidation and anti-angiogenesis capacities than EGCG. Ovarian follicles and uterine endometrial glands were not affected by either EGCG or pro-EGCG. Vitamin E had no effect on endometriosis. In conclusion, pro-EGCG significantly inhibited the development, growth and angiogenesis of experimental endometriosis in mice with high efficacy, bioavailability, anti-oxidation and anti-angiogenesis capacities. Pro-EGCG could be a potent anti-angiogenesis agent for endometriosis.


[Study on the cause-specific mortality attributable to smoking among males in Tianjin].
Prevalence rates related to smoking and second hand smoking exposure were high in Tianjin, particularly among males. Our study aimed to analyze all cause of deaths attributable to smoking in male citizens in Tianjin. Data on 38 312 death cases aged 18-69 years old were collected from 2010 to 2012. Odds ratio of deaths on different disease and excess deaths attributed to smoking, after adjusting age and education level were calculated. 22.57% of the male death cases were caused by smoking in Tianjin, and smokers'5 years of life loss due to the habit of smoking. Compared to the non-smokers, the mortality risks appeared as:lung cancer (OR = 3.10, 95% CI:2.80-3.44), heart disease (OR = 1.47, 95% CI:1.36-1.59), and stroke (OR = 1.41, 95% CI:1.30-1.53). The mortality risk attributed to smoking was higher in urban than that in rural areas. Factors as smoking initiated at early age and plenty daily cigarette consumption were both associated with risk of high mortality. Results from our study addressed the problem that smoking had been a major risk factor for mortality and productivity loss in male adults in Tianjin. Prevention programs and initiatives on reducing the rates of smoking and second hand smoking should be strengthened to decrease the smoking-related deaths in Tianjin.


Real-time target tracking of soft tissues in 3D ultrasound images based on robust visual information and mechanical simulation.
In this paper, we present a real-time approach that allows tracking deformable structures in 3D ultrasound sequences. Our method consists in obtaining the target displacements by combining robust dense motion estimation and mechanical model simulation. We perform evaluation of our method through simulated data, phantom data, and real-data. Results demonstrate that this novel approach has the advantage of providing correct motion estimation regarding different ultrasound shortcomings including speckle noise, large shadows and ultrasound gain variation. Furthermore, we show the good performance of our method with respect to state-of-the-art techniques by testing on the 3D databases provided by MICCAI CLUST'14 and CLUST'15 challenges.


Relations of Ruminal Fermentation Parameters and Microbial Matters to Odd- and Branched-Chain Fatty Acids in Rumen Fluid of Dairy Cows at Different Milk Stages.
The purpose of this research was to evaluate whether relationships exist between odd- and branched-chain fatty acids (OBCFAs) originating from milk fat and the corresponding data of ruminal fermentation parameters, microbial populations, and base contents that were used to mark microbial protein in rumen. Nine lactating Holstein dairy cows with similar body weights and parity were selected in this study, and the samples of rumen and milk were collected at the early, middle, and late stages, respectively. The rumen and milk samples were collected over three consecutive days from each cow, and the ruminal and milk OBCFA profiles, ruminal fermentation parameters, bacterial populations, and base contents were measured. The results showed that the concentrations of OBCFAs, with the exception of C11:0 and C15:0, were significantly different between milk and rumen (p < 0.05). The concentrations of anteiso-fatty acids in milk were higher than those in rumen, and the contents of linear odd-chain fatty acids were higher than those of branched-chain fatty acids in both milk and rumen. Significant relationships that existed between the concentrations of C11:0, iso-C15:0, anteiso-C15:0, C15:0, and anteiso-C17:0 in rumen and milk (p < 0.05). The total OBCFA content in milk was positively related to the acetate molar proportion but negatively correlated with isoacid contents (p < 0.05). The populations of Ruminococcus albus, R. flavefacients, and Eubacterium ruminantium were significantly related to milk C13:0 contents (p < 0.05). The adenine/N ratio was negatively related to milk OBCFA content (p < 0.05) but positively associated with the iso-C15:0/iso-C17:0 ratio (p < 0.05). Milk OBCFAs were significantly correlated with ruminal fermentation parameters, ruminal bacterial populations, and base contents. Milk OBCFAs had the potential to predict microbial nitrogen flow, and the prediction equations for ruminal microbial nitrogen flow were established for OBCFAs in dairy milk.


Effects of stuttering severity and therapy involvement on role entrapment of people who stutter.
The primary purpose of this study was to examine whether a group of university students would report role entrapment of people who stutter (PWS) in the form of occupational stereotyping. The study also examined whether severity of stuttering (mild or severe) and level of therapy involvement (choosing or not choosing to attend therapy) affected the perceptions of role entrapment. To examine these issues, 260 students completed the Vocational Advice Scale (VAS) [Gabel, R. M., Blood, G. W., Tellis, G., & Althouse, M. T. (2004). Measuring role entrapment of people who stutter. Journal of Fluency Disorders, 29, 27-49]. Results suggested that stuttering severity and the level of therapy involvement did not appear alter the judges' reports for all of the careers except for the career of speech therapist. For the career of speech therapist, therapy involvement improved the participants' reports and stuttering severity had no effect. Additionally, findings suggested that university students reported that 16 of the careers listed on the VAS were appropriate choices for people who stutter and were less certain about advising for 27 of the careers. Thus, the findings from this study do not support the notion that stuttering leads to role entrapment in the form vocational stereotyping and variations in therapy involvement or stuttering severity do not change perceptions of role entrapment. LEARNER OUTCOMES: The reader will be able to (1) identify common stereotypes of PWS, (2) describe the possible effects of stereotyping and role entrapment, and (3) describe the effects of severity and therapy involvement of role entrapment of PWS.


Serum‑derived hepatitis C virus can infect human glioblastoma cell line SF268 and activate the PI3K‑Akt pathway.
Extra‑hepatic manifestations are frequently observed in hepatitis C virus (HCV)‑infected patients; however the underlying mechanisms remain largely unknown. In the present study, the human glioblastoma SF268 cell line (the precise origin of the cell type is not clear) was infected with HCV using HCV‑positive serum, and viral replication was assessed by immunofluorescence, reverse transcription‑polymerase chain reaction (PCR), quantitative PCR and western blotting following infection. HCV core protein and HCV RNA were detected in HCV‑positive serum‑infected SF268 cells at day 4 post‑infection, while no infection was observed in cells exposed to HCV‑negative serum. The mean HCV RNA levels at day 4 post‑infection were up to 5.00 IU/ml log10; however, HCV RNA and immunostaining for core protein were negative when cultured to day 6 or longer. The data suggest that human glioblastoma SF268 cells were transiently infected with HCV. AKT serine/threonine kinase phosphorylation was also detected in HCV‑infected SF268 cells at day 4 post‑infection. To the best of our knowledge, this is the first demonstration that a human glioblastoma cell line can be infected with serum‑derived HCV. The results provide evidence that HCV infection can occur in cells of the central nervous system. Neurological disorder‑associated phosphoinositide 3‑kinase‑AKT signaling pathway was activated in parallel with HCV infection, suggesting that SF268 may serve as an in vitro model for investigating HCV‑nervous system cell interactions.


MURCS association with encephalocele: report of a second case.
We report a female fetus with occipital encephalocele, dysraphism of the cervical spine, right renal agenesis and Mullerian agenesis. Additional findings included posterior cleft palate, absent left umbilical artery and Meckel's diverticulum. This fetus had the features of MURCS association with occipital encephalocele. This is the second report of encephalocele with MURCS association.


[The distribution of Sn2+ after application as a complex (author's transl)].
On animal experiments was shown that Sn2+ after i.v. application with 113Sn as radioactiv indicator was deposited in the skeleton. Experiments were done with citrat-, tartrat-, pyrophosphat-, phosphat- and Sn2+/HCl-complexes. The importance of the results for the use of Sn2+-solutions in Nuclear Medicine for men are discussed.