Urethral stricture following transurethral prostatectomy.
Urethral stricture is the most common late complication of transurethral prostatectomy. Uroflowmetry is recommended as the routine screening procedure for strictures postoperatively. If maximal urinary flow rate (Qmax) is below 10 mL/second the patients should be investigated further. The etiology of urethral stricture is still unclear. Further studies are necessary to evaluate the possible etiologic role of infected urine pre- and/or postoperatively, urethral catheterization pre- and postoperatively, catheter material, and the type and size of the resectoscope. A narrow urethra is probably a predisposing factor for stricture formation, but this is not definitively clarified. Only few randomized studies have been performed to evaluate the different prophylactic methods against development of strictures postresection. Resection via perineal urethrotomy, perhaps preceded by urethral calibration, seems to be a way to avoid anterior urethral strictures. The effects of internal urethrotomy preoperatively on stricture formation are conflicting. Further randomized studies are necessary.


Multivalency in supramolecular chemistry and nanofabrication.
Multivalency is a powerful and versatile self-assembly pathway that confers unique thermodynamic and kinetic behavior onto supramolecular complexes. The diversity of the examples of supramolecular multivalent systems discussed in this perspective shows that the concept of multivalency is a general phenomenon, and that any supramolecular interaction can be employed in multivalent displays to attain the attractive aspects characteristic of multivalent interactions. After a general introduction reviewing the general aspects of multivalency, a number of different supramolecular multivalent complexes are discussed that highlight the different features of multivalent interactions. In contrast to the many biochemical multivalent interactions, supramolecular multivalent interactions are ideal to attain a quantitative and fundamental understanding of multivalency. Several examples in which multivalency has been utilized in supramolecular nanofabrication schemes are described in detail.


Feasibility of DAIly NURSE: A nursing intervention to change nursing staff behaviour towards encouraging residents' daily activities and independence in the nursing home.
To examine the feasibility of DAIly NURSE and a nursing intervention to encourage nursing home residents' daily activities and independence. Nursing home residents are mainly inactive during the day. DAIly NURSE was developed to change nursing behaviour towards encouraging nursing home residents' activities and independence by creating awareness. It consists of three components: education, coaching-on-the-job and policy. A mixed-method study. The feasibility of DAIly NURSE in practice was tested in six psychogeriatric nursing home wards, using attendance lists (reach), evaluation questionnaires (fidelity, dose received and barriers), notes made by the researcher (dose delivered and fidelity) and a focus group interview (dose received and barriers) with nursing home staff (n = 8) at the end of the study. The feasibility study showed that all three components (education, coaching-on-the-job and policy) were implemented in practice. The attendance rate in the workshops was high (average: 82%). Nursing home staff were satisfied with the workshops (mean score 9 out of 10 points) and agreed that DAIly NURSE was feasible in daily nursing care practice. Recommendations to optimise the feasibility of DAIly NURSE included the following: Add video observations of a specific moment of the day to create awareness of nursing behaviour; educate all nursing staff of the ward during the workshops; and organise information meetings for family members before the start of the intervention. Nursing staff were satisfied with the intervention and provided recommendations for adjustments to the content of the three components. The most important adjustment is the use of video observations to create awareness of nursing staff behaviour. DAIly NURSE, consisting of education, coaching-on-the-job and policy, is feasible in nursing home practice. DAIly NURSE might help to change nursing behaviour towards encouraging residents' daily activities and independence.


Use of inert gas jets to measure the forces required for mechanical gene transfection.
Transferring genes and drugs into cells is central to how we now study, identify and treat diseases. Several non-viral gene therapy methods that rely on the mechanical disruption of the plasma membrane have been proposed, but the success of these methods has been limited due to a lack of understanding of the mechanical parameters that lead to cell membrane permeability. We use a simple jet of inert gas to induce local transfection of plasmid DNA both in vitro (HeLa cells) and in vivo (chicken chorioallantoic membrane). Five different capillary tube inner diameters and three different gases were used to treat the cells to understand the dependency of transfection efficiency on the dynamic parameters. The simple setup has the advantage of allowing us to calculate the forces acting on cells during transfection. We found permeabilization efficiency was related to the dynamic pressure of the jet. The range of dynamic pressures that led to transfection in HeLa cells was small (200 ± 20 Pa) above which cell stripping occurred. We determined that the temporary pores allow the passage of dextran up to 40 kDa and reclose in less than 5 seconds after treatment. The optimized parameters were also successfully tested in vivo using the chorioallantoic membrane of the chick embryo. The results show that the number of cells transfected with the plasmid scales with the dynamic pressure of the jet. Our results show that mechanical methods have a very small window in which cells are permeabilized without injury (200 to 290 Pa). This simple apparatus helps define the forces needed for physical cell transfection methods.


Dysplastic melanocytic nevi: a reproducible histologic definition emphasizing cellular morphology.
Histologic criteria commonly used to diagnose dysplastic melanocytic nevi (DMN) have not been correlated adequately with biology nor subjected to rigorous reproducibility studies. To address these failings, we developed histologic definitions emphasizing cellular morphology based on the appearance of typical melanocytes in sun-protected buttock skin, fully-evolved atypia in the vertical component of metastasizing primary cutaneous melanomas, and slight and moderate degrees of atypia defined within these limits in selected varieties of DMN. Reproducibility of our histologic definitions were tested by using two pathologists working independently to assess single routine tissue sections of 19 melanocytic lesions on two occasions at least 6 mo apart. Lesions included five previously diagnosed primary invasive cutaneous melanomas, seven lesions selected for gross morphologic features characteristic of DMN, and four solar lentigines and three common acquired nevomelanocytic nevi preselected for typical appearance and stable growth history. For the primary pathologist using the grading scheme, agreement rates between first and second readings were 84% for final diagnosis and 79% for the highest degree of cellular atypia; for the secondary pathologist, agreement rates for first and second readings for both parameters were 84%. Agreement rates comparing second readings of final diagnosis and highest degree of cellular atypia by the two pathologists were 89% and 79%, respectively. Most of the architectural and host response features commonly associated with DMN were less reproducible. In conclusion, we demonstrated very good reproducibility of histologic definitions used to differentiate the intraepidermal component of DMN from that of melanoma and benign melanocytic and nevomelanocytic hyperplasias, based on a biologic correlation emphasizing cellular morphology. Reproducible histologic definitions are a requisite first step in defining a clinical-pathologic correlation for DMN.


Influence of the restoration quality on the success of pulpotomy treatment: a preliminary retrospective study.
The aim of this study was to evaluate the clinical status of pulpotomy treatment with calcium hydroxide and to correlate it with the quality of restoration of the treated teeth. Patients were retrieved from the files of the Operative Dentistry clinics (FOUFPel) between 1996 and 2000. Twenty-two patients were recalled, which had 23 teeth treated with pulpotomy due to exposure by caries. Seven anterior and 16 posterior teeth composed the evaluated group, being all restored with composite resin. The age varied from 15-50 years (mean 23.9) and the follow-up mean was 34.52 months. Clinical and radiographic examinations were performed to evaluate the clinical status of treatment. The criteria used, clinically favorable and failure, were based on the following clinical exams: pulp vitality; sensitivity; and periapical alterations. The quality of the restorations was based on the USPHS criteria. Pulpotomy treatment was ranked as clinically favorable in 10 teeth (43.5%), 4 in anterior and 6 in posterior teeth. Failure was verified in 13 teeth (56.5%), 4 anterior and 9 posterior. From the group clinically favorable, 90% of the restorations were ranked as clinically satisfactory, while only 10% were unsatisfactory. In the failure group, 77.8% of the restorations were classified was unsatisfactory and 22.2% were ranked as satisfactory. The statistical analysis (Fisher´s exact test) demonstrated that there is a statistically significant association between the clinical status of pulpotomy and restoration quality (p<0.05). Within the limitation of the study, it was verified that the quality of restoration could influence the favorable clinical status of pulpotomized teeth. Randomized clinical trials are required to confirm these preliminary data.


Status of Schistosoma mansoni prevalence and intensity of infection in geographically apart endemic localities of Ethiopia: a comparison.
Schistosomiasis is one of the chronic and neglected tropical diseases affecting rural communities. Heavy infections contribute to anemia and can retard children's growth, physical activity and cognitive function. This study was conducted in order to determine the prevalence, intensity and variation of Schistosoma mansoni infection among human subjects in geographically apart localities. The prevalence and intensity of Schistosoma mansoni infection was assessed in three geographically apart endemic areas of Ethiopia from May to August 2010 through cross-sectional approach. A total of 1073 individuals (528 males and 545 females) were found eligible for the study. Their age ranged from 5-60 years with mean age of 11 years in Wondo Genet, 22 years in Kemissie and 24 years in Sille-Elgo. Small plastic sheets were distributed to the study participants and sizable stool specimens were collected and examined using Kato-Katz method (41.7mg template). The prevalence of Schistosoma mansoni infection among the study participants in Kemissie, Wondo Genet and Sille-Elgo was 89.6%, 59.9%, and 31.6%, respectively. The highest geometric mean of egg per gram of stool for Kemissie, Wondo Genet and Sille-Elgo was, 5208 and 346, 8472 and 252, 3960 and 91, respectively. It was observed that there was comparable variation in the prevalence and intensity of infection among the study localities. Moreover, it is indicated that S. mansoni is still an ongoing public health problem which requires integrated intervention activities in the country.


Elevated blood lactate is associated with increased motor cortex excitability.
No information has yet been provided about the influence of blood lactate levels on the excitability of the cerebral cortex, in particular, of the motor cortex. The aim of the present study was to examine the effects of high blood lactate levels, induced with a maximal cycling or with an intravenous infusion, on motor cortex excitability. The study was carried out on 17 male athletes; all the subjects performed a maximal cycling test on a mechanically braked cycloergometer, whereas 6 of them were submitted to the intravenous infusion of a lactate solution (3 mg/kg in 1 min). Before the exercise or the injection, at the end, as well as 5 and 10 min after the conclusion, venous blood lactate was measured and excitability of the motor cortex was evaluated by using the transcranial magnetic stimulation. In both of these experimental conditions, it was observed that an increase of blood lactate is associated with a decrease of motor threshold, that is, an enhancement of motor cortex excitability. We conclude by hypothesizing that in the motor cortex the lactate could have a protective role against fatigue.


Synthesis and evaluation of acyl protein thioesterase 1 (APT1) inhibitors.
Lipid-modified proteins play decisive roles in important biological processes such as signal transduction, organisation of the cytoskeleton and vesicular transport. Lipidation of these proteins is essential for correct biological function. Among the modifications with lipids, prenylation and myristoylation are well understood. However, the machinery of palmitoylation is still under investigation. Recently, an enzyme, acyl protein thioesterase 1 (APT1), that may play a regulatory role in the palmitoylation cycle of H-Ras and G-protein alpha subunits, was purified. Motivated by this work, several inhibitors of APT1 were designed, synthesized and biologically evaluated leading to highly active compounds.


The Effect of COVID 19 on Liver Parenchyma Detected and measured by CT scan Hounsfield Units.
COVID 19 may affect organs other than lungs, including liver, leading to parenchymal changes. These changes are best assessed by unenhanced computed tomography (CT). We aim to investigate the effect of COVID 19 on liver parenchyma by measuring the attenuation in CT scan Hounsfield unit (HU). A cohort of patients, who tested COVID 19 polymerase chain reaction positive, were enrolled and divided into two groups: fatty liver (FL) group (HU ≤ 40) and nonfatty liver (NFL) group (HU > 40) according to liver parenchyma attenuation measurements by high resolution noncontrast CT scan. The CT scan was performed on admission and on follow up (10-14 days later). Liver enzyme tests were submitted on admission and follow up. Three hundred and two patients were enrolled. Liver HU increased significantly from 48.9 on admission to 53.4 on follow up CT scan (P<0.001) in all patients. This increase was more significant in the FL group (increased from 31.9 to 42.9 [P =0.018]) Liver enzymes were abnormal in 22.6% of the full cohort. However, there was no significant change in liver enzymes between the admission and follow up in both groups. The use of unenhanced CT scan for assessment of liver parenchymal represents an objective and noninvasive method. The significant changes in parenchymal HU are not always accompanied by significant changes in liver enzymes. Increased HU values caused by COVID 19 may be due to either a decrease in the fat or an increase in the fibrosis in the liver.


Is there any Relationship Between Bladder Trabeculation and Efficacy and Safety of Intravesical Botulinum Toxin A Injection in Refractory Idiopathic Overactive Bladder Women?
Intradetrusor injection of botulinum toxin A (BTX-A) might serve as a minimally invasive substitute in patients with refractory idiopathic overactive bladder (RIOAB). The aim of this study was to evaluate the clinical outcomes related to two different doses of abo-BTX-A (AboBTX-A) in patients with RIOAB. This prospective clinical trial was performed on 55 women with RIOAB. After determination of trabeculation grade, 300 (no or mild) or 500 (moderate or severe) unit of AboBTX-A (Dysport) was intravesicaly injected. Before 1, 3, and 6 months after intervention, lower urinary tract symptoms during 24 h were recorded. Of the study population, 62% had severe bladder trabeculation. The mean duration of overactive bladder (OAB) was 1.76 versus 5.85 years, for no or mild versus severe trabeculation, respectively. After injections of 300- and 500-unit dosage, there were 19% and 26% early complications such as urinary retention. There was a statistically significant difference between the two groups in OAB score after 1 month (P < 0.001) and duration of OAB symptoms, over three follow-up times (P < 0.001). The mean preinjection OAB scores between patients with and without recurrence were statistically significant (29.36 vs. 25.07; P < 0.03). Urinary tract infection as a late complication was distinguished in four patients. In RIOAB, by adjusted dosage of AboBTX-A related to the grade of bladder trabeculation, in addition to maintain efficacy, consequent complications might not be affected by dosage and the drug dosage could be increased to nearly 60% with less concern associated to complication.


Assessing the Invasion Risk of Humulus scandens Using Ensemble Species Distribution Modeling and Habitat Connectivity Analysis.
Given the rapid spread of invasive alien plant species in Europe and limited information regarding their distribution and dispersion patterns, we analyzed the invasive risk of Humulus scandens, a species with an increased invasive potential. We collected occurrence records from Romania within an EU funded project and literature data, in order to perform an ensemble distribution model. Environmental variables varied from downscaled topoclimatic continuous entries to categorical ones, such as soil class, texture, or land use. Results showed potential core areas of the species within the study region. By inverting the probability output of the models, we have created a resistance surface which helped us model its dispersion patterns. Further, we assessed the probability of invasion for each resulted corridor using the species dispersion ecology and created an invasion risk map. H. scandens is highly influenced by milder climates and areas with constant flooding events, thus we found that the Tisa basin and its tributaries can be under a high invasion risk, spreading through the entire catchment, in Central, Western, and Northern Romania, towards the Eastern Carpathians. The Danube acted as a dispersion corridor for major river systems in southern Romania, but the dispersion capability of the species dropped in steppe areas with higher aridity and limited water course network. This approach is useful for creating adequate action plans in relation to invasive alien plant species, and should urgently be regarded, as results show a potentially large distribution of H. scandens across entire water catchment areas, with devastating effects on natural ecosystems.


Global and regional analysis of climate and human drivers of wildfire.
Identifying and quantifying the statistical relationships between climate and anthropogenic drivers of fire is important for global biophysical modelling of wildfire and other Earth system processes. This study used regression tree and random forest analysis on global data for various climatic and human variables to establish their relative importance. The main interactions found at the global scale also apply regionally: greatest wildfire burned area is associated with high temperature (> 28 °C), intermediate annual rainfall (350-1100 mm), and prolonged dry periods (which varies by region). However, the regions of highest fire incidence do not show clear and systematic behaviour. Thresholds seen in the regression tree split conditions vary, as do the interplay between climatic and anthropogenic variables, so challenges remain in developing robust predictive insight for the most wildfire-threatened regions. Anthropogenic activities alter the spatial extent of wildfires. Gross domestic product (GDP) density is the most important human predictor variable at the regional scale, and burned area is always greater when GDP density is minimised. South America is identified as a region of concern, as anthropogenic factors (notably land conversions) outweigh climatic drivers of wildfire burned area.


Heterogeneous nucleation at a wall near a wetting transition: a Monte Carlo test of the classical theory.
While for a slightly supersaturated vapor the free energy barrier ΔF(hom)(*), which needs to be overcome in a homogeneous nucleation event, may be extremely large, nucleation is typically much easier at the walls of the container in which the vapor is located. While no nucleation barrier exists if the walls are wet, for incomplete wetting of the walls, described via a nonzero contact angle Θ, classical theory predicts that nucleation happens through sphere-cap-shaped droplets attracted to the wall, and their formation energy is ΔF(het)(*) = ΔF(hom)(*)f(Θ), with f(Θ) = (1-cosΘ)(2)(2+cosΘ)/4. This prediction is tested through simulations for the simple cubic lattice gas model with nearest-neighbor interactions. The attractive wall is described in terms of a local 'surface field', leading to a critical wetting transition. The variation of the contact angle with the strength of the surface field is determined by using thermodynamic integration methods to obtain the wall free energies which enter Young's equation. Obtaining the chemical potential as a function of the density for a system with periodic boundary conditions (and no walls), the droplet free energy of a spherical droplet in the bulk is obtained for a wide range of droplet radii. Similarly, ΔF(het)(*) is obtained for a system with two parallel walls. We find that the classical theory is fairly accurate if a line tension correction for the contact angle is taken into account.


The effect of ionization on the global minima of small and medium sized silicon and magnesium clusters.
We re-examine the question of whether the geometrical ground state of neutral and ionized clusters are identical. Using a well defined criterion for being "identical" together, the extensive sampling methods on a potential energy surface calculated by density functional theory, we show that the ground states are in general different. This behavior is to be expected whenever there are metastable configurations which are close in energy to the ground state, but it disagrees with previous studies.


Salmonella Outbreaks Associated with Not Ready-to-Eat Breaded, Stuffed Chicken Products - United States, 1998-2022.
Not ready-to-eat (NRTE) breaded, stuffed chicken products (e.g., chicken stuffed with broccoli and cheese) typically have a crispy, browned exterior that can make them appear cooked. These products have been repeatedly linked to U.S. salmonellosis outbreaks, despite changes to packaging initiated in 2006 to identify the products as raw and warn against preparing them in a microwave oven (microwave) (1-4). On April 28, 2023, the U.S. Department of Agriculture proposed to declare Salmonella an adulterant* at levels of one colony forming unit per gram or higher in these products (5). Salmonella outbreaks associated with NRTE breaded, stuffed chicken products during 1998-2022 were summarized using reports in CDC's Foodborne Disease Outbreak Surveillance System (FDOSS), outbreak questionnaires, web postings, and data from the Minnesota Department of Health (MDH)† and the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS). Eleven outbreaks were identified in FDOSS. Among cultured samples from products obtained from patients' homes and from retail stores during 10 outbreaks, a median of 57% of cultures per outbreak yielded Salmonella. The NRTE breaded, stuffed chicken products were produced in at least three establishments.§ In the seven most recent outbreaks, 0%-75% of ill respondents reported cooking the product in a microwave and reported that they thought the product was sold fully cooked or did not know whether it was sold raw or fully cooked. Outbreaks associated with these products have occurred despite changes to product labels that better inform consumers that the products are raw and provide instructions on safe preparation, indicating that consumer-targeted interventions are not sufficient. Additional Salmonella controls at the manufacturer level to reduce contamination in ingredients might reduce illnesses attributable to NRTE breaded, stuffed chicken products.


Possible overestimation of surface disinfection efficiency by assessment methods based on liquid sampling procedures as demonstrated by in situ quantification of spore viability.
The standard test methods used to assess the efficiency of a disinfectant applied to surfaces are often based on counting the microbial survivors sampled in a liquid, but total cell removal from surfaces is seldom achieved. One might therefore wonder whether evaluations of microbial survivors in liquid-sampled cells are representative of the levels of survivors in whole populations. The present study was thus designed to determine the "damaged/undamaged" status induced by a peracetic acid disinfection for Bacillus atrophaeus spores deposited on glass coupons directly on this substrate and to compare it to the status of spores collected in liquid by a sampling procedure. The method utilized to assess the viability of both surface-associated and liquid-sampled spores included fluorescence labeling with a combination of Syto 61 and Chemchrome V6 dyes and quantifications by analyzing the images acquired by confocal laser scanning microscopy. The principal result of the study was that the viability of spores sampled in the liquid was found to be poorer than that of surface-associated spores. For example, after 2 min of peracetic acid disinfection, less than 17% ± 5% of viable cells were detected among liquid-sampled cells compared to 79% ± 5% or 47% ± 4%, respectively, when the viability was evaluated on the surface after or without the sampling procedure. Moreover, assessments of the survivors collected in the liquid phase, evaluated using the microscopic method and standard plate counts, were well correlated. Evaluations based on the determination of survivors among the liquid-sampled cells can thus overestimate the efficiency of surface disinfection procedures.


Cells of origin of propriospinal and ascending supraspinal fibers in a lizard (Lacerta galloti).
The location of cells of origin of propriospinal and ascending supraspinal fibers has been determined by injecting horseradish peroxidase (HRP) unilaterally into various parts of the spinal cord of the lizard Lacerta galloti. The distribution of retrogradely labeled cells after unilateral high spinal cord injections suggests that ascending supraspinal fibers are derived from neurons in the following areas: in the cervical intumescence in most areas of the spinal gray, particularly ipsilaterally, in thoracic and lumbar segments, in deeper situated areas, especially contralaterally. The presence of cells of origin of long descending propriospinal pathways has been demonstrated following HRP-injections into the lumbar intumescence.


A research design for the quantification of the neuropeptides substance p and calcitonin gene-related Peptide in rat skin using Western blot analysis.
To describe and standardize a protocol that overcomes the technical limitations of Western blot (WB) analysis in the quantification of the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) following nociceptive stimuli in rat skin. Male Wistar rats (Rattus norvegicus albinus) weighing 250 to 350 g were used in this study. Elements of WB analysis were adapted by using specific manipulation of samples, repeated cycles of freezing and thawing, more thorough maceration, and a more potent homogenizer; increasing lytic reagents; promoting greater inhibition of protease activity; and using polyvinylidene fluoride membranes as transfer means for skin-specific protein. Other changes were also made to adapt the WB analysis to a rat model. University research center. Western blot analysis adapted to a rat model. This research design has proven effective in collecting and preparing skin samples to quantify SP and CGRP using WB analysis in rat skin. This study described a research design that uses WB analysis as a reproducible, technically accessible, and cost-effective method for the quantification of SP and CGRP in rat skin that overcomes technical biases.


Making a national donor research program a reality: Concepts for operationalizing a system.
Deceased donor research remains an elusive goal for improving organ utilization and function. Many working in this field have cited the barriers that impede the conduct of such trials. Recent reports from the Academy of Medicine and individual authors provide a general framework on which a National Donor Research Program could be built. This paper provides one observer's viewpoint on how such a program could be operationalized.


Mechanisms for lung function impairment and airway hyperresponsiveness following chronic hypoxia in rats.
Although chronic normobaric hypoxia (CH) alters lung function, its potential to induce bronchial hyperreactivity (BHR) is still controversial. Thus the effects of CH on airway and tissue mechanics separately and changes in lung responsiveness to methacholine (MCh) were investigated. To clarify the mechanisms, mechanical changes were related to end-expiratory lung volume (EELV), in vivo results were compared with those in vitro, and lung histology was assessed. EELV was measured plethysmographically in two groups of rats exposed to 21 days of CH (11% O(2)) or to normoxia. Total respiratory impedance was measured under baseline conditions and following intravenous MCh challenges (2-18 microg x kg(-1) x min(-1)). The lungs were then excised and perfused, and the pulmonary input impedance was measured, while MCh provocations were repeated under a pulmonary capillary pressure of 5, 10, and 15 mmHg. Airway resistance, tissue damping, and elastance were extracted from the respiratory impedance and pulmonary input impedance spectra. The increases in EELV following CH were associated with decreases in airway resistance, whereas tissue damping and elastance remained unaffected. CH led to the development of severe BHR to MCh (206 +/- 30 vs. 95 +/- 24%, P < 0.001), which was not detectable when the same lungs were studied in vitro at any pulmonary capillary pressure levels maintained. Histology revealed pulmonary arterial vascular remodeling with overexpression of alpha-smooth muscle actin antibody in the bronchial wall. These findings suggest that, despite the counterbalancing effect of the increased EELV, BHR develops following CH, only in the presence of intact autonomous nervous system. Thus neural control plays a major role in the changes in the basal lung mechanics and responsiveness following CH.


In situ passive solid-phase adsorption of micro-algal biotoxins as a monitoring tool.
Laboratory and field studies of the passive solid-phase adsorption toxin tracking (SPATT) method have been carried out around the world. A wide range of marine micro-algal toxins have been detected and the potential of the method to provide reliable, sensitive, time-integrated sampling to monitor the occurrence of toxic algal bloom events has been demonstrated. The method has several important advantages over current phytoplankton and shellfish monitoring methods. Trials of various adsorption substrates have been carried out and the best candidates have been selected for the lipophilic marine biotoxin groups; however, research continues to locate suitable substrates for the more polar water-soluble compounds such as domoic acid and the saxitoxins. The technique has also been successfully applied to the detection of a range of freshwater cyanobacterial toxins.


Effects of phthalates on normal human breast cells co-cultured with different fibroblasts.
Whether or not phthalates play a role in breast carcinogenesis remains to be determined. The goal of this study was to explore the effects of phthalates on the growth of normal MCF-10A breast cells modulated by breast fibroblasts. Fibroblasts were derived from normal mammary tissue adjacent to both estrogen receptor (ER) positive and negative primary breast cancers, which were grown separately from nontumorigenic MCF-10A epithelial cells. MCF-10A co-culture cells were treated with 10 nM 17β-estradiol (E2), Butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), and di(20ethylhexyl) phthalate (DEHP) (10 and 100 nM). After incubation for 120 hours, the cells were harvested and extracted for MTT assay. Western blot analysis was used to evaluate the proliferative pathway proteins and the effects on ER α. Only fibroblasts from ER (+) breast cancer significantly stimulated proliferation of MCF-10A cells. Exposure of the co-culture to E2, BBP, DBP, DEHP, and E2 combined with one of these phthalates resulted in significantly increased cell proliferation, as well as proliferating cell nuclear antigen (PCNA) and ER α expressions. The present study demonstrates that phthalates express a significant influence in fibroblast-epithelial interactions, similarly to the effects of E2 on breast cells. The effects of phthalates on normal breast cells depend upon ER modulating actions. In breast carcinogenesis, phthalates should be considered as having endocrine disrupting potential, even at low concentrations.


Four Italian experiences on vaccination policies: results and lessons.
In 2018 the Council of Europe adopted a Recommendation on strengthened cooperation against vaccine preventable diseases. Among EU Member States, Italy has a long-lasting tradition of immunization policies implemented in the context of the National Health Service over the last forty years. We identify, report and critically appraise four immunization strategies implemented in Italy in recent years and quantitatively assess their impact on coverage rates and other selected indicators. First: the regional law that suspended mandatory vaccination in the Veneto Region in 2007 to stimulate a proactive approach to vaccine uptake was not successful. Second: a strengthened political commitment started in 2014 brought to the release of an innovative and updated National Immunization Prevention Plan and to encouraging increase in vaccine confidence and vaccination uptake. Third: the success of social media influencers is exemplified by the case of Roberto Burioni, professor of microbiology, who in 2015 started a personal social media campaign to contrast anti-vaccinists. Fourth: The new 2017 Italian law extending mandatory vaccinations has successfully impacted on vaccine coverage which increased by more than 1% and 4% for polio and MMR vaccines, respectively, in the first six months since its entering into force, and has continued to raise in 2018. Our data and real-life case studies offer to the broader European public health community a solid basis for discussion and ground to evaluate similar polices implemented in different European settings, with the common goal to share best practices and promote the culture of immunization.


Developmental Exposure to Endocrine Disrupting Chemicals and Type 1 Diabetes Mellitus.
Exposure to endocrine disrupting chemicals (EDCs) may have implications for the development of type 1 diabetes mellitus (T1DM), especially if exposure occurs during development. Exposure to EDCs during fetal or early life can disrupt the development of both the immune system and the pancreatic beta cells, potentially increasing susceptibility to T1DM later in life. Developmental exposure to some EDCs can cause immune system dysfunction, increasing the risk of autoimmunity. In addition, developmental exposure to some EDCs can affect beta cell development and function, influencing insulin secretion. These changes may increase stress on the beta cells, and identify them as a target to the immune system. Developmental exposure to EDCs that disrupt metabolism by increasing insulin resistance or obesity may also stress the beta cells. Exposure to these EDCs during development may play a role in the pathogenesis of T1DM, and requires further research.


Human Papillomavirus Genotyping among Different Cervical Smears in Duhok/Iraq.
Background/Objective: Cervical cancer ranks the second among the most common gynecologic cancers. This study was established to determine the distribution of cervical HPV genotypes among different Pap readings in Duhok/Iraq. Methods: Between January and September-2016, HPV-DNA was tested in 64 women. Genotyping was carried out by the hybridization reverse blot technique. Cervical smears were taken, performed by ThinPrep technique and stained by Pap stain. Results: Twenty six (40.6%) cases were positive for HPV, 12 (46.2%) in normal and 14 (53.8%) in abnormal Pap smears. 39 (19 high-risk and 16 low-risk) genotypes were identified. The high risk group comprised 6 HPV16, 4 HPV18, 2 HPV66, 2 HPV52, 2 HPV39, 1 HPV56, 1 HPV31 and 1 HPV45. The 16 low risk strains encompassed 4 HPV6 strains, 4 HPV71, 2 HPV54 and 2 HPV83, HPV11, HPV61 HPV84, and HPV62. Mixed infections were described in 4 women (6.25%), limited to the NILM, ASC-US and LSIL smears. They included variable admixtures of 7 high risk genotypes, HPV39 (both copies), HPV66 (both copies), HPV52, HPV31, HPV45 and 6 low risk strains: HPV83, HPV6, HPV11, HPV54, HPV62 and HPV71. Conclusions: The higher frequency of HR-HPV than the LR-HPV with identification of 4 mixed cases indicates that our women are at risk of developing cervical cancer. Detection of HR-HPV in NILM and ASC-US smears with restriction of some strains to these 2 categories highlights the great value of HPV genotyping as a surrogate test to pick up unscreened women at risk of developing cervical malignancy particularly when a proper screening program is absent.


Is polygyny a risk factor in the transmission of HIV in sub- Saharan Africa? A systematic review.
Using a systematic literature review approach, this paper focused on the role of polygyny in the spread of HIV/AIDS in sub-Saharan Africa (SSA) countries. The widespread practice of polygyny is one feature of many SSA contexts that may be relevant to understanding patterns of HIV prevalence. Building on the conflicting studies on the importance of polygyny, this study investigated whether or not polygyny is a conduit for elevating HIV transmission in SSA countries. Findings showed that polygyny as an institution is perhaps less of a concern; rather the implication that men and women who are in polygamous relationships are also more likely to engage in extra-marital sex - raises secondary questions about their patterns of sexual networking and concurrent sexual partnerships. The findings however show that polygyny amplifies risky sexual behaviours such as sexual networking and concurrent sexual partnerships, all of which were found to be significantly associated with the risk of HIV transmission. This demonstrates that targeting risky sexual behaviours in a broader marital context may be more important for HIV risk reduction than targeting polygyny as an institution.


Splat-cooled alloys in the Ag-Sn-Cu system.
Strength, dimensional change during setting, and corrosion resistance have been measured for amalgams prepared from splat-cooled alloys of different compositions in the Ag-Sn-Cu system. The amalgam with optimum values of these properties was made from the alloy containing 60 at. % Ag, 25 at. % Sn, and 15 at.% Cu. Tensile strengths for amalgams from this alloy were about 8000 psi, dimensional change during setting near zero, and corrosion resistance was good. X-Ray diffraction showed that the gamma1 and gamma2 phases had essentially disappeared after about 24 hr. At the latter time Cu6Sn5 was present.


Low-dose endostatin normalizes the structure and function of tumor vasculature and improves the delivery and anti-tumor efficacy of cytotoxic drugs in a lung cancer xenograft murine model.
To some extent endostatin normalizes tumor vasculature. However, the optimum time window and optimum drug dose for tumor vascular normalization need to be explored. Here we investigate the effect of low-dose endostatin on the structure and function of tumor vasculature and the delivery and anti-tumor efficacy of cytotoxic drugs. A lung cancer xenograft murine model was treated with low-dose endostatin for 10 days. The structure and function of the tumor vasculature were evaluated using various techniques. Paclitaxel was added in different schedules. Endostatin caused a significant reduction in microvessel density. Tumor vascular walls after endostatin treatment were better structured. Tumor blood perfusion was increased on day six after endostatin administration. On days three, six, and 10, Evans blue extravasation into the parenchyma of tumors was decreased. On days three and six, endostatin-treated mice had greater paclitaxel delivery. The time window of vascular normalization was approximately three to six days. On days one to three, and days four to six, combined therapy with paclitaxel significantly inhibited tumor growth. Low-dose endostatin aids normalization of tumor vasculature. This resulted in improved delivery of cytotoxic drugs to the tumor, which closely correlates with synergistic efficacy when combined with paclitaxel during the normalization window.


Purification of carbonic anhydrase isozyme VI (CA-VI) from swine saliva.
Salivary or secreted carbonic anhydrase (CA), which constitutes a new class of CA, designated CA-VI, was isolated. Swine CA-VI purified from swine saliva by inhibitor-affinity chromatography and ion exchange chromatography had a specific activity of 5,468 units/mg. The molecular weight was 250,000, as determined by gel filtration under non-denaturing conditions, and the subunit molecular weight was found to be 37,000 by sodium dodecyl sulfate polyacrylamide gel electrophoresis, indicating that swine CA-VI consists of 7 subunits. The treatment of the enzyme with endo-N-acetylglucosaminidase F reduced its subunit molecular weight from 37,000 to 35,000 and 32,000. We raised a rabbit antibody against purfied swine CA-VI. Double immunodiffusion showed that anti-swine CA-VI serum reacted with swine CA-VI and swine saliva, but not with hemolysate (containing CA-I and CA-Il) or muscle extracts (containing CA-III). The concentration of CA-VI in swine saliva, measured using single radial immunodiffusion, was 0.027 +/- 0.017 mg/mg total protein.


Risk factors for anastomotic leakage after surgery for colorectal cancer: results of prospective surveillance.
Anastomotic leakage in operations for colorectal cancer not only results in morbidity and mortality, but also increases the risk of local recurrence and worsens prognosis. So a better understanding of risk factors for developing anastomotic leakage in colorectal cancer surgery is important to surgeons. The aim of this study was to determine the incidence and risk factors for clinical anastomotic leakage after elective surgery for colorectal cancer. We conducted prospective surveillance of all elective colorectal resections performed by a single surgeon in a single university hospital from November 2000 to July 2004. The outcomes of interest was clinical anastomotic leakage. Eighteen independent clinical variables were examined by univariate and multivariate analyses. A total of 391 patients undergoing elective operations for colorectal cancer were admitted to the program. Clinical anastomotic leakage was identified in 11(2.8%) patients. Univariate and multivariate analyses showed that preoperative steroid use (odds ratio=8.7), longer duration of operation (odds ratio=9.9), and wound contamination (odds ratio=7.8) were independently predictive of clinical anastomotic leakage. Although there were no statistical differences in leakage rates between patients with and without covering stoma, all four patients requiring reoperation for leakage were without covering stoma. Preoperative steroid use, longer duration of operation, and contamination of the operative field were independent risk factors for developing clinical anastomotic leakage after elective resection for colorectal cancer. Surgeons should be aware of such high-risk patients, which would help them to decide whether to create a diversion stoma during surgery.


Spatiotemporal organization of myoclonic twitching in sleeping human infants.
During the perinatal period in mammals when active sleep predominates, skeletal muscles twitch throughout the body. We have hypothesized that myoclonic twitches provide unique insight into the functional status of the human infant's nervous system. However, assessments of the rate and patterning of twitching have largely been restricted to infant rodents. Thus, here we analyze twitching in human infants over the first seven postnatal months. Using videography and behavioral measures of twitching during bouts of daytime sleep, we find at all ages that twitching across the body occurs predominantly in bursts at intervals of 10 s or less. We also find that twitching is expressed differentially across the body and with age. For example, twitching of the face and head is most prevalent shortly after birth and decreases over the first several months. In addition, twitching of the hands and feet occurs at a consistently higher rate than does twitching elsewhere in the body. Finally, the patterning of twitching becomes more structured with age, with twitches of the left and right hands and feet exhibiting the strongest coupling. Altogether, these findings support the notion that twitches can provide a unique source of information about typical and atypical sensorimotor development.


A pilot study of the reliability and validity of the Caregiver Activity Survey - Intellectual Disability (CAS-ID).
People with Down's syndrome (DS) are at increased risk of Alzheimer-type dementia (AD) when compared to the general population. Despite AD being a serious progressive disorder, little attention has been paid to the impact of the illness on formal caregivers. In the general population, the Caregiver Activity Survey (CAS) is used to measure time spent by family caregivers assisting people with AD in their day-to-day activities of living. In order to plan appropriate models of health and social care effectively for people with AD and DS, it is imperative that the care requirements of individuals at different stages of dementia are realized. An amended version of this survey, the Caregiver Activity Survey - Intellectual Disability (CAS-ID), was developed and tested for use by professional caregivers in the present study. The CAS-ID was administered to 30 people with DS and their caregivers. Convergent validity was tested by comparing the results of the CAS-ID to other validated tests for cognitive and functional impairment in individuals with DS. Test-retest and inter-rater reliability were investigated. The final version of the CAS-ID consists of eight items: dressing, bathing/showering, grooming, toileting, eating and drinking, housekeeping, nursing care-related activities, and supervision/ behaviour management. The scale had excellent test-retest reliability, and correlated strongly with the Down Syndrome Mental Status Examination (DSMSE; r = -0.770), the Test for Severe Impairment (TSI; r = -0.881) and the Daily Living Skills Questionnaire (DLSQ; r = -0.855). The present authors provide preliminary evidence for the validity and reliability of the CAS-ID. This instrument offers a means of identifying and measuring care and resources requirements as this population experiences symptoms of dementia. Such information may help assist healthcare professionals in planning supports and services to address the care challenges evidenced at different stages of the disease process.


The Role of Mycangial Fungi Associated with Ambrosia Beetles (Euwallacea interjectus) in Fig Wilt Disease: Dual Inoculation of Fusarium kuroshium and Ceratocystis ficicola Can Bring Fig Saplings to Early Symptom Development.
The ambrosia beetle, Euwallacea interjectus, is a wood-boring pest and a vector of Ceratocystis ficicola, a pathogenic fungus causing fig (Ficus carica) wilt disease (FWD) in Japan. The ambrosia fungi, Fusarium kuroshium and Neocosmospora metavorans, have been frequently isolated from heads (including mycangia) of wild and reared adult female E. interjectus, respectively. However, the exact mechanisms driving FWD as well as the interactions between F. kuroshium and C. ficicola in fig orchard remain unclear. To verify the role of the mycangial fungi in the FWD progression, fig saplings were subjected to inoculation treatments (T1, F. kuroshium; T2, N. metavorans, reference positive control; T3, C. ficicola; T4, F. kuroshium + C. ficicola, realistic on-site combination). T3 and T4 saplings began wilting approximately 12 days after inoculation, leading to eventual death. Median duration from inoculation to death of the T4 saplings was approximately four days significantly faster than that of the T3 saplings. Xylem sap-conduction test indicated that dysfunction and necrosis area were considerably wider in the T4 saplings than in T3 saplings. These results demonstrate that the synergistic action of F. kuroshium and C. ficicola contributed to accelerated wilting in the saplings. Based on these discoveries, we proposed a model for system changes in the symbiosis between E. interjectus and its associated fungi in FWD in Japan.


[Acute hysterectomy for huge submucous leiomyoma prolaps].
To present a case of huge submucous leiomyoma prolaps to the vagina with severe haemorrhage and its management and to analyse current articles with this rare complication. A case report, review article. Department of Gynecology and Obstetrics Trinec Hospital. A case report of huge submucous leiomyoma prolaps in 49-year-old woman. The patient presented at our department with sudden onset of profuse vaginal bleeding. The vaginal and utrasound examination was performed with diagnosis of huge submucous leiomyoma obturating upper third of the vagina. The cervix was not palpable, rised up. While manipulating with the leiomyoma the bleeding exceeded. The patient agreed with abdominal hysterectomy without adnexectomy. Then the patinent colapsed and the operation was performed immediately, taking care of changed anatomy--the line between the vaginal wall and the uterus was almost invisible caused by "non-existing cervix" and the uterus was partialy inverted into the vagina. The haemoglobin level failed from 124 g/l to 95 g/l with no need of tranfusion. The patient quickly recovered and was dimised the sixth day after the operation. Uterine myomas in their submucous localisation may protrude through the cervix into the vagina and cause rare but very serious complications--profuse vaginal bleeding and non-puerperal inversion of the uterus, and thus need very urgent management.


A right inguinoscrotal swelling: the importance of histological analysis.
Myxofibrosarcoma of the spermatic cord is a rare condition. We present an unusual case of a 69-year-old gentleman who presented to the emergency department on two occasions with a right inguinoscrotal swelling. We will explore the diagnostic difficulties encountered and subsequent management. We will also highlight the importance of histological analysis when unexpected findings are encountered.


Infrared absorption spectra of matrix-isolated cis, cis-HOONO and its ab initio CCSD(T) anharmonic vibrational bands.
The infrared absorption spectra of matrix-isolated cis, cis-peroxynitrous acid (HOONO and DOONO) in argon have been observed. Six of the nine fundamental vibrational modes for cis, cis-HOONO have been assigned definitively, and one tentatively. Coupled-cluster, ab initio anharmonic force field calculations were used to help guide some of the assignments. The experimental matrix frequencies (cm(-1)) for cis, cis-HOONO are (a' modes) nu1 = 3303+/-1, nu2 = 1600.6+/-0.6, nu3 = 1392+/-1, nu4 = 922.8+/-0.5, nu5 = 789.7+/-0.4, nu6 = 617+/-1; and (a" mode) nu8 = 462+/-1. The fundamentals for the deuterated isotopomer, cis, cis-DOONO, are (a' modes) nu1 = 2447.2+/-0.6, nu2 = 1595.7+/-0.7, nu3 = 1089.1+/-0.4, nu4 = 888.1+/-0.4, nu5 = 786.6+/-0.5, nu6 = 613.9+/-0.9; and (a" mode) nu8 = 456.5+/-0.5.


Screening of Differentially Expressed Genes and Localization Analysis of Female Gametophyte at the Free Nuclear Mitosis Stage in Pinus tabuliformis Carr.
Female sterility is a common phenomenon in the plant world, and systematic research has not been carried out in gymnosperms. In this study, the ovules of No. 28 sterile line and No. 15 fertile line Pinus tabuliformis were used as materials, and a total of 18 cDNA libraries were sequenced by the HiSeqTM 4000 platform to analyze the differentially expressed genes (DEGs) and simple sequence repeats (SSRs) between the two lines. In addition, this study further analyzed the DEGs involved in the signal transduction of plant hormones, revealing that the signal pathways related to auxin, cytokinin, and gibberellin were blocked in the sterile ovule. Additionally, real-time fluorescent quantitative PCR verified that the expression trend of DEGs related to plant hormones was consistent with the results of high-throughput sequencing. Frozen sections and fluorescence in situ hybridization (FISH) were used to study the temporal and spatial expression patterns of PtRab in the ovules of P. tabuliformis. It was found that PtRab was significantly expressed in female gametophytes and rarely expressed in the surrounding diploid tissues. This study further explained the molecular regulation mechanism of female sterility in P. tabuliformis, preliminarily mining the key factors of ovule abortion in gymnosperms at the transcriptional level.


Sterol transfer between cyclodextrin and membranes: similar but not identical mechanism to NPC2-mediated cholesterol transfer.
Niemann--Pick C disease is an inherited disorder in which cholesterol and other lipids accumulate in the late endosomal/lysosomal compartment. Recently, cyclodextrins (CD) have been shown to reduce symptoms and extend lifespan in animal models of the disease. In the present studies we examined the mechanism of sterol transport by CD using in vitro model systems and fluorescence spectroscopy and NPC2-deficient fibroblasts. We demonstrate that cholesterol transport from the lysosomal cholesterol-binding protein NPC2 to CD occurs via aqueous diffusional transfer and is very slow; the rate-limiting step appears to be dissociation of cholesterol from NPC2, suggesting that specific interactions between NPC2 and CD do not occur. In contrast, the transfer rate of the fluorescent cholesterol analogue dehydroergosterol (DHE) from CD to phospholipid membranes is very rapid and is directly proportional to the acceptor membrane concentration, as is DHE transfer from membranes to CD. Moreover, CD dramatically increases the rate of sterol transfer between membranes, with rates that can approach those mediated by NPC2. The results suggest that sterol transfer from CD to membranes occurs by a collisional transfer mechanism involving direct interaction of CD with membranes, similar to that shown previously for NPC2. For CD, however, absolute rates are slower compared to NPC2 for a given concentration, and the lysosomal phospholipid lysobisphosphatidic acid (LBPA) does not stimulate rates of sterol transfer between membranes and CD. As expected from the apparent absence of interaction between CD and NPC2, the addition of CD to NPC2-deficient fibroblasts rapidly rescued the cholesterol accumulation phenotype. Thus, the recent observations of CD efficacy in mouse models of NPC disease are likely the result of CD enhancement of cholesterol transport between membranes, with rapid sterol transfer occurring during CD--membrane interactions.


Lipid-lowering and antioxidative activities of 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate in cholesterol-fed rats.
Polyphenols appear to have antioxidant activities and may mediate lipid lowering. Four groups of rats, a high-cholesterol control (HC), HC+lovastatin, HC+3,4-di(OH)-cinnamate, and HC+3,4-di(OH)-hydrocinnamate, were given a semi-synthetic diet. The cinnamate derivative or lovastatin (0.1 g/100 g) supplements were given for 6 weeks. The plasma total cholesterol concentration was significantly lowered by the 3,4-di(OH)-cinnamate supplement compared to the control or lovastatin group. The 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate supplements significantly lowered both the hepatic cholesterol and triglyceride levels, while lovastatin only lowered the hepatic cholesterol. The hepatic HMG-CoA reductase activities were significantly lower in the 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate groups than in the control or lovastatin group. The ACAT activity was only significantly lower in the lovastatin group compared to the other groups. With regards the hepatic antioxidant enzyme system, the CAT activity was significantly higher in the 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate groups compared to the control or lovastatin group. The two cinnamate derivatives resulted in an increased hepatic GSH-Px activity. Meanwhile, all the supplements significantly lowered the hepatic thiobarbituric acid reactive substances (TBARS) content. However, the 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate supplements did not alter the neutral sterol and total fecal sterol. Both cinnamate derivatives were potent in lipid-lowering and altering the antioxidative enzyme. Furthermore, these results also suggest that 3,4-di(OH)-cinnamate is more effective than 3,4-di(OH)-hydrocinnamate in its lipid-lowering action.


Second primary breast cancer in BRCA1 and BRCA2 mutation carriers: 10-year cumulative incidence in the Breast Cancer Family Registry.
BReast CAncer genes 1 and 2 (BRCA1 and BRCA2) mutation carriers diagnosed with breast cancer are at increased risk of developing a second primary breast cancer. Data from high-risk clinics may be subject to different biases which can cause both over and underestimation of this risk. Using data from a large multi-institutional family registry we estimated the 10-year cumulative risk of second primary breast cancer including more complete testing information on family members. We prospectively followed 800 women diagnosed with breast cancer from the Breast Cancer Family Registry (BCFR) who were carriers of a BRCA1 or BRCA2 pathogenic mutation or a variant of unknown clinical significance. In order to limit survival and ascertainment bias, cases were limited to those diagnosed with a first primary breast cancer from 1994 to 2001 and enrolled in the BCFR within 3 years after their cancer diagnosis. We excluded women enrolled after being diagnosed with a second breast cancer. We calculated 10-year incidence of second primary breast cancers. The 10-year incidence of a second primary breast cancer was highest in BRCA1 mutation carriers (17 %; 95 % CI 11-25 %), with even higher estimates in those first diagnosed under the age of 40 (21 %; 95 % CI 13-34 %). Lower rates were found in BRCA2 mutation carriers (7 %; 95 % CI 3-15 %) and women with a variant of unknown clinical significance (6 %; 95 % CI 4-9 %). Whereas the cumulative 10-year incidence of second primary breast cancer is high in BRCA1 mutation carriers, the estimates in BRCA2 mutation carriers and women with variants of unknown clinical significance are similar to those reported in women with sporadic breast cancer.


Carotid arterial stent implantation follow-up and results in 50 patients: preliminary report.
Carotid artery stenting (CAS) is considered as a safe and effective procedure for treatment of carotid artery stenosis. Evaluation of this procedure's complications is essential for proper clinical decision-making. This study aimed to evaluate the cardiovascular events after CAS among our patients in Isfahan, Iran. This case-series study was conducted on fifty patients from December 2013 to May 2016. These patients were referred to the cardiology centers of Isfahan, Iran by a neurologist, for stenting of extracranial carotid arteries. The second step was examining the patients by cardiac interventionist. Stenting was performed on symptomatic patients with carotid artery stenosis of more than 50 percent or asymptomatic patients with more than 70 percent carotid artery stenosis on Doppler ultrasonography. Neurologic evaluation was performed at baseline, during hospital stay, and follow-up. Transient ischemic attack (TIA)/Stroke and Myocardial infarction (MI) questionnaires were filled out by a cardiologist over telephone interviews with the patients, for follow-up of one month, six months and at the end of study. Carotid Doppler ultrasonography was performed before and 6 months after stenting for evaluation of restenosis. Indeed, during the follow-up study, the major adverse cardiac events (MACE) were evaluated. All data were analyzed through SPSS v.17. The mean age of patients was 70.73 (±14.01) years old (range: 48-89 years old). Composite endpoint of death, stroke, and MI was totally 8 percent. The rate of carotid arterial restenosis (Luminal arterial narrowing>50%) was 8%. Despite the fact that carotid stenting is new in our center, our results can be compared to other important studies.


Liver/kidney microsomal antibody type 1 targets CYP2D6 on hepatocyte plasma membrane.
Liver/kidney microsomal antibody type 1 (LKM1) is the marker of type 2 autoimmune hepatitis (AIH) and is detected in up to 6% of patients with hepatitis C virus (HCV) infection. It recognises linear and conformational epitopes of cytochrome P450IID6 (CYP2D6) and may have liver damaging activity, provided that CYP2D6 is accessible to effector mechanisms of autoimmune attack. The presence of LKM1 in the plasma membrane was investigated by indirect immunofluorescence and confocal laser microscopy of isolated rat hepatocytes probed with 10 LKM1 positive sera (five from patients with AIH and five from patients with chronic HCV infection) and a rabbit polyclonal anti-CYP2D6 serum. Serum from both types of patient stained the plasma membrane of non-permeabilised cells, where the fluorescent signal could be visualised as discrete clumps. Conversely, permeabilised hepatocytes showed diffuse submembranous/cytoplasmic staining. Adsorption with recombinant CYP2D6 substantially reduced plasma membrane staining and LKM1 immunoblot reactivity. Plasma membrane staining of LKM1 colocalised with that of anti-CYP2D6. Immunoprecipitation experiments showed that a single 50 kDa protein recognised by anti-CYP2D6 can be isolated from the plasma membrane of intact hepatocytes. AIH and HCV related LKM1 recognise CYP2D6 exposed on the plasma membrane of isolated hepatocytes. This observation supports the notion that anti-CYP2D6 autoreactivity may be involved in the pathogenesis of liver damage.


Primary results of salvage liver transplantation in the patients with unresectable recurrent hepatocellular carcinoma after initial liver resection.
Salvage liver transplantation (SLT) is a treatment choice for recurrent HCC fulfilling the Milan criteria. However, there is no consensus on the value of SLT for recurrent HCC beyond the Milan criteria, especially for unresectable HCC. Eleven patients with recurrent HCC underwent SLT in Tongji Hospital between January 2003 and July 2010. All the 11 patients were considered unresectable because of deteriorated liver function, multiple bilobar tumors or vascular invasion. The outcomes and prognostic factors of these patients were analyzed. At a median follow up of 30 months, six patients were alive. Four patients died from HCC recurrence, and one died from gastric cancer. The 1-, 2-, and 3- year recurrence and overall survival rates after SLT were 58.4%, 72.3% and 86.1%, respectively, and 90.9%, 40.6% and 40.6%, respectively. Vascular invasion, recurrent HCC beyond the Milan criteria and early recurrence within 18 months after initial resection were negative prognostic factors of SLT for recurrent HCC. SLT can be recommended as an alternative treatment for recurrent HCC fulfilling the Milan criteria. For those beyond the Milan criteria or with vascular invasion, or early recurrence after initial resection, however, SLT is not beneficial and should not be recommended.


Early add-on administration of mepolizumab and intravenous immunoglobulin effective in treating eosinophilic granulomatosis with polyangiitis.
Treatment of eosinophilic granulomatosis with polyangiitis (EGPA) remains a challenge because currently available therapies, corticosteroids and immunomodulators, do not always control symptoms and are often associated with significant morbidity and relapse. Mepolizumab has been demonstrated to be an effective add-on therapy with steroid-sparing effect in cases of relapsing or refractory EGPA. Intravenous immunoglobulin (IVIG) therapy is effective against mononeuritis multiplex or heart failure in patients with EGPA who do not respond to corticosteroid-cyclophosphamide treatment. We present two cases of EGPA in which earlier add-on administration of adjunct mepolizumab and IVIG led to significant improvement in EGPA symptoms and prevention of flare-up of the disease. We suggested that earlier add-on combination administration of IVIG and mepolizumab might be a useful adjunct treatment to induce clinical remission of EGPA and improve the rate of remission, decrease relapse rate, and allow for reduced glucocorticoid use without any serious adverse drug effects.


Acoustic microstreaming around a gas bubble.
The problem of acoustic microstreaming that develops around a gas bubble in an ultrasound field is considered. It is shown that the solutions obtained previously by Wu and Du [(1997). J. Acoust. Soc. Am. 101, 1899-1907], which are based on the assumption that viscous effects are essential only within a thin boundary layer while beyond the boundary layer the liquid can be considered to be inviscid, lead to a severe underestimation of the power of acoustic streaming. An improved theory is suggested that corrects the errors of the previous theory and extends its limits. The proposed theory treats the entire bulk of the liquid outside the bubble and the gas inside the bubble as viscous heat-conducting fluids. No restrictions are imposed on the size of the bubble relative to the viscous, thermal, and sound wavelengths in the ambient liquid and those in the internal gas medium. All modes of the bubble's motion (volume pulsation, translation, and shape oscillations) are taken into account. Expressions for the radial and tangential stresses produced by the acoustic streaming are also derived. Numerical examples for parameters of interest are presented.


Light-Induced Surface Tension Gradients for Hierarchical Assembly of Particles from Liquid Metals.
Achieving control over the motion of dissolved particles in liquid metals is of importance for the meticulous realization of hierarchical particle assemblies in a variety of nanofabrication processes. Brownian forces can impede the motion of such particles, impacting the degree of perfection that can be realized in assembled structures. Here, we show that light-induced Marangoni flow in liquid metals (i.e., liquid-gallium) with Laguerre-Gaussian (LGpl) lasers as heating sources is an effective approach to overcome Brownian forces on particles, giving rise to predictable assemblies with a high degree of order. We show that by carefully engineering surface tension gradients in liquid-gallium using non-Gaussian LGpl lasers, the Marangoni and convective flow that develops in the fluid drives the trajectory of randomly dispersed particles to assemble into 100 μm wide ring-shaped particle assemblies. Careful control over the parameters of the LGpl laser (i.e., laser mode, spot size, and intensity of the electric field) can tune the temperature and fluid dynamics of the liquid-gallium as well as the balance of forces on the particle. This in turn can tune the structure of the ring-shaped particle assembly with a high degree of fidelity. The use of light to control the motion of particles in liquid metals represents a tunable and rapidly reconfigurable approach to spatially design surface tension gradients in fluids for more complex assembly of particles and small-scale solutes. This work can be extended to a variety of liquid metals, complementary to what has been realized in particle assembly out of ferrofluids using magnetic fields.


Pharmacological studies on a new dihydrothienopyridine calcium antagonist, S-312-d. 5th communication: anticonvulsant effects in mice.
S-312, S-312-d, but not S-312-l, L-type calcium channel antagonists, showed anticonvulsant effects on the audiogenic tonic convulsions in DBA/2 mice; and their ED50 values were 18.4 (12.8-27.1) mg/kg, p.o. and 15.0 (10.2-23.7) mg/kg, p.o., respectively, while that of flunarizine was 34.0 (26.0-44.8) mg/kg, p.o. Although moderate anticonvulsant effects of S-312-d in higher doses were observed against the clonic convulsions induced by pentylenetetrazole (85 mg/kg, s.c.) or bemegride (40 mg/kg, s.c.), no effects were observed in convulsions induced by N-methyl-D-aspartate, picrotoxin, or electroshock in Slc:ddY mice. S-312-d may be useful in the therapy of certain types of human epilepsy.


Combinatorial discovery of new methanol-tolerant non-noble metal cathode electrocatalysts for direct methanol fuel cells.
Combinatorial synthesis and screening were used to identify methanol-tolerant non-platinum cathode electrocatalysts for use in direct methanol fuel cells (DMFCs). Oxygen reduction consumes protons at the surface of DMFC cathode catalysts. In combinatorial screening, this pH change allows one to differentiate active catalysts using fluorescent acid-base indicators. Combinatorial libraries of carbon-supported catalyst compositions containing Ru, Mo, W, Sn, and Se were screened. Ternary and quaternary compositions containing Ru, Sn, Mo, Se were more active than the "standard" Alonso-Vante catalyst, Ru(3)Mo(0.08)Se(2), when tested in liquid-feed DMFCs. Physical characterization of the most active catalysts by powder X-ray diffraction, gas adsorption, and X-ray photoelectron spectroscopy revealed that the predominant crystalline phase was hexagonal close-packed (hcp) ruthenium, and showed a surface mostly covered with oxide. The best new catalyst, Ru(7.0)Sn(1.0)Se(1.0), was significantly more active than Ru(3)Se(2)Mo(0.08), even though the latter contained smaller particles.


PATIENT SATISFACTION AFTER BREAST RECONSTRUCTION: IMPLANTS VS. AUTOLOGOUS TISSUES.
Breast reconstruction is increasingly present in the treatment of breast cancer. It may be accomplished with implants or autologous tissues. This cross-sectional study evaluates patients satisfaction and quality of life in women after successful autologous or implant breast reconstruction. 109 women who successfully underwent breast reconstruction between 2007 and 2016 were included. The patients completed the BREAST-Q questionnaire at follow-up visits. Additional data were collected retrospectively from the hospital charts regarding complications, smoking, chemotherapy, radiotherapy, unilateral or bilateral reconstruction, BMI and comorbidities. Mann-Whitney U Test was applied to evaluate differences between the autologous breast reconstruction group (n = 50) and the implant breast reconstruction group (n = 59). Women with a successful autologous reconstruction were significantly more satisfied with their reconstructed breasts than women with successful alloplastic breast reconstruction as measured by the BREAST-Q breasts module (p = 0. 00596), psycho-social well-being module (p=0.04) and sexual well-being module (p=0.00068). Furthermore, there is a higher degree of satisfaction in patients who have not undergone radiotherapy, with no complications and with a normal BMI for implant reconstruction group as well as in non-smokers, and bilateral reconstructions for flap reconstruction group. The findings of our study are in agreement with the data found in the literature, attributing greater satisfaction with physical, mental and social wellbeing, as well as with elements having repercussion on sexual wellbeing, to autologous breast reconstruction. Autologous breast reconstruction leads to higher patient satisfaction than implant breast reconstruction. This study may help patients and medical teams in their decision-making process regarding breast reconstruction. This pilot study opens several questions that need further investigations in a larger prospective studyKeywords: Breast reconstruction, breast-Q, satisfaction, implant, autologous tissue.


S-Nitrosylation of α1-Antitrypsin Triggers Macrophages Toward Inflammatory Phenotype and Enhances Intra-Cellular Bacteria Elimination.
Background: Human α1-antitrypsin (hAAT) is a circulating anti-inflammatory serine-protease inhibitor that rises during acute phase responses. in vivo, hAAT reduces bacterial load, without directly inhibiting bacterial growth. In conditions of excess nitric-oxide (NO), hAAT undergoes S-nitrosylation (S-NO-hAAT) and gains antibacterial capacity. The impact of S-NO-hAAT on immune cells has yet to be explored. Aim: Study the effects of S-NO-hAAT on immune cells during bacterial infection. Methods: Clinical-grade hAAT was S-nitrosylated and then compared to unmodified hAAT, functionally, and structurally. Intracellular bacterial clearance by THP-1 macrophages was assessed using live Salmonella typhi. Murine peritoneal macrophages were examined, and signaling pathways were evaluated. S-NO-hAAT was also investigated after blocking free mambranal cysteine residues on cells. Results: S-NO-hAAT (27.5 uM) enhances intracellular bacteria elimination by immunocytes (up to 1-log reduction). S-NO-hAAT causes resting macrophages to exhibit a pro-inflammatory and antibacterial phenotype, including release of inflammatory cytokines and induction of inducible nitric oxide synthase (iNOS) and TLR2. These pro-inflammatory effects are dependent upon cell surface thiols and activation of MAPK pathways. Conclusions: hAAT duality appears to be context-specific, involving S-nitrosylation in a nitric oxide rich environment. Our results suggest that S-nitrosylation facilitates the antibacterial activity of hAAT by promoting its ability to activate innate immune cells. This pro-inflammatory effect may involve transferring of nitric oxide from S-NO-hAAT to a free cysteine residue on cellular targets.


NMR and LC-MSn characterisation of two minor saponins from Ilex paraguariensis.
Two minor saponins obtained from the methanolic extract of the leaves of Ilex paraguariensis have been characterised by 13C-NMR, 1H-NMR, API-MS and chemical hydrolysis as oleanolic acid-3-O-(beta-D-glucopyranosyl-(1-->3)-alpha-L-arabinopyranosyl)-(28-->1)- beta-D-glucopyranosyl ester (guaiacin B) and oleanolic acid-3-O-(beta-D-glucopyranosyl-(1-->3)-(alpha-L-rhamnopyranosyl- (1-->2))-alpha-L-arabinopyranosyl)-(28-->1)-beta-D-glucopyranosyl ester (nudicaucin C). Both are isomeric forms of the known matesaponins 1 (MSP 1) and 2 (MSP 2) and differ only by the nature of the aglycone: they have oleanolic acid instead of ursolic acid, as found in the matesaponins. These minor saponins have not been fully separated from their major isomers MSP 1 and 2 and were characterised by in-mixture NMR analysis, LC-MS and LC-MSn experiments.


[The place of endoscopic treatment in portal hypertension].
A POTENTIALLY SEVERE EVENT: Upper gastrointestinal haemorrhage in a cirrhotic patient is always extremely serious, particularly in the case of rupture of the oesophageal varices, which is the most frequent cause. THE TWO POLES OF TREATMENT: Early vasoactive treatment permits elastic ligature in optimal conditions using an endoscope. The prevention of other complications of cirrhosis is an essential element in the management of these patients.


Obstructed Defecation Syndrome After Delivery Trauma.
Obstructed defecation syndrome (ODS) occurs in about 7% of adults; it seems that the etiology of pelvic floor disorders is multifactorial. Pregnancy and childbirth damage to the pelvic nerve and muscles are proposed causes for this condition. The precise role of vaginal delivery (VD) is not clearly defined, although in recent studies association of pelvic floor disorder with Operative vaginal delivery and episiotomy has been proposed. In this prospective study, we assessed the outcome of stapled transanal rectal resection (STARR) in females with one of the two modes of delivery (VD or caesarean section (C/S). We used Longo's ODS score for the assessment of the severity of pelvic floor malfunction. Stapled Trans Anal Rectal Resection (STARR) procedure was performed using two circular staplers. Follow-up was done 12 months after the discharge. To assess the role of episiotomy in patient with VD, we divided them into two subgroups; females who had VD with episiotomy (Vd + epi) and females who had VD alone. Data were analyzed using SPSS version 20 software. P values less than 0.05 were considered statistically significant. In 30 consecutive females undergoing STARR for the treatment of ODS, who enrolled in this prospective study, 19 (63.3%) had Vaginal Delivery VD and 11 (36.7%) had Cesarean Section (C/S). The ODS score before the surgery was higher in females who had C/S, although there was no significant difference between VD and C/S groups in terms of the percentage of the ODS score improvement after the STARR surgery. Higher ODS score in females who had C/S showed that C/S could not protect the pelvic organ from pregnancy and delivery trauma. It seems that episiotomy has a protective effect during VD; it can reduce the severity of trauma in pelvic organs during childbearing.


[3 new cases of internal male pseudohermaphroditism].
The authors report 3 new cases of Male Internal Pseudohermaphrodism. It is a scarce entity. The discovery is fortuous during the cure of hernia or cryptorchidism. The family history has nothing particular. The main problem of this syndrome is its treatment. Our attitude consisted in conserving the mullerian derivatives and treating the hernia or the cryptorchidism. Hysterectomy is not justified for the following reasons; no case of cancerisation of the mullerian derivatives has not yet been reported. The vasa deferens and uterus are in intimate relationship; the dissection is therefore dangerous. We did not perform systematic castration in order to protect fertility. The removal of the testis is performed only when the gland is intraabdominal and undescendable considering the major risk of cancerisation.


Morphological transformation and DNA adduct formation by dibenz[a,h]anthracene and its metabolites in C3H10T1/2CL8 cells.
The major routes of metabolic activation of dibenz[a,h]-anthracene (DBA) have been studied in transformable C3H10T1/2CL8 (C3H10T1/2) mouse embryo fibroblasts in culture. The morphological transforming activities of three potential intermediates formed by metabolism of DBA by C3H10T1/2 cells, trans-3,4-dihydroxy-3,4-dihydro-DBA-(DBA-3,4-diol), trans-dihydroxy-3,4-dihydro-DBA-anti-1,2-oxide (DBA-3,4-diol-1,2-oxide) and DBA-5,6-oxide were determined. DBA-3,4-diol-1,2-oxide was a strong morphological transforming agent giving a mean of 73% dishes with Type II or III foci and 1.63 Type II and III foci per dish at 0.5 microgram/ml. DBA-3,4-diol produced a mean of 42% dishes with Type II or III foci and 0.81 Type II and III foci per dish at 2.5 micrograms/ml. DBA gave a mean of 24% dishes with Type II or III foci and 0.29 Type II and III foci per dish at 2.5 micrograms/ml. DBA-5,6-oxide was found to be inactive. DNA adducts of DBA, DBA-3,4-diol, DBA-3,4-diol-1,2-oxide, DBA-1,4/2,3-tetrol and DBA-5,6-oxide in C3H10T1/2 cells were analyzed by 32P-postlabeling method. DBA gave 11 adducts, nine of which were observed in the DNA of cells treated with DBA-3,4-diol and seven from cells treated with DBA-3,4-diol-1,2-oxide. Two of these adducts that appear in each of the treatment groups have been identified as the product of the interaction of DBA-3,4-diol-1,2-oxide with 2'-deoxyguanosine. Furthermore, there is evidence for DBA-DNA adducts in cells treated with DBA, DBA-3,4-diol and DBA-3,4-diol-1,2-oxide arising from metabolism to (+,-)-trans,trans-3,4,10,11-tetrahydroxy-3,4,10,11-tetrahydro-DBA (DBA-3,4,10,11-bis-diol). These results are based on co-migration of C3H10T1/2 DNA adducts with skin DNA adducts formed after topical treatment of mice with DBA-3,4,10,11-bis-diol. In C3H10T1/2 cells, DBA is metabolically activated through DBA-3,4-diol, which is further activated via the DBA-3,4-diol-1,2-oxide and DBA-3,4,10,11-bis-diol pathways. No evidence is provided for the metabolism of DBA by the K-region pathway.


Low molecular weight RNAs with homologies to cellular DNA at sites of adenovirus DNA insertion in hamster or mouse cells.
The adenovirus type 2 (Ad2)-transformed hamster cell line HE5 contains one or very few integrated copies of Ad2 DNA. At the site of insertion of Ad2 DNA, the cellular DNA sequence has been completely preserved and has homologies to small unpolyadenylated, cytoplasmic RNAs of 300 nucleotides in length and to minority populations of smaller RNAs present in HE5 cells and in normal hamster cells. The 300-nucleotide RNA is present on average in approximately 20 copies per cell. This RNA, and shorter RNAs, reveal homologies to the hamster DNA sequence of approximately 400 nucleotides to the right of the site of insertion of Ad2 DNA, which is present in one or very few copies per genome. The nucleotide sequence of the DNA segment homologous to this RNA does not contain open reading frames in excess of a sequence encoding 18 amino acids. Thus, it is unlikely that the small RNAs are actually translated and their function is unknown. The nucleotide sequence does not exhibit similarities to known low mol. wt. RNAs of eukaryotic origin. The low mol. wt. cellular RNA has been found in HE5 cells, in other hamster cell lines and organs, and also in mouse cells. There are differences with respect to size and abundance in the RNAs smaller than 300 nucleotides between HE5 cells and LSH hamster embryo cells. The adenovirus type 12 (Ad12)-induced mouse tumor CBA-12-1-T carries greater than 30 copies of integrated Ad12 DNA. The cellular DNA sequence at the site of Ad12 DNA insertion exhibits homologies to small RNAs (approximately 300 nucleotides long) from mouse cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Factors associated with adherence to an accelerometer protocol in older adults.
Adherence to protocols of accelerometer use by participants of research studies is crucial to ensure the most accurate measure of their physical activity. We used data from a study of 201 individuals 65 years of age and older to examine whether aging effects on physical and cognitive health limit the ability of an older adult to be adherent to an accelerometer protocol. A comparison of participants who met the adherent person criteria with those who did not showed that the percentage of participants whose income is $20,000 or greater, the percentage of participants who reported white race, and the mean number of school grades completed were significantly different between the 2 groups. Logistic regression analyses showed that the best multivariate model to predict being a valid person included Instrumental Activities of Daily Living score, while the best multivariate model to predict being an adherent person included Modified Guralnik Lower Body Score and Mini-Mental State Examination Score. This study found that certain measures of physical and cognitive functioning were the best predictors of adherence to an accelerometer protocol among older adults.


Small molecule integrin antagonists in cancer therapy.
Integrins are a large family of dimeric receptors composed by alpha and beta subunits that, once bound to extra-cellular matrix (ECM) proteins, regulate a variety of cellular processes such as cell motility, migration, and proliferation. The integrins transduce signals from inside-out and outside-in the cell, thus representing the cellular link to the external environment. For these properties, integrin activation has been involved in pathological processes like tumor growth and metastasis formation. Recent advances in the elucidation of the crystallographic structures of the alphavbeta3 and alphaIIbeta3 integrins are promoting studies focused to the search of small molecule antagonists that can block the integrin binding to ECM and inhibit the biological effects exerted by these receptors. In this review we will focus on small molecule antagonists of alphavbeta3 and alphavbeta5 integrin as tools for cancer therapy while other integrins will only be briefly mentioned. Cilengitide (cyclic peptidic alphavbeta3 and alphavbeta5 antagonist) is currently in clinical trials for anti cancer therapy. Combination of integrin alphavbeta3 antagonists and other traditional therapeutic approaches may represent a future strategy to inhibit tumor growth and metastasis spreading.


MPP+ induces the endoplasmic reticulum stress response in rabbit brain involving activation of the ATF-6 and NF-kappaB signaling pathways.
Inhibition of mitochondrial function and the subsequent generation of oxidative stress are strongly suggested to underlie MPTP/MPP+-induced neurotoxicity, which has been used extensively as a model for Parkinson disease. In the present study we have examined the hypothesis that MPP+ targets the endoplasmic reticulum. Because rabbits possess more genetic similarities to primates than to rodents we have selected this animal model system for our MPP+ neurotoxicity studies. MPP+ was administered directly into the brain of New Zealand white rabbits via the intracisternal route, and the effects on tissue from the substantia nigra were examined. Here we demonstrate that MPP+ in a dose-dependent manner induces the loss of tyrosine hydroxylase activity, oxidative DNA damage, and activation of the endoplasmic reticulum stress response. The endoplasmic reticulum response, mediated by activation of ATF-6 and NF-kappaB, leads to activation of gadd 153. These effects correlate with the activation of caspase-3 and of c-Jun N-terminal kinase (JNK) kinase. We propose that pharmacological agents that inhibit the perturbation of endoplasmic reticulum function or the activation of JNK may represent a potential therapeutic approach for the prevention of neurotoxin-induced Parkinson disease.


Entrainment of a driven oscillator as a dynamical phase transition.
Large deviation theory has emerged as the natural language with which to study transitions between dynamical phases, such as the glass transition. Here we use this approach to show that the entrainment of an oscillator to an external driving force can be described as a phase transition between two regions in a joint space-time representation. Specifically, we numerically obtain exact solutions of the large deviation function for a discrete, finite model of an oscillator under a periodically varying external force. We find that the first derivative of the expectation value of the current diverges in the limit of large system size. For weak forcing, perturbation theory allows us to relate the observed frequency of the oscillator to the spectrum of eigenvalues for the unforced system. We find that in the entrainment region where the oscillator exhibits the frequency of the driving force, there is a strong coupling between the ground state and excited states.


Value of Doppler ultrasonography in management of patients with follicular thyroid biopsy specimens.
To perform a statistical evaluation with use of Bayes' theorem, evaluating the prognostic value of Doppler flow analysis, to determine the probability of cancer in thyroid nodules with a prior follicular biopsy specimen. The medical literature was reviewed to identify studies in which ultrasonographic Doppler flow analysis was performed on thyroid nodules with a prior fine-needle aspiration biopsy sample showing follicular cytologic features. For inclusion in the study, all nodules must have had pathologic confirmation of the final diagnosis. The pretest probability of cancer was considered to be the incidence of carcinoma within the population studied. The posttest or conditional probability was calculated by using Bayes' theorem. Two well-designed prospective studies met the criteria for inclusion. The sensitivity of demonstration of intranodular flow by Doppler analysis for detection of thyroid carcinoma ranged from 80% to 86%. The specificity of intranodular flow indicating cancer ranged from 85% to 89%. The incidence of thyroid cancer (pretest probability) ranged from 12% to 14%. Application of Bayes' theorem indicated that the posttest probability of thyroid cancer declined to 3% when no central intranodular flow was present and increased to nearly 50% in the presence of intranodular flow. Doppler flow analysis, when performed on thyroid nodules with follicular cytologic findings on fine-needle aspiration biopsy, can provide extremely useful information regarding the probability of malignant involvement. This information can be used in the decision-making process about the need for, and the extent of, surgical resection of follicular lesions.


[Purification and identification of a novel ACE inhibitory peptide derived from the mud snail Bellamya purificata by RP-HPLC/MALDI-TOF MS].
Bellamya purificata is one of mud snails in fresh water found in China. The purification and identification of an angiotensin I-converting enzyme (ACE) inhibitory peptide extracted from Bellamya purificata hydrolysate are described. The peptide was purified twice with semi-preparative reversed-phase high performance liquid chromatography (RP-HPLC) to obtain an active fraction with an inhibitory concentration 50% (IC50) of 43.5 micromol/L. The primary structure of the purified peptide was identified by the high performance liquid chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS) and the martix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) combining with the amino acid composition analysis. Finally, it was identified as a tetrapeptide and sequenced as Lys-Glu-Ile-Trp (KEIW), which has the common characters of ACE inhibitory peptide extracted from selfish muscle. The structure identification results from the two methods were also compared in this study. The results from ESI-MS included a lot of information, such as the total ion current chromatogram and ultraviolet scan spectrum. However, the exact structure could only be from the MALDI-TOF MS analysis, in which the exact MS/MS spectrum could be obtained. Furthermore, the m/z measurement precision of MALDI-TOF MS was 0.0001 and much better than that of 0.1 of ESI-MS.


A magnetosome-associated cytochrome MamP is critical for magnetite crystal growth during the exponential growth phase.
Magnetotactic bacteria use a specific set of conserved proteins to biomineralize crystals of magnetite or greigite within their cells in organelles called magnetosomes. Using Magnetospirillum magneticum AMB-1, we examined one of the magnetotactic bacteria-specific conserved proteins named MamP that was recently reported as a new type of cytochrome c that has iron oxidase activity. We found that MamP is a membrane-bound cytochrome, and the MamP content increases during the exponential growth phase compared to two other magnetosome-associated proteins on the same operon, MamA and MamK. To assess the function of MamP, we overproduced MamP from plasmids in wild-type (WT) AMB-1 and found that during the exponential phase of growth, these cells contained more magnetite crystals that were the same size as crystals in WT cells. Conversely, when the heme c-binding motifs within the mamP on the plasmid was mutated, the cells produced the same number of crystals, but smaller crystals than in WT cells during exponential growth. These results strongly suggest that during the exponential phase of growth, MamP is crucial to the normal growth of magnetite crystals during biomineralization.


Physical therapy management of an athlete with a Kim lesion using physical agents, manual therapy, and therapeutic exercise: a case report.
Several operative procedures have been described for treating a Kim lesion. However, no physical therapy intervention has been documented as conservative treatment for these cases. The purpose of this report was to describe a physical therapy management protocol for an athlete with a Kim lesion. A 22-year-old female volleyball athlete presented to physical therapy with an 8-month history of right shoulder pain when performing the serve and attack sports gestures. Pain was 5/10 on the visual analogue scale (VAS). Pain was localized along the glenohumeral joint, around the long head of the biceps brachii tendon, and at the subscapularis tendon insertion. Shoulder range of motion (ROM) was limited to flexion (150°), abduction (158°), and internal rotation (80°). Kim lesion was confirmed by clinical tests (Kim test and Jerk test) and via magnetic resonance imaging. Shoulder functional outcomes were verified through the University of California Los Angeles (UCLA) shoulder rating scale. Upper extremity sensorimotor control was verified in bimanual support by stabilometry on a baropodometer. Core function was assessed through a plank test and a side plank test. The 8-week course of treatment included manual therapy, physical agents, shoulder and scapular mobilizations, resistance and sensorimotor exercises, core strengthening, and functional exercises. Physical therapy interventions resulted in a decrease in VAS pain (3/10), an increase in shoulder ROM (10.8°) and in UCLA shoulder score (from 22 to 33 points), a reduction in the center of pressure displacement (27-56%), and an increase in plank test (45%) and side plank test (21-29%) performance. The athlete had a full return to sport after the treatment. We concluded that the protocol used for conservative management of Kim lesion resulted in clinical satisfactory physical and functional outcomes for the athlete.


A Friendly Complexing Agent for Spectrophotometric Determination of Total Iron.
Iron, one of the most common metals in the environment, plays a fundamental role in many biological as well as biogeochemical processes, which determine its availability in different oxidation states. Its relevance in environmental and industrial chemistry, human physiology, and many other fields has made it necessary to develop and optimize analysis techniques for accurate determination. Spectrophotometric methods are the most frequently applied in the analytical determination of iron in real samples. Taking advantage of the fact that desferrioxamine B, a trihydroxamic acid used since the 1970s in chelation therapy for iron overload treatment, forms a single stable 1:1 complex with iron in whichever oxidation state it can be found, a smart spectrophotometric method for the analytical determination of iron concentration was developed. In particular, the full compliance with the Lambert-Beer law, the range of iron concentration, the influence of pH, and the interference of other metal ions have been taken into account. The proposed method was validated in terms of LoD, LoQ, linearity, precision, and trueness, and has been applied for total iron determination in natural water certified material and in biological reference materials such as control human urine and control serum.


Nuclear or cytoplasmic expression of survivin: what is the significance?
Growing evidence suggests that survivin expression in cancer cell nuclei may represent an important prognostic marker to predict disease outcome for cancer patients. Current reports in this research area, however, are inconsistent and propose opposing conclusions regarding the significance and prognostic value of survivin nuclear expression. The aim of our study is to review and discuss the data reported in the original publications. We have also provided new experimental data to support our view regarding the possible reasons for the observed inconsistencies in the literature. This would alert researchers to pay attention to potential pitfalls in the determination of nuclear or cytoplasmic expression of survivin for the future.