Balloon dilatation of intrahepatic duct and biliary-enteric anastomosis strictures. Long term results.
From June 1984 to December 1986, 13 patients with 15 benign bile duct strictures were treated by Gruntzig balloon dilatation via the T-tube fistula or transhepatic route. The patients were 7 men and 6 women; ages ranged from 24 to 63 years old. The site of strictures were hepatojejunostomy in six, right intrahepatic duct in 4, left intrahepatic duct in 4 and one choledochoduodenostomy. Eleven out of 13 patients with bile duct strictures had intrahepatic stones. Ninety-three percent (14/15) of the strictures were successfully dilated by the Gruntzig balloon catheter. After the biliary stent was inserted for 2 to 6 months, follow-up cholangiogram or choledochoscopy revealed good patency of the biliary tree. Ninety-one percent (10/11) of the intrahepatic stones were removed completely by choledochoscopy. No major complication was found during balloon dilatation, except tolerable wound pain. Five patients (45%) developed symptoms during the follow-up period of 5 to 7 1/2 years. Two patients complained of right upper quadrant (RUQ) pain and 3 patients developed acute cholangitis which was treated by percutaneous biliary drainage again or laparotomy. Balloon dilatation for biliary-enteric anastomosis and intrahepatic duct strictures is a non-surgical, simple and effective procedure, but the incidence of restenosis rate is high and up to 45% within a long-term follow-up period of 5 to 7 1/2 years.


Human meiotic recombination products revealed by sequencing a hotspot for homologous strand exchange in multiple HNPP deletion patients.
The HNPP (hereditary neuropathy with liability to pressure palsies) deletion and CMT1A (Charcot-Marie-Tooth disease type 1A) duplication are the reciprocal products of homologous recombination events between misaligned flanking CMT1A-REP repeats on chromosome 17p11. 2-p12. A 1.7-kb hotspot for homologous recombination was previously identified wherein the relative risk of an exchange event is 50 times higher than in the surrounding 98.7% identical sequence shared by the CMT1A-REPs. To refine the region of exchange further, we designed a PCR strategy to amplify the recombinant CMT1A-REP from HNPP patients as well as the proximal and distal CMT1A-REPs from control individuals. By comparing the sequences across recombinant CMT1A-REPs to that of the proximal and distal CMT1A-REPs, the exchange was mapped to a 557-bp region within the previously identified 1.7-kb hotspot in 21 of 23 unrelated HNPP deletion patients. Two patients had recombined sequences suggesting an exchange event closer to the mariner-like element previously identified near the hotspot. Five individuals also had interspersed patches of proximal or distal repeat specific DNA sequence indicating potential gene conversion during the exchange of genetic material. Our studies provide a direct observation of human meiotic recombination products. These results are consistent with the hypothesis that minimum efficient processing segments, which have been characterized in Escherichia coli, yeast, and cultured mammalian cells, may be required for efficient homologous meiotic recombination in humans.


Serum lipids in normal and abnormal subjects; observations on controlled experiments.
The relationship of diet to serum lipids and to atherosclerosis is a controversial subject. The data presented indicate that diets containing very large amounts of vegetable fat are consistently associated with a sharp fall in serum cholesterol and phospholipid, whereas administration of equal amounts of fat of animal origin is associated with a rise of the serum lipids to levels noted on an average mixed diet. In critical evaluation of elderly hospitalized diabetic patients with advanced atherosclerosis it was observed that there was close mathematical correlation between serum content of cholesterol, "lipoproteins," and phospholipids. There was no obvious correlation between the degree or kind of atherosclerosis and any one of the lipid entities followed. Coronary occlusion occurred in a patient with one of the lowest levels of cholesterol and of lipoprotein.


Urinary excretion, osmolarity and electrolytes after bolus-injection of fenoterol in female rabbits.
The effects of bolus injections of 1.0-80.0 micrograms/kg body weight fenoterol on urinary excretion, osmolarity and electrolytes were studied in unanesthetized, water-loaded rabbits. In animals infused initially with isotonic solution over 2 h with 60 ml/h and thereafter over 10 h with 45 ml/h, urine excretion was 538 ml/12 h, sodium excretion was 65.4 mmol/12 h, and potassium excretion was 4.8 mmol/12 h. In animals injected with 5.0-80.0 micrograms/kg body weight fenoterol, a strong antidiuresis occurred, lasting for 2 (10.0 micrograms/kg) to 4 h (80.0 micrograms/kg). Due to the strong antidiuresis, urinary osmolarity was significantly elevated for 2 (10.0 micrograms/kg) to 3 h (80.0 micrograms/kg). The changes of sodium excretion after fenoterol injection were very similar to those of urine excretion. Maximum reduction of sodium excretion was found after injection of 10.0-80.0 micrograms/kg body weight fenoterol, the effect lasting for 1 h (10.0 micrograms/kg) to 4 h (80.0 micrograms/kg). Potassium excretion was significantly reduced after injection of 5.0-80.0 micrograms/kg body weight fenoterol. In contrast to all the other parameters measured, potassium excretion remained significantly reduced until the end of the infusion period in animals treated with 10.0-80.0 micrograms/kg body weight fenoterol and was not dose dependent. Our data presented in this work extend earlier findings in the rabbit in that bolus injection of fenoterol also results in a drastic decrease of urine and electrolyte excretion. The results are discussed with special reference for the management of acute fetal distress with betamimetics and to the development of pulmonary edema that has been shown to occur under therapy with betamimetics on both female rabbits and humans.


[Effects of Schwann cells promoting nitric oxide secretion of bone marrow mesenchymal stem cells derived endothelial cells].
To study the effect of Schwann cells (SCs) promoting the function of nitric oxide (NO) secretion of bone marrow mesenchymal stem cells (BMSCs) derived endothelial cells so as to lay the experimental foundation for research of the effect of nerves on vessels during the process of tissue engineering bone formation. SCs were collected from 1-day-old Sprague Dawley (SD) rats, and identified through S100 immunohistochemistry (IHC). BMSCs were collected from 2-week-old SD rats and induced into endothelial cells (IECs), which were identified through von Willebrand factor (vWF) and CD31 immunofluorescence (IF). Transwell system was used for co-culture of SCs and IECs without contact as the experimental group, and simple culture of IECs served as the control group. The NO concentration in the medium was measured at 1, 3, 5, and 7 days after culture; the mRNA expressions of nitric oxide synthetase 2 (NOS2) and NOS3 were detected by real-time fluorescence quantitative PCR (RT -qPCR) at 1, 3, 7, and 10 days. SCs and IECs were identified through morphology and immunology indexes of S100 IHC, vWF and CD31 IF. Significant differences were found in the NO concentration among different time points in 2 groups (P < 0.05); the NO concentration of the experimental group was significantly higher than that of the control group at the other time points (P < 0.05) except at 3 days. NOS2 mRNA expression of the experimental group was significantly higher than that of the control group (P < 0.05); difference was significant in the NOS2 mRNA expression among different time points in 2 groups (P < 0.05). NOS3 mRNA expression of the experimental group was significantly higher than that of the control group at the other time points (P < 0.05) except at 10 days. No significant difference was found in NOS3 mRNA expression among different time points in the experimental group (F = 6.673, P = 0.062), but it showed significant differences in the control group (F = 36.581, P = 0.000). SCs can promote NO secretion of BMSCs derived endothelial cells, which is due to promoting the activity of NOS.


Solar photodegradation of a textile azo dye using synthesized ZnO/Bentonite.
The present work is devoted to the synthesis of a new photocatalyst ZnO (7.5%)/Bentonite prepared by impregnation method and its successful application for the degradation of Solophenyl Red 3BL (SR 3BL) under solar light (∼660 W/m2). The X-ray diffraction (XRD) indicates mixed phases of the nanocomposite catalyst (ZnO/Bentonite), characterized by scanning electron microscopy, X-ray fluorescence and attenuated total reflection. The optical properties confirm the presence of the Wurtzite ZnO phase with an optical gap of 3.27 eV. The catalyst dose (0.25-1 gL-1), pH solution (2.5-11) and initial dye concentration (5-75 mg/L) are optimized. The optimal pH (∼6.7) is close to the natural environment. The photodegradation yield increases with decreasing the SR 3BL concentration. The equilibrium is reached within 160 min and the data are well fitted by the Langmuir-Hinshelwood model; the SR 3BL disappearance obeys to a first-order kinetic with an apparent rate constant of 10-2 mn-1. The best yield of SR 3BL photodegradation (92%) is achieved for a concentration of 5 mg/L and a catalyst dose of 0.75 gL-1 at free pH.


Nondestructive label-free detection of peritumoral white matter damage using cross-polarization optical coherence tomography.
To improve the quality of brain tumor resections, it is important to differentiate zones with myelinated fibers destruction from tumor tissue and normal white matter. Optical coherence tomography (OCT) is a promising tool for brain tissue visualization and in the present study, we demonstrate the ability of cross-polarization (CP) OCT to detect damaged white matter and differentiate it from normal and tumor tissues. The study was performed on 215 samples of brain tissue obtained from 57 patients with brain tumors. The analysis of the obtained OCT data included three stages: 1) visual analysis of structural OCT images; 2) quantitative assessment based on attenuation coefficients estimation in co- and cross-polarizations; 3) building of color-coded maps with subsequent visual analysis. The defining characteristics of structural CP OCT images and color-coded maps were determined for each studied tissue type, and then two classification tests were passed by 8 blinded respondents after a training. Visual assessment of structural CP OCT images allows detecting white matter areas with damaged myelinated fibers and differentiate them from normal white matter and tumor tissue. Attenuation coefficients also allow distinguishing all studied brain tissue types, while it was found that damage to myelinated fibers leads to a statistically significant decrease in the values of attenuation coefficients compared to normal white matter. Nevertheless, the use of color-coded optical maps looks more promising as it combines the objectivity of optical coefficient and clarity of the visual assessment, which leads to the increase of the diagnostic accuracy of the method compared to visual analysis of structural OCT images. Alteration of myelinated fibers causes changes in the scattering properties of the white matter, which gets reflected in the nature of the received CP OCT signal. Visual assessment of structural CP OCT images and color-coded maps allows differentiating studied tissue types from each other, while usage of color-coded maps demonstrates higher diagnostic accuracy values in comparison with structural images (F-score = 0.85-0.86 and 0.81, respectively). Thus, the results of the study confirm the potential of using OCT as a neuronavigation tool during resections of brain tumors.


Wavefront coding image reconstruction via physical prior and frequency attention.
Wavefront coding (WFC) is an effective technique for extending the depth-of-field of imaging systems, including optical encoding and digital decoding. We applied physical prior information and frequency domain model to the wavefront decoding, proposing a reconstruction method by a generative model. Specifically, we rebuild the baseline inspired by the transformer and propose three modules, including the point spread function (PSF) attention layer, multi-feature fusion block, and frequency domain self-attention block. These models are used for end-to-end learning to extract PSF feature information, fuse it into the image features, and further re-normalize the image feature information, respectively. To verify the validity, in the encoding part, we use the genetic algorithm to design a phase mask in a large field-of-view fluorescence microscope system to generate the encoded images. And the experimental results after wavefront decoding show that our method effectively reduces noise, artifacts, and blur. Therefore, we provide a deep-learning wavefront decoding model, which improves reconstruction image quality while considering the large depth-of-field (DOF) of a large field-of-view system, with good potential in detecting digital polymerase chain reaction (dPCR) and biological images.


Association of hypertension and its treatment with dementia and cognitive functioning.
Hypertension is known to induce many pathological changes in the body, including cardiac hypertrophy, atherosclerosis, micro-aneurisms and stroke. Besides these conspicuous pathologies, it also has subtle effects on the functioning of the brain. These cognitive changes have received little attention despite the fact that they make a large impact on the daily functioning of affected persons. The present study was conducted to assess the effect of hypertension and related factors on cognitive functions in an Indian population. A cohort of young hypertensive subjects was recruited after obtaining informed consent. Subjects with confounding factors, such as substance use, neurological disorders, endocrinopathies, inflammatory conditions and psychiatric illnesses, were excluded. The average systolic and diastolic blood pressure of the subjects since the onset of illness and prescription of drugs were noted from the records. Compliance was assessed with the help of information given by the subjects and their close relatives. The mini-mental state examination and a battery of neuropsychological tests (digit span test, trail making test, Stroop test, visuospatial working memory matrix and word fluency test) were applied to all participants. Univariate regression analysis was used for the assessment of association and a one-way analysis of variance was performed on categorical variables. The mean age of the subjects was 52 years, and the average duration of hypertension 9 years. Twelve subjects had dementia which could be attributed to the subtle effects of hypertension only. Blood pressure (both systolic and diastolic) had a significant negative association with the cognitive tests. Cognitive impairment was also seen in subjects who reported poor drug compliance and those using beta blockers, while calcium channel blockers played a protective role. Hypertension was associated with a significant decline in cognitive functioning in younger subjects. Good compliance with drugs and the use of calcium channel blockers had a protective effect on hypertension-induced cognitive decline.


[Repetitive movements of the upper limbs: results of exposure evaluation and clinical investigation in the production and packaging of ice cream].
An evaluation was made of the degree of exposure to risk and the frequency of disorders attributable to biomechanical overload of the upper limb in workers employed on packaging in an ice cream factory. The risks were first evaluated against a checklist, then subsequently an assessment was made of the tasks found to feature the highest risks, using an ergonomic analysis method. The method identified several jobs, such as placing ice cream coupes and such like in boxes, as requiring a large number of actions per minute (> 30) and considerable muscular strength. The 59 female workers performing the packaging operations were given a risk-targeted physical examination. The clinical test detected an extremely high frequency of carpal tunnel syndrome, (7.1%) epicondylitis (5.2%) and scapulo-humeral periarthritis (3.5%) in the over 35 years age group, with respect to a control population not exposed to risk. The authors conclude that the repetitiveness of the actions, the use of gloves due to prolonged contact with frozen products and the effects of the low temperatures themselves, may have favoured the spread of the disorders that appeared in this population of workers. These findings must be further supported by more in-depth epidemiological studies.


Electrospinning of Ag Nanowires/polyvinyl alcohol hybrid nanofibers for their antibacterial properties.
In order to developing a sort of flexible fibrous mats with outstanding and durable antibacterial activates, silver nanowires incorporated into polyvinyl alcohol (PVA) nanofibers were fabricated by electrospun method. Uniform Ag nanowires (NWs) were synthesized through a template-free method of solvothermal combined with polyol process, and then, they were dispersed in PVA solution. At last, Ag NWs embedded in PVA (Ag NWs/PVA) hybrid nanofibrous films were gained by electrospun of the mixed solution. The antibacterial activity of Ag NWs/PVA nanofibers against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was investigated by the methods of absorption and turbidity. Ag NWs with a mean diameter of 86nm were demonstrated to be uniformly incorporated into PVA nanofibers, forming a core-sheath nanocable structure. The as-prepared flexible and free-standing Ag NWs/PVA nanofibrous films show outstanding antimicrobial activities against both E. coli and S. aureus. It's found that both matrix polymer of PVA and enrichment of active {111} facets present in Ag NWs are favorable for the antibacterial performance.


Development of the nursing process through action research.
Implementation of the nursing process in practical nursing can be achieved in accordance with the principles of action research. A pre-requisite of the action research is a knowledge of the basic principles and the component areas of the nursing process, and of the opportunities for applying the nursing process to practical work. The documentation of the nursing of the patient is one clear object in which the model of the nursing process takes concrete shape. Another prominent form of action is the analysis of the content of the nursing, and on the basis of this framework the needs of individual patients can be determined and evaluated. Important methods in action research are consulting and work guidance. The researcher, together with the workers, endeavours to develop the work of nursing and to seek opportunities and methods to carry out the nursing process model.


Multicolor Mechanochromism of a Polymer/Silica Composite with Dual Distinct Mechanophores.
The development of a multicolor mechanochromic polymer/silica composite is achieved by using two distinct types of mechanochromophores. The multicolor mechanochromism of the composite containing diarylbibenzofuranone in silica-rich domains and naphthopyran in the polymer-rich domain is observed. The obtained composite shows blue, green, and orange colors according to the intensity of applied mechanical stimuli, solvent addition, and lapse of time. This unique multicolor mechanochromic behavior is evaluated by solid-state UV-vis absorption spectroscopy, ab initio steered molecular dynamics simulations, and computed minimum energy paths on force-modified potential energy surfaces. The unique mechanochromism is attributed to the difference in properties, activated colors, and domain locations between the two mechanochromophores.


Identification of women at risk for unwanted pregnancy.
Concern about increasing rates of unwanted pregnancy, particularly among adolescents, has led to consideration of steps necessary to develop effective intervention programs. In order to reach a young woman for counseling and contraceptive assistance before she places herself at risk for unintended pregnancy, it seems necessary to develop the capability for identifying high-risk individuals without reference to sexual history. The authors describe a preliminary attempt to predict contraceptively unprotected coitus from responses to projective test stimuli, noting that the problem is so urgent that even early and necessarily incomplete work in this area may have merit in stimulating further research in identification of women at risk for unwanted pregnancy.


[OKT4 epitope deficiency in a patient with thymoma and hypogammaglobulinemia].
A 61-year-old male stonecutter was in excellent health until December 1988 when he was admitted to Miyagikenritsu Semine Hospital with an abnormality on chest X-ray film. Chest X-ray film revealed a left anterior mass that was confirmed on chest CT scan and MRI. Biochemical examinations and serum protein electrophoresis demonstrated hypoproteinemia (5.4 g/dl) and hypogammaglobulinemia (7.9%, 0.43 g/dl). Lymphocyte subset analysis showed OKT4 epitope deficiency (OKT4 0.1% and Leu3a 28.4%), and decrease of CD4/CD8 ratio (0.65). An encapsulated anterior mediastinal mass and the thymus were resected on January 9, 1989, without difficulty. Histology revealed a thymoma with a spindle cell epithelial component. OKT4 epitope deficiency in a patient with Good's syndrome (thymoma with hypogammaglobulinemia) was our diagnosis. There was no change in the patient's serum immunoglobulin level after thymectomy. Fifteen cases of Good's syndrome have been reported in Japan, but this is the first report of OKT4 epitope deficiency with Good's syndrome in Japan.


Morphometric and molecular identification of individual barnacle cyprids from wild plankton: an approach to detecting fouling and invasive barnacle species.
The present study used DNA barcodes to identify individual cyprids to species. This enables accurate quantification of larvae of potential fouling species in the plankton. In addition, it explains the settlement patterns of barnacles and serves as an early warning system of unwanted immigrant species. Sequences from a total of 540 individual cypris larvae from Taiwanese waters formed 36 monophyletic clades (species) in a phylogenetic tree. Of these clades, 26 were identified to species, but 10 unknown monophyletic clades represented non-native species. Cyprids of the invasive barnacle, Megabalanus cocopoma, were identified. Multivariate analysis of antennular morphometric characters revealed three significant clusters in a nMDS plot, viz. a bell-shaped attachment organ (most species), a shoe-shaped attachment organ (some species), and a spear-shaped attachment organ (coral barnacles only). These differences in attachment organ structure indicate that antennular structures interact directly with the diverse substrata involved in cirripede settlement.


Evidence-based medicine and the anecdote: Uneasy bedfellows or ideal couple?
Over the past 30 years, there has been a resurgence in the use of storytelling and narrative in medicine. At first glance, the trend to incorporate art forms into medicine appears to run counter to the rise of the more objective and positivist evidence-based medicine movement. In the present article, the authors provide examples of the use of storytelling and narrative in medicine, describe their origins, and contrast this approach with evidence-based medicine. The authors suggest that storytelling and narrative offer a complement to the science of evidence-based medicine. Finally, the authors describe a program of research to develop and evaluate the use of storytelling as a communication tool between physicians and parents/caregivers of children presenting to the emergency department.


Acceleration-induced near-loss of consciousness: the "A-LOC" syndrome.
There is an insidious phenomenon that can occur when aircrew are exposed to +Gz stress even at levels that are insufficient to cause +Gz-induced loss of consciousness (G-LOC). Under these circumstances aircrew exhibit an altered state of awareness that was termed Almost Loss of Consciousness (A-LOC) by the U.S. Navy in the late 1980's. A-LOC is a syndrome that includes a wide variety of cognitive, physical, emotional, and physiological symptoms. While A-LOC has been observed in centrifuge studies and reported in flight for over 15 yr, a definitive description of the syndrome does not exist. Nine subjects were exposed to short +6, 8, and 10 Gz pulses of increasing duration until they experienced G-LOC. Instrumentation included two channels of ECG and near infrared spectroscopy (NIRS) to measure relative cerebral tissue oxygenation (rSo2). Subjects indicated +Gz-induced visual symptoms (light loss, LL) by pressing a switch when LL began and releasing it when total vision was restored. Short-term memory loss was assessed using a simple math task. Data analysis included a description and the time course of the physical, physiological, cognitive, and emotional responses. There were 66 episodes of A-LOC that were identified out of a total of 161 +Gz pulse exposures. Many incidents of sensory abnormalities, amnesia, confusion, euphoria, difficulty in forming words, and reduced auditory acuity were documented. Often these responses occurred in multiple subjects and at different +Gz levels. One of the most common symptoms was a disconnection between cognition and the ability to act on it. There was a significant reduction in rSo2 over baseline, greater overshoot in rSo2 (increase in oxygenation above baseline after the +Gz exposure), faster fall in rSo2 during +Gz stress, and prolonged recovery time associated with A-LOC as compared with +Gz exposures without symptoms. Evaluation of the range of symptoms associated with A-LOC can lead to a program to increase pilots' awareness of the phenomenon and further our understanding of the relationship between the outward symptoms and the underlying physiological changes.


Photoluminescent materials based on silica doped with lanthanide complexes of 4'-formylbenzo-15-crown-5.
Photoluminescent materials were prepared by introducing lanthanide complexes of 4'-formylbenzo-15-crown-5 (C15H20O6) into a silica matrix obtained by the sol-gel method. The new lanthanide complexes [Ln(C15H20O6)(NO3)3(H2O)2] (Ln3+ = Sm3+, Eu3+ and Tb3+) were synthesized and were fully characterised using spectroscopic techniques, and elemental and thermogravimetric analysis. Photoluminescence measurements were performed for the isolated Eu3+ and Tb3+ complexes as well as for their related silica based materials. A detailed comparative analysis on the photoluminescent properties of the EU3+ complex and of its derived silica material was carried out.


Toothache and self-medication practices: a study of patients attending a niger delta tertiary hospital in Nigeria.
There is evidence that self-medication practices among dental patients with toothache are common, and despite the adverse clinical consequences, there is a paucity of literature on it, and only few programs are available for its control. The aim was to assess the self-medication practices among adult dental patients suffering from toothache. An instrument adapted from modified form of 117-item self-report questionnaire based on world Health Organization guidelines for students' substance use survey and open-ended questionnaire was administered to adult patients attending the Dental and Maxillofacial Surgery Clinic of this Health Institution for a period of 6 months. The results show that 80.6% (287/356) subjects indulged in self-medication practices. Majority of the patients 42.9% (123/287) were in the 2-4(th) decades of life, whereas the male: female ratio was 1.3:1. The most commonly abused medications/substance was analgesics/non-steroidal anti-inflammatory drug (243/287; 24.5%), antibiotics (233/287; 23.5%), "touch and go" (187/287; 18.8%). The practice of self-medication cut across all social strata, P < 0.01 (significant) and only 3.8% (11/287) subjects admitted knowledge of the dosage and side-effects of the used medications/substances. The toothache not being serious initially (112/287; 22.5%) and time constraints to attend dental clinic (93/287; 18.7%) were the major reasons for self-medication. This study suggests that the practice of self-medication is common among adult dental patients with toothache in Nigeria. This should be reduced to the barest minimum by dental health education, upgrading of dental health facilities, and enforcement of drug control mechanisms.


Viscoelastic Properties of Confluent MDCK II Cells Obtained from Force Cycle Experiments.
The local mechanical properties of cells are frequently probed by force indentation experiments carried out with an atomic force microscope. Application of common contact models provides a single parameter, the Young's modulus, to describe the elastic properties of cells. The viscoelastic response of cells, however, is generally measured in separate microrheological experiments that provide complex shear moduli as a function of time or frequency. Here, we present a straightforward way to obtain rheological properties of cells from regular force distance curves collected in typical force indentation measurements. The method allows us to record the stress-strain relationship as well as changes in the weak power law of the viscoelastic moduli. We derive an analytical function based on the elastic-viscoelastic correspondence principle applied to Hertzian contact mechanics to model both indentation and retraction curves. Rheological properties are described by standard viscoelastic models and the paradigmatic weak power law found to interpret the viscoelastic properties of living cells best. We compare our method with atomic force microscopy-based active oscillatory microrheology and show that the method to determine the power law coefficient is robust against drift and largely independent of the indentation depth and indenter geometry. Cells were subject to Cytochalasin D treatment to provoke a drastic change in the power law coefficient and to demonstrate the feasibility of the approach to capture rheological changes extremely fast and precisely. The method is easily adaptable to different indenter geometries and acquires viscoelastic data with high spatiotemporal resolution.


Adolescent internalizing symptoms and negative life events: the sensitizing effects of earlier life stress and cortisol.
Although adolescence is marked by increased negative life events and internalizing problems, few studies investigate this association as an ongoing longitudinal process. Moreover, while there are considerable individual differences in the degree to which these phenomena are linked, little is known about the origins of these differences. The present study examines early life stress (ELS) exposure and early-adolescent longitudinal afternoon cortisol level as predictors of the covariation between internalizing symptoms and negative life events across high school. ELS was assessed by maternal report during infancy, and the measure of cortisol was derived from assessments at ages 11, 13, and 15 years. Life events and internalizing symptoms were assessed at ages 15, 17, and 18 years. A two-level hierarchical linear model revealed that ELS and cortisol were independent predictors of the covariation of internalizing symptoms and negative life events. Compared to those with lower levels of ELS, ELS-exposed adolescents displayed tighter covariation between internalizing symptoms and negative life events. Adolescents with lower longitudinal afternoon cortisol displayed tighter covariation between negative life events and internalizing symptoms, while those with higher cortisol demonstrated weaker covariation, partially due to increased levels of internalizing symptoms when faced with fewer negative life events.


Cytomegalovirus retinitis in hospitalized people living with HIV in the late antiretroviral therapy era in São Paulo, Brazil.
There is scarce information on AIDS-related cytomegalovirus (CMV) retinitis in middle-income countries. The objectives of this study were to identify the prevalence of active CMV retinitis in severely immunosuppressed people living with HIV (PLWHIV) and to describe its main features. This retrospective cohort study was carried out at a tertiary center in São Paulo, Brazil. We included hospitalized adults PLWHIV with CD4 count ≤100 cells/μL, ≥ one quantitation of CMV DNA in plasma, and indirect ophthalmoscopy evaluation. Thirty-eight (21.6%) of 176 participants had at least an ophthalmoscopy diagnosis and only 3 (1.7%) individuals presented active CMV retinitis. All these participants were male, and retinitis was asymptomatic in 2 cases. Two participants had extraocular end-organ CMV disease and detectable CMV DNA in plasma. These results show a low prevalence of active CMV retinitis in the evaluated population. However, 2 of 3 participants had asymptomatic active CMV retinitis and a fifth of participants had at least one ophthalmoscopy diagnosis, suggesting the need for routine ophthalmologic evaluation in hospitalized severely immunosuppressed PLWHIV. The profile of participants with active CMV retinitis was similar to that described in the pre-ART era and quantitation of CMV DNA in plasma was variable.


Magnetic Resonance Lymphography of Lymphatic Vessels in Upper Extremity With Breast Cancer-Related Lymphedema.
Magnetic resonance lymphangiography (MRL) has been proven to be able to visualize pathological lymphatic networks and accompanying complications through subcutaneous injection of commonly used contrast agents. However, no comprehensive prior studies have previously been reported regarding MRL for the evaluation of upper extremity lymphedema in patients with breast cancer-related lymphedema (BCRL). In this study, we establish a novel MRL protocol to characterize the normal and abnormal characteristics of different clinical stages of BCRL in patients using high-spatial-resolution MRL. Fifty females with unilateral upper extremity BCRL underwent MRL. Lymphatic vessel morphology in normal and affected limbs was compared. The appearance, distribution pattern, morphologic characteristics, and maximum transversal diameter of the lymphatic vessels, dermal backflow, and regeneration of lymphatic vessels were analyzed. Lymph fluid was retained in the subcutis of the affected limbs, and no edema was observed in the subfascial compartment. In stage 1, tortuous and dilated lymphatic vessels exhibited a beaded appearance, and their diameters were larger than those in the contralateral forearm (P < 0.05). In stage 2, the dilated lymphatic vessels exhibited larger diameters. "Dermal backflow" and tiny regenerated lymphatic vessels appeared. The thickened subcutaneous tissue showed a honeycomb pattern induced by soft tissue fibrosis and adipose hypertrophy. In stage 3, disordered and unrecognizable affected lymphatic vessels were observed with many small regenerated lymphatics and confluent dermal backflow; the tissue fibrosis was more serious. Each stage presents different characteristics, and the deformity degree of the lymphatic network is consistent with the severity of the disease. Magnetic resonance lymphangiography could provide adequate information for clinical staging in patients with BCRL.


Early statin therapy in elderly patients presenting with acute coronary syndrome causing less heart failure.
Elderly patients are less likely to receive statin therapy because of concerns about their side-effects. However, 80% of deaths related to coronary heart disease occur in patients above the age of 65 years. This study evaluated the potential benefit of early administration of statins in elderly patients presenting with an acute coronary syndrome. This was a prospective cohort study of 774 elderly patients (>65 years) with acute coronary syndrome. The patients were divided into two groups. The first group, consisting of 611 patients, received statins within the first 24 hours of admission, while the second group, consisting of 163 patients, received statins after the first 24 hours. The end points studied included death, heart failure/pulmonary edema, stroke and recurrent myocardial infarction during hospitalization. Multivariable logistic regression analysis, adjusting for baseline demographics, co-morbidities and chronic statin therapy, showed that the occurrence of heart failure/pulmonary edema during hospitalization was relatively lower among those who received statins within 24 hours of admission (odds ratio: 0.5, 95% CI: 0.27-0.94, p=0.03). The C statistic for the model was 0.79. Elderly patients presenting with acute coronary syndrome seem to benefit from early statin therapy, and have significantly lower rates of heart failure and pulmonary edema than those who are administered statins at a later stage.


Effect of pomegranate seed oil on egg production, egg quality and yolk fatty acid deposition in laying hen.
Pomegranate seed oil (PSO) contains punicic acid as well as conjugated linolenic acid isomers, including α-eleostearic and catalpic acids, along with phytosterols, especially β-sitosterol, campesterol and stigmasterol, with lipotropic impact and egg fortifying effect in laying hens. The present experiment was designed to examine the effects of PSO on egg production, egg quality, blood lipids and yolk fatty acid deposition in laying hens. A total of 360 Hy-line laying hens (w-80), at 25 weeks of age, were randomly allotted to five dietary treatments in a completely randomized design during a 10-week period. Experimental treatments consisted of a basal diet or supplementation of 1, 2, 3 and 4 g PSO/kg to basal diet. Performance indicators and fatty acid composition of egg yolk were evaluated during different experimental periods. Blood lipid attributes were evaluated at the end of the experiment. Dietary supplementation of 4 g PSO/kg feed increased daily feed intake and egg production rate of laying hens (p < 0.05). There was not any significant influence of experimental treatments on egg quality, whereas an increasing trend observed in egg yolk colour of hens received dietary graded levels of PSO. Dietary supplemental 4 g/kg PSO increased the proportion of yolk poly-unsaturated fatty acid (PUFA) concentration (p < 0.05). Furthermore, the PUFA to saturated fatty acid ratio increased after dietary supplementation of 1 or 4 g/kg PSO (p < 0.05). Serum concentration of cholesterol, triacylglycerol and low-density lipoprotein decreased in response to the supplementation of more than 3 g PSO/kg in the feed (p < 0.05). In conclusion, dietary supplementation with 4 g/kg PSO improved production rate and decreased blood lipids in laying hens. Moreover, dietary supplemental PSO modified yolk fatty acid deposition without detrimental effects on the egg quality.


Is the pathogenic ergot fungus a conditional defensive mutualist for its host grass?
It is well recognized, that outcomes of mutualistic plant-microorganism interactions are often context dependent and can range from mutualistic to antagonistic depending on conditions. Instead, seemingly pathogenic associations are generally considered only harmful to plants. The ergot fungus (Claviceps purpurea) is a common seed pathogen of grasses and cereals. Ergot sclerotia contain alkaloids which can cause severe toxicity in mammals when ingested, and thus the fungal infection might provide protection for the host plant against mammalian herbivores. Theoretically, the net effect of ergot infection would positively affect host seed set if the cost is not too high and the defensive effect is strong enough. According to our empirical data, this situation is plausible. First, we found no statistically significant seed loss in wild red fescue (Festuca rubra) inflorescences due to ergot infection, but the seed succession decreased along increasing number of sclerotia. Second, in a food choice experiment, sheep showed avoidance against forage containing ergot. Third, the frequency of ergot-infected inflorescences was higher in sheep pastures than surrounding ungrazed areas, indicating a protective effect against mammalian grazing. We conclude that, although ergot can primarily be categorized as a plant pathogen, ergot infection may sometimes represent indirect beneficial effects for the host plant. Ergot may thus serve as a conditional defensive mutualist for its host grass, and the pathogenic interaction may range from antagonistic to mutualistic depending on the situation.


Calcium and colon cancer.
Calcium has been hypothesized as being a regulator of cell proliferation in the colon. Epidemiologic studies suggest that ingestion of higher levels of dietary calcium are related to a decreased risk for colon cancer. Short term studies in vitro and in vivo of the proliferative behavior of human and animal colon mucosa verify that calcium does modulate proliferative response. Preliminary clinical studies suggest that the hyperproliferative mucosa of patients at high risk for colon cancer, based on proliferation analysis of biopsied mucosa, became decidedly less proliferative when the subjects were given oral calcium. Our studies address the molecular mechanisms by which calcium controls mucosal proliferation and the ways in which tumor cells circumvent this regulation.


Wear of 3D printed and CAD/CAM milled interim resin materials after chewing simulation.
The purpose of this in vitro study was to investigate the wear resistance and surface roughness of three interim resin materials, which were subjected to chewing simulation. Three interim resin materials were evaluated: (1) three-dimensional (3D) printed (digital light processing type), (2) computer-aided design and computer-aided manufacturing (CAD/CAM) milled, and (3) conventional polymethyl methacrylate interim resin materials. A total of 48 substrate specimens were prepared. The specimens were divided into two subgroups and subjected to 30,000 or 60,000 cycles of chewing simulation (n = 8). The wear volume loss and surface roughness of the materials were compared. Statistical analysis was performed using one-way analysis of variance and Tukey's post-hoc test (α=.05). The mean ± standard deviation values of wear volume loss (in mm3) against the metal abrader after 60,000 cycles were 0.10 ± 0.01 for the 3D printed resin, 0.21 ± 0.02 for the milled resin, and 0.44 ± 0.01 for the conventional resin. Statistically significant differences among volume losses were found in the order of 3D printed, milled, and conventional interim materials (P<.001). After 60,000 cycles of simulated chewing, the mean surface roughness (Ra; μm) values for 3D printed, milled, and conventional materials were 0.59 ± 0.06, 1.27 ± 0.49, and 1.64 ± 0.44, respectively. A significant difference was found in the Ra value between 3D printed and conventional materials (P=.01). The interim restorative materials for additive and subtractive manufacturing digital technologies exhibited less wear volume loss than the conventional interim resin. The 3D printed interim restorative material showed a smoother surface than the conventional interim material after simulated chewing.


Leaf hydraulic conductance declines in coordination with photosynthesis, transpiration and leaf water status as soybean leaves age regardless of soil moisture.
Photosynthesis requires sufficient water transport through leaves for stomata to remain open as water transpires from the leaf, allowing CO2 to diffuse into the leaf. The leaf water needs of soybean change over time because of large microenvironment changes over their lifespan, as leaves mature in full sun at the top of the canopy and then become progressively shaded by younger leaves developing above. Leaf hydraulic conductance (K(leaf)), a measure of the leaf's water transport capacity, can often be linked to changes in microenvironment and transpiration demand. In this study, we tested the hypothesis that K(leaf) would decline in coordination with transpiration demand as soybean leaves matured and aged. Photosynthesis (A), stomatal conductance (g(s)) and leaf water potential (Ψ(leaf)) were also measured at various leaf ages with both field- and chamber-grown soybeans to assess transpiration demand. K(leaf) was found to decrease as soybean leaves aged from maturity to shading to senescence, and this decrease was strongly correlated with midday A. Decreases in K(leaf) were further correlated with decreases in g(s), although the relationship was not as strong as that with A. Separate experiments investigating the response of K(leaf) to drought demonstrated no acclimation of K(leaf) to drought conditions to protect against cavitation or loss of g(s) during drought and confirmed the effect of leaf age in K(leaf) observed in the field. These results suggest that the decline of leaf hydraulic conductance as leaves age keeps hydraulic supply in balance with demand without K(leaf)becoming limiting to transpiration water flux.


Successful transplantation of bovine testicular cells to heterologous recipients.
While heterologous germ cell transplantation was successful in pigs and goats, autologous transplantation alone has been reported to result in donor-derived spermatogenesis in cattle. The objective of this study was to investigate whether the transplantation of heterologous germ cells could result in colonization of recipient testes in cattle of different breeds. Testicular cells were isolated from 8 Bos taurus donor bull calves and then transferred into 15 Bos indicus-cross bull calves. All animals were prepubertal, donors were aged 5-7 months and recipients 5-11 months, and scrotal circumferences ranged from 15 to 22 cm. Single cell suspensions of donor testicular cells, prepared by enzymatic digestion, were labelled with fluorescent dyes PKH26 or CFDA-SE, before transfer into the rete testis of recipients under ultrasonographic guidance. To assess the longevity of colonization by donor cells, recipients were castrated 2-30 weeks after cell transfer. Donor cells were observed in 15/25 (60%) of the testes that received PKH26-labelled cells, whereas no CFDA-SE-positive cell was identified in any recipients. The maturity of the donors or recipients (measured by scrotal circumference) did not affect colonization potential. In freshly isolated tubules, clumps of PKH26-positive cells were observed, which indicated either cell division or extensive local colonization of specific areas of the tubules. In frozen sections, PKH26-positive cells were identified on the seminiferous tubule basement membrane, which indicated that these cells had successfully migrated from the tubule lumen and were likely to be spermatogonia. We conclude that PKH26 was more suitable for labelling donor testis cells and donor cells can be identified up to 6 months following transfer. These results indicate that allogeneic transplantation of testicular cells can occur between Bos taurus and Bos indicus cattle. Further studies will investigate functionality of transferred testicular cells.


Persistence of weight loss and acquired behaviors 2 y after stopping a 2-y calorie restriction intervention.
Background: Calorie restriction (CR) influences aging processes and extends average and maximal life spans. The CALERIE 2 (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy Phase 2) study was the first randomized clinical trial to examine the metabolic and psychological effects of CR in nonobese humans.Objective: We conducted a 2-y follow-up study of adults who underwent 2 y of CR or ad libitum (control) consumption and determined whether weight loss and acquired behaviors persisted after the study ended when participants determined their own lifestyle behaviors.Design: In this prospective, longitudinal study, we assessed differences in weight, body composition, psychological function, and energy expenditure in 39 nonobese [body mass index (in kg/m2): 22-28] men and women (25% CR: n = 24; control: n = 15) 12 and 24 mo after they completed the CALERIE 2 study at Pennington Biomedical.Results: Of 39 participants who were in the follow-up study, 29 subjects (CR: n = 18; control: n = 11) completed all visits at follow-up months 12 and 24. After the CR intervention, a mean ± SEM weight loss of 9.0 ± 0.6 kg was observed in the CR group, in which only 54% of the weight was regained 2 y later. Despite such a regain, weight, the percentage of body fat, and fat mass remained significantly reduced from baseline throughout follow-up and remained significantly less than in the control group (P < 0.05). At follow-up, the CR group retained higher degrees of dietary restraint and avoidance of certain foods.Conclusion: After a 2-y intensive CR intervention, ∼50% of CR-induced weight loss was maintained 2 y later, which was probably the result of lasting effects on acquired behaviors and dietary restraint. This trial was registered at clinicaltrials.gov as NCT00943215.


Communication in a crisis in UK ambulance services: What is needed to improve incident communication?
Communication during a major incident or business disruption is essential for all organisations, but to the emergency services it is paramount. Timely and accurate communications are critical but present many challenges to all responders, particularly the blue-light sector. There are many layers and components to communication, including command and control, technical solutions and the inherent cultures within each of the ambulance services. While ambulance services have the same tools available to them as their partners in the police and fire service, they appear at times to be disadvantaged, but why is this? Is it organisational culture, access to training or simply the attitude and experience of responding individuals and commanders? UK NHS ambulance services are often the 'gateway to health', so failure to communicate is not an option. This paper will discuss the communication challenges that the ambulance service regularly face and the options that are available when dealing with complex or major incidents.


A process evaluation of a Training of Trainers (TOT) model of men's health training.
This study set out to identify the mediators of diffusion of a Training of Trainers (ToT) programme; focusing on ENGAGE, Ireland's national men's health training programme, we explored the process (planning, implementation and maintenance) of using a ToT model of training to affect change in gender sensitive health and social service provision for men. Our findings indicate that an experiential learning approach in combination with mechanisms for feedback and fostering peer-based support during training and beyond are key strategies that foster individual (Trainer), community (of Trainers) and organizational (Trainer workplaces) level ownership. Moreover, by adapting in response to feedback, ENGAGE was able to remain relevant over a number years and to different cohorts of Trainers. As such, core strategies used by ENGAGE could be used to inform new models of health training elsewhere.


Description of the zoeal stages of Periclimenes aegylios Grippa d'Udekem d'Acoz, 1996 (Crustacea: Decapoda: Palaemonidae) reared in the laboratory.
The eight zoeal stages of the Mediterranean shrimp Periclimenes aegylios are described and illustrated in detail, using laboratory-reared specimens. This study improved the partial and unpublished descriptions of the zoeae of this species. The complete and accurate definition of the morphology of all the stages now allows comparison of the zoeae of P. aegylios with those of other Mediterranean Periclimenes species, as well as the allopatric Atlantic P. sagittifer, from which P. aegylios was separated in 1996.


Dental emergence among urban Zambian school children: an assessment of the accuracy of three methods in assigning ages.
In situations where birth records are unavailable and stated ages are unreliable, the emergence of the permanent dentition can serve as an indicator of age. Due to substantial variation in the timing of tooth emergence, a sample (n = 721) of Zambian school children, with known ages, was examined to provide a tooth emergence reference standard for the area. Three methods for assigning ages were utilized and their accuracy assessed. A random test sample was withheld from the original study in order to further evaluate the methods' accuracy. The three methods-1) number of teeth, 2) regression and 3) probit analysis-were applied to Zambian children, and estimates of age were made. Predicted ages were compared to actual ages to determine the percentage of accuracy in three categories-(+/-) .5, +/- 1.0 and +/- 2.0 years- and paired t-tests were conducted. Each of the three methods was then applied to the test sample, and their accuracy was evaluated in the same manner. Methods 1 and 2 were found to provide the higher percentage of correct ages within +/- .5 years, assigning roughly 39% of both male and female children within this increment. This was also the case at the next increment, with methods 1 and 2 assigning a higher percentage (66-76%) of children to the +/- 1.0 year category, while the accuracy of method 3 was quite a bit lower. The results for the test sample were very similar to those of the main sample. The overall accuracy of methods 1 and 2 was very similar in both the main and test samples, while method 3 had lower accuracy and t-tests indicated significant differences. Therefore, due to ease of application in the field setting, method 1, mean age per number of teeth emerged, is the method of choice.


Prognostic impact of high c-Met expression in ovarian cancer: a meta-analysis.
High c-Met expression has been observed in epithelial ovarian cancer (EOC). However, its clinicopathological impacts remain controversial. We conducted this meta-analysis to evaluate the pathologic and prognostic significance of c-Met overexpression in patients with EOC. A systematic computerized search of the electronic databases PubMed, PMC, EMBASE, and Google scholar (up to April 2018) was carried out. From seven studies, 568 patients with EOC were included in the meta-analysis. Although there was no statistical significance, EOCs with c-Met overexpression tended to show higher FIGO stage (III-IV) (odds ratio = 2.18, 95% confidence interval: 0.86-5.53, p = 0.10) and higher rate of lymph node metastasis (odds ratio = 3.05, 95% confidence interval: 0.85-10.98, p = 0.09), compared with tumors with low c-Met expression. In terms of prognosis, patients with c-Met-high EOC showed significantly worse survival than those with c-Met-low tumor (hazard ratio = 2.11, 95% confidence interval: 1.51-2.94, p < 0.0001). In conclusion, this meta-analysis indicates that high c-Met expression represents an adverse prognostic marker for patients with EOC.


Obstacles and approaches to clinical database research: experience at the University of California, San Francisco.
With increasing availability of clinical data in machine-readable form, and decreasing cost of storing and manipulating that data, retrospective research using clinical databases has become more feasible. Nonetheless, much of the potential for clinical research using these data remains unrealized. Obstacles to clinical database research include difficulty accessing data, difficulty using retrospective data to draw valid inferences about medical tests and treatments, and a shortage of investigators trained and interested in using a clinical database to answer their questions. At the University of California, San Francisco, we have developed a Clinical Database Research Program (CDRP) to try to overcome these obstacles. The CDRP maintains a relational database of patient data obtained from diverse sources and a small staff dedicated to providing such data to researchers. The CDRP staff also provides support for design and analysis of studies using the database--the development of methods for such studies is our primary research interest. Finally, to increase the number of investigators using the database for research, we are integrating training in clinical epidemiology and clinical research methods into residency and fellowship training, and offering an elective in clinical database research for trainees who wish to undertake a specific project.


Neuronal Mechanisms of Visual Attention.
Advances on several fronts have refined our understanding of the neuronal mechanisms of attention. This review focuses on recent progress in understanding visual attention through single-neuron recordings made in behaving subjects. Simultaneous recordings from populations of individual cells have shown that attention is associated with changes in the correlated firing of neurons that can enhance the quality of sensory representations. Other work has shown that sensory normalization mechanisms are important for explaining many aspects of how visual representations change with attention, and these mechanisms must be taken into account when evaluating attention-related neuronal modulations. Studies comparing different brain structures suggest that attention is composed of several cognitive processes, which might be controlled by different brain regions. Collectively, these and other recent findings provide a clearer picture of how representations in the visual system change when attention shifts from one target to another.


Enantioselective Addition of Dialkyl Malonates to β-Arylethenesulfonyl Fluorides under High-Pressure Conditions.
Application of high-pressure conditions enables enantioselective Michael-type addition of dialkyl malonates to β-arylethenesulfonyl fluorides. The reaction is efficiently catalyzed with 5 mol % of tertiary amino-thiourea at 9 kbar. Chiral alkanesulfonyl fluorides are formed in yields of up to 96% and enantioselectivities of up to 92%. Functionalization of the adducts via sulfur fluoride exchange (SuFEx) reaction and desulfonylative cyclization is demonstrated.


The role of selective dorsal rhizotomy in cerebral palsy: critical evaluation of a prospective clinical series.
This is a prospective observational study of a consecutive series of 34 children with spastic cerebral palsy treated at a single center. 10 had spastic quadriplegia and 24 had spastic diplegia. All were followed for at least one year. After selective dorsal rhizotomy (SDR), all children received one month of physical therapy at the center and were prescribed a program of physical therapy in their community. The children were assessed before and one year after SDR and physical therapy, using the Ashworth Scale, deep tendon reflex response, range of motion and the Gross Motor Function Measure. The results show that there is often a decrease in lower-extremity spasticity and functional improvement after SDR with physical therapy, but that there is considerable variability in outcome. Randomized prospective clinical trials with masked objective outcome measures are needed to determine the efficacy of SDR.


Observations on the culture of M. leprae in Medium V. A preliminary report.
This paper reports the preliminary findings of an investigation using Medium V for culture of M. leprae. The medium was prepared adhering to the procedures adopted by Veeraraghavan. Tissues from 7 cases of lepromatous leprosy (Bacteriological Index of 3 or more) were inoculated into Medium V and incubated at 8-10 degrees C for 72 hours. Quantitative estimation of leprosy bacilli were made employing the enumeration technique of Veeraraghavan. There was no evidence of multiplication in any of the cultures. The findings are in conformity with those of Kato (1983) and of Katoch and Desikan (1983).


Efruxifermin in non-alcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a trial.
Preclinical and clinical data suggest that fibroblast growth factor 21 (FGF21) is anti-fibrotic, improves metabolic status and has potential to treat non-alcoholic steatohepatitis (NASH). We assessed the safety and efficacy of efruxifermin, a long-acting Fc-FGF21 fusion protein, for the treatment of NASH. BALANCED was a randomized, placebo-controlled study in patients with NASH conducted at 27 centers in the United States (ClinicalTrials.gov NCT03976401 ). Eighty patients, stratified by hepatic fat fraction (HFF) and fibrosis stage, were randomized using a centrally administered minimization algorithm 1:1:1:1 to receive placebo (n = 21) or efruxifermin 28 mg (n = 19), efruxifermin 50 mg (n = 20) or efruxifermin 70 mg (n = 20) via weekly subcutaneous injection for 16 weeks. The primary endpoint-absolute change from baseline in HFF measured as magnetic resonance imaging-proton density fat fraction at week 12-was met. For the full analysis set, the least squares mean absolute changes (one-sided 97.5% confidence interval) from baseline in HFF were -12.3% (-infinity (-inf), -10.3), -13.4% (-inf, -11.4) and -14.1% (-inf, -12.1) in the 28-, 50- and 70-mg groups, respectively, versus 0.3% (-inf, 1.6) in the placebo group, with statistically significant differences between efruxifermin groups and placebo (P < 0.0001 each). Overall, 70 of 79 patients who received the study drug (89%) experienced at least one treatment-emergent adverse event (TEAE), with the majority grade 1-2 (64 (81%)), five (6%) grade 3 and one grade 4. The most commonly reported drug-related TEAEs were grade 1-2 gastrointestinal (36 (46%)). Treatment with efruxifermin significantly reduced HFF in patients with F1-F3 stage NASH, with an acceptable safety profile.


Dysregulated repair in asthmatic paediatric airway epithelial cells: the role of plasminogen activator inhibitor-1.
Asthma is associated with structural changes to airways such as extracellular matrix deposition and epithelial damage. Evidence suggests that asthmatic airway epithelial repair is abnormal and that elevated plasminogen activator inhibitor-1 levels observed in asthma may be involved in the epithelial repair process and in excessive matrix accumulation. To assess the ability of asthmatic airway epithelial cells (AECs) to repair mechanically induced wounds and to investigate the role that plasminogen activator inhibitor-1 plays in the repair process. AECs were isolated from atopic asthmatic and healthy non-atopic children by bronchial brushing, subcultured and wound repair experiments were performed. Plasminogen activator inhibitor-1 gene expression was assessed using real-time PCR while protein activity was measured in cell lysates as well as plasma. The role of plasminogen activator inhibitor-1 in epithelial proliferation and wound repair was investigated using siRNA. Cells from asthmatic children have a significantly longer repair time in comparison with cells from otherwise healthy donors. Plasminogen activator inhibitor-1 mRNA expression was up-regulated 68-fold in freshly isolated asthmatic cells compared with normal cells, and protein levels were also significantly elevated in the asthmatic cell lysates, but plasma levels were similar in both groups. Plasminogen activator inhibitor-1 cells expression increased in both cohorts during culture. Gene silencing substantially reduced the rate of proliferation in asthmatic and healthy cells. Mechanical wounding of epithelial monolayers induced plasminogen activator inhibitor-1 expression in asthmatic and non-asthmatic cohorts, while gene silencing delayed wound repair of healthy cell, with minimal effect on those from asthmatics. Asthmatic AECs are inherently dysfunctional in their ability to repair wounds; plasminogen activator inhibitor-1 mRNA and protein activity are constitutively up-regulated in asthmatic epithelium and play functional roles in both proliferation and repair of healthy cells. In asthmatic cells, elevated plasminogen activator inhibitors-1 levels fail to stimulate epithelial repair.


Manipulating the Electronic Structure of Nickel via Alloying with Iron: Toward High-Kinetics Sulfur Cathode for Na-S Batteries.
The sluggish conversion kinetics and severe shuttle effect in room-temperature Na-S (RT Na-S) batteries cause knotty issues, such as poor rate performance, fast capacity decay as well as low Coulombic efficiency, which seriously impede their practical application. Therefore, exploiting cost-effective and efficient electrocatalysts for absorbing soluble long-chain sodium polysulfides (NaPSs) and expediting NaPSs conversion is of paramount importance. Herein, catalyst mining is first conducted by density functional theory calculations, which reveal that the alloying of Fe into Ni can tailor the electronic structure, leading to lower reaction energy barrier for polysulfide conversion. Based on this, FeNi3@hollow porous carbon spheres (FeNi3@HC) as a promising sulfur host for RT Na-S batteries are rationally designed and fabricated. As expected, the S@FeNi3@HC cathode exhibits an excellent cycling stability (591 mAh g-1 after 500 cycles at 2 A g-1) and outstanding rate performance (383 mAh g-1 at 5 A g-1). Our work demonstrates an effective strategy (i.e., alloying strategy with a rich electron state) to design superior electrocatalysts for RT Na-S batteries.


Low Temperature Nitriding of Metal Alloys for Surface Mechanical Performance.
Metallic alloys are, by essence, ductile and stiff and can support loads without sudden rupture. This ductility becomes a disadvantage when applications require wear resistance. In this case, the hardening of the surface is required while retaining a core performance. Here, nitriding at low temperatures has proven to be beneficial and has potential. In fact, any phase transitions or unwanted compound precipitations that occur at higher temperatures have to be avoided as they would have a deleterious effect on the chemical homogeneity and mechanical properties. The present contribution summarizes the achievements made with such treatments on metallic alloys. We considered the most popular treatments, namely plasma, implantation, and gas nitridings.


[Quality of life in the course of deinstitutionalisation-- part IV of the Berlin Deinstitutionalisation Study].
As part of the Berlin Deinstitutionalisation Study, quality of life was assessed in 142 patients at two points of time. Discharged patients were reassessed one year after discharge. Patients who stayed in hospital were reinterviewed 1 1/2-2 years after the initial assessment. Discharged patients had more leisure activities, more often a "good friend", and more frequent social contacts. They were less often victim of a crime within the last year. In a cross-sectional comparison, they were significantly more satisfied with their life than patients who were still in hospital. In the latter group, only satisfaction with mental health improved significantly between first and second interview. Discharged patients became significantly more satisfied with their life in general, with leisure activities, with accommodation, and with mental health between initial assessment and follow-up. The findings demonstrate an improvement of quality of life in long-term hospitalised patients after discharge.


[Development of highly sensitive enzyme immunoassay to measure urinary beta-core fragment in patients with gynecological cancer].
In addition to human chorionic gonadotropin (hCG) and its free subunits, low molecular weight hCG beta-related fragments have been previously demonstrated in pregnancy urine and in the urine of patients with trophoblastic and nontrophoblastic tumors. The urinary beta-core fragment in particular is focused on as a new tumor marker in gynecological malignancies. We developed an EIA for the beta-core fragment using the monoclonal antibody (MoAb229) which specifically recognized the core portion of hCG beta. By measuring with MoAb229-EIA, it was clearly revealed that urine obtained from normal pregnant women as well as from patients with choriocarcinoma and nontrophoblastic ovarian cancer contains a large amount of the beta-core fragment when separated on Sephadex G-100. We conclude that our MoAb229-EIA is a useful tool to use in detecting the beta-core fragment, a new tumor marker, in the urine of gynecological cancer patients.


The populatin dynamics of Onchocerca volvulus microfilariae during treatment with suramin and diethylcarbamazine.
During treatment with suramin the numbers of O. volvulus microfilariae in the blood, urine, sputum, and anterior chambers of the eye fell before those in the skin. When diethylcarbamazine (DEC) was given after suramin, increased numbers of microfilariae appeared in the blood, urine, cerebrospinal fluid (CSF) and sputum, but the increase in the blood was less marked, and of shorter duration, than in similar patients receiving DEC without previous suramin. Microfilariae are thought to enter the urine, sputum and CSF directly from the blood by penetrating the capillary walls in the glomeruli, pulmonary alveoli, and choroid plexuses. Those in the aqueous humour do not appear to come directly from the bloodstream. The total numbers of microfilariae in the skin of some heavily infected onchocerciasis patients are estimated, as are the total numbers moving into the blood-stream under the influence of DEC and the proportion which escape into the urine, sputum and CSF. It is concluded that the majority of the microfilariae which appear in the blood during DEC therapy must be destroyed in the body, probably in the liver.


Comparisons of phosphorus ligation properties in P(CH2NR)3P.
Bicyclic P(CH2NMe)3P was synthesized, and its reactions with MnO2, elemental sulfur, p-toluenesulfonyl azide, BH3.THF, and W(CO)5(THF) were shown to furnish a variety of products in which the PC3 and/or the PN3 phosphorus are oxidized/coordinated. In contrast, reactions of the previously known P(CH2NPh)3P with Mo(0) and Ru(II) precursors were shown to afford products in which only the PC3 phosphorus is coordinated. The contrast in reactivity of P(CH2NR)3P (R = Me, Ph) with the aforementioned reagents is discussed in terms of steric and electronic factors. The new compounds are characterized by analytical and spectroscopic (IR, 1H, 31P, and 13C NMR) methods. The results of crystal and molecular structure X-ray analyses of the previously known compounds P(CH2O)3P and P(CH2NPh)3P and 6 of the 14 new compounds obtained in this investigation are presented. Salient features of these structures and the analysis of the Tolman cone angles calculated from their structural parameters are discussed in terms of the effects of constraint in the bicyclic moieties. Evidence is presented for greater M-P sigma bonding effects on coordination of the PC3 phosphorus of P(CH2NR)3P (R = Me, Ph) than are present in PMe3 analogues of group 6B metal carbonyls. From 1JBP data on the BH3 adducts of P(CH2NMe)3P, it is suggested that the free bases MeC(CH2NMe)3P < P(CH2NMe)3P < (Me2N)3P < P(MeNCH2CH2)3N increase in Lewis basicity at the PN3 phosphorus in the order shown. Substantial differences in 31P chemical shifts in the bicyclic compounds discussed herein relative to their acyclic analogues do not seem to be associated with the relatively small bond angle changes that occur around either the PN3 or the PC3 trivalent phosphorus atoms.


High-efficient Screening Method for Identification of Key Genes in Breast Cancer Through Microarray and Bioinformatics.
The aim of the present study was to identify key pathways and genes in breast cancer and develop a new method for screening key genes with abnormal expression based on bioinformatics. Three microarray datasets GSE21422, GSE42568 and GSE45827 were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were analyzed using GEO2R. The gene ontology (GO) and pathway enrichment analysis were established through DAVID database. The protein-protein interaction (PPI) network was performed through the Search Tool for the Retrieval of Interacting Genes (STRING) database and managed by Cytoscape. The overall survival (OS) analysis of the 4 genes including AURKA, CDH1, CDK1 and PPARG that had higher degrees in this network was uncovered Kaplan-Meier analysis. A total of 811 DEGs were identified in breast cancer, which were enriched in biological processes, including cell cycle, mitosis, vessel development and lipid metabolic. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the up-regulated DEGs were particularly involved in cell cycle, progesterone-mediated oocyte maturation and leukocyte transendothelial migration, while the down-regulated DEGs were mainly involved in regulation of lipolysis, fatty acid degradation and glycerolipid metabolism. Through PPI network analysis, 14 hub genes were identified. Among them, the high expression of AURKA, CDH1 and CDK1 were associated with worse OS of breast cancer patients; while the high expression of PPARG was linked with better OS. The present study identified key pathways and genes involved in breast cancer which are potential molecular targets for breast cancer treatment and diagnosis.


Mixed-Substituted Single-Source Precursors for Si1-xGex Thin Film Deposition.
A series of new mixed-substituted heteronuclear precursors with preformed Si-Ge bonds has been synthesized via a two-step synthesis protocol. The molecular sources combine convenient handling with sufficient thermal lability to provide access to group IV alloys with low carbon content. Differences in the molecule-material conversion by chemical vapor deposition (CVD) techniques are described and traced back to the molecular design. This study illustrates the possibility of tailoring the physical and chemical properties of single-source precursors for their application in the CVD of Si1-xGex coatings. Moreover, partial crystallization of the Si1-xGex has been achieved by Ga metal-supported CVD growth, which demonstrated the potential of the presented precursor class for the synthesis of crystalline group IV alloys.


[History of the discovery and study of tick-borne encephalitis in Russia: three Far Eastern expeditions (1937-1939)].
The review provides a brief historical outline of the discovery and study of tick-borne encephalitis (TBE) during three expeditions to the Far East (19371939). As a result of the Far Eastern expeditions, the TBE virus was discovered, numerous strains were isolated, a vector-borne transmission pathway was established, the main features of epidemiology, clinic and pathomorphology of the disease were described, serotherapy was tested, first inactivated "brain" vaccine against TBE was developed and its effectiveness was proved. The history of the discovery and study of TBE is marked by the heroism of researchers and tragic events illness of some participants, death during the development of the first vaccine, arrest of L.A. Zilber and two performers.


A Meta-Analysis of the Reliability of Four Field-Based Trunk Extension Endurance Tests.
This meta-analysis aimed to estimate the inter- and intra-tester reliability of endurance measures obtained through trunk extension field-based tests and to explore the influence of the moderators on the reliability estimates. The reliability induction rate of trunk extension endurance measures was also calculated. A systematic search was conducted using various databases, and subsequently 28 studies were selected that reported intraclass correlation coefficients for trunk extension endurance measures. Separate meta-analyses were conducted using a random-effects model. When possible, analyses of potential moderator variables were carried out. The inter-tester average reliability of the endurance measure obtained from the Biering-Sorensen test was intraclass correlation coefficient (ICC) = 0.94. The intra-session reliability estimates of the endurance measures recorded using the Biering-Sorensen test, the prone isometric chest raise test, and the prone double straight-leg test were ICC = 0.88, 0.90, and 0.86, respectively. The inter-session average reliability of the endurance measures from the Biering-Sorensen test, the prone isometric chest raise test, and the dynamic extensor endurance test were ICC = 0.88, 0.95, and 0.99, respectively. However, due to the limited evidence available, the reliability estimates of the measures obtained through the prone isometric chest raise, prone double straight-leg, and dynamic extensor endurance tests should be considered with a degree of caution. Position control instruments, tools, and familiarization session demonstrated a statistical association with the inter-session reliability of the Biering-Sorensen test. The reliability induction rate was 72.8%. Only the trunk extension endurance measure obtained through the Biering-Sorensen test presented sufficient scientific evidence in terms of reliability to justify its use for research and practical purposes.


Prevalence and Impact of Intimate Partner Violence (IPV) Among an Ethnic Minority Population.
The present study examined the prevalence of lifetime experiences of physical and psychological intimate partner violence (IPV) among members of the Turkish ethnic minority population in Flanders. In addition, this study explored how lifetime IPV victimization affects ethnic minority victims' current mental, relational, and sexual well-being. Using a population-based representative sample, data from 392 adult Turkish women and men were investigated. Lifetime experiences of physical violence were reported by 14.3% of the Turkish respondents, while 66.0% reported at least one incidence of psychological abuse. Women were much more likely than men to report physical IPV victimization, but no gender differences were found for psychological IPV. With regard to the impact of IPV, it was found that lifetime IPV experiences do not appear to affect victims' current mental health. However, higher levels of physical and/or psychological IPV victimization were related to increased levels of relationship dissatisfaction, anxious and avoidant attachment orientations, sexual dissatisfaction, sexual dysfunction (with distress), and to decreased levels of sexual communication. These adverse relational and sexual outcomes of IPV victimization were mainly present among women but were also, to a lesser degree, relevant for men.


Assessing finasteride-associated sexual dysfunction using the FAERS database.
Postmarketing reports suggest that finasteride causes sexual dysfunction despite a low incidence reported in clinical trials. Therefore, the extent of risk remains unknown. To determine whether the risk of sexual dysfunction is higher among individuals treated with finasteride compared to a baseline risk for all other drugs using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. A case by non-case disproportionality approach was used whereby a reporting odds ratio (ROR) with 95% confidence interval (CI) was calculated. The National Ambulatory Medical Care Survey (NAMCS) was used to confirm results. A significant disproportionality in reporting of sexual dysfunction with the use of finasteride was observed whether finasteride was indicated for hair loss (ROR = 138.17, 95% CI: 133.13, 143.4), prostatic hyperplasia (ROR = 93.88, 95% CI: 84.62, 104.16) or any indication (ROR = 173.18, 95% CI: 171.08, 175.31). When these results were stratified by age, disproportionality was strongest at 31-45 years. Use of finasteride has led to an increase in reports of sexual dysfunction where it is believed to be the primary suspect.


Genetic structure and dispersal in peripheral populations of a marine fish (Pacific cod, Gadus macrocephalus) and their importance for adaptation to climate change.
Small and isolated peripheral populations, which are often remnants of glacial refugia, offer an opportunity to determine the magnitude and direction of fine-scale connectivity in high gene flow marine species. When located at the equatorial edge of a species' range, these populations may also harbor genetic diversity related to survival and reproduction at higher temperatures, a critical resource for marine species facing warming ocean temperatures. Pacific cod (Gadus macrocephalus), a marine fish in the North Pacific, has already experienced major shifts in biomass and distribution linked to climate change. We estimated the magnitude and direction of connectivity between peripheral populations of Pacific cod at the southern edge of the species' range, by conducting restriction site-associated DNA (RAD) sequencing and individual assignment on fish collected around the Korean Peninsula during the spawning season. Three populations on the western, eastern, and southern Korean coasts were highly differentiated (FST = 0.025-0.042) and relatively small (Ne = 433-1,777). Ten putative dispersers and estimates of contemporary migration rates revealed asymmetrical, west-to-east movement around the Korean Peninsula, at a higher rate than predicted by indirect estimates of connectivity (FST ). Allele frequencies at 87 RAD loci were decisively correlated with strong marine temperature gradients between the warmer southern coast and the cooler waters of the eastern and western coasts. Despite relatively small sample sizes, our data suggest asymmetrical dispersal and gene flow, potentially involving adaptive alleles, between peripheral populations inhabiting markedly different thermal regimes. Our study emphasizes the conservation value of peripheral populations in high gene flow marine fish species.


Dynamics of PTH secretion in hemodialysis patients as determined by the intact and whole PTH assays.
Renal hyperparathyroidism is assessed by measurement of parathyroid hormone (PTH) levels. The intact PTH assay (I-PTH) not only reacts with 1-84 PTH but also with large, truncated fragments of non-1-84 PTH. Because the whole PTH assay (W-PTH) is specific for 1-84 PTH, non-1-84 PTH is determined by subtracting W-PTH from I-PTH values. These large circulating PTH fragments may exert a hypocalcemic effect by contributing to skeletal resistance to 1-84 PTH. The dynamic secretion of both 1-84 PTH and non-1-84 PTH was evaluated during the induction of hypo- and hypercalcemia in eight hemodialysis patients. The basal ionized calcium concentration was 1.23 +/- 0.03 mmol/L at which time I-PTH, W-PTH, and non-1-84 PTH values were 276 +/- 78 pg/mL, 164 +/- 48 pg/mL, and 102 +/- 28 pg/mL, respectively. The induction of hypo- and hypercalcemic changes resulted in a sigmoidal response for all three PTH moieties, I-PTH, W-PTH, and non-1-84 PTH. During hypocalcemia, maximal values of W-PTH were greater than those of non-1-84 PTH. But during hypercalcemia, minimal values of W-PTH and non-1-84 PTH were similar. Neither the set points nor the basal/maximal ratios for W-PTH, I-PTH, and non-1-84 PTH were different. At the baseline ionized calcium concentration, the W-PTH (1-84 PTH)/non-1-84 PTH ratio was 1.53 +/- 0.15. Changes in ionized calcium resulted in a sigmoidal relationship with hypocalcemia, increasing this ratio to a maximum of 2.01 +/- 0.30 and hypercalcemia decreasing this ratio to a minimum of 1.18 +/- 0.15 (P < 0.01 vs baseline for both hypo- and hypercalcemia). Although acute changes in serum calcium produce similar secretory responses in 1-84 PTH and non-1-84 PTH, the secretory responses are not proportional for these PTH moieties. Changes in the serum calcium concentration modulate the ratio of 1-84 PTH/non-1-84 PTH in a sigmoidal pattern with hypocalcemia maximizing this ratio. Whether changes in the 1-84 PTH/non-1-84 PTH ratio specifically modulate the calcemic action and other biologic effects of 1-84 PTH remain to be determined.


Ketoacidosis in type 2 diabetes--is it type 1 and 1/2 diabetes?
A 64-year-old female with a background of type 2 diabetes became acutely unwell after being transferred from insulin to liraglutide, which is one of the new glucagon like peptide 1 analogues. On assessment in accident and emergency, she was diagnosed with diabetic ketoacidosis and pancreatits. Glutamic acid decarboxylase antibodies were positive at 45 (0-1 U/ml) and C-peptide was low <94 pmol/l in keeping with the diagnosis of latent autoimmune diabetes of adults (LADA). This type of diabetes is characterised by slow autoimmune destruction of β cells of pancreas and can often be mistaken for type 2 diabetes. Patients suffering from LADA or type 1 and 1/2 diabetes require insulin to prevent ketoacidosis. She recovered with insulin treatment.


DSA diagnosis of pulmonary embolization from intracardial thrombus in a patient with permanent pacing catheter.
Pulmonary embolization in patients with implanted pacemakers is rare and an intracardiac thrombus attached to the distal end of a newly implanted ventricular endocardial electrode following removal of a previously implanted lead is a curiosity. We have documented such a case by digital subtraction angiography, a minimally invasive procedure that demonstrates both an intracardiac thrombus and secondary pulmonary embolization in a single procedure, which also allows simplified follow-up evaluation following therapy.


Glucocorticoids and selumetinib are highly synergistic in RAS pathway-mutated childhood acute lymphoblastic leukemia through upregulation of BIM.
New drugs are needed for the treatment of relapsed acute lymphoblastic leukemia and preclinical evaluation of the MEK inhibitor, selumetinib, has shown that this drug has excellent activity in those leukemias with RAS pathway mutations. The proapoptotic protein, BIM is pivotal in the induction of cell death by both selumetinib and glucocorticoids, suggesting the potential for synergy. Thus, combination indices for dexamethasone and selumetinib were determined in RAS pathway-mutated acute lymphoblastic leukemia primagraft cells in vitro and were indicative of strong synergism (combination index <0.2; n=5). Associated pharmacodynamic assays were consistent with the hypothesis that the drug combination enhanced BIM upregulation over that achieved by a single drug alone. Dosing of dexamethasone and selumetinib singly and in combination in mice engrafted with primary-derived RAS pathway-mutated leukemia cells resulted in a marked reduction in spleen size which was significantly greater with the drug combination. Assessment of the central nervous system leukemia burden showed a significant reduction in the drug-treated mice, with no detectable leukemia in those treated with the drug combination. These data suggest that a selumetinib-dexamethasone combination may be highly effective in RAS pathway-mutated acute lymphoblastic leukemia. An international phase I/II clinical trial of dexamethasone and selumetinib (Seludex trial) is underway in children with multiply relapsed/refractory disease.


On the Prediction of Upwelling Events at the Colombian Caribbean Coasts from Modis-SST Imagery.
The upwelling cores on the Caribbean Colombian coasts are mainly located at the Peninsula de la Guajira and Cabo de la Aguja. We used monthly averaged Moderate Resolution Imaging Spectroradiometer (MODIS) sea surface temperature as the only information to build up a prediction model for the upwelling events. This comprised two steps: (i) the reduction of the complexity by means of the Karhunen-Loève transform and (ii) a prediction model of time series. Two prediction models were considered: (a) a parametric autoregressive-moving average (ARMA) time series from the Box-Jenkins methodology and (b) a harmonic synthesis model. The harmonic synthesis also comprised of two steps: the maximum entropy spectral analysis and a least-squares harmonic analysis on the set of frequencies. The parametric ARMA time series model failed at the time of prediction with a very narrow range, and it was quite difficult to apply. The harmonic synthesis allowed prediction with a horizon of six months with a correlation of about 0.80. The results can be summarized using the time series of the weights of the different oscillation modes, their spatial structures with the nodal lines, and a high confidence model with a horizon of prediction of about four months.


miR-297 modulates multidrug resistance in human colorectal carcinoma by down-regulating MRP-2.
Colorectal carcinoma is a frequent cause of cancer-related death in men and women. miRNAs (microRNAs) are endogenous small non-coding RNAs that regulate gene expression negatively at the post-transcriptional level. In the present study we investigated the possible role of microRNAs in the development of MDR (multidrug resistance) in colorectal carcinoma cells. We analysed miRNA expression levels between MDR colorectal carcinoma cell line HCT116/L-OHP cells and their parent cell line HCT116 using a miRNA microarray. miR-297 showed lower expression in HCT116/L-OHP cells compared with its parental cells. MRP-2 (MDR-associated protein 2) is an important MDR protein in platinum-drug-resistance cells and is a predicted target of miR-297. Additionally miR-297 was down-regulated in a panel of human colorectal carcinoma tissues and negatively correlated with expression levels of MRP-2. Furthermore, we found that ectopic expression of miR-297 in MDR colorectal carcinoma cells reduced MRP-2 protein level and sensitized these cells to anti-cancer drugs in vitro and in vivo. Taken together, our findings suggest that miR-297 could play a role in the development of MDR in colorectal carcinoma cells, at least in part by modulation of MRP-2.


Proliferative phase endosperm promoters from Arabidopsis thaliana.
Endosperm accounts for a large proportion of human nutrition and is also a major determinant of seed viability and size, not only in cereals, but also in species with ephemeral endosperms, such as soybean and oilseed rape. The extent of endosperm proliferation early in seed development is a crucial component in setting seed size; therefore, a biotechnological approach for the modification of this trait requires promoters active in early endosperm. To find such promoters, we constructed an array based on cDNAs extracted from developing Arabidopsis seeds enriched for proliferating endosperm. Hybridization with RNA extracted from vegetative and reproductive tissues, including endosperm, and subsequent data filtering yielded sets of endosperm-expressed and endosperm-preferred genes, including many hundreds not previously identified in array experiments designed to detect genes expressed in Arabidopsis seeds. Of eight promoters selected for validation, seven were active in early endosperm, three with no detected activity elsewhere in the plant. Therefore, this strategy has yielded proliferative phase endosperm promoters which should be useful in altering seed size.


Development of integrated preamplifier for high-frequency ultrasonic transducers and low-power handheld receiver.
This paper describes the design of a front-end circuit consisting of an integrated preamplifier with a Sallen-Key Butterworth filter for very-high-frequency ultrasonic transducers and a low-power handheld receiver. This preamplifier was fabricated using a 0.18-μm 7WL SiGe bi-polar complementary metal oxide semiconductor (BiCMOS) process. The Sallen-Key filter is used to increase the voltage gain of the front-end circuit for high-frequency transducers which are generally low in sensitivity. The measured peak voltage gain of the frontend circuits for the BiCMOS preamplifier with the Sallen-Key filter was 41.28 dB at 100 MHz with a-6-dB bandwidth of 91%, and the dc power consumption of the BiCMOS preamplifier was 49.53 mW. The peak voltage gain of the front-end circuits for the CMOS preamplifier with the Sallen-Key filter was 39.52 dB at 100 MHz with a-6-dB bandwidth of 108%, and the dc power consumption of the CMOS preamplifier was 43.57 mW. Pulse-echo responses and wire phantom images with a single-element ultrasonic transducer have been acquired to demonstrate the performance of the front-end circuit.


Stent fracture: an unusual cause of late restenosis after sirolimus-eluting stent placement.
Stent fracture is uncommon but may have consequences including restenosis. To date, stent fractures reported have been related to aggressive post dilation. We describe a case that involves fracture of a stent deployed to nominal pressure. Unlike most stent fractures reported that involve stent struts only our case demonstrated circumferential disruption with complete separation of the stent segments.


Pseudoephedrine and circadian rhythm interaction on neuromuscular performance.
This study analyzed the effects of pseudoephedrine (PSE) provided at different time of day on neuromuscular performance, side effects, and violation of the current doping cut-off threshold [World Anti-Doping Agency (WADA)]. Nine resistance-trained males carried out bench press and full squat exercises against four incremental loads (25%, 50%, 75%, and 90% one repetition maximum [1RM]), in a randomized, double-blind, cross-over design. Participants ingested either 180 mg of PSE (supra-therapeutic dose) or placebo in the morning (7:00 h; AM(PLAC) and AM(PSE)) and in the afternoon (17:00 h; PM(PLAC) and PM(PSE)). PSE enhanced muscle contraction velocity against 25% and 50% 1RM loads, only when it was ingested in the mornings, and only in the full squat exercise (4.4-8.7%; P < 0.05). PSE ingestion raised urine and plasma PSE concentrations (P < 0.05) regardless of time of day; however, cathine only increased in the urine samples. PSE ingestion resulted in positive tests occurring in 11% of samples, and it rose some adverse side effects such us tachycardia and heart palpitations. Ingestion of a single dose of 180 mg of PSE results in enhanced lower body muscle contraction velocity against low and moderate loads only in the mornings. These mild performance improvements are accompanied by undesirable side effects and an 11% risk of surpassing the doping threshold.


Clinical efficacy of subgingivally delivered simvastatin gel in chronic periodontitis patients.
Simvastatin (SMV), a new locally delivered drug of class statins, is a specific competitive inhibitor of 3-hydroxy-2-methyl-glutaryl coenzyme A reductase. Statins, besides having lipid-lowering abilities, also have pleiotropic effects like host modulation and bone regeneration. The present study was designed to investigate the effectiveness of SMV, 1.2 mg, in an indigenously prepared biodegradable controlled-release gel as an adjunct to scaling and root planing (SRP). A total of 60 sites, with pocket depth ≥5 mm, two from each of 30 patients after SRP, were categorized into two treatment groups, for subgingival placement of placebo (Gp 1) or SMV (Gp 2). Clinical parameters were recorded at baseline and at 1, 3 and 6 months comprising plaque index, gingival index, probing pocket depth (PPD) and clinical attachment level (CAL). The osseous changes were evaluated radiographically by measuring vertical gain, INFRA 1 and angle of the defect, INFRA 2 from baseline to 6 months. All subjects tolerated the drug, without any post-application complication. The treatment improved the periodontal condition in both the groups but significant reductions in PPD (p= 0.04), and INFRA 1 (p= 0.000), along with gain in CAL (p= 0.02) and INFRA 2 (p= 0.000) were observed in Gp 2. In one site, an unexpected 5 mm decrease in INFRA 1 was found. Local drug delivery of SMV enhanced the beneficial effect of SRP, in pocket reduction, gain in CAL and bone fill.


Molding of the regenerate in mandibular distraction: Part 1: Laboratory study.
Distraction osteogenesis has evolved as a mainstream surgical technique for lengthening and augmentation of the hypoplastic mandible. As clinical experience accumulated, there developed the need to "mold" the bony regenerate to avoid the development of postdistraction malocclusion and to achieve the desired craniofacial form. Although the potential to mold the regenerate has important clinical implications, the safety and efficacy of such an acute manipulation of the bony regenerate form have not yet been investigated in the laboratory. The purpose of this study was to determine if the distraction regenerate could be molded and result in a bony union. Four adult female dogs underwent bilateral mandibular distraction with an external multiplanar device (Stryker, Osteonics). After a latency period of 5 days, the mandibles underwent linear (anteroposterior) and angular (superoinferior) distraction to produce an anterior open bite of approximately 30 degrees. At the conclusion of the distraction procedure, the distraction sites were molded to close the open bite. In two dogs, the maneuver was performed over 3 days by changing the angulation of the devices (gradual molding), and in the other two dogs, molding was achieved with a single movement (acute molding). In the latter, the distraction devices were adjusted and reapplied to allow for anatomical fixation during the consolidation period of 49 days. According to the research protocol, the mandibles were assessed serially by cephalograms and computed tomography (CT) scans. All dogs survived the study without complications. The bony regenerate was easily molded in both groups to close the surgically created open bite. After molding, all the regenerates showed CT scan evidence of solid bone (consolidation), which was classified as "extended" on the Hamanishi scale. After the dogs were killed and soft tissue was removed, the regenerate seemed to be robust on gross examination without any evidence of fibrous nonunion. In addition, histological study of the regenerate confirmed the bony union. The study demonstrates that the mandible can be successfully molded into a desired anatomical position immediately after distraction without producing a fibrous union. Furthermore, it has been demonstrated that the bony regenerate is sufficiently malleable before consolidation to undergo either acute or gradual angular molding without disturbing osteogenic potential. The ability to mold the regenerate without the fear of creating a fibrous union or destroying bony potential provides the surgeon the capability to optimize the dental occlusion and mandibular form as part of the distraction treatment process.