Residues W320 and Y328 within the binding site of the μ-opioid receptor influence opiate ligand bias.
The development of G protein-biased agonists for the μ-opioid receptor (MOR) offers a clear drug discovery rationale for improved analgesia and reduced side-effects of opiate pharmacotherapy. However, our understanding of the molecular mechanisms governing ligand bias is limited, which hinders our ability to rationally design biased compounds. We have investigated the role of MOR binding site residues W320 and Y328 in controlling bias, by receptor mutagenesis. The pharmacology of a panel of ligands in a cAMP and a β-arrestin2 assay were compared between the wildtype and mutated receptors, with bias factors calculated by operational analysis using ΔΔlog(τ/KA) values. [3H]diprenorphine competition binding was used to estimate affinity changes. Introducing the mutations W320A and Y328F caused changes in pathway bias, with different patterns of change between ligands. For example, DAMGO increased relative β-arrestin2 activity at the W320A mutant, whilst its β-arrestin2 response was completely lost at Y328F. In contrast, endomorphin-1 gained activity with Y328F but lost activity at W320A, in both pathways. For endomorphin-2 there was a directional shift from cAMP bias at the wildtype towards more β-arrestin2 bias at W320A. We also observe clear uncoupling between mutation-driven changes in function and binding affinity. These findings suggest that the mutations influenced the balance of pathway activation in a ligand-specific manner, thus identifying residues in the MOR binding pocket that govern ligand bias. This increases our understanding of how ligand/receptor binding interactions can be translated into agonist-specific pathway activation.


Riboflavin levels in maternal milk: the influence of vitamin B2 status during the third trimester of pregnancy.
The aim of the present investigation was to study the relationship between riboflavin status during the third trimester of pregnancy and levels of this vitamin in transition milk (days 13 to 14 of lactation) and mature milk (day 40 of lactation). The pregnancies and lactation periods of 57 healthy women between 18 and 35 years of age (27+/-3.7 years) were monitored, vitamin intake during the third trimester was determined by recording the consumption of foods over five days and by registering the quantities provided by dietary supplements. Riboflavin status during this stage of pregnancy was determined via the measurement of the activation of erythrocyte glutathione reductase (EGR) by flavine adenine dinucleotide (FAD). Milk riboflavin levels were determined by fluorometry. Those subjects with riboflavin intakes below recommended (1.6 mg/day) (Group L) showed lower consumption of milk products (305.2+/-88.5 g/day) than did those with greater intakes (Group H) (507.9+/-137.2 g/day). The consumption of riboflavin containing supplements was very low and was seen only in two H subjects. Transition and mature milk riboflavin levels were significantly higher in H subjects (948.1+/-700.1 nmol/L for transition milk and 993.8+/-436.6 nmol/L for mature milk) than L subjects (574.9+/-258.7 nmol/L for transition milk and 725.4+/-254.3 nmol/L for mature milk). Subjects with alpha-EGR coefficients over 1.2 in the third trimester showed significantly lower mature milk riboflavin levels (704.1+/-241.8 nmol/L) than did subjects with more satisfactory alpha-EGR coefficients (996.4+/-302.9 nmol/L). The influence of maternal vitamin B2 status during pregnancy on breast milk riboflavin levels was confirmed.


An improved method for the sensitive monitoring of low density lipoprotein modification by myeloperoxidase.
The aim of this investigation was to compare an improved fluorometric method with an UV absorbance assay for their ability to monitor low density lipoprotein (LDL) modification by myeloperoxidase (MPO) and to evaluate determining factors influencing the modification of LDL. Using absorbance at 234 nm to study the kinetics of LDL aggregation, and a native fluorescence assay for protein oxidation, we found that all components of the MPO/H2O2/Cl- system may have rate determining effects on LDL modification. While the lipoprotein modification rate correlated positively with enzyme concentration, variation of the concentration of H2O2 had a biphasic effect on the maximal rate of LDL modification with both methods. Furthermore, a positive association was found between the maximal rate of LDL modification and the acidity of the medium, with a pathophysiologically relevant optimal rate at a slightly acidic pH of 5-6, but hardly any modification above pH 6.8. In summary, both methods provide simple and useful tools for the continuous monitoring of LDL modification by the MPO/H2O2/Cl- system, but the more sensitive fluorometric method is preferable, since it allows the application of experimental conditions which are much closer to the situation in vivo.


Superradiant linear Raman amplification in plasma using a chirped pump pulse.
A theoretical and numerical investigation of small-signal Raman backscattering from a chirped pump pulse in plasma shows that an ultrashort probe pulse will grow superradiantly, i.e., with an amplitude that scales with the propagation length while contracting self-similarly. These features are commonly associated with the nonlinear stages of Raman amplification in the pump depletion and Compton regimes. We show that the superradiant scaling results in very broad-bandwidth amplification due to gain distributed in frequency as well as spatially. Since different frequencies excite the plasma at different positions, wave breaking is avoided, and prepulses and pedestals are substantially suppressed. Linear chirped pulse amplification in plasma could provide a very broad-bandwidth alternative to solid state laser amplifiers, potentially usable for optical pulses a few cycles in duration.


The lipophilic muramyl peptide MTP-PE is a potent inhibitor of HIV replication in macrophages.
Cultured monocyte-derived macrophages were productively infected with human immunodeficiency virus in vitro. Treatment of these cells shortly after infection and several times thereafter with the free form of MTP-PE had an inhibitory effect on virus production. When the liposomal formulation of MTP-PE was used, higher levels of protection were achieved. The drug was not only effective when added to cells immediately after infection, but it also reduced virus production by cells with an established infection. When the liposomal formulation of MTP-PE was used only one treatment was required to achieve maximal effects. During these studies it was noted that the placebo liposomes had some effect in reducing the reverse transcriptase levels found in the supernatants of infected cells. This reduction could not be explained by direct cytotoxic effect. Both free and liposomal MTP-PE lipid significantly prevented formation of giant cells during the course of infection as well as reduced the cell associated viral antigen.


An Innovative Approach to Retention: Thermoplastic Retainer.
The aim of this study was to design and introduce a retainer that overcomes the common shortcomings seen in other retainers. Hard thermoplastic sheet of 0.5 mm thickness is vacuum or pressure-molded onto the patient cast. Lingual portion of the retainer is trimmed according to the contours of the anterior teeth. Contact points between the maxillary and mandibular anterior teeth are marked on the retainer and reduced. Punch cut holes are placed on the retainer for the exit of flash and air bubbles while fixation. The retainer is bonded onto the lingual surface of the anterior teeth using composite. A 1-month review of the retainer showed no patient discomfort, occlusal interference, or bond failure. The aim of the article was found to have been achieved. Initial evaluation has shown positive findings. Long-term clinical findings will determine the overall success of this new retainer. As compared with other retainers, thermoplastic retainer has shown reduced tendency to debond from occlusal forces, decreased patient discomfort, and occlusal interference.


Battery-free, lightweight, injectable microsystem for in vivo wireless pharmacology and optogenetics.
Pharmacology and optogenetics are widely used in neuroscience research to study the central and peripheral nervous systems. While both approaches allow for sophisticated studies of neural circuitry, continued advances are, in part, hampered by technology limitations associated with requirements for physical tethers that connect external equipment to rigid probes inserted into delicate regions of the brain. The results can lead to tissue damage and alterations in behavioral tasks and natural movements, with additional difficulties in use for studies that involve social interactions and/or motions in complex 3-dimensional environments. These disadvantages are particularly pronounced in research that demands combined optogenetic and pharmacological functions in a single experiment. Here, we present a lightweight, wireless, battery-free injectable microsystem that combines soft microfluidic and microscale inorganic light-emitting diode probes for programmable pharmacology and optogenetics, designed to offer the features of drug refillability and adjustable flow rates, together with programmable control over the temporal profiles. The technology has potential for large-scale manufacturing and broad distribution to the neuroscience community, with capabilities in targeting specific neuronal populations in freely moving animals. In addition, the same platform can easily be adapted for a wide range of other types of passive or active electronic functions, including electrical stimulation.


A microscopy-based kinetic analysis of yeast vacuolar protein sorting.
Saccharomyces cerevisiae is amenable to studying membrane traffic by live-cell fluorescence microscopy. We used this system to explore two aspects of cargo protein traffic through prevacuolar endosome (PVE) compartments to the vacuole. First, at what point during Golgi maturation does a biosynthetic vacuolar cargo depart from the maturing cisternae? To address this question, we modified a regulatable fluorescent secretory cargo by adding a vacuolar targeting signal. Traffic of the vacuolar cargo requires the GGA clathrin adaptors, which arrive during the early-to-late Golgi transition. Accordingly, the vacuolar cargo begins to exit the Golgi near the midpoint of maturation, significantly before exit of a secretory cargo. Second, how are cargoes delivered from PVE compartments to the vacuole? To address this question, we tracked biosynthetic and endocytic cargoes after they had accumulated in PVE compartments. The results suggest that stable PVE compartments repeatedly deliver material to the vacuole by a kiss-and-run mechanism.


In situ generation of uranium alkyl complexes.
A new method for generating uranium alkyl complexes is described. Although homoleptic uranium alkyl complexes are notoriously unstable and difficult to work with, by generating such species in situ, a wide range of alkyl complexes can be accessed from UI(3)(THF)(4).


Injuries in racket sports among Slovenian players.
On the sample of 83 top Slovenian athletes we have studied the frequency of injuries among table tennis, tennis and badminton players, types of injuries and severity of injuries--the latter based on data of players absences from training and/or competition processes. The most liable parts to injuries are shoulder girdle (17.27%), spine (16.55%) and ankle (15.83%), while foot (10.07%) and wrist (12.23%) are slightly less liable to injuries. The most frequent injuries in racket sports pertain to muscle tissues. According to this data, the majority of injuries occur halfway through a training session or a competition event, mostly during a competition season. The injuries primarily pertain to muscle tissues; these are followed by joint and tendon injuries. There are no differences between male and female players. Compared to other racket sports players, table tennis players suffer from fewer injuries.


A survey on the utilization of disposable quadrant articulators.
This study evaluated utilization of the six most popular disposable quadrant articulators presently used in crown fabrication. Most general practitioners and crown and bridge laboratory technicians reported that they frequently or always used disposable quadrant articulators for single units and simple three-unit fixed partial dentures. All evaluated articulators demonstrated an inability to maintain and repeat the centric stop position. The disposable quadrant articulator, used in combination with dual-arch impressions, is a viable method for fabricating single and short-span restorations. While a nonrepeatable centric stop was present in all six articulators evaluated, the method was considered a time-efficient and cost-saving alternative to traditional all-metal simple-hinge articulators.


Coil embolization of intracranial aneurysms, the LSUHSC-S experience.
We evaluated and compared patient selection and outcome statistics during the first 18 months of the Louisiana State Health Sciences Center-Shreveport (LSUHSC-S) neurointerventional suite operation, specifically focusing on endovascular occlusion of intracranial aneurysms. A retrospective analysis of 67 patients with 68 cerebral aneurysms that were treated at the LSUHSC-S from July 2006 to December 2007 was conducted. All procedures were performed with the patients under general anesthesia and with systemic heparinization using live simultaneous roadmapping. The presence of residual aneurysmal filling was determined at the end of each procedure. A total of 67 patients underwent 70 endovascular coil embolization procedures for 68 intracranial aneurysms. Mean age of the patients was 51 years (range 15-89 years). There was a slight female preponderance (58.2% vs 41.8%). The vast majority of aneurysms undergoing coil embolization had ruptured (83.8%). Most were located in anterior circulation and (77.9%) were small (< 10 mm) in size (91.2%). Endovascular remodeling was attempted in 21 procedures (30%). Following embolization, complications were observed in 20 cases (28.6%). Though a greater proportion of complications occurred following procedures involving the posterior circulation, there was no statistical significance (p = 0.126, Chi-Square). Complete post-embolization occlusion was achieved with 33 aneurysms (47%). Near complete occlusion (> 90%) was seen in 65 (91.4%). There was no statistical association between location of the aneurysm and incomplete post procedure occlusion (p = 0.794, Chi-square). Our experience with coil embolization of intracranial aneurysms shows encouraging results and mirrors published rates of immediate post procedures near complete occlusion rates of approximately 90%.


Eyes of Africa: The Genetics of Blindness: Study Design and Methodology.
This report describes the design and methodology of the "Eyes of Africa: The Genetics of Blindness," a collaborative study funded through the Human Heredity and Health in Africa (H3Africa) program of the National Institute of Health. This is a case control study that is collecting a large well phenotyped data set among glaucoma patients and controls for a genome wide association study. (GWAS). Multiplex families segregating Mendelian forms of early-onset glaucoma will also be collected for exome sequencing. A total of 4500 cases/controls have been recruited into the study at the end of the 3rd funded year of the study. All these participants have been appropriately phenotyped and blood samples have been received from these participants. Recent GWAS of POAG in African individuals demonstrated genome-wide significant association with the APBB2 locus which is an association that is unique to individuals of African ancestry. This study will add to the existing knowledge and understanding of POAG in the African population.


The origins of supraspinal projections to lumbosacral and cervical levels of the spinal cord in the gray short-tailed Brazilian opossum, Monodelphis domestica.
Retrograde tracing techniques were used to identify supraspinal neurons that project to sacral, lumbar and cervical levels of the spinal cord in the gray short-tailed Brazilian opossum, Monodelphis domestica. Injections of Fast Blue, True Blue or wheat germ agglutinin conjugated to horseradish peroxidase into the sacral or lumbar cord labeled neurons in hypothalamic and brainstem nuclei reported to innervate the same levels in other mammals. Injections at cervical levels produced extensive labeling in the same areas as well as labeling within the isocortex, the medial preoptic area, the central and basomedial amygdaloid nuclei, the medial and interposed nuclei of the cerebellum, and several additional areas of the brainstem. In some of the cases, lumbar injections of wheat germ agglutinin conjugated to horseradish peroxidase were combined with a contralateral hemisection of the thoracic cord in order to determine laterality. The origins of monoaminergic projections were assessed using the retrograde transport of True Blue from the cervical cord and immunofluorescence for serotonin and tyrosine hydroxylase. Our results suggest that the origins of supraspinal projections to the spinal cord of Monodelphis are similar to those described for the North American opossum, Didelphis virginiana. Differences appear to exist, however, particularly in the amount of isocortex containing corticospinal neurons, the existence of spinal projections from the amygdala and preoptic area, the degree of rubrospinal somatotopy, and the origins of certain monoaminergic projections.


Measurement performance assessment for the ITER CXRS Edge diagnostic system.
Measurement performance assessment has been carried out for the latest design of the ITER Charge Exchange Recombination Spectroscopy (CXRS) Edge diagnostic system. Several plasma scenarios, covering all expected baseline operation regimes for ITER, were used. Various impurity (He, Be, C, and Ne) concentrations for the system whole spatial range (0.5 < r/a < 1.0) were considered. Statistical errors for the measurements of low-Z impurity temperature, density, and rotation velocity were calculated. Other non-statistical error sources were reviewed, including the presence of wall reflections, effects on the active charge-exchange line shape, calibration, and positioning uncertainties. Minimal impurity concentrations, allowing measurements with required accuracy, were obtained. It was shown that the CXRS Edge system will be able to measure primary plasma parameters with required accuracy, space, and time resolution.


Gastrointestinal microbes increase arsenic bioaccessibility of ingested mine tailings using the simulator of the human intestinal microbial ecosystem.
It is widely accepted that the use of total metal concentrations in soil overestimates metal risk from human ingestion of contaminated soils. In vitro simulators have been used to estimate the fraction of arsenic present in soil that is bioaccessible in the human digestive track. These approaches assume that the bioaccessible fraction remains constant across soil total metal concentrations and that intestinal microbiota do not contribute to arsenic release. Here, we evaluate both of these assumptions in two size fractions (bulk and <38 microm) of arsenic-rich mine tailings from the Goldenville, Lower Seal Harbour, and Montague Gold Districts, Nova Scotia. These samples were evaluated using an in vitro gastrointestinal model, the Simulator of the Human Intestinal Ecosystem (SHIME). Arsenic bioaccessibility, which ranged between 2 and 20% in the small intestine and 4 and 70% in the colon, was inversely related to total arsenic concentration in the mine tailings. Additionally, arsenic bioaccessibility was greater in the bulk fraction than in the <38 microm fraction in the small intestine and colon while colon microbes increased the bioaccessibility of arsenic in mine tailings. These results suggest that the practice of using a constant percent arsenic bioaccessibility across all metal concentrations in risk assessment should be revisited.


Decreased dietary protein or energy intake and plasma growth hormone levels of the pregnant pig, its fetuses and developing progeny.
The effects of low protein diets on plasma growth hormone were studied in pregnant pigs, fetuses and the developing progeny. Pregnant pigs were fed 18%, 3% or 0.5% protein diet throughout the gestation period. At 10, 13 and 15 week of gestation, fetuses were removed from the uterus after the dam had been bled to death. Plasma samples were used for growth hormone determinations. In a second experiment, 2-day old pigs from another set of pregnant pigs fed the diet containing 18%, 3% or 0.5% protein during gestation were cross-fostered to control nursing dams and weaned at 4 weeks of age to a standard diet. Plasma obtained at regular intervals was used for growth hormone determination. Plasma growth hormone was significantly higher in dams fed 0.5% protein after week 13 of gestation. High growth hormone (ten times the dam GH level) was observed in all fetuses irrespective of maternal dietary manipulation. Offspring of severely protein deprived pits (0.5% protein) had significantly elevated growth hormone levels up to 12 weeks of age in spite of cross fostering to a control dam after birth. The data suggest that there is little or no effect of maternal protein restriction on fetal growth hormone levels but the persistent high growth hormone levels in the progeny of severely malnourished pigs indicate a possible impairment of the production, release or catabolism of growth hormone and/or its releasing factor.


Current Understanding of the Roles of Gut-Brain Axis in the Cognitive Deficits Caused by Perinatal Stress Exposure.
The term 'perinatal environment' refers to the period surrounding birth, which plays a crucial role in brain development. It has been suggested that dynamic communication between the neuro-immune system and gut microbiota is essential in maintaining adequate brain function. This interaction depends on the mother's status during pregnancy and/or the newborn environment. Here, we show experimental and clinical evidence that indicates that the perinatal period is a critical window in which stress-induced immune activation and altered microbiota compositions produce lasting behavioral consequences, although a clear causative relationship has not yet been established. In addition, we discuss potential early treatments for preventing the deleterious effect of perinatal stress exposure. In this sense, early environmental enrichment exposure (including exercise) and melatonin use in the perinatal period could be valuable in improving the negative consequences of early adversities. The evidence presented in this review encourages the realization of studies investigating the beneficial role of melatonin administration and environmental enrichment exposure in mitigating cognitive alteration in offspring under perinatal stress exposure. On the other hand, direct evidence of microbiota restoration as the main mechanism behind the beneficial effects of this treatment has not been fully demonstrated and should be explored in future studies.


Low doses of dexamethasone can produce a hypocorticosteroid state in the brain.
The synthetic glucocorticoid dexamethasone (dex) blocks stress-induced hypothalamic-pituitary-adrenal (HPA) activation primarily at the level of the anterior pituitary because multidrug resistance P-glycoprotein hampers its penetration in the brain. Here, we tested the hypothesis that central components of the HPA axis would escape dex suppression under conditions of potent peripheral glucocorticoid action. We subchronically treated rats with low or high doses of dex. The animals were subjected on the last day of treatment for 30 min to a restraint stressor after which central and peripheral markers of HPA axis activity were measured. Basal and stress-induced corticosterone secretion, body weight gain, adrenal and thymus weight, as well as proopiomelanocortin mRNA in the anterior pituitary were reduced in a dose-dependent manner by dex administered either 5 d sc or 3 wk orally. In the brain, the highest dose dex suppressed CRH mRNA and CRH heteronuclear RNA in the paraventricular nucleus (PVN). However, in the peripherally active low-dose range of dex CRH mRNA and heteronuclear RNA showed resistance to suppression, and CRH mRNA expression in the PVN was in fact enhanced under the long-term treatment condition. In the PVN, c-fos mRNA was suppressed by the highest dose of dex, but this effect showed a degree of resistance after long-term oral treatment. c-fos mRNA responses in the anterior pituitary followed those in PVN and reflect central drive of the HPA axis even if corticosterone responses are strongly reduced. The results support the concept that low doses of dex can create a hypocorticoid state in the brain.


Highlights in muscle relaxants.
The aim of this article is to provide an overview on neuromuscular blocking agents and a rational selection of the most appropriate agents, along with pharmacological and pharmacoeconomic considerations on neuromuscular blockers and their antagonists. Neuromuscular blocking agents are used during anesthesia to facilitate endotracheal intubation and provide surgically required paralysis. There is continuing development in the field of neuromuscular blocking agents, with new products appearing at regular intervals. All new agents come at increased costs. The proportion of anesthesia-related drug costs on a per-patient basis are small and vary from country to country, but account for no more than 12% of hospital drug budgets. However, given the large number of anesthetics performed over time, the total cost is significant. Moreover, such costs should be put into the perspective of the operating theater and patient admission costs. Appropriate selection of neuromuscular blocking agents can help not only to reduce biological costs secondary to complications, but also to make operating lists proceed smoothly and without incident. The paucity of outcome studies in relation to anesthetic drugs is not surprising given that anesthesia is used to facilitate the provision of therapy rather than being therapeutic in its own right. Accordingly, the assessment of anesthetic drugs has a different priority to therapeutic drugs. As anesthetic drugs are nontherapeutic, it is also difficult to determine the best choice of agent. However, new neuromuscular blocking agents are marketed on the basis of improvements in the frequency of side effects, safety, reliability, duration, reversibility and undesirable hemodynamic effects.


Psychiatric Emergency Department Visits After Regional Expansion of Community Health Centers.
Regional primary health care system capacity may affect the demand for psychiatric visits to the emergency department (ED). In the United States, community health centers (CHCs), which serve low-income regions regardless of individuals' ability to pay, expanded primary care services by over 70% in the past decade. No research, however, evaluates whether this expansion affects overall psychiatric ED visits. This hypothesis is tested in 143 U.S. counties that expanded CHC services. For the years 2006 through 2011, 18.84 million psychiatric outpatient ED visits were aggregated by county-year for the 143 U.S. counties with a participating CHC. The rate of psychiatric ED cases in a county-year is the dependent variable. Two independent variables were examined: total patients seen at CHCs and total patients receiving mental health services at CHCs. Fixed-effects regression methods controlled for county effects, year effects, and other health care and sociodemographic factors. Psychiatric ED visits fell below expected levels in county-years where the volume of overall CHC patients rose (coefficient=-0.059; standard error=0.027, p=0.03). Findings indicate no relation between the volume of mental health patients seen at CHCs and psychiatric ED visits. An increase in general primary health care to an underserved population, in the form of CHCs, corresponds with a decline in psychiatric ED visits. This result coheres with a recent Medicaid expansion experiment in which increased access to general primary care reduced the prevalence of undiagnosed and untreated depression. Findings, if replicated, may hold policy implications for regional health systems.


George Papanicolaou's Efforts to Develop Novel Cytologic Methods for the Early Diagnosis of Endometrial Carcinoma.
Toward the end of his career, Dr. George Papanicolaou became interested in human endometrial explants placed into tissue culture. The initial focus of his studies was on phagocytic cells emanating from endometrial explants and their role in cleansing the uterine cavity after each menstrual cycle and in sterilizing the uterine cavity in the face of infection. Papanicolaou also observed that growth rates of explanted normal and pathologic endometrial tissues differed considerably. Explants of endometrial malignancies exhibited not only increased growth rates but also visible proliferation of cells with readily identifiable cytologic features of malignancy. Acknowledging that cytologic screening for early diagnosis of intrauterine malignancies had up to that point not proven to be reliable as screening for cervical cancer, he hoped that the tissue culture explant technique could prove to be a new adjunctive diagnostic method for the diagnosis of endometrial and other female genital tract malignancies not readily detectible by other diagnostic procedures. Papanicolaou's untimely death in 1962 cut short his progress in this area of study.


The effect of individual liveweight and use of teaser rams prior to mating on the reproductive performance of ewe hoggets.
To determine the effects of liveweight (LW) and use of teaser rams prior to mating on both the mating performance and pregnancy rate of ewe hoggets. Romney hoggets (n=841) were weighed and randomly assigned to one of two treatment groups; either exposed to seven harnessed, vasectomised (teaser) rams for 17 days prior to the breeding period (n=283); or not exposed to teaser rams (unteased, n=558). Harnessed Perendale rams were then introduced for two oestrous cycles. Using crayon marks, hoggets were identified as having been mated during the first 17 days only, during the second 17 days only, during both periods, or not mated. All mated hoggets were then scanned for pregnancy using ultrasound, 48 days after the end of the breeding period, and identified as being either non-pregnant, or as single-, twin or triplet-bearing. Hoggets mated in either the first 17 days only or in both the first and second 17-day periods were heavier than those mated in the second period only (p<0.001). Those mated in the first or second 17-day period only, and those mated in both periods were all heavier prior to mating than those not mated at all (p<0.001). Twin-bearing hoggets were heavier than both their single-bearing and non-pregnant counterparts (p<0.001). A greater proportion of the teased hoggets were mated in the first 17 days only compared with unteased hoggets (62.6 vs 32.1%; p<0.001). In contrast, more of the unteased hoggets were marked in the second 17-day period only (p<0.001). A greater proportion of mated, unteased hoggets were found to be non-pregnant in comparison to their teased counterparts (17.8 vs 11.2%; p=0.02). Heavier hoggets at breeding were more likely to be mated in the first 17 days of the breeding period and more likely to be twin-bearing. Use of teaser rams for 17 days prior to the breeding period increased the proportion of hoggets mated in the first 17 days, increased conception rates, and thus increased the proportion of pregnant hoggets. These results indicate that farmers should utilise teasers for 17 days prior to commencement of the breeding period and avoid mating hoggets that weigh below 36 kg.


Educational and health impact of the Baume Report: 'A Cutting Edge: Australia's Surgical Workforce'.
The Baume Report (1994) on Australia's surgical workforce had the potential to impact upon the health and educational sectors. This paper analyses the recommendations of this report and their impact at the time and 15 years later (2009). A questionnaire-based study was performed with the 18 senior Fellows and the Royal Australasian College of Surgeons (RACS) solicitor who had been instrumental in facilitating responses to the review. The 19 respondents were asked to evaluate 22 areas from the Baume Report. The most highly ranked areas identified as being reasonable in 1994 were: additional funding being made available for more training positions, identifying workforce deficits, moving towards compulsory continuing professional development and having evidence of competence before introducing new technology. In 2009, the most highly ranked areas were: funding for more training positions; compulsory continuing professional development, involving the profession in improvements and broadening the training environment beyond public hospitals. Areas considered to be substantially addressed were: the selection process and encouragement of diversity, workforce numbers and deficits, confirming the educational merit of the training program and the role of professional colleges. The Baume Report highlighted many issues including workforce planning, the role of professional organisations in society and the complex interface between health and education. Issues of ongoing standards through a surgical career, access for patients to surgical services, funding for more training posts to provide the appropriate workforce level and distribution, and the assessment and introduction of technology remain priorities. Time has not diminished the relevance of these issues. WHAT IS KNOWN ABOUT THIS TOPIC?: The impact of key government reviews can always be substantial. The Baume Report was directed to postgraduate specialist medical training, particularly surgical training. There have been substantial changes in the health and educational sectors since the report, with significantly more regulation and transparency. WHAT DOES THIS PAPER ADD?: Analysis of the Baume Report after 15 years by the senior office bearers of the RACS who were actively involved in handling and implementing many of the recommendations provides an insight into the dynamics of specialist training. It outlines the significant changes that have occurred and the things that still need to be done. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS?: Professional bodies have an influential presence across society. They are particularly focused on the standards required to become a practitioner of that profession and the ongoing maintenance of these standards. However, this comes with responsibility for and accountability to society and the community. External reviews, particularly with a political imperative, change both the dynamics and key relationships, issues that the professional bodies must commit to addressing in a positive manner.


Evaluation of the key words used in articles of the Acta Cirurgica Brasileira from 1997 to 2012.
To evaluate the key words used in Acta Cirurgica Brasileira from 1997 to 2012. All the key words of all articles published in regular issues between 1997 and 2012 were analyzed, ensuring that these key words were in the MeSH database (Medical Subjects Headings) and the most used subject headings and most wrong repeated key words were ranked. > 4230 key words used in 990 articles were analyzed. Only 579 key words (13.68%) were not in the MeSH database, considering that there was a statistically significant decrease over the years (p<0.001). The three most used key words were Rats, Dogs and Wound healing. Among the wrong ones, the key words were Adhesions, Experimental surgery and Anatomosis. There was a gradual improvement in the amount of key words used that belonged to the MeSH database, and there were 618 articles (62.42%) with all key words correct.


Engineering and expression of a RhoA peptide against respiratory syncytial virus infection in plants.
MAIN CONCLUSION : A RhoA-derived peptide fused to carrier molecules from plants showed enhanced biological activity of in vitro assays against respiratory syncytial virus compared to the RhoA peptide alone or the synthetic RhoA peptide. A RhoA-derived peptide has been reported for over a decade as a potential inhibitor of respiratory syncytial virus (RSV) infection both in vitro and in vivo and is anticipated to be a promising alternative to monoclonal antibody-based therapy against RSV infection. However, there are several challenges to furthering development of this antiviral peptide, including improvement in the peptide's bioavailability, development of an efficient delivery system and identification of a cost-effective production platform. In this study, we have engineered a RhoA peptide as a genetic fusion to two carrier molecules, either lichenase (LicKM) or the coat protein (CP) of Alfalfa mosaic virus. These constructs were introduced into Nicotiana benthamiana plants using a tobacco mosaic virus-based expression vector and targets purified. The results demonstrated that the RhoA peptide fusion proteins were efficiently expressed in N. benthamiana plants, and that two of the resulting fusion proteins, RhoA-LicKM and RhoA2-FL-d25CP, inhibited RSV growth in vitro by 50 and 80 %, respectively. These data indicate the feasibility of transient expression of this biologically active antiviral RhoA peptide in plants and the advantage of using a carrier molecule to enhance target expression and efficacy.


Performance of broiler breeder hens on wire and litter floors.
Two experiments were conducted with broiler breeder hens to study the influence of litter versus wire floor on weight and specific gravity of eggs. In Experiment 1, one group of broiler breeder hens was maintained on litter and the other on wire. Specific gravity was significantly higher for eggs from hens kept on litter floors. When hens on wire floors had access to litter in a feeder, an increase in egg specific gravity was noted within one day. In Experiment 2, broiler breeder hens, 52 weeks of age, were separated into three treatments: litter floor, wire floor, and wire floor with old litter material in feeder. When hens received 3.22% dietary calcium, the egg specific gravity was highest (P less than .05) from hens on the litter floor, intermediate from hens on wire with access to litter, and lowest from hens on wire without access to litter. Hens on wire with access to litter consumed 18.3 g litter/bird/day, corresponding to an additional intake of 352 mg calcium and 93 mg phosphorus. They also received 4700 mg calcium and 790 mg phosphorus from the feed. The specific gravity of eggs from hens with access to litter was higher than for eggs from those hens without access to the litter when hens received diets with 1.0 and .15% calcium. No significant differences were found in egg whites among treatments. The hens on wire with access to litter and fed 1.0 or .25 or 3.22% dietary calcium consumed 24.5, 28.5, and 18.9 g more of litter, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Single-dose ceftriaxone therapy of gonococcal ophthalmia neonatorum.
Ceftriaxone (125 mg) given as a single intramuscular dose without topical therapy was evaluated in seven infants with smear-positive gonococcal ophthalmia neonatorum. Neisseria gonorrhoeae was isolated from the eyes of six infants, and four of these isolates were penicillinase-producing N. gonorrhoeae. Two infants had concomitant ocular infection with Chlamydia trachomatis. All seven infants, when seen at follow-up, showed marked clinical improvement. Conjunctivitis resolved completely in four infants. One infant was lost to subsequent follow-up, while two infants had persistent ophthalmia due to C. trachomatis. Follow-up eye cultures for N. gonorrhoeae were all negative.


Membrane-Based Clarification and Fractionation of Red Wine Lees Aqueous Extracts.
Polyvinylidenefluoride (PVDF) hollow fiber membranes prepared in laboratory through the inversion phase method were characterized and used to clarify an aqueous extract from red wine lees. Steady-state permeate fluxes of 53 kg/m2h were obtained in the treatment of the aqueous extract in selected operating conditions. Suspended solids were completely retained by the hollow fiber membranes while bioactive compounds, including polyphenols, anthocyanins, and resveratrol were recovered in the permeate stream. The clarified stream was then fractionated by nanofiltration (NF). Three different commercial membranes, in flat-sheet configuration (NP010 and NP030 from Microdyn-Nadir, MPF36 from Koch Membrane Systems), were selected and tested for their productivity and selectivity towards sugars and bioactive compounds, including phenolic compounds, anthocyanins, and resveratrol. All selected membranes showed high retention towards anthocyanins (higher than 93%). Therefore, they were considered suitable to concentrate anthocyanins from clarified wine lees extracts at low temperature. On the other hand, NF permeate streams resulted enriched in phenolic compounds and resveratrol. Among the selected membranes, the MPF36 exhibited the lowest retention towards resveratrol (10%) and polyphenols (26.3%) and the best separation factor between these compounds and anthocyanins.


Mitochondrial cytochrome b gene in two developmental stages of human malarial parasite Plasmodium falciparum.
The cytochrome b gene of the mitochondrial ubiquinol-cytochrome c reductase (complex III of electron transport chain) was characterized in two developmental stages of human malarial parasite cultivated in vitro. The cytochrome b gene spanning the nucleotide position 4691 to 5930 in 6-kb mitochondrial DNA from gametocytic (sexual) and intraerythrocytic (asexual) stages of Plasmodium falciparum (a T9,94 mutant line) were in vitro amplified from total DNA using polymerase chain reaction (PCR). It was found that the parasites from both stages contained the PCR product approximately 1.2 kb in length that was localized in mitochondria. The nucleotide sequences of cytochrome b gene at Qi/quinone binding site from both stages were analyzed using thermal cycle sequencing and were found to be the same. The amount of this gene from both stages of the parasite were determined by using the quantitative PCR method. The results showed that the amount of the cytochrome b gene produced from the sexual stage was seven times higher than that obtained from the asexual stage. Our results would provide basic information on the regulation of cytochrome b and the 6-kb mitochondrial DNA during growth and development of the sexual and asexual stages of the malarial parasite in the mammalian host.


Grainyhead-Like Genes Family May Act as Novel Biomarkers in Colon Cancer.
The Grainyhead-like (GRHL) genes family were reported to participate in the development of a number of diseases. This study was designed to investigate the role of GRHL genes family in colon cancer (CC). In this study, the transcriptional levels of GRHL genes family in patients with CC from GEPIA were explored. Meanwhile, the immunohistochemical data of the GRHL genes family were also obtained in the HPA database. Additionally, we re-identified the mRNA of these genes via real-time PCR. Furthermore, the association between the levels of GRHL genes and stage plot as well as survival condition including overall survival and disease-free survival of patients with CC was analyzed. Finally, by transfecting with specific-siRNA, clone formation assay was performed to observe the role of GRHL genes family in the proliferation of SW480 human colon cancer cells. We found that the mRNA and protein levels of GRHL1, GRHL2 and GRHL3 were significantly higher in CC tissues than in normal colon tissues. Additionally, GRHL1, GRHL2 and GRHL3 were significantly associated with the stages of CC. The Kaplan-Meier plotter showed that the low levels of GRHL1, GRHL2 and GRHL3 conferred a better overall survival of patients with CC while the high levels of GRHL1 and GRHL3 were associated with poor disease-free survival. Knockdown of GRHL1, GRHL2 and GRH L3 siHgnificantly inhibited the ability of colony formation of human colon cancer cells. Our study demonstrated that GRHL genes are involved in the prognosis and survival in patients with CC, the inhibition of which may suppress the proliferation of colon cancer cells.


The Effect of Antibiotic Prophylaxis on Post-Operative Infection in Patients Undergone Flexible Cystos-copy.
The aim of this study is to determine whether antibiotic prophylaxis is required in this outpatient procedure. A non-randomised, prospective observational study that included 184 patients subjected to flexible cystoscopy divided into three groups: - Group 1:60 patients with prophylaxis of 500 mg of ciprofloxacin;- Group 2:62 patients with prophylaxis of 3 g of phosphomycin; and Group 3:62 without antibiotic prophylaxis. Prior to inclusion in the study, absence of infection was checked by means of a urine culture obtained 7 days before the procedure. An analysis was made of urinary infection after 7 days, the cystoscopy indications and its diagnosis, the presence of comorbidities, and the urinary symptoms during the following 7 days. The mean age of the patients in Group 1 was 65.3 (SD: 12.5) years, 66.7 (10.8) years in Group 2, and 66.9 (10.8) years in Group 3 (P = .7). Bacteriuria was present in 15% of the patients in Group 1, compared to 22.6% in Group 2, and 12.9% in Group 3, with the differences not statistically significant. In multivariate analysis, it was observed that there was no association with the appearance of bacteriuria between the groups for age (P = .8), diabetes (P = .2), smoking (P = .4), lower urinary tract symptoms (P = .7), or immunosuppression (P = .6). The use of ciprofloxacin or phosphomycin as prophylaxis does not appear to be indicated in flexible cystoscopy in our health area.


CD8 dimer usage on alpha beta and gama delta T lymphocytes from equine lymphoid tissues.
Eight murine monoclonal antibodies (mAb) were used to identify the equine CD8 alpha or CD8 beta chains and to define the expression of these chains on lymphocytes from various lymphoid tissues. CD8 alpha was a 39 kDa protein and CD8 beta was a 32 kDa protein. Both chains were expressed on most of the CD8+ T lymphocytes in the peripheral blood, spleen, thymus, mesenteric lymph nodes and ileal intraepithelial lymphocytes (IEL), however, in each lymphoid compartment a percentage of lymphocytes expressed only the CD8 alpha chain. The largest percentage of CD8 alpha alpha expressing T lymphocytes was 37.7% of the IELs. Purified T lymphocytes from the ileum expressing CD8 alpha beta co-expressed the alpha beta T cell receptor (TCR). In contrast, purified CD8+ T lymphocytes from the PBMC co-expressed either the alpha beta or gamma delta TCR by RT-PCR. Use of pooled anti-CD8 alpha mAb of the murine IgG2a isotype and rabbit complement resulted in lysis of the entire CD8 expressing population in peripheral blood mononuclear cells (PBMC). These results indicated that CD8 dimer usage by equine T lymphocytes is similar to other species and that the mAb described can be further used to separate equine CD8+ T lymphocyte subsets from the lymphoid tissues to define their function in protection against viral and other infections.


An improved secretion signal enhances the secretion of model proteins from Pichia pastoris.
Proteins can be secreted from a host organism with the aid of N-terminal secretion signals. The budding yeast Pichia pastoris (Komagataella sp.) is widely employed to secrete proteins of academic and industrial interest. For this yeast, the most commonly used secretion signal is the N-terminal portion of pre-pro-α-factor from Saccharomyces cerevisiae. However, this secretion signal promotes posttranslational translocation into the endoplasmic reticulum (ER), so proteins that can fold in the cytosol may be inefficiently translocated and thus poorly secreted. In addition, if a protein self-associates, the α-factor pro region can potentially cause aggregation, thereby hampering export from the ER. This study addresses both limitations of the pre-pro-α-factor secretion signal. We engineered a hybrid secretion signal consisting of the S. cerevisiae Ost1 signal sequence, which promotes cotranslational translocation into the ER, followed by the α-factor pro region. Secretion and intracellular localization were assessed using as a model protein the tetrameric red fluorescent protein E2-Crimson. When paired with the α-factor pro region, the Ost1 signal sequence yielded much more efficient secretion than the α-factor signal sequence. Moreover, an allelic variant of the α-factor pro region reduced aggregation of the E2-Crimson construct in the ER. The resulting improved secretion signal enhanced secretion of E2-Crimson up to 20-fold compared to the levels obtained with the original α-factor secretion signal. Similar findings were obtained with the lipase BTL2, which exhibited 10-fold enhanced secretion with the improved secretion signal. The improved secretion signal confers dramatic benefits for the secretion of certain proteins from P. pastoris. These benefits are likely to be most evident for proteins that can fold in the cytosol and for oligomeric proteins.


Investigation and Validation of Molecular Characteristics of Endometrium in Recurrent Miscarriage and Unexplained Infertility from a Transcriptomic Perspective.
Recurrent miscarriage (RM) and unexplained infertility (UI) are gordian knots in reproductive medicine, which are troubling many patients, doctors, and researchers. Although these two diseases of early pregnancy have a significant impact on human reproductive health, little is known about the specific mechanisms, which caused treatment difficulties. This study focused on the molecular signatures underlying the pathological phenotypes of two diseases, with the hope of using statistical methods to identify the significant core genes. An unbiased Weighted Correlation Network Analysis (WGCNA) algorithm was used for endometrial transcriptome data analysis and the disease-related gene modules were screened out. Through enrichment analysis of the candidate genes, we found similarities between both diseases and shared enrichment of immune-related pathways. Therefore, we used immune algorithms to assess the infiltration of immune cells and found abnormal increases of CD8+T cells and neutrophils. In order to explore the molecular profile behind the immunophenotypic changes, we used the SVM algorithm and LASSO regression to identify the core genes with diagnostic capacity in both diseases and discussed their significance of immune disorders in the endometrium. In the end, the satisfactory diagnostic ability of these core genes was verified in the broader group. Our results demonstrated the presence of immune disorders in non-pregnancy tissues of RM and UI, and identified the core molecules of this phenotype, and discuss mechanisms. This provides exploratory evidence for the in-depth understanding of the mechanism of RM and UI and may provide potential targets for their future treatment.


Group B streptococci inhibit the chemotactic activity of the fifth component of complement.
Infection with group B streptococci (GBS) is associated with a poor acute inflammatory response in which neutrophils fail to localize at the site of invasion. In the present studies, we have examined the effects of group B streptococci on C-derived chemotactic activity in human serum. Fresh human serum was activated to form C5a and C5adesarg by incubation with zymosan. The activated serum was then incubated with group B organisms, centrifuged, and the supernatants tested for chemotactic activity for human polymorphonuclear leukocytes. Group B organisms caused a dose-dependent decrease in C-dependent chemotactic activity. The degree of inhibition was profound with 1 X 10(9) bacteria/ml (10% of control). Experiments indicated that significant chemotactic factor inactivation occurred within 2 min of exposure to GBS organisms, while maximal inhibition occurred after 30 min incubation. A number of different strains of GBS of types I, II, and III possessed inhibitory activity. In contrast, group D streptococci, Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae failed to inhibit the C-derived chemotactic activity in human serum. Group A streptococci that were M protein positive also inactivated C-dependent chemotactic activity in serum, as previously reported. The inhibitory activity of the GBS strains could be abolished by heat or trypsin treatment but not by neuraminidase, pronase, or pepsin. C5a levels in zymosan-activated serum as measured by RIA were not decreased after incubation with an inhibitory strain suggesting that absorption was not involved. SDS-PAGE analysis revealed that group B streptococci degrade the C5a molecule, increasing its electrophoretic mobility by removing a fragment with a m.w. of approximately 650 Da. Thus, one of the reasons for the poor inflammatory response at the site of GBS infection may reside in the ability of these pathogens to inactivate C-derived inflammatory mediators. The GBS C5a-ase activity probably serves as an additional virulence factor for these organisms contributing to the poor inflammatory response characteristic of group B streptococcal infection.


Computerized ordering of ultrasound examinations.
A uniform format for requesting ultrasound examinations was developed in response to the installation of a computerized communication system within the hospital. This format consists of a sequence of eight question-lists (screens), which are presented to the referring physicians on a computer video terminal and from which he selects appropriate information with a light pen. With computerized ordering, it is now possible for the ultrasonographer to be assured of always receiving study indications and relevant patient clinical information while knowing that the referring physician has been advised of study contraindications, scheduling advice, and the proper patient preparation.


Catalytic asymmetric dihydroxylation of olefins with reusable OsO(4)(2-) on ion-exchangers: the scope and reactivity using various cooxidants.
Exchanger-OsO(4) catalysts are prepared by an ion-exchange technique using layered double hydroxides and quaternary ammonium salts covalently bound to resin and silica as ion-exchangers. The ion-exchangers with different characteristics and opposite ion selectivities are specially chosen to produce the best heterogeneous catalyst that can operate using the various cooxidants in the asymmetric dihydroxylation reaction. LDH-OsO(4) catalysts composed of different compositions are evaluated for the asymmetric dihydroxylation of trans-stilbene. Resin-OsO(4) and SiO(2)-OsO(4) designed to overcome the problems associated with LDH-OsO(4) indeed show consistent activity and enantioselectivity in asymmetric dihydroxylation of olefins using K(3)Fe(CN)(6) and molecular oxygen as cooxidants. Compared to the Kobayashi heterogeneous systems, resin-OsO(4) is a very efficient catalyst for the dihydroxylation of a wide variety of aromatic, aliphatic, acyclic, cyclic, mono-, di-, and trisubstituted olefins to afford chiral vicinal diols with high yields and enantioselectivities irrespective of the cooxidant used. Resin-OsO(4) is recovered quantitatively by a simple filtration and reused for a number of cycles with consistent activity. The high binding ability of the heterogeneous osmium catalyst enables the use of an equimolar ratio of ligand to osmium to give excellent enantioselectives in asymmetric dihydroxylation in contrast to the homogeneous osmium system in which excess molar quantities of the expensive chiral ligand to osmium are invariably used. The complexation of the chiral ligand (DHQD)(2)PHAL, having very large dimension, a prerequisite to obtain higher ee, is possible only with the OsO(4)(2-) located on the surface of the supports.


Analyzing the effect of cell rearrangement on Delta-Notch pattern formation.
The Delta-Notch system plays a vital role in many areas of biology and typically forms a salt and pepper pattern in which cells strongly expressing Delta and cells strongly expressing Notch are alternately aligned via lateral inhibition. In this study, we consider cell rearrangement events, such as cell mixing and proliferation, that alter the spatial structure itself and affect the pattern dynamics. We model cell rearrangement events by a Poisson process and analyze the model while preserving the discrete properties of the spatial structure. We investigate the effects of the intermittent perturbations arising from these cell rearrangement events on the discrete spatial structure itself in the context of pattern formation and by using an analytical approach, coupled with numerical simulation. We find that the homogeneous expression pattern is stabilized if the frequency of cell rearrangement events is sufficiently large. We analytically obtain the balanced frequencies of the cell rearrangement events where the decrease of the pattern amplitude, as a result of cell rearrangement, is balanced by the increase in amplitude due to the Delta-Notch interaction dynamics. Our framework, while applied here to the specific case of the Delta-Notch system, is applicable more widely to other pattern formation mechanisms.


Axon Guidance and Collective Cell Migration by Substrate-Derived Attractants.
Neurons have evolved specialized growth structures to reach and innervate their target cells. These growth cones express specific receptor molecules that sense environmental cues and transform them into steering decisions. Historically, various concepts of axon guidance have been developed to better understand how axons reach and identify their targets. The essence of these efforts seems to be that growth cones require solid substrates and that major guidance decisions are initiated by extracellular cues. These sometimes highly conserved ligands and receptors have been extensively characterized and mediate four major guidance forces: chemoattraction, chemorepulsion, contact attraction and contact repulsion. However, during development, cells, too, do migrate in order to reach molecularly-defined niches at target locations. In fact, axonal growth could be regarded as a special case of cellular migration, where only a highly polarized portion of the cell is elongating. Here, I combine several examples from genetically tractable model organisms, such as Drosophila or zebrafish, in which cells and axons are guided by attractive cues. Regardless, if these cues are secreted into the extracellular space or exposed on cellular surfaces, migrating cells and axons seem to keep close contact with these attractants and seem to detect them right at their source. Migration towards and along such substrate-derived attractants seem to be particularly robust, as genetic deletion induces obvious searching behaviors and permanent guidance errors. In addition, forced expression of these factors in ectopic tissues is highly distractive too, regardless of the pattern of other endogenous cues. Thus, guidance and migration towards and along attractive tissues is a powerful steering mechanism that exploits affinity differences to the surroundings and, in some instances, determines growth trajectories from source to target region.


Prevalence and identification of Cryptosporidium species in paediatric patients with diarrhoea.
To determine the prevalence of Cryptosporidium infection in children with diarrhoea, identify associated factors and identify the parasite using Polymerase Chain Reaction (PCR). A total of 138 diarrhoeic faecal samples were collected between August 2011 and February 2013, from children under 12 years of age, admitted to paediatric units of Teaching Hospitals, Kandy and Peradeniya, Sirimawo Bandaranayake Childrens' Hospital, Peradeniya and District General Hospital, Matale. One hundred faecal samples collected from healthy children were used as controls. All control and test samples were screened for the presence of Cryptosporidium oocysts with Modified Ziehl-Neelsen (MZN) method and PCR. Prevalence of Cryptosporidium infection among children with diarrhoea was 5.7%. All the cases positive for Cryptosporidium were below 3 years of age. The majority (7 out of 8) of the positive cases had watery diarrhoea while none of the healthy children excreted Cryptosporidium oocysts in the faeces. Of the 8 positive cases, 6 had a history of animal contact. A large proportion of positive cases used pipe borne municipal water. The majority (66.6%) of positive cases did not consume boiled cooled water. We were able to identify C. parvum from one of the eight cases that had diarrhoea. The current study shows that Cryptosporidium is one of the aetiological agents responsible for childhood watery diarrhoea in Sri Lanka, thus stressing the importance of routine stool examination for Cryptosporidium oocysts. This study recommends boiling water as an important measure to prevent the transmission of Cryptosporidium oocysts. Further molecular studies are needed to determine the other species of Cryptosporidium responsible for cryptosporidiosis in children in Sri Lanka.


Plasma apolipoproteins A-I and B in survivors of myocardial infarction and in a control group.
The values of apolipoproteins (apo) A-I and B were determined in a population sample of hospital outpatients with a standardized method to verify if the cutpoints calculated in a cross-sectional study in the US are usable with other populations. We also tested the apolipoproteins' ability to discriminate between healthy people and survivors of myocardial infarction. In the studied population the apo A-I value corresponding to the HDL-cholesterol decisional centile is 1.12 g/L for males and 1.17 g/L for females; the apo B value corresponding to the LDL-cholesterol decisional centile is 1.23 g/L for males and 1.14 g/L for females. These values are quite close to the cutpoints proposed for the American population (1.20 g/L for both apolipoproteins). In comparison with the LDL- and HDL-cholesterol decisional concentrations, the cutpoints for apolipoproteins allow a correct classification of a greater percentage of postmyocardial infarction patients (16% higher for apo B and 5% for apo A-I). Standardized assays coupled with a reference database allow a better clinical use of apolipoprotein measurements.


[Effects of KT1-32 on acute gastric lesions and duodenal ulcers induced in rats].
We studied the effects of KT1-32 (sodium guaiazulene 3-sulfonate) on development of various acute gastric lesions and duodenal ulcers induced in rats. Male Donryu or Sprague-Dawley rats (220-270 g), fasted (but allowed free access to water) for 24 or 48 hr before the experiments, were used. KT1-32 (dissolved in distilled water, 10-100 mg/kg), given p.o. or intraduodenally (i.d.), dose-dependently inhibited the development of gastric lesions induced by HCl X ethanol (60% ethanol in 150 mM HCl), HCl X aspirin (aspirin 100 mg/kg in 150 mM HCl) or aspirin (150 mg/kg in pylorus-ligated preparation) and Shay ulcers (14 hr pylorus ligation). KT1-32 (30 and 100 mg/kg), given p.o. twice (9.5 hr apart), significantly inhibited the development of duodenal ulcers induced by mepirizole (200 mg/kg, s.c.), but did not inhibit gastric lesions developed simultaneously. KT1-32 (30 and 100 mg/kg), given p.o. or i.d., significantly reduced gastric acid secretion when examined using pylorus ligation preparations. KT1-32 (100 mg/kg, i.d.) had no effect on basal and suppressed duodenal HCO3- secretion by mepirizole. These results suggest that KT1-32 is a promising drug for the treatment of gastritis and peptic ulcers.


National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene trial: advancing the science of recruitment and breast cancer risk assessment in minority communities.
One of the first chemoprevention trials conducted in the western hemisphere, the National Surgical Adjuvant Breast and Bowel Project's (NSABP) Breast Cancer Prevention Trial (BCPT), demonstrated the need to evaluate all aspects of recruitment in real time and to implement strategies to enroll racial and ethnic minority women. The purpose of this report is to review various patient recruitment efforts the NSABP developed to enhance the participation of racial and ethnic minority women in the Study of Tamoxifen and Raloxifene (STAR) trial and to describe the role that the recruitment process played in the implementation and understanding of breast cancer risk assessment in minority communities. The NSABP STAR trial was a randomized, double-blinded study comparing the use of tamoxifen 20 mg/day to raloxifene 60 mg/day, for a 5-year period, to reduce the risk of developing invasive breast cancer. Eligible postmenopausal women were required to have a 5-year predicted breast cancer risk of 1.66% based on the modified Gail Model. For the current report, eligibility and enrollment data were tabulated by race/ethnicity for women who submitted STAR risk assessment forms (RAFs). A total of 184,460 RAFs were received, 145,550 (78.9%) from white women and 38,910 (21.1%) from minority women. Of the latter group, 21,444 (11.6%) were from African Americans/blacks, 7913 (4.5%) from Hispanics/Latinas, and 9553 (5.2%) from other racial or ethnic groups. The percentages of risk-eligible women among African Americans, Hispanics/Latinas, others, and whites were 14.2%, 23.3%, 13.7%, and 57.4%, respectively. Programs targeting minority enrollment submitted large numbers of RAFs, but the eligibility rates of the women referred from those groups tended to be lower than the rates among women referred outside of those programs. The average number of completed risk assessments increased among minority women over the course of the recruitment period compared to those from whites. We have not addressed all identified barriers to the recruitment of minorities in clinical research. Our risk assessments and recruitment results do not reflect the modified Gail Model for African Americans. Recruitment strategies used in STAR for racial and ethnic minorities contributed to doubling the minority enrollment compared to that in the BCPT and increased the awareness of breast cancer risk assessment in minority communities. Incorporation of new information into models to improve the risk estimation of diverse populations should prove beneficial.


The Induced Immune Response in Patients With Infectious Spondylodiscitis: A Prospective Observational Cohort Study.
Infectious spondylodiscitis is a rare infection of the intervertebral disc and the adjacent vertebral bodies that often disseminates and requires long-term antibiotic therapy. Immunologic profiling of patients with infectious spondylodiscitis could allow for a personalized medicine strategy. We aimed to examine the induced immune response in patients with infectious spondylodiscitis during and after antibiotic therapy. Furthermore, we explored potential differences in the induced immune response depending on the causative pathogen and the dissemination of the disease. This was a prospective observational cohort study that enrolled patients with infectious spondylodiscitis between February 2018 and August 2020. A blood sample was collected at baseline, after four to six weeks of antibiotic therapy (during antibiotic therapy), and three to seven months after end of antibiotic therapy (post-infection). The induced immune response was assessed using the standardized functional immune assay TruCulture®. We used a panel of three immune cell stimuli (lipopolysaccharide, Resiquimod and polyinosinic:polycytodylic acid) and an unstimulated control. For each stimulus, the induced immune response was assessed by measuring the released concentration of Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, Interferon-γ (IFN-γ) and Tumor necrosis factor-α (TNF-α) in pg/mL. In total, 49 patients with infectious spondylodiscitis were included. The induced immune responses were generally lower than references at baseline, but the cytokine release increased in patients after treatment with antibiotic therapy. Post-infection, most of the released cytokine concentrations were within the reference range. No significant differences in the induced immune responses based on stratification according to the causative pathogen or dissemination of disease were found. We found lower induced immune responses in patients with infectious spondylodiscitis at baseline. However, post-infection, the immune function normalized, indicating that an underlying immune deficiency is not a prominent factor for spondylodiscitis. We did not find evidence to support the use of induced immune responses as a tool for prediction of the causative pathogen or disease dissemination, and other methods should be explored to guide optimal treatment of patients with infectious spondylodiscitis.


Correlates of frequency of HIV testing among men who have sex with men in Washington, DC.
In Washington, DC, the leading mode of HIV transmission is through men who have sex with men (MSM) behavior. This study explored differences between frequent HIV testers (men testing at least twice a year) and annual or less frequent testers (men testing once a year or less) in DC. Nearly, one-third of MSM reported testing for HIV at least four times in the prior two years. In the multivariable model, frequent testers had significantly higher odds of being aged 18-34 (aOR =1.94), knowing their last partner's HIV status (aOR=1.86), having 5+ partners in the last year (aOR=1.52), and having seen a health-care provider in the last year (aOR=2.28). Conversely, frequent testers had significantly lower odds of being newly HIV positive (aOR=0.27), and having a main partner at last sex (vs. casual/exchange partner; aOR=0.59). Medical providers need to be encouraged to consistently offer an HIV test to their patients, especially those who are sexually active and who have not tested recently.


Hematin promotes complement alternative pathway-mediated deposition of C3 activation fragments on human erythrocytes: potential implications for the pathogenesis of anemia in malaria.
Childhood malaria caused by Plasmodium falciparum is often characterized by severe anemia at low parasite burdens; the mechanism(s) responsible for this pathology remain to be defined. We have reported, based on clinical observations and in vitro models, that complement control proteins on erythrocytes such as CR1, the immune adherence receptor specific for C3b, may be reduced in childhood malaria, suggesting a possible role for complement in erythrocyte destruction. Intravascular lysis of iE by P. falciparum leads to release of erythrocyte breakdown products such as hemoglobin and hematin, which have inflammatory properties. In the present article, we demonstrate that in serum and in anticoagulated whole blood, moderate concentrations of hematin activate the alternative pathway of complement and promote deposition of C3 activation and breakdown products on erythrocytes. The degree of C3 fragment deposition is directly correlated with erythrocyte CR1 levels, and erythrocytes opsonized with large amounts of C3dg form rosettes with Raji cells, which express CR2, the C3dg receptor which is expressed on several types of B cells in the spleen. Thus, the reaction mediated by hematin promotes opsonization and possible clearance of the youngest (highest CR1) erythrocytes. A mAb specific for C3b, previously demonstrated to inhibit the alternative pathway of complement, completely blocks the C3 fragment deposition reaction. Use of this mAb in nonhuman primate models of malaria may provide insight into mechanisms of erythrocyte destruction and thus aid in the development of targeted therapies based on inhibiting the alternative pathway of complement.


Seizing the Connection: Exploring the Interplay Between Epilepsy and Glycemic Control in Diabetes Management.
Epilepsy, a neurological disorder characterized by recurrent seizures, and diabetes, a metabolic disorder characterized by impaired regulation of glucose levels, are two distinct conditions that may appear unrelated at first glance. Nevertheless, recent scholarly investigations have revealed these entities' intricate and ever-evolving interplay. This review initially delves into the intricate interplay between epilepsy and its potential ramifications on glycemic control. Seizures, particularly those accompanied by convulsive manifestations, have the potential to induce acute perturbations in blood glucose levels via diverse mechanisms, encompassing the liberation of stress hormones, the emergence of insulin resistance, and the dysregulation of the autonomic nervous system. Comprehending these intricate mechanisms is paramount in customizing productive strategies for managing diabetes in individuals with epilepsy. On the contrary, it is worth noting that diabetes can substantially impact the trajectory and control of epilepsy. The correlation between hyperglycemia and an elevated susceptibility to seizures, as well as the potential for exacerbating the intensity of epilepsy, has been established. This narrative review offers a concise exposition of the intricate interplay between epilepsy and glycemic control within diabetes management. The objective of exploring reciprocal influences, underlying mechanisms, and common risk factors is to augment the clinical comprehension of this intricate interconnection. In essence, this acquired knowledge possesses the potential to serve as a guiding compass for healthcare professionals, enabling them to craft bespoke therapeutic approaches that enhance the holistic welfare of individuals grappling with the coexistence of epilepsy and diabetes.


Functional Mechanisms of Mitochondrial Respiratory Chain Supercomplex Assembly Factors and Their Involvement in Muscle Quality.
Impairment of skeletal muscle function causes disabilities in elderly people. Therefore, in an aged society, prevention and treatment of sarcopenia are important for expanding healthy life expectancy. In addition to aging, adipose tissue disfunction and inflammation also contribute to the pathogenesis of sarcopenia by causing the combined state called 'sarcopenic obesity'. Muscle quality as well as muscle mass contributes to muscle strength and physical performance. Mitochondria in the skeletal muscles affect muscle quality by regulating the production of energy and reactive oxygen species. A certain portion of the mitochondrial respiratory chain complexes form a higher-order structure called a "supercomplex", which plays important roles in efficient energy production, stabilization of respiratory chain complex I, and prevention of reactive oxygen species (ROS) generation. Several molecules including phospholipids, proteins, and certain chemicals are known to promote or stabilize mitochondrial respiratory chain supercomplex assembly directly or indirectly. In this article, we review the distinct mechanisms underlying the promotion or stabilization of mitochondrial respiratory chain supercomplex assembly by supercomplex assembly factors. Further, we introduce regulatory pathways of mitochondrial respiratory chain supercomplex assembly and discuss the roles of supercomplex assembly factors and regulatory pathways in skeletal muscles and adipose tissues, believing that this will lead to discovery of potential targets for prevention and treatment of muscle disorders such as sarcopenia.


PDMS-based microfluidic device with multi-height structures fabricated by single-step photolithography using printed circuit board as masters.
We have developed a method for fabricating microfluidic devices with multi-height structures using single step photolithography. The whole fabrication process is executed by conventional printed circuit board (PCB) technology without the need of having access to clean room facilities. Specifically designed "windows" and "rims" architectures were printed on films that were used as photomasks. Different levels of protruding features on the PCB master were produced by exposing a photomask followed by chemical wet etching. Poly(dimethylsiloxane) (PDMS) was then moulded against the positive relief master to generate microfluidic structures. In this report, we described the fabrication of a microfluidic device featured with a multi-height "sandbag" structure for particle entrapment and peripheral microchannels. Controlled immobilization of biological cells and immunocytochemcial staining assays were performed to demonstrate the applicability of the microfluidic device for cellular analysis. The integrity of the microdevice remained stable under applied pressure, indicating the robustness of the elastic PDMS structures for analytical operation. The simple microfabrication process requires only low-cost materials and minimal specialized equipment and can reproducibly produce mask lines of about 20 microm in width, which is sufficient for most microfluidic applications.


Effect of metal ions on growth of Pseudomonas aeruginosa and siderophore and protein production.
Pseudomonas aeruginosa (GRC1) isolated from potato rhizosphere, grew better on succinate medium than tryptic soy medium and produced hydroxamate type of siderophore in iron-deficient succinate medium. When the strain GRC1 was grown in the presence of different metal ion compounds, viz. ZnSO4, MnSO4, MnCl2 and FeCl3 at 6 and 12 microM concentrations individually, ZnSO4 (12 microM) promoted siderophore production but suppressed the growth and protein content of test organism. MnCl2 and FeCl3 (12 microM) enhanced the growth, whereas MnCl2 and MnSO4 (12 microM) induced protein contents of strain GRC1.


Sparse optimization of mutual synchronization in collectively oscillating networks.
We consider a pair of collectively oscillating networks of dynamical elements and optimize their internetwork coupling for efficient mutual synchronization based on the phase reduction theory developed by Nakao et al. [Chaos 28, 045103 (2018)]. The dynamical equations describing a pair of weakly coupled networks are reduced to a pair of coupled phase equations, and the linear stability of the synchronized state between the networks is represented as a function of the internetwork coupling matrix. We seek the optimal coupling by minimizing the Frobenius and L1 norms of the internetwork coupling matrix for the prescribed linear stability of the synchronized state. Depending on the norm, either a dense or sparse internetwork coupling yielding efficient mutual synchronization of the networks is obtained. In particular, a sparse yet resilient internetwork coupling is obtained by L1-norm optimization with additional constraints on the individual connection weights.


Persistent Self-Induced Larmor Precession Evidenced through Periodic Revivals of Coherence.
Interferometric measurements of an optically trapped exciton-polariton condensate reveal a regime where the condensate pseudo-spin precesses persistently within the driving optical pulse. For a single 20 μs optical pulse, the condensate pseudo-spin undergoes over 10^{5} full precessions with striking frequency stability. The emergence of the precession is traced to polariton nonlinear interactions that give rise to a self-induced out-of-plane magnetic field, which in turn drives the system spin dynamics. The Larmor precession frequency and trajectory are directly influenced by the condensate density, enabling the control of this effect with optical means. Our results accentuate the system's potential for the realization of magnetometry devices and can lead to the emergence of spin-squeezed polariton condensates.


Autogenous demineralized dentin matrix from extracted tooth for the augmentation of alveolar bone defect: a prospective randomized clinical trial in comparison with anorganic bovine bone.
The aim of this study was to prospectively evaluate the clinical efficacy and histological outcome of the autogenous tooth graft material (AutoBT) compared to that of anorganic bovine bone (Bio-Oss® , Geistlich, Switzerland) in post-extraction alveolar bone augmentation. A total of 33 graft sites in 24 patients were included in this study. AutoBT was used in 21 sites of 15 patients and Bio-Oss® was used in 12 sites of 9 patients for alveolar bone augmentation 2-4 weeks after dental extraction. Vertical dimension of grafted bone was measured both at the time of graft placement and at implant fixture placement after 6 months. Trephine cores were harvested for the histomorphometric evaluations during implant placement when feasible. The primary stability of implant fixture was also measured. Infection of graft material or graft bed was not observed and graft sites healed without any notable complications in both groups. The vertical dimensions of alveolar bone increased by 5.38 ± 2.65 mm in AutoBT group and 6.56 ± 3.54 mm in Bio-Oss® group at 6 months post-extraction. Histomorphometrically, new bone formation of AutoBT-grafted site was 31.24 ± 13.87% while that of Bio-Oss® was 35.00 ± 19.33%. The implant stability quotient (ISQ) of implants placed in AutoBT-grafted sites measured 72.80 ± 10.81 while those placed in Bio-Oss® -grafted sites measured 70.0 ± 12.86. There were no statistically significant differences between measurements of the two groups. Autogenous demineralized dentin matrix from extracted tooth grafted to extraction sockets for the augmentation of vertical dimension was as effective as augmentation using anorganic bovine bone. Both groups showed favorable wound healing, similar amount of implant stability, and histologically confirmed new bone formation. Thus, the results of this study suggest that autogenous tooth graft material is a viable option for alveolar bone augmentation following dental extraction.


European perspectives on big data applied to health: The case of biobanks and human databases.
The paradigm shift to a knowledge-based economy has incremented the use of personal information applied to health-related activities, such as biomedical research, innovation, and commercial initiatives. The convergence of science, technology, communication and data technologies has given rise to the application of big data to health; for example through eHealth, human databases and biobanks. In light of these changes, we enquire about the value of personal data and its appropriate use. In order to illustrate the complex ground on which big data applied to health develops, we analyse the current situation of the European Union and two cases: the Catalan VISC+/PADRIS and the UK Biobank, as perspectives. Personal health-related data in the context of the European Union is being increasingly used for big data projects under diverse schemes. There, public and private sectors participate distinctively or jointly, pursuing very different goals which may conflict with individual rights, notably privacy. Given that, this paper advocates for stopping the unjustified accumulation and commercialisation of personal data, protecting the interests of citizens and building appropriate frameworks to govern big data projects for health. A core tool for achieving such goals is to develop consent mechanisms which allow truly informed but adaptable consent, conjugated with the engagement of donors, participants and society.


Bactericidal effects of a high-power, red light-emitting diode on two periodontopathic bacteria in antimicrobial photodynamic therapy in vitro.
Light-emitting diodes have been investigated as new light activators for photodynamic therapy. We investigated the bactericidal effects of high-power, red light-emitting diodes on two periodontopathic bacteria in vitro. A light-emitting diode (intensity: 1100 mW/cm(2) , peak wavelength: 650 nm) was used to irradiate a bacterial solution for either 10 or 20 s. Bacterial solutions (Porphyromonas gingivalis or Aggregatibacter actinomycetemcomitans) at a concentration of 2.5 × 10(6) c.f.u./mL were mixed with an equal volume of either methylene blue or toluidine blue O (0-20 μg/mL) and added to titer plate wells. The plate wells were irradiated with red light-emitting diode light from a distance of 22 or 40 mm. The contents were diluted, and 50 μL was smeared onto blood agar plates. After 1 week of culturing, bacterial c.f.u. were counted. The light-emitting diode energy density was estimated to be approximately 4 and 8 J/cm(2) after 10 and 20 s of irradiation, respectively. Red light-emitting diode irradiation for 10 s from a distance of 22 mm, combined with methylene blue at concentrations >10 μg/mL, completely killed Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. High-power, red light-emitting diode irradiation with a low concentration of dye showed effective bactericidal effects against two periodontopathic bacteria.


Biobanks as a Central Part of the Finnish Growth and Genomic Strategies: How to Balance Privacy in an Innovation Ecosystem?
Finland has aimed to make itself an international leader in genomic research and related business and, in working towards that goal, has enacted biobank legislation. The Biobank Act requires biobanks to gain approval, be supervised, and register at the national level. Numerous other laws may also apply in any given research setting, such as the Personal Data Act, the Medical Research Act, and the Act on Medical Use of Human Organs and Tissues.In terms of privacy protection, anonymization is generally not permitted under Finnish law and therefore most biobanks pseudonomize data and samples. However, the broad understanding of what is identifiable data in Finland has created difficulties in sharing with non-EU countries. Furthermore, consent to biobank research is only applicable to the sample and related data, not to data stored in other health-related registries, and consent is only to the field of research for that particular biobank. These restrictions impede the sharing of samples and data for research.


Selection and characterization of specific nanobody against bovine virus diarrhea virus (BVDV) E2 protein.
Bovine viral diarrhea-mucosal disease (BVD-MD) is caused by bovine viral diarrhea virus (BVDV), and results in abortion, stillbirth, and fetal malformation in cows. Here, we constructed the phage display vector pCANTAB 5E-VHH and then transformed it into Escherichia coli TG1-competent cells, to construct an initial anti-BVDV nanobody gene library. We obtained a BVDV-E2 antigen epitope bait protein by prokaryotic expression using the nucleotide sequence of the E2 gene of the BVDV-NADL strain published in GenBank. Phage display was used to screen the anti-BVDV nanobody gene library. We successfully constructed a high quality phage display nanobody library, with an initial library capacity of 4.32×105. After the rescue of helper phage, the titer of the phage display nanobody library was 1.3×1011. The BVDV-E2 protein was then expressed in Escherichia coli (DE3), and a 49.5 kDa band was observed with SDS-PAGE analysis that was consistent with the expected nanobody size. Thus, we were able to isolate one nanobody that exhibits high affinity and specificity against BVDV using phage display techniques. This isolated nanobody was then used in Enzyme Linked Immunosorbent Assay and qRT-PCR, and ELISA analyses of BVDV infection of MDBK cells indicated that the nanobodies exhibited good antiviral effect.


Stereoselective intramolecular [4 + 3] cycloadditions of nitrogen-stabilized chiral oxyallyl cations via epoxidation of N-tethered allenamides.
The first intramolecular [4 + 3] cycloaddition reaction using nitrogen-stabilized chiral oxyallyl cations that are tethered to furan or diene through the nitrogen atom is described here. Formation of these nitrogen-stabilized chiral oxyallyl cations is achieved by a chemoselective epoxidation of chiral allenamides via syringe pump addition of dimethyl dioxirane. The ensuing cycloaddition can be carried out with a range of different lengths for the tether, and high diastereoselectivities can be obtained when using chiral allenamides with shorter tethers.


Magnitude of risk factors for chronic noncommunicable diseases in adolescents and young adults in Brazil: A population-based study.
Estimate the magnitude and factors associated with risk factors for chronic noncommunicable diseases in adolescents and young adults in Brazil. Cross-sectional study that analyzed data from the 2019 National Health Survey. The population of interest was adolescents and young adults aged 15 to 24 years. Data were collected through individual interviews during home visits. Dependent variables included major risk factors for chronic noncommunicable diseases. Demographic and socioeconomic characteristics were used as independent variables. Multiple Poisson regression models were used to assess the relationship between independent variables and risk factors. A total of 10,460 individuals (5,001 men and 5,459 women) were included. Regardless of sex, the most prevalent risk factors were insufficient fruit and vegetable consumption (92.6%) and leisure-time physical inactivity (43.3%). The prevalence rates of tobacco smokers, alcohol consumption once a month or more, and alcohol abuse were 8.9%, 28.7%, and 18.5%, respectively. Regular consumption of soft drinks and/or artificial juices was described by 17.2%. The prevalence of overweight was 32.5%. Young adults, males, and individuals with lower educational levels, of black race/skin color, with lower household income, and residents of urban areas had a higher prevalence for most risk factors. Differences in the determinants were found for some factors. Inequalities between Brazilian regions were recorded for seven of the nine factors analyzed. The most socioeconomically developed regions had the highest prevalence of most risk factors. The high magnitude of risk factors indicates a potential increase in the burden of chronic noncommunicable diseases in a future scenario for Brazil.


Radiation Major Hepatectomy Using Ablative Dose Yttrium-90 Radioembolization in Patients with Hepatocellular Carcinoma 5 cm or Larger.
To evaluate the safety and effectiveness of ablative radioembolization for large hepatocellular carcinoma (HCC) while preserving a small future liver remnant (FLR). Twenty-five patients with large HCC of ≥5 cm requiring treatment for >60% of the total liver volume and having well-preserved liver function were treated with ablative glass microsphere radioembolization at a single institution from January 2017 to December 2021. Radioembolization was performed with a mean absorbed dose of >150 Gy, and the FLR per nontumor liver volume (NTLV) was set at >30%. Changes in liver function, adverse events, duration of response (DoR) in a treated area, time-to-progression (TTP), and overall survival (OS) were retrospectively investigated. The largest tumor diameter and planned dose per treated volume were 11.4 cm ± 3.9 and 242.3 Gy ± 63.6 (169.4 Gy ± 45.9 per whole liver volume), respectively. All patients remained at Child-Pugh Class A for 90 days. No patient experienced Grade 3‒4 hyperbilirubinemia or new ascites. One patient (lung dose, 27.8 Gy) developed radiation pneumonitis requiring transient steroid treatment. According to the posttreatment dosimetry, the tumorous and nontumorous liver absorbed doses were 418.8 Gy ± 227.4 and 69.0 Gy ± 32.1, respectively. The median DoR in a treated area and TTP were 22.0 and 17.1 months, respectively. The 5-year OS rate was 83.2%. Ablative radioembolization of large HCC of ≥5 cm can be performed safely and effectively in patients with preserved liver function when FLR/NTLV exceeds 30%.


Advanced visualization platform for surgical operating room coordination: distributed video board system.
One of the major challenges for day-of-surgery operating room coordination is accurate and timely situation awareness. Distributed and secure real-time status information is key to addressing these challenges. This article reports on the design and implementation of a passive status monitoring system in a 19-room surgical suite of a major academic medical center. Key design requirements considered included integrated real-time operating room status display, access control, security, and network impact. The system used live operating room video images and patient vital signs obtained through monitors to automatically update events and operating room status. Images were presented on a "need-to-know" basis, and access was controlled by identification badge authorization. The system delivered reliable real-time operating room images and status with acceptable network impact. Operating room status was visualized at 4 separate locations and was used continuously by clinicians and operating room service providers to coordinate operating room activities.


Morbidity of local therapy for locally advanced metastatic breast cancer: an analysis of the Surveillance, Epidemiology, and End Results (SEER)-Medicare Registry.
Limited data exist to guide the management of in-breast tumors that can produce physical and emotional discomfort in the setting of metastatic disease. We evaluated the morbidity of local therapy (LT) among patients with locally advanced metastatic breast cancer. Patients with de novo T4M1 breast cancer diagnosed between 2005 and 2011 were identified from the SEER-Medicare database. We assessed receipt of care for loco-regional morbidity before and after LT. Among 3660 patients with T4M1 disease, 1558 (43%) underwent LT [surgery (19%), radiation (15%), both (9%)]. Before LT, few patients were reported to have loco-regional morbidity (7.9% vs. 6.7% for no LT, P = 0.17). Following LT, patients were reported to have more loco-regional morbidity than patients who did not have LT (22.6% vs. 7.9%). More patients without baseline loco-regional morbidity were reported to have received care for loco-regional morbidity documented after LT compared to baseline loco-regional morbidity reported in patients without LT (19.9% vs. 6.3%, P < 0.001). The need to address loco-regional morbidity is relatively infrequent among patients with T4M1 disease who do not undergo LT. Receipt of care for loco-regional morbidity was higher following LT. For patients without existing loco-regional morbidity, risks of LT may outweigh potential benefits.


Whole-Genome Duplication and Purifying Selection Contributes to the Functional Redundancy of Auxin Response Factor (ARF) Genes in Foxtail Millet (Setaria italica L.).
Auxin response factors (ARFs) play crucial roles in auxin-mediated response, whereas molecular genetics of ARF genes was seldom investigated in Setaria italica, an important crop and C4 model plant. In the present study, genome-wide evolutionary analysis of ARFs was performed in S. italica. Twenty-four SiARF genes were identified and unevenly distributed on eight of the nine chromosomes in S. italica. Duplication mode exploration implied that 13 SiARF proteins were originated from whole-genome duplication and suffered purifying selection. Phylogeny reconstruction of SiARFs by maximum likelihood and neighbor-joining trees revealed SiARFs could be divided into four clades. SiARFs clustered within the same clade shared similar gene structure and protein domain composition, implying functional redundancy. Moreover, amino acid composition of the middle regions was conserved in SiARFs belonged to the same clade. SiARFs were categorized into either activators or repressors according to the enrichment of specific amino acids. Intrinsic disorder was featured in the middle regions of ARF activators. Finally, expression profiles of SiARFs under hormone and abiotic stress treatment not only revealed their potential function in stress response but also indicate their functional redundancy. Overall, our results provide insights into evolutionary aspects of SiARFs and benefit for further functional characterization.


Effects of pioglitazone on expressions of matrix metalloproteinases 2 and 9 in kidneys of diabetic rats.
The changes in matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions were examined in the kidneys of diabetic rats to investigate the degradative pathway of collagen type IV (C-IV) and the protective effects of pioglitazone on an experimental model of diabetic nephropathy. In 54 SD rats used in our study, 18 served as normal controls. Diabetes mellitus was induced in 36 age- and weight-matched rats by intraperitoneal injection of streptozotocin (70 mg/kg); 18 of the diabetic rats were allocated at random to receive pioglitazone [20 mg.kg(-1).d(-1)] in their drinking water and 18 served as diabetic controls. Rats were killed after 2, 4, or 8 weeks of treatment. Kidneys were examined pathomorphologically and the expressions of MMP-2, MMP-9, and C-IV were analyzed by immunohistochemistry, and the results were quantified by image analysis techniques. Diabetes mellitus was associated with a decrease in the expression of MMP-2 in the glomeruli (P < 0.05, vs control). By contrast, MMP-2 expression in the interstitium increased, but not significantly (P > 0.05, vs control). The expression of MMP-9 did not show any change when comparing the three groups (P > 0.05, vs control). STZ-diabetic rats were also associated with an increase in the expression of C-IV in the glomeruli and the interstitium (P < 0.05, vs control). All diabetes-associated changes in MMP-2 expression were attenuated by pioglitazone treatment in association with reduced C-IV accumulation. These results indicate that a decrease in MMP-2 expression in the glomeruli of diabetic rats may lead to impairment of C-IV degradation and contribute to the matrix accumulation in diabetic nephropathy. Pioglitazone treatment, which can attenuate the decrease of glomerular MMP-2 and the increase of C-IV degradation, has curative effects on diabetic nephropathy.