Prognostic value of exercise-induced ventricular ectopic activity for mortality after acute myocardial infarction.
To evaluate the importance of ventricular ectopic activity on the predischarge treadmill exercise test for predicting mortality in patients after acute myocardial infarction (AMI), 163 patients with uncomplicated AMI were studied using symptom limited low-level treadmill exercise testing and 24-hour ambulatory electrocardiographic monitoring before hospital discharge. All patients were followed for at least 2 years or until recurrent AMI, coronary artery bypass grafting or death. Seventeen patients (10%) died during the follow-up period, 15 patients (9%) had recurrent AMI and 45 patients (28%) underwent bypass surgery. Ventricular ectopic activity was the only single treadmill abnormality that predicted subsequent cardiac death; angina pectoris, electrocardiographic ST-segment depression and a hypotensive blood pressure response did not. The mortality rate in the 20 patients with exercise-induced ventricular ectopic activity was 25%, compared with 8% in those without (p less than 0.004). Furthermore, in this patient population, exercise-induced ventricular ectopic activity was a much better predictor of cardiac death than that detected by ambulatory monitoring. Thus, ventricular ectopic activity on the predischarge treadmill exercise test is an important risk factor for death after AMI.


The incidence of congenital syphilis in the United Kingdom: February 2010 to January 2015.
To estimate the incidence of congenital syphilis in the UK. Prospective study. United Kingdom. Children born between February 2010 and January 2015 with a suspected diagnosis of congenital syphilis were reported through an active surveillance system. Number of congenital syphilis cases and incidence. For all years, reported incidence was below the WHO threshold for elimination (<0.5/1000 live births). Seventeen cases (12 male, five female) were identified. About 50% of infants (8/17) were born preterm (<37 weeks' gestation): median birthweight 2000 g (865-3170 g). Clinical presentation varied from asymptomatic to acute disease, including severe anaemia, hepatosplenomegaly, rhinitis, thrombocytopaenia, skeletal damage, and neurosyphilis. One infant was deaf and blind. Median maternal age was 20 years (17-31) at delivery. Where maternal stage of infection was recorded, 6/10 had primary, 3/10 secondary and 1/10 early latent syphilis. Most mothers were white (13/16). Country of birth was recorded for 12 mothers: UK (n = 6), Eastern Europe (n = 3), Middle East (n = 1), and South East Asia (n = 2). The social circumstances of mothers varied and included drug use and sex work. Some experienced difficulty accessing health care. The incidence of congenital syphilis is controlled and monitored by healthcare services and related surveillance systems, and is now below the WHO elimination threshold. However, reducing the public health impact of this preventable disease in the UK is highly dependent on the successful implementation of WHO elimination standards across Europe. Congenital syphilis incidence in the UK is at a very low level and well below the WHO elimination threshold.


Adherence to NICU transfusion guidelines: data from a multihospital healthcare system.
We critically reviewed every NICU blood component transfusion (packed erythrocytes, platelets, frozen plasma (FP) and cryoprecipitate) administered during a one-year period. This was done to determine the proportion of transfusions given out of compliance with the Intermountain Healthcare transfusion guidelines, and to look for patterns of non-compliance that could be addressed by quality improvement measures. A detailed review was made of every transfusion administered to patients with a date of birth of 1 January 2006 through 31 December 2006, in any of three level III, perinatal-center-associated NICUs within Intermountain Healthcare. During 2006 the three NICUs cared for 1759 neonates. Seventeen percent of these received one or more (median 3) erythrocyte transfusions, 4% received one or more (median 3) platelet transfusions, 6% received one or more (median 1) FP infusions and 2% received cryoprecipitate (median 1 dose). Seventy percent of the erythrocyte transfusions were given in compliance with the guidelines, as were 69% of the platelet transfusions, 65% of the FP transfusions and 94% of the cryoprecipitate administrations. Patients who received large numbers of transfusions were more likely to receive transfusion that violated the guidelines. Forty-five percent of patients who received 1 to 3 transfusions received all transfusions within guidelines. However, only 18% of patients who received 4 to 10 transfusions received all within guidelines. No patient who received >10 transfusions received all within the guidelines. Erythrocyte transfusions given early in the hospital course were likely to be within guidelines; 72% (588/818) in the first 29 days were compliant with guidelines, but compliance fell to 61% (144/237) for transfusions administered after 29 days (P=0.002). About half of the platelet transfusions given early in the hospital course were in violation of guidelines, but after day 9, 83% of platelet transfusions were compliant with guidelines (P=0.000). Opportunities exist in our healthcare system to improve compliance with our transfusion guidelines. Such opportunities are greatest among neonates receiving multiple transfusions, among those receiving erythrocyte transfusions late in their NICU course and among those receiving platelet transfusions early in their NICU course.


Considering how farm animal welfare concerns may contribute to more sustainable diets.
This paper investigates how consumers can be guided towards healthy diets from sustainable and more animal-friendly food systems, in times when no single food system can be considered the best. In order to provide an alternative, the paper focuses on how farm animal welfare concerns can be translated into potential consumer goals, inspired by the "Three Rs" principles of Replacement, Reduction and Refinement, originally developed to systematically improve the welfare of laboratory animals. After some adaptations, the three goals established are 1) to eat less meat, and/or 2) "less and better" meat, and/or 3) "less worrisome" animal protein, respectively, which imply choices described in the literature on consumer behavior. This literature shows that the goal of eating less meat is relatively straightforward, but needs to be made more prominent, and that the goals of eating "less and better" meat or eating "less worrisome" animal protein need more nuances regarding the specific trade-offs that should be made in terms of species, production types and geographic locations. This may help to better integrate the repercussions of food choices for human health, animal welfare, climate change and biodiversity, the relative importance of which varies between countries and consumer segments. In conclusion, it should be emphasized that Reduction, Replacement and Refinement are not just different parts of the same process to meet human health and animal welfare challenges, but also powerful options to combat the climate, biodiversity and-last but not least-food security challenges of the next few decades.


Gemcitabine sensitizes pancreatic cancer cells to the CTLs antitumor response induced by BCG-stimulated dendritic cells via a Fas-dependent pathway.
There are increasing evidences suggesting that chemotherapeutic agents can enhance the cytotoxic T lymphocytes (CTLs) antitumor effect, but the precise mechanism is not fully explained. This study aims to investigate whether gemcitabine (GEM) can sensitize pancreatic cancer cells to the CTLs antitumor response, and explore the potential mechanism. Cell counting kit-8 assays (CCK-8) were performed to determine the tumor cell proliferation. Flow cytometric analysis was conducted to analyze maturation of DCs and the expression of Fas. An Annexin V FITC Apoptosis Detection Kit was performed to detect tumor cell apoptosis. CytoTox 96 Nonradioactive Cytotoxicity assays were used to determine T cell-mediated tumor cell lysis. First, it was demonstrated that Bacillus Calmette Guérin (BCG) could be used to induce effective CTLs antitumor response. Then, GEM inhibited the growth of SW1990 cells, induced apoptosis and upregulated the Fas expression even at a low concentration. When antagonistic anti-Fas mAb ZB4 was preincubated with GEM-treated SW1990 cells, the lysis induced by CTLs was reduced. Moreover, agonistic anti-Fas mAb CH11 induced more apoptosis of GEM-treated SW1990 cells. Our results show that GEM sensitizes pancreatic cancer cells to the CTLs antitumor response, and the sensitization is associated with upregulation of Fas on pancreatic cancer cells.


Exploring the potential of third-generation microalgae bio-alcohol and biodiesel in arresting particulate smoke emissions and greenhouse gases using CART.
Due to the rise in vehicular emissions, the rapid deterioration of the atmospheric air quality is a cause for concern in a global scale. In this context, the objective of this study is to explore the effect of post-injection parameters on a continuous active regeneration trap (CART) to mitigate harmful greenhouse gases (GHG) and particulate smoke emissions (PSE) using diesel fuel reformulated by long-chain microalgae bio-alcohol and low-density microalgae biodiesel. Furthermore, the efficiency of the CART unit is analyzed based on its ability to mitigate the harmful emissions without sacrificing the engine performance characteristics. From the study, it was observed that the maximum de-smoke efficiency of 67.85% is observed at a post-injection timing (PIT) of 20°CA aTDC at a post-injection mass (PIM) of 4 mg for low load condition while operating on microalgae biodiesel. While operating on microalgae bio-alcohol, the maximum de-smoke CART efficiency was observed as 67.25% and 55.78% for low and medium load conditions at a PIT and PIM of 20°CA aTDC and 2 mg while operating on the microalgae bio-alcohol. Likewise, the maximum de-HC CART efficiency was obtained at a PIT and PIM of 10°CA aTDC and 1 mg with a reduction of about 75% and 73.8% for medium and high load conditions. A slight reduction in oxides of nitrogen with the complete elimination of carbon monoxide emissions is observed after CART treatment for both the fuels.


Pituitary stalk section transiently impairs the acquisition of shuttle box avoidance behavior.
Three days after stalk section, rats displayed a marked deficit in acquiring a shuttle box avoidance response. The performance of stalk sectioned rats was similar to that of 3-day hypophysectomized rats. At eighteen days after stalk section acquisition of the avoidance response was, however, not different from that of sham-operated controls. Stalk sectioned rats that showed poor performance at three days and that were tested again at eighteen days displayed similar avoidance behavior at eighteen days as their sham-operated controls. The results suggest that pituitary stalk section impairs performance of an active avoidance response. The transient nature of this effect may be due to disruption and subsequent regeneration of vascular contact between pituitary and brain.


Persisting right-sided chylothorax in a patient with chronic lymphocytic leukemia: a case report.
Chylothorax caused by chronic lymphocytic leukemia is very rare and the best therapeutic approach, especially the role of modern immunochemotherapy, is not yet defined. We present the case of a 65-year-old male Caucasian patient with right-sided chylothorax caused by a concomitantly diagnosed chronic lymphocytic leukemia. As first-line treatment four cycles of an immunochemotherapy, consisting of fludarabine, cyclophosphamide and rituximab were administered. In addition, our patient received total parenteral nutrition for the first two weeks of treatment. Despite the very good clinical response of the lymphoma to treatment, the chylothorax persisted and percutaneous radiotherapy of the thoracic duct was applied. However, eight weeks after the radiotherapy the chylothorax still persisted and our patient agreed to a surgical intervention. A ligation of the thoracic duct via a muscle sparing thoracotomy was performed, resulting in a complete cessation of the pleural effusion. Apart from the first two weeks our patient was treated on an out-patient basis for nearly six months. In this case of chylothorax caused by chronic lymphocytic leukemia, immunochemotherapy in combination with conservative treatment, and even consecutive radiotherapy, were not able to stop pleural effusion, despite the very good clinical response of the chronic lymphocytic leukemia to treatment.Out-patient management using repetitive thoracocenteses can be safe as bridging until definitive surgical ligation of the thoracic duct.


Cytotoxic activity of ex-vivo generated IFNα-induced monocyte-derived dendritic cells in brain glioma patients.
Recent studies have revealed that besides the important role in triggering the adoptive antitumor immunity, dendritic cells (DCs) possess direct cytotoxic antitumor activity. Here, we investigated brain glioma patient monocyte-derived DCs generated in the presence of IFNα and GM-CSF (IFN-DCs). These DCs were characterized by reduced cytotoxic activity against TRAIL-resistant HEp-2 cells. The impairment of DC cytotoxic function was observed mainly in high-grade glioma patients and associated with poor survival. The dysfunction of patient DC cytotoxicity was partially restored under in vitro pretreatment of DCs with double-stranded human DNA as well as rIL-2. In contrast to healthy donors, IFN-DCs in a part of high-grade glioma patients also failed to lyse primary autologous or allogeneic glioma cells. Our findings point to possible contribution of DC impairment in tumor pathogenesis in brain glioma and justify the necessity to evaluate and correct DC cytotoxic function when exploring DCs as cancer vaccines in glioma.


Fasting and postprandial regulation of the intracellular localization of adiponectin and of adipokines secretion by dietary fat in rats.
Dietary fat sources modulate fasting serum concentration of adipokines, particularly adiponectin. However, previous studies utilized obese animals in which adipose tissue function is severely altered. Thus, the present study aimed to assess the postprandial regulation of adipokine secretion in nonobese rats that consumed high-fat diet (HFD) composed of different types of fat for a short time. The rats were fed a control diet or a HFD containing coconut, safflower or soybean oil (rich in saturated fatty acid, monounsaturated fatty acid or polyunsaturated fatty acid, respectively) for 21 days. The serum concentrations of adiponectin, leptin, retinol, retinol-binding protein-4 (RBP-4), visfatin and resistin were determined at fasting and after refeeding. Adiponectin multimerization and intracellular localization, as well as the expression of endoplasmic reticulum (ER) chaperones and transcriptional regulators, were evaluated in epididymal white adipose tissue. In HFD-fed rats, serum adiponectin was significantly decreased 30 min after refeeding. With coconut oil, all three multimeric forms were reduced; with safflower oil, only the high-molecular-weight (HMW) and medium-molecular-weight (MMW) forms were decreased; and with soybean oil, only the HMW form was diminished. These reductions were due not to modifications in mRNA abundance or adiponectin multimerization but rather to an increment in intracellular localization at the ER and plasma membrane. Thus, when rats consumed a HFD, the type of dietary fat differentially affected the abundance of endoplasmic reticulum resident protein 44 kDa (ERp44), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ (PPARγ) mRNAs, all of which are involved in the post-translational processing of adiponectin required for its secretion.Leptin, RBP-4, resistin and visfatin serum concentrations did not change during fasting, whereas modest alterations were observed after refeeding. The short-term consumption of a HFD affected adiponectin localization in adipose tissue, thereby decreasing its secretion to a different magnitude depending on the dietary fat source. Evaluating the fasting serum concentration of adipokines was not sufficient to identify alterations in their secretion, whereas postprandial values provided additional information as dynamic indicators.


Retinal wholemounts: a simple method for precise mapping.
A simple and inexpensive method to analyse retinal wholemounts is described. It allows the definition of regularly spaced sites to map regional specializations of the retina under light microscopy. After attaching a piece of translucent millimetre graph paper behind the slide holding the preparation, the two grid patterns of the graph paper and of the eye-piece grid are used in combination for the definition of sites for analysis and the return to specific areas as small as 50-100 microns2. The present method is simpler and offers several advantages when compared to others based on X-Y movements of the microscope stage or on photographic montage.


Milestones in the development of cardioplegia.
Long before there was a possibility for the application of cardioplegia to clinical situations, physiologists and surgeons studied the influence of various cations on function of the myocardial cell. These monumental studies helped set the stage for the eventual practical application of various means of myocardial preservation once open cardiac surgical techniques became available. This presentation attempts to summarize early research effort from the work of Sidney Ringer in 1878 until the present time. The historical progression of myocardial protective strategies is reviewed in a sequential fashion, highlighting major contributions and practices of investigators at the time. It is hoped that such a review of the accomplishments of our colleagues past and present will improve our perspective regarding current applications of such knowledge and that it may stimulate further inquiry toward improving present-day myocardial preservation strategies.


A community mental health innovation in mass media preventive education: the alternatives project.
An innovative mental health primary and secondary prevention program employing mass media was conducted in the Louisville metropolitan area. For 60 weeks during public service announcement time slots, 21 educational mental health and mental retardation messages were aired on local major radio and television stations. Three project goals were established: (a) improved mental health attitudes; (b) increased awareness of community mental health resources; and (c) increased utilization of community mental health resources. Systematic evaluation, based on data from client-initiated telephone contacts and surveys of the community, indicated that the project appeared to be successful in increasing awareness and utilization of community mental health resources. Positive change was indicated, overall, for attitudes related to cognitive structuring of problem situations. Attitudes related to behavioral resolution of problem situations appeared to be generally uninfluenced. Implications and future directions for the utilization of mass media in community mental health are discussed.


The nevus comedonicus syndrome: a case report with emphasis on associated internal manifestations.
A 14-year-old boy with nevus comedonicus, multiple congenital abnormalities of the spine, and a central nervous system disorder is described. The associated abnormalities previously reported with nevus comedonicus are summarized. Thorough evaluation of patients with nevus comedonicus may disclose the occurrence of certain internal abnormalities in syndromic association.


Orthodontic repositioning of a lingually positioned transmigrated mandibular canine.
This case report presents the successful orthodontic repositioning of a transmigrated and lingually positioned mandibular canine with conventional mechanics. Treatment began with the aim of creating space for the four permanent canines that had not yet erupted. Cervical headgear, mesial slice, and extraction of the deciduous teeth were executed, but only the right canines erupted; moreover, the mandibular left canine had become lingually transmigrated. Multibracket therapy was performed with the orthodontic repositioning of both left canines in 2 steps. They were repositioned, and good alignment was obtained. To our knowledge, this is the first case report describing the orthodontic repositioning of a lingually transmigrated canine with conventional double-arch mechanics. This treatment was successful and without significant complications, even though this approach can be challenging and time-consuming.


Mechanical behavior of the human lumbar spine. I. Creep analysis during static compressive loading.
The in vitro viscoelastic "creep" behavior was examined in 18 cadaveric human lumbar motion segments subjected to static axial compressive loads. Axial deformation was followed for 30 min under constant applied load. Compressive material constants (moduli and viscosity coefficients) were then determined for each intervertebral disc using a linearization method based on a Taylor series expansion of experimental data for the "three parameter" viscoelastic creep model. The degree of disc degeneration and bone mineral content (BMC) were also assessed. Good correlation between the experimentally determined and model predicted strain values were found, with the average error less than 1%. We found that motion segments from older and more degenerated lumbar discs were less stable and had lower material constants than segments from younger and less degenerated discs. Material constants and BMC correlated closely, suggesting that an interdependency of disc and vertebral body properties exists. No correlation between the creep characteristics and disc height, disc area, segment level, or sex were noted.


Perseverative and compulsive-like staring causes uncertainty about perception.
Earlier studies have found that perseverative checking provokes memory distrust for checked stimuli, suggesting that compulsive checking is a counter-productive strategy to increase memory confidence. Obsessive Compulsive (OC) uncertainty also occurs for functions other than memory, like perception. Uncertainty about perception in OC patients gives rise to prolonged attending to the issues that patients feel uncertain about. In an experiment with 40 healthy volunteers, it was tested whether OC-like, perseverative (visual) attending induces OC-like experiences of dissociation and perceptual uncertainty. Participants had to look at an object (a gas stove or a light bulb) during a pre-test and a post-test. In between these tests, participants in the experimental condition were asked to stare at an object that was the same as the to-be-looked-at object during the pre/post-tests. Participants in the control condition stared at an object that was different from the object they looked at during pre/post-test. Both in the experimental and control conditions, dissociation was observed; the effects were equally strong. Critically, with regards to OC-like perceptual uncertainty, the effects were significantly stronger in the experimental condition. The findings indicate that OC-like perseveration induces distrust, not only about memory, but also about perception. To explain the results, we suggest that perseveration interferes with spreading of activation and that cognitive uncertainty (and possibly derealisation) is the experiential end-product of perseveration. It is suggested that all forms of OC perseveration share such interference and that all undermine confidence in cognitive operations.


Adaptive branching in evolution and epigenesis.
We describe one of the simplest models that exhibit an adaptive branching behaviour. It is analysed both experimentally and formally, and its successive bifurcations provide a good model of what R. Thom called 'generalized catastrophes'. Two theorems on the stochastic adaptivity of the algorithm to very general shapes of target are given. The model further displays the phenomenon of abortive branching: each macroscopic branching appears after a burst of microscopic branchings that stop growing after a very short time. The mathematical analysis of the model explains why and how this behaviour occurs. Possible applications of these models to Evolution (natural and artificial) and Epigenesis are briefly mentioned, and a higher dimensional version is applied to growing a tree in a space of shapes in the context of a database of medical images.


Drought and biodiversity in Grasslands.
The local species richness of four different grassland fields fell an average of 37% during a 1988 drought that decreased above-ground living plant mass by an average of 47%. Despite the return to more normal plant mass and precipitation during the next two years, there was no significant recovery in species richness in the 46 permanent plots, suggesting that local species richness became recruitment limited. The drought led to the loss of annual species independent of their abundance. For perennial grasses, perennial forbs, legumes and woody species, the probability of a species being lost from a plot was significantly negatively correlated with its predrought abundance. These results demonstrate that environmentally extreme conditions can limit species richness by causing the local extinction of rare species. Because droughts of this intensity occur about every 50 years in the prairie, periodic drought may have limited prairie diversity. Moreover, if the accumulation of greenhouse gases leads to a more variable or extreme climate, it could cause increased rates of species extinctions.


Diphenyleneiodonium, an NAD(P)H oxidase inhibitor, also potently inhibits mitochondrial reactive oxygen species production.
Diphenyleneiodonium (DPI) has frequently been used to inhibit reactive oxygen species (ROS) production mediated by flavoenzymes, particularly NAD(P)H oxidase. This study was undertaken to examine if DPI could also inhibit production of superoxide and H2O2 by mitochondria, the major source of cellular ROS. Detection of mitochondrial superoxide by lucigenin-derived chemiluminescence (CL) with unstimulated monocytes/macrophages showed that DPI at concentrations that inhibit NAD(P)H oxidase markedly diminished the production of superoxide by mitochondrial respiration. Similarly, the extracellular H2O2 derived from mitochondrial respiration as detected by luminol-derived CL in the presence of horseradish peroxidase was also greatly reduced by DPI. DPI was as potent as rotenone in inhibiting the production of superoxide and H2O2 by mitochondrial respiration. With substrate-supported isolated mitochondria, DPI was shown to reduce mitochondrial superoxide production probably through inhibiting NADH-ubiquinone oxidoreductase (complex I).


Expansion of mossy fibers and CA3 apical dendritic length accompanies the fall in dendritic spine density after gonadectomy in male, but not female, rats.
Androgen loss is an important clinical concern because of its cognitive and behavioral effects. Changes in androgen levels are also suspected to contribute to neurological disease. However, the available data on the effects of androgen deprivation in areas of the brain that are central to cognition, like the hippocampus, are mixed. In this study, morphological analysis of pyramidal cells was used to investigate if structural changes could potentially contribute to the mixed cognitive effects that have been observed after androgen loss in males. Male Sprague-Dawley rats were orchidectomized or sham-operated. Two months later, their brains were Golgi-impregnated for morphological analysis. Morphological endpoints were studied in areas CA3 and CA1, with comparisons to females either intact or 2 months after ovariectomy. CA3 pyramidal neurons of orchidectomized rats exhibited marked increases in apical dendritic arborization. There were increases in mossy fiber afferent density in area CA3, as well as robust enhancements to dendritic structure in area CA3 of orchidectomized males, but not in CA1. Remarkably, apical dendritic length of CA3 pyramidal cells increased, while spine density declined. By contrast, in females overall dendritic structure was minimally affected by ovariectomy, while dendritic spine density was greatly reduced. Sex differences and subfield-specific effects of gonadal hormone deprivation on the hippocampal circuitry may help explain the different behavioral effects reported in males and females after gonadectomy, or other conditions associated with declining gonadal hormone secretion.


Establishment and characterization of Xenopus oviduct cells in primary culture.
Based on a previously established procedure for Xenopus hepatocytes, we describe tubular oviduct cells in primary culture which continue to secrete substantial quantities of egg jelly for several days, as can be visualized microscopically. Freshly isolated cells exhibited a culture shock response [A. P. Wolffe, J. F. Glover, and J. R. Tata (1984) Exp. Cell Res. 154, 581], from which they recovered by the third day in culture. This recovery was characterized by (a) the diminished synthesis of heat shock proteins hsp 70 and hsp 85, (b) the cessation of the drop in number of estrogen receptor, and (c) the enhanced rate of synthesis of cellular and secreted proteins. The oviduct estrogen receptor had the same characteristics as those in other estrogen target tissues and was present in the same amount as in adult female Xenopus hepatocytes [A. J. Perlman, A. P. Wolffe, J. Champion, and J. R. Tata (1984) Mol. Cell. Endocrinol. 38, 51]. Unlike the latter in primary culture [M. P. R. Tenniswood, P. F. Searle, A. P. Wolffe, and J. R. Tata (1983) Mol. Cell. Endocrinol. 30, 329], oviduct cell cultures did not actively metabolize either estradiol or progesterone (t1/2 approximately equal to 55 and 7 h, respectively). The successful establishment and characterization of primary cultures of both liver and oviduct cells now fulfil the conditions required for investigating the basis for tissue specificity of regulation by estrogen of Xenopus egg protein gene expression in primary cell culture.


Touching on translation.
During the last decade, the idea of a "translational" approach has become commonplace within the field of neuroscience. Despite the rapid adaptation of this theoretical framework, few examples of hypothesis-driven translation start with a pre-clinical finding and end with a positive clinical result and no examples of a novel medication have been developed in this way for the treatment of cognition-related disorders. Whereas instances of successful translation exist, most of these are the result of post-hoc hypothesis testing, rather than a priori hypothesis creation. Indeed, part of this disconnection between pre-clinical and clinical results has been driven by paradigms used at both the pre-clinical level (measurement of behaviors that might not be relevant to a patient population) and the clinical level (use of test batteries that cannot be modeled in a pre-clinical environment). However, automated cognition batteries that require responses to stimuli displayed upon a video monitor are decreasing the distance between pre-clinical and clinical behavioral studies. In the last 5 years, numerous papers have been published demonstrating that cognitive functions can be measured in a similar manner in the rodent as in a clinical setting via touch-screen-equipped operant boxes. Here, we argue that the touch-screen approach has the potential of being a powerful tool for the translation of pre-clinical hypotheses into positive clinical findings.


Solitary fibrous tumor of the pleura: ultrasonographic imaging findings of 3 cases.
Solitary fibrous tumor (SFT) of the pleura is a rare tumor of mesenchymal origin. Although radiographic findings of thoracic computed tomography and magnetic resonance imaging in the evaluation of SFTs of the pleura have been documented, the value of ultrasonography is uncertain. We presented the ultrasonographic findings of 3 pathologically proven cases of SFTs arising from the visceral pleura. In all the cases, thoracic ultrasonography demonstrated homogeneous, hypoechoic, hemicycle, extrapulmonary lesions, which showed respiratory movement with the adjacent lung, consistent with pedunculated tumors. Preoperative thoracic ultrasonography could be useful in the evaluation of patients with pleural tumors, especially SFTs.


A comparison of analogue and digital techniques in upper gastrointestinal examinations: absorbed dose and diagnostic quality of the images.
This study was performed to investigate whether patient exposure and diagnostic quality of the image is significantly influenced by the introduction of digital image acquisition techniques. Evaluation was performed for three different techniques (analogue, analogue fluoro + digital radiography, digital) in examination of the upper gastrointestinal tract. The evaluation was done from data acquired in three different departments. Patient exposure was recorded as KERMA-area product (KAP) and the individual patient readings were normalised to a standard size patient. Image quality was assessed using visual grading with a reference image. The recorded KAP values were significantly higher (22.3 Gycm2) for the fully digital technique compared to the others (analogue 6.8 Gycm2, analogue + digital 3.6 Gycm2). This was due mostly to an increased number of exposures. The diagnostic quality of the image was, however, also regarded to be slightly lower for the technique giving the lowest patient dose with the smallest number of exposures (analogue + digital). The digital examination technique, as used in this study, thus resulted in significantly higher patient dose without any significant gain in diagnostic quality of the image.


The war within: a personal account of coping with systemic lupus erythematosus.
Coping with a serious illness is a hardship both for patients and their loved ones. In this article, insight into the seriously ill patient is provided through the chronicle of a sufferer of systemic lupus erythematosus. It is presented here for the benefit of social workers and health care professionals who may aid such patients.


Mosaic trisomy 2 in myelodysplastic syndromes and acute myeloblastic leukemias.
We present a short report here of two more patients with trisomy 2 as the sole chromosomal abnormality in a hematologic malignancy. Although trisomy 2 is a recognized abnormality in neoplasms, particularly hepatoblastomas, to the best of our knowledge only three other cases have been reported with trisomy 2, in patients with a hematologic malignancy. The two cases presented here of myelodysplastic syndrome transforming to acute myeloblastic leukemia and chronic myelomonocytic leukemia showed trisomy 2 as the sole abnormality.


Management of preseptal and orbital cellulitis.
Orbital cellulitis describes an infection involving the soft tissues posterior to the orbital septum, including the fat and muscle within the bony orbit. This condition may be associated with severe sight and life-threatening complications. Despite significant advances in antimicrobial therapies and diagnostic technologies, the management of orbital cellulitis often remains challenging, and rapid diagnosis and prompt initiation of therapy are important in minimizing complications and optimizing outcomes. This review summarizes the distinctive characteristics of preseptal and orbital cellulitis, with a focus on anatomic considerations, predisposing conditions, approaches to evaluation, and management strategies.


Design of a Dynamic Force Measurement System for Training and Evaluation of Suture Surgical Skills.
The aim of this study is to present the SurgeForce system, a tissue handling training device for analysis of dynamic force applied to the tissue and objective assessment of basic surgical skills during the suture process. The SurgeForce system consists of a mechanical base formed by two platforms joint with three stainless steel springs and a three axial digital accelerometer attached to the upper platform, which detects the dynamic force caused by a surgeon when performing a suture task over a synthetic tissue pad. Accelerometer data is sent to a control unit where preprocessing to transform the raw data into a force signal is done, and then, the force signal is sent to a computer application, which register the force exerted over the synthetic tissue pad. For validation, 17 participants (6 surgeons and 11 medical students) performed three simple interrupted sutures with knot tying using the SurgeForce system. Ten force-based metrics were proposed to evaluate their performance during the suturing task. Results of the validation showed statistical differences in 8 of 10 force-based parameters for assessment of basic surgical skills during the suture task. The SurgeForce system demonstrated its capacity to differentiate force-based performance of surgeons and medical students. The SurgeForce system has been successfully validated. This system was able to distinguish force performance between experts and novices, showing its potential to distinguish surgeons with basic suture skills from those who are not yet prepared.


Evaluation of facial soft tissue parameters for Palestinians using Holdaway analysis.
The aims of this study were to evaluate soft-tissue measurements for a Palestinian sample population with normal occlusion by Holdaway's analysis, and to check the applicability of Holdaway values to the Palestinian population. Normal Holdaway values for Palestinians will be established if their parameters do not match those of Holdaway. Cephalometric radiographs of 93 Palestinian university students with normal occlusion (63 women, mean age: 20.1 ± 2.1 years; 30 men, mean age: 20.2 ± 2.4 years) were traced and evaluated. Cephalometric landmarks were located according to Holdaway analysis. Ten linear and two angular measurements were produced on each radiograph. The soft-tissue measurements for the Palestinians were similar to the Holdaway norms, except for the soft-tissue convexity angle and soft-tissue chin thickness, which were larger than the Holdaway averages. The Palestinian sample had a narrower range for normal nose prominence, as well as thicker lips, deeper superior and inferior sulci, and thicker soft-tissue chins than the Holdaway values. We determined normal values for the Holdaway soft-tissue analysis for Palestinians, which are appropriate for use in orthodontic practices in these territories.


The divergent ventilatory and heart rate response to moderate hypercapnia in infants with apnoea of infancy.
Inspired CO2 is a potent ventilatory stimulant exhibiting a paradoxical inhibitory effect on breathing at high concentrations. Severe respiratory depression as a result of CO2 rebreathing during sleep has been implicated as a possible trigger factor in sudden infant death syndrome (SIDS). To investigate the ventilatory and heart rate (HR) responses to inhaled CO2 in infants with apnoea of infancy, a group believed to be at increased risk of SIDS. Thirty one infants with severe sleep related apnoea, 31 infants with mild recurrent apnoea, and 31 age and sex matched controls for the infants with severe sleep related apnoea were studied. HR was computed from digitised RR intervals, "ventilation" was recorded by inductance plethysmography, and PCO2 and PO2 were monitored by transcutaneous electrodes. The ventilatory and HR responses to CO2 were expressed as percentage increase in ventilation and change in HR/unit change in transcutaneous PCO2. The mean increase in transcutaneous PCO2 during CO2 challenge (0.45 kPa = 3.4 mm Hg) resulted in a mean increase in ventilation of 291%/1 kPa (7.3 mm Hg) increase in transcutaneous PCO2, with no difference between the groups. A significant difference between infants with severe sleep related apnoea and mild recurrent apnoea versus controls (p < 0.02, p < 0.01, respectively) was found in their HR response to CO2 challenge: HR decreased in 12 severe sleep related apnoea infants and 10 infants with mild recurrent apnoea, but only in two controls. Infants with apnoea of infancy frequently show a paradoxical decrease in HR during CO2 challenge, possibly because of an insufficient ability to mobilise cardiovascular defence mechanisms when challenged with hypercapnia.


BimEL-dependent apoptosis induced in peripheral blood lymphocytes with n-butyric acid is moderated by variation in expression of c-myc and p21(WAF1).
We have examined the effect of sodium butyrate (SB) on the viability of normal peripheral blood lymphocytes (PBLs) in vitro and the effect of this agent on the expression of 20 apoptosis-related genes. Data suggest that PBL treated with 2 mmol L(-1) SB resisted for at least 8 h the destructive activity of the agent, but eventually 30% of cells died within 72 h. As documented by flow cytometry and cytochrome c release study, cells underwent mitochondrial-derived apoptosis. While the expression of the majority of genes examined by RT-PCR and Western blots remained indifferent to 2 mmol L(-1) SB, the cellular levels of BimEL, c-myc, p53, and p21(WAF1) varied profoundly with the time of SB treatment. The Bax activator BimEL increased rapidly, driving cells toward apoptosis likely controlled by c-myc and p21(WAF1) activities. The c-myc, exercising the role of mediator of the function of BimEL and inhibitor of p21(WAF1) expression, decreased significantly for several hours after adding SB but within 48 h it returned to close to its original value. An apoptosis inhibitor and executive caspase substrate p21(WAF1) increased early at the beginning of treatment but subsequently, within a time frame of 72 h, profoundly dropped in terms of both a caspase-dependent and caspase-independent way. We suggest that variations in c-myc and p21(WAF1) expression delay apoptosis making PBL resistant to SB for several hours, and together with fast catabolism of SB in vivo protect PBL against the destructive activity of this anti-cancerous metabolite of colonic bacteria.


Correction to: Shuangxia decoction alleviates p-chlorophenylalanine induced insomnia through the modification of serotonergic and immune system.
The original article contains mistake. The authors want to add Wenhui Pei as first co-author and Fang Fang as co-corresponding author.


[Gynecological-obstetrical psychosomatics (theoretical and practical considerations on education)].
Theoretical concepts of psychosomatics are presented in the first section with special emphasis on psychosomatics in gynecology and obstetrics. In the second part, some examples are presented to demonstrate the realization of psychosomatic thinking in the setting of a university clinic. Arising difficulties are discussed.


Monitoring the Instant Creation of a New Fluorescent Signal for Evaluation of DNA Conformation Based on Intercalation Complex.
Here we report the monitoring the instant creation of a new fluorescent signal (FS) aroused from a positively charged water-soluble fluorogenic probe, ethidium bromide (EtBr) in the presence of a radical initiator, ammonium persulfate (APS) and an accelerator, tetraethylmetilendiamine (TEMED) for evaluation of deoxyribonucleic acid (DNA) conformation. The results revealed that the occurred FS (λex = 430 nm; λmax = 525 nm) is a reduced form of EtBr (λex = 480 nm; λmax = 617 nm) and it is completely distinct from hydroethidine (λex = 350 nm; λmax = 430 nm), which is two-electron reduced form of EtBr. It was noticed that EtBr was reduced to a new FS during the polymerization of N, N dimethyacrylamide (DMAA) too, at 25 °C in the presence of APS and TEMED or at 55 °C with only APS, and the rate of formation of FS was increased upon treatment time. The effect of nanoclays such as Laponite XLG® and Laponite XLS®, which provide a protective environment for DNA in nature, were also investigated through the reduction process of EtBr in the absence and presence of a water soluble monomer DMAA. We demonstrated that DNA conformation might be evaluated by monitoring FS effectuated during the reduction of EtBr in the presence of nanoclays having positively and negatively charged surfaces. Protective property of DNA against the formation of reduced product was elucidated by carrying out the polymerization at 55 °C. The results revealed that the monitoring of formation of FS in the presence of radical initiator could lead to elucidate the conformation of DNA upon formation of intercalator complex.


Sharp bounds on the relative treatment effect for ordinal outcomes.
For ordinal outcomes, the average treatment effect is often ill-defined and hard to interpret. Echoing Agresti and Kateri, we argue that the relative treatment effect can be a useful measure, especially for ordinal outcomes, which is defined as γ=pr{Yi(1)>Yi(0)}-pr{Yi(1)<Yi(0)} , with Yi(1) and Yi(0) being the potential outcomes of unit i under treatment and control, respectively. Given the marginal distributions of the potential outcomes, we derive the sharp bounds on γ, which are identifiable parameters based on the observed data. Agresti and Kateri focused on modeling strategies under the assumption of independent potential outcomes, but we allow for arbitrary dependence.


A rare case of regressively changed lipomatous hypertrophy of the interatrial septum presenting with anemia and recurrent fever.
Lipomatous hypertrophy of the interatrial septum (LHIS) is characterized by excessive accumulation of adipose tissue within some segments of the interatrial septum. Only one published case so far describes fever as a presenting feature of LHIS. On the other hand, systemic symptoms including anemia and fever are well-known clinical presentations of cardiac myxomas. We report an unusual case of a 79-year-old woman who was thoroughly but unsuccessfully investigated for recurrent fever and anemia in several specialized departments over the course of 4 years. Computed tomography scan showed a pathological mass localized in the interatrial septum and spreading to ascending aorta. Histological analysis of the biopsy samples from surgery revealed the unexpected diagnosis of regressively changed LHIS. We discuss the clinical and pathologic features of this lesion suggesting that its regressive changes may be associated with inflammation and can cause systemic symptoms such as fever and anemia.


A historical study of American patients with anti-neutrophil cytoplasmic antibody negative pauci-immune glomerulonephritis.
Anti-neutrophil cytoplasmic antibodies (ANCA) play an important role in the pathogenesis of ANCA-associated vasculitis. The lack of ANCA antibodies may indicate a variation in clinical presentation and outcomes of this disease. We identified 74 adult patients between 1995 and 2009 with the diagnosis of pauci-immune glomerulonephritis. Demographics, histological features, and treatment outcomes were compared between ANCA-positive and ANCA-negative patients. These factors were correlated with renal function at presentation and follow-up. Of the 74 patients, 57 were ANCA-positive, and 17 were ANCA-negative. Demographics and mean Birmingham Vasculitis Activity Score were similar between ANCA-negative and ANCA-positive patients at presentation. Renal function was significantly worse at presentation in the ANCA-negative patients (eGFR 16.59 vs. 31.89 ml/min/1.73 m(2), p = 0.03). Patients in the ANCA-negative group had a significantly higher interstitial fibrosis score compared to the ANCA-positive group (2.1 vs.1.6, p = 0.04). The median time to remission was shorter in the ANCA-negative patients (51 vs. 78 days, p = 0.01). Long-term renal function and 1-year patient and renal survival were similar between ANCA-negative and ANCA-positive patients. Baseline eGFR, percentage of normal glomeruli, glomerular sclerosis, and tubulointerstitial scarring predicted eGFR at 1 year in both groups similarly. This is the first historical review of American patients with pauci-immune glomerulonephritis, comparing patients with ANCA-negative and ANCA-positive serology. Although ANCA-negative patients present with lower eGFR and more interstitial fibrosis, 1-year and long-term outcomes in both groups are similar.


Peripheral and intestinal lymphocyte activation after in vitro exposure to cow's milk antigens in normal subjects and in patients with Crohn's disease.
We studied in Crohn's disease and controls the in vitro activation of either peripheral (PBMNC) or intestinal (LPMNC) mononuclear cells in response to the cow's milk antigen beta-lactoglobulin (Blg). The activation of mononuclear cells was investigated by analyzing the kinetics of the transferrin receptor (T9 antigen) and interleukin 2 receptor (Tac antigen) expression. In both controls and Crohn's disease patients Blg (1 microgram/ml) induced a significant (P less than 0.01) increase of T9 and Tac expression by both PBMNC and LPMNC cultured for 3 days. After Blg exposure the counts of T9- and Tac-bearing cells were significantly (P less than 0.05) higher in PBMNC cultures from healthy controls than in those from patients with Crohn's disease. In both groups peripheral T-enriched cell suspensions did not express T9 and Tac when stimulated with Blg but were restored to express either antigen by the addition of 10% autologous adherent cells. In LPMNC cultures from patients with Crohn's disease the Tac expression after 3 days of Blg stimulation was significantly (P less than 0.05) higher than in the autologous PBMNC. Data from this study indicate that in both controls and patients with Crohn's disease lymphocytes sensitized to Blg occur in the circulation as well as in the gut lamina propria. Our data also suggest that in Crohn's disease an increased proportion of lymphocytes sensitized to Blg are recruited from the circulation into the site of the intestinal lesion.


The lncRNA MALAT1 protects the endothelium against ox-LDL-induced dysfunction via upregulating the expression of the miR-22-3p target genes CXCR2 and AKT.
CXCR2 plays a key role in protecting the integrity of the endothelium. Emerging evidence has demonstrated that the long ncRNAs (lncRNA) Human metastasis associated lung adenocarcinoma transcript 1 (MALAT1) participates in the regulation of the pathophysiological processes. However, whether there is crosstalk between CXCR2 and MALAT1 remains unknown. In this study, we demonstrated that MALAT1 was upregulated in patients with unstable angina. MALAT1 silencing significantly downregulated the expression of the miR-22-3p target gene CXCR2 via reversing the effect of the miR-22-3p, resulting in the aggravation of Oxidized low-density lipoprotein (ox-LDL)-induced endothelial injury; this process was associated with the AKT pathway. Thus, MALAT1 protects the endothelium from ox-LDL-induced endothelial dysfunction partly through competing with miR-22-3p for endogenous RNA.


Management of postcardiotomy hypertension by microcomputer-controlled administration of sodium nitroprusside.
Manual administration of sodium nitroprusside in patients who have undergone cardiac operations can be associated with wide swings in mean systemic arterial pressure. Moreover, it is necessary for constant attention to be paid in order to minimize these potentially catastrophic arterial pressure changes. A microcomputer-based controller was constructed in the belief that it might improve the accuracy of systemic arterial pressure control as well as relieve the clinical staff of a time-consuming task. Comparison was made of the effectiveness of manual control versus computer control of sodium nitroprusside infusion in two groups of patients with similar clinical characteristics. In the manual control group the mean systemic arterial pressure could be maintained within 5 mm Hg of the target pressure only half (52%) of the time. In the computer-controlled group the mean systemic arterial pressure was maintained within 5 mm Hg of the target pressure 94% of the time (p less than 0.005). Thus, computerized control of sodium nitroprusside infusion eliminated the need for an intensive care unit nurse to be "locked into" the task of making frequent adjustments of infusion rate. Of even greater importance, control of mean systemic arterial pressure was more precise.


A Novel Nickel Pincer Complex in the Active Site of Lactate Racemase.
Put through the pincer: A recent study revealed the structure of the Ni-containing active site of lactate racemase. The Ni is coordinated by a SCS pincer ligand derived from a nicotinic acid mononucleotide.


Quantification of trantinterol, its two metabolites and their primary conjugated metabolites in human plasma by ultra-high-performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.
A highly rapid, selective and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to simultaneously determine trantinterol, its major phase-I metabolites and their primary conjugated metabolites in human plasma. Waters Oasis HLB C18 solid phase extraction cartridges were used in the sample preparation. The separation was carried out on an ACQUITY UPLC™ BEH C18 column with methanol/0.2% formic acid (30:70, v/v) as the mobile phase at a flow rate of 0.25 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer in selective reaction monitoring (SRM) mode with the use of an electrospray ionization (ESI) source. The linear calibration curves for trantinterol, tert-butyl hydroxylated trantinterol (tert-OH-trantinterol) and 1-carbonyl trantinterol (trantinterol-COOH) were obtained in the concentration ranges of 0.200-250, 0.108-4.00 and 0.0840-5.02 ng/mL, respectively (r(2)≥0.99). The intra- and inter-day precision (relative standard deviation, RSD) values were less than 13%, and the accuracy (relative error, RE) was within ±9.9%, as determined from quality control (QC) samples for the analytes. The concentrations of conjugated forms of trantinterol and tert-OH- trantinterol in plasma were determined using selective enzyme hydrolysis. The method described herein was fully validated and successfully applied for the pharmacokinetic study of trantinterol in healthy volunteers after oral administration.


Construction and validation of an immune infiltration-related risk model for predicting prognosis and immunotherapy response in low grade glioma.
Low grade glioma (LGG) is considered a heterogeneous tumor with highly variable survival and limited efficacy of immunotherapy. To identify high-risk subsets and apply immunotherapy effectively in LGG, the status and function of immune infiltration in the glioma microenvironment must be explored. Four independent glioma cohorts comprising 1,853 patients were enrolled for bioinformatics analysis. We used ConsensusClusterPlus to cluster patients into four different immune subtypes based on immune infiltration. The immune-infiltration signature (IIS) was constructed by LASSO regression analysis. Somatic mutation and copy number variation (CNV) analyses were performed to explore genomic and transcriptomic traits in the high- and low- risk groups. The correlation between response to programmed cell death 1 (PD-1) blockade and the IIS risk score was confirmed in an in vivo glioma model. Patients were clustered into four different immune subtypes based on immune infiltration, and the high immune infiltration subtype was associated with worse survival in LGG. The high immune infiltration subtype had stronger inflammatory response, immune response and immune cell chemotaxis. The IIS, consisting of EMP3, IQGAP2, METTL7B, SLC1A6 and TNFRSF11B, could predict LGG malignant progression, which was validated with internal clinical samples. M2 macrophage infiltration positively correlated with the IIS risk score. The high-risk group had significantly more somatic mutations and CNVs. The IIS risk score was related to immunomodulatory molecules and could predict immunotherapy clinical benefit. In vivo, immunotherapy-sensitive glioma model exhibited higher IIS risk score and more infiltration of immune cells, especially M2 macrophages. The IIS risk score was decreased in an immunotherapy-sensitive glioma model after anti-PD1 immunotherapy. Different immune subtypes of LGG had unique immune cell infiltration characteristics, and the high immune infiltration subtype was associated with immunosuppressive signaling pathways. A novel IIS prognostic model based on immune infiltration status was constructed for immunophenotypic classification, risk stratification, prognostication and immunotherapy response prediction in LGG.


Macromolecular cytosolic delivery: cell membranes as the primary obstacle.
The "evolution" of a thing, a custom, an organ is thus by no means its progressus toward a goal, even less a logical progressus by the shortest route and with the least expenditure of force, but a succession of more or less profound, mutually independent processes of subduing, plus the resistances they encounter, the attempts at transformation for the purpose of defense and reaction, and the results of successful counteractions. The form is fluid, but the "meaning" is even more so.


Primary diffuse leptomeningeal atypical teratoid rhabdoid tumor (AT/RT) demonstrating atypical imaging findings in an adolescent patient.
Atypical teratoid rhabdoid tumor (AT/RT) is a highly malignant central nervous system embryonal tumor, which typically affects the posterior fossa of young children. Primary diffuse leptomeningeal AT/RT, affecting the leptomeninges without any intraparenchymal mass in the brain and spinal cord, is an extremely rare form of AT/RT. Only 5 such cases have been reported previously, none of which underwent Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET). We herein report a case of primary leptomeningeal AT/RT in an adolescent patient who underwent computed tomography, magnetic resonance imaging and FDG-PET. The computed tomography and magnetic resonance imaging indicated diffusely thickened leptomeninges without any intraparenchymal masses in the head and spine. Furthermore, there were multiple nodules on the thickened leptomeninges. On FDG-PET, the thickened leptomeninges and nodules demonstrated a lower standardized uptake value than that of the normal cerebral cortex. Biopsy and histopathological studies confirmed the diagnosis of AT/RT. Despite its rare occurrence, it is important to recognize primary diffuse leptomeningeal AT/RT for correct diagnosis and management of patients.


Long-term outcome of live donor kidney transplantation for renal amyloidosis.
The short-term outcome of kidney transplantation in patients with amyloidosis has been reported. The aim of this study is to investigate long-term results in patients with renal amyloidosis. We studied results of renal transplantation in 23 amyloidotic transplant recipients compared with those in a control group of 47 nonamyloidotic patients. Amyloidosis was secondary to familial Mediterranean fever (FMF) in 16 patients, whereas it was primary (idiopathic) in 7 transplant recipients. The 2 groups were homogeneous regarding age, sex, HLA matching, immunosuppression, and duration of transplantation. Five- and 10-year actuarial graft survival rates were similar in both groups (79.35% versus 84.04% and 65.92% versus 56.61%, respectively ). Five- and 10-year actuarial patient survival rates also were similar (80% versus 94% and 68% versus 87%, respectively). Moreover, 72.4% of controls experienced at least 1 rejection episode, whereas only 43.5% of amyloidotic transplant recipients experienced 1 or more such events (P = 0.02). Nonetheless, mean serum creatinine concentrations did not differ between the 2 groups during the observation period. Maintenance colchicine therapy prevented the recurrence of both FMF symptoms and amyloidosis. Recurrence was documented in only 1 amyloidotic transplant recipient (4.3%) 10 years posttransplantation. Significant gastrointestinal (GI) problems were more frequent in amyloidotic patients (65% versus 38%; P = 0.03). Amyloidotic patients with GI problems, except for 2 patients, were administered cyclosporine. Eleven of these patients had FMF, which appeared to reflect the effects of both cyclosporine and colchicine. Infections were similar in the groups; whereas amyloidotic patients had significantly lower blood pressures. In our experience, long-term (5 to 10 years) outcome of live related donor kidney transplantation in patients with amyloidosis is similar to that in the general transplant population.


Anti-proliferative and apoptosis inducing effect of nimbolide by altering molecules involved in apoptosis and IGF signalling via PI3K/Akt in prostate cancer (PC-3) cell line.
Prostate cancer is responsible for major deaths globally after lung cancer. Nimbolide is an important constituent of neem, and it acts as a potent inhibitor for many cancer cells. The present study was designed to evaluate the effects of nimbolide on apoptosis and insulin-like growth factor (IGF) signalling molecules in androgen-independent prostate cancer (PC-3) cells line. Nimbolide (0.5-2 μM) treatment resulted in 50% inhibition at a dose of 2 μM in the PC-3 cell line. The mRNA expression of Fas ligand, Fas-associated death domain receptor (FADDR), Bcl-2-associated X protein (Bax), Bcl-2-associated death promoter (Bad), phosphatidylinositide 3-kinases (PI3K), Akt, IGF1, IGF1 receptor (IGF1R) and IGF binding protein 3 were quantified by reverse transcription polymerase chain reaction and protein expression of Bax, cytochrome c, X-linked inhibitor of apoptosis protein (XIAP), B-Cell Lymphoma 2 (Bcl-2), caspases -8, -9, -10 and -3, poly(ADP-ribose) polymerase (PARP), cleaved PARP, IGF1R, PI3K, Akt, p-Akt was determined by western blot analysis, in nimbolide-treated PC-3 cell line. Nimbolide-induced apoptosis by activating DNA fragmentation in PC-3 cells. Nimbolide treatment increased the mRNA of Fas ligand, FADDR, Bax, Bad and IGF binding protein 3, decreased PI3K, Akt, IGF1 and IGF1R, increased protein expression of caspases 8, 3, 10, 9, Bax and cytochrome c and decreased the expression of XIAP, Bcl2, cleaved PARP, p-Akt and IGF1R. The results suggest that nimbolide acts as a potent anti-cancer agent by inducing apoptosis and inhibiting cell proliferation via PI3K/Akt pathway in PC-3 cells.


Estimation and use of recreational fishing values in management decisions.
In many countries, commercial and recreational fishing compete for access to marine resources. In some cases, recreational catch outweighs commercial harvest and may threaten species otherwise protected from commercial fishing. This has led to increasing calls for improved management of recreational fishing in the broader context of general fisheries management. As a result, fisheries managers face the challenge to decide how to allocate the available marine resources between competing uses. In this paper, we review and explain two common approaches that have been used to support recreational fishing allocation decisions. While economic activity analysis is an appropriate tool to assess how a change in resource allocation would affect regional economic activity (economic contributions and impacts), it is ill-suited to assess associated gains or losses in welfare of society as a whole (economic efficiency). Hence, economic activity analysis and social cost-benefit analysis complement each other, with each providing a different set of information answering a different set of questions. Unfortunately, both types of analysis use the term "economic value" suggesting that they are alternative approaches that provide the same information, whereas in fact they are not. If the objective of fishery managers is to ensure that society as a whole is made better off, the appropriate metric is economic value as defined by welfare economics. Under this definition, all goods and services provided by marine resources that are beneficial to humans have economic value. This includes non-use values such as the continued existence of an endangered marine species. The aim of this paper is to support managers and policymakers in allocating marine resources by reviewing relevant economic principles, concepts, and tools in the context of recreational fishing, including the use and challenges of estimating the non-market benefits generated by recreational fishing experiences.


Maternal and perinatal outcomes of pregnant patients with colorectal cancer: a population-based study.
This study aimed to investigate the maternal and perinatal outcomes of pregnant patients with CRC using a large population-based database. A retrospective cohort study was conducted using the Nationwide Inpatient Sample (NIS) from 2009 to 2019. Pregnant patients with and without CRC were compared for demographic characteristics, comorbidities, maternal and perinatal outcomes, and hospital burden. The study included 306 pregnancies with CRC and 40,887,353 pregnancies without CRC. Pregnant patients with CRC were older and more likely to be White. A significant association was observed between CRC and a history of inflammatory bowel disease or a family history of gastrointestinal cancer. Pregnant patients with CRC had higher odds of maternal death (AOR 260.99, 95% CI 33.36-2041.64), cardiac arrhythmia (AOR 13.73, 95% CI 4.21-44.76), acute kidney injury (AOR 32.6, 95% CI 5.29-200.77), severe sepsis (AOR 163.98, 95% CI 22.05-1219.65), and respiratory failure (AOR 31.67, 95% CI 4.11-243.98). Furthermore, the CRC group experienced higher odds of cesarean section (AOR 1.78, 95% CI 1.05-3.03), preterm birth (AOR 4.16, 95% CI 2.05-8.47), and intrauterine death (AOR 13.18, 95% CI 3.33-52.16). Distinct differences in maternal and perinatal outcomes were observed based on the location of CRC. Pregnant patients with CRC faced higher hospital charges and had longer hospital stays during delivery hospitalization compared to those without CRC. Pregnant patients with CRC are at increased risk for adverse maternal and perinatal outcomes, emphasizing the importance of early detection, timely intervention, and comprehensive management during pregnancy.


Scientific Best Practices for Primary Sequence Confirmation and Sequence Variant Analysis in the Development of Therapeutic Proteins.
In this commentary, we will provide a high-level introduction into LC-MS product characterization methodologies deployed throughout biopharmaceutical development. The ICH guidelines for early and late phase filings is broad so that it is applicable to diverse biotherapeutic products in the clinic and industry pipelines. This commentary is meant to address areas of protein primary sequence confirmation and sequence variant analysis where ambiguity exists in industry on the specific scope of work that is needed to fulfill the general guidance that is given in sections Q5b and Q6b. This commentary highlights the discussion and outcomes of two recent workshops centering on the application of LC-MS to primary structure confirmation and sequence variant analysis (SVA) that were held at the 2018 and 2019 CASSS Practical Applications of Mass Spectrometry in the Biotechnology Industry Symposia in San Francisco, CA and Chicago, IL, respectively. Recommendations from the conferences fall into two distinct but related areas; 1) consolidation of opinions amongst industry stakeholders on the specific definitions of peptide mapping and peptide sequencing for primary structure confirmation and the technologies used for both, as they relate to regulatory expectations and submissions and 2) development of fit-for-purpose strategy to define appropriate assay controls in SVA experiments.


Draft genome sequence of mcr-1-mediated colistin-resistant Escherichia coli ST359 from chicken carcasses in Northeastern Brazil.
Considering that polymyxin is a drug of last resort in the treatment of humans infected by multidrug-resistant bacteria, the occurrence of plasmid-mediated colistin resistance mcr gene among Gram-negative bacteria in foods must be investigated. We present herein the draft genome sequence of a phenotypically colistin-resistant Escherichia coli carrying mcr-1 in chicken carcasses from a public market. Total genomic DNA from the strain was sequenced by means of the Illumina MiSeq. The assembled contigs were annotated and manually curated. In silico analyses were performed to detect significant epidemiologic (serotyping and MLST) and structural features related plasmids identification, virulence and resistome. The ST359 E. coli strain presented a conserved 747 bp mcr-1 gene within a 9431 kb contig compatible with the IncX4 plasmid, which has been identified as a key vector for the global dissemination of mcr determinants among Enterobacteriacea. Other genes encoding for multidrug resistance such as blaCTX-M-2 and blaTEM-1B, and the virulence factors astA, cma, gad, iroN, ipfA, mchF were also detected. We reported a draft genome of a colistin-resistant E. coli ST359 associated with an IncX4 plasmid containing the gene mcr-1. The genomic data can be useful in epidemiological and evolutionary investigations on the spread of colistin-resistance among Enterobacteriacea in the food chain.


Short-Coupled Ventricular Fibrillation.
Short-coupled ventricular fibrillation (SCVF) is a distinct phenotype among individuals with unexplained cardiac arrest accounting for 7% to 14% of cases of idiopathic ventricular fibrillation (IVF). VF is typically initiated by a trigger premature ventricular contraction with a short-coupling interval of less than 350 milliseconds. In the absence of specific electrocardiographic features or provocative tests, the diagnosis remains challenging and requires documentation of VF onset. Most cases are diagnosed during follow-up at the time of VF recurrence. SCVF is characterized by a high risk of VF recurrence. Insertion of an implantable cardioverter-defibrillator and quinidine are the keystones of SCVF management.


The impact of torture on interpersonal threat and reward neurocircuitry.
Torture adversely influences emotional functioning, but the neurophysiological mechanisms underpinning its impact are unknown. This study examined how torture exposure affects the neural substrates of interpersonal threat and reward processing. Male refugees with (N = 31) and without (N = 27) torture exposure completed a clinical interview and functional magnetic resonance imaging scan where they viewed fear, happy and neutral faces. Between-group activations and neural coupling were examined as moderated by posttraumatic stress disorder symptom severity and cumulative trauma load. Posttraumatic stress disorder symptom severity and trauma load significantly moderated group differences in brain activation and connectivity patterns. Torture survivors deactivated the ventral striatum during happy processing compared to non-torture survivor controls as a function of increased posttraumatic stress disorder symptom severity - particularly avoidance symptoms. The ventral striatum was more strongly coupled with the inferior frontal gyrus in torture survivors. Torture survivors also showed left hippocampal deactivation to both fear and happy faces, moderated by trauma load, compared to controls. Stronger coupling between the hippocampus and frontal, temporoparietal and subcortical regions during fear processing was observed, with pathways being predicted by avoidance and hyperarousal symptoms. Torture exposure was associated with distinct brain activity and connectivity patterns during threat and reward processing, dependent on trauma exposure and posttraumatic stress disorder symptom severity. Torture appears to affect emotional brain functioning, and findings have the potential to guide more targeted interventions for torture survivors.


Presentation delay in patients affected with exudative age-related macular degeneration.
Presentation delay (i.e. duration of visual symptoms before initial presentation) is an established critical parameter for visual prognosis in patients with exudative age-related macular degeneration (ARMD) considering the natural history of the disease and the limitations of current treatments. The purpose of this study was to determine the duration of presentation delay and its evolution in two periods 4 years apart. Presentation delay in 1598 patients affected with exudative ARMD was retrospectively reviewed during two similar 8-month periods in 1994 and 1998 in a tertiary referral center. The proportions of patients examined either within 1 month, between 1 and 3 months, and between 3 and 6 months after onset of symptoms, respectively, increased between 1994 and 1998 from 23% to 33%, from 27% to 32.5%, and from 14% to 18.5%. The proportions of patients examined between 6 and 12 months and after 12 months decreased from 16% to 12% and from 20% to 4%, respectively. Furthermore, the proportion of patients presenting with a first eye involvement during the first month following the onset of symptoms rose from 42% in 1994 to 52% in 1998. All these differences were statistically significant. This first specific review of presentation delay in exudative ARMD showed a significant decrease in this parameter between 1994 and 1998 that should be taken into account when assessing the overall evolution of visual outcome. Further studies are warranted to ascertain that these findings reflect a global improvement in the management of macular diseases.


Recent progress in ellagitannin chemistry.
Continuing studies on the total synthesis of ellagitannin plant metabolites have led to the preparation of the dimeric antitumor compound, coriariin A, as well as designed structural analogues. In related investigations, the synthesis of a 2,4-hexahydroxydiphenoyl (HHDP)-bearing glucopyranose structure has been achieved. This species is related to the geraniin family of ellagitannins, and its subsequent chemistry is suggestive of a mechanistic rationale for the observation that the HHDP units within (3,6-bridged)2,4-HHDP-containing ellagitannins invariably are oxidized further in vivo. Companion studies designed to assay the immunomodulatory properties of coriariin A and analogues have led to the thesis that tumor necrosis factor alpha (TNFalpha) serves as a mediator of this ellagitannin's tumor remissive activity. Furthermore, certain tannins and tannin analogues appear to act in an immunosuppressive capacity with peripheral blood monocytes that were exposed to the bacterially derived septic shock inducing agent lipid A.


Are benzodiazepines still the medication of choice for patients with panic disorder with or without agoraphobia?
Recently, pharmacological treatment guidelines for panic disorder have changed as newer treatment options have become available. The authors examined how the use of psychotropic drugs has shifted over the course of 10 years to determine if prescribing patterns have changed to reflect these revised treatment guidelines. A total of 443 patients with panic disorder were enrolled in the Harvard/Brown Anxiety Research Project, a prospective longitudinal study of anxiety disorders. These patients were interviewed over the course of 10 years to examine their use of psychotropic medications. Despite efforts aimed at increasing the use of selective serotonin reuptake inhibitors (SSRIs) in patients with panic disorder (e.g., APA's practice guideline for panic disorder, Food and Drug Administration approval of particular SSRIs for the treatment of panic disorder), only a modest increase in their use was found. Treatment patterns for psychotropic drugs appear to have remained stable over the past decade, with benzodiazepines being the most commonly used medication for panic disorder. In comparison, SSRI use throughout the follow-up period has remained low. Patients using an SSRI did not have a more favorable clinical course than those using a benzodiazepine, nor were there significantly better rates of remission in patients using SSRIs and benzodiazepines concomitantly. These results highlight a gap between pharmacological treatment guidelines and actual delivery of care in that recommendations to use SSRIs to treat panic disorder are not being followed. Factors potentially associated with promoting and ignoring treatment recommendations are discussed.


Social coordination: patience is a virtue for vervet monkeys.
Free-ranging vervet monkeys can solve a complex, multi-player coordination problem, learning to remain outside a 'forbidden circle' imposed by one member of the troop, in the absence of any social learning, communication, or policing by more dominant animals.


Differential response to gefitinib of cells expressing normal EGFR and the mutant EGFRvIII.
Epidermal growth factor receptor (EGFR) is frequently amplified and/or mutated in a number of human tumours and abnormal signalling from this receptor is believed to contribute to the malignant phenotype seen in these tumours. Gefitinib is a small molecule inhibitor that specifically binds and inhibits the EGFR tyrosine kinase and has been shown to inhibit the growth, proliferation, survival and invasion of a range of tumour cells overexpressing EGFR. However, clinical response to gefitinib has failed to correlate with EGFR levels and activity, indicating that other molecular mechanisms such as downstream signalling and mutations could be of importance in predicting clinical response. We therefore investigated the effect of the specific EGFR inhibitor gefitinib on the phosphorylation level, signalling and growth of cells expressing the naturally occurring constitutively active EGFR variant EGFRvIII, a low nontransforming level of EGFR and a high transforming level of EGFR. Results show that levels of gefitinib sufficient to suppress EGFR phosphorylations, EGFR-mediated proliferation and EGFR-mediated anchorage-independent growth are not sufficient to inhibit these features in cells expressing EGFRvIII. Furthermore, the data indicate that long-term exposure of EGFRvIII-expressing cells to low concentrations of gefitinib (0.01-0.1 microM) result in increased phosphotyrosine load of the receptor, increased signalling to ERK and stimulation of proliferation and anchorage-independent growth, presumably by inducing EGFRvIII dimerisation. Higher concentrations of gefitinib (1-2 microM), on the other hand, significantly decreased EGFRvIII phosphotyrosine load, EGFRvIII-mediated proliferation and anchorage-independent growth. Further studies are needed to investigate the implications of these important findings in the clinical setting.


Opinion leaders in the medical community attract more attention than randomized controlled trials in shoulder surgery.
The objective of this study was to determine whether opinion leaders in the medical community attract more attention than randomized controlled trials (RCT) in shoulder surgery. A PubMed search to retrieve all therapeutic and diagnosis RCT shoulder studies was carried out. Three opinion leaders were chosen from among the last ten presidents of the European Shoulder and Elbow Society based on the number of publications. Their studies were also retrieved from PubMed. The metrics of the studies were determined through ResearchGate and Web of Science. The year of publication, impact factor of the journal, level of evidence, number of citations, number of reads, research interest, and reported conflicts of interest were recorded for every study. Two-hundred forty-five shoulder RCTs and 236 opinion leader studies met the inclusion criteria. The opinion leader studies were read significantly more times than the RCTs (p = 0.04). The mean impact factor for RCT studies was 2.84 (SD 3.9) while it was of 1.99 (SD1.14) in the opinion leader group (p < 0.001). Most of the studies of the opinion leaders were level IV (73.3%), while only 6.3% of their papers were categorized as levels I-II. Conflict of interest was present in 19.6% of the RCTs and in 32.2% of the opinion leader studies (p < 0.001). The medical community pays more attention to opinion leader studies in shoulder surgery than to RCT studies even though RCTs are published in higher impact factor journals and opinion leader studies are mainly level IV evidence studies.


Benchmarking of medication incidents reporting and medication error rates in a JCI accredited university teaching hospital at a GCC country.
The benchmarking for medication incidents rate is not regarded as a recognized key performance measure or indicator in national or international organizations. The absence of benchmarking the medication incidents results in the loss of a self-governing perception of how well we performed compared to other peers. This 600-bed tertiary, Joint Commission International (JCI) accredited hospital retrospective analysis looked at all medication management-related events from January-2018 to December-2021. The study design follows descriptive, cross-sectional, retrospective prevalence research. The rate of medication incidents that resulted in harm declined from Q3-2019 to Q4-2021. A significant increase in Pharmacy interventions/clarifications was recorded. Additionally, a significant increase in incidents reported with no-harm coupled with a significant reduction in incidences of serious events from 2019 to 2020. Finally, no-harm events were significantly reduced from 2020 to 2021. The Pharmacy's study analyzed every medication incident documented from 2019 to 2021. 99.7% of reported incidents were classified as no-harm (near misses). There was an exponential decrease from Q1-2020 to Q1-202. A significant increase in incidents fell in the category of (near misses) with no-harm and a significant reduction in serious events. Pharmacy interventions/clarifications saw a massive increase and impact from Q3-2018 to Q2-2019, compared to the same period in 2018. By preventing medical incidents, benchmarking, and analyzing incidents and the reporting system, the use of information technology could dramatically reduce the rate of drug incidents. This study found that benchmarking medication incidents is valuable, as it can help identify areas where improvements can be made, implement strategies to improve safety, and track progress over time. The benchmark was recommended to be below 100 incidents for every 10,000 prescriptions/orders processed, and for E-I categories, below one incident for every 10,000 prescriptions/orders processed. This will help develop a worldwide standard with an absolved culture with non-punitive consequences.


Fabrication of a hydroxyapatite-PDMS microfluidic chip for bone-related cell culture and drug screening.
Bone is an important part of the human body structure and plays a vital role in human health. A microfluidic chip that can simulate the structure and function of bone will provide a platform for bone-related biomedical research. Hydroxyapatite (HA), a bioactive ceramic material, has a similar structure and composition to bone mineralization products. In this study, we used HA as a microfluidic chip component to provide a highly bionic bone environment. HA substrates with different microchannel structures were printed by using ceramic stereolithography (SLA) technology, and the minimum trench width was 50 μm. The HA substrate with microchannels was sealed by a thin polydimethylsiloxane (PDMS) layer to make a HA-PDMS microfluidic chip. Cell culture experiments demonstrated that compared with PDMS, HA was more conducive to the proliferation and osteogenic differentiation of the human foetal osteoblast cell line (hFOB). In addition, the concentration gradient of the model drug doxorubicin hydrochloride (DOX) was successfully generated on a Christmas tree structure HA-PDMS chip, and the half maximal inhibitory concentration (IC50) of DOX was determined. The findings of this study indicate that the HA-PDMS microfluidic chip has great potential in the field of high-throughput bone-related drug screening and bone-related research.


When to extubate the croup patient: the "leak" test.
The reliability of "leak" as a criterion for elective extubation of children with croup treated with nasotracheal intubation was studied during the three month "croup epidemic" in Ontario of September 1, 1983 to November 30, 1983. Twenty-eight patients experienced 36 extubations; 31 planned and five accidental. Three of 23 (13 per cent) planned extubations with "leak" required reintubation whereas three of eight (38 per cent) children electively extubated after seven days of intubation without "leak" required reintubation. "Leak" is a helpful but not absolute prognostic indicator of a successful extubation.


Delayed Intracranial Hemorrhage in Anticoagulated Geriatric Patients After Ground Level Falls.
The reported risk of delayed intracranial hemorrhage (ICH) in a trauma patient on warfarin is estimated to be between 0.6% and 6%. The risk of delayed ICH in trauma patients taking novel oral anticoagulants (NOACs) is not well-defined. We hypothesized that there was a significant number of delayed presentations of ICH in patients on NOACs. A retrospective review of our trauma registry was performed on geriatric patients (age older than 64 years) who were initially evaluated at our level I trauma center, had fall from standing height or less, and were anticoagulated (warfarin or NOACs), from April 2017 to March 2018. Seventy-seven patients met inclusion criteria. The mean age was 80 ± 7.7 years and 46% of patients were male. The admission head computed tomography scan was positive in 20.8% of patients. Positive scans were more common in patients on warfarin vs. NOACs (30% vs. 14%; p = 0.074) and had a significantly higher Injury Severity Score (median [interquartile range]: 9 [3-15] vs. 5 [1-9]; p = 0.030) and Abbreviated Injury Scale-Head score (median [interquartile range]: 1 [0-3] vs. 1 [0-2]; p = 0.035). The agreement between loss of consciousness (LOC) and ICH was 72% (κ = -0.064; p = 0.263). Fifty-one percent of patients had a repeat head CT. New ICH was diagnosed in 9.6% of patients. All of these patients were on NOACs. A fall from standing or less in anticoagulated geriatric patients is a significant mechanism of injury resulting in ICH. The absence of LOC does not eliminate the possibility of ICH. There is a significant risk of delayed ICH for patients on NOACs and repeat evaluations should be performed. A prospective multicenter evaluation of this finding is warranted.


Increased norepinephrine turnover in the median preoptic nucleus following reduced extracellular fluid volume.
The role of noradrenergic input to fluid balance regulatory systems in the anterior hypothalamus was studied by examination of norepinephrine (NE) turnover during reduction of systemic extracellular fluid volume. Extracellular fluid volume was decreased iso-osmotically by subcutaneous polyethylene glycol (PEG), known to increase thirst and vasopressin secretion. NE turnover was assessed by measuring the decline of NE concentration in brain micropunches after administration of alpha-methyl tyrosine in PEG- or sham-treated groups. Several hypothalamic areas were investigated, including the median preoptic area (MnPO), preoptic area (POA), paraventricular nucleus, supraoptic nucleus (SON), subfornical organ, ventromedial hypothalamus, and posterior hypothalamus. Volume-depleted animals showed significantly increased NE turnover in the MnPO, an important area for integration of fluid balance information. The POA and the SON also showed trends toward increased NE turnover. All other areas showed no difference in NE turnover between volume-depleted and normal animals. These results are consistent with previous findings that NE innervation to the MnPO is important in the control of fluid balance and also support the hypothesis that basal forebrain NE projections facilitate thirst and vasopressin secretion.


Consolidating a research agenda for vaccine mandates.
A workshop on mandatory vaccination was pitched to the World Public Health Congress in 2019 and the resultant special issue was pitched to Vaccine in 2020. During this project, the COVID-19 pandemic pushed vaccine policy to the forefront of global public health policy, and the imposition of vaccine mandates prompted a new wave of scholarship in the field. This introductory article employs the heuristic of Lasswell's (1956) policy cycle to synthesise the findings of the articles in the special issue. It considers the temporal lifetime of mandates and highlights findings regarding: the emergence of mandates as a policy option, public support and policy instrument design, what matters in the implementation of mandates, and what we can learn from evaluating them. The second half of the paper categorizes the included papers in terms of what aspects of mandates they study and the methods they employ to do so, in order to formulate a guide for future researchers of vaccine mandates. Scholars study either speculative or existing mandates - research can address several stages of the policy cycle or just one of them, ranging from attitudinal research to implementation studies and impact studies. Historical and contextual studies that take deep dives into a particular mandate are a much needed resource for studying emerging mandates, too, and scoping and framework- building work will undoubtedly be valuable in understanding and appreciating the wealth of knowledge production in this growing field. This special issue can serve as a roadmap for a consolidation of this interdisciplinary research agenda, and provide a helpful resource for decisionmakers at this historical juncture.


Arsenic biomethylation by photosynthetic organisms.
Arsenic (As) is a ubiquitous element that is widespread in the environment and causes numerous health problems. Biomethylation of As has implications for its mobility and toxicity. Photosynthetic organisms may play a significant role in As geochemical cycling by methylating it to different As species, but little is known about the mechanisms of methylation. Methylated As species have been found in many photosynthetic organisms, and several arsenite S-adenosylmethionine (SAM) methyltransferases have been characterized in cyanobacteria and algae. However, higher plants may not have the ability to methylate As. Instead, methylated arsenicals in plants probably originate from microorganisms in soils and the rhizosphere. Here, we propose possible approaches for developing 'smart' photosynthetic organisms with an enhanced and sensitive biomethylation capacity for bioremediation and safer food.


Steroid-free immunosuppression in organ transplantation.
Although steroids have been the cornerstone of immunosuppressive regimens to treat and prevent rejection in organ transplantation, the past decade has seen many successful attempts to minimize or eliminate steroid use. This has been undertaken to decrease the diverse side effects seen with chronic steroid treatment. These efforts have focused on both steroid avoidance and complete elimination, and have been successful across broad patient groups. The key to these efforts has been the adoption of induction protocols with either lymphocyte-depleting agents or anti-interleukin-2 strategies, coupled with the use of the newer maintenance immunosuppressants. In this review, we address the feasibility and benefits of steroid-free and steroid avoidance protocols in kidney, pancreas, liver, and heart transplantation.


Hamstring muscle length and lumbar lordosis in subjects with different lifestyle and work setting: comparison between individuals with and without chronic low back pain.
Shortened hamstring muscle length has been noted in persons with low back pain (LBP). Prolonged sitting postures, such as those adopted during different work settings and sedentary lifestyle has been associated with hamstring shortness and LBP. The purpose of this study was to investigate the effect of lifestyle and work setting on hamstring length and lumbar lordosis in subjects with and without LBP and to identify the relationship between hamstring muscles length and lumbar lordosis in individuals with different lifestyle and work setting. A total of 508 subjects between the ages of 20 and 65 were selected. Subjects were categorized into two groups of individuals with and without LBP. A questionnaire was used to obtain information about the subjects' lifestyle and work setting. Hamstring muscle length and lumbar lordosis were measured in all subjects. The results showed no significant difference in the number of subjects with different work setting or lifestyle in individuals with and without LBP. Hamstring muscle length or lumbar lordosis was not affected by type of work setting and lifestyle. Our data showed significant difference in hamstring length and no significant difference in lumbar lordosis between subjects with and without LBP in all categories. Lumbar lordosis was not different between individuals with and without hamstring tightness in normal and LBP subjects with different work setting and lifestyle. The findings of this study did not support the assumption that work setting and sedentary lifestyle would lead to hamstring tightness in subjects with LBP. It seems that work setting and lifestyle was not a contributing factor for hamstring tightness in subjects with LBP.


Hydraulic lift: Substantial nocturnal water transport between soil layers by Artemisia tridentata roots.
Diel soil water potential fluctuations reflected daytime depletion and nocturnal resupply of water in upper soil layers. Transpiration suppression experiments demonstrated that water absorption by roots caused the daytime depletion. The soil water potential data and experimental results suggest that at night water absorbed from moist soil by deeper roots is transported to and lost from roots into drier upper soil layers. The deeper roots appear to absorb and transport water both day and night. Implications for the efficiency of deep roots and water storage, nutrient uptake and water parasitism in upper soil layers are discussed.


Agricultural Applications for Antimicrobials. A Danger to Human Health: An Official Position Statement of the Society of Infectious Diseases Pharmacists.
The use of antibiotics in agriculture, particularly in food-producing animals, is pervasive and represents the overwhelming majority of antibiotic use worldwide. The link between antibiotic use in animals and antibiotic resistance in humans is unequivocal. Transmission can occur by ingesting undercooked meats harboring resistant bacteria, by direct contact of animals by animal handlers, and by various other means. Antibiotics used in aquaculture and antifungals used in horticulture are also an evolving threat to human health. Regulations aimed at decreasing the amount of antibiotics used in food production to limit the development of antibiotic resistance have recently been implemented. However, further action is needed to minimize antibiotic use in agriculture. This article describes the extent of this current problem and serves as the official position of the Society of Infectious Diseases Pharmacists on this urgent threat to human health.


LuxS contributes to virulence in avian pathogenic Escherichia coli O78:K80:H9.
Avian pathogenic Escherichia coli (APEC) cause avian colibacillosis, a poultry disease characterized by multiple organ infections resulting in significant economic loss in the poultry industry. Several virulence factors are important for disease manifestation in APEC of which, role of quorum sensing has not been investigated. Quorum sensing is a population dependent cell-cell signaling system which modulates numerous physiological processes such as biofilm formation and virulence in multiple species. LuxS, a well-known controller in the QS, plays a role in regulating virulence in various bacterial species. Here we investigated the role of LuxS in regulating virulence in APEC O78:K80:H9. Mutation of luxS resulted in a significant reduction of virulence in APEC O78:K80:H9, evidenced by both in vivo and in vitro assays such as decreased invasion of internal organs in chicken embryo, reduced lethality in chicken embryo lethality assay, and altered lipopolysaccharide (LPS) profile. In addition, the abilities of the knockout strain to survive in chicken macrophage cell lines and to invade in chicken embryo fibroblast cells were significantly diminished. Further, structure and expression level of the LPS profile was significantly altered in the knockout strain, which may be one of the contributing factors for the persistence and virulence of APEC. Complementation of luxS gene in trans restored the virulence of the knockout strain to the level of wild-type bacteria. Taken together, these results show that LuxS contributes to the virulence in APEC O78:K80:H9 strain and partly explain the role played by LuxS in the pathogenesis of APEC strains.


circPUM1 Promotes Tumorigenesis and Progression of Ovarian Cancer by Sponging miR-615-5p and miR-6753-5p.
Circular RNAs (circRNAs) have been reported to participate in the molecular mechanism of human cancers. The PUM1 gene has been confirmed to be closely related to tumorigenesis and progression of ovarian cancer. In the present study, we explored the function and underlying molecular mechanism of circPUM1 in ovarian cancer. qRT-PCR analysis showed upregulation of circPUM1 in ovarian cancer tissues compared with normal ovaries. Gain- and loss-of-function experiments indicated that circPUM1 increased cell proliferation, migration, and invasion and inhibited cell apoptosis. Intraperitoneal injection of circPUM1-knockout tumor cells in nude mice resulted in a decrease in the metastatic ability of the tumor. Bioinformatics analysis and dual-luciferase reporter assays revealed that circPUM1 upregulated the expression of nuclear factor kappa B (NF-κB) and MMP2 by sponging miR-615-5p and miR-6753-5p. Further studies showed that exosomal circPUM1 acted on peritoneal mesothelial cells and increased tumor metastasis. In conclusion, our study indicates that circPUM1 not only promotes ovarian cancer proliferation, migration and invasion, but also acts on the peritoneum and contributes to metastasis of cancer in the form of cancer-derived exosomes.