Amiloride improves locomotor recovery after spinal cord injury.
Amiloride is a drug approved by the United States Food and Drug Administration, which has shown neuroprotective effects in different neuropathological conditions, including brain injury or brain ischemia, but has not been tested in spinal cord injury (SCI). We tested amiloride's therapeutic potential in a clinically relevant rat model of contusion SCI inflicted at the thoracic segment T10. Rats receiving daily administration of amiloride from 24 h to 35 days after SCI exhibited a significant improvement in hindlimb locomotor ability at 21, 28, and 35 days after injury, when compared to vehicle-treated SCI rats. Rats receiving amiloride treatment also exhibited a significant increase in myelin oligodendrocyte glycoprotein (MOG) levels 35 days after SCI at the site of injury (T10) when compared to vehicle-treated controls, which indicated a partial reverse in the decrease of MOG observed with injury. Our data indicate that higher levels of MOG correlate with improved locomotor recovery after SCI, and that this may explain the beneficial effects of amiloride after SCI. Given that amiloride treatment after SCI caused a significant preservation of myelin levels, and improved locomotor recovery, it should be considered as a possible therapeutic intervention after SCI.


Alters in dissociative identity disorder. Metaphors or genuine entities?
How should the different identities (i.e., alters) that are thought to be typical for dissociative identity disorder (DID) be interpreted? Are they just metaphors for different emotional states or are they truly autonomous entities that are capable of willful action? This issue is important because it has implications for the way in which courts may handle cases that involve DID patients. Referring to studies demonstrating that alters of DID patients differ in their memory performance or physiological profile, some authors have concluded that alters are more than just metaphors. We argue that such line of reasoning is highly problematic. There is little consensus among authors about the degree to which various types of memory information (implicit, explicit, procedural) may leak from one to the other alter. Without such theoretical accord, any given outcome of memory studies on DID may be taken as support for the assumption that alters are in some sense "real." As physiological studies on alter activity often lack proper control conditions, most of them are inconclusive as to the status of alters. To date, neither memory studies nor psychobiological studies have delivered compelling evidence that alters of DID patients exist in a factual sense. As a matter of fact, results of these studies are open to multiple interpretations and in no way refute an interpretation of alters in terms of metaphors for different emotional states.


Experimental transmission of West Nile virus by Culex nigripalpus from Honduras.
As a result of concerns regarding the geographic spread of West Nile virus (WNV) to Central America, we evaluated the potential for Honduran Culex nigripalpus Theobald to transmit this virus. We tested individual mosquitoes captured in Olancho Province, Honduras, in September 2003. Mosquitoes were allowed to feed on 2- to 4- day-old chickens previously inoculated with a New York strain (Crow 397-99) of WNV. Infection rates in Cx. nigripalpus ranged from 81%-96% after feeding on chickens with viremias between 10(6.3) and 10(7.4) plaque-forming units per milliliter. Development of a disseminated infection was directly correlated with holding time after the infectious blood meal as 68% (19/28) of the mosquitoes tested 20 days after the infectious blood meal had a disseminated infection as compared to 38% (15/40) of the mosquitoes tested 14 days after feeding on the same viremic chickens (viremia = 10(6.97.4)). Nearly all (4/5) Cx. nigripalpus with a disseminated infection that fed on susceptible chickens transmitted virus by bite. In addition, 8 (57%) of 14 Cx. nigripalpus with a disseminated infection transmitted virus when tested by a capillary tube feeding assay. Based on its efficiency of viral transmission in this study and its role in the transmission of the closely related St. Louis encephalitis virus in the southeastern United States, Cx. nigripalpus should be considered a potentially important vector of WNV in Honduras and the rest of Central America.


Snowbeds are more affected than other subalpine-alpine plant communities by climate change in the Swiss Alps.
While the upward shift of plant species has been observed on many alpine and nival summits, the reaction of the subalpine and lower alpine plant communities to the current warming and lower snow precipitation has been little investigated so far. To this aim, 63 old, exhaustive plant inventories, distributed along a subalpine-alpine elevation gradient of the Swiss Alps and covering different plant community types (acidic and calcareous grasslands; windy ridges; snowbeds), were revisited after 25-50 years. Old and recent inventories were compared in terms of species diversity with Simpson diversity and Bray-Curtis dissimilarity indices, and in terms of community composition with principal component analysis. Changes in ecological conditions were inferred from the ecological indicator values. The alpha-diversity increased in every plant community, likely because of the arrival of new species. As observed on mountain summits, the new species led to a homogenization of community compositions. The grasslands were quite stable in terms of species composition, whatever the bedrock type. Indeed, the newly arrived species were part of the typical species pool of the colonized community. In contrast, snowbed communities showed pronounced vegetation changes and a clear shift toward dryer conditions and shorter snow cover, evidenced by their colonization by species from surrounding grasslands. Longer growing seasons allow alpine grassland species, which are taller and hence more competitive, to colonize the snowbeds. This study showed that subalpine-alpine plant communities reacted differently to the ongoing climate changes. Lower snow/rain ratio and longer growing seasons seem to have a higher impact than warming, at least on plant communities dependent on long snow cover. Consequently, they are the most vulnerable to climate change and their persistence in the near future is seriously threatened. Subalpine and alpine grasslands are more stable, and, until now, they do not seem to be affected by a warmer climate.


Emerging Techniques in Minimally Invasive Surgery. Pros and Cons.
New trends have emerged regarding the best minimally invasive access approaches to perform gastrointestinal surgery. However, these newer approaches are seen critically by those who demand a more strict assessment of outcomes and safety. An international panel of expert gathered at the 2014 American College of Surgeons Meeting with the goal of providing an evidence-based understanding of the real value of these approaches in gastrointestinal surgery. The panel has compared the efficacy and safety of most established approaches to gastrointestinal diseases to those of new treatment modalities: peroral esophageal myotomy vs. laparoscopic myotomy for achalasia, transgastric vs. transvaginal approach, and single-incision vs. multi-port access minimally invasive surgery. The panel found that (1) the outcome of these new approaches was not superior to that of established surgical procedures; (2) the new approaches are generally performed in few highly specialized centers; and (3) transgastric and transvaginal approaches might be safe and feasible in very experienced hands, but cost, training, operative time, and tools seem to limit their application for the treatment of common procedures such as cholecystectomy and appendectomy. Because the expected advantages of new approaches have yet to be proven in controlled trials, new approaches should be considered for adoption into practice only after thorough analyses of their efficacy and effectiveness and appropriate training.


Impact of phase-feeding on the growth performance of broilers subjected to high environmental temperatures.
Experiments were conducted to evaluate the effects of phase feeding (PF) on broilers subjected to heat stress during the grower and finisher periods. Birds were fed diets containing lysine, sulfur amino acid (SAA), or threonine levels based on NRC (1994) recommendations or predictions from linear regression equations (PF). With PF, diets were switched every other day, resulting in steadily decreasing lysine, SAA, and threonine levels. In Experiment 1 (42 to 56 d), growth performance was unaffected (P > 0.05) by diet, and cost per kilogram of weight gain did not differ (P > 0.05) between treatments. In Experiments 2 (23 to 42 d) and 3 (42 to 63 d) birds were housed in environmental chambers and subjected to high (15 h at 35 C, 9 h at 23.9 C) or normal (23.9 C) temperatures. In both experiments, heat stress reduced (P < 0.05) growth performance and increased (P < 0.05) percentage leg yield. Moreover, heat stress decreased percentage breast yield (P < 0.05) in Experiment 2. Growth performance and carcass yield were unaffected (P > 0.05) by PF relative to birds fed NRC-based diets, with the exception of feed efficiency, which was reduced (P < 0.05) by PF under normal temperatures in Experiment 2. Data indicated that dietary lysine, SAA, and threonine levels may be reduced every other day under a PF program without adversely affecting growth performance or carcass yield of birds exposed to high environmental temperatures. Cost analysis indicated that savings might be available with PF under high temperature conditions.


Analysis of hepatitis C virus-positive organs in liver transplantation.
The authors of this study note that in liver transplantation (LT), the survival rates of hepatitis C virus (HCV)-positive donors and HCV-negative receivers are comparable to those of HCV-negative donors and recipients. Direct-acting antiviral (DAA) therapies have nearly 100% effectiveness in treating HCV. Between 2006 and 2016, the percentages of HCV-positive patients on the waiting list and HCV-positive LT recipients fell by 8.2 percent and 7.6 percent, respectively. Records from April 1, 2014, in which the donor and receiver were both at least 18 years old and had a positive HCV status, were the only ones eligible for the study. The analysis for this study was restricted to the first transplant recorded for each patient using a data element that documented the number of prior transplants for each recipient, although some recipients appeared multiple times in the data set. HCV-positive recipients or people with fulminant hepatic failure were the main beneficiaries of primary biliary cirrhosis among HCV-positive donors. However, there is still a reticence to use HCV-positive donor organs in HCV recipients due to clinical and ethical considerations. Similar survival rates between HCV-positive donors and recipients and HCV-negative donors and receivers illustrate the efficacy of these DAA regimens.


The advantage of intergenic regions as genomic features for machine-learning-based host attribution of Salmonella Typhimurium from the USA.
Salmonella enterica is a taxonomically diverse pathogen with over 2600 serovars associated with a wide variety of animal hosts including humans, other mammals, birds and reptiles. Some serovars are host-specific or host-restricted and cause disease in distinct host species, while others, such as serovar S. Typhimurium (STm), are generalists and have the potential to colonize a wide variety of species. However, even within generalist serovars such as STm it is becoming clear that pathovariants exist that differ in tropism and virulence. Identifying the genetic factors underlying host specificity is complex, but the availability of thousands of genome sequences and advances in machine learning have made it possible to build specific host prediction models to aid outbreak control and predict the human pathogenic potential of isolates from animals and other reservoirs. We have advanced this area by building host-association prediction models trained on a wide range of genomic features and compared them with predictions based on nearest-neighbour phylogeny. SNPs, protein variants (PVs), antimicrobial resistance (AMR) profiles and intergenic regions (IGRs) were extracted from 3883 high-quality STm assemblies collected from humans, swine, bovine and poultry in the USA, and used to construct Random Forest (RF) machine learning models. An additional 244 recent STm assemblies from farm animals were used as a test set for further validation. The models based on PVs and IGRs had the best performance in terms of predicting the host of origin of isolates and outperformed nearest-neighbour phylogenetic host prediction as well as models based on SNPs or AMR data. However, the models did not yield reliable predictions when tested with isolates that were phylogenetically distinct from the training set. The IGR and PV models were often able to differentiate human isolates in clusters where the majority of isolates were from a single animal source. Notably, IGRs were the feature with the best performance across multiple models which may be due to IGRs acting as both a representation of their flanking genes, equivalent to PVs, while also capturing genomic regulatory variation, such as altered promoter regions. The IGR and PV models predict that ~45 % of the human infections with STm in the USA originate from bovine, ~40 % from poultry and ~14.5 % from swine, although sequences of isolates from other sources were not used for training. In summary, the research demonstrates a significant gain in accuracy for models with IGRs and PVs as features compared to SNP-based and core genome phylogeny predictions when applied within the existing population structure. This article contains data hosted by Microreact.


High-performance liquid chromatographic and first derivative of the ratio spectrophotometric determination of amlodipine and valsartan in their binary mixtures.
Amlodipine besylate (AML) is a long-acting calcium channel blocker used as an antihypertensive agent. Valsartan (VAL) is also used to treat hypertension, either alone or in combination with other agents. Two-component mixtures of AML and VAL were analyzed by HPLC and the ratio spectra of the first derivative spectrophotometric technique. The spectrophotometric method depends on the first derivative of the ratio-spectra by measurements of the amplitudes at 234.0 nm for VAL and 351.0 nm for AML. Calibration graphs were established for 0.5-20 microg/mL AML and 1-32 microg/mL VAL using the ratio spectra of the first derivative spectrophotometric method. In the HPLC method, an ACE 5 C18 (4.6 x 150 mm, 5 microm) RP column at 30 degrees C with the mobile phase methanol-acetonitrile-NaH2PO4.H2O buffer, including 5 mL/L triethylamine and adjusted to pH 3.0 (42 + 18 + 40, v/v/v) at 2.0 mL/min flow rate was used to separate both compounds with detection at 254.0 nm. Linearity was obtained in the concentration range of 0.5-500 microg/mL for AML and 5.0-900 microg/mL for VAL. The proposed methods have been extensively validated. These methods allow a number of cost- and time-saving benefits. They were successfully applied to the determination of AML and VAL in synthetic mixtures and in a pharmaceutical dosage form. There was no significant difference between the performance of the proposed methods regarding the mean and SD values. The proposed methods are simple, rapid, and suitable for QC applications.


Polymers mediate a one-pot route for functionalized quantum dot barcodes with a large encoding capacity.
With the increasing demands for high-throughput multiplexed bioassays, quantum dot (QD)-encoded microbeads as biocarriers for various bioreactions have attracted considerable attention. However, three key requirements for these biocarriers are still longstanding issues: a stable fluorescence intensity, a large encoding capacity and abundant surface functional groups. Here, a novel one-pot strategy is developed, generating functionalized QD-encoded microspheres with a strong fluorescence intensity and optical stability. With poly(styrene-co-maleic anhydride) (PSMA) molecules as mediators, the encapsulation of QDs and carboxylation of the bead surface are integrated together, greatly improving the preparation efficiency and guaranteeing their potential application in biodetection. Moreover, the mechanism for preparing QD-doped beads is further proposed, which helps to precisely manipulate the preparation process and accurately encode the beads. Through this approach, a single- and dual-color barcode library of QD-encoded microspheres has been successfully established, which demonstrates their great potential in suspension arrays.


Hand function and tactile perception in a sample of children with myelomeningocele.
The purpose of this investigation were to study the relationships between hand function abilities and tactile perception, and the level of spinal cord lesion and status of hydrocephalus in a sample of 17 children with myelomeningocele. Fourteen children showed impaired hand function, and eight showed tactile dysfunction. Statiscally significant differences in hand function scores and graphesthesia scores were obtained for children with increased severity of hydrocephalus and high-level lesions. Of the 48 correlation coefficients computed between the hand function and tactile perception measures used, only one was statistically significant. This lack of correlation may indicate that hand function and tactile perception in children with myelomeningocele are unrelated factors. Clinical implications of impaired hand function and tactile perception were discussed.


Roles of substance P and somatostatin on transmission of nociceptive information induced by formalin in spinal cord.
Nociceptive response induced by 0.5% Formalin in the hindpaw of mice had two peaks, 0-5 min (first phase) and 15-20 min (second phase). By using the distinct biphasic response, the nature of the transmitter systems activated by Formalin in the spinal cord was studied for the purpose of determining the difference of the role of substance P (SP) and somatostatin (SST). The injection of (D-Pro2, D-Trp7,9)SP, (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP and SP antiserum inhibited only the first phase response. The i.t. injection of -Aminoheptanoyl-Phe-D-Trp-Lys-(OBz)-Thr- (an SST antagonist), SST antiserum and cysteamine (an SST depletor) inhibited only the second phase. This result indicates that SP is involved in the transmission of the first phase, and SST is involved in the transmission of the second phase of the Formalin-induced nociceptive response. With regard to other nociceptive stimuli, two i.t. SP antagonists produced a significant analgesia in the hot plate and tail pinch tests but had no effect in the acetic acid writhing test. However, i.t. SST antagonist and cysteamine produced a significant analgesia in the writhing test but had no effect in the hot plate and tail pinch test. These results suggest that SP participates in the transient pain induced by such acute stimuli as hot plate, tail pinch and the first phase of Formalin response and that SST participates in the prolonged and inflammatory pain induced by stimuli such as acetic acid and the second phase response.


Thymic stromal lymphopoietin receptor-mediated IL-6 and CC/CXC chemokines expression in human airway smooth muscle cells: role of MAPKs (ERK1/2, p38, and JNK) and STAT3 pathways.
Thymic stromal lymphopoietin (TSLP) plays a pivotal role in allergic diseases such as asthma, chronic obstructive pulmonary disease, and atopic dermatitis. Enhanced TSLP expression has been detected in asthmatic airways that correlated with both the expression of Th2-attracting chemokines and with disease severity. Although cumulative evidence suggests that human airway smooth muscle (HASM) cells can initiate or perpetuate the airway inflammation by secreting a variety of inflammatory cell products such as cytokines and chemokines, the role of TSLP in this pathway is not known. In the current study, we sought to investigate whether HASM cells express the TSLP receptor (TSLPR) and whether it is functional. We first demonstrated that primary HASM cells express the transcript and protein of both TSLPR subunits (TSLPR and IL-7Ralpha). Functionally, TSLPR-mediated HASM activation induced a significant increase in CXC (IL-8/CXCL8), CC (eotaxin-1/CCL11) chemokines, and proinflammatory cytokine IL-6 expression. Furthermore, using biochemical and genetic approaches, we found that TSLP-induced proinflammatory gene expression in HASM involved the transcriptional mechanisms, MAPKs (ERK1/2, p38, and JNK), and STAT3 activation. Finally, TSLPR immunoreactivity in bronchial sections from mild allergic asthmatics suggested the potential in vivo TSLP targeting of HASM. Altogether, our data suggest that the TSLPR-mediated HASM activation induces proinflammatory cytokine and chemokines release that may facilitate inflammatory immune cells recruitment in airways. In addition, it may be inferred that TSLPR is involved in the pathogenesis of allergic asthma through the activation of HASM cells by TSLP.


SARS-CoV-2 detection using reverse transcription strand invasion based amplification and a portable compact size instrument.
Rapid nucleic-acid based tests that can be performed by non-professionals outside laboratory settings could help the containment of the pandemic SARS-CoV-2 virus and may potentially prevent further widespread lockdowns. Here, we present a novel compact portable detection instrument (the Egoo Health System) for extraction-free detection of SARS-CoV-2 using isothermal reverse transcription strand invasion based amplification (RT-SIBA). The SARS-CoV-2 RT-SIBA assay can be performed directly on crude oropharyngeal swabs without nucleic acid extraction with a reaction time of 30 min. The Egoo Health system uses a capsule system, which is automatically sealed tight in the Egoo instrument after applying the sample, resulting in a closed system optimal for molecular isothermal amplification. The performance of the Egoo Health System is comparable to the PCR instrument with an analytical sensitivity of 25 viral RNA copies per SARS-CoV-2 RT-SIBA reaction and a clinical sensitivity and specificity between 87.0-98.4% and 96.6-98.2% respectively.


Time-gated confocal microscopy reveals accumulation of exocyst subunits at the plant-pathogen interface.
Polarized exocytosis is essential for plant development and defence. The exocyst, an octameric protein complex that tethers exocytotic vesicles to the plasma membrane, targets exocytosis. Upon pathogen attack, secreted materials form papillae to halt pathogen penetration. To determine if the exocyst is directly involved in targeting exocytosis to infection sites, information about its localization is instrumental. Here, we investigated exocyst subunit localization in the moss Physcomitrella patens upon pathogen attack and infection by Phytophthora capsici. Time-gated confocal microscopy was used to eliminate autofluorescence of deposited material around infection sites, allowing the visualization of the subcellular localization of exocyst subunits and of v-SNARE Vamp72A1-labelled exocytotic vesicles during infection. This showed that exocyst subunits Sec3a, Sec5b, Sec5d, and Sec6 accumulated at sites of attempted pathogen penetration. Upon pathogen invasion, the exocyst subunits accumulated on the membrane surrounding papilla-like structures and hyphal encasements. Vamp72A1-labelled vesicles were found to localize in the cytoplasm around infection sites. The re-localization of exocyst subunits to infection sites suggests that the exocyst is directly involved in facilitating polarized exocytosis during pathogenesis.


Implementation-The Missing Link in the Research Translation Pipeline: Is It Any Wonder No One Ever Implements Evidence-Based Practice?
Despite the exponential growth in the evidence base for stroke rehabilitation, there is still a paucity of knowledge about how to consistently and sustainably deliver evidence-based stroke rehabilitation therapies in clinical practice. This means that people with stroke will not consistently benefit from research breakthroughs, simply because clinicians do not always have the skills, authority, knowledge or resources to be able to translate the findings from a research trial and apply these in clinical practice. This "point of view" article by an interdisciplinary, international team illustrates the lack of available evidence to guide the translation of evidence to practice in rehabilitation, by presenting a comprehensive and systematic content analysis of articles that were published in 2016 in leading clinical stroke rehabilitation journals commonly read by clinicians. Our review confirms that only a small fraction (2.5%) of published stroke rehabilitation research in these journals evaluate the implementation of evidence-based interventions into health care practice. We argue that in order for stroke rehabilitation research to contribute to enhanced health and well-being of people with stroke, journals, funders, policy makers, researchers, clinicians, and professional associations alike need to actively support and promote (through funding, conducting, or disseminating) implementation and evaluation research.


[Activation of cholesterogenesis in response to ionizing irradiation of the animal body].
The assumption is made that ionizing radiation induces cholesterogenesis activation in different cells of mammalian organism as an early reaction to the harmful effect necessary for restoration of biomembranes. Liver cells activate adaptively the cholesterol synthesis in the animal body irradiated with lethal doses in response to the injury to radiosensitive cells in order to make them recover and compensate for their functions (with the gastrointestinal syndrome, for instance, to compensate for the cholesterol-producing function of the intestine and to make it recover). With lethal radiation doses, a change in the lipid content and metabolism of microsomal membrane lipids of the liver is associated with activation of synthetic functions of the liver due to compensation of the injury to radiosensitive tissues.


Biological plausibility for carbon monoxide as a copollutant in PM epidemiologic studies.
Several recent epidemiologic studies investigating the short-term effects of particulate matter (PM) concentrations have shown carbon monoxide (CO) to have the strongest and most consistent statistical relationship with hospital admissions for cardiac diseases. This article suggests a potential hypothesis for these epidemiologic observations. Oxygen (O2) is transported, in reversible combination with hemoglobin, from the lungs to the tissues, where it diffuses into cardiac myocytes. Within the myocyte a portion of the O2 diffuses directly to the mitochondria, while the remaining O2 is transported by facilitated diffusion bound to myoglobin, a heme protein found in muscle. Within the mitochondria, O2 reacts to produce adenosine triphosphate (ATP), a high-energy phosphate compound that provides energy for all cell functions. Accordingly, the sustained production of ATP depends on the continuous delivery of O2 to the mitochondria, and failure at any point in the O2 transport system will compromise ATP production and myocardial function. Myoglobin, a fundamental constituent of cardiac muscle is essential for delivering O2 to the mitochondria. Myoglobin concentrations in cardiac tissue were 50% lower in patients with heart failure than in patients dying from noncardiac causes. Myoglobin concentrations are also severely depressed in animal models of congestive heart failure. Consequently, the role of myoglobin as a cellular transporter of O2 is seriously impaired by heart disease. Carbon monoxide reduces O2 transport to the tissues and, within the tissues, binds with myoglobin to form carboxymyoglobin (COMb). Thus, in cardiac patients CO further exacerbates the disease-related loss of myoglobin function. This further disrupts O2 transport and promotes adverse consequences for the compromised heart. Moreover, during hypoxia CO has the propensity of leaving the blood and binding with myoglobin in the intracellular compartment. Elderly persons with preexisting cardiopulmonary disorders appear to be at maximum risk of harmful health effects due to ambient air pollution exposure. Many of these disorders result in generalized or regional hypoxia. It is reasonable to hypothesize that CO also moves out of the blood of these patients and into the heart tissue whenever they are under hypoxic stress, such as exercise. Accordingly, CO binds with the marginal myoglobin concentrations present in the hearts of cardiac patients and further compromises cardiac function, resulting in poor tolerance of activity. Therefore, reduced cardiac myoglobin in people with heart disease, further exacerbated by CO moving into the cardiac tissue during episodes of hypoxia, may account for the positive association between ambient CO concentrations and hospitalization for heart disease.


Psychological effects of earthquakes in children: prospects for brief behavioral treatment.
Treatment of child earthquake survivors is a relatively less investigated issue in disaster research. A review of the evidence on the mental health effects of earthquakes, risk factors, and findings from treatment studies may provide useful insights into effective treatment of traumatized children. Studies of child and adolescent earthquake survivors included the PILOTS database (electronic index for literature on psychological trauma) and relevant evidence from various studies of adult earthquake survivors. Evidence points to elevated rates of posttraumatic stress disorder (PTSD), depression, and earthquake-related fears in children and adolescents. Traumatic stress appears to be mediated by loss of control over fear induced by exposure to unpredictable and uncontrollable earthquakes. This implies that interventions enhancing sense of control over fear are likely to be most effective. Recent studies indeed show that a control focused behavioral treatment (CFBT) involving mainly encouragement for self-exposure to feared situations is highly effective in facilitating recovery from earthquake trauma. Evidence also suggests that CFBT can be delivered through booklets and similar media. Pilot studies suggest that CFBT has promise in effective treatment of PTSD in children. Further research is needed to confirm these preliminary findings and to develop self-help tools for children.


Comparison of non-mydriatic retinal photography with ophthalmoscopy in 2159 patients: mobile retinal camera study.
To determine whether non-mydriatic Polaroid retinal photography was comparable to ophthalmoscopy with mydriasis in routine clinic screening for early, treatable diabetic retinopathy. Prospective study of ophthalmoscopic findings according to retinal camera screening and ophthalmoscopy and outcome of referral to ophthalmologist. Outpatient diabetic clinics of three teaching hospitals and three district general hospitals. 2159 Adults selected randomly from the diabetic clinics, excluding only those registered as blind or those in wheelchairs and unable to enter the screening vehicle. Numbers of patients and eyes correctly identified by each technique as requiring referral with potentially treatable retinopathy (new vessel formation and maculopathy) and congruence in numbers of microaneurysms, haemorrhages, and exudates reported. Camera screening missed two cases of new vessel formation and did not identify a further 12 but indicated a need for referral. Ophthalmoscopy missed five cases of new vessel formation and indicated a need for referral in another four for other reasons. Maculopathy was reported in 147 eyes with camera screening alone and 95 eyes by ophthalmoscopy only (chi 2 = 11.2; p less than 0.001), in 66 and 29 of which respectively maculopathy was subsequently confirmed. Overall, 38 eyes received laser treatment for maculopathy after detection by camera screening compared with 17 after ophthalmoscopic detection (chi 2 = 8.0; p less than 0.01). Camera screening underestimated numbers of microaneurysms (chi 2 = 12.9; p less than 0.001) and haemorrhages (chi 2 = 7.4; p less than 0.01) and ophthalmoscopy underestimated hard exudates (chi 2 = 48.2; p less than 0.001). Non-mydriatic Polaroid retinal photography is at least as good as ophthalmoscopy with mydriasis in routine diabetic clinics in identifying new vessel formation and absence of retinopathy and is significantly better in detecting exudative maculopathy.


Physical inactivity: a risk factor and target for intervention in renal care.
Regular physical activity is associated with an increased quality of life and reduced morbidity and mortality in the general population and in patients with chronic kidney disease (CKD). Physical activity, cardiorespiratory fitness, and muscle mass decrease even in the early stages of CKD, and continue to decrease with disease progression; notably, full recovery is generally not achieved with transplantation. The combined effects of uraemia and physical inactivity drive the loss of muscle mass. Regular physical activity benefits cardiometabolic, neuromuscular and cognitive function across all stages of CKD, and therefore provides an approach to address the multimorbidity of the CKD population. Interestingly, maintenance of muscle health is associated with renoprotective effects. Despite evidence of its benefits, physical activity and exercise management are not routinely addressed in the care of these patients. Although studies defining the optimum frequency, duration and intensity of physical activity are lacking, evidence from related fields can guide practical approaches to the care of patients with renal disease. Optimization of metabolic and nutritional status alongside promotion of physical activity is recommended. Behavioural approaches are now recognized as crucial in helping patients to adopt lifestyle changes and might prove valuable in integrating physical activity into renal care.


Activation of insect cell adenylate cyclase by Bacillus thuringiensis delta-endotoxins and melittin. Toxicity is independent of cyclic AMP.
Insecticidal Bacillus thuringiensis (Bt) delta-endotoxins are cytolytic to a range of insect cell lines in vitro. Addition of Bt var. aizawai or var. israelensis toxins to Mamestra brassicae (cabbage moth) cells in vitro increased intracellular cyclic AMP, which was paralleled by activation of adenylate cyclase in isolated membranes. Var. kurstaki toxin, which does not lyse M. brassicae cells, had no effect on cyclic AMP concentrations in intact cells, but was able to stimulate adenylate cyclase in membrane preparations. In contrast, the bee-venom toxin melittin, which is also cytolytic, increased intracellular cyclic AMP in whole cells, but inhibited adenylate cyclase in isolated membranes. Octopamine and forskolin also increased cyclic AMP in cells, but were not cytolytic. When added to cells at concentrations exceeding their LC90 (concentration causing 90% cell death), melittin and var. israelensis toxins caused cell lysis without a concomitant increase in intracellular cyclic AMP. Taken together, these results suggest that activation of adenylate cyclase by cytolytic toxins is a secondary effect (related perhaps to interactions of these toxins with membrane lipids) and is neither necessary nor sufficient for cytolysis.


Selection of helical braided flow diverter stents based on hemodynamic performance and mechanical properties.
Although flow diversion is a promising procedure for the treatment of aneurysms, complications have been reported and it remains poorly understood. The occurrence of adverse outcomes is known to depend on both the mechanical properties and flow reduction effects of the flow diverter stent. To clarify the possibility of designing a flow diverter stent considering both hemodynamic performance and mechanical properties. Computational fluid dynamics (CFD) simulations were conducted based on an ideal aneurysm model with flow diverters. Structural analyses of two flow diverter models exhibiting similar flow reduction effects were performed, and the radial stiffness and longitudinal flexibility were compared. In CFD simulations, two stents-Pore2-d35 (26.77° weave angle when fully expanded, 35 μm wire thickness) and Pore3-d50 (36.65°, 50 μm respectively)-demonstrated similar flow reduction rates (68.5% spatial-averaged velocity reduction rate, 85.0% area-averaged wall shear stress reduction rate for Pore2-d35, and 68.6%, 85.4%, respectively, for Pore3-d50). However, Pore3-d50 exhibited greater radial stiffness than Pore2-d35 (40.0 vs 21.0 mN/m at a 3.5 mm outer diameter) and less longitudinal flexibility (0.903 vs 0.104 N·mm bending moments at 90°). These measurements indicate that changing the wire thickness and weave angle allows adjustment of the mechanical properties while maintaining the same degree of flow reduction effects. The combination of CFD and structural analysis can provide promising solutions for an optimized stent. Stents exhibiting different mechanical properties but the same flow reduction effects could be designed by varying both the weave angle and wire thickness.


From embracing to managing risks.
To assess developments over time in the capture, curation and use of quality and safety information in managing hospital services. Four acute National Health Service hospitals in England. 111.5 hours of observation of hospital board and directorate meetings, and 72 hours of ward observations. 86 interviews with board level and middle managers and with ward managers and staff. There were substantial improvements in the quantity and quality of data produced for boards and middle managers between 2013 and 2016, starting from a low base. All four hospitals deployed data warehouses, repositories where datasets from otherwise disparate departmental systems could be managed. Three of them deployed real-time ward management systems, which were used extensively by nurses and other staff. The findings, particularly relating to the deployment of real-time ward management systems, are a corrective to the many negative accounts of information technology implementations. The hospital information infrastructures were elements in a wider move, away from a reliance on individual professionals exercising judgements and towards team-based and data-driven approaches to the active management of risks. They were not, though, using their fine-grained data to develop ultrasafe working practices.


Expression of cardiotoxin-2 gene. Cloning, characterization and deletion analysis of the promoter.
This report is the first study of the regulation of expression of a toxin gene and it also demonstrates the novel finding that the cardiotoxin (CTX)-2 gene from Naja sputatrix is expressed in the venom gland as well as in other tissues in the snake, such as liver, heart and muscle. The venom gland produces a 500-bp (spliced) CTX-2 mRNA as the final transcript. However, the liver produces two types of CTX-2 mRNA, of which the unspliced transcript (1 kb) is predominant; the 500 bp spliced transcript is the minor species. This differential expression of the CTX gene has been attributed to the usage of alternative promoter consisting of independent TATA boxes and corresponding transcription initiation sites. Among the several transcription factors that have been identified by a search of the TFIID database, the participation of two glucocorticoid elements in the expression of the CTX gene has been demonstrated by promoter deletion analysis. Putative binding sites for SP-1, C/EBP, CACCC-binding factor and at least two unknown binding factors have also been identified by DNase I footprinting of the promoter.


Mathematical model of COVID-19 spread in Turkey and South Africa: theory, methods, and applications.
A comprehensive study about the spread of COVID-19 cases in Turkey and South Africa has been presented in this paper. An exhaustive statistical analysis was performed using data collected from Turkey and South Africa within the period of 11 March 2020 to 3 May 2020 and 05 March and 3 of May, respectively. It was observed that in the case of Turkey, a negative Spearman correlation for the number of infected class and a positive Spearman correlation for both the number of deaths and recoveries were obtained. This implied that the daily infections could decrease, while the daily deaths and number of recovered people could increase under current conditions. In the case of South Africa, a negative Spearman correlation for both daily deaths and daily infected people were obtained, indicating that these numbers may decrease if the current conditions are maintained. The utilization of a statistical technique predicted the daily number of infected, recovered, and dead people for each country; and three results were obtained for Turkey, namely an upper boundary, a prediction from current situation and lower boundary. The histograms of the daily number of newly infected, recovered and death showed a sign of lognormal and normal distribution, which is presented using the Bell curving method parameters estimation. A new mathematical model COVID-19 comprised of nine classes was suggested; of which a formula of the reproductive number, well-poseness of the solutions and the stability analysis were presented in detail. The suggested model was further extended to the scope of nonlocal operators for each case; whereby a numerical method was used to provide numerical solutions, and simulations were performed for different non-integer numbers. Additionally, sections devoted to control optimal and others dedicated to compare cases between Turkey and South Africa with the aim to comprehend why there are less numbers of deaths and infected people in South Africa than Turkey were presented in detail.


Allopregnanolone impairs episodic memory in healthy women.
Allopregnanolone is an endogenous neuroactive steroid that, through its binding to the gamma-aminobutyric acid (GABA) A receptor, has GABA-active properties. Animal studies indicate that allopregnanolone administration results in diminished learning and memory impairment. The aim of the current study was to investigate the effect of intravenously administered allopregnanolone on episodic memory, semantic memory, and working memory in healthy women. Twenty-eight healthy women were included in the study. The participants were scheduled for the memory tests twice in the follicular phase. During the test sessions, an intravenous allopregnanolone and placebo infusion were administered in a double-blinded, randomized order at intervals of 48 h. Before and 10 min after the allopregnanolone/placebo injections, memory tasks were performed. The study demonstrated that allopregnanolone impaired episodic memory in healthy women. There was a significant difference between pre- and postallopregnanolone injection episodic memory scores (p < 0.05), whereas there was no change in episodic memory performance following the placebo injections. There was also a significant difference between allopregnanolone and placebo postinjection episodic memory scores (p < 0.05). There were no effects of allopregnanolone on the semantic memory task or working memory task. Intravenous allopregnanolone impairs episodic memory in healthy women, but there is a high degree of individual variability.


A second binding site revealed by C-terminal truncation of calpain small subunit, a penta-EF-hand protein.
The subunits in calpain and in the related penta-EF-hand (PEF) proteins are bound through contacts between the unpaired EF-hand 5 from each subunit. To study subunit binding further, a tetra-EF-hand 18 kDa N- and C-terminally truncated form of the calpain small subunit was prepared (18k). This protein does not combine with the calpain large subunit to form active calpain, but forms homodimers in solution, as shown by ultracentrifugation. The X-ray structure of the 18k protein in the presence of cadmium was solved to a resolution of 2.0 A. The structure of the monomer is almost identical to the known structure of the calpain small subunit, but the 18k protein forms an oligomer in the crystal by the use of two binding sites. One of these sites is an artefact arising from the C-terminal truncation, but the other is a naturally occurring site that is fully exposed to water in intact purified calpain. The characteristics of this site suggest that it may be important in binding other protein modulators involved in the regulation of calpain and of PEF proteins.


Enhancement of NbO2-based oscillator neuron device performance via cryogenic operation.
The Niobium Dioxide (NbO2) oscillator neuron has garnered significant interest because of its simple structure compared to conventional CMOS-based circuits. However, the limited on/off resistance ratio narrows the range of series resistances that satisfy the self-oscillation conditions and limits its use in large-scale synaptic arrays. In this study, we report the possibility of improving the performance of NbO2-based oscillator neuron devices through cryogenic operation. The study emphasizes two crucial parameters: the on/off resistance ratio and the oscillation amplitude, both of which are essential for accurate weighted sum classification. The data suggest that these parameters can be effectively enhanced under cryogenic conditions. In addition, we revealed that 120K is the optimal temperature for cryogenic operation, as it represents the temperature where the on/off resistance ratio ceases to increase. As a result, we revealed that the series resistance range satisfying the self-oscillation condition in a single oscillator increases from 20 kΩ to 126 kΩ. The research also probes the maximum possible array size at each temperature. At 300 K, representation is only possible for a 5 × 5 array, but at 120 K, a 30 × 30 array can be represented as a frequency. The evidence implies that the 120 K conditions not only broaden the range of series resistors that can be connected to a single oscillator but also increases the array size, thereby representing different weighted sum currents as frequencies. The research indicates that using carefully optimized cryogenic operation could be a viable method to enhance the necessary NbO2 properties for an oscillator neuron device.


A critical assessment of the current status of non-erosive reflux disease.
Non-erosive reflux disease (NERD) has assumed increasing prominence in studies of gastroesophageal reflux disease (GERD), but it remains a challenge to define NERD precisely and to define its place in the investigation and treatment of GERD. Most simply, NERD may be defined as GERD in an individual who has no evidence of erosions at endoscopy. Unfortunately, the characteristic symptoms of GERD--heartburn and regurgitation--are insufficient to identify all GERD patients and, hence, the diagnosis of NERD is hampered by the lack of clear criteria for the symptomatic diagnosis of GERD. The diagnosis of NERD is hampered further by limited interobserver agreement on the endoscopic diagnosis of erosive esophagitis and by the fact that endoscopy is often performed soon after patients have discontinued therapy. Improvements in endoscopic technology will increase the likelihood of identifying small erosions or other reflux-related lesions; however, this will increase the proportion of patients considered to have erosive esophagitis without defining precisely what constitutes NERD. It is important to recognize that NERD is but one manifestation of GERD and that it, like other manifestations of GERD, is associated with a marked diminution in patients' quality of life. However, this recognition apart, there seems to be little practical benefit or understanding to be gained in clinical practice or clinical research from considering NERD as a distinct entity or from studying NERD patients in isolation. Advances in understanding the pathogenesis of GERD and its symptoms may be better served by categorizing GERD with respect to the spectrum of its histologic, functional, endoscopic and symptomatic manifestations rather than by studying NERD, a manifestation that is characterized solely by the absence of esophageal erosions.


Imaging after Pancreatic Surgery: Expected Findings and Postoperative Complications.
Pancreatic surgery is considered one of the most technically challenging surgical procedures, despite the evolution of modern techniques. Neoplasms remain the most common indication for pancreatic surgery, although inflammatory conditions may also prompt surgical evaluation. The choice of surgical procedure depends on the type and location of the pathologic finding because different parts of the pancreas have separate vascular supplies that may be shared by adjacent organs. The surgical approach could be conventional or minimally invasive (laparoscopic, endoscopic, or robotic assisted). Because of the anatomic complexity of the pancreatic bed, perioperative complications may be frequently encountered and commonly involve the pancreatic-biliary, vascular, lymphatic, or bowel systems, irrespective of the surgical technique used. Imaging plays an important role in the assessment of suspected postoperative complications, with CT considered the primary imaging modality, while MRI, digital subtraction angiography, and molecular imaging are considered ancillary diagnostic tools. Accurate diagnosis of postoperative complications requires a solid understanding of pancreatic anatomy, surgical indications, normal postoperative appearance, and expected postsurgical changes. The practicing radiologist should be familiar with the most common perioperative complications, such as anastomotic leak, abscess, and hemorrhage, and be able to differentiate these entities from normal anticipated postoperative changes such as seroma, edema and fat stranding at the surgical site, and perivascular soft-tissue thickening. In addition to evaluation of the primary operative fossa, imaging plays a fundamental role in assessment of the adjacent organ systems secondarily affected after pancreatic surgery, such as vascular, biliary, and enteric complications. Published under a CC BY 4.0 license. Test Your Knowledge questions are available in the supplemental material. See the invited commentary by Winslow in this issue.


Borderline tumours of the ovary: Common practice in the Netherlands.
Discordance between frozen section diagnosis and the definite histopathological diagnosis and the fact that the frozen section result is not always unambiguous, may contribute to differences in clinical practice regarding perioperative treatment and follow-up of borderline ovarian tumours (BOTs) patients amongst gynaecologic oncologists, which may lead to over- and undertreatment. The aim of the study was to map the Dutch gynaecologists' preferred treatment and follow-up strategy in case of BOTs. A questionnaire was sent to all Dutch gynaecologists involved in ovarian surgery with perioperative frozen section analysis, and the outcomes were assessed using descriptive statistics. Nearly half of the respondents (41.0%) would not perform a staging procedure in case of a BOT. In case of an ambiguous frozen section diagnosis, tending towards invasive carcinoma, a considerable number (sBOT 56.4%; mBOT 30.8%) would perform a lymph node sampling as part of the staging procedure. A relaparotomy/relaparoscopy, to perform a lymph node sampling in case of a serous or mucinous carcinoma after a BOT frozen section diagnosis, would be performed by 97.4% and 48.7% of the respondents, respectively. A considerable number of gynaecologists would perform a staging procedure that is recommended for ovarian cancer in case of an ambiguous BOT frozen section diagnosis, especially for serous tumours. In addition, nearly all gynaecologists would perform a second procedure including a lymph node sampling in case of a serous invasive carcinoma after a BOT frozen section diagnosis, which applies to half of the gynaecologists in case of a mucinous carcinoma.


The lived experience of volunteering in a palliative care biography service.
Many patients approaching death experience hopelessness, helplessness, and a depressed mood, and these factors can contribute to a difficult end-of-life (EoL) period. Biography services may assist patients in finding meaning and purpose at this time. The aim of our study was to investigate the lived experience of volunteers involved in a biography service in Melbourne, Australia, using a qualitative methodology. The participants were 10 volunteers who had participated in a biography service within a private palliative care service. Each volunteer was interviewed separately using a study-specific semistructured interview guide. The transcripts of these interviews were then subjected to thematic analysis. Analysis yielded the following themes: motivations for volunteering; dealing with death, dying, and existential issues; psychosocial benefits of volunteering; and benefits and challenges of working with patients and their families. Our results indicated that volunteering gave the volunteers a deeper appreciation of existential issues, and helped them to be more appreciative of their own lives and gain a deeper awareness of the struggles other people experience. They also suggested that volunteers felt that their involvement contributed to their own personal development, and was personally rewarding. Furthermore, the results highlighted that volunteers found that encounters with family members were sometimes challenging. While some were appreciative, others imposed time limits, became overly reliant on the volunteers, and were sometimes offended, hurt, and angered by what was included in the final biography. It is hoped that the findings of the current study will provide direction for improvements in the biography services that will benefit patients, family members, and volunteers. In particular, our findings highlight the need to provide ongoing support for volunteers to assist them in handling the challenges of volunteering in a palliative care setting.


Cleavage of Notch1 by granzyme B disables its transcriptional activity.
Granzyme-mediated cell death is the main pathway for cytotoxic lymphocytes to kill virus-infected and tumour cells. A major player in this process is GrB (granzyme B), which triggers apoptosis in both caspase-dependent and caspase-independent pathways. A caspase-independent substrate of GrB is the highly conserved transmembrane receptor Notch1. The GrB cleavage sites in Notch1 and functional consequences of Notch1 cleavage by GrB were unknown. In the present study, we confirmed that Notch1 is a direct and caspase-independent substrate of GrB. We demonstrate that GrB cleaved the intracellular Notch1 domain at least twice at two distinct aspartic acids, Asp1860 and Asp1961. GrB cleavage of Notch1 can occur in all subcellular compartments, during maturation of the receptor, at the membrane, and in the nucleus. GrB also displayed perforin-independent functions by cleaving the extracellular domain of Notch1. Overall, cleavage of Notch1 by GrB resulted in a loss of transcriptional activity, independent of Notch1 activation. We conclude that GrB disables Notch1 function, probably resulting in anti-cellular proliferation and cell death signals.


The role of density-dependent and -independent processes in spawning habitat selection by salmon in an Arctic riverscape.
Density-dependent (DD) and density-independent (DI) habitat selection is strongly linked to a species' evolutionary history. Determining the relative importance of each is necessary because declining populations are not always the result of altered DI mechanisms but can often be the result of DD via a reduced carrying capacity. We developed spatially and temporally explicit models throughout the Chena River, Alaska to predict important DI mechanisms that influence Chinook salmon spawning success. We used resource-selection functions to predict suitable spawning habitat based on geomorphic characteristics, a semi-distributed water-and-energy balance hydrologic model to generate stream flow metrics, and modeled stream temperature as a function of climatic variables. Spawner counts were predicted throughout the core and periphery spawning sections of the Chena River from escapement estimates (DD) and DI variables. Additionally, we used isodar analysis to identify whether spawners actively defend spawning habitat or follow an ideal free distribution along the riverscape. Aerial counts were best explained by escapement and reference to the core or periphery, while no models with DI variables were supported in the candidate set. Furthermore, isodar plots indicated habitat selection was best explained by ideal free distributions, although there was strong evidence for active defense of core spawning habitat. Our results are surprising, given salmon commonly defend spawning resources, and are likely due to competition occurring at finer spatial scales than addressed in this study.


[Psychiatry of women: an new field of research in mental health].
This paper presents the state of the art of our current knowledge in the field of female psychiatry. This domain of mental health studies the particularities of psychological distress in women. It is a new concept, and its creation is subtended by some clinical and epidemiological realities. The creation of this very interesting field of research has been promoted on the one hand because of the existence of certain female-specific psychiatric disorders (premenstrual syndrome, post-partum psychopathologies, pseudocyesis, Ferjol's syndrome and menopause-related disorders) and on the other hand because the vast majority of mental diseases may be expressing major gender-related variations (prevalence, natural history of disease, symptomatology, prognosis and treatment outcome). Research in female psychiatry has numerous goals. First of all, the sex-based differences in the prevalence of mental disorders (e.g., depression, schizophrenia, anxiety, anorexia nervosa, personality disorders) has to be understood (are they artefacts, or the expression of hormonal or genetic influence, or a consequence of social factors, or even the result of brain development?). Second, the specific nature of some of these diseases is under investigation (e.g., is postnatal depression a classical major depressive disorder or a puerperal-specific disease?). And third, treatments must be adapted accordingly. Indeed, the study of female psychiatry attempts the integration of the gender-effect in order to improve the treatment modalities.


[Comparative analysis between breath test, serological immunoassay and rapid-urease test for detection of Helicobacter pylori infection in Mexican patients with non-investigated dyspepsia].
There are multiple Helicobacter pylori (Hp) detection tests, some are invasive and other noninvasive. The diagnostic accuracy of these methods varies according to the prevalence of the disease. To determine the diagnostic accuracy of the breath test, serology and rapid urease test, considering gastric biopsy with Giemsa stain as the gold standard in Hp-infected subjects with uninvestigated dyspepsia. Eighty four subjects (64 women, mean age 45 years) who were referred for dyspeptic symptoms were evaluated. Also, 20 healthy volunteers (12 men, average age 38 years) were evaluated. All the subjects underwent hystological analysis with Giemsa stain, breath test (Heliprobe®), rapid urease test (CLOtest®) and serological immunoassay (Hexagon®). Overall, Hp infection was diagnosed by histological analysis in 59 subjects (49 patients and 10 healthy subjects). Positivity to breath test, rapid urease test and serology were 56%, 46% and 44% respectively. Agreement with the histological analysis was 0.902 for the breath test, 0.620 for rapid urease test and 0.45 for serology. The area under the curve for the breath test was 0.95, for the rapid urease test was 0.82 and for serological test was 0.74. In our population, the breath test shown to have a diagnostic accuracy equivalent to histological analysis by Giemsa in subjects with uninvestigated dyspepsia.


A Bayesian hierarchal modeling approach to shortening phase I/II trials of anticancer drug combinations.
In phase I/II anticancer drug-combination trials, trial design to evaluate toxicity and efficacy has been studied by dividing the trial into 2 stages, followed by seamless execution of the 2 stages. In the first stage, admissible dose combinations in toxicity are identified, followed by patient assignment among the identified admissible dose combinations using adaptive randomization in the second stage. When patients are assigned using adaptive randomization, it is desirable to determine a more appropriate dose combination by taking into consideration both drug efficacy and toxicity; however, during the course of this determination and evaluation of toxicity and efficacy, there remains a concern that the trial duration might be prolonged. Therefore, we proposed a trial design to assign patients adaptively to more appropriate dose combinations in both toxicity and efficacy and to shorten trial duration without compromising trial performance. When selecting the dose combination for subsequent cohorts, unobserved data are treated as missing data, which are imputed using a data augmentation algorithm involving a gamma process. Probabilities associated with toxicity and efficacy are estimated applying a Bayesian hierarchical model to the imputed data, thereby allowing more patients to be assigned more appropriate dose combinations in both toxicity and efficacy through adaptive randomization. Results of simulation studies suggested that the proposed approach shortened trial duration without significantly compromising the performance of the trial as compared with existing approaches. We believe that the proposed approach will expedite drug development time and reduce costs associated with clinical development.


A fish protein hydrolysate alters fatty acid composition in liver and adipose tissue and increases plasma carnitine levels in a mouse model of chronic inflammation.
There is growing evidence that fish protein hydrolysate (FPH) diets affect mitochondrial fatty acid metabolism in animals. The aim of the study was to determine if FPH could influence fatty acid metabolism and inflammation in transgene mice expressing human tumor necrosis factor alpha (hTNFα). hTNFα mice (C57BL/6 hTNFα) were given a high-fat (23%, w/w) diet containing 20% casein (control group) or 15% FPH and 5% casein (FPH group) for two weeks. After an overnight fast, blood, adipose tissue, and liver samples were collected. Gene expression and enzyme activity was analysed in liver, fatty acid composition was analyzed in liver and ovarian white adipose tissue, and inflammatory parameters, carnitine, and acylcarnitines were analyzed in plasma. The n-3/n-6 fatty acid ratio was higher in mice fed the FPH diet than in mice fed the control diet in both adipose tissue and liver, and the FPH diet affected the gene expression of ∆6 and ∆9 desaturases. Mice fed this diet also demonstrated lower hepatic activity of fatty acid synthase. Concomitantly, a lower plasma INF-γ level was observed. Plasma carnitine and the carnitine precursor γ-butyrobetaine was higher in the FPH-group compared to control, as was plasma short-chained and medium-chained acylcarnitine esters. The higher level of plasma acetylcarnitine may reflect a stimulated mitochondrial and peroxisomal β-oxidation of fatty acids, as the hepatic activities of peroxisomal acyl-CoA oxidase 1 and mitochondrial carnitine palmitoyltransferase-II were higher in the FPH-fed mice. The FPH diet was shown to influence hepatic fatty acid metabolism and fatty acid composition. This indicates that effects on fatty acid metabolism are important for the bioactivity of protein hydrolysates of marine origin.


Improvement of barrier function and stimulation of colonic epithelial anion secretion by Menoease Pills.
Menoease Pills (MP), a Chinese medicine-based new formula for postmenopausal women, has been shown to modulate the endocrine and immune systems. The present study investigated the effects of MP and one of its active ingredients, ligustrazine, on epithelial barrier and ion transport function in a human colonic cell line, T84. Colonic transepithelial electrophysiological characteristics and colonic anion secretion were studied using the short circuit current (ISC) technique. RT-PCR was used to examine the expression of cytoplasmic proteins associated with the tight junctions, ZO-1 (zonula occludens-1) and ZO-2 (zonula occludens-2). Pretreatment of T84 cells with MP (15 microg/mL) for 72 h significantly increased basal potential difference, transepithelial resistance and basal ISC. RT-PCR results showed that the expressions of ZO-1 and ZO-2 were significantly increased after MP treatment, consistent with improved epithelial barrier function. Results of acute stimulation showed that apical addition of MP produced a concentration-dependent (10-5,000 microg/mL, EC50 = 293.9 microg/mL) increase in ISC. MP-induced ISC was inhibited by basolateral treatment with bumetanide (100 micromol/L), an inhibitor of the Na+-K+-2Cl- cotransporter, apical addition of Cl- channel blockers, diphenylamine-2, 2'-dicarboxylic acid (1 mmol/L) or glibenclamide (1 mmol/L), but not 4, 4'-diisothiocyanostilbene-2, 2'-disulfonic acid or epithelial Na+ channel blocker, amiloride. The effect of MP on ZO-1 and ZO-2 was mimicked by Ligustrazine and the ligustrazine-induced ISC was also blocked by basolateral application of bumetanide and apical addition of diphenylamine-2, 2'-dicarboxylic acid or glibenclamide, and reduced by a removal of extracellular Cl-. The results of the present study suggest that MP and lligustrazine may improve epithelial barrier function and exert a stimulatory effect on colonic anion secretion, indicating the potential use of MP and its active ingredients for improvement of GI tract host defense and alleviation of constipation often seen in the elderly.


Insights into the Lignocellulose-Degrading Enzyme System of Humicola grisea var. thermoidea Based on Genome and Transcriptome Analysis.
Humicola grisea var. thermoidea is a thermophilic ascomycete and important enzyme producer that has an efficient enzymatic system with a broad spectrum of thermostable carbohydrate-active (CAZy) enzymes. These enzymes can be employed in lignocellulose biomass deconstruction and other industrial applications. In this work, the genome of H. grisea var. thermoidea was sequenced. The acquired sequence reads were assembled into a total length of 28.75 Mbp. Genome features correlate with what was expected for thermophilic Sordariomycetes. The transcriptomic data showed that sugarcane bagasse significantly upregulated genes related to primary metabolism and polysaccharide deconstruction, especially hydrolases, at both pH 5 and pH 8. However, a number of exclusive and shared genes between the pH values were found, especially at pH 8. H. grisea expresses an average of 211 CAZy enzymes (CAZymes), which are capable of acting in different substrates. The top upregulated genes at both pH values represent CAZyme-encoding genes from different classes, including acetylxylan esterase, endo-1,4-β-mannosidase, exoglucanase, and endoglucanase genes. For the first time, the arsenal that the thermophilic fungus H. grisea var. thermoidea possesses to degrade the lignocellulosic biomass is shown. Carbon source and pH are of pivotal importance in regulating gene expression in this organism, and alkaline pH is a key regulatory factor for sugarcane bagasse hydrolysis. This work paves the way for the genetic manipulation and robust biotechnological applications of this fungus. IMPORTANCE Most studies regarding the use of fungi as enzyme producers for biomass deconstruction have focused on mesophile species, whereas the potential of thermophiles has been evaluated less. This study revealed, through genome and transcriptome analyses, the genetic repertoire of the biotechnological relevant thermophile fungus Humicola grisea. Comparative genomics helped us to further understand the biology and biotechnological potential of H. grisea. The results demonstrate that this fungus possesses an arsenal of carbohydrate-active (CAZy) enzymes to degrade the lignocellulosic biomass. Indeed, it expresses more than 200 genes encoding CAZy enzymes when cultivated in sugarcane bagasse. Carbon source and pH are key factors for regulating the gene expression in this organism. This work shows, for the first time, the great potential of H. grisea as an enzyme producer and a gene donor for biotechnological applications and provides the base for the genetic manipulation and robust biotechnological applications of this fungus.


A robust method for processing scanning probe microscopy images and determining nanoobject position and dimensions.
Processing of scanning probe microscopy (SPM) images is essential to explore nanoscale phenomena. Image processing and pattern recognition techniques are developed to improve the accuracy and consistency of nanoobject and surface characterization. We present a robust and versatile method to process SPM images and reproducibly estimate nanoobject position and dimensions. This method is using dedicated fits based on the least-square method and the matrix operations. The corresponding algorithms have been implemented in the FabViewer portable application. We illustrate how these algorithms permit not only to correct SPM images but also to precisely determine the position and dimensions of nanocrystals and adatoms on surface. A robustness test is successfully performed using distorted SPM images.


Portal vein resection without reconstruction during Appleby operation in a patient with pancreatic body carcinoma with cavernous transformation.
The prognosis of pancreatic body carcinoma has been poor due to cancerous invasion of major vessels. Resection of the involved vessels may improve resectability and prognosis. We report a patient who had a pancreatic body carcinoma with cavernous transformation of the portal vein, in whom the portal vein was resected without reconstruction during an Appleby operation. A 67 year-old man was admitted for evaluation of back pain. Enhanced computed tomography showed no main trunk of the portal vein but a developed collateral circulation. Celiac angiography revealed encasement of the common hepatic, splenic and celiac artery. Venous angiography revealed obstruction of the portal and splenic veins with cavernous transformation surrounding these veins. Pre-operative diagnosis was carcinoma in the pancreatic body, which invaded the portal vein, the celiac and common hepatic arteries. The Appleby operation combined with resection of the portal vein without reconstruction could be performed, by preserving collateral vessels and monitoring hepatic venous oxygen saturation (ShvO2) to prevent hepatic ischemia caused by occlusion of the portal vein. The post-operative course was uneventful.


Cdk-mediated phosphorylation of the Kvβ2 auxiliary subunit regulates Kv1 channel axonal targeting.
Kv1 channels are concentrated at specific sites in the axonal membrane, where they regulate neuronal excitability. Establishing these distributions requires regulated dissociation of Kv1 channels from the neuronal trafficking machinery and their subsequent insertion into the axonal membrane. We find that the auxiliary Kvβ2 subunit of Kv1 channels purified from brain is phosphorylated on serine residues 9 and 31, and that cyclin-dependent kinase (Cdk)-mediated phosphorylation at these sites negatively regulates the interaction of Kvβ2 with the microtubule plus end-tracking protein EB1. Endogenous Cdks, EB1, and Kvβ2 phosphorylated at serine 31 are colocalized in the axons of cultured hippocampal neurons, with enrichment at the axon initial segment (AIS). Acute inhibition of Cdk activity leads to intracellular accumulation of EB1, Kvβ2, and Kv1 channel subunits within the AIS. These studies reveal a new regulatory mechanism for the targeting of Kv1 complexes to the axonal membrane through the reversible Cdk phosphorylation-dependent binding of Kvβ2 to EB1.


Vascular endothelial growth factor causes translocation of p47phox to membrane ruffles through WAVE1.
Growth factors initiate cytoskeletal rearrangements tightly coordinated with nuclear signaling events. We hypothesized that the angiogenic growth factor, vascular endothelial growth factor (VEGF), may utilize oxidants that are site-directed to a complex critical to both cytoskeletal and mitogenic signaling. We identified the WASP-family verprolin homologous protein-1 (WAVE1) as a binding partner for the NADPH oxidase adapter p47phox within membrane ruffles of VEGF-stimulated cells. Within 15 min of VEGF stimulation, p47phox coprecipitated with WAVE1, with the ruffle and oxidase agonist Rac1, and with the Rac1 effector PAK1. VEGF also increased p47phox phosphorylation, oxidant production, and ruffle formation, all of which were dependent upon PAK1 kinase activity. The antioxidant Mn (III) tetrakis(4-benzoic acid) porphyrin and ectopic expression of either the p47-binding WAVE1 domain or the WAVE1-binding p47phox domain decreased VEGF-induced ruffling, whereas the active mutant p4-(S303D, S304D,S328D) stimulated oxidant production and formation of circular dorsal ruffles. Both kinase-dead PAK1-(K298A) and Mn (III) tetrakis(4-benzoic acid) porphyrin decreased c-Jun N-terminal kinase (JNK) activation by VEGF, whereas dominant-negative JNK did not block ruffle formation, suggesting a bifurcation of mitogenic and cytoskeletal signaling events at or distal to the oxidase but proximal to JNK. Thus, WAVE1 may act as a scaffold to recruit the NADPH oxidase to a complex involved with both cytoskeletal regulation and downstream JNK activation.


Chromogenic assay for equine plasminogen.
A functional assay for equine plasminogen was established, using urokinase as the activator, a synthetic chromogenic substrate, a computer-assisted centrifugal analyzer, and acidified/neutralized plasma. One documented effect of plasma acidification appears to be inactivation of alpha-2-antiplasmin. Intra- and interassay precision testing yielded coefficients of variation of 4.1% (n = 10) and 5.6% (n = 26), respectively. Plasminogen was stable in equine plasma stored up to 1 week at 4 C and up to 5 months at -70 C. Plasminogen in nonacidified equine plasma was not activated by urokinase, streptokinase, tissue plasminogen activator, or tissue plasminogen activator plus soluble fibrin. Streptokinase also failed to activate plasminogen in acidified/neutralized equine plasma.


Anti-müllerian Hormone During Natural Cycle Presents Significant Intra and Intercycle Variations When Measured With Fully Automated Assay.
Anti-Müllerian hormone (AMH) is an important ovarian reserve marker for baseline assessment and therapeutic strategy in fertility treatments, which is considered reliable when measured on any day of the cycle. Recent data have pointed toward significant fluctuations of AMH and questioned whether a single measurement is reliable for clinical decision-making. The aim of this study was to evaluate whether the AMH does have significant variations during a natural cycle when a fully automated assay is used for the sample analysis. We performed a prospective study including healthy volunteers with regular cycles, from April to December 2017. Blood samples for AMH, FSH, LH, estradiol, and progesterone were obtained on day 2/3, day 10, day of LH surge, luteal phase and day 2/3 of subsequent menses. AMH analysis was performed with Elecsys® AMH automated assay. Trial was registered with clinical.trials.gov: NCT03106272. One hundred samples from 22 women with a mean age of 30.74 ± 0.11 years and a BMI of 23.23 ± 0.63 kg/m2 were analyzed. There was a substantial longitudinal fluctuation in AMH levels, indicated by the coefficient of variation (CV) intra-cycle of 0.2070 ± 0.143. A positive correlation between LH and AMH concentrations was found at the moment of LH rise (p < 0.0001). Absolute intra-individual inter-cyclic variability was 0.75 ng/mL (range: 0.03-2.81 ng/mL) and inter-cycle CV was 0.28 (Confidence interval: 0.16-0.39; p < 0.0001). According to our results, with the use of a fully automated assay in natural cycle, AMH shows significant intra- and inter-cycle variations, which are not caused by analytical variability. Future investigations, evaluating AMH dynamics and the best time for AMH assessment should be conducted.


Opinions of Finnish small animal owners about surgery and pain management in small animals.
To examine the opinions among small animal owners regarding the management of pain and surgery in small animals. A questionnaire was presented to 800 owners of dogs or cats who visited one of the four participating clinics in Finland in February 2006. A total of 482 owners completed the questionnaire (60.3 per cent response rate); 90 per cent of the respondents were female. Owners classified surgical procedures (for example, fracture repair, skin tumour removal and neutering) as more painful than medical conditions (otitis externa and lameness). In addition, owners disagreed most with statements that they had received sufficient information on the appropriate methods of management of animal pain and that the recognition of animal pain is easy. With respect to surgical procedures, owners expressed greatest concern in relation to the animal experiencing fear or anxiety during hospitalisation and the presence of postoperative pain. The animal owners had concerns about the presence and management of animal pain, fear and anxiety. Knowledge of these animal owner opinions could aid veterinary practitioners when communicating with their clients on medical and surgical patient management. Furthermore, studies are merited to clearly define how best to successfully respond to these owner attitudes.


[Ultrastructure of the cerebrospinal fluid-brain barrier of the cerebral ventricles and blood-brain barrier of the vascular plexus in experimental aseptic leptomeningitis].
The CSF-encephalic barrier of brain ventricles was examined at the submicroscopic level at different times of experimental aseptic leptomeningitis. In the acute period of the pathology, (3 to 7 days) the integrity of the bar was found to be disturbed because of acute inflammatory phenomena. In the subacute period (15 to 30 days), CSF hypertension was demonstrable. In the chronic period (90 days), the development of dystrophic and degenerative processes in the structures of the ependyma and vascular plexus were related to the disorders in CSF- and hemodynamics of the brain. Occlusion of the CSF tract was found to be associated with the impairment of the integrity of the blood- and CSF-encephalic barriers, marked edema end disintegration of the nerve tissue.


Chloroquine and bafilomycin A mimic lysosomal storage disorders and impair mTORC1 signalling.
Autophagy is dependent upon lysosomes, which fuse with the autophagosome to complete the autophagic process and whose acidic interior permits the activity of their intraluminal degradative enzymes. Chloroquine (CQ) and bafilomycin A1 (BafA) each cause alkalinisation of the lumen and thus impair lysosomal function, although by distinct mechanisms. CQ diffuses into lysosomes and undergoes protonation, while BafA inhibits the ability of the vacuolar type H+-ATPase (v-ATPase) to transfer protons into the lysosome. In the present study, we examine the impact of CQ and BafA on the activity of mammalian target of rapamycin complex 1 (mTORC1), inhibition of which is an early step in promoting autophagy. We find each compound inhibits mTORC1 signalling, without affecting levels of protein components of the mTORC1 signalling pathway. Furthermore, these effects are not related to these agents' capacity to inhibit autophagy or the reduction in amino acid supply from lysosomal proteolysis. Instead, our data indicate that the reduction in mTORC1 signalling appears to be due to the accumulation of lysosomal storage material. However, there are differences in responses to these agents, for instance, in their abilities to up-regulate direct targets of transcription factor EB (TFEB), a substrate of mTORC1 that drives transcription of many lysosomal and autophagy-related genes. Nonetheless, our data imply that widely used agents that alkalinise intralysosomal pH are mimetics of acute lysosomal storage disorders (LSDs) and emphasise the importance of considering the result of CQ and BafA on mTORC1 signalling when interpreting the effects of these agents on cellular physiology.


Bacterial death comes full circle: targeting plasmid replication in drug-resistant bacteria.
It is now common for bacterial infections to resist the preferred antibiotic treatment. In particular, hospital-acquired infections that are refractory to multiple antibiotics and ultimately result in death of the patient are prevalent. Many of the bacteria causing these infections have become resistant to antibiotics through the process of lateral gene transfer, with the newly acquired genes encoding a variety of resistance-mediating proteins. These foreign genes often enter the bacteria on plasmids, which are small, circular, extrachromosomal pieces of DNA. This plasmid-encoded resistance has been observed for virtually all classes of antibiotics and in a wide variety of Gram-positive and Gram-negative organisms; many antibiotics are no longer effective due to such plasmid-encoded resistance. The systematic removal of these resistance-mediating plasmids from the bacteria would re-sensitize bacteria to standard antibiotics. As such, plasmids offer novel targets that have heretofore been unexploited clinically. This Perspective details the role of plasmids in multi-drug resistant bacteria, the mechanisms used by plasmids to control their replication, and the potential for small molecules to disrupt plasmid replication and re-sensitize bacteria to antibiotics. An emphasis is placed on plasmid replication that is mediated by small counter-transcript RNAs, and the "plasmid addiction" systems that employ toxins and antitoxins.


Adaptive Policies to Balance Health Benefits and Economic Costs of Physical Distancing Interventions during the COVID-19 Pandemic.
Policy makers need decision tools to determine when to use physical distancing interventions to maximize the control of COVID-19 while minimizing the economic and social costs of these interventions. We describe a pragmatic decision tool to characterize adaptive policies that combine real-time surveillance data with clear decision rules to guide when to trigger, continue, or stop physical distancing interventions during the current pandemic. In model-based experiments, we find that adaptive policies characterized by our proposed approach prevent more deaths and require a shorter overall duration of physical distancing than alternative physical distancing policies. Our proposed approach can readily be extended to more complex models and interventions.


The delta subunit of RNA polymerase, RpoE, is a global modulator of Streptococcus mutans environmental adaptation.
The delta subunit of RNA polymerase, RpoE, is widespread in low-G+C Gram-positive bacteria and is thought to play a role in enhancing transcriptional specificity by blocking RNA polymerase binding at weak promoter sites and stimulating RNA synthesis by accelerating core enzyme recycling. Despite the well-studied biochemical properties of RpoE, a role for this protein in vivo has not been defined in depth. In this study, we show that inactivation of rpoE in the human dental caries pathogen Streptococcus mutans causes impaired growth and loss of important virulence traits, including biofilm formation, resistance to antibiotics, and tolerance to environmental stresses. Complementation of the mutant with rpoE expressed in trans restored its phenotype to wild type. The luciferase fusion reporter showed that rpoE was highly transcribed throughout growth and that acid and hydrogen peroxide stresses repressed rpoE expression. Transcriptome profiling of wild-type and ΔrpoE cells in the exponential and early stationary phase of growth, under acid and hydrogen peroxide stress and under both stresses combined, revealed that genes involved in histidine synthesis, malolactic fermentation, biofilm formation, and antibiotic resistance were downregulated in the ΔrpoE mutant under all conditions. Moreover, the loss of RpoE resulted in dramatic changes in transport and metabolism of carbohydrates and amino acids. Interestingly, differential expression, mostly upregulation, of 330 noncoding regions was found. In conclusion, this study demonstrates that RpoE is an important global modulator of gene expression in S. mutans which is required for optimal growth and environmental adaptation.


Group 3 ILCs: Peacekeepers or Troublemakers? What's Your Gut Telling You?!
A complex network of interactions exists between the microbiome, the epithelium, and immune cells that reside along the walls of the gastrointestinal tract. The intestinal immune system has been assigned with the difficult task of discriminating between commensal, harmless bacteria, and invading pathogens that translocate across the epithelial monolayer. Importantly, it is trained to maintain tolerance against commensals, and initiate protective immune responses against pathogens to secure intestinal homeostasis. Breakdown of this fine balance between the host and its intestinal microbiota can lead to intestinal inflammation and subsequently to development of inflammatory bowel disease (IBD). A decade since their discovery, innate lymphoid cells (ILCs) are now recognized as important regulators of intestinal homeostasis. ILC3s have emerged as a critical subset in the gut. They are the most phenotypically diverse ILC population and interact directly with numerous different cell types (haematopoietic and non-haematopoeitic), as well as interface with the bacterial flora. In addition to their contribution to intestinal pathogen immunity, they also mitigate against tissue damage occurring following acute injury, by facilitating tissue repair and regeneration, a key function in the maintenance of intestinal homeostasis. However, in chronic inflammation the tables are turned and ILC3s may acquire a pro-inflammatory phenotype in the gut. Chronic ILC activation can lead to persistent inflammation contributing to IBD and/or colorectal cancer. In this review, we discuss current knowledge of group 3 ILCs and their contributions to intestinal homeostasis and disease leading to novel therapeutic targets and clinical approaches that may inform novel treatment strategies for immune-mediated disorders, including IBD.


White matter mapping using diffusion tensor MRI.
Diffusion tensor MRI is used to define trajectories that reflect the long-range order of in vivo white matter (WM) fiber tracts. Fiber tracking is particularly prone to cumulative error from noise and partial volume along the length of the trajectory paths, but the overall shape of each path is anatomically meaningful. By considering only the long-range similarity of path shapes, a method of constructing 3D maps of specific WM structures has been developed. A trajectory is first computed from an operator-selected seed voxel, located within the anatomical structure of interest (SOI). Voxels from the same structure are then automatically identified based on the similarity of trajectory path shapes, assessed using Pearson's correlation coefficient. The corpus callosum and pyramidal tracts in 14 patients with multiple sclerosis, and in 10 healthy controls were mapped by this method, and the apparent diffusion coefficient (ADC) was measured. The ADC was significantly higher in patients than in controls, and higher in the corpus callosum than in the pyramidal tracts for both groups. Using this method the different functional structures in the WM may be identified and mapped. Within these maps, MRI parameters can be measured for subsequent comparison with relevant clinical data.


On the mechanism of selenium tolerance in selenium-accumulating plants. Purification and characterization of a specific selenocysteine methyltransferase from cultured cells of Astragalus bisculatus.
Selected members of the genus Astragalus (Fabaceae) are known for their ability to accumulate high levels of selenium, mainly in the form of Se-methyl-selenocysteine. With the aid of cell cultures we have investigated the molecular basis for selenium tolerance of these plants. It is shown that cultured cells from a selenium-accumulating Astragalus species synthesize Se-methyl-selenocysteine in contrast to those of a non-accumulating species and do not unspecifically incorporate selenium into proteins. The purification and biochemical characterization of a selenocysteine methyltransferase from cultured Astragalus bisculatus cells is described, which does not accept cysteine as a substrate. We propose that this enzyme plays a crucial role in conferring selenium tolerance.


Vanadium dioxide devices for terahertz wave modulation: a study of wire grid structures.
Vandium dioxide (VO2) shows promise as the basis for a terahertz wave modulator due to its phase transition properties. Its insulator-metal-transition (IMT) can be induced either through temperature changes, optically or electronically. Recently, a metal-VO2 wire grid structure was proposed which was able to increase the modulation depth (MD) from 0.65 to 0.9, suggesting that these simple metallic structures could greatly increase the difference in terahertz transmission for the insulating and metallic states of VO2 based structures. In this paper, we have found that the increase in MD decreases with increasing VO2 conductivity in the metallic state, resulting in a maximum modulation depth of approximately 0.95 for wire grid structures that preserves a high transmission in the insulating state. Surprisingly, we find that deposition of VO2 on top of metallic structures results in reduced performance. However, we find that devices based upon VO2 alone can achieve unexpectedly high performance. In this work we present a device with a switchable wire-grid polariser effect over a broadband frequency range (from 0.3 to 2 THz). To our knowledge this is the first such broadband metamaterial based solely on VO2. The ability to switch on a metamaterial property like this to produce a polarisation effect is very useful for future terahertz optical devices such as rotators and waveplates.


Frontal brain electrical asymmetry and cardiac vagal tone predict biased attention to social threat.
Individual differences in attention biases for motivationally significant stimuli have been reported in clinical and normative populations. Few studies, however, have attempted to examine potential biological mechanisms underlying differences in the cognitive processing of emotional stimuli. The present study examined the extent to which two well-validated psychophysiological vulnerability markers of affective style [i.e., frontal electroencephalogram (EEG) asymmetry and cardiac vagal tone] predicted biased attention toward rapid presentations (approximately 250 ms) of angry and happy facial expressions. We found that right frontal EEG asymmetry and low cardiac vagal tone, taken together, predicted approximately 37% of the variability in attentional vigilance for angry faces. Frontal EEG asymmetry and cardiac vagal tone did not predict attention for happy faces, independently of each other. Our results provide preliminary evidence that two well established psychophysiological indicators of affective style bias early processing of motivationally salient stimuli.


Acknowledging the Risk for Traumatic Brain Injury in Women Veterans.
Since the Iraq and Afghanistan wars began, an unprecedented number of women have been engaging in combat operations. Likewise, the number of women using Department of Veterans Affairs (VA) services has doubled since 2001. Military service, and deployment to combat in particular, poses certain risks for traumatic brain injury (TBI)-for all service members. However, women may have additional military and nondeployment risk factors such as intimate partner violence (IPV). We briefly review the definition and classification issues related to TBI, as well as common acute and chronic health symptoms after TBI. Specific sex differences in prognosis after TBI, in particular the neurobehavioral symptoms, are also reviewed. We then focus on the emerging literature regarding TBI in women veterans including the etiologies, outcomes, and unique challenges this population faces. The article concludes with suggestions for enhanced screening by VA and non-VA providers alike, as well as directions for future research and clinical inquiry.


Diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia.
Excessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (VAP). However, successful validation of the usefulness of potential markers in this setting is exceptionally rare. We sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP. A prospective, multicentre, validation study of patients with suspected VAP was conducted in 12 intensive care units. VAP was confirmed following bronchoscopy by culture of a potential pathogen in bronchoalveolar lavage fluid (BALF) at >10(4) colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1β), IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were quantified in BALF. Diagnostic utility was determined for biomarkers individually and in combination. Paired BALF culture and biomarker results were available for 150 patients. 53 patients (35%) had VAP and 97 (65%) patients formed the non-VAP group. All biomarkers were significantly higher in the VAP group (p<0.001). The area under the receiver operator characteristic curve for IL-1β was 0.81; IL-8, 0.74; MMP-8, 0.76; MMP-9, 0.79 and HNE, 0.78. A combination of IL-1β and IL-8, at the optimal cut-point, excluded VAP with a sensitivity of 100%, a specificity of 44.3% and a post-test probability of 0% (95% CI 0% to 9.2%). Low BALF IL-1β in combination with IL-8 confidently excludes VAP and could form a rapid biomarker-based rule-out test, with the potential to improve antibiotic stewardship.


[Hereditary spherocytosis. Review. Part II. Symptomatology, outcome, complications, and treatment].
Hereditary spherocytosis must always be suspected in children with anemia, hyperbilirubinemia, splenomegaly or cholelithiasis, in the asymptomatic individual with an affected relative, and in the neonate with hyperbilirubinemia with no blood group incompatibility; its early detection is key to avoid kernicterus. Follow-up of these patients is based on periodical control and supply of information on the adequate management of hemolytic or aplastic crisis, and early detection of cholelithiasis. The decision to perform splenectomy is usually associated with quality of life rather than life-threatening risk, and it should result from a consensus between patient, parents and physicians. The postsplenectomy follow-up is based on control of compliance with the prophylactic antibiotic therapy and the early diagnosis of infectious disorders.


Environmental gains in the collection of packaging waste obtained in Uskudar district by changing the collection type.
The collection of packaging wastes separately from domestic wastes is a legal requirement and has become a necessity due to the need for raw materials today. Due to the legislative requirements, disruptions in practice constitute an obstacle to create a successful waste management policy. The subject of this study is to provide a system that will help the administrators of the district municipalities who want to collect the packaging wastes with their own means. In Uskudar municipality defined as a pilot area, environmental gains have been achieved by collecting packaging wastes separately from domestic wastes in two different days. The results of the collection of packaging wastes from households separately from domestic wastes were analyzed by separate collection days of district municipalities. Waste characterization studies are carried out, and the evaluation is presented. In this study, it was determined that the environmental gains obtained by changing only the packaging waste collection days yielded important results. The classical collection model, Uskudar Model and the effect of not collecting packaging wastes on ecosystem and people were examined by life cycle analysis.Implications: The importance of the environmental contribution of the proper packaging waste collection system. Environmental contributions provided by recycling only by changing the collection system. Revealing the environmental contributions of the packaging waste collection system through life cycle analysis.


Minimally invasive reduction and percutaneous fixation versus open reduction and internal fixation for displaced intra-articular calcaneal fractures: A systematic review of the literature.
The aim of this article is to systematically identify and analyse research evidence available to compare the outcomes of minimally invasive reduction and percutaneous fixation (MIRPF) versus open reduction and internal fixation (ORIF) for displaced intra-articular calcaneal fractures.Articles from 2000 to 2016 were searched through MEDLINE (PubMed), Cochrane Library, Embase, ScienceDirect, Scopus and ISI Web of Knowledge using Boolean logic and text words. Of the 570 articles identified initially, nine were selected including three randomized controlled trials and six retrospective comparative studies.All nine studies had a total of 1031 patients with 1102 displaced intra-articular calcaneal fractures. Mean follow-up was 33 months. Of these, 602 (54.6%) were treated with MIRPF and 500 (45.4%) were treated with ORIF.Overall incidence of wound-related complications in patients treated with MIRPF was 4.3% (0% to 13%) compared with 21.2% (11.7% to 35%) in the ORIF groupFunctional outcomes were reported to be better in the minimally invasive group in all studies; however, the results did not reach statistical significance in some studies. All the studies had methodological flaws that put them at either 'unclear' or 'high' risk of bias for multiple domains.Overall quality of the available evidence is poor in support of either surgical technique due to small sample size, flaws in study designs and high risk of bias for various elements. Individual studies have reported minimally invasive techniques to be an effective alternative with lower risk of wound complications and better functional outcomes. Cite this article: EFORT Open Rev 2018;3:418-425. DOI: 10.1302/2058-5241.3.170043.