A paddy field study of arsenic and cadmium pollution control by using iron-modified biochar and silica sol together.
Under flooded conditions in paddy soil, the mobility of As increases while the mobility of Cd decreases. The opposite geochemical behavior of As and Cd makes it difficult to reduce their mobilities simultaneously. Our recent study found that combined applications of biochar and zero-valent iron successfully reduced the mobilities of As and Cd simultaneously. On this basis, in the present study, an iron-modified biochar (Fe-BC) was developed, and its effect on decreasing the accumulations of As and Cd in rice was verified in a 2-year field trial. In addition, previous studies indicated that silicon fertilizer can also reduce As and Cd accumulation in rice grain. Hence, the effect of the combined or separate application of Fe-BC and silica sol on As and Cd accumulation in rice grain was investigated. Over the 2-year field trial, the grain yields decreased in the following order: iron-modified biochar plus silica sol (Fe-BC plus Si) > silica sol (Si) > Fe-BC > control (CK). Concentrations of As and Cd in brown rice were in the order: Fe-BC plus Si < Si ≈ Fe-BC < CK. The treatments of Fe-BC and Fe-BC plus Si significantly increased the soil pH and thus decreased available As and available Cd in the soil. In addition, significantly positive correlations between available As and As in brown rice and between available Cd and Cd in brown rice were found. In conclusion, co-application of iron-modified biochar and silica sol should be a recommended strategy to reduce the accumulation of As and Cd in rice grains.


Analyte stability in clinical chemistry quality control materials.
Maximum stability of analytes in chemistry control materials is desired. Stability testing is customarily performed by manufacturers, both prior to distribution of products and during the period following distribution when the products are in the field. Users and evaluators of such materials periodically have reported on experienced stability of various analytes in distributed manufactured products. A wide variety of both testing protocols and definitions of acceptable stability have characterized published reports on the topic. In the present review, we summarize published studies on control material stability in clinical chemistry, review criteria employed to define instability, and present an approach to evaluating stability of analytes involving both statistical and clinical criteria.


Understanding the influence of power and empathic perspective-taking on collaborative natural resource management.
Public engagement in collaborative natural resource management necessitates shared understanding and collaboration. Empathic perspective-taking is a critical facilitator of shared understanding and positive social interactions, such as collaboration. Yet there is currently little understanding about how to reliably generate empathic perspective-taking and collaboration, particularly in situations involving the unequal distribution of environmental resources or power. Here we examine how experiencing the loss or gain of social power influenced empathic perspective-taking and behavior within a computer-mediated scenario. Participants (n = 180) were randomly assigned to each condition: high resources, low resources, lose resources, gain resources. Contrary to our expectations, participants in the perspective-taking condition, specifically those who lost resources, also lost perspective taking and exhibited egoistic behavior. This finding suggests that resource control within the collaborative process is a key contextual variable that influences perspective-taking and collaborative behavior. Moreover, the observed relationship between perspective-taking and egoistic behavior within a collaborative resource sharing exercise suggests that when resource control or access is unequal, interventions to promote perspective-taking deserve careful consideration.


Cyanopyridine Based Bipolar Host Materials for Green Electrophosphorescence with Extremely Low Turn-On Voltages and High Power Efficiencies.
Low driving voltage and high power efficiency are basic requirements when practical applications of organic light emitting diodes (OLEDs) in displays and lighting are considered. Two novel host materials m-PyCNmCP and 3-PyCNmCP incorporating cyanopyridine moiety as electron-transporting unit are developed for use in fac-tris(2-phenylpyridine)iridium(III) (Ir(ppy)3) based green phosphorescent OLEDs (PhOLEDs). Extremely low turn-on voltages of 2.01 and 2.27 V are realized, which are even lower than the theoretical limit of the emitted photon energy (hv)/electron charge (e) (2.37 V) of Ir(ppy)3. High power efficiency of 101.4 lm/W (corresponding to a maximum external quantum efficiency of 18.4%) and 119.3 lm/W (24.7%) are achieved for m-PyCNmCP and 3-PyCNmCP based green PhOLEDs. The excellent EL performance benefits from the ideal parameters of host materials by combining cyano and pyridine to enhance the n-type feature. The energetic favorable alignment of HOMO/LUMO levels of hosts with adjacent layers and the dopant for easy charge injections and direct charge trapping by dopant, their bipolar feature to balance charge transportations, sufficiently high triplet energy and small singlet/triplet energy difference (0.38 and 0.43 eV) combine to be responsible for the extremely low driving voltages and high power efficiencies of the green PhOLEDs.


Does Federalism Prevent Democratic Accountability? Assigning Responsibility for Rates of COVID-19 Testing.
Does federalism prevent citizens from holding governments accountable for their actions? The pandemic represents the ideal scenario for testing the effects of federalism on democratic accountability because citizens are highly motivated to hold governments accountable for preventing or failing to prevent the rapid transmission of the virus. Previous research suggests that a number of institutional and political factors complicate the accountability function in federal systems. We add to this literature by assessing the effect of one political factor, exclusivity (measured in terms of policy variation at one level), on accountability. The coronavirus pandemic provides a unique opportunity to assess this factor given the high levels of issue saliency, media attention, and low levels of intergovernmental and interparty conflict it has generated. Drawing on original data from the May 2020 Democratic Checkup Survey and public data from the Canadian National Microbiology Laboratory, our preliminary findings suggest that interprovincial policy variation with respect to coronavirus testing is not correlated with public assessments of the adequacy of provincial testing, and so it seems that Canadians are not able to assign responsibility to the correct level of government despite ideal conditions for doing so.


SRP54 mediates circadian rhythm-related, temperature-dependent gene expression in Drosophila.
Recent studies have shown that alternative splicing (AS) plays an important role in regulating circadian rhythm. However, it is not clear whether clock neuron-specific AS is circadian rhythm dependent and what genetic and environmental factors mediate the circadian control of AS. By genome-wide RNA sequencing, we identified SRP54 is one of the Clock (Clk) dependent alternative splicing factors. Genetic interaction between Clock and SRP54 alleles showed that the enhancement of the circadian phenotype increased with temperature, being strongest at 29 °C and weakest at 18 °C. The alternative splicing and differential gene expression profile of Clock and SRP54 overlapped with the circadian-related gene profiles identified in various genome-wide studies, indicating that SRP54 is involved in circadian rhythm. By analyzing of the RNA-seq results at different temperatures, we found the roles of Clock and SRP54 are temperature dependent. We also found multiple novel temperature-dependent transcripts not documented in current databases.


The Phonological Development of Mandarin Voiceless Affricates in Three- to Five-Year-Old Children.
This study investigates the phonological development of Mandarin voiceless affricates produced by Mandarin-speaking children. Thirty-six monolingual Mandarin-speaking children and twelve adults participated in a speech production task. Auditory-based transcription analysis and acoustic analysis were utilized to quantify the relative order of affricate acquisition. Both methods yielded earlier acquisition of alveopalatal affricates at age three than retroflex and alveolar affricates, whereas they differed in the acquisition order of retroflex and alveolar affricates. The former revealed that both retroflex and alveolar affricates were acquired at age five, regardless of aspiration, while the latter yielded earlier acquisition of retroflex than alveolar affricates. Possible reasons for the discrepancy are discussed in relation to the different nature of the two methods. Overall, the observed acquisition order of Mandarin voiceless affricates suggests that child speech development is a complex process, and is influenced by various factors including oromotor maturation and language-specific phoneme frequencies in the ambient language.


Dietary Patterns in 1125 Iranian Women: Adequacy of Energy and Micronutrient Intakes and Weight Statuses.
Women's nutrition status includes significant effects on their children and household health. The purpose of this study was to assess energy and micronutrient intake adequacy in Iranian women. This study was a part of the Urban HEART Study, which has jointly been developed by the World Health Organization (WHO) Centre for Health Development, Kobe, Japan. In total, anthropometric and dietary intake data were collected from 1125 women in southern Tehran municipality districts. A 24-h recall questionnaire was completed by the expert nutritionists and the participants' anthropometric statuses were assessed. Food intakes were calculated in grams per capita per day. Micronutrients and energy requirements were adapted from WHO/Food and Agriculture Organization (FAO) tables and Iran National Food Consumption Survey, respectively. Nearly 71.5% of the women were overweight or obese [body mass index (BMI) ≥25 kg/m2]. Furthermore, 1.2% of the women were underweight (BMI <18.5 kg/m2), while 27.3% had normal weight (BMI = 18.5--24.9 kg/m2). The mean bread/cereal and vegetable intakes were significantly higher in obese group, compared to that in normal/under/overweight group (375.6 g/day ± 151.4, P = 0.05; and 331.4 g/day ± 227.5, P = 0.02), respectively]. Women in the lean group significantly consumed higher quantities of cakes/pastries and had the lowest calcium and iron adequacy ratios, compared to other groups (p = 0.001, P = 0.03, and P = 0.05, respectively). These findings suggest that Iranian women, especially those who reside in the southern areas of Tehran, need to change their dietary habits to maintain their health. Moreover, being under/normal weight does not necessarily mean following healthy diets.


Reflex bradycardia induced by hydralazine in sino-aortic deafferented conscious rats.
1. It is generally recognized that the vasodilator hydralazine produces hypotension accompanied by baroreflex-mediated tachycardia. In some experimental conditions, however, the accompanying heart rate change is bradycardia, a paradoxical response which has not been satisfactorily explained. The present study examined the possibility of hydralazine-induced bradycardia being mediated by vagal or sympathetic afferents activated by changes in left ventricular pressure. 2. Systolic blood pressure and heart rate responses to hydralazine were recorded in conscious normotensive intact rats by a tail cuff method and compared with responses in animals subjected to previous sino-aortic deafferentation (SAD) to remove the influence of the arterial baroreflex. Responses were also obtained after blockade of myocardial afferent vagal C-fibres with urethane, of efferent vagal impulses to the heart with methylatropine, of positive inotropic effects of hydralazine with atenolol, and of prostanoid sensitization of myocardial nerve fibres with indomethacin. 3. Hydralazine produced hypotension and tachycardia in intact rats, and hypotension and bradycardia in SAD animals. In intact rats, this pattern was not affected by any of the pretreatments, while in SAD rats, all pretreatments reversed the bradycardia to hydralazine. 4. The present results indicate that suppression of the arterial baroreflex by SAD propitiates the appearance of a bradycardiac response to hydralazine. This reaction probably results from activation of a vagal cardiodepressant reflex originating in the heart, as suggested by its blockade by drugs acting at various sites along the reflex arch.


Ovarian activity and oestrous signs among group-housed, lactating sows: influence of behaviour, environment and production.
Animal welfare concerns require the development of housing systems that allow the animals to express their natural behaviour. One example of this is the group-housing system for lactating sows. The present study aimed at exploring ovarian activity in such a system. Thirty-eight sows farrowing individually outdoors during spring and summer, and indoors during autumn and winter, and group-housed in groups of four during weeks 3-7 of the lactation period, were monitored regarding reproductive functions, behaviour and production during their first to fourth lactation period. Average ovulation frequency during lactation was 47%. Only 50% of these ovulating cases were accompanied by a standing oestrus. Lactational ovulation frequency was higher in later parities (p < 0.001). Ovulation frequency was higher (p < 0.05) during winter (74%) and spring (69%), than during summer (10%) and autumn (23%). Occurrence of lactational ovulation was associated with some aspects of suckling behaviour and also with litter weight gain (p < 0.05). Forty-nine per cent of the lactational ovulations occurred during the seventh week of lactation. Timing of ovulation seemed positively (p = 0.08) associated with weight loss during lactation. Compared with the sows that were anoestrus during lactation, oestradiol-17beta values were higher (p < 0.05) only in the week before occurrence of lactational ovulation. Weaning-to-oestrous interval was prolonged (p < 0.05) among the sows that ovulated during lactation. The present study identifies several factors influencing ovarian activity among group-housed sows, thereby providing tools for the control of lactational ovulation in group-housing systems.


Anesthetic considerations in chest trauma.
At the R. Adams Cowley Shock Trauma Center, participation of anesthesiologists in the care of thoracic trauma victims begins with the initial assessment of patients on arrival by helicopter or ambulance. It continues with management of the airway, stabilization of hemodynamics, intraoperative management, patient care in the PACU and critical care setting, and acute pain management. By using a team approach involving anesthesia, surgery, and critical care, the care of trauma victims with thoracic injury continues to be enhanced.


A qualitative study of barriers and facilitators of the charge nurse role.
This qualitative study examines the barriers and facilitators to the role of charge nurse at a medical center. The authors interviewed 42 nursing personnel, including charge nurses (12), head nurses (10), staff nurses (11), and supervisory personnel (9). A total of 24 barriers and facilitators in three categories were identified: personal (11), interpersonal (8), and organizational (5). These factors could be used to inform developmental coaching and educational programs for charge nurses.


Revealing the secret life of pre-implantation embryos by time-lapse monitoring: A review.
High implantation success following in vitro fertilization cycles are achieved via the transfer of embryos with the highest developmental competence. Multiple pregnancies as a result of the transfer of several embryos per cycle accompany with various complication. Thus, single-embryo transfer (SET) is the preferred practice in assisted reproductive technique (ART) treatment. In order to improve the pregnancy rate for SET, embryologists need reliable biomarkers to aid their selection of embryos with the highest developmental potential. Time-lapse technology is a noninvasive alternative conventional microscopic assessment. It provides uninterrupted and continues the survey of embryo development to transfer day. Today, there are four time-lapse systems that are commercially available for ART centers. In world and Iran, the first time lapse babies were born in 2010 and 2015, respectively, conceived by SET. Here, we review the use of time-lapse monitoring in the observation of embryogenesis as well as its role in SET. Although, the findings from our review support common use of time-lapse monitoring in ART centers; but, future large studies assessing this system in well-designed trials are necessary.


Sacral nerve stimulation for the management of voiding dysfunction.
Voiding dysfunction is common, and patients with urge incontinence, frequency/urgency syndromes, and chronic urinary retention are challenging to treat once conservative therapies (such as pharmacologic agents, pelvic floor rehabilitation, and intermittent catheterization) have been exhausted. Sacral nerve stimulation (SNS) is a new, minimally invasive, reversible therapy for the management of refractory voiding dysfunction and provides an attractive therapeutic alternative for patients with this condition. In this review, the role of SNS in the management of voiding dysfunction is examined critically, and the efficacy, risks, and benefits of this new modality are evaluated.


Viral and host genetic factors influence encephalomyocarditis virus-induced polymyositis in adult mice.
Recent research findings implicate picornaviruses in the etiology of human polymyositis/dermatomyositis and suggest that genetic factors play a role in susceptibility to these diseases. We compared 2 variants of encephalomyocarditis (EMC) virus for their ability to induce polymyositis in adult mice, and evaluated what role the genetic background of the host plays in the degree of myositis induced. While BALB/c mice developed minimal myositis when infected with a diabetogenic variant (EMC-D), the same strain inoculated with a newly isolated myopathic variant (EMC-221A) developed viral dose-dependent elevations in muscle-associated enzymes, bilateral limb muscle weakness, and the histopathologic changes of severe polymyositis. Mice with different genetic backgrounds showed significantly different susceptibilities to EMC-221A. These data suggest that the severity of polymyositis induced by EMC virus is influenced by both the viral and host genomes.


[The role computerized telethermography in the diagnosis of fibromyalgia syndrome].
Fibromyalgia syndrome is a form of extraarticular rheumatism of unknown origin; its diagnosis is fundamentally based on clinical and anamnestic findings, on characteristics of pain and on number and sites of tender points, very painful areas to palpation. At present there is no laboratory or instrumental test available for a more objective diagnosis. The Authors verified the utility of telethermography for fibromyalgia syndrome diagnosis to point out a possible specific pattern; in particular the tender points were studied, even to find some analogy to myofascial syndromes trigger points, which appear as hot spot to telethermography. The telethermographic patterns of 156 patients with fibromyalgia syndrome have been compared with tender point maps obtained from same subjects and with telethermographic data of patients affected by spine osteoarthritis and normal controls. The patients with fibromyalgia syndrome showed a non specific hyperthermic pattern, corresponding to painful muscular areas, comparable with pattern of osteoarthritic patients. This phenomenon can be interpreted as a greater thermic emission by hypertonic muscles. Therefore, telethermography in fibromyalgia syndrome cannot represent a basic diagnostic tool but can support the clinical diagnosis and play an important role in the follow-up of patients.


Ingratiation Attempts in Real Life: Determinants of Their Success.
A total of 272 students at a German university were asked to write down the story of an ingratiation attempt they had made and one they had received. They were then asked to reflect on each episode via a questionnaire. All but one participant reported that they had performed at least one of the four tactics postulated in Jones's ingratiation theory: compliments, favor-doing, opinion conformity, and positive self-presentation. In the case of received ingratiation, we found higher success ratings for nondependent (vs. dependent) partners, for just-being-friendly (vs. attraction-seeking) as the attributed motive, and for honest (vs. nonhonest) compliments and self-presentation. Female senders reported more success than did males (interpretable through existing research on gender differences). Finally, success levels were higher in the sender than in the receiver condition. Thus with our new autobiographical method we have extended the validity of three known determinants of the success of ingratiation attempts and discovered two "novel" factors deserving further research.


Mechanical power curve measured in the wake of pied flycatchers indicates modulation of parasite power across flight speeds.
How aerodynamic power required for animal flight varies with flight speed determines optimal speeds during foraging and migratory flight. Despite its relevance, aerodynamic power provides an elusive quantity to measure directly in animal flight. Here, we determine the aerodynamic power from wake velocity fields, measured using tomographical particle image velocimetry, of pied flycatchers flying freely in a wind tunnel. We find a shallow U-shaped power curve, which is flatter than expected by theory. Based on how the birds vary body angle with speed, we speculate that the shallow curve results from increased body drag coefficient and body frontal area at lower flight speeds. Including modulation of body drag in the model results in a more reasonable fit with data than the traditional model. From the wake structure, we also find a single starting vortex generated from the two wings during the downstroke across flight speeds (1-9 m s-1). This is accomplished by the arm wings interacting at the beginning of the downstroke, generating a unified starting vortex above the body of the bird. We interpret this as a mechanism resulting in a rather uniform downwash and low induced power, which can help explain the higher aerodynamic performance in birds compared with bats.


Norepinephrine increases alveolar fluid reabsorption and Na,K-ATPase activity.
The purpose of this study was to determine whether alpha-adrenergic receptor agonists have a role in alveolar fluid reabsorption, via Na,K-ATPase, in the alveolar epithelium. Alveolar fluid reabsorption increased approximately twofold with increasing concentrations of norepinephrine (NE) as compared with control rats. Treatment with the nonselective alpha-adrenergic receptor agonist, octopamine, and the specific alpha(1) agonist, phenylephrine, increased alveolar fluid reabsorption by 54 and 40%, respectively, as compared with control. The specific alpha(1)-adrenergic receptor antagonist, prazosin, inhibited the stimulatory effects of NE by approximately 30%, whereas alpha(2)-adrenergic antagonist, yohimbine, did not prevent the stimulatory effects of NE. The administration of ouabain, Na,K-ATPase inhibitor, prevented the NE-mediated increase in alveolar fluid reabsorption. In parallel with these changes, NE increased Na,K-ATPase activity and protein abundance in alveolar epithelial type II cells via the alpha(1)- and beta-adrenergic receptor. We report here that NE increased alveolar fluid reabsorption via the activation of both alpha(1)- and beta-adrenergic receptors, but not alpha(2)-adrenergic receptors. These effects are due to increased activity and abundance of the Na,K-ATPase in the basolateral membrane of ATII cells.


Efficacy of a topical bovine-derived thrombin solution as a hemostatic agent in a rodent model of hepatic injury.
Hemorrhage is a major concern in patients undergoing hepatic surgery or in those with hepatic trauma. In these cases, employing traditional hemostatic strategies can be problematic due to the diffuse nature of hepatic hemorrhage and limited opportunities for direct hemostasis. This study assessed the efficacy of a bovine-derived thrombin solution, (BT), as a topical liquid agent to augment hemostasis and survival following severe hepatic hemorrhage in a rat model. Heart rate (HR), arterial blood pressure (ABP), packed cell volume (PCV), and overall survival were evaluated in 54 rats randomly assigned to receive topical application of BT, saline, or suture ligation applied immediately to a liver lobe following controlled laceration. Six additional rats received liver laceration with no applied treatment. Intravenous fluid resuscitation was initiated and HR and ABP were recorded for 60 min, after which survivors were recovered from anesthesia. Rats were then monitored for 72 h, after which survivors were euthanized. There was no significant difference in survival time, percentage survival, intra-operative ABP or HR, or post-operative PCV between treatment groups. There is insufficient evidence to recommend BT as the sole therapy using this delivery method for mitigating severe hemorrhage from liver injury.


Recoil anisotropy following multiphoton dissociation via near-resonant intermediate states.
Expressions are derived for the moments beta(n) of the anisotropy of fragment recoil following multiphoton dissociation. The results for all possible two- and three-photon excitation pathways from a sigma or pi initial state, with prompt dissociation, are listed in tabular and graphical form, thereby facilitating the identification of pathways compatible with experimental data. The consequence of possible interference between multiple-excitation pathways is discussed. In addition, allowance is made for rotation of the parent molecule in the dissociating state on the time scale of its dissociation, with specific equations for three cases: fully resolved rotation on excitation, significant but unresolved rotation, and the intermediate case of partially resolved excitation. Finally, expressions are given for the consequence of significant rotation in a near-resonant intermediate state. It is pointed out that the effects of rotation can lead to a strong variation of the anisotropic moments over an excitation band, and that the absence of rotational features does not necessarily imply that the effects of rotation on recoil anisotropy can be ignored. The application of the theory is illustrated for a number of model systems, restricted to diatomic molecules with possible rotation but subsequent axial recoil. However, the expressions are easily adapted to polyatomic systems, provided that any fragment rotation is unresolved.


The roles of drug therapy given via the endotracheal tube to neonates.
Many drugs are given to intubated neonates by the inhalation route. The optimum aerosol delivery system, however, has not been identified and there are many challenges in delivering drugs effectively to the lower airways of intubated neonates. The effectiveness of surfactant in prematurely born infants and nitric oxide has been robustly investigated. Other drugs are being used on very limited evidence.


Effect of Cardiovascular Injury on Catabolism of Adenosine and Adenosine 5-'Triphosphate in Systemic Blood in a Freely Moving Rat Model In Vivo.
Previous studies have shown that catabolism of adenosine 5'-triphosphate (ATP) in red blood cell (RBC) may be a key factor for cardiovascular protection and maintaining cardiovascular homeostasis. To investigate the effect of cardiovascular injury on adenosine and ATP catabolism in systemic blood using a freely moving rat model in vivo. After acclimatized to the experimental environment, Sprague Dawley (SD) rats were each given either isoproterenol (30 mg/kg) or saline (1 mL/kg) by subcutaneous (sc) injection. Blood samples were collected sequentially for up to 6 hours for measurement of red blood cell (RBC) concentrations of adenine nucleotides and plasma concentrations of adenosine and its oxypurine metabolites. We have found isoproterenol induced 50% mortality under the experimental condition. Plasma concentrations of adenosine (ADO) and uric acid (UA) and red blood cell (RBC) concentrations of adenosine 5'-diphosphate (ADP) and adenosine 5'-monophosphate (AMP) in RBC were significantly higher in the isoproterenol treated rats (p < 0.05 for all the comparison). On the other hand, plasma concentrations of hypoxanthine (HYP) were higher in the control group (p < 0.05), but there was no statistically significant changes in ATP concentrations in the RBC (p > 0.05). Cardiovascular injury induced by isoproterenol resulted in breakdown of ATP to ADP and AMP in the RBC and also breakdown of ADO to UA in plasma and other tissues.


Oxoglutarate dehydrogenase complex controls glutamate-mediated neuronal death.
Brain injury is accompanied by neuroinflammation, accumulation of extracellular glutamate and mitochondrial dysfunction, all of which cause neuronal death. The aim of this study was to investigate the impact of these mechanisms on neuronal death. Patients from the neurosurgical intensive care unit suffering aneurysmal subarachnoid hemorrhage (SAH) were recruited retrospectively from a respective database. In vitro experiments were performed in rat cortex homogenate, primary dissociated neuronal cultures, B35 and NG108-15 cell lines. We employed methods including high resolution respirometry, electron spin resonance, fluorescent microscopy, kinetic determination of enzymatic activities and immunocytochemistry. We found that elevated levels of extracellular glutamate and nitric oxide (NO) metabolites correlated with poor clinical outcome in patients with SAH. In experiments using neuronal cultures we showed that the 2-oxoglutarate dehydrogenase complex (OGDHC), a key enzyme of the glutamate-dependent segment of the tricarboxylic acid (TCA) cycle, is more susceptible to the inhibition by NO than mitochondrial respiration. Inhibition of OGDHC by NO or by succinyl phosphonate (SP), a highly specific OGDHC inhibitor, caused accumulation of extracellular glutamate and neuronal death. Extracellular nitrite did not substantially contribute to this NO action. Reactivation of OGDHC by its cofactor thiamine (TH) reduced extracellular glutamate levels, Ca2+ influx into neurons and cell death rate. Salutary effect of TH against glutamate toxicity was confirmed in three different cell lines. Our data suggest that the loss of control over extracellular glutamate, as described here, rather than commonly assumed impaired energy metabolism, is the critical pathological manifestation of insufficient OGDHC activity, leading to neuronal death.


Brexpiprazole in the treatment of schizophrenia and agitation in Alzheimer's disease.
Schizophrenia is a disabling psychiatric disorder marked by progressive loss of functionality in activities of daily living with each relapse. Antipsychotics, the mainstay of therapy for schizophrenia, treat hallucinations and delusions but may have intolerable side effects, including metabolic disturbances and extrapyramidal symptoms. Brexpiprazole, a second-generation antipsychotic with dopamine partial agonist properties, was approved by the US FDA in 2015 for the treatment of schizophrenia and adjunctive treatment of major depressive disorder and by the EU in 2018 for adults with schizophrenia. Additionally, brexpiprazole has recently been studied for the treatment of agitation in Alzheimer's dementia, an area of largely unmet need. Overall, well-tolerated brexpiprazole expands the armamentarium of treatment options available for these conditions.


Protease-activated receptor-induced Akt activation--regulation and possible function.
Thrombin induces the activation of the platelet serine/threonine kinase Akt. Akt activation is dependent on its phosphorylation at Thr308 and Ser473. The mechanism by which thrombin induces Akt phosphorylation is controversial, as is the role of Akt in platelet function. To investigate how protease-activated receptors (PARs) stimulate Akt and the role that Akt plays in human platelet function. Platelets were stimulated through PAR1 or PAR4. Specific inhibitors were used to evaluate, by Western blotting, signaling pathways regulating Akt phosphorylation, and the role of activated Akt was evaluated by aggregometry and flow cytometry. Phospholipase C (PLC) controls Akt phosphorylation elicited by PARs. Stimulation of PAR1 or PAR4 resulted in rapid Akt phosphorylation, independently of secreted ADP and phosphatidylinositol-3-kinase (PI3K) activation. Akt phosphorylation approximately 60 s after PAR1 stimulation became entirely dependent on the purinergic receptor P2Y(12) and the activation of PI3K. In contrast, PAR4 partially sustained Akt phosphorylation independently of P2Y(12) and PI3K for up to 300 s. Pharmacologic inhibition of Akt reduced P-selectin expression and fibrinogen binding in platelets stimulated through PAR1, and delayed platelet aggregation in response to submaximal PAR1 or PAR4 stimulation, although aggregation at 300 s was unaffected. Platelet PAR stimulation causes rapid Akt phosphorylation downstream of PLC, whereas with continuous stimulation, ADP and PI3K are required for maintaining Akt phosphorylation. Activated Akt regulates platelet function by modulating secretion and alpha(IIb)beta(3) activation.


Comparative morphology of cheliceral muscles using high-resolution X-ray microcomputed-tomography in palpimanoid spiders (Araneae, Palpimanoidea).
Spiders are important predators in terrestrial ecosystems, yet we know very little about the principal feeding structures of spiders, the chelicerae, which are functionally equivalent to "jaws" or "mandibles" and are an extremely important aspect of spider biology. In particular, members of Palpimanoidea have evolved highly unusual cheliceral morphologies and functions, including high-speed, ballistic movements in mecysmaucheniid spiders, the fastest arachnid movements known thus far, and the elongated, highly maneuverable chelicerae of archaeids that use an attack-at-a-distance strategy. Here, using micro-Computed-Tomography scanning techniques, we perform a comparative study to examine cheliceral muscle morphology in six different spider specimens representing five palpimanoid families. We provide a hypothesis for homology in palpimanoid cheliceral muscles and then compare and contrast these findings with previous studies on other non-palpimanoid spiders. We document and discuss two sets of cheliceral muscles in palpimanoids that have not been previously observed in other spiders or which may represent a position shift compared to other spiders. In the palpimanoids, Palpimanus sp., Huttonia sp., and Colopea sp. showed similar cheliceral muscle anatomy. In Eriauchenius ranavalona, which has highly maneuverable chelicerae, some of the muscles have a more horizontal orientation, and there is a greater degree of cheliceral muscle divergence. In Zearchaea sp. and Aotearoa magna, some muscles have also shifted to a more horizontal orientation, and in Zearchaea sp., a species with a ballistic, high-speed predatory strike, there is a loss of cheliceral muscles. This research is a first step toward understanding cheliceral form and function across spiders.


"Sink or Swim": An Ethnographic Study of Nurse Educators in Academic Culture.
The aim of this study was to describe the cultural context of academic nurse educators through the use of ethnography. This cultural context has seldom been explored from the perspective of nursing faculty. Twelve interviews, followed by ethnographic data analysis, identified domains with related components describing this culture. Participants cited metaphors of water (e.g., sink or swim, keeping head above water) in describing the culture. Challenges included demanding workloads, challenging interchanges, negotiating a complex bureaucracy, and finding trusted individuals willing to provide a network of support. Faculty reported interactions to be guarded, uncivil, and conflict avoidant within a bureaucracy of slow pace of work, resistance to change, heavy workloads, and requirements for scholarship that are not clear or consistently enforced. Clinical nurses who enter the academic culture must learn patterned ways of thinking and earn credibility. A key to adaptation is finding colleagues who will provide a support network.


Endoscopic Doppler ultrasound after injection therapy for peptic ulcer hemorrhage.
A positive Doppler signal in endoscopic Doppler ultrasound at index endoscopy predicts a high risk for rebleeding from peptic ulcer. The aim of this study was to evaluate if a negative Doppler status immediately after injection therapy may exclude a rebleeding from peptic ulcer in a high-risk cohort. Twenty consecutive patients (pts) (age: 68 (33-91) yrs; 11 female) with peptic ulcer bleeding were enrolled. All patients with an actively bleeding ulcer and those with a non-actively bleeding, but Doppler-positive ulcer were treated by injection of adrenaline (1:10,000 dilution). Treatment was performed during index endoscopy until the Doppler status was negative. Patients were followed-up clinically and endoscopically (including Doppler ultrasound) for bleeding recurrence. Patients were treated by injection of 12 (6 to 20) mL of adrenaline solution until Doppler scan was negative. During follow-up four pts (20%) had a clinically overt rebleeding episode. At control endoscopy three ulcers were actively bleeding and another two were Doppler positive without rebleeding (total: five of eighteen (27.7%) Doppler-positive ulcers). Two of the twenty pts required surgical therapy due to rebleeding (10%). A negative endoscopic Doppler status immediately after injection therapy is not helpful to identify patients with no risk for rebleeding from peptic ulcer.


[DNA ploidy of stem cells and prognosis of ductal adenocarcinoma of the pancreas].
The findings on DNA stem line ploidy of ductal adenocarcinomas of the pancreas, which have hitherto been published in the literature, are rather contradictory last but not least due to methodological problems. Thus, the DNA stem line ploidy and its prognostic significance were examined by Feulgen image cytometry on 10 microns sections of 100 paraffin-embedded radically resected ductal carcinomas of the pancreas from the records. In that process the parts of the tumour with the highest grade of malignancy were preferentially investigated. The aneuploidy rate (42%) was conspicuously low if compared with other adenocarcinomas. A highly significant positive correlation between DNA ploidy and histological grading according to Klöppel et al. could be observed, while there was only a tendency towards a positive correlation of DNA ploidy and post-surgical tumour stage. Regarding the 1-year survival rate, the DNA aneuploid tumour cases were significantly more unfavourable than the DNA peridiploid ones (p < 0.05). The prognostically decisive parameter, however, was the histological grading (p < 0.00005), which also showed the best stratification of the patient population. However, contrary to expectations the postsurgical stage of the primary tumour and the nodular state were only of low prognostic significance. The reason for that is on the one hand that the distribution over the pT-stages (in 81% pT2 tumours) is unbalanced, and on the other hand that the actual tumour cell dissemination is only insufficiently represented in the post-surgical staging.


Development and validation of a risk score to predict 30-day mortality in patients with atrial fibrillation-related stroke: GPS-GF score.
Objective Stroke due to atrial fibrillation (AF) is common and frequently devastating. However, there is no specific tool to accurately estimate the risk of mortality. This study aims to develop and validate a comprehensive risk score for predicting 30-day mortality in the patients with AF-related stroke. Methods A retrospective multi-center clinical study was performed based on the data from the project of secondary prevention of stroke in patients with nonvalvular AF in Shaanxi province, China. A total of 1077 consecutive patients were randomly classified into derivation (66.7%, n = 718) and internal validation cohort (33.3%, n = 359). Independent predictors of 30-day mortality were obtained using univariate and multivariable analyses. The area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow test were used to assess model discrimination and calibration, respectively. Results Two hundred patients (18.6%) of 1077 participants died within 30 days. An 8-point score was generated from the five independent predictors for 30-day mortality including Glasgow Coma Scale, pneumonia, midline shift on brain images, blood glucose, and female sex, which was named GPS-GF. The resulting score showed good discrimination (AUROC) and well calibrated (Hosmer-Lemeshow test) in the derivation (0.909; p = 0.102) and internal validation cohort (0.922; p = 0.153). Compared with iScore, the GPS-GF score exhibited remarkably better discriminative power and predictive accuracy regarding the 30-day mortality in patients with AF-related stroke. Conclusion The GPS-GF score is a simple and valid tool for predicting 30-day mortality in patients with AF-related stroke.


Effects of Exposure to WwTW Effluents over Two Generations on Sexual Development and Breeding in Roach Rutilus rutilus.
Exposure to environmental estrogens in wastewater treatment works (WwTW) effluents induces feminized responses in male fish, including the development of eggs in male testes. However, the impacts on the offspring of exposed fish are not well understood. In this study, we examined whether roach (Rutilus rutilus) from mothers that had been exposed to an undiluted WwTW effluent from early life to sexual maturity had altered susceptibility to gonadal feminization and an impaired capacity to reproduce. For males from both WwTW effluent exposed mothers and dilution water exposed mothers, effluent exposure for up to 3 years and 9 months induced feminized male gonads, although the intersex condition was relatively mild. There was no difference in the severity of gonadal feminization in roach derived from either WwTW effluent exposed or dilution water exposed mothers. Furthermore, a breeding study revealed that roach with effluent-exposed mothers reproduced with an equal success as roach with mothers exposed to clean water. Roach exposed to the effluent for 3 years in this study were able to reproduce successfully. Our findings provide no evidence for impacts of WwTW effluent exposure on reproduction or gonadal disruption in roach down the female germ line and add to existing evidence that male roach with a mild intersex condition are able to breed competitively.


Construction of a Colorectal Cancer Prognostic Risk Model and Screening of Prognostic Risk Genes Using Machine-Learning Algorithms.
This study is aimed at constructing a prognostic risk model for colorectal cancer (CRC) using machine-learning algorithms to provide accurate staging and screening of credible prognostic risk genes. We extracted CRC data from GSE126092 and GSE156355 of the Gene Expression Omnibus (GEO) database and datasets from TCGA to analyze the differentially expressed genes (DEGs) using bioinformatics analysis. Among the 330 shared DEGs related to CRC prognosis, we divided the analysis period into different phases and applied univariate COX regression, LASSO, and multivariate COX regression analysis. GO analysis and KEGG analysis revealed that the functions of these DEGs were primarily focused on cell cycle, DNA replication, cell mitosis, and other related functions, and this confirmed our results from a biological perspective. Finally, a prognostic risk model for CRC based on the CHGA, CLU, PLK1, AXIN2, NR3C2, IL17RB, GCG, and AJUBA genes was constructed, and the risk score enabled us to predict the prognosis for CRC. To obtain a comprehensive and accurate model, we used both internal and external evaluations, and the model was able to correctly differentiate patients with CRC into a high-risk group with poor prognosis and a low-risk group with good prognosis. The AUC values of the 3-, 5-, and 10-year survival ROC curves were 0.715, 0.721, and 0.777, respectively, according to the internal evaluation, and the AUC values were 0.606, 0.698, and 0.608, respectively, for the external evaluation using GSE39582 from the GEO database. We determined that CLU, PLK1, and IL17RB could be considered to be independent prognostic factors for CRC with significantly different expression (P < 0.05). Using machine-learning methods, a prognostic risk model comprised of eight genes was constructed. Not only does this model provide improved treatment guidance, but it also provides a novel perspective for analyzing survival conditions at a deeper biological level.


The Relationship Between Reminiscence Functions, Optimism, Depressive Symptoms, Physical Activity, and Pain in Older Adults.
The study purpose was to examine the association between reminiscence functions, optimism, depressive symptoms, physical activity, and pain in older adults with chronic lower extremity osteoarthritis pain. One hundred ninety-five community-dwelling adults were interviewed using the Modified Reminiscence Functions Scale, Brief Pain Inventory, Life Orientation Test-Revised, Center for Epidemiologic Studies Short Depression Scale, and Physical Activity Scale for the Elderly in random counterbalanced order. Structural equation modeling supported chronic pain as positively associated with depressive symptoms and comorbidities and unrelated to physical activity. Depressive symptoms were positively associated with self-negative reminiscence and negatively associated with optimism. Spontaneous reminiscence was not associated with increased physical activity or reduced pain. Individuals may require facilitated integrative reminiscence to assist them in reinterpreting negative memories in a more positive way. Facilitated integrative reminiscence about enjoyed past physical activity is a potential way to increase physical activity, but must be tested in future research. [Res Gerontol Nurs. 2016; 9(5):223-231.].


Patents and the Global Diffusion of New Drugs.
Analysis of the timing of launches of 642 new drugs in 76 countries during 1983–2002 shows that patent and price regulation regimes strongly affect how quickly new drugs become commercially available in different countries. Price regulation delays launch, while longer and more extensive patent rights accelerate it. Health policy institutions and economic and demographic factors that make markets more profitable also speed up diffusion. The estimated effects are generally robust to controlling for endogeneity of policy regimes with country fixed effects and instrumental variables. The results highlight the important role of policy choices in driving the diffusion of new innovations.


HIV-associated neurocognitive disease continues in the antiretroviral era.
Despite the ability to suppress viral replication with antiretroviral therapy, HIV-associated neurocognitive disturbances can still be detected in nearly half of patients. Neurologic dysfunction before initiating or in the absence of antiretroviral treatment is primarily the result of neuronal dysfunction or loss from direct viral effects, whereas that in patients receiving antiretroviral therapy appears to be associated at least in part with inflammation driven by chronic low-level infection. Contributing factors may include genetic differences in HIV and human hosts and aging of patients. This article summarizes a presentation on HIV-associated neurocognitive disorder made by David B. Clifford, MD, at an International AIDS Society-USA Continuing Medical Education course in New York in October 2007.


Acetabular roof arc angles and anatomic biomechanical superior acetabular weight bearing area.
Acetabular fracture involves whether superior articular weight bearing area and stability of the hip are assessed by acetabular roof arc angles comprising medial, anterior and posterior. Many previous studies, based on clinical, biomechanics and anatomic superior articular surface of acetabulum showed different degrees of the angles. Anatomic biomechanical superior acetabular weight bearing area (ABSAWBA) of the femoral head can be identified as radiographic subchondral bone density at superior acetabular dome. The fracture passes through ABSAWBA creating traumatic hip arthritis. Therefore, acetabular roof arc angles of ABSAWBA were studied in order to find out that the most appropriate degrees of recommended acetabular roof arc angles in the previous studies had no ABSAWBA involvement. ABSAWBA of femoral head was identified 68 acetabular fractures and 13 isolated pelvic fractures without unstable pelvic ring injury were enrolled. Acetabular roof arc angle was measured on anteroposterior, obturator and iliac oblique view radiographs of normal contralateral acetabulum using programmatic automation controller digital system and measurement tools. Average medial, anterior and posterior acetabular roof arc angles of the ABSAWBA of 94 normal acetabulum were 39.09 (7.41), 42.49 (8.15) and 55.26 (10.08) degrees, respectively. Less than 39°, 42° and 55° of medial, anterior and posterior acetabular roof arc angles involve ABSAWBA of the femoral head. Application of the study results showed that 45°, 45° and 62° from the previous studies are the most appropriate medial, anterior and posterior acetabular roof arc angles without involvement of the ABSAWBA respectively.


Best practices in the rehabilitation of acute musculoskeletal disorders in workers with injuries: an integrative review and analysis of evolving trends.
Strategies for the restoration of function and job performance in workers with musculoskeletal disorders have changed considerably since industrial rehabilitation became a distinct specialization in the 1980s. A rich body of research concerning approaches to medical and rehabilitative management of these disorders exists, resulting in a large number of hybrid approaches worldwide. This integrative review examined the evidence base for best practices in the rehabilitation of acute musculoskeletal workplace injuries, and also mapped the evolution of approaches over the past thirty years. Contextual factors that may have contributed to change were assessed through analysis of changing practice trends and review of descriptive literature over time. A clear movement away from simplistic, unidimensional approaches towards comprehensive workplace interventions is evident. Economic concerns and growing government and insurance regulation of workplace safety and injury management were the likely drivers of change. While the contributions of various elements of disability management in the workplace were examined, many features of onsite interventions remain to be examined. A strong body of research has produced notable advances in management of acute musculoskeletal workplace injury. Research concerning the delivery of workplace-based interventions, the role of workplace environment factors and a range of worker outcomes will further advance knowledge in this field.


Macrophage and monocyte subsets in response to ischemic stroke.
Ischemic stroke is a leading cause of disability and mortality. Despite extensive efforts in stroke research, the only pharmacological treatment currently available is arterial recanalization, which has limited efficacy only in the acute phase of stroke. The neuroinflammatory response to stroke is believed to provide a wider time window than recanalization and has therefore been proposed as an attractive therapeutic target. In this review, we provide an overview of recent advances in the understanding of cellular and molecular responses of distinct macrophage populations following stroke, which may offer potential targets for therapeutic interventions. Specifically, we discuss the role of local responders in neuroinflammation, including the well-studied microglia as well as the emerging players, border-associated macrophages, and macrophages originating from the skull bone marrow. Additionally, we focus on the behavior of monocytes stemming from distant tissues such as the bone marrow and spleen. Finally, we highlight aging as a crucial factor modulating the immune response, which is often neglected in animal studies.


Pericardial Windows: The Limited Diagnostic Value of Non-Targeted Pericardial Biopsy.
Pericardial window, in addition to promoting pericardial drainage, can also provide samples of the pericardium for anatomopathological examination. However, such biopsies' contribution to clarifying the etiology of pericardial effusion has been debated. To analyze the diagnostic value of non-targeted pericardial biopsy obtained from pericardial window procedures. Data from 80 patients who had undergone parietal pericardial biopsies from 2011 to 2020 were retrospectively reviewed. Statistical significance was considered if p < 0.05. Fifty patients were male (62.5%,) and 30 were female (37.5%). The median age was 52 years (interquartile range: 29 to 59) and 49 years (interquartile range: 38 to 65), respectively (p = 0.724). The suspected etiology of pericardial effusion was neoplastic in 31.3%, unclear in 25%, tuberculosis in 15%, autoimmune in 12.5%, edemagenic syndrome in 7.5%, and other miscellaneous conditions in 8.8%. The most frequent approach for pericardial drainage and biopsy was subxiphoid (74%), followed by video-assisted thoracoscopy (22%). Overall, in 78.8% of the biopsies, the histopathologic findings were compatible with nonspecific inflammation, and only 13.7% of all biopsies yielded a conclusive histopathological diagnostic. Those suffering from cancer and pericardial effusion had a higher proportion of conclusive histopathologic findings (32% had pericardial neoplastic infiltration). The hospital mortality rate was 27.5%, and 54.5% of the patients who died in the hospital had cancer. No deaths were attributed to cardiac tamponade or the drainage procedure. Our results showed that pericardial window is a safe procedure, but it had little value to clarify the pericardial effusion etiology and no impact on the planned therapy for the primary diagnosis besides the cardiac decompression.


Graphics for dissemination of meta-analyses to staff nurses.
Meta-analytic findings can be useful to nurses seeking research results to guide practice, but graphics used by meta-analysts take time to master. Simpler displays can be created by staff development educators if they understand commonly used meta-analytic displays. For instance, simplified versions of 'forest plots', a common metaphoric display can be created to introduce staff nurses to meta-analytic findings published in the Cochrane Database of Systematic Reviews and similar databases.


Oral immunisation against typhoid fever in Indonesia with Ty21a vaccine.
When tested under conditions of moderate transmission of typhoid fever, a liquid formulation of the oral typhoid fever vaccine Ty21a had a protective efficacy of 96% in Egypt, and an enteric coated capsule formulation had an efficacy of 67% in Chile. We compared the two formulations under conditions of intense transmission of typhoid fever in Indonesia in a randomised, double-blind trial. 20,543 subjects (age range 3-44 years) received either three doses of enteric coated capsules containing placebo or live Ty21a, or three doses of lyophilised placebo or live Ty21a reconstituted with phosphate buffer. During 30 months of follow-up, the rate of blood-culture-positive typhoid fever among controls was 810/100,000 per year. Rates of typhoid fever were 379/100,000 per year for subjects who received the liquid formulation of vaccine and 468/100,000 per year for subjects who received enteric coated capsules. The protective efficacies of the liquid and enteric coated formulations were 53% and 42%, respectively. Neither formulation protected against infection with Salmonella paratyphi A. No major side-effects were noted, but the overall incidence of side-effects was greater in the vaccine groups. Under conditions of intense transmission, Ty21a protected against typhoid fever; however, because Ty21a will not protect all individuals, there is a need for additional approaches to prevent the disease.


Anticonvulsant activity of some 4-aminobenzamides.
A series of 4- aminobenzamides of some simple primary and secondary amines were prepared and evaluated for anticonvulsant effects. The compounds were tested in mice against seizures induced by electroshock and pentylenetetrazole ( metrazole ) and in the rotorod assay for neurologic deficit. For those N-alkyl amides tested, 4-amino-N- amylbenzamide (6) was the most potent against maximal electroshock seizures (MES): ED50 = 42.98 mg/kg; however, the N- cyclohexylbenzamide (8) showed the greatest protective index (PI = TD50/ED50), 2.8. The introduction of a second aromatic ring produced more potent compounds, with d,l-4-amino-N-(alpha-methylbenzyl)-benzamide (12) showing the highest level of activity. This compound has an anti-MES ED50 of 18.02 mg/kg in mice when administered intraperitoneally (ip) and a TD50 of 170.78 mg/kg (PI = 9.5) in the same species. These data compare quite favorably with those for phenobarbital and phenytoin in the same assays.


Variation in groundwater manganese in Finland.
Increasing evidence has emerged that Mn derived from drinking water could be a health risk, especially for children. This study aimed to provide more information on the variation in Mn concentrations in well water and factors that affect manganese concentrations in groundwater in the natural environment. The geochemical data consisted of analyses of single water samples (n = 5311) that were taken only once and data from monitoring sites where water samples (n = 4607) were repeatedly taken and analyzed annually from the same wells. In addition, the well-specific results from six wells at monitoring sites were described in detail. We obtained the data on water samples from the groundwater database of Geological Survey of Finland. In single samples, Mn concentrations varied from < 0.02 µg/l to 5800 µg/l in bedrock well waters and up to 6560 µg/l in Quaternary deposit well waters. Results from single water samples from bedrock wells and Quaternary deposit wells indicated that the dissolved oxygen content has an inverse association with the Mn concentration. When the dissolved oxygen O2 levels were lower, the Mn concentrations were higher. No clear association was found between the Mn concentration and the pH or depth of the well for single samples. Part of Mn was particle bound, because total Mn was higher than soluble Mn in most measured samples. In the monitoring survey, large variation in Mn concentrations was found in bedrock well water in Kemijärvi, 114-352 µg/l, and in dug well water in Hämeenkoski, 8.77-2640 µg/l. Seasonal and spatial variability in Mn concentrations in water samples from two bedrock wells was large at monitoring sites in northern Finland. Variability in the Mn concentrations in groundwater can be large, even in the same area. These data suggest that single measurements of the Mn concentration from a water source may not reveal the Mn status, and measurement of both the total and soluble Mn concentrations may be recommended.


Reduced maximal inhibition in phenotypic susceptibility assays indicates that viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound receptor for entry.
Maraviroc is a CCR5 antagonist in clinical development as one of a new class of antiretrovirals targeting human immunodeficiency virus type 1 (HIV-1) coreceptor binding. We investigated the mechanism of HIV resistance to maraviroc by using in vitro sequential passage and site-directed mutagenesis. Serial passage through increasing maraviroc concentrations failed to select maraviroc-resistant variants from some laboratory-adapted and clinical isolates of HIV-1. However, high-level resistance to maraviroc was selected from three of six primary isolates passaged in peripheral blood lymphocytes (PBL). The SF162 strain acquired resistance to maraviroc in both treated and control cultures; all resistant variants were able to use CXCR4 as a coreceptor. In contrast, maraviroc-resistant virus derived from isolates CC1/85 and RU570 remained CCR5 tropic, as evidenced by susceptibility to the CCR5 antagonist SCH-C, resistance to the CXCR4 antagonist AMD3100, and an inability to replicate in CCR5 Delta32/Delta32 PBL. Strain-specific mutations were identified in the V3 loop of maraviroc-resistant CC1/85 and RU570. The envelope-encoding region of maraviroc-resistant CC1/85 was inserted into an NL4-3 background. This recombinant virus was completely resistant to maraviroc but retained susceptibility to aplaviroc. Reverse mutation of gp120 residues 316 and 323 in the V3 loop (numbering from HXB2) to their original sequence restored wild-type susceptibility to maraviroc, while reversion of either mutation resulted in a partially sensitive virus with reduced maximal inhibition (plateau). The plateaus are consistent with the virus having acquired the ability to utilize maraviroc-bound receptor for entry. This hypothesis was further corroborated by the observation that a high concentration of maraviroc blocks the activity of aplaviroc against maraviroc-resistant virus.


Electron track simulation using ETMICRO.
A new Monte Carlo code ETMICRO (Electron Transport code for MICROdosimetry) is now available for tracing the electrons down to 10 eV in liquid water. ETMICRO employs much the same frame of track construction as the previous programs except that the plasmon excitation is left out of consideration and thus there is no delocalisation of energy deposition. The inverse mean free path data and the corresponding differential values (DIMFPs) were prepared by adopting the Drude model parameters that were derived from a new optical data set for liquid water. The potential of electrons causing direct damage on DNA has been estimated as functions of the energy of electrons and their distance from DNA in an arbitrary direction.


Edaravone, a Free Radical Scavenger, Delayed Symptomatic and Pathological Progression of Motor Neuron Disease in the Wobbler Mouse.
Edaravone, a free radical scavenger is used widely in Japanese patients with acute cerebral infarction. This antioxidant could have therapeutic potentials for other neurological diseases. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the upper and the lower motor neuron, leading to death within 3-5 years after onset. A phase III clinical trial of edaravone suggested no significant effects in ALS patients. However, recent 2nd double-blind trial has demonstrated therapeutic benefits of edaravone in definite patients diagnosed by revised El Escorial diagnostic criteria of ALS. Two previous studies showed that edaravone attenuated motor symptoms or motor neuron degeneration in mutant superoxide dismutase 1-transgenic mice or rats, animal models of familial ALS. Herein we examined whether this radical scavenger can retard progression of motor dysfunction and neuropathological changes in wobbler mice, sporadic ALS-like model. After diagnosis of the disease onset at the postnatal age of 3-4 weeks, wobbler mice received edaravone (1 or 10 mg/kg, n = 10/group) or vehicle (n = 10), daily for 4 weeks by intraperitoneal administration. Motor symptoms and neuropathological changes were compared among three groups. Higher dose (10 mg/kg) of edaravone treatment significantly attenuated muscle weakness and contracture in the forelimbs, and suppressed denervation atrophy in the biceps muscle and degeneration in the cervical motor neurons compared to vehicle. Previous and the present studies indicated neuroprotective effects of edaravone in three rodent ALS-like models. This drug seems to be worth performing the clinical trial in ALS patients in the United States of American and Europe, in addition to Japan.


Sly1 protein bound to Golgi syntaxin Sed5p allows assembly and contributes to specificity of SNARE fusion complexes.
Fusion of transport vesicles with their target organelles involves specific membrane proteins, SNAREs, which form tight complexes bridging the membranes to be fused. Evidence from yeast and mammals indicates that Sec1 family proteins act as regulators of membrane fusion by binding to the target membrane SNAREs. In experiments with purified proteins, we now made the observation that the ER to Golgi core SNARE fusion complex could be assembled on syntaxin Sed5p tightly bound to the Sec1-related Sly1p. Sly1p also bound to preassembled SNARE complexes in vitro and was found to be part of a vesicular/target membrane SNARE complex immunoprecipitated from yeast cell lysates. This is in marked contrast to the exocytic SNARE assembly in neuronal cells where high affinity binding of N-Sec1/Munc-18 to syntaxin 1A precluded core SNARE fusion complex formation. We also found that the kinetics of SNARE complex formation in vitro with either Sly1p-bound or free Sed5p was not significantly different. Importantly, several presumably nonphysiological SNARE complexes easily generated with Sed5p did not form when the syntaxin was first bound to Sly1p. This indicates for the first time that a Sec1 family member contributes to the specificity of SNARE complex assembly.


Analysis of 5-hydroxymethylfurfural in foods by gas chromatography-mass spectrometry.
A new, simple and selective method for the analysis of 5-hydroxymethylfurfural (HMF) in foods by gas chromatography coupled to mass spectrometry (GC-MS) is proposed. Several derivatising procedures based on the formation of an HMF silylated derivative using different reagents were studied. Among the derivatising reagents examined, N,O-bis-trimethylsilyltrifluoroacetamide (BSTFA) provided the best derivatisation yield. Sample clean-up was also optimised, using either liquid-liquid extraction with dichloromethane or solid-phase extraction (SPE) with several commercially available cartridges, and the best results were obtained using ENV+ cartridges. Quality parameters such as day-to-day and run-to-run precision (RSD<10%), linearity (between 25 and 700 ng g(-1)) and detection limit (6 ng g(-1)) were established. This method was successfully applied to the analysis of HMF content in several Spanish food samples from a local market, such as jam, honey, orange juice and bakery products.


Diabetes and risk of occupational injury: a cohort study.
To investigate if diabetes is associated with a higher risk of occupational (workplace or commuting) injury. Medication data from the Finnish Prescription Register were used to identify diabetes cases in 2004 in a large employee cohort (the Finnish Public Sector study). These data were linked to injury records obtained from the Federation of Accident Insurance Institutions. A total of 1020 diabetes cases (median age 52 years, range 20 to 65 years; 66% women) and their 5234 age- and sex-matched controls were followed up until 2011. Sex-stratified Cox proportional hazards models, adjusting for age, occupational status, obesity and health behaviours, were applied. Because of the small number of men in the cohort, injury types and locations were only examined among women. During the median follow-up of 6.7 years, 25% of the participants with diabetes (n=252) and 20% of those without (n=1051) experienced an occupational injury. The association between diabetes and injury was stronger in women than men (P=0.048). Diabetes was associated with a higher risk of workplace (hazard ratio 1.37, 95% CI 1.11 to 1.69) and commuting (hazard ratio 1.36, 95% CI 1.03 to 1.79) injury in women. With regard to different injury types and locations, diabetes was associated with bone fractures, dislocations, sprains and strains, and injuries to upper and lower extremities. In men, there was an association between insulin-treated diabetes and commuting injury (hazard ratio 3.14, 95% CI 1.52 to 6.49). Diabetes was associated with workplace and commuting injuries in women. Men with insulin-treated diabetes had a higher risk of commuting injuries.


Whole blood transfusion versus component therapy in adult trauma patients with acute major haemorrhage.
In the era of damage control resuscitation of trauma patients with acute major haemorrhage, transfusion practice has evolved to blood component (component therapy) administered in a ratio that closely approximates whole blood (WB). However, there is a paucity of evidence supporting the optimal transfusion strategy in these patients. The primary objective was therefore to establish if there is an improvement in survival at 30 days with the use of WB transfusion compared with blood component therapy in adult trauma patients with acute major haemorrhage. A systematic literature search was performed on 15 December 2019 to identify studies comparing WB transfusion with component therapy in adult trauma patients and mortality at 30 days. Studies which did not report mortality were excluded. Methodological quality of included studies was interpreted using the Cochrane risk of bias tool, and rated using the Grading of Recommendations Assessment, Development and Evaluation approach. Search of the databases identified 1885 records, and six studies met the inclusion criteria involving 3255 patients. Of the three studies reporting 30-day mortality (one randomised controlled trial (moderate evidence) and two retrospective (low and very low evidence, respectively)), only one study demonstrated a statistically significant difference between WB and component therapy, and two found no statistical difference. Two retrospective studies reporting in-hospital mortality found no statistical difference in unadjusted mortality, but both reported statistically significant logistic regression analyses demonstrating that those with a WB transfusion strategy were less likely to die. Recognising the limitations of this systematic review relating to the poor-quality evidence and limited number of included trials, it does not provide evidence to support or reject use of WB transfusion compared with component therapy for adult trauma patients with acute major haemorrhage. CRD42019131406.


Glial Fibrillary Acidic Protein in Blood as a Disease Biomarker of Neuromyelitis Optica Spectrum Disorders.
Glial fibrillary acidic protein (GFAP) is a type III intermediate filament protein found in astrocytes in the brain. Damaged astrocytes release GFAP into cerebrospinal fluid and blood. Thus, GFAP levels in these body fluids may reflect the disease state of neuromyelitis optica spectrum disorder (NMOSD), which includes astrocytopathy, characterized by pathogenic antibodies against aquaporin 4 located on astrocytes. Recently, single-molecule array technology that can detect these synaptic proteins in blood, even in the subfemtomolar range, has been developed. Emerging evidence suggests that GFAP protein is a strong biomarker candidate for NMOSD. This mini-review provides basic information about GFAP protein and innovative clinical data that show the potential clinical value of blood GFAP levels as a biomarker for NMOSD.


The human multidrug-resistance-associated protein MRP1 mediates ATP-dependent transport of unconjugated bilirubin.
Results of previous studies have suggested that UCB (unconjugated bilirubin) may be transported by MRP1/Mrp1 (multidrug-resistance-associated protein 1). To test this hypothesis directly, [3H]UCB transport was assessed in plasma-membrane vesicles from MDCKII cells (Madin-Darby canine kidney II cells) stably transfected with human MRP1 or MRP2; wild-type MDCKII cells served as controls. As revealed by Western blotting, transfection achieved abundant expression of MRP1 and MRP2. [3H]UCB uptake was measured in the presence of 60 microM human serum albumin at a free (unbound) concentration of UCB (B(F)) ranging from 5 to 72 nM and in the presence of 3 mM ATP or 3 mM AMP-PCP (adenosine 5'-[beta,gamma-methylene]triphosphate). MRP1-transfected vesicles showed transport activity three and five times higher respectively compared with MRP2 or wild-type vesicles, whose transport did not differ significantly. [3H]UCB transport was stimulated 4-fold by 1.5 mM GSH, occurred into an osmotically sensitive space, was inhibited by 3 microM MK571 and followed saturative kinetics with K(m)=10+/-3 nM (B(F)) and V(max)=100+/-13 pmol x min(-1) x (mg of protein)(-1). UCB significantly inhibited the transport of LTC4 (leukotriene C4), a leukotriene substrate known to have high affinity for MRP1. Collectively, these results prove directly that MRP1 mediates ATP-dependent cellular export of UCB and supports its role in protecting cells from bilirubin toxicity.


Echocardiography and laboratory outcomes of COVID-19 in children with a history of Kawasaki disease: a preliminary observation.
Infection with SARS-CoV-2 virus has been associated with cardiovascular sequelae including multisystem inflammatory syndrome (MIS-C) in children. Patients with a prior history of Kawasaki disease, may be more susceptible to changes in echocardiographic or laboratory findings after COVID-19. The objective of this study was to investigate the echocardiographic and laboratory findings in children with a prior history of Kawasaki disease after SARS-CoV-2 infection. In this study, we performed a retrospective chart review of 41 children younger than 18 years old who were diagnosed with COVID-19 from April to August of 2022 and had a prior history KD. We included echocardiography and blood draw data obtained at the last outpatient follow-up at our hospital for KD, and within 4 months of SARS-CoV-2 infection. Echocardiographic data obtained from 82 age-matched and gender matched controls were also included for comparison. We found that COVID-19 resulted in slightly higher RCA Z-scores within the first month after infection (mean ± SE, 1.20 ± 0.18 vs. 0.83 ± 0.18, p = 0.030), although this increase did not result in coronary artery dilatation, defined as a Z-score of at least 2.5. In addition, we found that degree of RCA dilatation after COVID-19 infection was negatively correlated with the change in monocyte percentage (Pearson's correlation coefficient-0.363, p = 0.020). Moreover, RCA Z-score changes were lower in patients who received at least one dose of mRNA COVID-19 vaccine when compared those who did not receive any (mean ± SE, -0.23 ± 0.16 vs. 0.39 ± 0.17, p = 0.031). In this pilot study we found that COVID-19 infection resulted in slightly higher RCA Z-scores in children with a prior history of KD, although not large enough to be classified as coronary aneurysms. While these changes could be the result of measurement imprecision or interobserver variation, further study of the cardiac outcomes of COVID-19 infection in children with a prior history of KD are needed in the future.


The absence of bumblebees on an oceanic island blurs the species boundary of two closely related orchids.
Oceanic islands offer valuable natural laboratories for studying evolution. The Izu Islands, with their recent geological origin, provide an exceptional opportunity to explore the initial evolution on oceanic islands. Another noteworthy aspect is the absence of bumblebee species on most Izu Islands. We used ecological, morphological, and molecular data to investigate the impact of bumblebee absence on the evolution of two closely related orchid species, Goodyera henryi and Goodyera similis, focusing on Kozu Island, the Izu Islands. Our investigation revealed that while G. henryi exclusively relies on a bumblebee species for pollination on the mainland, G. similis is pollinated by scoliid wasps on both the mainland and the island. Intriguingly, all specimens initially categorized as G. henryi on Kozu Island are hybrids of G. henryi and G. similis, leading to the absence of pure G. henryi distribution on the island. These hybrids are pollinated by the scoliid wasp species that also pollinates G. similis on the island. The absence of bumblebees might result in sporadic and inefficient pollination of G. henryi by scoliid wasps, consequently promoting hybrid proliferation on the island. Our findings suggest that the absence of bumblebees can blur plant species boundaries.


Brain metastasis in non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations: a report of seven cases and literature review.
Brain metastasis (BM) arising from non-small cell lung cancer (NSCLC) with rare epidermal growth factor receptor (EGFR) mutations is quite rare. The prognosis and therapeutic effects of BM remain enigmatic. To the best of our knowledge, this is the first report to make a separate analysis of BM from NSCLC patients with original uncommon EGFR mutations. We retrospectively reviewed 7 cases of BM arising from 42 cases of uncommon EGFR mutated lung cancer in Tianjin Medical University Cancer Institute and Hospital. We also performed a literature review to assess therapeutic features and outcomes.


Mitochondrial DNA analysis in primary congenital glaucoma.
To screen mitochondrial DNA (mtDNA) for nucleotide variations in primary congenital glaucoma (PCG). The entire coding region of the mitochondrial genome was amplified by polymerase chain reaction from 35 PCG patients and 40 controls. The full mtDNA genome except the D-loop was sequenced. All sequences were analyzed against mitochondrial reference sequence NC_012920. MtDNA sequencing revealed a total of 132 and 58 nucleotide variations in PCG and controls, respectively. Of 132 nucleotide variations, 42 (31.81%) were non-synonymous and 82 (62.12%) were synonymous changes, and 8 were in RNA genes. The highest number of nucleotide variations were recorded in complex I followed by complex IV, then complex V. Eight patients (22.85%) had potentially pathogenic mtDNA nucleotide changes and twenty (57.14%) had mtDNA sequence changes associated with elevated reactive oxygen species (ROS) production. Mitochondria not only constitute the energy-generating system in the cell, but are also critically involved in calcium signaling and apoptosis. Mitochondrial function can be affected by mutations in mitochondrial and nuclear DNA, chemical insults to components of the electron transport chain, and a lack of substrates such as oxygen. Mitochondrial dysfunction results in an excessive generation of free radicals and reduced mitochondrial respiration. Developing trabecular meshwork (TM) is deficient in antioxidant enzymes, and thus is more susceptible to oxidative stress (OS) induced damage. Previous studies have documented certain mtDNA sequence variations associated with elevated ROS levels and OS. Three such changes (G10398A, A12308G, and G13708A) were present in our patients. Elevated ROS may cause OS. This OS may further damage mtDNA and may cause decreased mitochondrial respiration. This may lead to impaired growth, development and differentiation of TM and consequently trabecular-dysgenesis, which is a characteristic feature of PCG. OS affects both TM and retinal ganglion cells (RGCs) and may be involved in the neuronal death affecting the optic nerve in glaucoma. There are several studies which point to mitochondrial dysfunction in different types of glaucoma and critically participate in RGC death. Recent studies also implicate mitochondrial dysfunction-associated OS as a risk factor for glaucoma patients. It has been reported that elevated hydrostatic pressure causes breakdown of the mitochondrial network by mitochondrial fission and induce cristae depletion and cellular ATP reduction in differentiated RGC-5 cells in vitro as well as in vivo. A total of 44 novel mtDNA variations were identified in this study. Non-synonymous mtDNA variations may adversely affect respiratory chain, impair OXPHOS pathway result in low ATP production, high ROS production and impair growth, development and differentiation of TM lead to trabecular-dysgenesis and consequently RGC's death. Such cases with mtDNA variations and consequent OS may benefit by early diagnosis and prompt management by antioxidant therapy. This may delay OS induced injury to TM and RGCs and hence improve visual prognosis.


Paraquat-induced injury of type II alveolar cells. An in vitro model of oxidant injury.
Paraquat, a widely used herbicide, causes severe, often fatal lung damage. In vivo studies suggest the alveolar epithelial cells (types I and II) are specific targets of paraquat toxicity. This study used 51Cr-labeled type II cells to demonstrate that paraquat (10-5 M) resulted in type II cell injury in vitro, independent of interacting immune effector agents. With 51Cr release expressed as the cytotoxic index (Cl), type II cell injury was found to accelerate with increasing paraquat concentrations (10(-5) M, 10(-4) M, and 10(-3) M, resulting in a Cl of 12.5 +/- 2.2, 22.8 +/- 1.8, and 35.1 +/- 1.9, respectively). Paraquat-induced cytotoxicity (10(-4) M, with a Cl of 22.8 +/- 1.8) was effectively reduced by catalase 1,100 U/ml (Cl 8.0 +/- 3.2, p less than 0.001), superoxide dismutase, 300 U/ml (Cl 17.4 +/- 1.7, p less than 0.05), alpha tocopherol, 10 micrograms/ml (Cl 17.8 +/- 1.6, p less than 0.05). Paraquat toxicity (10(-3) M) was potentiated in the presence of 95% O2 with an increase in Cl from 31.1 +/- 1.7 to 36.4 +/- 2.3 (p less than 0.05). Paraquat-induced type II cell injury was noted as early as 4 h incubation by electron microscopic evidence of swelling of mitochondrial cristae and dispersion of nuclear chromatin. Thus, this in vitro model indicates that paraquat-induced type II cell injury can be quantified, confirmed by morphologic ultrastructural changes, significantly reduced by antioxidants, and potentiated by hyperoxia.


Comparison of motor proficiency and functional ambulation in Duchenne muscular dystrophy with healthy peers.
The study was aimed to investigate the difference between boys with Duchenne muscular dystrophy (DMD) and healthy peers in terms of gross and fine motor proficiency, and determine the relationship between motor proficiency and ambulation. A total of 24 boys with DMD and 22 healthy peers were evaluated. Demographics and physical characteristics were recorded. The Bruininks Oseretsky Test of Motor Proficiency-Short Form (BOTMP-SF) was administered to evaluate gross and fine motor proficiency in both groups. The 6-minute walk test (6MWT) was performed to evaluate functional walking capacity and North Star Ambulatory Assessment (NSAA) was used to determine ambulatory status of boys with DMD. The gross motor proficiency score was significantly lower in boys with DMD (p = 0.001). No difference was found between the groups in terms of fine motor proficiency (p = 0.962). The gross motor function of BOTMP-SF was significantly related to 6MWT distance (r = 0.696, p = 0.001) and NSAA (r = 0.738, p = 0.001). No relationship was found between BOTMP-SF fine motor proficiency and 6MWT distance (r = 0.210, p = 0.361), and NSAA (r = -0.020, p = 0.928). There were significant correlations between running speed and agility with 6MWT distance (r = 0.585, p = 0.005) and NSAA (r = 0.650, p = 0.056). Boys with DMD were more affected in aspects of gross motor proficiency than healthy peers, while fine motor proficiency were found same. The gross motor proficiency was found more related to the level of ambulation.


Self-Care Activities among People with Multiple Sclerosis in Denmark: Use and User Characteristics.
People with multiple sclerosis (PwMS) are known to use a wide range of medical and non-medical treatments. This study aims at investigating the use of self-care activities within this patient group. The study follows a descriptive cross-sectional design based on an online survey among members of the Danish Multiple Sclerosis Society's permanent respondent panel. The results of the study indicate that the respondents carry out a wide variety of self-care activities. These activities comprise conventional activities as well as complementary and alternative medicine (CAM)-based activities. The self-care activities are mainly kept up for non-specific and preventive purposes, with primarily personal or non-specific issues as the primary source of inspiration. Comparative analyses indicate that respondents with a low level of self-care more often are men, belong to the young age group and have a low level of education, a low level of self-assessed state of health, a low level of self-assessed quality of life (QoL), and an unknown subdiagnosis. Respondents with a high level of self-care are more often women and have a high level of self-assessed QoL. A wide variety of self-care activities are carried out by PwMS, comprising conventional as well as CAM-based activities. The purposes of such activities are manifold, but they are mainly of non-specific and preventive nature. Differences in background characteristics exist between groups of low and high levels of self-care.


Current status of carbon dioxide angiography.
Unfamiliarity of endovascular surgeons with carbon dioxide (CO2) angiography is one of the main reasons for its limited use. This review is intended to familiarize the reader with the principles and applications of that modality. We conducted a comprehensive review of contemporary literature related to CO2 angiography and its use in the field of vascular and endovascular surgery, including technical details and diagnostic and interventional applications. Cardinal physicochemical characteristics of CO2 include buoyancy, ultralow viscosity, and nonmixing with blood. Because of the risk of neurotoxicity, intra-arterial CO2 angiography should only be performed below the diaphragm. Venous CO2 angiography can be performed anywhere in the torso and extremities. Ultralow viscosity enables intraprocedural imaging during vascular interventions without the need to exchange for an angiographic catheter. Benefits, advantages, and emerging applications of CO2 angiography are listed. Potential complications and their avoidance and troubleshooting are discussed. CO2 holds promise as an effective and versatile angiographic contrast agent. It is also a valuable modality for the guidance of endovascular interventions. Current availability of easy to use, safe, and portable CO2 delivery systems will likely expand the use of that modality even beyond the traditional indications of renal insufficiency and iodinated contrast allergy.


Biological function of laminin-5 and pathogenic impact of its deficiency.
The basement membrane glycoprotein laminin-5 is a key component of the anchoring complex connecting keratinocytes to the underlying dermis. It is secreted by keratinocytes as a cross-shaped heterotrimer of alpha3, beta3 and gamma2 chains and serves as a ligand of various transmembrane receptors, thereby regulating keratinocyte adhesion, motility and proliferation. In intact skin, laminin-5 provides essential links to both the hemidesmosomal alpha6beta4 integrin and the collagen type VII molecules which form the anchoring fibrils inserting into the dermis. If the basement membrane is injured, laminin-5 production increases rapidly. It then serves as a scaffold for cell migration, initiates the formation of hemidesmosomes and accelerates basement membrane restoration at the dermal-epidermal junction. Mutations of the laminin-5 genes or auto-antibodies against one of the subunits of laminin-5 may lead to a significant lack of this molecule in the epidermal basement membrane zone. The major contributions of laminin-5 to the resistance of the epidermis against frictional stress but also for basement membrane regeneration and repair of damaged skin are reflected by the phenotype of Herlitz junctional epidermolysis bullosa, which is caused by an inherited absence of functional laminin-5. This lethal disease becomes manifest in widespread blistering of skin and mucous membranes, impaired wound healing and chronic erosions containing exuberant granulation tissue. Here, we discuss current understanding of the biological functions of laminin-5, the pathogenic impact of its deficiency and implications on molecular approaches towards a therapy of junctional epidermolysis bullosa.


The Atypical Response Regulator AtvR Is a New Player in Pseudomonas aeruginosa Response to Hypoxia and Virulence.
Two-component systems are widespread in bacteria, allowing adaptation to environmental changes. The classical pathway is composed of a histidine kinase that phosphorylates an aspartate residue in the cognate response regulator (RR). RRs lacking the phosphorylatable aspartate also occur, but their function and contribution during host-pathogen interactions are poorly characterized. AtvR (PA14_26570) is the only atypical response regulator with a DNA-binding domain in the opportunistic pathogen Pseudomonas aeruginosa Macrophage infection with the atvR mutant strain resulted in higher levels of tumor necrosis factor alpha secretion as well as increased bacterial clearance compared to those for macrophages infected with the wild-type strain. In an acute pneumonia model, mice infected with the atvR mutant presented increased amounts of proinflammatory cytokines, increased neutrophil recruitment to the lungs, reductions in bacterial burdens, and higher survival rates in comparison with the findings for mice infected with the wild-type strain. Further, several genes involved in hypoxia/anoxia adaptation were upregulated upon atvR overexpression, as seen by high-throughput transcriptome sequencing (RNA-Seq) analysis. In addition, atvR was more expressed in hypoxia in the presence of nitrate and required for full expression of nitrate reductase genes, promoting bacterial growth under this condition. Thus, AtvR would be crucial for successful infection, aiding P. aeruginosa survival under conditions of low oxygen tension in the host. Taken together, our data demonstrate that the atypical response regulator AtvR is part of the repertoire of transcriptional regulators involved in the lifestyle switch from aerobic to anaerobic conditions. This finding increases the complexity of regulation of one of the central metabolic pathways that contributes to Pseudomonas ubiquity and versatility.


Aphasia from the inside: The cognitive world of the aphasic patient.
The purpose of this study was to analyze the question: how do people with aphasia experience the world? Three questions are approached: (1) how is behavior controlled in aphasia, considering that a normal linguistic control is no longer available; (2) what is the pattern of intellectual abilities in aphasia; and (3) what do aphasia patients' self-report regarding the experience of living without language. In aphasia, behavior can no longer be controlled through the "second signal system" and only the first signal system remains. Available information suggests that sometimes no verbal abilities may be affected in aphasia. However, an important variability is observed: whereas, in some patients, evident nonverbal defects are found; in other patients, performance verbal abilities are within normal limits. Several self-reports of recovered aphasic patients explain the experience of living without language. Considering that language represents the major instrument of cognition, in aphasia, surrounding information is evidently interpreted in a partially different way and cognitive strategies are reorganized, resulting in an idiosyncratic cognitive world.


The Abrams geriatric self-neglect scale: introduction, validation and psychometric properties.
Self-neglect is an imprecisely defined entity with multiple clinical expressions and adverse health consequences, especially in the elderly. However, research has been limited by the absence of a measurement instrument that is both inclusive and specific. Our goal was to establish the psychometric properties of a quantitative instrument, the Abrams Geriatric Self-Neglect Scale (AGSS). We analyzed data from a 2007 case-control study of 71 cognitively intact community-dwelling older self-neglectors that had used the AGSS. The AGSS was validated against two "gold standards": a categorical definition of self-neglect developed by expert consensus; and the clinical judgment of a geriatric psychiatrist using chart review. Frequencies were examined for the six scale domains by source (Subject, Observer, and Overall Impression). Internal consistency was estimated for each source, and associations among the sources were evaluated. Internal consistency estimates for the AGSS were rated as "good," with the Subject responses having the lowest alpha and omega (0.681 and 0.692) and the Observer responses the highest (0.758 and 0.765). Subject and Observer scores had the lowest association (0.578, p < 0.001). Using expert consensus criteria as the primary "gold standard," the Observer and Overall Impression subscales were "good" at classifying self-neglect, while the Subject subscale was "fair." The AGSS correctly classified and quantified self-neglect against two "gold standards." Sufficient correlations among multiple sources of information allow investigators and clinicians to choose flexibly from Subject, Observer, or Overall Impression. The lower internal consistency estimates for Subject responses are consistent with self-neglectors' propensity to disavow symptoms. Copyright © 2017 John Wiley & Sons, Ltd.


Central nervous system tumours profile at a referral center in the Brazilian Amazon region, 1997-2014.
Tumours of the Central Nervous System (CNS) are an important cause of mortality from cancer. Epidemiological data on neoplams affecting the CNS are scarce in Brazil, especially in the Amazon region. The study aims at describing the histopathological profile of CNS tumours cases at a high-complexity referral cancer center. This study has described a 17-year-series profile of CNS tumours, registered at a high-complexity referral cancer center in Pará state, from January 1997 until July 2014 in the Brazilian Amazon Region. Data was gathered from histopathology reports kept in the hospital's cancer registry and 949 cases of CNS tumours were analyzed. The most common histopathology were neuroepithelial tumours (approx. 40%) and meningioma was the most frequent especific tumor histologic subtype (22.2%). Neuroepithelial tumours were more frequent in patients with ages ranging from less than a year to 19 years, whereas metastatic tumours were prevalent in patients over 40 years of age. It was not found temporal trends during the studied period. The knowledge of these tumours profile is valuable for the understanding of cancer epidemiology in the region, since its prevalence is currently underreported and more awareness on the disease is needed.


Using ultrasound to assess the fetus at risk.
In early pregnancy, ultrasonic scanning is valuable if the patient's menstrual history is unreliable or if uterine size is less than expected. The crown-rump length of the embryo can be measured from the sixth week of gestation, and pulsation of the heart detected from the seventh. The crown-rump length of the early embryo gives precise information about maturity. Somewhat later in pregnancy, fetal maturity and growth rate can be assessed accurately by measurement of the biparietal diameter. The head circumference and the fetal upper abdominal circumference together give the head-abdomen ratio, which can be helpful in assessing fetal nutrition. The abdominal circumference also may be used to predict fetal weight.


Plexciton Dirac points and topological modes.
Plexcitons are polaritonic modes that result from the strong coupling between excitons and plasmons. Here, we consider plexcitons emerging from the interaction of excitons in an organic molecular layer with surface plasmons in a metallic film. We predict the emergence of Dirac cones in the two-dimensional band-structure of plexcitons due to the inherent alignment of the excitonic transitions in the organic layer. An external magnetic field opens a gap between the Dirac cones if the plexciton system is interfaced with a magneto-optical layer. The resulting energy gap becomes populated with topologically protected one-way modes, which travel at the interface of this plexcitonic system. Our theoretical proposal suggests that plexcitons are a convenient and simple platform for the exploration of exotic phases of matter and for the control of energy flow at the nanoscale.