Quantum potentiality revisited.
Heisenberg offered an interpretation of the quantum state which made use of a quantitative version of an earlier notion, [Formula: see text], of Aristotle by both referring to it using its Latin name, potentia, and identifying its qualitative aspect with [Formula: see text] The relationship between this use and Aristotle's notion was not made by Heisenberg in full detail, beyond noting their common character: that of signifying the system's objective capacity to be found later to possess a property in actuality. For such actualization, Heisenberg required measurement to have taken place, an interaction with external systems that disrupts the otherwise independent, natural evolution of the quantum system. The notion of state actualization was later taken up by others, including Shimony, in the search for a law-like measurement process. Yet, the relation of quantum potentiality to Aristotle's original notion has been viewed as mainly terminological, even by those who used it thus. Here, I reconsider the relation of Heisenberg's notion to Aristotle's and show that it can be explicated in greater specificity than Heisenberg did. This is accomplished through the careful consideration of the role of potentia in physical causation and explanation, and done in order to provide a fuller understanding of this aspect of Heisenberg's approach to quantum mechanics. Most importantly, it is pointed out that Heisenberg's requirement of an external intervention during measurement that disrupts the otherwise independent, natural evolution of the quantum system is in accord with Aristotle's characterization of spontaneous causation. Thus, the need for a teleological understanding of the actualization of potentia, an often assumed requirement that has left this fundamental notion neglected, is seen to be spurious.This article is part of the themed issue 'Second quantum revolution: foundational questions'.


Protection from doxorubicin-induced cardiac toxicity in mice with a null allele of carbonyl reductase 1.
Doxorubicin is a highly effective antineoplastic agent, but it can produce the serious side effects of acute cardiac injury and chronic congestive heart failure. Carbonyl reductase (CBR) has been implicated in the development of doxorubicin-induced cardiotoxicity. To test whether a decrease in CBR levels was protective against doxorubicin toxicity, we created a null allele of the Cbr1 gene. Mice with one functional copy of the gene (Cbr1 +/-) were healthy and grossly normal despite having decreased levels of Cbr1 transcript and protein. Control and Cbr1 +/- mice were administered doxorubicin at 20 mg/kg i.p. Cbr1 +/- mice showed decreased circulating levels of the cardiotoxic metabolite, doxorubicinol, after administration. Within 2 weeks, 91% of wild-type mice were severely affected (n = 11) compared with 18% of Cbr1 +/- mice (n = 11). Echocardiography and histological analysis showed that Cbr1 +/- mice were protected from gross and cellular level pathologies associated with doxorubicin treatment. Demonstration that inhibition of carbonyl reductase blocks the toxic effects on the heart has important implications for improving the use of doxorubicin in chemotherapy.


Metastatic Merkel cell carcinoma (MCC) of pancreas and breast: a unique case.
Merkel cell carcinoma (MCC) is a rare potentially fatal skin tumor affecting older and immunosuppressed individuals. It is highly malignant with high rates of metastasis and poor survival.We present a case of a 67-year-old woman with a palpable mass in the upper abdomen. An abdominal CT revealed a mass in the tail of the pancreas. Two weeks before, lumpectomy of a 3.5 cm tumor of the left breast had been performed. Histology showed a primary neuroendocrine carcinoma of the mammary gland. The patient's medical history was significant for a 0.7 × 0.9 cm MCC removed from her left forearm 2.5 years ago. There was no evidence of vascular involvement or peritoneal disease and by all criteria was resectable. A somatostatin receptor scintigraphy showed an enhanced uptake in the pancreatic tail region. The tumor was immunohistochemically strong staining for synaptophysin and CD56. The diagnosis of a metastatic-MCC in the tail of the pancreas was made. Further histological investigation of the prior removed neuroendocrine breast tumor and the MCC of the left forearm confirmed neuroendocrine origin and identical histology to the previously resected MCC of the left forearm. In this article, we aim to highlight that MCC has the potential to spread even in unusual organs, such as pancreas or breast, and therefore a diligent follow-up should be applied in patients with MCC.


Estimated dopamine D₂ receptor occupancy and remission in schizophrenia: analysis of the CATIE data.
In treating schizophrenia, 65% to 80% occupancy of dopamine D₂ receptors optimizes therapeutic efficacy while minimizing risks of extrapyramidal symptoms and cognitive impairments. However, it is unclear as to whether it is necessary to keep D₂ receptor occupancy within this therapeutic window to maintain clinical response. The data set from phase 1 of the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) trial was reappraised. Thirty patients receiving risperidone (12 patients), olanzapine (12 patients), or ziprasidone (6 patients) fulfilled the following definition of remission and were included: a score of 3 or less on the 8 specific items in the Positive and Negative Syndrome Scale (ie, P1, P2, P3, N1, N4, N6, G5, and G9; adopted from Andreasen et al, 2005) at the initial assessment and months 1, 2, and 6. Peak and trough D₂ receptor occupancy levels at month 6 were estimated from plasma antipsychotic concentrations using population pharmacokinetic analysis and our D₂ prediction model. Estimated mean ± SD peak and trough D₂ receptor occupancy levels at month 6 were 70.3% ± 9.8% and 60.5% ± 20.2%, respectively; among these individuals, 46.7% (14 patients) did not achieve continuous blockade of 65% or greater (ie, trough D₂ occupancy of <65%). In conclusion, approximately half of patients with remission did not achieve continuous blockade of estimated D₂ receptor occupancy 5% or greater. These results extend our previous findings and suggest that sustained D₂ receptor occupancy greater than 65% may not always be necessary for the maintenance treatment of schizophrenia.


Optimizing health and health care systems for children with special health care needs using the life course perspective.
To date, life course research in maternal and child health has largely focused on elucidating fetal and early life influences on adult health and less on promoting the health of children with special health care needs (CSHCN). Consideration of life course theory (LCT) for CSHCN is especially important given their increasing prevalence and comorbidity, their disproportionate vulnerability to weaknesses or instability in the health care system, and the growing evidence linking child and adult health and quality of life. In this commentary we seek to advance the consideration of LCT for CSHCN. We (1) briefly summarize key issues and the importance of a life course approach for CSHCN; (2) present illustrative findings from population-based cross-sectional data that serve to generate hypotheses that can be more rigorously examined when population-based longitudinal data become available; and (3) discuss the application of life course principles as a driving force in the continued implementation and improvement of integrated systems of care for CSHCN.


Mommio's Recipe Box: Assessment of the Cooking Habits of Mothers of Preschoolers and Their Perceptions of Recipes for a Video Game.
Vegetables are an important part of a healthy diet because they help prevent several chronic diseases. Mothers of preschoolers reported difficulty getting their young children to eat vegetables, and many did not know how to cook child-pleasing recipes. The cooking habits of mothers of preschoolers, their perceptions of recipes designed for their children, and the involvement of their children in food preparation were assessed to inform a food parenting video game called Mommio. A cross-sectional survey design was used. Eligibility criteria included mothers of 3- to 5-year-old children who reported difficulty getting their children to eat vegetables. Participants completed a demographic questionnaire with questions about their food preparation practices. They were asked to select up to 4 of the 10 provided recipes they wanted to try and to prepare and report back on their experiences. Most (46) of the 50 recipes included in Mommio's in-game recipe box were evaluated at least once and some up to 5 times with a total of 85 evaluations. This well-educated, mostly employed, sample of 27 mothers of preschoolers preferred simple, quick recipes. They ate primarily at home, made dinners from scratch, and indicated that the 46 recipes were generally simple, quick, and easy to prepare. Involvement in preparation enhanced their child's acceptance of the food. Prior food and preparation preferences influenced the children's acceptance of the dish at the ensuing meal. The high rate of home recipe preparation indicated that including a recipe selection and preparation component in a food parenting video game could be attractive and may enhance effectiveness. Mothers reported that the recipes provided were generally easy to prepare, tasted good, and the instructions were easy to understand, suggesting they could be helpful to the mothers when playing a vegetable parenting game. Some mothers reported that involving their children in recipe preparation influenced their children's willingness to eat the vegetables. The highest rated recipes are being included in the game, and mothers will be encouraged to involve their children in recipe preparation.


9,10-Dioxoanthracenyldithiocarbamates effectively inhibit the proliferation of non-small cell lung cancer by targeting multiple protein tyrosine kinases.
Anthraquinones have attracted considerable interest in the realm of cancer treatment owing to their potent anticancer properties. This study evaluates the potential of a series of new anthraquinone derivatives as anticancer agents for non-small-cell lung cancer (NSCLC). The compounds were subjected to a range of tests to assess their cytotoxic and apoptotic properties, ability to inhibit colony formation, pro-DNA damage functions, and capacity to inhibit the activity of tyrosine kinase proteins (PTKs). Based on the research findings, it has been discovered that most active derivatives (i84, i87, and i90) possess a substantial capability to impede the viability of NSCLC while having mostly a negligible effect on the human kidney cell line. Moreover, the anthraquinones displayed pro-apoptotic and genotoxic attributes while blocking the phosphorylation of multiple PTKs. Collectively, our findings indicate that these derivatives may demonstrate promising potential as effective anticancer agents for lung cancer treatment.


Inverse target- and cue-priming effects of masked stimuli.
The processing of a visual target that follows a briefly presented prime stimulus can be facilitated if prime and target stimuli are similar. In contrast to these positive priming effects, inverse priming effects (or negative compatibility effects) have been found when a mask follows prime stimuli before the target stimulus is presented: Responses are facilitated after dissimilar primes. Previous studies on inverse priming effects examined target-priming effects, which arise when the prime and the target stimuli share features that are critical for the response decision. In contrast, 3 experiments of the present study demonstrate inverse priming effects in a nonmotor cue-priming paradigm. Inverse cue-priming effects exhibited time courses comparable to inverse target-priming effects. Results suggest that inverse priming effects do not arise from specific processes of the response system but follow from operations that are more general.


Identifying Children in Middle Childhood Who Are at Risk for Reading Problems.
The purpose of this study was to identify and evaluate a universal screening battery for reading that is appropriate for older elementary students in a response to intervention model. Multiple measures of reading and reading correlates were administered to 230 fourth-grade children. Teachers rated children's reading skills, academic competence, and attention. Children were classified as not-at-risk or at-risk readers based on a three-factor model reflecting reading comprehension, word recognition/decoding, and word fluency. Predictors of reading status included group-administered tests of reading comprehension, silent word reading fluency, and teacher ratings of reading problems. Inclusion of individually administered tests and growth estimates did not add substantial variance. The receiver-operator characteristic curve analysis yielded an area under the curve index of 0.90, suggesting this model may both accurately and efficiently screen older elementary students with reading problems.


Tobacco imagery in entertainment media: evolution of tobacco-free movies and television programmes rules in India.
Tobacco imagery in films and television increased in India after it ended conventional tobacco advertising in 2004. The Ministry of Health and Family Welfare (MoHFW) introduced rules to eliminate this tobacco imagery in 2005 which took effect in amended form in 2012. This study presents the enablers and barriers in development and implementation of the regulations to curb tobacco imagery in films and television in India. We reviewed legislation, evolving regulations, parliamentary questions, judicial decisions, Bollywood trade publications and relevant news articles from 2003 to 2019 and interviewed key informants. Based on the WHO reports and civil society demands, the MoHFW issued a complete ban on tobacco imagery in movies and television programmes in 2005. The Ministry of Information and Broadcasting (MoIB) joined the film industry in opposing the rules. A filmmaker challenged the rules in court, which ruled that they violated constitutional freedoms. On appeal by MoHFW, the Supreme Court allowed the rules to take effect. Continuing opposition by MoIB and the film industry weakened the rules and delayed implementation until 2012. As of 2020, rather than a ban, all films with tobacco imagery require strong editorial justification, 100 s of antitobacco messages produced by the MoHFW, and a static health warning at the bottom of screen during tobacco imagery display. In 2015, less than 48% of movies had tobacco imagery compared with 89% in 2005. Although, not a ban, MoHFW, supported by local advocates and WHO, issued regulations that resulted in a substantial drop in on-screen tobacco imagery and increased exposure to antitobacco messages. India's experience informs WHO Framework Convention on Tobacco Control parties as they develop and implement policies to curb tobacco imagery in entertainment media.


A study of cerebral blood flow and metabolism in epileptic psychosis using positron emission tomography and oxygen.
Data are presented on four groups using positron tomography and 15 O inhalation. Compared to age-matched volunteer controls, epileptic patients show regions of low blood flow and hypometabolism as found in previous studies. Epileptic psychotic and non-psychotic patients have been compared, and the main differences noted were lower rOER in the psychotic group, especially in frontal, temporal and basal ganglia regions. When a group of psychotic patients receiving neuroleptic drugs was compared to those free of these medications the rOER was higher in the treated sample, and the rCBF fell, significantly in some areas. These data are discussed in the light of other reports of positron tomography in psychosis.


Proof of systemic safety of a lidocaine ointment in the treatment of patients with anorectal pain.
The aim of the study was to demonstrate that repeated anorectal administration of a 5% lidocaine ointment (CAS 137-58-6; LidoPosterine Salbe, Posterisan akut Rektalsalbe) in the treatment of patients with acute anorectal pain does not result in systemically efficacious plasma concentrations of lidocaine. In an open single-center study 24 male or female patients with anorectal pain due to hemorrhoids, anal fissures, fistulas or proctitis administered lidocaine ointment as a single anorectal dose (2.5 g ointment corresponding to 125 mg lidocaine) followed by repeated administration (2.5 g ointment t.i.d.) for 4 days. Safety evaluation was performed with respect to plasma concentrations of lidocaine, vital signs, electrocardiogram (ECG), physical findings and adverse events. Blood samples were drawn prior to the first single administration and at 13 time points over the first 24 h in order to create a pharmacokinetic profile. Blood samples were also drawn prior to administration of the last dose on day 5 and thereafter using the identical time points for blood sampling as on day 1. Vital signs and ECG were recorded immediately before and 1 and 4 h after the first and last administration, respectively. Adverse events and skin tolerability were also recorded at predefined times during the study period. After a single dose of 125 mg lidocaine the average extent of exposure in terms of the AUC(tau,sd) during a 6 h dosage interval amounted to 397.7 ng/ml x h (geometric mean). C(max,sd) reached a mean value of 131.8 ng/ml (geometric mean). Only a minor accumulation of the lidocaine plasma concentrations was observed after multiple dose application. The geometric mean of the AUC(tau,md) (503.8 ng/ml x h, tau = 6 h) and the geometric mean of C(max,md) (145.9 ng/ml) were slightly higher than the corresponding single dose values. The AUC accumulation ratio was calculated as 127% (90% CI: 108-148%) and the C(max) accumulation ratio reached 120% (90% CI: 101-139%). Plasma peak concentrations of lidocaine in all subjects remained with a sufficient safety margin below the minimal effective therapeutic plasma concentration (1.5 microg/ml) as well as by an order of magnitude below toxic concentrations (5 microg/ml). There were neither unexpected, serious nor severe adverse events. There were no clinically relevant findings with respect to vital signs and ECG. Repeated anorectal administration of a 5% lidocaine ointment proved to be safe with respect to systemic plasma concentrations of lidocaine and vital signs.


Nonthermal Plasma Synthesis of Nanocrystals: Fundamental Principles, Materials, and Applications.
Nonthermal plasmas have emerged as a viable synthesis technique for nanocrystal materials. Inherently solvent and ligand-free, nonthermal plasmas offer the ability to synthesize high purity nanocrystals of materials that require high synthesis temperatures. The nonequilibrium environment in nonthermal plasmas has a number of attractive attributes: energetic surface reactions selectively heat the nanoparticles to temperatures that can strongly exceed the gas temperature; charging of nanoparticles through plasma electrons reduces or eliminates nanoparticle agglomeration; and the large difference between the chemical potentials of the gaseous growth species and the species bound to the nanoparticle surfaces facilitates nanocrystal doping. This paper reviews the state of the art in nonthermal plasma synthesis of nanocrystals. It discusses the fundamentals of nanocrystal formation in plasmas, reviews practical implementations of plasma reactors, surveys the materials that have been produced with nonthermal plasmas and surface chemistries that have been developed, and provides an overview of applications of plasma-synthesized nanocrystals.


Morphology and immunophenotyping of a monolateral ovotestis in a 46,XderY/45,X mosaic individual with ambiguous genitalia.
Disorders of sexual development represent a pathologic and clinical challenge. Many different clinical syndromes exist, and several classifications have been proposed in relation to different risks for malignant degeneration. The morphology, cytogenetics, and immunophenotype of a monolateral ovotestis in a 3-month-old individual with ambiguous genitalia and right inguinal mass are reported. The inguinal mass consisted of a tiny female genital tract with a hermaphroditic gonad with focal placental-like alkaline phosphatase-stained gonocytes; chromosome analysis disclosed a mosaic constitution: 46,XderY/45,X with a rearranged Y chromosome. A sharp morphologic distinction between true hermaphroditism and mixed gonadal dysgenesis probably does not exist, and cytogenetic characterization is mandatory. The presence of placental-like alkaline phosphatase-stained gonocytes indicates a high risk of malignant transformation, and justifies the surgical removal of the dysgenetic gonad. Fertility is unlikely.


Cost-effectiveness and cost-utility of Internet-based computer tailoring for smoking cessation.
Although effective smoking cessation interventions exist, information is limited about their cost-effectiveness and cost-utility. To assess the cost-effectiveness and cost-utility of an Internet-based multiple computer-tailored smoking cessation program and tailored counseling by practice nurses working in Dutch general practices compared with an Internet-based multiple computer-tailored program only and care as usual. The economic evaluation was embedded in a randomized controlled trial, for which 91 practice nurses recruited 414 eligible smokers. Smokers were randomized to receive multiple tailoring and counseling (n=163), multiple tailoring only (n=132), or usual care (n=119). Self-reported cost and quality of life were assessed during a 12-month follow-up period. Prolonged abstinence and 24-hour and 7-day point prevalence abstinence were assessed at 12-month follow-up. The trial-based economic evaluation was conducted from a societal perspective. Uncertainty was accounted for by bootstrapping (1000 times) and sensitivity analyses. No significant differences were found between the intervention arms with regard to baseline characteristics or effects on abstinence, quality of life, and addiction level. However, participants in the multiple tailoring and counseling group reported significantly more annual health care-related costs than participants in the usual care group. Cost-effectiveness analysis, using prolonged abstinence as the outcome measure, showed that the mere multiple computer-tailored program had the highest probability of being cost-effective. Compared with usual care, in this group €5100 had to be paid for each additional abstinent participant. With regard to cost-utility analyses, using quality of life as the outcome measure, usual care was probably most efficient. To our knowledge, this was the first study to determine the cost-effectiveness and cost-utility of an Internet-based smoking cessation program with and without counseling by a practice nurse. Although the Internet-based multiple computer-tailored program seemed to be the most cost-effective treatment, the cost-utility was probably highest for care as usual. However, to ease the interpretation of cost-effectiveness results, future research should aim at identifying an acceptable cutoff point for the willingness to pay per abstinent participant.


A fresh look at interferon-alpha signaling and treatment outcomes in chronic hepatitis C.
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. The current standard therapy for chronic hepatitis C (CHC) consists of a combination of pegylated IFN alpha (pegIFNalpha) and ribavirin. It achieves a sustained viral clearance in only 50-60% of patients. To learn more about molecular mechanisms underlying treatment failure, we investigated IFN-induced signaling in paired liver biopsies collected from CHC patients before and after administration of pegIFNalpha. In patients with a rapid virological response to treatment, pegIFNalpha induced a strong up-regulation of IFN-stimulated genes (ISGs). As shown previously, nonresponders had high expression levels of ISGs before therapy. Analysis of posttreatment biopsies of these patients revealed that pegIFNalpha did not induce expression of ISGs above the pretreatment levels. In accordance with ISG expression data, phosphorylation, DNA binding, and nuclear localization of STAT1 indicated that the IFN signaling pathway in nonresponsive patients is preactivated and refractory to further stimulation. Some features characteristic of nonresponders were more accentuated in patients infected with HCV genotypes 1 and 4 compared with genotypes 2 and 3, providing a possible explanation for the poor response of the former group to therapy. Taken together with previous findings, our data support the concept that activation of the endogenous IFN system in CHC not only is ineffective in clearing the infection but also may impede the response to therapy, most likely by inducing a refractory state of the IFN signaling pathway.


Estimation of cancer risks from radiotherapy of benign diseases.
The effective-dose method which was proposed by the ICRP (International Commission of Radiation Protection) for the estimation of risk to the general population from occupational or environmental, low-dose radiation exposure is not adequate for estimating the risk of cancer induction by radiotherapy of malignant or nonmalignant diseases. The risk of cancer induction by radiotherapy of benign diseases should be based on epidemiologic data directly derived from follow-up studies of patients who had been given radiotherapy for nonmalignant diseases in the past. Risk factors were derived from epidemiologic studies of patients treated with irradiation for nonmalignant diseases to be used for selecting treatment options and optimizing treatment procedures. In most cases, cancer risks estimated by the effective-dose method may overestimate the true risks by one order of magnitude, yet in other cases even may underestimate it. The proposed method using organ-specific risk factors may be more suitable for treatment planning.


Evolution and progression of Barrett's oesophagus to oesophageal cancer.
Cancer cells are shaped through an evolutionary process of DNA mutation, cell selection and population expansion. Early steps in this process are driven by a set of mutated driver genes and structural alterations to the genome through copy number gains or losses. Oesophageal adenocarcinoma (EAC) and the pre-invasive tissue, Barrett's oesophagus (BE), provide an ideal example in which to observe and study this evolution. BE displays early genomic instability, specifically in copy number changes that may later be observed in EAC. Furthermore, these early changes result in patterns of progression (that is, 'born bad', gradual or catastrophic) that may help to describe the evolution of EAC. As only a small proportion of patients with BE will go on to develop cancer, a better understanding of these patterns and the resulting genomic changes should improve early detection in EAC and may provide clues for the evolution of cancer more broadly.


Mindfulness and contemplative approaches in education.
There is a growing and promising quantitative evidence base on mindfulness in schools, which has continued to emerge over the last two years and which consistently suggests small to moderate impacts across a range of outcomes, most strongly and reliably on psycho-social health and well-being, especially mental health problems, with less definitive but promising evidence for small effects on behaviour, cognition, learning, and physical health. The overlapping field of 'contemplative education' is less concerned with measurable outcomes, aiming instead to put the learner, and their self-reflective mindfulness at the heart of the teaching and learning process. Interest is growing on how best to implement mindfulness and integrate it into the policies, practice and ethos of the whole institution, with some promising early findings, mainly from qualitative data. There is a particular and growing emphasis, supported by some emerging quantitative evidence, on the need for teachers to learn mindfulness themselves and establish their own practice if they are to cultivate mindfulness in schools effectively.


Oxygen vacancy control as a strategy to achieve highly reliable hafnia ferroelectrics using oxide electrode.
Recently, hafnia ferroelectrics with two spontaneous polarization states have attracted marked attention for non-volatile, super-steep switching devices, and neuromorphic application due to their fast switching, scalability, and CMOS compatibility. However, field cycling-induced instabilities are a serious obstacle in the practical application of various low-power electronic devices that require a settled characteristic of polarization hysteresis. In this work, a large reduction in the field cycling-induced instabilities and significantly improved ferroelectric properties were observed in a Hf0.5Zr0.5O2 (HZO) thin film with a RuO2 oxide electrode. The oxide electrode can supply additional oxygen to the HZO film, consequently minimizing the oxygen vacancies at the interface which is the origin of low reliability. From the material and electrical analysis results, we verified that HZO with the RuO2 electrode has less non-ferroelectric dead layers and fewer oxygen vacancies at the interface, resulting in excellent switching properties and improved reliability. This result suggests a beneficial method to produce high-quality hafnia thin films free from interfacial defects and with stable field cycling electrical properties for actual applications.


Dietary magnesium depletion affects metabolic responses during submaximal exercise in postmenopausal women.
Magnesium is an essential mineral that is required for optimal biological function including energy metabolism. Although national nutritional surveys indicate that usual magnesium intakes do not meet recommendations, particularly among older women, diet-induced magnesium depletion is considered rare among humans without concurrent illness. We examined the effects of dietary magnesium restriction on biochemical measures of magnesium nutriture and physiologic responses during submaximal exercise in 10 postmenopausal women, 45-71 y old, not receiving hormone replacement therapy. The women consumed diets containing conventional foods with varying magnesium content totaling 112 mg/8.4 MJ (2000 kcal) supplemented with 200 mg magnesium daily for 35d (control), then 112 mg/8.4 MJ for 93d (depletion) followed by 112 mg/8.4 MJ supplemented with 200 mg magnesium/d for 49d (repletion) in a depletion-repletion experiment. RBC magnesium concentration (P < 0.05), magnesium retention (P < 0.05) and skeletal muscle magnesium concentration (P < 0.05) decreased when dietary magnesium was restricted. Peak oxygen uptake, total and cumulative net oxygen uptake determined by using indirect calorimetry and peak heart rate increased (P < 0.05) during standardized submaximal work with restricted compared with adequate dietary magnesium. These findings indicate that dietary magnesium depletion can be induced in otherwise healthy women; it results in increased energy needs and adversely affects cardiovascular function during submaximal work. This may also explain previous observations of increased energy cost during standardized exercise in physically active men and women considered to have reduced magnesium nutriture.


Telemedicine After COVID-19: Incorporating Virtual Visits Into Your Practice.
The use of telemedicine services within orthopaedics increased rapidly as a result of the COVID-19 pandemic. Telemedicine may improve access to care and save time and money for patients and clinicians; however, limitations such as technical issues and limited physical examination may reduce its widespread adoption. Virtual visits generally produce equivalent satisfaction and clinical outcomes compared with those performed in person. Although telemedicine has served many different roles within orthopaedic practices, its main utility is for patients who have to travel significant distances and for visits that do not require physical examination to determine a treatment plan. Several regulations govern the use of telemedicine. Most notably, clinicians must be licensed to practice medicine in the state in which the patient is located during the appointment. Although compliance issues remain a potential source of legal issues, experts cite misdiagnosis from limited physical examination as the most likely reason for medical liability. Clinicians should be familiar with techniques for virtual physical examination and should provide instruction to patients before the visit to optimize data obtained.


Barriers to gene flow in the marine environment: insights from two common intertidal limpet species of the Atlantic and Mediterranean.
Knowledge of the scale of dispersal and the mechanisms governing gene flow in marine environments remains fragmentary despite being essential for understanding evolution of marine biota and to design management plans. We use the limpets Patella ulyssiponensis and Patella rustica as models for identifying factors affecting gene flow in marine organisms across the North-East Atlantic and the Mediterranean Sea. A set of allozyme loci and a fragment of the mitochondrial gene cytochrome C oxidase subunit I were screened for genetic variation through starch gel electrophoresis and DNA sequencing, respectively. An approach combining clustering algorithms with clinal analyses was used to test for the existence of barriers to gene flow and estimate their geographic location and abruptness. Sharp breaks in the genetic composition of individuals were observed in the transitions between the Atlantic and the Mediterranean and across southern Italian shores. An additional break within the Atlantic cluster separates samples from the Alboran Sea and Atlantic African shores from those of the Iberian Atlantic shores. The geographic congruence of the genetic breaks detected in these two limpet species strongly supports the existence of transpecific barriers to gene flow in the Mediterranean Sea and Northeastern Atlantic. This leads to testable hypotheses regarding factors restricting gene flow across the study area.


Prostaglandins: an alternative concept for induction of labor.
Vaginal suppositories of prostaglandin E2 constitute a highly efficient and acceptable method for inducing labor in patients with both favorable and unfavorable cervices. Both the failure of induction and consequent cesarean section rates can be dramatically reduced.


The candidate vaccine strain Brucella ovis ∆abcBA is protective against Brucella melitensis infection in mice.
Brucellosis is a major zoonotic disease, and Brucella melitensis is the species most often associated with human infection. Vaccination is the most efficient tool for controlling animal brucellosis, with a consequent decrease of incidence of human infections. Commercially available live attenuated vaccines provide some degree of protection, but retain residual pathogenicity to human and animals. In this study, Brucella ovis ∆abcBA (Bo∆abcBA), a live attenuated candidate vaccine strain, was tested in two formulations (encapsulated with alginate and alginate plus vitelline protein B [VpB]) to immunize mice against experimental challenge with B. melitensis strain 16M. One week after infection, livers and spleens of immunized mice had reduced numbers of the challenge strain B. melitensis 16M when compared with those of nonimmunized mice, with a reduction of approximately 1-log10 of B. melitensis 16M count in the spleens from immunized mice. Moreover, splenocytes stimulated with B. melitensis antigens in vitro secreted IFN-γ when mice had been immunized with Bo∆abcBA encapsulated with alginate plus VpB, but not with alginate alone. Body and liver weights were similar among groups, although spleens from mice immunized with Bo∆abcBA encapsulated with alginate were larger than those immunized with Bo∆abcBA encapsulated with alginate plus VpB or nonimmunized mice. This study demonstrated that two vaccine formulations containing Bo∆abcBA protected mice against experimental challenge with B. melitensis.


Sinistrin clearance for determination of glomerular filtration rate: a reappraisal of various approaches using a new analytical method.
Several approaches are available to estimate the glomerular filtration rate (GFR) from the sinistrin clearance. To compare such approaches, GFR was estimated in six healthy volunteers, both after a bolus injection and a bolus dose followed by a 6-hour infusion. A recently developed high-performance liquid chromatography method was used for the determination of sinistrin levels, enabling precise measurements in plasma and urine samples with high sensitivity. Blood and urine were sampled up to 6 hours. Four calculation methods for estimating GFR were applied: 1) classical ratio of urinary excretion rate over plasma concentration (UV/P); 2) two-point (log-linear regression slope times monocompartmental volume of distribution) after bolus; 3) ratio of dose over area under the curve (D/AUC) after bolus; and 4) ratio of infusion rate over steady-state concentration during infusion (Rinf/P). The results obtained by fitting a pharmacokinetic model to all the plasma and urine data served as the standard against which the performance of the respective calculation methods were examined. The UV/P method performed poorly on bolus data, mainly by underestimating GFR at late times; on both bolus and infusion data, it suffered from important imprecisions on the urinary volume. The two-point method appeared applicable only between 2 and 4 hours after the bolus dose. The D/AUC method with extrapolation to infinity was highly reliable when integrating the concentrations up to 3 hours or more after the bolus dose. The Rinf/P method was satisfactory if applied later than 2 to 3 hours after the loading dose. The advantages and drawbacks of each method have to be evaluated in relation to the particular clinical setting in which GFR is to be estimated.


Extent of surgical resections for intraductal papillary mucinous neoplasms.
Intraductal papillary mucinous neoplasms (IPMNs) can involve the main pancreatic duct (MD-IPMNs) or its secondary branches (BD-IPMNs) in a segmental of multifocal/diffuse fashion. Growing evidence indicates that BD-IPMNs are less likely to harbour cancer and in selected cases these lesions can be managed non operatively. For surgery, clarification is required on: (1) when to resect an IPMN; (2) which type of resection should be performed; and (3) how much pancreas should be resected. In recent years parenchyma-sparing resections as well as laparoscopic procedures have being performed more frequently by pancreatic surgeons in order to decrease the rate of postoperative pancreatic insufficiency and to minimize the surgical impact of these operations. However, oncological radicality is of paramount importance, and extended resections up to total pancreatectomy may be necessary in the setting of IPMNs. In this article the type and extension of surgical resections in patients with MD-IPMNs and BD-IPMNs are analyzed, evaluating perioperative and long-term outcomes. The role of standard and parenchyma-sparing resections is discussed as well as different strategies in the case of multifocal neoplasms.


The pathophysiology of bone disease in gastrointestinal disease.
Reduced bone mass and the increased risk of fracture in gastrointestinal diseases have a multifactorial pathogenesis. Undoubtedly, genetics play an important role, but other factors such as systemic inflammation, malnutrition, hypogonadism, glucocorticoid therapy in inflammatory bowel disease (IBD) and other lifestyle factors, such as smoking or being sedentary, may contribute to reduced bone mass. At a molecular level the proinflammatory cytokines that contribute to the intestinal immune response in IBD and probably also in coeliac disease are also known to enhance bone resorption. The discovery of the role of the receptor to activated NFkappaB (RANK) interaction with its ligand RANKL in orchestrating the balance between bone resorption and formation may link mucosal and systemic inflammation with bone remodelling, since RANK-RANKL are also involved in lymphopoiesis and T-cell apoptosis. Low circulating leptin in response to weight loss in any gastrointestinal disease may be an important factor in reducing bone mass. This report will summarize current concepts regarding gastrointestinal diseases (primarily IBD, coeliac disease and postgastrectomy states) and low bone mass and fracture.


Hospital-legal partnership at Toronto Hospital for Sick Children: the first Canadian experience.
Operating a hospital-legal partnership on a pro bono basis positively impacts patients' families by providing legal assistance for non-medical issues that affect the health of their children and their ability to care for their children. This article describes a formative evaluation of the first hospital-legal partnership in Canada, established at The Hospital for Sick Children in Toronto in 2009, which was carried out through file reviews and interviews with staff, lawyers and family members. The early indications of success of this partnership suggest that its use as a template for similar programs at other Canadian healthcare institutions should be considered.


Disruption and destabilization of meibomian lipid films caused by increasing amounts of ceramides and cholesterol.
We evaluated quantitatively direct effects of ceramide (Cer) and free cholesterol (FC) on meibomian lipid films (MLF) using a Langmuir trough (LT) and a Brewster angle microscope (BAM). Meibum was obtained from healthy volunteers. A series of mixtures of meibum with Cer or FC (mixed MLF) taken in different ratios were tested. Standard rheologic parameters, such as elasticity and hysteresis of MLF, were computed. BAM was used to study the morphology of MLF. Pure MLF were capable of withstanding multiple compression/expansion cycles with little hysteresis observed (1.9 J/G meibum). The films made of either pure CER or pure FC were clearly collapsible, and had much higher rigidity and hysteresis than pure meibum. Adding progressively higher amounts of CER or FC to meibum had a strong impact on the rigidity, stability, and morphology of the mixed MLF: their hysteresis increased many fold compared to pure meibum. A concomitant increase in the rigidity and collapsibility of the mixed MLF was observed. Cer and FC changed the surface properties of mixed MLF in a way that implied their destabilization and/or disruption. One of the mechanisms that might lead to these effects is strong aggregation of meibum lipids with FC or Cer that leads to the formation of smaller particles of meibum surrounded by a thinner layer of FC or Cer. As Cer and FC can be elevated in meibum and the tear film because of certain pathologic processes, or can be of exogenous nature, our results can explain (partially) a less stable tear film in those subjects.


Postoperative magnetic resonance imaging can predict neurological recovery after surgery for cervical spondylotic myelopathy: a prospective study with blinded assessments.
Factors that can predict the recovery of cervical spondylotic myelopathy (CSM) patients postoperatively are of significant interest to physicians and patients and their families. Magnetic resonance imaging (MRI) scans are a common method of examination after surgery, and thus of interest as a predictor of outcome. To investigate whether findings on MRI at 6 months postoperatively could predict recovery at 1 year in CSM patients. In 52 consecutive prospective patients, MRI was performed preoperatively and 6 months postoperatively. T1 and T2 signal change (area, height, and segmentation) and spinal cord re-expansion were measured. Outcome measures evaluated at 1 year postoperatively were compared with preoperative values. Univariate and stepwise multiple regressions were undertaken. Using univariate analysis, patients whose cord failed to re-expand had poorer outcome according to the modified Japanese Orthopedic Association score and Nurick score (P = .014) and grip test (P = .006) postoperatively. Stepwise multivariate regression showed lack of cord re-expansion to be predictive of prognosis postoperatively in the modified Japanese Orthopedic Association score (P = .013) and Berg Balance Scale (P = .014), and walking test (P = .011). Postoperative hyperintense T2 signal change was predictive of worse outcome on the Berg Balance Scale (P = .014) and walking test (P = .020), Nurick score (P = .001), and Short Form-36 scores (P = .020). In cases in which the T2 signal intensified, there was a poorer outcome on Nurick scores (P = .013), grip test (P = .017), and Short Form-36 scores (P = .030). Findings on postoperative MRI at 6 months is of predictive value in determining outcomes in CSM patients. The persistence and type of T2 signal change and lack of re-expansion of the cord correlate with poorer recovery and likely reflect irreversible structural changes in the spinal cord.


A general practice workplace-based assessment instrument: Content and construct validity.
Introduction: Relatively few general practice (GP) workplace-based assessment instruments have been psychometrically evaluated. This study aims to establish the content validity and internal consistency of the General Practice Registrar Competency Assessment Grid (GPR-CAG).Methods: The GPR-CAG was constructed as a formative assessment instrument for Australian GP registrars (trainees). GPR-CAG items were determined by an iterative literature review, expert opinion and pilot-testing process. Validation data were collected, between 2014 and 2016, during routine clinical teaching visits within registrars' first two general practice training terms (GPT1 and GPT2) for registrars across New South Wales and the Australian Capital Territory. Factor analysis and expert consensus were used to refine items and establish GPR-CAG's internal structure. GPT1 and GPT2 competencies were analysed separately.Results: Data of 555 registrars undertaking GPT1 and 537 registrars undertaking GPT2 were included in analyses. A four-factor, 16-item solution was identified for GPT1 competencies (Cronbach's alpha range: 0.71-0.83) and a seven-factor 27-item solution for GPT2 competencies (Cronbach's alpha: 0.63-0.84). The emergent factor structures were clinically characterisable and resonant with existing medical education competency frameworks.Discussion: This study establishes initial evidence for the content validity and internal consistency of GPR-CAG. GPR-CAG appears to have utility as a formative GP training WBA instrument.


Prospective Clinical Trial of Corneal Reconstruction With Biomaterial-Free Cultured Oral Mucosal Epithelial Cell Sheets.
To investigate the efficacy and safety of transplantation with biomaterial-free cultured oral mucosal epithelial cell sheets (COMECs) for ocular reconstruction in subjects with total limbal stem cell deficiency. A prospective clinical trial (NCT02149732) was conducted in 8 subjects with total limbal stem cell deficiency after approval from the institutional review board of Seoul National University Hospital (H-0707-043-213) and the Ministry of Food and Drug Safety of Korea. COMECs were prepared in a culture system without the use of any temperature-sensitive polymers or carriers. The COMECs were transplanted without suture fixation. Four subjects underwent penetrating keratoplasty after stabilization of the COMEC transplant. Stable epithelialization, changes in visual acuity, and postoperative complications were evaluated for 6 months. Corneal cytokeratins (K) of 4 subjects who underwent penetrating keratoplasty were stained with an immunofluorescent agent. The ocular surface was successfully reconstructed in 6 eyes. Complete stable epithelialization was achieved within a mean of 53.6 days. Visual improvement (≥2 lines) was achieved in 62.5% of the eyes. K12 (corneal phenotype), K4, and K13 (mucosal phenotype) were well expressed in grafts after keratoplasty, whereas K1, K8, and K19 were barely expressed. No ocular infections, local tumor formation, or remarkable systemic complications were observed. Ocular reconstruction using COMECs failed in 2 eyes, which had full symblepharon in 4 quadrants. Transplanting biomaterial-free COMECs seems to be an efficient and safe procedure to reconstruct the ocular surface in patients who are completely limbal stem cell deficient without a full symblepharon.


Fatty acid profile and meat quality of young bulls fed ground soybean or ground cottonseed and vitamin E.
The objective of this study was to evaluate the fatty acid profile and qualitative characteristics of meat from feedlot young bulls fed ground soybean or ground cottonseed, with or without supplementation of vitamin E. A total of 40 Red Norte young bulls, with an initial average age of 20 months, and an initial average BW of 339±15 kg, were allotted in a completely randomized design using a 2×2 factorial arrangement, with two oilseeds, and daily supplementation or not of 2500 IU of vitamin E. The experimental period was for 84 days, which was preceded by an adaptation period of 28 days. The treatments were ground soybean (SB), ground soybean plus vitamin E (SBE), ground cottonseed (CS) and ground cottonseed plus vitamin E (CSE). The percentage of cottonseed and soybean in the diets (dry matter basis) was 24% and 20%, respectively. Diets were isonitrogenous (13% CP) and presented similar amount of ether extract (6.5%). The animals were slaughtered at average live weight of 464±15 kg, and samples were taken from the longissimus dorsi muscle for the measurement of fatty acid concentration and the evaluation of lipid oxidation and color of the beef. Before fatty acid extraction, muscle tissue and subcutaneous fat of the longissimus dorsi were separated to analyze fatty acid profile in both tissues. Supplementation of vitamin E did not affect fatty acid concentration, lipid oxidation and color (P>0.05). Subcutaneous fat from animals fed CS diet had greater C12:0, C16:0 and C18:0 contents (P<0.03). In addition, CS diets reduced the C18:1 and C18:2 cis-9, trans-11 contents in subcutaneous fat (P<0.05). The muscle from animals fed CS tended to higher C16:0 and C18:0 contents (P<0.11), and decreased C18:1, C18:2 cis-9, trans-11 and C18:3 contents (P<0.05) compared with SB. The Δ9-desaturase index was greater in muscle from animals fed SB (P<0.01). At 42 days of age, meat from cattle fed SB had a greater lipid oxidation rate (P<0.05). Meat from animals fed SB diets had less lightness and redness indices than meat from animals fed CS diets after 14 days of age. In conclusion, the addition of ground cottonseed in the finishing diets did increase the saturated fatty acid content of the longissimus dorsi. However, animals fed cottonseed exhibited greater lightness and redness of beef. In this study, the addition of vitamin E did not affect qualitative characteristics of meat.


Transport stress-induced cerebrum oxidative stress is not mitigated by activating the Nrf2 antioxidant defense response in newly hatched chicks.
Transportation of newly hatched chicks from the hatchery to the farm is inevitable, especially for parent stock and grandsire parent stock chicks. However, the possible effects of transport stress in the newly hatched chicks are poorly understood. The aim of this study was to determine the adaptive responses to transport stress by activing the nuclear factor-erythroid 2-related factor 2 (Nrf2)-induced antioxidant defense. One hundred twenty newly hatched chicks were divided into 3 groups (control group, transport group, and simulation transport group) for 2, 4, and 8 h of real or simulated transportation. Transport stress could cause oxidative stress in the cerebrum of newly hatched chicks by increasing lipid peroxidation and production of free radicals and decreasing the activities of antioxidant enzymes and the glutathione:oxidized glutathione ratio. Transport stress activated the Nrf2 signaling pathway and triggered the transcription of antioxidant parameters. However, transport stress-induced cerebrum oxidative stress was not mitigated by activating the Nrf2 antioxidant defense response in newly hatched chicks.


Combined interleukin 1/interleukin 2 therapy of mice injected with highly metastatic Friend leukemia cells: host antitumor mechanisms and marked effects on established metastases.
Peritumoral injection of recombinant human interleukin 1 beta (IL-1 beta) in mice transplanted subcutaneously with Friend erythroleukemia cells (FLC) resulted in a marked increase in survival time and inhibition of metastatic tumor growth in liver and spleen. In contract, IL-2 treatment alone did not significantly inhibit the development of FLC metastases. A synergistic antitumor effect was observed after combined IL-1/IL-2 therapy of these mice. The antitumor action of IL-1/IL-2 treatment was abolished or markedly reduced in mice treated with antibodies to CD4 or CD8 antigens, whereas antibodies to asialo-GM1 were ineffective. A clear-cut increase in the percentage of CD4+ cells was observed in the spleens of cytokine-treated mice on days 17 and 23. On day 23 of cytokine therapy, CD8+ cells were increased in both spleens and lymph nodes. On day 17, infiltrates of host-reactive cells (i.e., lymphocytes, granulocytes, and monocytes) were observed in both spleen and liver from FLC-injected mice treated with IL-1/IL-2, in association with tumor cells. On days 17 and 23, spleen cells and cells recovered from mesenteric lymph nodes of IL-1/IL-2-treated mice exerted a potent antitumor effect as determined by Winn assay experiments. This antitumor activity was abolished by preincubation of spleen cells with anti-CD8 antibody, but not by treatment with antibodies to asialo-GM1; antibodies to CD4 exerted only a slight effect. Combined IL-1/IL-2 therapy was more effective on established (i.e., 6-7-d) FLC tumors than on early (i.e., 1-d) tumor-transplanted mice. IL-1/IL-2 treatments were also highly effective in increasing survival time of mice from which the subcutaneous primary tumors were excised 7 d after FLC injection. These data indicate that in mice injected with FLC, the antitumor effects of IL-1/IL-2 are mediated by CD4+ and CD8+ cells (but not NK cells), and suggest that this combined cytokine treatment may be effective against established metastatic tumors.


The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents.
The resistance mechanisms to azole antifungal agents were investigated in this study with two pairs of Candida glabrata clinical isolates recovered from two separate AIDS patients. The two pairs each contained a fluconazole-susceptible isolate and a fluconazole-resistant isolate, the latter with cross-resistance to itraconazole and ketoconazole. Since the accumulation of fluconazole and of another unrelated substance, rhodamine 6G, was reduced in the azole-resistant isolates, enhanced drug efflux was considered as a possible resistance mechanism. The expression of multidrug efflux transporter genes was therefore examined in the azole-susceptible and azole-resistant yeast isolates. For this purpose, C. glabrata genes conferring resistance to azole antifungals were cloned in a Saccharomyces cerevisiae strain in which the ATP binding cassette (ABC) transporter gene PDR5 was deleted. Three different genes were recovered, and among them, only C. glabrata CDR1 (CgCDR1), a gene similar to the Candida albicans ABC transporter CDR genes, was upregulated by a factor of 5 to 8 in the azole-resistant isolates. A correlation between upregulation of this gene and azole resistance was thus established. The deletion of CgCDR1 in an azole-resistant C. glabrata clinical isolate rendered the resulting mutant (DSY1041) susceptible to azole derivatives as the azole-susceptible clinical parent, thus providing genetic evidence that a specific mechanism was involved in the azole resistance of a clinical isolate. When CgCDR1 obtained from an azole-susceptible isolate was reintroduced with the help of a centromeric vector in DSY1041, azole resistance was restored and thus suggested that a trans-acting mutation(s) could be made responsible for the increased expression of this ABC transporter gene in the azole-resistant strain. This study demonstrates for the first time the determinant role of an ABC transporter gene in the acquisition of resistance to azole antifungals by C. glabrata clinical isolates.


In response to protein load podocytes reorganize cytoskeleton and modulate endothelin-1 gene: implication for permselective dysfunction of chronic nephropathies.
Effacement of podocyte foot processes occurs in many proteinuric nephropathies and is accompanied by rearrangement of the actin cytoskeleton. Here, we studied whether protein overload affects intracellular pathways, leading to cytoskeletal architecture changes and ultimately to podocyte dysfunction. Mouse podocytes bound and endocytosed both albumin and IgG via receptor-specific mechanisms. Protein overload caused redistribution of F-actin fibers instrumental to up-regulation of the prepro-endothelin (ET)-1 gene and production of the corresponding peptide. Increased DNA-binding activity for nuclear factor (NF)-kappaB and Ap-1 nuclear proteins was measured in nuclear extracts of podocytes exposed to excess proteins. Both Y27632, which inhibits Rho kinase-dependent stress fiber formation, and jasplakinolide, an F-actin stabilizer, decreased NF-kappaB and Ap-1 activity and reduced ET-1 expression. This suggested a role for the cytoskeleton, through activated Rho, in the regulation of the ET-1 peptide. Focal adhesion kinase (FAK), an integrin-associated nonreceptor tyrosine kinase, was phosphorylated by albumin treatment via Rho kinase-triggered actin reorganization. FAK activation led to NF-kappaB- and Ap-1-dependent ET-1 expression. These data suggest that reorganization of the actin cytoskeletal network in response to protein load is implicated in modulation of the ET-1 gene via Rho kinase-dependent FAK activation of NF-kappaB and Ap-1 in differentiated podocytes. Increased ET-1 generation might alter glomerular permselectivity and amplify the noxious effect of protein overload on dysfunctional podocytes.


Monte Carlo Simulations Comparing Fisher Exact Test and Unequal Variances t Test for Analysis of Differences Between Groups in Brief Hospital Lengths of Stay.
We examined type I and II error rates for analysis of (1) mean hospital length of stay (LOS) versus (2) percentage of hospital LOS that are overnight. These 2 end points are suitable for when LOS is treated as a secondary economic end point. We repeatedly resampled LOS for 5052 discharges of thoracoscopic wedge resections and lung lobectomy at 26 hospitals. Unequal variances t test (Welch method) and Fisher exact test both were conservative (ie, type I error rate less than nominal level). The Wilcoxon rank sum test was included as a comparator; the type I error rates did not differ from the nominal level of 0.05 or 0.01. Fisher exact test was more powerful than the unequal variances t test at detecting differences among hospitals; estimated odds ratio for obtaining P < .05 with Fisher exact test versus unequal variances t test = 1.94, with 95% confidence interval, 1.31-3.01. Fisher exact test and Wilcoxon-Mann-Whitney had comparable statistical power in terms of differentiating LOS between hospitals. For studies with LOS to be used as a secondary end point of economic interest, there is currently considerable interest in the planned analysis being for the percentage of patients suitable for ambulatory surgery (ie, hospital LOS equals 0 or 1 midnight). Our results show that there need not be a loss of statistical power when groups are compared using this binary end point, as compared with either Welch method or Wilcoxon rank sum test.


Individual differences in working memory capacity predict learned control over attentional capture.
Although individual differences in working memory capacity (WMC) typically predict susceptibility to attentional capture in various paradigms (e.g., Stroop, antisaccade, flankers), it sometimes fails to correlate with the magnitude of attentional capture effects in visual search (e.g., Stokes, 2016), which is 1 of the most frequently studied tasks to study capture (Theeuwes, 2010). But some studies have shown that search modes can mitigate the effects of attentional capture (Leber & Egeth, 2006). Therefore, the present study examined whether or not the relationship between WMC and attentional capture changes as a function of the search modes available. In Experiment 1, WMC was unrelated to attentional capture, but only 1 search mode (singleton-detection) could be employed. In Experiment 2, greater WMC predicted smaller attentional capture effects, but only when multiple search modes (feature-search and singleton-detection) could be employed. Importantly this relationship was entirely independent of variation in attention control, which suggests that this effect is driven by WMC-related long-term memory differences (Cosman & Vecera, 2013a, 2013b). The present set of findings help to further our understanding of the nuanced ways in which memory and attention interact. (PsycINFO Database Record


Toner Savings Based on Quasi-Random Sequences and a Perceptual Study for Green Printing.
Toner savings in monochromatic printing are an important target for improving green computing performance and more specifically green printing. In order to extend the lifetime of the printer cartridge, some options are available for laser printers, usually reducing the number of dots with respect to the normal print quality. However available algorithms and patents do not provide a method for dynamically adapting the percentage of toner savings to the required printing quality. In this paper, we introduce a new quasi-random sequence-based algorithm for reducing the number of dots in the printing process, able to achieve optimal discrepancy and low computational complexity, for all print quality levels. In order to reduce patterns in the removed dots, blue noise dithering is applied when the desired percentage of toner savings is moderate. The proposed solution can be easily implemented in the printer firmware, given its low computational complexity. In order to verify the results from a perceptual point of view, an extended test with 135 volunteers and more than 5000 comparisons has been performed, besides checking that toner is effectively saved. Results show that the proposed approach can produce a reduction of the perceived quality almost directly proportional to the number of monochromatic dots skipped, with only a reduced influence from the font used. The perceptual results are better in the proposal than in the previous approaches. The proposed algorithm appears to be a promising technique for improving green printing in monochromatic laser printers without using custom fonts.


Novel Therapeutic Approaches Targeting the Renin-Angiotensin System and Associated Peptides in Hypertension and Heart Failure.
Despite the success of renin-angiotensin system (RAS) blockade by angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor (AT1R) blockers, current therapies for hypertension and related cardiovascular diseases are still inadequate. Identification of additional components of the RAS and associated vasoactive pathways, as well as new structural and functional insights into established targets, have led to novel therapeutic approaches with the potential to provide improved cardiovascular protection and better blood pressure control and/or reduced adverse side effects. The simultaneous modulation of several neurohumoral mediators in key interconnected blood pressure-regulating pathways has been an attractive approach to improve treatment efficacy, and several novel approaches involve combination therapy or dual-acting agents. In addition, increased understanding of the complexity of the RAS has led to novel approaches aimed at upregulating the ACE2/angiotensin-(1-7)/Mas axis to counter-regulate the harmful effects of the ACE/angiotensin II/angiotensin III/AT1R axis. These advances have opened new avenues for the development of novel drugs targeting the RAS to better treat hypertension and heart failure. Here we focus on new therapies in preclinical and early clinical stages of development, including novel small molecule inhibitors and receptor agonists/antagonists, less conventional strategies such as gene therapy to suppress angiotensinogen at the RNA level, recombinant ACE2 protein, and novel bispecific designer peptides.


Unveiling the secrets of snakes: Analysis of environmental, socioeconomic, and spatial factors associated with snakebite risk in Paraná, Southern Brazil.
The state of Paraná is home to three out of the five medically significant snake genera in Brazil and lacks of snakebite epidemiology studies. This study aimed to ascertain the spatial, environmental, and socioeconomic factors associated with snakebite risk by analyzing notification data of cases in the state of Paraná. Notification and socioeconomic data were gathered from the online platforms of the National System of Notifiable Diseases (SINAN) and the Brazilian Institute of Geography and Statistics (IBGE). Land cover and land use maps were obtained from the Mapbiomas platform in raster format and subsequently converted into vectors using QGis software. The proportions of land use and land cover in square kilometers (km2) were then calculated. All acquired data were tabulated using Microsoft Excel 365 software. For spatial analysis, GeoDa software version 1.20 was utilized to calculate the Global and Local Moran indices, assessing spatial correlations. Between 2007 and 2021, 12,877 notifications were recorded, with an average incidence of 8.22/100,000 inhabitants in the state, 8166 (63.41%) caused by Bothrops, 1534 (11.91%) caused by Crotalus, 56 (0.43%) caused by Micrurus. 1703 (13.22%) caused by non-venomous snake species, and the remaining cases did not have the identified causative species. The incidents caused by Bothrops and Crotalus showed different distribution patterns. Spatial analysis revealed that key factors contributing to snakebite risk included the presence of native forests, mangroves, apicuns, and monospecific planted forests. The population group at the highest risk comprised rural residents and workers. Furthermore, the absence of basic sanitation and proper garbage collection and disposal exhibited positive correlations with snakebites. Conversely, intensive farming practices with substantial mechanization and pastures demonstrated negative spatial correlations. This study has enabled the identification of the primary factors associated with snakebite risk, facilitating more targeted efforts to prevent snakebite accidents among vulnerable populations.


The perspective of Canadian health care professionals on abortion service during the COVID-19 pandemic.
The COVID-19 pandemic and pandemic response created novel challenges for abortion services. Canada was uniquely positioned to transition to telemedicine because internationally common restrictions on abortion medication were removed before the pandemic. We sought to characterize the experiences of abortion health care professionals in Canada during the COVID-19 pandemic and the impact of the pandemic response on abortion services. We conducted a sequential mixed methods study between July 2020 and January 2021. We invited physicians, nurse practitioners and administrators to participate in a cross-sectional survey containing an open-ended question about the impact of the pandemic response on abortion care. We employed an inductive codebook thematic analysis, which informed the development of a second, primarily quantitative survey. Our initial survey had 307 respondents and our second had 78. Fifty-three percent were family physicians. Our first survey found respondents considered abortion access essential. We identified three key topicss: access to abortion care was often maintained despite pandemic-related challenges (e.g. difficulty obtaining tests, additional costs); change of practice to low-touch medication abortion care and provider perceptions of patient experience, including shifting demand, telemedicine acceptability and increased rural access. The second survey indicated uptake of telemedicine medication abortion among 89% of participants except in Quebec, where regulations meant procedures were nearly exclusively surgical. Restrictions did not delay care according to 76% of participants. Canadian health care professionals report their facilities deemed abortion an essential service. Provinces and territories, except Quebec, described a robust pandemic transition to telemedicine to ensure access to services. An accompanying podcast is available in the Supplementary Data, in which the authors Dr Madeleine Ennis and Kate Wahl discuss their research on how family planning care and access to abortion services have changed during the COVID-19 pandemic.


Evaluation of a Collaborative Protocolized Approach by Community Pharmacists and General Medical Practitioners for an Australian Minor Ailments Scheme: Protocol for a Cluster Randomized Controlled Trial.
Internationally, governments have been investing in supporting pharmacists to take on an expanded role to support self-care for health system efficiency. There is consistent evidence that minor ailment schemes (MASs) promote efficiencies within the health care system. The cost savings and health outcomes demonstrated in the United Kingdom and Canada open up new opportunities for pharmacists to effect sustainable changes through MAS delivery in Australia. This trial aims to evaluate the clinical, economic, and humanistic impact of an Australian Minor Ailments Service (AMAS) compared with usual pharmacy care in a cluster randomized controlled trial (cRCT) in Western Sydney, Australia. The cRCT design has an intervention group and a control group, comparing individuals receiving a structured intervention (AMAS) with those receiving usual care for specific health ailments. Participants will be community pharmacies, general practices, and patients located in Western Sydney Primary Health Network (WSPHN) region. A total of 30 community pharmacies will be randomly assigned to either intervention or control group. Each will recruit 24 patients, aged 18 years or older, presenting to the pharmacy in person with a symptom-based or product-based request for one of the following ailments: reflux, cough, common cold, headache (tension or migraine), primary dysmenorrhea, or low back pain. Intervention pharmacists will deliver protocolized care to patients using clinical treatment pathways with agreed referral points and collaborative systems boosting clinician-pharmacist communication. Patients recruited in control pharmacies will receive usual care. The coprimary outcomes are rates of appropriate recommendation of nonprescription medicines and rates of appropriate medical referral. Secondary outcomes include self-reported symptom resolution, health services resource utilization, and EuroQoL Visual Analogue Scale. Differences in primary outcomes between groups will be analyzed at the individual patient level accounting for correlation within clusters with generalized estimating equations. The economic impact of the model will be evaluated by cost-utility and cost-effectiveness analysis compared with usual care. The study began in July 2018. Thirty community pharmacies were recruited. Pharmacists from the 15 intervention pharmacies were trained. A total of 27 general practices consented. Pharmacy patient recruitment began in August 2018 and was completed on March 31, 2019. This study may demonstrate the efficacy of a protocolized intervention to manage minor ailments in the community and will assess the clinical, economic, and humanistic impact of this intervention in Australian pharmacy practice. Pharmacists supporting patient self-care and appropriate self-medication may contribute to greater efficiency of health care resources and integration of self-care in the health system. The proposed model and developed educational content may form the basis of a national MAS service in Australia, using a robust framework for management and referral for common ailments. Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618000286246; http://www.anzctr.org.au/ACTRN12618000286246.aspx. DERR1-10.2196/13973.


Horseradish peroxidase-catalyzed oxidation of acetaminophen to intermediates that form polymers or conjugate with glutathione.
Horseradish peroxidase catalyzed the polymerization of acetaminophen. Addition of reduced glutathione (GSH) to reaction mixtures resulted in decreased polymerization and formation of minor amounts of GSH-acetaminophen conjugates. The conjugates were identified as 3-(glutathion-S-yl)acetaminophen and 3-(glutathion-S-yl)diacetaminophen. Horseradish peroxidase also catalyzed polymerization of synthetic 3-(glutathion-S-yl)acetaminophen to a dimer conjugate. In contrast to acetaminophen, 3-(glutathion-S-yl)acetaminophen oxidation was slowly catalyzed by horseradish peroxidase. However, in reaction mixtures containing equimolar concentrations of acetaminophen and synthetic 3-(glutathion-S-yl)acetaminophen, the formation of 3-(glutathion-S-yl)diacetaminophen and 3-(diglutathion-S-yl)diacetaminophen was rapid and accounted for approximately 95% of the products, whereas acetaminophen polymers accounted for only 5% of the products. These findings suggest that horseradish peroxidase catalyzed the one-electron oxidation of acetaminophen to N-acetyl-p-benzosemiquinone imine which preferentially polymerized rather than reacted with GSH. N-Acetyl-p-benzosemiquinone imine may also oxidize 3-(glutathion-S-yl)acetaminophen to form acetaminophen and 3-(glutathion-S-yl)-N-acetyl-p-benzosemiquinone imine. The data indicate that once this conjugate radical is formed it reacts with either N-acetyl-p-benzosemiquinone minine or 3-(glutathion-S-yl)-N-acetyl-p-benzosemiquinone imine via a radical termination mechanism.


Regulation of reactivated contraction in teleost retinal cone models by calcium and cyclic adenosine monophosphate.
We have been using lysed cell models of teleost retinal cones to examine the mechanism of contraction in nonmuscle cells. We have previously reported that dark-adapted retinas can be lysed with the detergent Brij-58 to obtain cone motile models that undergo Ca++- and adenosine triphosphate (ATP)-dependent reactivated contraction. In this report we further dissect the roles of ATP and Ca++ in activation of contraction and force production by (a) characterizing the Ca++ and nucleotide requirements in more detail, (b) by analyzing the effects of inosine triphosphate (ITP) and the ATP analog ATP gamma S and (c) by testing effects of cyclic adenosine monophosphate (cAMP) on reactivated cone contraction. Exposing lysed cone models to differing free Ca++ concentrations produced reactivated contraction at rates proportional to the free Ca++ concentration between 3.16 X 10(-8) and 10(-6) M. A role for calmodulin (CaM) in this Ca++ regulation was suggested by the inhibition of reactivated contraction by the calmodulin inhibitors trifluoperazine and calmidazolium ( R24571 ). The results of analysis of nucleotide requirements in lysed cone models were consistent with those of smooth muscle studies suggesting a role for myosin phosphorylation in Ca++ regulation of contraction. ATP gamma S and ITP are particularly interesting in that ATP gamma S, on the one hand, can be used by kinases to phosphorylate proteins (e.g., myosin light chains) but resists cleavage by phosphatases or adenosine triphosphatases (ATPases), e.g., myosin ATPase. ITP, on the other hand, can be used by myosin ATPase but does not support Ca++/calmodulin mediated phosphorylation of myosin light chains by myosin light chain kinase. Thus, these nucleotides provide an opportunity to distinguish between the kinase and myosin ATPase requirements for ATP. When individual nucleotides were tested with cone motile models, the nucleotide requirement was highly specific for ATP; not only ITP and ATP gamma S, but also guanosine triphosphate, cytosine triphosphate, adenylyl-imidodiphosphate (AMPPNP) failed to support reactivated contraction when substituted for ATP throughout the incubation. However, if lysed cones were initially incubated with ATP gamma S and then subsequently incubated with ITP, the cones contracted to an extent that was comparable to that observed with ATP. As observed in skinned smooth muscle, adding cAMP to contraction medium strongly inhibited contraction in lysed cone models.


The ductal origin of structural and functional heterogeneity between pancreatic islets.
Islets form in the pancreas after the first endocrine cells have arisen as either single cells or small cell clusters in the epithelial cords. These cords constitute the developing pancreas in one of its earliest recognizable stages. Islet formation begins at the time the cords transform into a branching ductal system, continues while the ductal system expands, and finally stops before the exocrine tissue of ducts and acini reaches its final expansion. Thus, islets continuously arise from founder cells located in the branching and ramifying ducts. Islets arising from proximal duct cells locate between the exocrine lobules, develop strong autonomic and sensory innervations, and pass their blood to efferent veins (insulo-venous efferent system). Islets arising from cells of more distal ducts locate within the exocrine lobules, respond to nerve impulses ending at neighbouring blood vessels, and pass their blood to the surrounding acini (insulo-acinar portal system). Consequently, the section of the ductal system from which an islet arises determines to a large extent its future neighbouring tissue, architecture, properties, and functions. We note that islets interlobular in position are frequently found in rodents (rats and mice), whereas intralobularly-located, peripheral duct islets prevail in humans and cattle. Also, we expound on bovine foetal Laguesse islets as a prominent foetal type of type 1 interlobular neuro-insular complexes, similar to neuro-insular associations frequently found in rodents. Finally, we consider the probable physiological and pathophysiological implications of the different islet positions within and between species.


FFT-based analysis of periodic structures in microacoustic devices.
Periodic structures utilized as transducer or reflector elements play an important role in microacoustic wave devices. Such structures can be described using approximate analytical models. However, to obtain the accuracy required for reliable device simulation, numerical methods have to be employed. In this contribution, we present an efficient numerical approach to calculate the dispersion curves associated with microacoustic modes propagating in periodic structures; the method is demonstrated for the case of Love wave modes. The computational efficiency is related to the utilization of the FFT algorithm in a hybrid Method of Moments (MoM)/Mode-Matching analysis. From the obtained dispersion curves, characteristic parameters such as the stopband width can be obtained which can be used in a coupling-of-modes (COM) model of the structure.


Temporal trends in in vitro antimicrobial susceptibility patterns of bacteria isolated from foals with sepsis: 1979-2010.
Monitoring the development of antimicrobial resistance is important for the rational selection of appropriate antimicrobial drugs to initiate treatment of foals with sepsis. To identify temporal trends in antimicrobial susceptibility patterns of bacteria isolated from foals with sepsis. Retrospective review of medical records. Foals aged <30 days with a diagnosis of sepsis, confirmed by culture of bacteria, were included. Susceptibility data, expressed as minimum inhibitory concentrations (MICs) (MIC50 , MIC90 , MIC range) and percent of isolates that were susceptible to a particular antimicrobial drug, were compared for bacteria isolated from foals during 3 different time periods: 1979-1990, 1991-1997 and 1998-2010. The Cochran-Armitage trend test and the Jonckheere-Terpstra test were used for statistical analysis. A total of 1091 bacterial isolates were cultured from 588 foals. Enterobacteriaceae, Actinobacillus spp. and β-haemolytic Streptococcus spp. showed a decrease in percent of isolates susceptible to gentamicin over time. Enterobacteriaceae, Actinobacillus spp. and β-haemolytic Streptococcus spp. showed an increase in MIC values for amikacin. Enterobacteriaceae showed a decrease in percent of isolates susceptible to ceftiofur. Enterococcus spp. and Pseudomonas spp. showed increased MIC values to ceftiofur. Enterobacteriaceae showed increased MIC values to ceftizoxime. Enterococcus spp. became more resistant to imipenem and showed increased MIC values to ticarcillin/clavulanic acid. In contrast, several trends in increased susceptibility were also seen. Based on these in vitro results, the combination of amikacin and ampicillin remains an appropriate choice for initiating treatment of sepsis in foals while awaiting culture and susceptibility test results, although increasing development of resistance to amikacin was demonstrated. The decrease in in vitro activity of ceftiofur against Enterobacteriaceae is of concern. Similarly, the development of resistance of Enterococcus spp. to imipenem is an important finding that warrants monitoring in the future. Judicious use of antimicrobials is therefore crucial.


Hepatic cancer stem cells and drug resistance: Relevance in targeted therapies for hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have indicated an association between drug resistance and the existence of the cancer stem cells (CSCs) as tumor initiating cells. The CSCs are resistant to conventional chemotherapies and might be related to the mechanisms of the ATP Binding Cassette (ABC) transporters and alterations in the CSCs signaling pathways. Therefore, to contribute to the development of new HCC treatments, further information on the characterization of CSCs, the modulation of the ABC transporters expression and function and the signaling pathway involved in the self renewal, initiation and maintenance of the cancer are required. The combination of transporters modulators/inhibitors with molecular targeted therapies may be a potent strategy to block the tumoral progression. This review summarizes the association of CSCs, drug resistance, ABC transporters activities and changes in signaling pathways as a guide for future molecular therapy for HCC.


Ecological drivers of shark distributions along a tropical coastline.
As coastal species experience increasing anthropogenic pressures there is a growing need to characterise the ecological drivers of their abundance and habitat use, and understand how they may respond to changes in their environment. Accordingly, fishery-independent surveys were undertaken to investigate shark abundance along approximately 400 km of the tropical east coast of Australia. Generalised linear models were used to identify ecological drivers of the abundance of immature blacktip Carcharhinus tilstoni/Carcharhinus limbatus, pigeye Carcharhinus amboinensis, and scalloped hammerhead Sphyrna lewini sharks. Results indicated general and species-specific patterns in abundance that were characterised by a range of abiotic and biotic variables. Relationships with turbidity and salinity were similar across multiple species, highlighting the importance of these variables in the functioning of communal shark nurseries. In particular, turbid environments were especially important for all species at typical oceanic salinities. Mangrove proximity, depth, and water temperature were also important; however, their influence varied between species. Ecological drivers may promote spatial diversity in habitat use along environmentally heterogeneous coastlines and may therefore have important implications for population resilience.


Clustering of Neuropsychiatric Disease in First-Degree and Second-Degree Relatives of Patients With Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative condition primarily involving the motor system. There is increasing epidemiologic evidence of an association between ALS and a wider spectrum of neurodegenerative and neuropsychiatric disorders among family members, including schizophrenia and psychotic illness and suicidal behavior. To examine the frequency and range of neuropsychiatric conditions that occur within individual first-degree and second-degree relatives of patients with ALS. In this population-based, case-control family aggregation study, all 202 patients included in the Irish ALS Register between January 1, 2012, and January 31, 2014, with definite, probable, or possible ALS as defined by El Escorial criteria were invited to participate. A total of 75 patients were unable or refused to participate and were excluded; the remaining 127 patients with incident ALS were genotyped for the C9orf72 repeat expansion and 132 age- and sex-matched controls were included in the study. The prevalence of defined neuropsychiatric disease in first-degree and second-degree relatives of patients with ALS and matched controls was determined. Mean (SD) age at diagnosis of the 127 patients in the study (58 women and 69 men) was 64.2 (10.7) years. Data from 2116 relatives of patients with ALS were reported, including 924 first-degree relatives, 1128 second-degree relatives, and 64 third-degree relatives. Data from controls were reported from 829 first-degree and 1310 second-degree relatives. A total of 77 patients with ALS (61.4%) and 51 control participants (38.6%) reported at least 1 first-degree or second-degree relative with a history of schizophrenia, psychosis, suicide, depression, alcoholism, or autism (relative risk [RR], 1.50; 95% CI, 1.08-2.17; P = .02). Cluster analysis suggested the following 2 subgroups based on the number of family members with a neuropsychiatric condition: expected (0-2) and high (≥3). Within the high subgroup, ALS kindreds presented a significantly higher rate of psychiatric illness than did controls (28 of 39 [71.8%]; mean [SD] number of siblings, 4.29 [1.41]; P = .001). A strong family history of schizophrenia (RR, 3.40; 95% CI, 1.27-9.30; P = .02), suicide (RR, 3.30; 95% CI, 1.07-10.05; P = .04), autism (RR, 10.10; 95% CI, 1.30-78.80; P = .03), and alcoholism (RR, 1.48; 95% CI, 1.01-2.17; P = .045) was reported in ALS kindreds. A total of 5 of 29 probands (17.2%) with a strong family history of neuropsychiatric conditions (≥3 first-degree or second-degree relatives) carried the C9orf72 repeat expansion. Neuropsychiatric symptoms in addition to schizophrenia, including obsessive-compulsive disorder, autism, and alcoholism, occur more frequently in ALS kindreds than in controls. The presence of the C9orf72 repeat expansion does not fully account for this finding, suggesting the presence of additional pleiotropic genes associated with both ALS and neuropsychiatric disease in the Irish population.


Isolating quantum coherences in structural imaging using intermolecular double-quantum coherence MRI.
Intermolecular multiple-quantum coherence (iMQC) MR imaging provides a fundamentally different contrast mechanism. It allows probing tissue microstructure by tuning the direction and strength of the correlation gradient. However, iMQC images of a specific quantum-coherence can easily be contaminated by leakage signals from undesired quantum coherences (zero, single, and triple quantum coherence in this work). Using a modified double-quantum CRAZED imaging sequence, we show that signals originating from various coherence orders (M=0, 1, 2, 3) can be predicted in k-space and effectively isolated by means of a four-step phase cycling scheme and judicious choice of flip angles. Finally, preliminary data suggest the method to be able to provide information on trabecular bone architecture such as regional mean trabecular plate separation.


Prospective versus retrospective ECG gating for 64-detector CT of the coronary arteries: comparison of image quality and patient radiation dose.
To compare image quality and patient radiation dose in a group of patients who underwent 64-detector computed tomography (CT) coronary angiography performed with prospective electrocardiographic (ECG) gating with image quality and radiation dose in a group of patients matched for clinical features who underwent 64-detector CT coronary angiography performed with retrospective ECG gating. Institutional review board approval was obtained for this HIPAA-compliant study, and the informed consent requirement was waived due to the retrospective study design. Two independent reviewers separately scored coronary artery segment image quality and overall image quality for 100 cardiac CT studies (50 in each group). Interobserver variability was calculated. Patient radiation dose for the actual examination z-axis length was recorded, and a normalized dose was calculated for a 12-cm z-axis length of a typical heart. The two groups matched well for clinical characteristics and CT parameters. There was good agreement for coronary artery segment image quality scores between the independent reviewers (kappa = 0.72). Of the 1253 coronary artery segments scored, the number of coronary artery segments that could not be evaluated in each group was similar (1.1% [seven of 614] in the prospective group vs 1.5% [10 of 647] in the retrospective group, P = .53). Image quality scores were not significantly different when matched for chest cross-sectional area (P > .05). Mean patient radiation dose was 77% lower for prospective gating (4.2 mSv) than for retrospective gating (18.1 mSv) (P < .01). Use of 64-detector CT coronary angiography performed with prospective ECG gating has similar subjective image quality scores but 77% lower patient radiation dose when compared with use of retrospective ECG gating.


Maternal Cardiac Diastolic Dysfunction by Doppler Echocardiography in Women with Preeclampsia.
Preeclampsia may lead to heart failure in late pregnancy and early puerperium. Diastolic dysfunction may be the cause of heart failure in these patients. There is paucity of data on diastolic dysfunction in patients with preeclampsia. To assess cardiac diastolic dysfunction in women with preeclampsia by Doppler echocardiography and to correlate severity of dysfunction with severity of preeclampsia. One hundred and fifty nulliparous women in age group of 20-35 years were recruited for the study. Among these, 120 women with preeclampsia were taken as cases and 30 normotensive women as controls. Doppler echocardiography was carried out between 28-36 weeks of gestation in both groups to assess and grade severity of diastolic dysfunction. Of 120 women with preeclampsia, 61 had mild preeclampsia and 59 had severe preeclampsia. Diastolic dysfunction was seen in 25(20.8%) cases. Among these, grade I diastolic dysfunction was seen in 40% and the rest 60% had grade II diastolic dysfunction. In the mild preeclampsia group, only 2(3.3%) patients had diastolic dysfunction. Both had grade I dysfunction. Of severe preeclampsia patients, 8(13.6%) had grade I and 15(25.4%) had grade II diastolic dysfunction (p=0.001). None of these progressed to heart failure or pulmonary oedema. Systolic function assessed by left ventricular ejection fraction was normal in all cases. All controls had normal systolic and diastolic functions. Cardiac diastolic dysfunction occurred in one-fifth of women with preeclampsia. Grade of diastolic dysfunction correlated with the severity of preeclampsia.


Identification of proteins that interact with a protein of interest: applications of the yeast two-hybrid system.
The yeast two-hybrid system is a molecular genetic test for protein interaction. Here we describe a step by step procedure to screen for proteins that interact with a protein of interest using the two-hybrid system. This process includes, construction and testing of the bait plasmid, screening a plasmid library for interacting fusion proteins, elimination of false positives and deletion analysis of true positives. This procedure is designed to allow investigators to identify proteins and their encoding cDNAs that have a biologically significant interaction with your protein of interest.


High abundance of novel environmental chlamydiae in a Tyrrhenian coastal lake (Lago di Paola, Italy).
For a long time the bacterial phylum of Chlamydiae exclusively consisted of one family of obligate intracellular bacteria, the Chlamydiaceae, which encompassed causative agents of severe diseases. In the 1990s, environmental chlamydiae were discovered as symbionts of free-living amoebae and other eukaryotic hosts. During a sampling campaign in September 2008, while monitoring Planctomycetes, we retrieved 20 almost full-length 16S rRNA gene sequences affiliated with Chlamydiales from a lake at the Tyrrhenian coast of central Italy (Lago di Paola, Latium). Two main clusters were identified. The nine sequences within the tight cluster I shared ∼98% identity, just like the six sequences of cluster II. The 16S rRNA sequence identity between the two novel groups was with 88% higher than with all known families of the order Chlamydiales. Four types of less frequent chlamydial 16S rRNA sequences were also detected. Two oligonucleotide probes were designed, and optimized. Chl282 targets the cluster I and almost all other Chlamydiales, while Chl282bis targets the cluster II and few other sequences. By catalysed reporter deposition fluorescence in situ hybridization (CARD-FISH), we identified in the Lago di Paola picoplankton abundant tiny cells with dot-shaped morphology and, interestingly, rarely also protists with intracellular pleomorphic chlamydiae. Abundances of the novel chlamydial clusters were up to 5 × 10(4) cells per millilitre. The two clusters were also detected in similar numbers during a second sampling in October 2010. This confirmed the relevance of the two newly described clusters of chlamydiae in Lago di Paola, not only enlarging the knowledge on the biodiversity of environmental chlamydiae in aquatic habitats, but also raising sanitary issues that should be addressed in the future.


[Involvement of the lungs in neurofibromatosis].
Two patients, a 66-year-old man (case 1) and a 55-year-old woman (case 2), had been known (for 40 and 35 years, respectively) to have type 1 neurofibromatosis. Dyspnoea, recently even at rest, had developed in both over the past few years. Both were emaciated (weight 62 kg, height 180 cm; 42 kg, 166 cm, respectively). In both the chest radiography had net-like increased interstitial markings. Computed tomography in case 1 showed largely subpleural small-blister-like changes bilaterally (honeycomb lung), while there were large apical cysts bilaterally in case 2. Lung function tests demonstrated restrictive changes in case 1 (vital capacity 48% of norm, relative one-second capacity 88%) and severe ventilation abnormality in case 2 (vital capacity 42% of norm, relative one-second capacity 47%). Both had marked hypoxaemia even at rest and the walking limit was 200 m in case 1, 40 m in case 2. The pulmonary changes were most likely manifestations of the neurofibromatosis. Symptomatic treatment consisted of long-term oxygen therapy with a portable liquid oxygen system (flow rate: 1-2 l/min at rest and 3-5 l/min on exercise; duration: 24 h/d). This achieved a walking distance without hypoxaemia of 500 and 200 m, respectively, with marked improvement in the patients' condition.


Mechanistic insights into electrocatalytic CO2 reduction within [Ru(II)(tpy)(NN)X]n+ architectures.
A series of Ru(II)-polypyridyl complexes of the design [Ru(II)(tpy)(NN)X](n+) (tpy = 2,2':6',2''-terpyridine; NN = bidentate polypyridine; X = Cl(-) or CH3CN; n = 1 or 2) have been synthesized and analyzed for their ability to function as electrocatalysts in the reduction of CO2 to CO. Varying the electron-donating/withdrawing character of the NN polypyridyl ligand has allowed for modification of electron density at the formally Ru(II) metal center. Complexes where X = Cl(-) display ligand substitution for CH3CN with differing rates of Cl(-) dissociation (k-Cl), therefore providing a degree of insight into the electron density and thus the chemical activity at the Ru(II) center. Detailed analysis of the cyclic voltammograms under argon vs. CO2 atmospheres using multiple switching potentials and scan rates ranging from ν = 25-2000 mV s(-1) has painted a picture of how monodentate ligand lability due to NN polypyridyl electron-donating character is related to electrocatalytic CO2 reduction activity of Ru(II)-polypyridyl complexes. From these studies, multiple mechanistic pathways towards generating the catalytically active [Ru(tpy(-))(NN(-))CO2](0) species are proposed and differ via the order of electrochemical and chemical processes.


The Effect of Moderate Intensity Aerobic Exercise on Affect and Exercise Intention in Active and Inactive College Students.
Physical activity has long been established as an essential behavior for vital physical and psychosocial health outcomes (16, 18), but lack of physical activity is still a rampant problem worldwide (7). Numerous factors influence physical activity participation, including affect, a measure of well-being. Research has found that affect increases following an exercise session, though some recent studies have discovered that affect tends to be lower when measured during exercise (14). Therefore, the purpose of this study was to explore the differences in affect between active and inactive college students during exercise. A total of 72 participants cycled for 30 minutes at 65-75% of their age-predicted maximal heart rate and completed the previously validated positive and negative affect scale (PANAS; 24) near the end of the exercise bout. Following the exercise session, participants completed measures to assess future exercise intention. No significant difference was found in affect between active and inactive individuals, suggesting that affect during exercise may not be a deterrent to physical activity as previously thought. However, a significant gender difference was present in positive affect. Namely, males reported experiencing higher levels of positive affect than females during the exercise bout, which may indicate that the males enjoyed the exercise more than females. Given these gender discrepancies, practitioners may need to consider using different training techniques or interventions for males and females.