Invariance properties of bacterial random walks in complex structures.
Motile cells often explore natural environments characterized by a high degree of structural complexity. Moreover cell motility is also intrinsically noisy due to spontaneous random reorientations and speed fluctuations. This interplay of internal and external noise sources gives rise to a complex dynamical behavior that can be strongly sensitive to details and hard to model quantitatively. In striking contrast to this general picture we show that the mean residence time of swimming bacteria inside artificial complex microstructures is quantitatively predicted by a generic invariance property of random walks. We find that while external shape and internal disorder have dramatic effects on the distributions of path lengths and residence times, the corresponding mean values are constrained by the sole free surface to perimeter ratio. As a counterintuitive consequence, bacteria escape faster from structures with higher density of obstacles due to the lower accessible surface.


ErbB3 ablation impairs PI3K/Akt-dependent mammary tumorigenesis.
The ErbB receptor family member ErbB3 has been implicated in breast cancer growth, but it has yet to be determined whether its disruption is therapeutically valuable. In a mouse model of mammary carcinoma driven by the polyomavirus middle T (PyVmT) oncogene, the ErbB2 tyrosine kinase inhibitor lapatinib reduced the activation of ErbB3 and Akt as well as tumor cell growth. In this phosphatidylinositol-3 kinase (PI3K)-dependent tumor model, ErbB2 is part of a complex containing PyVmT, p85 (PI3K), and ErbB3, that is disrupted by treatment with lapatinib. Thus, full engagement of PI3K/Akt by ErbB2 in this oncogene-induced mouse tumor model may involve its ability to dimerize with and phosphorylate ErbB3, which itself directly binds PI3K. In this article, we report that ErbB3 is critical for PI3K/Akt-driven tumor formation triggered by the PyVmT oncogene. Tissue-specific, Cre-mediated deletion of ErbB3 reduced Akt phosphorylation, primary tumor growth, and pulmonary metastasis. Furthermore, EZN-3920, a chemically stabilized antisense oligonucleotide that targets the ErbB3 mRNA in vivo, produced similar effects while causing no toxicity in the mouse model. Our findings offer further preclinical evidence that ErbB3 ablation may be therapeutically effective in tumors where ErbB3 engages PI3K/Akt signaling.


Sleep in the Acute Phase of Severe Traumatic Brain Injury: A Snapshot of Polysomnography.
Background and Objectives The onset of pervasive sleep-wake disturbances associated with traumatic brain injury (TBI) is poorly understood. This study aimed to (a) determine the feasibility of using polysomnography in patients in the acute, hospitalized stage of severe TBI and (b) explore sleep quality and sleep architecture during this stage of recovery, compared to patients with other traumatic injuries. Methods A cross-sectional case-control design was used. We examined the sleep of 7 patients with severe TBI (17-47 years; 20.3 ± 15.0 days postinjury) and 6 patients with orthopedic and/or spinal cord injuries (OSCI; 19-58 years; 16.9 ± 4.9 days postinjury). One night of ambulatory polysomnography was performed at bedside. Results Compared to OSCI patients, TBI patients showed a significantly longer duration of nocturnal sleep and earlier nighttime sleep onset. Sleep efficiency was low and comparable in both groups. All sleep stages were observed in both groups with normal proportions according to age. Conclusion Patients in the acute stage of severe TBI exhibit increased sleep duration and earlier sleep onset, suggesting that the injured brain enhances sleep need and/or decreases the ability to maintain wakefulness. As poor sleep efficiency could compromise brain recovery, further studies should investigate whether strategies known to optimize sleep in healthy individuals are efficacious in acute TBI. While there are several inherent challenges, polysomnography is a useful means of examining sleep in the early stage of recovery in patients with severe TBI.


An analysis of induction and adjuvant chemotherapy in the multidisciplinary treatment of squamous-cell carcinoma of the head and neck.
This study examines the role of combination chemotherapy with surgery and/or radiotherapy in the initial treatment of patients with advanced stage III and IV squamous-cell carcinoma of the head and neck (SCCHN). Two courses of initial (induction) cisplatin, bleomycin, and methotrexate with oral calcium leucovorin (PBM) were used with the principal intent of increasing the effectiveness of subsequent surgery and/or radiotherapy. Following induction chemotherapy and local treatment, disease-free patients who had responded to initial chemotherapy were entered into a randomized trial of adjuvant PBM. The response rates to induction PBM chemotherapy were a complete response (CR) rate of 26% and a partial response (PR) rate of 52%, for an overall response rate of 78%. A response to induction PBM was highly correlated with failure-free survival (P less than .0001). A Cox multistep regression analysis of potential prognostic factors was performed. After adjusting for the significant prognostic factors of performance status, initial tumor size, and primary tumor site, a response to induction chemotherapy remained independently associated with improved survival (P = .0002). The randomized trial of adjuvant chemotherapy demonstrated that such treatment significantly improved failure-free survival by decreasing local-regional failures. The benefit of adjuvant chemotherapy was particularly evident in patients who had a PR to induction chemotherapy (P = .01). The toxicity of this multidisciplinary approach was predictable and acceptable. Surgery and radiotherapy were not compromised by induction or adjuvant chemotherapy. Definitive evidence that chemotherapy can favorably influence survival awaits confirmation of these results by a randomized trial using a control arm of patients treated with conventional surgery and/or radiotherapy alone.


Surgery in India.
Surgical practice in India is mostly managed by the central and state governments and is totally government financed, offering free medical aid. However, with the economic growth and affluence of the middle-class population in urban areas, more and more hospitals, nursing homes, and clinics managed by the private sector are arising in cities and towns. Privately owned hospitals are built and managed by large industrial houses and trusts. It is essential, according to government directives, for these hospitals to have certain numbers of general beds that will provide for the economically weaker sections of the population. Medical insurance is popular amongst the urban population; in addition to well-established insurance companies, many new medical service reimbursement organizations are forming. Surgical care standards are uniformly high in the larger teaching institutions and hospitals run by the private sector in major cities in India, in which superspecialty surgical care that meets worldwide standards is available in addition to general surgical care. These hospitals are manned by surgeons holding master's degrees in general surgery, superspecialties, and subspecialties. In the hospitals and dispensaries in rural areas, only basic surgical facilities are available; for major surgical procedures, the patients are referred to the closest urban hospitals. Therefore, the government of India is placing more and more emphasis on building hospitals that offer better surgical facilities away from the cities and towns. A diploma course in surgery is run by the National Board of Surgery, and these diplomates are encouraged to practice more in rural areas and small hospitals. Economic constraints and the population explosion are the biggest hurdles to progress in surgical care, teaching, and research activities. With the advancement in education and growth of the economy, more and more multinationals are walking into the field of medical care, which is proving to be a great boon and providing a rapid increase in the health care expansion in this country. The World Health Organization and the World Bank are providing considerable aid for disease prevention, health care provision, and research activities.


Progression from frontal-parietal to mesial-temporal epilepsy after fluid percussion injury in the rat.
We recently described an in vivo model of post-traumatic epilepsy (PTE) in the rat where chronic spontaneous recurrent seizures appear following a single episode of fluid percussion injury (FPI). PTE, studied during the first 2 months post-injury, was focal and seizures originated predominantly from the frontal-parietal neocortex at or around the injury site. However, rarer bilateral seizures originating from a different and undefined focus were also observed. To shed light on the Posttraumatic Epileptogenic mechanisms and on the generation of bilateral seizures, we studied rats up to 7 months post-injury. In vivo paired epidural and depth-electrode recordings indicated that the anterior hippocampus evolves into an epileptic focus which initiates bilateral seizures. The rate of frontal-parietal seizures remained constant over time after 2 weeks post-injury, while the rate of hippocampal seizures greatly increased over time, suggesting that different mechanisms mediate neocortical and hippocampal post-traumatic epileptogenesis. Because of different temporal evolution of these foci, the epileptic syndrome was characterized by predominant frontal-parietal seizures early after injury, but by predominant mesio-temporal seizures at later time points. Pathological analysis demonstrated progressive hippocampal and temporal cortex pathology that paralleled the increase in frequency and duration of bilateral seizures. These results demonstrate that FPI-induced frontal-parietal epilepsy (FPE) progresses to mesial-temporal lobe epilepsy (MTLE) with dual pathology. These observations establish numerous similarities between FPI-induced and human PTE and further validate it as a clinically relevant model of PTE.


Fetal Alcohol Spectrum Disorders in a Southeastern County of the United States: Child Characteristics and Maternal Risk Traits.
To detail the characteristic traits of children with fetal alcohol spectrum disorders (FASDs) and maternal risk factors in a southeastern U.S. County. Independent samples were drawn from 2 different cohorts of first-grade students. All consented children (49.8%) were measured for height, weight, and head circumference, and those ≤ 25th centile entered the study along with a random sample drawn from all enrolled students. Study children were examined for physical growth, dysmorphology, and neurobehavior, and their mothers were interviewed. Total dysmorphology scores discriminated well the physical traits of children across the FASD continuum: fetal alcohol syndrome (FAS) = 15.8, partial FAS (PFAS) = 10.8, alcohol-related neurobehavioral disorder (ARND) = 5.2, and typically developing controls = 4.4. Additionally, a neurobehavioral battery distinguished children with each FASD diagnosis from controls. Behavioral problems qualified more children for FASD diagnoses than cognitive traits. Significant proximal maternal risk variables were as follows: reports of prepregnancy drinking, drinking in any trimester, and comorbid use of other drugs in lifetime and during pregnancy, especially alcohol and marijuana (14.9% among mothers of children with FASD vs. 0.4% for controls). Distal maternal risks included reports of other health problems (e.g., depression), living unmarried with a partner during pregnancy, and a lower level of spirituality. Controlling for other drug use during pregnancy, having a child diagnosed with a FASD was 17.5 times greater for women who reported usual consumption of 3 drinks per drinking day prior to pregnancy than for nondrinking mothers (p < 0.001, 95% CI = 5.1 to 59.9). There was no significant difference in the prevalence of FASD by race, Hispanic ethnicity, or socioeconomic status. The prevalence of FASD was not lower than 17.3 per 1,000, and weighted estimated prevalence was 49.0 per 1,000 or 4.9%. This site had the second lowest rate in the CoFASP study, yet children with FASD are prevalent.


TITE-gBOIN-ET: Time-to-event generalized Bayesian optimal interval design to accelerate dose-finding accounting for ordinal graded efficacy and toxicity outcomes.
One of the primary objectives of an oncology dose-finding trial for novel therapies, such as molecular-targeted agents and immune-oncology therapies, is to identify an optimal dose (OD) that is tolerable and therapeutically beneficial for subjects in subsequent clinical trials. These new therapeutic agents appear more likely to induce multiple low or moderate-grade toxicities than dose-limiting toxicities. Besides, for efficacy, evaluating the overall response and long-term stable disease in solid tumors and considering the difference between complete remission and partial remission in lymphoma are preferable. It is also essential to accelerate early-stage trials to shorten the entire period of drug development. However, it is often challenging to make real-time adaptive decisions due to late-onset outcomes, fast accrual rates, and differences in outcome evaluation periods for efficacy and toxicity. To solve the issues, we propose a time-to-event generalized Bayesian optimal interval design to accelerate dose finding, accounting for efficacy and toxicity grades. The new design named "TITE-gBOIN-ET" design is model-assisted and straightforward to implement in actual oncology dose-finding trials. Simulation studies show that the TITE-gBOIN-ET design significantly shortens the trial duration compared with the designs without sequential enrollment while having comparable or higher performance in the percentage of correct OD selection and the average number of patients allocated to the ODs across various realistic settings.


Brown Tumour As An Unusual But Preventable Cause Of Spinal Cord Compression: Case Report And Literature Review.
Brown tumour is an infrequent, focal, and benign osteolytic lesion which is a consequence of abnormal bone metabolism in hyperparathyroidism (both primary and secondary). It is also known as Osteoclastoma. In the present era, we rarely encounter skeletal disease caused by primary hyperparathyroidism. Although it is a rare presentation because of advancement of treatment but still can be encountered because of lack of standard care so we should have high index of suspicion to avoid this preventable complication. We report here a case of brown tumour in the thoracic vertebra of a young female patient with End Stage Renal Disease, who presented with backache and bilateral lower limb weakness. MRI of the spine showed multiple non 20 enhancing abnormal signals involving vertebral body of C2, posterior elements of C6, and bilateral sacral vertebra, suggestive of healed fractures versus bone forming tumours. She underwent laminectomy. Her histopathology report was consistent with brown tumour of hyperparathyroidism.


Discriminative Dissolution Method Development Through an aQbD Approach.
Using a one-factor-at-a-time approach for dissolution method and discrimination analysis can be time-consuming and may not yield the optimal and discriminative method. To address this, we have developed a two-stage workflow for the dissolution method development followed by demonstration of discrimination power through an analytical Quality by Design (aQbD) approach. In the first stage, an optimal dissolution method was achieved by determining the method operable design region (MODR) through a design of experiment study of the high-risk method-related parameters. In the second stage, we established a Formulation-Discrimination Correlation Diagram strategy to examine the method discrimination capability, through which one can determine the method discriminative design region (MDDR) and visualize the impact of each formulation parameter and their interactions on dissolution. The application of aQbD principles into a workflow provides a scientific-driven guidance for robust method development and demonstrating discrimination power for dissolution methods.


Depression as a Risk Factor for Physical Illness and Multimorbidity in a Cohort with No Prior Comorbidity.
This study examines whether depression is associated with the development of physical illness and multimorbidity, after controlling for socioeconomic, behavioral, and other potential confounders. This is a retrospective cohort study in which adult respondents to three nationally representative population health surveys were linked to health administrative databases in Ontario, Canada, and followed for 10 years from survey index. Respondents with any of the study outcome conditions at baseline were excluded to create a final cohort of 29,838 participants. The main exposure of interest was depression, measured using the Composite International Diagnostic Interview-Short Form for Major Depression. We controlled for age, body mass index, marital status, immigrant status, annual household income, smoking, alcohol consumption, physical activity, health status, and having a regular doctor. The outcome measure was the development of physical illness over 10 years of follow-up, defined as 1 of 15 common chronic conditions using administrative data. Among the 29,838 participants (15,259 [51%] female), 8% of females and 4% of males had depression at baseline. In this cohort with no comorbidities at baseline, even in the fully adjusted model, depression increased the risk of developing a first physical illness for females (hazard ratio [HR] 1.16; 95% CI, 1.07 to 1.26) and males (HR 1.20; 95% CI, 1.07 to 1.36) and increased the risk of developing a second physical illness for females (HR 1.16; 95% CI, 1.02 to 1.33) over 10 years of follow-up. For individuals with no prior comorbidities, depression is associated with a greater risk of developing subsequent physical illness and multimorbidity over time. Thus, depression identifies a population of people who may benefit from early identification, additional screening, and intervention. Further study needs to be done to determine whether interventions to manage and support people with depression can prevent or delay the increased risk of multimorbidity.


Managing and treating risk and uncertainty for health: a case study of diabetes among First Nation's people in Ontario, Canada.
'Risk' has become a key concept for understanding health care policies that are focused on prevention. Intervention no longer depends on the presence of an illness but rather an individual's risk of developing an illness. Through 'risk factors' individuals are subject to medical examination and surveillance to determine the real presence of danger, based on this abstract notion of risk. This paper explores 'risk' and its consequences for medical intervention by focusing on biomedical practices surrounding diabetes care among First Nations on Manitoulin Island, Ontario. The first section explores the process of diagnosing diabetes. The second section outlines the treatment regimens resulting from membership in this category. The theme linking these two processes is that both diagnosis and management of diabetes depend on inclusion into categories of 'risk'. Practices surrounding diagnosis focus on a population described 'at risk' for diabetes. First Nation's people. Similarly, practices surrounding management of diabetes focus on a population 'at risk' for secondary complications, referring to individuals with diabetes. As the following discussion outlines, it is through the quantitative assessment of risk that scientific uncertainty is translated into definitive therapy and the need for constant surveillance.


Universal patterns in egocentric communication networks.
Tie strengths in social networks are heterogeneous, with strong and weak ties playing different roles at the network and individual levels. Egocentric networks, networks of relationships around an individual, exhibit few strong ties and more weaker ties, as evidenced by electronic communication records. Mobile phone data has also revealed persistent individual differences within this pattern. However, the generality and driving mechanisms of social tie strength heterogeneity remain unclear. Here, we study tie strengths in egocentric networks across multiple datasets of interactions between millions of people during months to years. We find universality in tie strength distributions and their individual-level variation across communication modes, even in channels not reflecting offline social relationships. Via a simple model of egocentric network evolution, we show that the observed universality arises from the competition between cumulative advantage and random choice, two tie reinforcement mechanisms whose balance determines the diversity of tie strengths. Our results provide insight into the driving mechanisms of tie strength heterogeneity in social networks and have implications for the understanding of social network structure and individual behavior.


Maternal diet supplementation with methyl donors and increased parity affect the incidence of craniofacial defects in the offspring of twisted gastrulation mutant mice.
Diets rich in methyl-donating compounds, including folate, can provide protection against neural tube defects, but their role in preventing craniofacial defects is less clear. Mice deficient in Twisted gastrulation (TWSG1), an extracellular modulator of bone morphogenetic protein signaling, manifest both midline facial defects and jaw defects, allowing study of the effects of methyl donors on various craniofacial defects in an experimentally tractable animal model. The goal of this study was to examine the effects of maternal dietary supplementation with methyl donors on the incidence and type of craniofacial defects among Twsg1(-/-) offspring. Nulliparous and primiparous female mice were fed an NIH31 standard diet (control) or a methyl donor supplemented (MDS) diet (folate, vitamin B-12, betaine, and choline). Observed defects in the pups were divided into those derived mostly from the first branchial arch (BA1) (micrognathia, agnathia, cleft palate) and midline facial defects in the holoprosencephaly spectrum (cyclopia, proboscis, and anterior truncation). In the first pregnancy, offspring of mice fed the MDS diet had lower incidence of BA1-derived defects (12.8% in MDS vs. 32.5% in control; P = 0.02) but similar incidence of midline facial defects (6.4% in MDS vs. 5.2% in control; P = 1.0). Increased maternal parity was independently associated with increased incidence of craniofacial defects after adjusting for diet (from 37.7 to 59.5% in control, P = 0.04 and from 19.1 to 45.3% in MDS, P = 0.045). In conclusion, methyl donor supplementation shows protective effects against jaw defects, but not midline facial defects, and increased parity can be a risk factor for some craniofacial defects.


Vav family proteins couple to diverse cell surface receptors.
Vav proteins are guanine nucleotide exchange factors for Rho family GTPases which activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. Vav proteins contain several protein binding domains which can link cell surface receptors to downstream signaling proteins. Vav1 is expressed exclusively in hematopoietic cells and tyrosine phosphorylated in response to activation of multiple cell surface receptors. However, it is not known whether the recently identified isoforms Vav2 and Vav3, which are broadly expressed, can couple with similar classes of receptors, nor is it known whether all Vav isoforms possess identical functional activities. We expressed Vav1, Vav2, and Vav3 at equivalent levels to directly compare the responses of the Vav proteins to receptor activation. Although each Vav isoform was tyrosine phosphorylated upon activation of representative receptor tyrosine kinases, integrin, and lymphocyte antigen receptors, we found unique aspects of Vav protein coupling in each receptor pathway. Each Vav protein coprecipitated with activated epidermal growth factor and platelet-derived growth factor (PDGF) receptors, and multiple phosphorylated tyrosine residues on the PDGF receptor were able to mediate Vav2 tyrosine phosphorylation. Integrin-induced tyrosine phosphorylation of Vav proteins was not detected in nonhematopoietic cells unless the protein tyrosine kinase Syk was also expressed, suggesting that integrin activation of Vav proteins may be restricted to cell types that express particular tyrosine kinases. In addition, we found that Vav1, but not Vav2 or Vav3, can efficiently cooperate with T-cell receptor signaling to enhance NFAT-dependent transcription, while Vav1 and Vav3, but not Vav2, can enhance NFkappaB-dependent transcription. Thus, although each Vav isoform can respond to similar cell surface receptors, there are isoform-specific differences in their activation of downstream signaling pathways.


Duration of mating relates to fertility in mice.
In normal mating, house mice vary dramatically in the number and duration of intromissions that precede ejaculation. Also, some proportion of inseminations typically fails to yield litters. The present studies involved systematic observations of matings of females in natural estrus with males of proven fertility. After standardized observation of mating behavior culminating in ejaculation and a sperm plug, females were allowed to produce litters in undisturbed conditions. In two replications, greater numbers of intromissions and a longer latency from first intromission to ejaculation both correlated positively with litter size.


Stress-mediated convergence of splicing landscapes in male and female rock doves.
The process of alternative splicing provides a unique mechanism by which eukaryotes are able to produce numerous protein products from the same gene. Heightened variability in the proteome has been thought to potentiate increased behavioral complexity and response flexibility to environmental stimuli, thus contributing to more refined traits on which natural and sexual selection can act. While it has been long known that various forms of environmental stress can negatively affect sexual behavior and reproduction, we know little of how stress can affect the alternative splicing associated with these events, and less still about how splicing may differ between sexes. Using the model of the rock dove (Columba livia), our team previously uncovered sexual dimorphism in the basal and stress-responsive gene transcription of a biological system necessary for facilitating sexual behavior and reproduction, the hypothalamic-pituitary-gonadal (HPG) axis. In this study, we delve further into understanding the mechanistic underpinnings of how changes in the environment can affect reproduction by testing the alternative splicing response of the HPG axis to an external stressor in both sexes. This study reveals dramatic baseline differences in HPG alternative splicing between males and females. However, after subjecting subjects to a restraint stress paradigm, we found a significant reduction in these differences between the sexes. In both stress and control treatments, we identified a higher incidence of splicing activity in the pituitary in both sexes as compared to other tissues. Of these splicing events, the core exon event is the most abundant form of splicing and more frequently occurs in the coding regions of the gene. Overall, we observed less splicing activity in the 3'UTR (untranslated region) end of transcripts than the 5'UTR or coding regions. Our results provide vital new insight into sex-specific aspects of the stress response on the HPG axis at an unprecedented proximate level. Males and females uniquely respond to stress, yet exhibit splicing patterns suggesting a convergent, optimal splicing landscape for stress response. This information has the potential to inform evolutionary theory as well as the development of highly-specific drug targets for stress-induced reproductive dysfunction.


Prospects for high gain inertial fusion energy: an introduction to the second edition.
Part II of this special edition contains the remaining 11 papers arising from a Hooke discussion meeting held in March 2020 devoted to exploring the current status of inertial confinement fusion research worldwide and its application to electrical power generation in the future, via the development of an international inertial fusion energy programme. It builds upon increased coordination within Europe over the past decade by researchers supported by the EUROFusion Enabling Research grants, as well as collaborations that have arisen naturally with some of America's and Asia's leading researchers, both in the universities and national laboratories. The articles are devoted to informing an update to the European roadmap for an inertial fusion energy demonstration reactor, building upon the commonalities between the magnetic and inertial fusion communities' approaches to fusion energy. A number of studies devoted to understanding the physics barriers to ignition on current facilities are then presented. The special issue concludes with four state-of-the-art articles describing recent significant advances in fast ignition inertial fusion research. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.


Changes in postural strategy of the lower limb under mechanical knee constraint on an unsteady stance surface.
Joint constraint could limit the available degrees of freedom in a kinematic chain for maintaining postural stability. This study investigated adaptive changes in postural synergy due to bracing of bilateral knee joints, usually thought to have a trifling impact on upright stance. Twenty-four young adults were requested to maintain balance on a stabilometer plate as steadily as possible while wearing a pair of knee orthoses, either unlocked (the non-constraint (NC) condition) or locked to restrict knee motion (the knee constraint (KC) condition). Knee constraint led to a significant increase in the regularity of the stabilometer angular velocity. More than 95% of the variance properties of the joint angular velocities in the lower limb were explained by the first and second principal components (PC1 and PC2), which represented the ankle strategy and the combined knee and hip strategy, respectively. In addition to the increase trend in PC1 regularity, knee constraint enhanced the mutual information of the stabilometer angular velocity and PC1 (MISTBV-PC1) but reduced the mutual information of the stabilometer angular velocity and PC2 (MISTBV-PC2). The MISTBV-PC1 was also positively correlated to stance steadiness on the stabilometer in the KC condition. In summary, in the knee constraint condition, postural synergy on the stabilometer was reorganized to increase reliance on ankle strategies to maintain equilibrium. In particular, a stable stabilometer stance under knee constraint is associated with a high level of coherent ankle-stabilometer interaction.


Effect of polymer type on characterization and filtration performances of multi-walled carbon nanotubes (MWCNT)-COOH-based polymeric mixed matrix membranes.
Multi-walled carbon nanotubes (MWCNTs) can be used for the fabrication of mixed matrix polymeric membranes that can enhance filtration perfomances of the membranes by modifying membrane surface properties. In this study, detailed characterization and filtration performances of MWCNTs functionalized with COOH group, blended into polymeric flat-sheet membranes were investigated using different polymer types. Morphological characterization was carried out using atomic force microscopy, scanning electron microscopy and contact angle measurements. For filtration performance tests, protein, dextran, E. coli suspension, Xanthan Gum and real activated sludge solutions were used. Experimental data and analyses revealed that Polyethersulfone (PES) + MWCNT-COOH mixed matrix membranes have superior performance abilities compared to other tested membranes.


Neural Correlates of Anti-appetite Medications: An fMRI Meta-analysis.
Food craving is a health issue for a considerable proportion of the general population. Medications have been introduced to alleviate the craving or reduce the appetite via a neuropharmacological approach. However, the underlying cerebral processing of the medications was largely unknown. This study aimed to meta-analyze existing neuroimaging findings. PubMed, Web of Science, and Scopus were searched to identify relevant publications. Original studies that reported brain imaging findings using functional magnetic resonance imaging (fMRI) were initially included. The reported coordinates of brain activation available from the studies were extracted and metaanalyzed with the activation likelihood estimation (ALE) approach via the software GingerALE. The overall analysis pooling data from 24 studies showed that the right claustrum and insula were the targeted sites of altered cerebral processing of food cues by the medications. Subgroup analysis pooling data from 11 studies showed that these sites had reduced activity levels under medications compared to placebo. The location of this significant cluster partially overlapped with that attributable to affective value processing of food cues in a prior meta-analysis. No brain regions were found to have increased activity levels by medications. These neural correlates may help explain the physiological effect of food consumption by anti-appetite and anti-obesity medications.


Associations between stress and migraine and tension-type headache: results from a school-based study in adolescents from grammar schools in Germany.
Stress is considered the major contributor to migraine and tension-type headache in adolescents. Previous studies have focused on general stressors, whereas the aim of the present study was to investigate associations between individuals' stressful experiences and different types of headache. Adolescents from 10th and 11th grades of grammar schools filled in questionnaires. Stressful experiences were measured with the Trier Inventory of Chronic Stress. Type of headache was classified according to the International Classification of Headache Disorders. Linear regressions, adjusted for sex and grade, were calculated to estimate differences in stress scores that can be attributed to migraine, tension-type headache or miscellaneous headache. A total of 1260 questionnaires were analysed. Tension-type headache, migraine and co-existing migraine plus tension-type headache were found in 48.7%, 10.2% and 19.8% of the participants. In subjects with migraine or co-existing migraine plus tension-type headache, high increases in stress scores were found in all investigated dimensions, whereas much weaker and inconsistent associations were found in subjects with tension-type headache only. The characteristic of migraine is more associated with stressful experiences than this is the case for tension-type headache. This suggests that adolescent migraine patients might especially benefit from behavioural interventions regarding stress.


A Framework to Understand Extreme Space Weather Event Probability.
An extreme space weather event has the potential to disrupt or damage infrastructure systems and technologies that many societies rely on for economic and social well-being. Space weather events occur regularly, but extreme events are less frequent, with a small number of historical examples over the last 160 years. During the past decade, published works have (1) examined the physical characteristics of the extreme historical events and (2) discussed the probability or return rate of select extreme geomagnetic disturbances, including the 1859 Carrington event. Here we present initial findings on a unified framework approach to visualize space weather event probability, using a Bayesian model average, in the context of historical extreme events. We present disturbance storm time (Dst) probability (a proxy for geomagnetic disturbance intensity) across multiple return periods and discuss parameters of interest to policymakers and planners in the context of past extreme space weather events. We discuss the current state of these analyses, their utility to policymakers and planners, the current limitations when compared to other hazards, and several gaps that need to be filled to enhance space weather risk assessments.


Re-vaccination of 421 children with a past history of an adverse vaccine reaction in a special immunisation service.
In Australia an adverse event following immunisation (AEFI), with the exception of anaphylaxis and encephalopathy, is no longer considered an absolute contraindication to continuing vaccination with the suspect vaccine. Despite these recommendations there is a paucity of information on the re-vaccination of such children. To describe the re-vaccination of a large number of children with a past history of an AEFI. A review of children attending special immunisation services in three Australian tertiary care paediatric centres. During the review 970 children attended of whom 469 had experienced a past AEFI. Of these, 293 had experienced minor while 176 children had experienced significant neurological or allergic reactions. The majority (421/469) were re-vaccinated, with only one child having a significant neurological event; this was transient and resolved spontaneously. Re-vaccination of children who have a past history of an AEFI appears safe. A special immunisation service should be part of a comprehensive immunisation programme.


Ultrasoft, highly deformable microgels.
Microgels are colloidally stable, hydrogel microparticles that have previously been used in a range of (soft) material applications due to their tunable mechanical and chemical properties. Most commonly, thermo and pH-responsive poly(N-isopropylacrylamide) (pNIPAm) microgels can be fabricated by precipitation polymerization in the presence of the co-monomer acrylic acid (AAc). Traditionally pNIPAm microgels are synthesized in the presence of a crosslinking agent, such as N,N'-methylenebisacrylamide (BIS), however, microgels can also be synthesized under 'crosslinker free' conditions. The resulting particles have extremely low (<0.5%), core-localized crosslinking resulting from rare chain transfer reactions. AFM nanoindentation of these ultralow crosslinked (ULC) particles indicate that they are soft relative to crosslinked microgels, with a Young's modulus of ∼10 kPa. Furthermore, ULC microgels are highly deformable as indicated by a high degree of spreading on glass surfaces and the ability to translocate through nanopores significantly smaller than the hydrodynamic diameter of the particles. The size and charge of ULCs can be easily modulated by altering reaction conditions, such as temperature, monomer, surfactant and initiator concentrations, and through the addition of co-monomers. Microgels based on the widely utilized, biocompatible polymer polyethylene glycol (PEG) can also be synthesized under crosslinker free conditions. Due to their softness and deformability, ULC microgels are a unique base material for a wide variety of biomedical applications including biomaterials for drug delivery and regenerative medicine.


Polarization-mode dispersion effect of an acousto-optic tunable filter.
The effect of the polarization-mode dispersion (PMD) of an acousto-optic tunable filter (AOTF) is studied both theoretically and experimentally. A coupled-mode method derived from Maxwell's equations is proposed to study the evolution of the polarization of light and hence the deterministic dynamics of the PMD inside an AOTF. It is found that the PMD value of a typical AOTF is around several picoseconds and is adjustable by tuning the strength of the applied sound signal. A set of experimental data acquired by the wavelength scanning method is employed to check the validity of the proposed method. A high degree of similarity is observed between the experimental and the theoretical data.


Contemporary concepts of immunological function.
The science of Immunology, since its beginnings around the year 1900, has expanded to encyclopaedic dimensions and has had enjoyed two "golden ages," in the early 1900s and after the 1950s. By way of illustration, as many as 23 of the present total of 157 Nobel Laureates received their award for discoveries relevant to immunology, including the first in 1901 to Emil von Behring for the use of immune serum in the treatment of disease. The Nobel awards in Immunology will be used as theme points for the text of this lecture. In fact, this paper asks you to imagine a series of six lectures on Contemporary Concepts delivered at various times between 1900 and the present, specifically 1905, 1930, 1960, 1970, 1980 and today, May 1994.


Conservation and Genetics.
Humans are responsible for a cataclysm of species extinction that will change the world as we see it, and will adversely affect human health and wellbeing. We need to understand at individual and societal levels why species conservation is important. Accepting the premise that species have value, we need to next consider the mechanisms underlying species extinction and what we can do to reverse the process. One of the last stages of species extinction is the reduction of a species to a few populations of relatively few individuals, a scenario that leads invariably to inbreeding and its adverse consequences, inbreeding depression. Inbreeding depression can be so severe that populations become at risk of extinction not only because of the expression of harmful recessive alleles (alleles having no phenotypic effect when in the heterozygous condition, e.g., Aa, where a is the recessive allele), but also because of their inability to respond genetically with sufficient speed to adapt to changing environmental conditions. However, new conservation approaches based on foundational quantitative and population genetic theory advocate for active genetic management of fragmented populations by facilitating gene movements between populations, i.e., admixture, or genetic rescue. Why species conservation is critical, the genetic consequences of small population size that often lead to extinction, and possible solutions to the problem of small population size are discussed and presented.


Folate content of gluten-free food purchases and dietary intake are low in children with coeliac disease.
The lack of mandated folate enrichment of gluten-free (GF) grains in Canada has been suspected to contribute to suboptimal folate intake among children suffering from Celiac disease (CD). Children with CD on the gluten-free diet (GFD) face nutrient imbalances (higher fat/sugar, lower folate) from processed GF foods. The study objective examined folate intake in children with CD and folate content of household food purchases. Households collected food receipts for 30 days to assess folate content. Folate-rich foods were defined as ≥60 µg dietary folate equivalent (DFE)/100g. Two 24-hour recalls assessed children's intake. Households (n = 73) purchased >17,000 food items. Median child age was 10.5 y (IQR: 8.4-14.1). GF folate-rich foods represented <15% of all household food purchases and 69% of children had low folate intakes. Folate-rich foods consumed included legumes/GF-breakfast cereals. These represented 5% of GF-food purchases/intake. Few were fortified with folate. Findings highlight the need for mandated GF folate food fortification policy.


Negative mood states and related factors in a sample of adolescent secondary-school students in Barcelona (Spain).
Poor mental health is a common problem in adolescence. Little information is available, however, about the factors influencing negative mood states in otherwise healthy adolescents. We aimed to describe the mood states and related factors in a sample of adolescents in the city of Barcelona (Spain). We administered a health survey to a sample of 2,727 students from public, subsidized, and private schools in Barcelona, aged approximately 14, 16, and 18 years old. To analyze the associations among moods and related factors, we used bivariate logistic regression, and fitted multivariate logistic regressions using the statistically significant variables from the bivariate analysis. To examine the possible group effects of the school on individual students, we employed multilevel analysis. The frequencies of negative mood states increased with age, with girls consistently reporting more frequent negative mood states than boys. The factors associated with negative mood states were problematic alcohol use, perceived mistreatment or abuse, antisocial behavior, intention to use or current use of illegal drugs (not including cannabis), lower perceived academic performance, and feeling isolated. Mood states are influenced by lifestyle and social factors, about which there is little local information. To plan and implement appropriate public health interventions, more complete information about the possible areas of influence is required. To complement the information obtained from studies such as the present study, longitudinal and qualitative studies would be desirable.


Comparison of moxalactam (LY127935) and cefotaxime against anaerobic bacteria.
The in vitro activities of moxalactam (LY127935 [6059S]) and cefotaxime were compared with those of cefoxitin, cefamandole, cefuroxime, carbenicillin, and penicillin by agar dilution susceptibility testing of a variety of anaerobic bacteria. Moxalactam proved to be the most active agent tested against Bacteroides fragilis and other species of the B. fragilis group. Moxalactam and cefotaxime showed activity similar to the other drugs against the remaining species of Bacteroides, Fusobacterium, Actinomyces, Propionibacterium, and Veillonella. Penicillin was the most effective drug tested against most species of Clostridium, the anaerobic gram-positive cocci, and Eubacterium lentum.


Immunophenotypic assessment of clonal plasma cells and B-cells in bone marrow and blood in the diagnostic classification of early stage monoclonal gammopathies: an iSTOPMM study.
Monoclonal gammopathy of undetermined significance (MGUS) is the earliest discernible stage of multiple myeloma (MM) and Waldenström's macroglobulinemia (WM). Early diagnosis of MG may be compromised by the low-level infiltration, undetectable to low-sensitive methodologies. Here, we investigated the prevalence and immunophenotypic profile of clonal (c) plasma cells (PC) and/or cB-lymphocytes in bone marrow (BM) and blood of subjects with a serum M-component from the iSTOPMM program, using high-sensitive next-generation flow cytometry (NGF), and its utility in the diagnostic classification of early-stage MG. We studied 164 paired BM and blood samples from 82 subjects, focusing the analysis on: 55 MGUS, 12 smoldering MM (SMM) and 8 smoldering WM (SWM). cPC were detected in 84% of the BM samples and cB-lymphocytes in 45%, coexisting in 39% of cases. In 29% of patients, the phenotypic features of cPC and/or cB-lymphocytes allowed a more accurate disease classification, including: 19/55 (35%) MGUS, 1/12 (8%) SMM and 2/8 (25%) SWM. Blood samples were informative in 49% of the BM-positive cases. We demonstrated the utility of NGF for a more accurate diagnostic classification of early-stage MG.


A low-threshold self-referenced Ti:Sapphire optical frequency comb.
We demonstrate an octave-spanning, self-referenced optical frequency comb produced with a high-repetition-rate (frep=585 MHz) femtosecond Ti:Sapphire laser that requires less than 1 W of 532 nm pump power. The frequency comb was stabilized to a CW laser as required for optical clocks and low noise frequency synthesis. These results should be relevant for applications that require more-compact and efficient frequency combs.


Isolation, identification and increasing importance of 'free-living' amoebae causing human disease.
Amphizoic small amoebic protozoa are capable of existing both in 'free-living' and in 'parasitic' form depending on the actual conditions. Two genera (Naegleria and Acanthamoeba) have become recognised as opportunist human parasites. Since the first description in 1965 of a lethal case of primary amoebic meningoencephalitis (PAM) caused by Naegleria, many more (mostly lethal) cases have been reported, while granulomatous amoebic encephalitis (GAE), as well as eye (keratinitis, conjunctivitis, etc.), ear, nose, skin and internal organ infections caused by Acanthamoeba have also occurred in rapidly increasing numbers. Both pathogenic and non-pathogenic species of Naegleria and Acanthamoeba are found worldwide in water, soil and dust, where they provide a potential source of infection. Successful differential diagnosis and appropriate (specific) therapy depends on precise laboratory identification of the 'free-living' amoebae. In most cases, isolation from the environment can be achieved, but identification and differentiation of the pathogenic and non-pathogenic strains is not easy. The methods presently available do not fulfil completely the requirements for specificity, sensitivity and reliability. Morphological criteria are inadequate, while thermophilic character, pH dependency and even virulence in infected mice, are not unambiguous features of pathogenicity of the different strains. More promising are molecular methods, such as restriction endonuclease digestion of whole-cell DNA or mitochondrial DNA, as well as iso-enzyme profile analysis after iso-electric focusing and staining for acid phosphatase and propionyl esterase activity. Use of appropriate monoclonal antibodies has also yielded promising results in the differentiation of human pathogenic and non-pathogenic strains. However, quicker, simpler, more specific and reliable methods are still highly desirable. The significance of endosymbiosis (especially with Legionella strains) is not well understood. The results of a systematic survey in Hungary for the isolation and identification of 'free-living' amoebae, including an investigation of the Hungarian amoebic fauna, the isolation of possibly pathogenic Naegleria strains and of some Acanthamoeba strains from eye diseases, as well as the finding of a case of endosymbiosis, are also reported here.


Ultrasound image transmission via camera phones for overreading.
Emergency physicians using ultrasound frequently encounter unfamiliar findings during routine ultrasound examination. This is especially common for less experienced practitioners. To compare high-resolution thermal printer ultrasound images and images recorded and transmitted via commercial camera cell phones. This was a study comparing randomly selected images of actual ultrasound examinations performed in an academic level I ED with hospital-based emergency ultrasound credentialing. Two hospital credentialed emergency sonologists with extensive experience were asked to review 50 randomly selected images from actual patients as seen on a camera cell phone screen after being captured from a high-resolution thermal printout and sent to a similar phone. Reviewers recorded initial impression of the image and identified structures, measurements, and pathology. After hearing a brief clinical vignette, reviewer rated the images for image quality, detail, resolution, as previously defined, on a 10-point Likert scale. This process was then repeated with the original thermal printouts. Data were analyzed using descriptive statistics, agreement analysis, and the Student t test. Reviewers showed good interrater agreement for pathology and structure detection between phone and thermal printer images. There was no statistically significant difference in image quality, resolution, and detail between phone images and thermal printer images. However, there was statistically significantly increase in confidence in diagnosis for reviewers when using thermal printer images as compared with phone images, P = .003 and P = .02. Several phone images were felt to be suboptimal, and there was moderate agreement on these between reviewers. Ultrasound pictures recorded by one phone and then sent to another yielded images that showed no statistically significant differences from traditional high-resolution thermal printouts in image quality, detail, and resolution. Measurements were too small to be read on the camera phones, and reviewers had statistically significantly lower confidence in their diagnosis when using the camera phones to review images.


Limited photosynthetic plasticity in the leaf-succulent CAM plant Agave angustifolia grown at different temperatures.
In Agave angustifolia Haw., a leaf-succulent constitutive crassulacean acid metabolism (CAM) plant of tropical Panama, we tested whether nocturnal CO2 uptake and growth were reduced at night temperatures above 20°C. Unlike some CAM model species from habitats with pronounced day-night temperature variations, in A. angustifolia temperature affected little the relative contributions of CAM and C3 photosynthesis to growth. In plants grown under 12h light/dark regimes of 25/17, 30/22 and 35/27°C, biomass increased with temperature. Maintaining day temperature at 35°C and reducing night temperature from 27 to 17°C markedly lowered growth, a reduction partially reversed when roots were heated to 27°C. Across all treatments, whole-shoot δ13C values ranged between -14.6 and -13.2 ‰, indicating a stable proportion of CO2 was fixed at night, between 75 and 83%. Nocturnal acidification reflected growth, varying between 339 and 393μmol H+ g-1 fresh mass and 63-87μmol H+ cm-2. In outdoor open-top chambers, warming the air 3°C above ambient at night did not reduce biomass accumulation. The persistence of a high capacity for nocturnal CO2 fixation at the expense of a limited capacity for switching between C3 and CAM probably makes this Agave, and others like it, potential species for biomass production in seasonally-dry landscapes.


Evaluating Dual Task Neurological Costs with Functional Near-Infrared Spectroscopy: A Preliminary Report in Healthy Athletes.
Dual task assessments, which simultaneously challenge and assess cognitive and motor performance, have been used to improve the assessment of athletes with sports-related concussions (SRC). Our lab created a Dual Task Screen (DTS) to evaluate athletes with SRCs, and we have established that it is a valid behavioral measure, as it consistently elicits poorer behavioral performance under dual, compared to single, task conditions. Here, we used a Neuroimaging-Compatible (NC) version of the DTS, named the NC-DTS, which uses portable functional near-infrared spectroscopy (fNIRS) to assess behavioral performance and neural recruitment during single and dual tasks. Our study objective was to evaluate healthy athletes and establish whether the NC-DTS is a valid dual task neurological assessment that can elicit different patterns of neural recruitment during dual versus single task conditions. Twenty-five healthy collegiate athletes completed the NC-DTS in a single laboratory visit. The NC-DTS includes a lower and upper extremity subtask; both include single motor, single cognitive, and dual task conditions. The NC-DTS was administered in a block design, where conditions (i.e., single motor, single cognitive, and dual task) were repeated five times to generate average behavioral performance and task-dependent neural recruitment in superficial cortical regions including: prefrontal cortex, bilateral primary motor and sensory cortices, and posterior parietal cortex. Neural recruitment was measured with fNIRS and quantified using oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (HbR) metrics. A single-tailed, within subject t-test was used to compare average dual task behavioral performance to average single task behavioral performance. Pairwise comparisons, that were family-wise-error (FWE) corrected, were used to compare localized neural recruitment during dual versus single task conditions. As observed in previous studies, the NC-DTS elicited significantly poorer behavioral performance under dual, compared to single, task conditions. Additionally, dual task conditions of the NC-DTS elicited significantly greater neural recruitment in regions of the brain associated with attention allocation and task-specific demands in three of four comparisons. These preliminary results suggest that the NC-DTS is a valid dual task neurological assessment which warrants future work using the NC-DTS to evaluate athletes with SRCs.


Pasteurella aerogenes as an Asymptomatic Bacteriuria Agent.
'Asymptomatic bacteriuria' (ASB) is isolation of a specified quantitative count of bacteria in an appropriately collected urine specimen obtained from a person without symptoms or signs referable to urinary infection. Catheterized specimens are less likely to be contaminated compared with voided specimens; therefore, positive cultures of catheterized specimens are more likely to reflect true bladder bacteriuria even with low colony counts. The common pathogens for ASB are Escherichia coli, Klebsiella and Streptococcus spp. Pasteurella spp. was not previously reported as an ASB agent. ASB is important for pregnant women, children, individuals with obstructive uropathy, chronic renal failure and neutropenia, before the urologic procedures and after renal transplantation. Treatment of ASB is required for above situations. We report an 11-year-old-girl with neurogenic bladder who made clean intermittent catheterization and had Pasteurella aerogenes as an ASB agent.


Salt Stress and CTD PHOSPHATASE-LIKE4 Mediate the Switch between Production of Small Nuclear RNAs and mRNAs.
Phosphorylation of the RNA polymerase II (Pol II) C-terminal domain (CTD) regulates transcription of protein-coding mRNAs and noncoding RNAs. CTD function in transcription of protein-coding RNAs has been studied extensively, but its role in plant noncoding RNA transcription remains obscure. Here, using Arabidopsis thaliana CTD PHOSPHATASE-LIKE4 knockdown lines (CPL4RNAi ), we showed that CPL4 functions in genome-wide, conditional production of 3'-extensions of small nuclear RNAs (snRNAs) and biogenesis of novel transcripts from protein-coding genes downstream of the snRNAs (snRNA-downstream protein-coding genes [snR-DPGs]). Production of snR-DPGs required the Pol II snRNA promoter (PIIsnR), and CPL4RNAi plants showed increased read-through of the snRNA 3'-end processing signal, leading to continuation of transcription downstream of the snRNA gene. We also discovered an unstable, intermediate-length RNA from the SMALL SCP1-LIKE PHOSPHATASE14 locus (imRNASSP14 ), whose expression originated from the 5' region of a protein-coding gene. Expression of the imRNASSP14 was driven by a PIIsnR and was conditionally 3'-extended to produce an mRNA. In the wild type, salt stress induced the snRNA-to-snR-DPG switch, which was associated with alterations of Pol II-CTD phosphorylation at the target loci. The snR-DPG transcripts occur widely in plants, suggesting that the transcriptional snRNA-to-snR-DPG switch may be a ubiquitous mechanism to regulate plant gene expression in response to environmental stresses.


Partial vinylphenol reductase purification and characterization from Brettanomyces bruxellensis.
Brettanomyces is the major microbial cause for wine spoilage worldwide and causes significant economic losses. The reasons are the production of ethylphenols that lead to an unpleasant taint described as 'phenolic odour'. Despite its economic importance, Brettanomyces has remained poorly studied at the metabolic level. The origin of the ethylphenol results from the conversion of vinylphenols in ethylphenol by Brettanomyces hydroxycinnamate decarboxylase. However, no information is available on the vinylphenol reductase responsible for the conversion of vinylphenols in ethylphenols. In this study, a vinylphenol reductase was partially purified from Brettanomyces bruxellensis that was active towards 4-vinylguaiacol and 4-vinylphenol only among the substrates tested. First, a vinylphenol reductase activity assay was designed that allowed us to show that the enzyme was NADH dependent. The vinylphenol reductase was purified 152-fold with a recovery yield of 1.77%. The apparent K(m) and V(max) values for the hydrolysis of 4-vinylguaiacol were, respectively, 0.14 mM and 1900 U mg(-1). The optimal pH and temperature for vinylphenol reductase were pH 5-6 and 30 degrees C, respectively. The molecular weight of the enzyme was 26 kDa. Trypsic digest of the protein was performed and the peptides were sequenced, which allowed us to identify in Brettanomyces genome an ORF coding for a 210 amino acid protein.


The human materno-foetal relationship in malaria. II. Histological, ultrastructural and immunopathological studies of the placenta.
Histological and ultrastructural studies of four placentae heavily infectd with Plasmodium falciparum revealed large intervillous accumulations of erythrocytes containing parasites together with monocytes which had ingested pigment. These appearances were associated with focal syncytial necrosis, loss of syncytial microvilli and proliferation of cytotrophoblastic cells. In addition, marked irregular thickening of trophoblastic basement membranes and protrusion of tongue-like projections of syncytiotrophoblast into the basement membrane were observed. In six other placentae which contained scanty amounts of pigment but no parasites, representing past or inactive infection, no large collections of monocytes or abnormalities of trophoblast were apparent but basement membrane thickening was evident. Immunohistological studies revealed no significant differences between placentae positive for parasites and those containing pigment only, although the amount of certain immunoproteins and clotting factors was clearly increased above normal. These findings establish that P. falciparum infection in the placenta may result in substantial damage although lesions within the villus are rare. Furthermore, previous infection, although adequately controlled, may leave a heritage of pigment deposition, basement membrane thickening and immunopathological lesions. These results may thus account for both the high frequency of intra-uterine growth retardation and the rarity of congenital malaria in the presence of P. falciparum malaria.


Sensitization to apomorphine in pigeons is due to conditioning, subject to generalization but resistant to extinction.
Apomorphine (Apo) administration induces a persistent bout of pecking in pigeons and other birds. Repeated injections of Apo in pigeons lead to sensitization, i.e. the pecking response to a particular dose increases up to a dose-dependent asymptotic level. It is also known that Apo-induced pecking can be classically conditioned to the cage environment where the animals experience the effect of the drug. Here we address the question of whether, and to what extent, the sensitization effect arises as a consequence of a conditioning or of a pharmacological process. An extinction experiment demonstrated that an extinction procedure supposed to be effective in inhibiting the conditioned pecking response was not effective in suppressing the sensitization to Apo, thus casting provisional doubt on the conditioning hypothesis. However, a conditioning experiment demonstrated that the sensitization effect undoubtedly involved an important component of conditioning to an experimental cage environment, but also suggested that there was an additional component possibly not due to learning. A generalization experiment, however, showed that this second component was very probably due to a stimulus generalization effect deriving from conditioning to the home cage, suggesting that learning can account for most, if not all, of the increase in Apo-induced pecking and that an exclusively pharmacological sensitization process plays, at best, a minor role. The apparent contrast between the results of the first experiment, indicating that the sensitization is not affected by inhibitory conditioning, and the results of the last two experiments, suggesting that the sensitization is due to excitatory conditioning, can be resolved by assuming that Apo induces a drug-state-dependent conditioning. These results are related to findings and arguments concerning the sensitization to psychostimulant drugs in mammals.


Interactive Metronome training in children with attention deficit and developmental coordination disorders.
The objective of this study was to examine the efficacy of Interactive Metronome (Interactive Metronome, Sunrise, Florida, USA) training in a group of children with mixed attentional and motor coordination disorders to further explore which subcomponents of attentional control and motor functioning the training influences. Twelve children who had been diagnosed with attention deficit hyperactivity disorder, in conjunction with either developmental coordination disorder (n=10) or pervasive developmental disorder (n=2), underwent 15 1-h sessions of Interactive Metronome training over a 15-week period. Each child was assessed before and after the treatment using measures of attention, coordination, and motor control to determine the efficacy of training on these cognitive and behavioral realms. As a group, the children made significant improvements in complex visual choice reaction time and visuomotor control after the training. There were, however, no significant changes in sustained attention or inhibitory control over inappropriate motor responses after treatment. These results suggest Interactive Metronome training may address deficits in visuomotor control and speed, but appears to have little effect on sustained attention or motor inhibition.


Factors affecting managers' intention to adopt green supply chain management practices: evidence from manufacturing firms in Jordan.
Global sustainability movement encourages companies to adopt and implement green supply chain management (GSCM) practices across the organization. Moreover, the integration of green practices into traditional supply chain is still to be a difficult task in manufacturing sector. However, empirical studies regarding the identification of influential factors affecting GSCM adoption among supply chain managers in manufacturing sector are under researched. This study assesses the factors affecting GSCM adoption in Jordan manufacturing firms. A well-structured questionnaire was administered for data collection. A valid 376 responses were collected from different manufacturing firms in Jordan. The data were analyzed, and the proposed model was validated using the structural equation modeling (SEM) approach. Results reveal that four factors, namely, supplier, environmental, customer, and cost factors significantly influence the intention to adopt GSCM among managers. The firm size had significantly moderated the relationship between market/financial and GSCM adoption, internal factor and GSCM adoption. The study will help the policymakers to understand the drivers of GSCM adoption among managers and assist them in implementing GSCM practices according to the size of the firm. This study is first of its kind to analyze the role of firm size as a moderator on the relationship between market/financial, supplier, governmental, environmental, internal, customers, cost factors, and GSCM in the context of Jordon.


Charles Lindbergh and the "right stuff".
This paper undertakes a partial character study of Charles Lindbergh, focusing on those traits (confrontation with sources of fear, fascination with "realms beyond," meticulous observation, openness to his own unconscious) that seemed to enable him to cope so effectively, and suggesting some possible sources of these traits in his life circumstances.


In vitro antibacterial activity of Omani and African honey.
The study aims to investigate the antibacterial activity of honey obtained from different parts of Oman and compare it with that of honey obtained from elsewhere in Africa. A total of 24 honey samples (16 from different parts of Oman and eight from elsewhere in Africa) were investigated for their antibacterial activity against Staphylococcus aureus (NCTC 6571), Escherichia coli (NCTC 10418) and Pseudomonas aeruginosa (NCTC 10662) using standard antimicrobial assays. Marked variations in the antibacterial activity of the different honey samples were observed. Fourteen of the 16 Omani samples and five of the eight African samples showed antibacterial activity ranked as either fair, good or excellent to at least one of the three bacterial strains tested. Both Omani and African honeys possess in vitro antibacterial activity against the three bacterial strains tested, with 25% of the samples showing excellent antibacterial activity.


Asthma control in pregnancy is associated with pre-conception dietary patterns.
To examine pre-conception dietary patterns in pregnant asthmatic women and to identify associations between maternal diet and asthma control during pregnancy. Cross-sectional study. Pre-conception food frequency data were collected retrospectively. Asthma control was assessed using the Global Initiative for Asthma guidelines. Dietary patterns were derived using factor analysis. Binary logistic regression analyses were used to test the association between uncontrolled asthma and each dietary pattern (Z-score), with values presented as odds ratio and 95 % confidence interval. Antenatal clinic in a tertiary hospital, Adelaide, Australia, May 2009-July 2013. One hundred and fifty-eight asthmatic pregnant women. Three dietary patterns were identified: (i) 'high protein/fruit' (strong food group loadings for fish, meat, chicken, fruit); (ii) 'high fat/sugar/takeaway' (takeaway foods, crisps, refined grains); and (iii) 'vegetarian-type' (vegetables, fruit, soya milk, whole grains). A 1 sd increase in score on the high fat/sugar/takeaway pattern was associated with increased likelihood of uncontrolled asthma (adjusted OR=1·54; 95 % CI 1·07, 2·23; P=0·022). Women with uncontrolled asthma (n 115) had higher energy-adjusted intakes of saturated fat, monounsaturated fat, carbohydrate, sugar and fibre compared with women with controlled asthma (n 43, all P≤0·05). Pre-pregnancy dietary patterns may influence maternal asthma control. Our work highlights the importance of achieving a healthy diet before pregnancy that is low in saturated fat, sugar and takeaway foods, and therefore higher in lean meats, poultry and fish, as well as fruits, vegetables and whole grains. A healthy dietary pattern should be encouraged in all asthmatic women who are of childbearing age, and should additionally be promoted before pregnancy and beyond.


Critical quantum chaos and the one-dimensional harper model
We obtain numerically a scale-invariant distribution of the bandwidths S for the critical Harper model, which is closely described by a semi-Poisson P(S) = 4Sexp(-2S) curve. After a suitable unfolding of spectra, derived from different boundary conditions, a semi-Poisson level spacing distribution and a sub-Poisson linear number variance are deduced from the bandwidth distribution. The obtained results support possible universality of the critical spectral statistics and suggest its connection to spectral multifractality.


Protein kinase C phosphorylation modulates N- and C-terminal regulatory activities of the PITX2 homeodomain protein.
PKC phosphorylation regulates PITX2 DNA binding and transcriptional activity. Mutation of individual PKC sites demonstrates the functional regulation of PITX2 through phosphorylation. Immunoprecipitation of PITX2 and a PITX2 PKC mutant protein reveal specific in vivo phosphorylation by PKC in transfected cells. The transcriptional activity of PITX2 is negatively regulated by N-terminal phosphorylation and positively regulated by C-terminal phosphorylation. We demonstrate a mechanism of increased PITX2 transcriptional activation through protein interactions facilitated by phosphorylation of the PITX2 C-terminal tail. Phosphorylation of the PITX2 C terminus enhances the interaction with cellular factors. In corroboration with the PITX2 PKC functional studies, a newly identified C-terminal PITX2 mutation associated with Axenfeld-Rieger syndrome (ARS) demonstrates reduced phosphorylation. This mutation (PITX2 DeltaT1261) creates a frameshift mutation in codon 227 resulting in 11 novel amino acids downstream followed by premature truncation of the protein. Three PKC sites in the C-terminal tail and OAR domain are deleted, which results in decreased transcriptional activation. PITX2 DeltaT1261 is unable to interact with a cellular factor to synergistically activate transcription and demonstrates the first link of ARS with defective PITX2 protein interactions. Gene expression profiling of homozygous Pitx2 mutant mouse tissue reveals decreased Dlx2 expression as a potential molecular basis for developmental defects associated with ARS patients. Overall, phosphorylation imparts another level of regulation to the activity of the PITX2 homeodomain protein during development.


Extracellular vesicle characteristics in stored red blood cell concentrates are influenced by the method of detection.
Extracellular vesicles (EVs), including microvesicles and exosomes, are small phospholipid vesicles (≤1μm in diameter) that are present in blood products, accumulate during storage, and have a potential transfusion-related immunomodulatory role. Knowledge of EVs in stored blood products is limited due to the challenges and difficulties in detecting these heterogeneous submicron-sized vesicles. The aim of this study was to assess the impact of different approaches to characterize EVs in stored RBC products. Quantification and size-profiling of EVs in leukoreduced red cell concentrates (RCCs) were examined on day 3, 7, 21, and 42 of storage using tunable resistive plus sensing (TRPS), flow cytometer (FC), and dynamic light scatting (DLS) methods. Using the TRPS method, the concentration of EVs<200nm significantly increased throughout storage (p<0.05). This change in exosome concentration was not detectable with FC or DLS due to limitations in their ability to resolve particles <200nm and/or accurately determine EV concentration. Both the TRPS and FC demonstrate that the concentration of EVs≥200nm significantly increases in RCCs by day 42/43 compared to EVs present on day 3 (p<0.001). As the DLS measures the average size of particles in suspension, only an increase in the zeta-average size was observed during storage. EV size and concentration in RBC products is significantly influenced by the length of storage. Overall, this study shows that combining technologies may be important to improve the characterization and study of EVs in stored RCCs.


Arthroscopic Versus Mini-open Rotator Cuff Repair: A Randomized Trial and Meta-analysis.
Patients with complete rotator cuff tears who fail a course of nonoperative therapy can benefit from surgical repair. This randomized trial compared mini-open (MO) versus all-arthroscopic (AA) rotator cuff repair. Randomized controlled trial; Level of evidence, 1. Patients with rotator cuff tears were randomized to undergo MO or AA repair at 9 centers by 23 surgeons. The primary outcome (Western Ontario Rotator Cuff Index [WORC]) and secondary outcomes (American Shoulder and Elbow Surgeons [ASES] score, Shoulder Pain and Disability Index [SPADI] pain subscale, 12-Item Short Form Health Survey [SF-12], reported medication use, adverse events), as well as measurements of range of motion and strength, were collected at 1 month before surgery; at 2 and 6 weeks postoperatively; and at 3, 6, 12, 18, and 24 months postoperatively. A blinded radiologist evaluated rotator cuff integrity on magnetic resonance imaging (MRI) at baseline and 1 year. Intention-to-treat analysis of covariance with the preoperative WORC score, age, and tear size as covariates assessed continuous outcomes. Sex differences were assessed. A meta-analysis synthesized the primary outcome between MO and AA repair with previous trials. From 954 patients screened, 411 were ineligible (276 because of recovery with physical therapy), 449 were screened at surgery (175 ineligible), and 274 completed follow-up (138 MO and 136 AA). The AA and MO groups were similar before surgery. WORC scores improved from 40 preoperatively to 89 (AA) and 93 (MO) at 2 years, for an adjusted mean difference of 3.4 (95% CI, -0.4 to 7.2). There were no statistically significant differences between the AA and MO groups at any time point. All secondary patient-reported outcomes were not significantly different between the MO and AA groups, except the 2-year SPADI pain score (8 vs 12, respectively; P = .02). A similar recovery in range of motion and strength occurred in both groups over time. MRI indicated minimal improvement in muscle relative to fat (AA: n = 3; MO: n = 2), with most worsening (AA: n = 25; MO: n = 24) or remaining unchanged (AA: n = 70; MO: n = 70). Opioid use was significantly reduced after surgery (from 21% to 5%). The meta-analysis indicated no significant standardized mean difference between groups in the primary outcome across all pooled studies (standardized mean difference, -0.06 [95% CI, -0.34 to 0.22]). Both AA and MO rotator cuff repair provide large clinical benefits, with few adverse events. There is strong evidence of equivalent clinical improvements. NCT00128076.


[Transapical aortic valve replacement: a 5-years experience].
Transcatheter aortic valve replacement (TAVR) by transapical approach is accepted for severe aortic stenosis in patients with high risk for conventional surgical therapy. Herein is reported the initial clinical results of this technique in a reference center We conducted a longitudinal prospective single center study including 54 consecutive patients (mean age 79 ± 7.5 years, 59% male) who underwent, between November 2008 and October 2013, TAVR with Edwards Sapien valves throught transapical approach. The etiology was native aortic stenosis in 83% (mean gradient = 49 ± 18.3 mmHg and area = 0,7 cm2), 11% aortic disease and 3 patients had degenerated biological valvular prostheses, being 65% in class III/IV NYHA. The major comorbidities were coronary heart disease in 56% (status post-coronary surgery 37%), diabetes (37%), peripheral artery disease (31%) and chronic renal failure (24%). The logistic EuroSCORE was 19.8 ± 11.2 and EuroSCORE II 5.5 ± 3.5%, with STS mortality score 5.1 ± 3.7 and 23.7 ± 7.6 STS morbidity. Analysis following the VARC-2 criteria (Valve Academic Research Consortium), showed 30-day mortality of 5.6%; peri-procedural myocardial infarction 7.4%; disabling cerebral vascular accident 1.9%; severe haemorrhage 14.8%; major vascular complications 5.6%; pacemaker implantation 11%. Unplanned extracorporeal circulation was used in 5 cases and prosthetic dysfunction occurred in 4 patients (shift valve in 2 cases). The median hospital stay was 8.0 days, with re-hospitalization in 12.2% of cases. The composite VARC-2 endpoints were: device success = 90.7%; early safety at 30 days = 75.9% and clinical efficacy after 30 days= 83.7%. The transapical approach was found as an effective therapy for patients at high risk for conventional surgery.


Meta-analysis on anticoagulation and prevention of thrombosis and mortality among patients with lung cancer.
Venous thromboembolism (Wickham et al., 2012 [1]) is a leading cause of morbidity and mortality among patients with cancer; however, primary thromboprophylaxis is not routinely recommended. We performed a systematic review and meta-analysis of randomized control trials (RCTs) to measure the impact of primary VTE prevention and its effect on mortality among patients with lung cancer. With assistance from a master librarian, we searched Ovid, Scopus, DARE, CINAHL, MEDLINE, EMBASE, EBM reviews-Cochrane database of systematic reviews, EBM reviews-ACP journal, and EBM Reviews-Databases for relevant studies following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included articles addressing the role of anticoagulation in patients with lung cancer for primary VTE prevention for outpatients. The clinical outcomes were VTE occurrence, all-cause mortality, major and clinically relevant non-major bleeding. The results are presented as odds ratio (OR) and data were analyzed using R and R META package (Version 0.8-2, Author: Guido Schwarzer). Eleven studies with 5107 patients were included for the final analysis. We found 50% lower VTE occurrence in the prophylaxis group with low molecular weight heparin (LMWH) (OR: 0.50; 95% Confidence Interval (CI): 0.38-0.66; I2: 0%) without an increased bleeding risk (OR: 2.03; 95% CI: 0.78-5.25; I2: 71.1%). We found a mortality benefit when we grouped all VTE prevention modalities [LMWH, Warfarin, unfractionated heparin (UFH)] (OR: 0.75; 95% CI: 0.58-0.96; I2: 18.4%), but no significant difference when LMWH (OR: 0.74; 95% CI: 0.49-1.11; I2: 56.9%) and warfarin were analyzed individually (OR: 0.75; 95% CI: 0.47-1.21; I2: 0%). We found higher odds of bleeding combining all treatment modalities (OR: 3.06; 95% CI: 1.64-5.72; I2: 64.4%) with the greatest occurrence in the warfarin group (OR: 5.42; 95% CI: 3.48-8.45; I2: 45.7%). Primary VTE prophylaxis with LMWH reduces the occurrence of VTE among ambulatory patients with lung cancer, without apparent increase in bleeding risk. There is a measurable mortality benefit of anticoagulation strategies that remains elusive when the analysis is restricted to a single agent.


Respiratory syncytial virus: heterogeneity of subgroup B strains.
In order to investigate further possible structural differences among the two subgroups of respiratory syncytial virus (RSV), we analysed the antigenic characteristics and size of structural proteins of 20 subgroup A and 43 subgroup B strains by their reactions with monoclonal antibodies (MAbs) directed against the proteins of RSV using immunofluorescence, ELISA and radioimmunoprecipitation assays. The latter test also enabled determination of the size of different structural components. The 37 MAbs employed were generated by immunization with both subgroup A and B strains. They represented specificities for distinct epitopes on five different structural proteins. The subgroup A strains proved to be relatively uniform. The fusion (F) protein, nucleoprotein (NP) and matrix (M) proteins of all strains tested had the same Mr and all except one strain had a phosphoprotein (P protein) of the same Mr. The F and P proteins were lower in Mr in B strains compared to A strains, which confirmed previous findings. The Mr of the large surface glycoprotein (G protein) of subgroup A strains varied slightly, probably on the basis of differing glycosylation. By contrast, the subgroup B strains exhibited substantial variation in the Mr of the G and also the P proteins and in reactivity with MAbs directed against the G and F proteins. Three size classes of the P protein were identified in B strains: 33K to 34K, 32K to 33K, and 31K to 32K. Twenty-seven subgroup B strains failed to react with four anti-G MAbs representing a single epitope, G2; the remaining 16 strains reacted with these MAbs. We designated these two sets of variants of B strains B1, which lacked the epitope, and B2, which had the epitope. The B1 strains also varied in the size of the G and P proteins. In contrast, all B2 strains had large G proteins and all except two strains had relatively large P proteins (33K to 34K). All subgroup B1 and B2 strains exhibited the same sizes of NP, F and M proteins. We conclude that the subgroup B strains of RSV include two variants, B1 and B2, and that the major difference between them resides in the G and P proteins.


Fetal alcohol syndrome: the nurse practitioner perspective.
Fetal alcohol syndrome is the leading cause of mental retardation in the United States. The tragedy is that while FAS is irreversible, it is 100% preventable. FAS is caused by maternal consumption of alcohol during pregnancy. Alcohol is a teratogen and acts in different ways to produce physical and central nervous system malformations and defects in the developing embryo and fetus. FAS is characterized by a history of maternal alcohol ingestion, central nervous system dysfunction, growth deficiencies, and specific physical anomalies. Adolescents and adults with FAS have behavioral problems that differentiate them from other mentally disabled individuals. Nurse practitioners can have an impact on the prevalence of FAS by educating clients about FAS and its relationship to alcohol consumption. NPs need to carefully identify high-risk women and their partners before a pregnancy occurs and assist with interventions to stop active alcoholism or alcohol use during pregnancy. NPs have the capability to decrease the severity of alcohol's effects during pregnancy through education, counseling, and intervention. NPs have the skills to work with case-finding and early identification of infants and children who display signs and symptoms of FAS. With such case-finding, early identification, and prompt referral to the appropriate diagnostic and/or supportive community agencies, individuals with FAS can receive timely intervention to minimize the effects of FAS. Adults with behavioral problems can be assessed for FAS and referred for appropriate assistance as well. Finally, NPs can facilitate public awareness of FAS through educational efforts with individuals, families, and communities.


Thermomechanical Properties of Neutron Irradiated Al3Hf-Al Thermal Neutron Absorber Materials.
A thermal neutron absorber material composed of Al3Hf particles in an aluminum matrix is under development for the Advanced Test Reactor. This metal matrix composite was fabricated via hot pressing of high-purity aluminum and micrometer-size Al3Hf powders at volume fractions of 20.0, 28.4, and 36.5%. Room temperature tensile and hardness testing of unirradiated specimens revealed a linear relationship between volume fraction and strength, while the tensile data showed a strong decrease in elongation between the 20 and 36.5% volume fraction materials. Tensile tests conducted at 200 °C on unirradiated material revealed similar trends. Evaluations were then conducted on specimens irradiated at 66 to 75 °C to four dose levels ranging from approximately 1 to 4 dpa. Tensile properties exhibited the typical increase in strength and decrease in ductility with dose that are common for metallic materials irradiated at ≤0.4Tm. Hardness also increased with neutron dose. The difference in strength between the three different volume fraction materials was roughly constant as the dose increased. Nanoindentation measurements of Al3Hf particles in the 28.4 vol% material showed the expected trend of increased hardness with irradiation dose. Transmission electron microscopy revealed oxygen at the interface between the Al3Hf particles and aluminum matrix in the irradiated material. Scanning electron microscopy of the exterior surface of tensile tested specimens revealed that deformation of the material occurs via plastic deformation of the Al matrix, cracking of the Al3Hf particles, and to a lesser extent, tearing of the matrix away from the particles. The fracture surface of an irradiated 28.4 vol% specimen showed failure by brittle fracture in the particles and ductile tearing of the aluminum matrix with no loss of cohesion between the particles and matrix. The coefficient of thermal expansion decreased upon irradiation, with a maximum change of -6.3% for the annealed irradiated 36.5 vol% specimen.


Evaluation of the relative available energy of several dietary fiber preparations using breath hydrogen evolution in healthy humans.
A standardized simple, indirect method for assessing the relative energy of dietary fiber carbohydrates is not yet established. There is a need for a standardized in vivo assay. The objective of the present study was to evaluate the relative available energy (RAE) for 9 major dietary fiber materials (DFMs) based on fermentability from breath hydrogen excretion (BHE) in subjects. Fructooligosaccharide (FOS) was used as a reference. The study was conducted using a within-subject, repeated measures design and approved by the Ethical Committee of University of Nagasaki. After DFM ingestion, end-expiratory gas (750-mL) was collected at 1-h intervals for 8 h, as well as at 2-h intervals between 8 h and 14 h, and 30 min after waking up and 24 h after DFM ingestion. Breath hydrogen concentration was assessed with a gas chromatograph. The RAE of DFMs tested was evaluated based on the area under the curve (AUC) of BHE of FOS. Based on the ratio of AUC for 8 h, the RAE of polydextrose, partially hydrolysed guar gum, resistant maltodextrin and partially hydrolysed alginate was 1 kcal/g, and that of glucomannan, heat-moisture treatment and high-amylose cornstarch and cellulose was 0 kcal/g, while the RAE of all tested DEMs including cellulose and glucomannan was 1 kcal/g in the calculation based on AUCs for 14 h and 24 h in subjects. We suggest that a breath hydrogen collection period of 14 h or more could be used to measure RAE for a range of fiber preparations in vivo.


The Ehlers-Danlos syndrome and colonic perforation. Report of a case and physiologic assessment of underlying motility disorder.
The Ehlers-Danlos syndrome is a genetically determined disorder of connective tissue which is generally known for its features of fragile, hyperextensible skin, hypermobile joints, and tissue fragility. Less commonly, colorectal complications can occur, including bleeding, prolapse, and diverticulitis. A rare case of colonic perforation associated with Ehlers-Danlos syndrome is presented. Additionally, in vitro electromyographic studies of the colonic tissue were performed which suggested a possible link between abnormal myogenic activity and the colonic perforations. The authors recommend that treatment be either a permanent colostomy or a subtotal colectomy with anastomosis to the rectum for similar cases.


Association Between Intraoperative Landiolol Use and In-Hospital Mortality After Coronary Artery Bypass Grafting: A Nationwide Observational Study in Japan.
Ischemic heart disease is a leading cause of death worldwide, and coronary artery bypass grafting (CABG) is a major treatment. Landiolol is an ultra-short-acting beta-antagonist known to prevent postoperative atrial fibrillation. However, the effectiveness of intraoperative landiolol on mortality remains unknown. This study aimed to evaluate the association between intraoperative landiolol use and the in-hospital mortality in patients undergoing CABG. To conduct this retrospective cohort study, we used data from the Japanese Diagnosis Procedure Combination inpatient database. All patients who underwent CABG during hospitalization between July 1, 2010, and March 31, 2020, were included. Patients who received intraoperative landiolol were defined as the landiolol group, whereas the other patients were defined as the control group. The primary outcome was in-hospital mortality. Propensity score matching was used to compare the landiolol and control groups. In total, 118,506 patients were eligible for this study, including 25,219 (21%) in the landiolol group and 93,287 (79%) in the control group. One-to-one propensity score matching created 24,893 pairs. After propensity score matching, the in-hospital mortality was significantly lower in the landiolol group than that in the control group (3.7% vs 4.3%; odds ratio 0.85; 95% confidence interval 0.78 to 0.94; P = .010). Intraoperative landiolol use was associated with decreased in-hospital mortality in patients undergoing CABG. Further randomized controlled trials are required to confirm these findings.


Characterization of triacylglycerol hydrolase activities in isolated myocardial cells from rat heart.
Triacylglycerol (TG) hydrolase activities were characterized in myocytes isolated from rat hearts. Acid hydrolase activity with a pH optimum of 5 could be measured in myocyte homogenates, and the subcellular distribution suggested that this activity originated in lysosomes. Lipoprotein lipase (LPL) was also present in myocyte homogenates, as evidenced by TG hydrolase activity that was stimulated by serum and apolipoprotein CII, and inhibited by apolipoprotein CIII2, high ionic strength (NaCl and MgCl2, I = 1 M) and antibodies to LPL. Serum-independent neutral (pH 7.5) TG hydrolase activity was less sensitive to inhibition by 1 M-NaCl, by antibodies to LPL and by preincubation at 40 degrees C than was serum-stimulated hydrolase activity. Furthermore, there were modest but significant differences in the subcellular distribution of the serum-independent and serum-stimulated hydrolase activities. Hydrolase activities in myocyte homogenates could be solubilized by 7.2 mM-deoxycholate. Acid hydrolase activity was recovered in the unbound fraction after heparin-Sepharose chromatography, whereas LPL was bound to the affinity column and was eluted by 0.9-1.2 M-NaCl. Approximately one-third of the serum-independent TG hydrolase activity was not bound to the heparin-Sepharose affinity column. This unbound TG hydrolase activity had a pH optimum of 7 and was stimulated by 50 mM-MgCl2, but not by serum and was resistant to inhibition by high ionic strength (1 M-NaCl), to preincubation at 40 degrees C for 2 h, and by antibodies to LPL. It is concluded that, in addition to an acid lysosomal TG hydrolase and LPL, myocytes from rat heart contain a serum-independent TG hydrolase with unique characteristics.


Cardiolipin-Dependent Mitophagy Guides Outcome after Traumatic Brain Injury.
Mitochondrial energy production is essential for normal brain function. Traumatic brain injury (TBI) increases brain energy demands, results in the activation of mitochondrial respiration, associated with enhanced generation of reactive oxygen species. This chain of events triggers neuronal apoptosis via oxidation of a mitochondria-specific phospholipid, cardiolipin (CL). One pathway through which cells can avoid apoptosis is via elimination of damaged mitochondria by mitophagy. Previously, we showed that externalization of CL to the mitochondrial surface acts as an elimination signal in cells. Whether CL-mediated mitophagy occurs in vivo or its significance in the disease processes are not known. In this study, we showed that TBI leads to increased mitophagy in the human brain, which was also detected using TBI models in male rats. Knockdown of CL synthase, responsible for de novo synthesis of CL, or phospholipid scramblase-3, responsible for CL translocation to the outer mitochondrial membrane, significantly decreased TBI-induced mitophagy. Inhibition of mitochondrial clearance by 3-methyladenine, mdivi-1, or phospholipid scramblase-3 knockdown after TBI led to a worse outcome, suggesting that mitophagy is beneficial. Together, our findings indicate that TBI-induced mitophagy is an endogenous neuroprotective process that is directed by CL, which marks damaged mitochondria for elimination, thereby limiting neuronal death and behavioral deficits.SIGNIFICANCE STATEMENT Traumatic brain injury (TBI) increases energy demands leading to activation of mitochondrial respiration associated with enhanced generation of reactive oxygen species and resultant damage to mitochondria. We demonstrate that the complete elimination of irreparably damaged organelles via mitophagy is activated as an early response to TBI. This response includes translocation of mitochondria phospholipid cardiolipin from the inner membrane to the outer membrane where externalized cardiolipin mediates targeted protein light chain 3-mediated autophagy of damaged mitochondria. Our data on targeting phospholipid scramblase and cardiolipin synthase in genetically manipulated cells and animals strongly support the essential role of cardiolipin externalization mechanisms in the endogenous reparative plasticity of injured brain cells. Furthermore, successful execution and completion of mitophagy is beneficial in the context of preservation of cognitive functions after TBI.


The contribution of the prefrontal cortex to relevancy-based gating of visual and tactile stimuli.
Patients with lesions of the prefrontal cortex (PFC) show increased distractibility and impairments in inhibiting cortical responses to irrelevant stimuli. This study was designed to test the role of the PFC in the early modality-specific modulation of event-related potentials (ERPs) generated during a sensory selection task. The task required participants to make a scaled motor response to the amplitudes of visual and tactile stimuli presented individually or concurrently. Task relevance was manipulated and continuous theta burst stimulation (cTBS) was used to transiently inhibit PFC activity to test the contribution of the PFC to modulation of sensory gating. Electroencephalography (EEG) was collected from participants both before and after cTBS was applied. The somatosensory-evoked N70 ERP was shown to be modulated by task relevance before but not after cTBS was applied to the PFC, and downregulating PFC activity through the use of cTBS abolished any relevancy differences in N70 amplitude. In conclusion, this study demonstrated that early modality-specific changes in cortical somatosensory processing are modulated by attention, and that this effect is subserved by prefrontal cortical activity.