Less Is More - Estimation of the Number of Strides Required to Assess Gait Variability in Spatially Confined Settings.
Background: Gait variability is an established marker of gait function that can be assessed using sensor-based approaches. In clinical settings, spatial constraints and patient condition impede the execution of longer distance walks for the recording of gait parameters. Turning paradigms are often used to overcome these constraints and commercial gait analysis systems algorithmically exclude turns for gait parameters calculations. We investigated the effect of turns in sensor-based assessment of gait variability. Methods: Continuous recordings from 31 patients with movement disorders (ataxia, essential tremor and Parkinson's disease) and 162 healthy elderly (HE) performing level walks including 180° turns were obtained using an inertial sensor system. Accuracy of the manufacturer's algorithm of turn-detection was verified by plotting stride time series. Strides before and after turn events were extracted and compared to respective average of all strides. Coefficient of variation (CoV) of stride length and stride time was calculated for entire set of strides, segments between turns and as cumulative values. Their variance and congruency was used to estimate the number of strides required to reliably assess the magnitude of stride variability. Results: Non-detection of turns in 5.8% of HE lead to falsely increased CoV for these individuals. Even after exclusion of these, strides before/after turns tended to be spatially shorter and temporally longer in all groups, contributing to an increase of CoV at group level and widening of confidence margins with increasing numbers of strides. This could be attenuated by a more generous turn excision as an alternative approach. Correlation analyses revealed excellent consistency for CoVs after at most 20 strides in all groups. Respective stride counts were even lower in patients using a more generous turn excision. Conclusion: Including turns to increase continuous walking distance in spatially confined settings does not necessarily improve the validity and reliability of gait variability measures. Specifically with gait pathology, perturbations of stride characteristics before/after algorithmically excised turns were observed that may increase gait variability with this paradigm. We conclude that shorter distance walks of around 15 strides suffice for reliable and valid recordings of gait variability in the groups studied here.


Rate-Dependent Morphology of Li2O2 Growth in Li-O2 Batteries.
Compact solid discharge products enable energy storage devices with high gravimetric and volumetric energy densities, but solid deposits on active surfaces can disturb charge transport and induce mechanical stress. In this Letter, we develop a nanoscale continuum model for the growth of Li2O2 crystals in lithium-oxygen batteries with organic electrolytes, based on a theory of electrochemical nonequilibrium thermodynamics originally applied to Li-ion batteries. As in the case of lithium insertion in phase-separating LiFePO4 nanoparticles, the theory predicts a transition from complex to uniform morphologies of Li2O2 with increasing current. Discrete particle growth at low discharge rates becomes suppressed at high rates, resulting in a film of electronically insulating Li2O2 that limits cell performance. We predict that the transition between these surface growth modes occurs at current densities close to the exchange current density of the cathode reaction, consistent with experimental observations.


What are we capable of? The motivations of perpetrators in South Africa during the Apartheid era.
This article attempts to explain the motivations of perpetrators who committed violent acts in South Africa during the apartheid era. The relevant psychosocial literature is reviewed and the implicit and explicit explanations given during the amnesty hearings of the Truth and Reconciliation Committee by perpetrators working for the state security forces are analysed. The mental health of the South African society during this period is considered, as is the role of the former white South African government and its authorities in shaping the climate for a violent struggle involving all groups. The issues of individual versus social and state culpability, accountability, justice and reconciliation are explored and their implications for the future prevention of reoccurrences are assessed. The aim of the article is to prompt readers to ask the question: what are we capable of?


Primary care physicians and elder abuse: current attitudes and practices.
while estimates suggest that between 1.4% and 5.4% of older adults experience abuse, only 1 of 14 cases of elder abuse or neglect is ever reported to authorities. It is critical for clinicians to be aware of elder abuse in order to improve primary care. to understand Michigan primary care physicians' knowledge of and reporting practices for elder abuse, including the type of elder abuse education they received, the nature of their clinical practice, and the barriers that prevent them from reporting elder abuse. a 17-item survey was mailed to 855 primary care physicians in Michigan in 2 waves between October 2007 and December 2007. Of the 855 surveys mailed, 222 were returned for a response rate of 26%. The majority of physicians (131 [67%] of 197 physicians) believed that their training about elder abuse was not very adequate or not adequate at all. Physicians with fewer than 10 hours of training were more likely to rate their training as not adequate when compared to those who had more than 10 hours of clinical training (χ(2)=64.340, P<.001). Whether abuse was reported was highly correlated with whether it was suspected (χ(2)=26.195, P<.001). Those physicians who reported receiving formal training on the topic of elder abuse in residency programs and those who reported participating in CME activities while in practice were less likely to identify not recognizing abuse at time of patient visits as a barrier to reporting. recognizing the subtle signs of elder abuse continues to be a barrier for physicians who treat older adult patients. However, education may improve primary care physicians' ability to detect and recognize elder abuse.


Ferrocenes as new anticancer drug candidates: Determination of the mechanism of action.
Chemotherapy plays an essential role in the management of cancer worldwide. However, it is a non-specific treatment limited by major drawbacks, thus identification and testing of new promising molecular structures representing potential drug candidates are urgently needed. In this work, ferrocene complexes as potential antitumor drugs that display cytotoxicity in low micromolar concentrations against ovarian cancer cells A2780 and SK-OV-3 were investigated to identify their mode of action. Their mechanism of cellular accumulation was studied using differential pulse voltammetry and inductively coupled plasma - mass spectrometry. Their mode of cell death induction was determined by changes in the mitochondrial membrane potential, production of reactive oxygen species and by Annexin V staining. Transferrin receptors were identified as key mediators of intracellular accumulation of ferrocenes and the extent of cellular uptake reflected the anticancer activity of individual compounds. Functional analysis revealed activation of intrinsic apoptosis as a dominant mechanism leading to regulated cell death induced in ovarian cancer cells by ferrocenes. Ferrocenes represent a group of promising sandwich organometallic complexes exerting cytotoxic activity. We suggest their application not only as standalone chemotherapeutics but also as modifying substituents of known drugs to improve their antitumor effects.


Factors associated with self-concept: adolescents with intellectual and development disabilities share their perspectives.
How one perceives the self is critical to long-term development. The purpose of this study was to explore the self-perceptions of adolescents with intellectual and developmental disabilities. Participants included 51 adolescents with intellectual and developmental disabilities, their parents (n = 50), and teachers (n = 12). A mixed-methods design was used. Qualitative interviews revealed that although 55% of participants self-identified as having a disability, there was a lack of constructive or affirmative language used to describe disability. Overall, adolescents' understanding of disability appeared to be grounded in a deficit model. Quantitative analyses were used to explore demographic variables, adolescent' perception of parent support, and self-determination as possible predictors of global self-worth and social acceptance. Results indicate that family income and parent support are particularly salient for this population.


A componential emotion approach for the assessment of emotional awareness in youth.
The Levels of Emotional Awareness Scale for Children (LEAS-C) is a performance-based instrument that assesses emotional awareness in the structure of written responses to a set of real-life scenarios. While it is theoretically expected that emotional awareness develops with age, virtually no age differences have been established with the LEAS-C. The present study investigated whether an adaptation of the instructions and scoring procedure on the basis of the componential emotion approach could improve the validity of the LEAS-C and reveal the theoretically expected age differences. An adapted LEAS-C was administered to a sample of 574 children and adolescents and scored with the original and a new componential scoring procedure. An acceptable reliability for the original and a good reliability and a high interrater reliability for the componential scoring procedure were observed. Multigroup confirmatory factor analyses showed measurement invariance of factor loadings and intercepts across children (8 to 12 years) and adolescents (13 to 16 years) for all tested models, for both scoring procedures. A one-factor model fitted well for the total scores and self and other scores for both scoring procedures. The pattern of relationships with alexithymia, emotional intelligence, intelligence, personality, and social and emotional impairment as well as gender differences were comparable with prior research. Furthermore, the expected relationship with age was found, with stronger correlations for the componential than the original scoring procedure. In conclusion, analyses of the reliability, internal structure, and nomological network supported the adaptations of the LEAS-C on the basis of the componential emotion approach. (PsycINFO Database Record


VH gene replacement in thymocytes.
The quasi-monoclonal (QM) mouse has a functionally rearranged H chain gene inserted into its natural position in the IgH locus. In this position, the H chain gene is subject to many of the same activities as normally arranged H chain genes, including somatic hypermutation, V(H) gene replacement, and class switch recombination. Here, we have used this mouse strain to determine some of the rules that govern the V(D)J recombination activity of the IgH locus in thymus. We focused on the requirements for V(H) gene replacement. In normal mice, thymic DJ(H) rearrangements are common, but VDJ(H) rearrangements are not. We found intermediate products of V(H) replacement in double-positive CD4(+)CD8(+) cells of the QM thymus, demonstrating that the inserted V(H) gene was accessible and ruling out the possibility that a V(H) gene per se cannot be rearranged in the thymus. We found transcripts from the knocked-in H chain gene of QM, but no mu H chain protein was detectable in thymocytes. Cloning and sequencing of these transcripts revealed that some had been generated by V(H) gene replacement. Corresponding signal joints could also be identified. These results suggest that neither a B cell-specific signal nor an Ig protein are necessary to activate V(H)-to-VDJ(H) joining in thymocytes. Possible mechanisms remaining to account for overcoming the barrier to V(H) joining in thymocytes include the insertion of a transcriptionally active gene segment and/or the inactivation of a silencer.


Subsequent malignancies in children and adolescents after treatment for Hodgkin's disease.
We assessed the cumulative risk of malignancies following treatment for Hodgkin's disease in childhood and adolescence and investigated related patient and treatment characteristics. Medical records of 499 Hodgkin's disease patients treated between 1962 and 1993 were reviewed. There were 385 adolescents (> or = 10 years of age at diagnosis) and 114 preadolescents (< 10 years). Most patients (n = 346) were treated with radiation plus multiagent chemotherapy, while 30 received only chemotherapy and 123 only radiation therapy. Radiation doses ranged from 20 to 42 Gy. At a median follow-up duration of 9 years (range, 0.1 to 27.4), 25 patients have had second malignancies: 19 solid tumors, four acute nonlymphoblastic leukemias (ANLLs), 1 non-Hodgkin's lymphoma (NHL), and one chronic myeloid leukemia (CML). Three patients have had a third malignancy. The estimated cumulative risk of second malignancies increased from 1.5% at 5 years to 7.7% at 15 years. All but two of the patients with second malignancies were > or = 10 years of age at initial diagnosis, which reflects the higher risk among patients treated for Hodgkin's disease as adolescents (P = .01). Second malignancies were more common among female patients (P = .0002), even when those breast cancer were excluded (P = .007), and in those treated for recurrent Hodgkin's disease (P = .02). Patients with ANLL/NHL were older at diagnosis of Hodgkin's disease than those with solid tumors, (median age, 18.3 v 13.8 years; P = .04). There was no difference between groups treated with radiation therapy alone, chemotherapy alone, or radiation plus multiagent chemotherapy. Adolescents treated for Hodgkin's disease are at greater at risk of second malignancies than younger patients. Overall, adolescent females treated for recurrent Hodgkin's disease appear to be at greatest risk, while preadolescents appear to be protected from this late complication.


Neopterin production and tryptophan degradation in acute Lyme neuroborreliosis versus late Lyme encephalopathy.
Fourteen patients with Borrelia burgdorferi infection were investigated for possible abnormalities of tryptophan and neopterin metabolism. Four patients (2 were investigated before therapy, 2 when therapy had been already started) had acute Lyme neuroborreliosis, and 10 patients were investigated months to years after an acute infection. Increased concentrations of neopterin and of the tryptophan-degradation product, L-kynurenine, were detected in the cerebrospinal fluid of patients with acute Lyme neuroborreliosis; one patient presented with subnormal tryptophan. Similar but less marked changes were seen in the treated patients and in some of the patients with Lyme encephalopathy. No such abnormalities were seen in the serum of the patients. The data indicate a role of the immune system and particularly of endogenously formed cytokines, like interferon-gamma and tumour necrosis factor-alpha, effecting tryptophan and neopterin metabolism in patients with acute Lyme neuroborreliosis.


Structural basis of malodour precursor transport in the human axilla.
Mammals produce volatile odours that convey different types of societal information. In Homo sapiens, this is now recognised as body odour, a key chemical component of which is the sulphurous thioalcohol, 3-methyl-3-sulfanylhexan-1-ol (3M3SH). Volatile 3M3SH is produced in the underarm as a result of specific microbial activity, which act on the odourless dipeptide-containing malodour precursor molecule, S-Cys-Gly-3M3SH, secreted in the axilla (underarm) during colonisation. The mechanism by which these bacteria recognise S-Cys-Gly-3M3SH and produce body odour is still poorly understood. Here we report the structural and biochemical basis of bacterial transport of S-Cys-Gly-3M3SH by Staphylococcus hominis, which is converted to the sulphurous thioalcohol component 3M3SH in the bacterial cytoplasm, before being released into the environment. Knowledge of the molecular basis of precursor transport, essential for body odour formation, provides a novel opportunity to design specific inhibitors of malodour production in humans.


A realist review of community engagement with health research.
Introduction: Community engagement is increasingly recognized as a critical aspect of global health. Recent years have seen an expansion of community engagement activities linked to health research, but debates and inconsistencies remain about the aims of different types of engagement, mechanisms underpinning their implementation and impact, and influential contextual factors. Greater commitment to and consistency around community engagement by health research programs, implementers and funders requires a more coherent evidence base. This realist review is designed to improve our understanding of how and why community engagement contributes to intended and unintended outcomes (including research and ethical outcomes) in different contexts. Given the breadth and diversity of the literature on community engagement in health research, the review will initially focus on malaria research in low- and middle-income countries (LMICs) and draw on wider global health literature where needed. Methods and analysis: Community engagement in practice is often a complex set of interventions. We will conduct a realist review - a theory driven approach to evidence synthesis - to provide explanations for how and why community engagement with health research produces the pattern of outcomes observed across different contexts of application. We will consolidate evidence from a range of documents, including qualitative, quantitative and mixed method studies. The review will follow several stages: devising an initial programme theory, searching evidence, selecting appropriate documents, extracting data, synthesizing and refining the programme theory, and reiteration of these steps as needed. Ethics and dissemination: A formal ethics review is not required for this literature review. Findings will be disseminated in a peer reviewed journal, through national and international conferences, and through a set of short briefings tailored for audiences with an interest in community engagement. Outputs and presentations will be informed by and feed into our network of community engagement experts. PROSPERO registration number: CRD42019125687.


Deconstructing Haptic Feedback Information in Robot-Assisted Needle Insertion in Soft Tissues.
This paper evaluates the role and effectiveness of different types of haptic feedback in presenting relevant feedback information during needle insertion in soft tissues through a remotely operated robot. We carried out three experiments with human subjects to analyze the effect of grounded kinesthetic feedback, cutaneous vibrotactile feedback, and cutaneous pressure feedback for rendering the elastic and the viscous force components of a simplified needle-tissue interaction model in a simulated environment. Results showed that providing the two pieces of feedback information through different channels, i.e., kinesthetic and cutaneous, led to the best performance, yielding an improvement in detecting a different tissue layer with respect to providing both information through the same commercial grounded kinesthetic interface. Moreover, results indicate that cutaneous pressure feedback is more suited for rendering the elastic component of the interaction with respect to vibrotactile cutaneous sensations. Finally, results suggest that rendering this elastic component where the user holds the input interface is not so important, confirming that delocalized cutaneous sensations can be an effective solution.


Metagenomic Approaches to Assess Bacteriophages in Various Environmental Niches.
Bacteriophages are ubiquitous and numerous parasites of bacteria and play a critical evolutionary role in virtually every ecosystem, yet our understanding of the extent of the diversity and role of phages remains inadequate for many ecological niches, particularly in cases in which the host is unculturable. During the past 15 years, the emergence of the field of viral metagenomics has drastically enhanced our ability to analyse the so-called viral 'dark matter' of the biosphere. Here, we review the evolution of viral metagenomic methodologies, as well as providing an overview of some of the most significant applications and findings in this field of research.


Meaningful gait speed improvement during the first 60 days poststroke: minimal clinically important difference.
When people with stroke recover gait speed, they report improved function and reduced disability. However, the minimal amount of change in gait speed that is clinically meaningful and associated with an important difference in function for people poststroke has not been determined. The purpose of this study was to determine the minimal clinically important difference (MCID) for comfortable gait speed (CGS) associated with an improvement in the modified Rankin Scale (mRS) score for people between 20 to 60 days poststroke. This was a prospective, longitudinal, cohort study. The participants in this study were 283 people with first-time stroke prospectively enrolled in the ongoing Locomotor Experience Applied Post Stroke (LEAPS) multi-site randomized clinical trial. Comfortable gait speed was measured and mRS scores were obtained at 20 and 60 days poststroke. Improvement of >or=1 on the mRS was used to detect meaningful change in disability level. Mean (SD) CGS was 0.18 (0.16) m/s at 20 days and 0.39 (0.22) m/s at 60 days poststroke. Among all participants, 47.3% experienced an improvement in disability level >or=1. The MCID was estimated as an improvement in CGS of 0.16 m/s anchored to the mRS. Because the mRS is not a gait-specific measure of disability, the estimated MCID for CGS was only 73.9% sensitive and 57.0% specific for detecting improvement in mRS scores. We estimate that the MCID for gait speed among patients with subacute stroke and severe gait speed impairments is 0.16 m/s. Patients with subacute stroke who increase gait speed >or=0.16 m/s are more likely to experience a meaningful improvement in disability level than those who do not. Clinicians can use this reference value to develop goals and interpret progress in patients with subacute stroke.


Pornography consumption and psychosomatic and depressive symptoms among Swedish adolescents: a longitudinal study.
The aims of this longitudinal study were to identify predictors for continued pornography consumption and to investigate pornography consumption in relation to psychosomatic and depressive symptoms among a group of adolescents in Sweden. A longitudinal study in classroom environment in 53 randomly selected senior high school classes in mid-Sweden in years 2011 and 2013. Out of 477 participating boys and 400 girls in 2011, 224 boys (47%) and 238 girls (60%) participated in 2013. Higher pornography consumption at baseline and being born outside Sweden predicted continued pornography consumption at follow-up (adjusted R2 = 0.689). Psychosomatic symptoms at follow-up were predicted by higher pornography consumption at baseline (adjusted R2 = 0.254), being a girl, living with separated parents, and attending a vocational high school program. By contrast, depressive symptoms at follow-up were predicted by less pornography consumption at baseline (adjusted R2 = 0.122) and being a girl. Pornography consumption may, for some individuals, be associated to mental health issues. Differences between teenage boys and girls and between adolescents with diverse ethnic backgrounds imply that counseling and discussion about pornography need to be adjusted and individualized.


Inhaled Long-acting Anticholinergics and Urinary Tract Infection in Individuals with COPD.
Inhaled, long-acting anticholinergic medication (LAA), commonly used for moderate-to-severe chronic obstructive pulmonary disease (COPD), has been shown to decrease COPD hospitalizations, emergency department visits, and acute exacerbations but has also been associated with urinary tract infection (UTI) in a prior meta-analysis. The objective of this study was to verify if there was an association between LAA and UTI in older individuals with COPD. A population-based, real-world cohort study using health administrative data from Ontario, Canada was conducted. Incidence of UTI was compared between older people with physician-diagnosed COPD, who were new users of inhaled long-acting anticholinergics and new users of inhaled corticosteroids-a reference medication used in similar clinical settings that has no known association with UTI. Propensity score matching was used to minimize the effects of confounding. An overall association between LAA and various measures of UTI in older individuals was not found. However, in a priori defined stratified analyses, men newly initiated on LAA were 75% more likely to develop a UTI than men newly started on an inhaled corticosteroid (hazard ratio 1.75; 95% confidence interval 1.05-2.92). No significant association was seen in women. In conclusion, older men with COPD newly started on LAA are at increased risk of UTI. Men considering an inhaled LAA should be informed of this risk and, if they decide to take it, be provided with appropriate monitoring.


Residual antimalarials in malaria patients from Tanzania--implications on drug efficacy assessment and spread of parasite resistance.
Repeated antimalarial treatment for febrile episodes and self-treatment are common in malaria-endemic areas. The intake of antimalarials prior to participating in an in vivo study may alter treatment outcome and affect the interpretation of both efficacy and safety outcomes. We report the findings from baseline plasma sampling of malaria patients prior to inclusion into an in vivo study in Tanzania and discuss the implications of residual concentrations of antimalarials in this setting. In an in vivo study conducted in a rural area of Tanzania in 2008, baseline plasma samples from patients reporting no antimalarial intake within the last 28 days were screened for the presence of 14 antimalarials (parent drugs or metabolites) using liquid chromatography-tandem mass spectrometry. Among the 148 patients enrolled, 110 (74.3%) had at least one antimalarial in their plasma: 80 (54.1%) had lumefantrine above the lower limit of calibration (LLC = 4 ng/mL), 7 (4.7%) desbutyl-lumefantrine (4 ng/mL), 77 (52.0%) sulfadoxine (0.5 ng/mL), 15 (10.1%) pyrimethamine (0.5 ng/mL), 16 (10.8%) quinine (2.5 ng/mL) and none chloroquine (2.5 ng/mL). The proportion of patients with detectable antimalarial drug levels prior to enrollment into the study is worrying. Indeed artemether-lumefantrine was supposed to be available only at government health facilities. Although sulfadoxine-pyrimethamine is only recommended for intermittent preventive treatment in pregnancy (IPTp), it was still widely used in public and private health facilities and sold in drug shops. Self-reporting of previous drug intake is unreliable and thus screening for the presence of antimalarial drug levels should be considered in future in vivo studies to allow for accurate assessment of treatment outcome. Furthermore, persisting sub-therapeutic drug levels of antimalarials in a population could promote the spread of drug resistance. The knowledge on drug pressure in a given population is important to monitor standard treatment policy implementation.


Limitation of the antibiotic-eluting bone graft substitute: An example of gentamycin-impregnated calcium sulfate.
Patients with inadequate volume of alveolar processes or bone defects commonly require graft substitutes in oral, maxillofacial or orthopedic surgery. Ridge augmentation and reconstruction of facial bony defects with bone graft materials achieve better outcomes in functional and aesthetic rehabilitation. The injectable calcium sulfate filler is used widely in intra-operative applications. Calcium sulfate bone filler has been shown to upregulate bone formation-related mRNA genes in vitro and improve osseointegration in vivo. In addition, the bone graft substitute can be used as a drug delivery system for antibiotics to treat or prevent infections based on the clinical experiences. However, the influences of antibiotics addition on the calcium sulfate are not fully understood. In this study, calcium sulfate impregnated with gentamycin in different weight ratios was characterized. The results showed that gentamycin prolonged the hydration process and extended initial/final setting times of calcium sulfate. The addition of gentamycin slowed the conversion from calcium sulfate hemihydrate to dihydrate and changed the crystalline phase and microstructure. Higher amounts of gentamycin added resulted in faster degradation and lower mechanical strength of calcium sulfate. This study reveals that the extended setting time, decreased compressive strength, and the accelerated degradation of the gentamycin-impregnated calcium sulfate bone graft substitutes should be considered during intra-operative applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 80-87, 2018.


A PMLRARA transgene results in a retinoid-deficient phenotype associated with enhanced susceptibility to skin tumorigenesis.
The construction of transgenic FVB/N mice targeting the PMLRARA fusion gene under the control of a human MRP8 promoter recapitulated the phenotype of acute promyelocytic leukemia but had the unexpected result of multiple squamous papillomas of the skin (Brown et al., PROC: Natl. Acad. Sci. USA, 94:2551-2556, 1997). In addition, transgenic MRP8-PMLRARA mice exhibited a skin phenotype characteristic of vitamin A deficiency. The severity of the skin phenotype and spontaneous papilloma development correlated with the level of transgene expression. Papilloma formation was preceded by follicular hyperplasia and the expression of epidermal differentiation markers in the follicular epithelium. Mutations in the Ha or Ki alleles of ras were not detected in papillomas that developed on transgenic skin, and papilloma formation was accentuated on the C57/Bl6 background, unlike the usual resistance of this strain to skin tumor induction. Analysis of liver extracts from transgenic mice indicated a deficiency in the production of retinoic acid. Furthermore, affected transgenic epidermis had reduced levels of retinoic acid receptoralpha (RARalpha) and retinoic X receptor (RXRalpha), and supplementation with exogenous retinoic acid prevented the skin phenotype. When transgenic keratinocytes were grafted to nude mice, the resulting integument was normal, and conversely, when transgenic bone marrow was grafted to normal mice, a skin phenotype did not develop. Together these results suggest that local interruption of PML and RARalpha signaling in the skin, together with a systemic retinoid deficiency, initiates a tumor induction pathway that is independent of ras activation.


Comparison of health care utilization of postnatal programs in Sweden.
To describe the utilization of health care services, based on number of outpatient visits and readmissions, by mothers and newborns following discharge postnatally after having received various types of maternity care. The design was a cohort of Swedish women giving birth at full term. All together, 773 women and 782 newborns were followed using questionnaires, registry data, and medical chart notes. The information served as a basis for analyzing utilization of health care services during the first 28 days post-delivery. Of the women, 15% sought medical care and 1.7% were readmitted, whereas 17% of the newborns received medical care and 2.9% were readmitted. At 6 months, about half were exclusively being breastfed. There was no difference in need to seek health care or breastfeeding outcome owing to type of maternity care. Mothers with newborns sought care relatively frequently but rarely needed to be readmitted after discharge from the maternity care. The risk of readmission during the first month after childbirth was not greater for mothers and children who received care through the family suite or early discharge programs.


The histones associated with condensed and extended chromatin of mouse liver.
Histones were extracted from isolated mouse liver nuclei, and from mouse liver condensed and extended chromatin. Mouse liver histones were found to be very similar to those of calf thymus in their solubility properties, relative electrophoretic mobilities, and molecular weights as determined on SDS-polyacrylamide gels. Quantitative analysis by high-resolution gel electrophoresis demonstrated a remarkable similarity between the histones of condensed chromatin and those of extended chromatin. However, minor differences were found. A unique subspecies was found only in condensed chromatin histone and the relative amounts of fractions F2A1 and F2A2 differed in the two types of chromatin. The ratio of the parental to the acetylated form of F2A1 was identical in the two chromatin samples. Since DNA extracted from the condensed chromatin fraction consisted of approximately 50% satellite DNA, the general similarities between the histones of condensed and extended chromatin make it likely that even this simple, highly repetitive DNA is complexed with a number of histone subfractions.


Storing Renewable Energy in the Hydrogen Cycle.
An energy economy based on renewable energy requires massive energy storage, approx. half of the annual energy consumption. Therefore, the production of a synthetic energy carrier, e.g. hydrogen, is necessary. The hydrogen cycle, i.e. production of hydrogen from water by renewable energy, storage and use of hydrogen in fuel cells, combustion engines or turbines is a closed cycle. Electrolysis splits water into hydrogen and oxygen and represents a mature technology in the power range up to 100 kW. However, the major technological challenge is to build electrolyzers in the power range of several MW producing high purity hydrogen with a high efficiency. After the production of hydrogen, large scale and safe hydrogen storage is required. Hydrogen is stored either as a molecule or as an atom in the case of hydrides. The maximum volumetric hydrogen density of a molecular hydrogen storage is limited to the density of liquid hydrogen. In a complex hydride the hydrogen density is limited to 20 mass% and 150 kg/m(3) which corresponds to twice the density of liquid hydrogen. Current research focuses on the investigation of new storage materials based on combinations of complex hydrides with amides and the understanding of the hydrogen sorption mechanism in order to better control the reaction for the hydrogen storage applications.


Management of postoperative pulmonary hypertension by inhaled nitric oxide in a newborn with congenital diaphragmatic hernia.
Postero-lateral congenital diaphragmatic hernia (CDH) is a life threatening anomaly characterized by diaphragmatic defect and intrathoracic herniation of abdominal viscera. In patients with CDH, the lungs are hypoplastic and persistent pulmonary hypertension develops in most cases. Although, inhaled nitric oxide (iNO) results in a reduction in pulmonary hypertension with improvement in oxygenation, its benefit in the patients with CDH remains controversial. In this report, the authors present successful management of postoperative pulmonary hypertension by iNO in a newborn with CDH.


Lung cancer among textile workers in the Prato area of Italy.
The association between lung cancer and occupational exposure in the textile industry was investigated in a population-based case-referent study conducted in the Prato area of the province of Florence (Italy) where there is a concentration of textile factories. A complete response to a postal questionnaire was obtained for 207 cases (85.1%) and 440 referents (76.1%). Those who had ever worked in the textile industry had an odds ratio (OR) of 1.45 [95% confidence interval (95% CI) 1.0-2.1]; when nine different textile job titles were considered, an increased OR was observed only for rag sorters (OR 2.2, 95% CI 1.3-3.8) and weavers (OR 1.7, 95% CI 1.1-2.7). Analysis by different "time windows" showed an OR of 3.0 (95% CI 1.6-5.8) for rag sorters at work in the 1950s and an OR of 2.8 (95% CI 1.5-5.0) for weavers at work in the 1970s. This result supports the suggestion of two different carcinogenic exposures in the Prato textile industry (asbestos and mineral oils).


Automatic Detection of Acromegaly From Facial Photographs Using Machine Learning Methods.
Automatic early detection of acromegaly is theoretically possible from facial photographs, which can lessen the prevalence and increase the cure probability. In this study, several popular machine learning algorithms were used to train a retrospective development dataset consisting of 527 acromegaly patients and 596 normal subjects. We firstly used OpenCV to detect the face bounding rectangle box, and then cropped and resized it to the same pixel dimensions. From the detected faces, locations of facial landmarks which were the potential clinical indicators were extracted. Frontalization was then adopted to synthesize frontal facing views to improve the performance. Several popular machine learning methods including LM, KNN, SVM, RT, CNN, and EM were used to automatically identify acromegaly from the detected facial photographs, extracted facial landmarks, and synthesized frontal faces. The trained models were evaluated using a separate dataset, of which half were diagnosed as acromegaly by growth hormone suppression test. The best result of our proposed methods showed a PPV of 96%, a NPV of 95%, a sensitivity of 96% and a specificity of 96%. Artificial intelligence can automatically early detect acromegaly with a high sensitivity and specificity.


Outcomes, Mortality, and Cost Burden of Acute Kidney Injury and Hepatorenal Syndrome in Patients with Cirrhosis.
Cirrhosis is associated with an increased risk of acute kidney injury (AKI) and hepatorenal syndrome (HRS). Healthcare utilization and cost burden of AKI and HRS in cirrhosis is unknown. We aimed to analyze the health care use and cost burden associated with AKI and HRS in patients with cirrhosis in the United States by using real-world claims data. We conducted a case-control study using the Truven Health MarketScan Commercial Claims databases from 2007-2017. A total of 34,398 patients with cirrhosis with or without AKI and 4,364 patients with cirrhosis with or without HRS were identified using International Classification of Diseases, Ninth or Tenth Revision, codes and matched 1:1 by sociodemographic characteristics and comorbidities using propensity scores. Total and service-specific were quantified for the 12-months following versus the 12-months before the first date of AKI or HRS diagnosis and over 12-months following a randomly selected date for cirrhosis controls to capture entire disease burdens. The AKI and HRS group had a higher number of comorbidities and were associated with higher rates of readmission and mortality. The AKI and HRS groups had a significantly higher prevalence of ascites, spontaneous bacterial peritonitis (SBP), encephalopathy, gastrointestinal bleeding, septic shock, pulmonary edema, and respiratory failure. Compared to patients with cirrhosis only, AKI was associated with higher number of claims per person (AKI vs. cirrhosis only, 60.30 vs. 47.09; p<0.0001) and total annual median health care costs (AKI vs. cirrhosis only, $46,150 vs. $26,340; p<0.0001). Compared to patients with cirrhosis only, the HRS cohort was associated with a higher number of claims per person (HRS vs. cirrhosis only, 44.96 vs. 43.50; p<0.0009) and total annual median health care costs (HRS vs. cirrhosis only, $34,912 vs. $23,354; p<0.0001). Inpatient costs were higher than the control cohort for AKI (AKI vs. cirrhosis only, $72,720 vs. $29,111; p<0.0001) and HRS (HRS vs. cirrhosis only, $ 98,246 vs. $27,503; p<0.0001). Compared to the control cohort, AKI and HRS had a higher rate of inpatient admission, mean number of inpatient admissions, and mean total length of stay. AKI and HRS are associated with higher health care utilization and cost burden compared to cirrhosis alone, highlighting the importance for improved screening and treatment modalities.


Upcoming Revolutionary Paths in Preclinical Modeling of Pancreatic Adenocarcinoma.
To date, PDAC remains the cancer having the worst prognosis with mortality rates constantly on the rise. Efficient cures are still absent, despite all attempts to understand the aggressive physiopathology underlying this disease. A major stumbling block is the outdated preclinical modeling strategies applied in assessing effectiveness of novel anticancer therapeutics. Current in vitro preclinical models have a low fidelity to mimic the exact architectural and functional complexity of PDAC tumor found in human set, due to the lack of major components such as immune system and tumor microenvironment with its associated chemical and mechanical signals. The existing PDAC preclinical platforms are still far from being reliable and trustworthy to guarantee the success of a drug in clinical trials. Therefore, there is an urgent demand to innovate novel in vitro preclinical models that mirrors with precision tumor-microenvironment interface, pressure of immune system, and molecular and morphological aspects of the PDAC normally experienced within the living organ. This review outlines the traditional preclinical models of PDAC namely 2D cell lines, genetically engineered mice, and xenografts, and describing the present famous approach of 3D organoids. We offer a detailed narration of the pros and cons of each model system. Finally, we suggest the incorporation of two off-center newly born techniques named 3D bio-printing and organs-on-chip and discuss the potentials of swine models and in silico tools, as powerful new tools able to transform PDAC preclinical modeling to a whole new level and open new gates in personalized medicine.


Proton spectroscopy of the thalamus in a homogeneous sample of patients with easy-to-control juvenile myoclonic epilepsy.
Juvenile myoclonic epilepsy (JME) is a subtype of genetically determined generalized epilepsy that does not present abnormalities on conventional magnetic resonance imaging. The aim of this study was to identify metabolic alterations in the thalamus in a clinically homogeneous sample of patients with easy-to-control JME, using short-echo time proton magnetic resonance spectroscopy (MRS). We performed single-voxel (2 cm × 2 cm × 2 cm), short-echo time (TE = 35 ms) proton MRS of the thalamus in 21 patients with JME and in 14 healthy age-matched controls. We quantified N-acetylaspartate (NAA), total NAA, creatine (Cr), choline, and myo-inositol (MI), as well as the sum of glutamate and glutamine signals, all scaled to internal water content, and we calculated metabolite ratios using Cr as a reference. Values of p < 0.05 were considered significant. The MI level and the MI/Cr ratio were significantly lower in the thalami of patients diagnosed with JME than in those of the controls. Other metabolites and their ratios did not differ significantly between the two groups. In our sample of 21 JME patients, we identified lower levels of MI in the thalamus. No significant abnormalities were observed in the concentrations or ratios of other metabolites.


Evidence for auto/paracrine actions of vitamin D in bone: 1alpha-hydroxylase expression and activity in human bone cells.
Vitamin D is an important regulator of mineral homeostasis and bone metabolism. 1Alpha-hydroxylation of 25-(OH)D3 to form the bioactive vitamin D hormone, 1alpha,25-(OH)2D3, is classically considered to take place in the kidney. However, 1alpha-hydroxylase has been reported at extrarenal sites. Whether bone is a 1alpha,25-(OH)2D3 synthesizing tissue is not univocal. The aim of this study was to investigate an autocrine/paracrine function for 1alpha,25-(OH)2D3 in bone. We show that 1alpha-hydroxylase is expressed in human osteoblasts, as well as the vitamin D binding protein receptors megalin and cubilin. Functional analyses demonstrate that after incubation with the 1alpha-hydroxylase substrate 25-(OH)D3, the osteoblasts can produce sufficient 1alpha,25-(OH)2D3 to modulate osteoblast activity, resulting in induced alkaline phosphatase (ALP) activity, osteocalcin (OC) and CYP24 mRNA expression, and mineralization. The classical renal regulators of 1alpha-hydroxylase, parathyroid hormone, and ambient calcium do not regulate 1alpha-hydroxylase in osteoblasts. In contrast, interleukin (IL)-1beta strongly induces 1alpha-hydroxylase. Besides the bone-forming cells, we demonstrate 1alpha-hydroxylase activity in the bone resorbing cells, the osteoclasts. This is strongly dependent on osteoclast inducer RANKL. This study showing expression, activity, and functionality of 1alpha-hydroxylase unequivocally demonstrates that vitamin D can act in an auto/paracrine manner in bone.


How reliable is internet-based self-reported identity, socio-demographic and obesity measures in European adults?
In e-health intervention studies, there are concerns about the reliability of internet-based, self-reported (SR) data and about the potential for identity fraud. This study introduced and tested a novel procedure for assessing the validity of internet-based, SR identity and validated anthropometric and demographic data via measurements performed face-to-face in a validation study (VS). Participants (n = 140) from seven European countries, participating in the Food4Me intervention study which aimed to test the efficacy of personalised nutrition approaches delivered via the internet, were invited to take part in the VS. Participants visited a research centre in each country within 2 weeks of providing SR data via the internet. Participants received detailed instructions on how to perform each measurement. Individual's identity was checked visually and by repeated collection and analysis of buccal cell DNA for 33 genetic variants. Validation of identity using genomic information showed perfect concordance between SR and VS. Similar results were found for demographic data (age and sex verification). We observed strong intra-class correlation coefficients between SR and VS for anthropometric data (height 0.990, weight 0.994 and BMI 0.983). However, internet-based SR weight was under-reported (Δ -0.70 kg [-3.6 to 2.1], p < 0.0001) and, therefore, BMI was lower for SR data (Δ -0.29 kg m(-2) [-1.5 to 1.0], p < 0.0001). BMI classification was correct in 93 % of cases. We demonstrate the utility of genotype information for detection of possible identity fraud in e-health studies and confirm the reliability of internet-based, SR anthropometric and demographic data collected in the Food4Me study. NCT01530139 ( http://clinicaltrials.gov/show/NCT01530139 ).


Polyene toxicity in renal medulla: injury mediated by transport activity.
Polyene antibiotics such as amphotericin and nystatin increase membrane permeability and thus increase the amount of oxygen consumed in active electrolyte transport. In isolated perfused rat kidneys, the polyenes produced extensive injury to the medullary thick ascending limb, a segment of the nephron with limited oxygen supply. This damage was prevented if reabsorptive transport was inhibited by ouabain. Cell death under these circumstances thus appears to be mediated by increased oxygen demand for transport activity.


Comparison of posterior fossa decompression with and without duraplasty for the surgical treatment of Chiari malformation Type I in pediatric patients: a meta-analysis.
Surgery for Chiari malformation Type I (CM-I) is one of the most common neurosurgical procedures performed in children, although there is clearly no consensus among practitioners about which surgical method is preferred. The objective of this meta-analysis was to compare the outcome of posterior fossa decompression with duraplasty (PFDD) and posterior fossa decompression without duraplasty (PFD) for the treatment of CM-I in children. The authors searched Medline-Ovid, The Cochrane Library, and the conference proceedings of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons (2000-2007) for studies meeting the following inclusion criteria: 1) surgical treatment of CM-I; 2) surgical techniques of PFD and PFDD being reported in a single cohort; and 3) patient age < 18 years. Five retrospective and 2 prospective cohort studies involving a total of 582 patients met the criteria for inclusion in the meta-analysis. Of the 582 patients, 316 were treated with PFDD and 266 were treated with PFD alone. Patient age ranged from 6 months to 18 years. Patients undergoing PFDD had a significantly lower reoperation rate (2.1 vs 12.6%, risk ratio [RR] 0.23, 95% confidence interval [CI] 0.08-0.69) and a higher rate of cerebrospinal fluid-related complications (18.5 vs 1.8%, RR 7.64, 95% CI 2.53-23.09) than those undergoing PFD. No significant differences in either clinical improvement (78.6 vs 64.6%, RR 1.23, 95% CI 0.95-1.59) or syringomyelia decrease (87.0 vs 56.3%, RR 1.43, 95% CI 0.91-2.25) were noted between PFDD and PFD. Posterior fossa decompression with duraplasty is associated with a lower risk of reoperation than PFD but a greater risk for cerebrospinal fluid-related complications. There was no significant difference between the 2 operative techniques with respect to clinical improvement or decrease in syringomyelia.


Targeted sequencing of SMO and AKT1 in anterior skull base meningiomas.
OBJECTIVE Meningiomas located in the skull base are surgically challenging. Recent genomic research has identified oncogenic SMO and AKT1 mutations in a small subset of meningiomas. METHODS The authors performed targeted sequencing in a large cohort of patients with anterior skull base meningiomas (n = 62) to better define the frequency of SMO and AKT1 mutations in these tumors. RESULTS The authors found SMO mutations in 7 of 62 (11%) and AKT1 mutations in 12 of 62 (19%) of their cohort. Of the 7 meningiomas with SMO mutations, 6 (86%) occurred in the olfactory groove. Meningiomas with an SMO mutation presented with significantly larger tumor volume (70.6 ± 36.3 cm3) compared with AKT1-mutated (18.2 ± 26.8 cm3) and wild-type (22.7 ± 23.9 cm3) meningiomas, respectively. CONCLUSIONS Combined, these data demonstrate clinically actionable mutations in 30% of anterior skull base meningiomas and suggest an association between SMO mutation status and tumor volume. Genotyping of SMO and AKT1 is likely to be high yield in anterior skull base meningiomas with available surgical tissue.


Is honey able to potentiate the antioxidant and cytotoxic properties of medicinal plants consumed as infusions for hepatoprotective effects?
Due to the enormous variety of phytochemicals present in plants, their extracts have been used for centuries in the treatment of innumerable diseases, being perceived as an invaluable source of medicines for humans. Furthermore, the combination of different plants was reported as inducing an improved effect (synergism) in comparison with the additive activity of the plants present in those mixtures. Nevertheless, information regarding the effects of plant infusions added with honey is still rather scarce. Accordingly, the aim of this study was to evaluate the interaction between chestnut honey, a natural product with well-reported beneficial properties, and three medicinal plants (either as a single plant or as combinations of two and three plants), with regard to their antioxidant activity and hepatotoxicity. Antioxidant activity was evaluated by comparing the results from four different assays; hepatotoxicity was assessed in two different cell lines. Results were compared by analysis of variance and linear discriminant analysis. The addition of honey to the infusions had a beneficial result in both cases, producing a synergistic effect in all samples, except β-carotene bleaching inhibition for artichoke + milk thistle + honey preparation and also preparations with lower hepatotoxicity, except in the case of artichoke + honey. Moreover, from the discriminant linear analysis output, it became obvious that the effect of honey addition overcame that resulting from using single plant or mixed plant based infusions. Also, the enhanced antioxidant activity of infusions containing honey was confirmed by lower hepatotoxicity.


Paediatric palliative care in the NICU: A new era of integration.
We are entering a new era of integration between neonatal medicine and paediatric palliative care, with increasing recognition that the role and skills of palliative care extend beyond care of only the terminally ill infant. This paper addresses the principles of paediatric palliative care and how they apply in the NICU, considers who provides palliative care in this setting and outlines the key components of care. We consider how the international standards of palliative care pertain to neonatal medicine and how a fully integrated approach to care may be realised across these two disciplines. Palliative care is so much more than end-of-life care, offering a proactive and holistic approach which addresses the physical, emotional, spiritual and social needs of the infant and family. This is a truly interdisciplinary endeavour, relying on a harmonisation of the skills from both the neonatal and palliative care teams to deliver high-quality coordinated care.


AIDS and state developmental disability agencies: a national survey.
A survey of state developmental disability agencies was undertaken in October 1987 regarding AIDS policy development, education, and training and service provision. Of 44 states responding to the 27-item questionnaire, only 21 had formal AIDS policies. Policies varied considerably from state to state. Twenty-five of the responding states include information on AIDS in their staff training curriculum, with such training more likely to be provided to institutional staff than to community-based staff. Only 10 states reported AIDS prevention to be part of their client training programs, with training more likely to be found in institutional settings. Eleven states reported HIV positive cases, with such cases found more often in institutions than in community settings. Several states reported some type of segregation of HIV positive individuals. Policies, educational programming, and services to meet the special needs of persons with developmental disabilities are called for.


Molecular Dynamics Simulations of Proteins: Can the Explicit Water Model Be Varied?
In molecular mechanics simulations of biological systems, the solvation water is typically represented by a default water model which is an integral part of the force field. Indeed, protein nonbonding parameters are chosen in order to obtain a balance between water-water and protein-water interactions and hence a reliable description of protein solvation. However, less attention has been paid to the question of whether the water model provides a reliable description of the water properties under the chosen simulation conditions, for which more accurate water models often exist. Here we consider the case of the CHARMM protein force field, which was parametrized for use with a modified TIP3P model. Using quantum mechanical and molecular mechanical calculations, we investigate whether the CHARMM force field can be used with other water models: TIP4P and TIP5P. Solvation properties of N-methylacetamide (NMA), other small solute molecules, and a small protein are examined. The results indicate differences in binding energies and minimum energy geometries, especially for TIP5P, but the overall description of solvation is found to be similar for all models tested. The results provide an indication that molecular mechanics simulations with the CHARMM force field can be performed with water models other than TIP3P, thus enabling an improved description of the solvent water properties.


Managing marine disease emergencies in an era of rapid change.
Infectious marine diseases can decimate populations and are increasing among some taxa due to global change and our increasing reliance on marine environments. Marine diseases become emergencies when significant ecological, economic or social impacts occur. We can prepare for and manage these emergencies through improved surveillance, and the development and iterative refinement of approaches to mitigate disease and its impacts. Improving surveillance requires fast, accurate diagnoses, forecasting disease risk and real-time monitoring of disease-promoting environmental conditions. Diversifying impact mitigation involves increasing host resilience to disease, reducing pathogen abundance and managing environmental factors that facilitate disease. Disease surveillance and mitigation can be adaptive if informed by research advances and catalysed by communication among observers, researchers and decision-makers using information-sharing platforms. Recent increases in the awareness of the threats posed by marine diseases may lead to policy frameworks that facilitate the responses and management that marine disease emergencies require.


Vitamin D and patients with palliative cancer.
Vitamin D is a hormone that is synthesised in the skin in the presence of sunlight. Sufficient vitamin D levels are important-not only for a healthy skeleton-but also for a healthy immune system. Many patients with cancer have insufficient vitamin D levels, and low vitamin D levels are associated with increased 'all-cause mortality' and especially mortality due to cancer. Low vitamin D levels have also been associated with increased risk of infections, increased pain, depressive disorders and impaired quality of life. We review the role of vitamin D in the immune system, in relation to cancer disease, pain and depression. We have recently performed an observational study in 100 patients with palliative cancer in Sweden. The main result was that low vitamin D levels were associated with higher opioid dose, that is, more pain. We also describe a case report where vitamin D supplementation resulted in radically decreased opioid dose, less pain and better well-being. Vitamin D supplementation is not connected with any adverse side effects and is easy to administrate. Thus, we hypothesise that vitamin D-supplementation to patients with palliative cancer might be beneficial and could improve their well-being, decrease pain and reduce susceptibility to infections. However, more clinical studies in this field are needed before firm conclusions can be drawn.


Biomechanical approach in facilitating long-distance walking of elderly people using footwear modifications.
Long-distance walking is a convenient way for prompting physical activity of elderly people. However, walking ability declines with aging. This study assessed if silicone insoles with heel lifts (named here the prescribed insoles) could facilitate long-distance walking of older adults. Fifteen adults aged over 65, who did not have obvious lower-limb problems, walked on a treadmill for totally 60 min in two separate walking sessions: 1) with the prescribed insoles, and 2) with original insoles of the standardized shoes. Gait tests using force plates and a motion analysis system, and subjective evaluation using visual analog and Borg's CR10 scales were conducted at different time points of the treadmill walking. Objective gait anaylsis showed that without using the prescribed insoles, there were significant reductions (p < 0.05) in stance time, vertical ground reaction force, ankle dorsiflexion angle and ankle power generation of the dominant leg after the 60-minute treadmill walk. Such significant reductions were not observed in the same group of subjects upon using the prescribed insoles. Meanwhile, significant improvements in subjective perception of physical exertion, pain and fatigue were observed. Heel lifts and silicone insoles are generally used to relieve plantar pain and reduce strain of plantar flexors in patients. This study showed they might also be solutions to facilitate long-distance walking of older adults, an approach which could prompt their physical activity.


The REFORM study protocol: a cohort randomised controlled trial of a multifaceted podiatry intervention for the prevention of falls in older people.
Falls and fall-related injuries are a serious cause of morbidity and cost to society. Foot problems and inappropriate footwear may increase the risk of falls; therefore podiatric interventions may play a role in reducing falls. Two Cochrane systematic reviews identified only one study of a podiatry intervention aimed to reduce falls, which was undertaken in Australia. The REFORM trial aims to evaluate the clinical and cost-effectiveness of a multifaceted podiatry intervention in reducing falls in people aged 65 years and over in a UK and Irish setting. This multicentre, cohort randomised controlled trial will recruit 2600 participants from routine podiatry clinics in the UK and Ireland to the REFORM cohort. In order to detect a 10% point reduction in falls from 50% to 40%, with 80% power 890 participants will be randomised to receive routine podiatry care and a falls prevention leaflet or routine podiatry care, a falls prevention leaflet and a multifaceted podiatry intervention. The primary outcome is rate of falls (falls/person/time) over 12 months assessed by patient self-report falls diary. Secondary self-report outcome measures include: the proportion of single and multiple fallers and time to first fall over a 12-month period; Short Falls Efficacy Scale-International; fear of falling in the past 4 weeks; Frenchay Activities Index; fracture rate; Geriatric Depression Scale; EuroQoL-five dimensional scale 3-L; health service utilisation at 6 and 12 months. A qualitative study will examine the acceptability of the package of care to participants and podiatrists. The trial has received a favourable opinion from the East of England-Cambridge East Research Ethics Committee and Galway Research Ethics Committee. The trial results will be published in peer-reviewed journals and at conference presentations. Current Controlled Trials ISRCTN68240461 assigned 01/07/2011.


Ethical challenges with the left ventricular assist device as a destination therapy.
The left ventricular assist device was originally designed to be surgically implanted as a bridge to transplantation for patients with chronic end-stage heart failure. On the basis of the REMATCH trial, the US Food and Drug Administration and the US Centers for Medicare & Medicaid Services approved permanent implantation of the left ventricular assist device as a destination therapy in Medicare beneficiaries who are not candidates for heart transplantation. The use of the left ventricular assist device as a destination therapy raises certain ethical challenges. Left ventricular assist devices can prolong the survival of average recipients compared with optimal medical management of chronic end-stage heart failure. However, the overall quality of life can be adversely affected in some recipients because of serious infections, neurologic complications, and device malfunction. Left ventricular assist devices alter end-of-life trajectories. The caregivers of recipients may experience significant burden (e.g., poor physical health, depression, anxiety, and posttraumatic stress disorder) from destination therapy with left ventricular assist devices. There are also social and financial ramifications for recipients and their families. We advocate early utilization of a palliative care approach and outline prerequisite conditions so that consenting for the use of a left ventricular assist device as a destination therapy is a well informed process. These conditions include: (1) direct participation of a multidisciplinary care team, including palliative care specialists, (2) a concise plan of care for anticipated device-related complications, (3) careful surveillance and counseling for caregiver burden, (4) advance-care planning for anticipated end-of-life trajectories and timing of device deactivation, and (5) a plan to address the long-term financial burden on patients, families, and caregivers.Short-term mechanical circulatory devices (e.g. percutaneous cardiopulmonary bypass, percutaneous ventricular assist devices, etc.) can be initiated in emergency situations as a bridge to permanent implantation of ventricular assist devices in chronic end-stage heart failure. In the absence of first-person (patient) consent, presumed consent or surrogate consent should be used cautiously for the initiation of short-term mechanical circulatory devices in emergency situations as a bridge to permanent implantation of left ventricular assist devices. Future clinical studies of destination therapy with left ventricular assist devices should include measures of recipients' quality of end-of-life care and caregivers' burden.


Fast thought speed induces risk taking.
In two experiments, we tested for a causal link between thought speed and risk taking. In Experiment 1, we manipulated thought speed by presenting neutral-content text at either a fast or a slow pace and having participants read the text aloud. In Experiment 2, we manipulated thought speed by presenting fast-, medium-, or slow-paced movie clips that contained similar content. Participants who were induced to think more quickly took more risks with actual money in Experiment 1 and reported greater intentions to engage in real-world risky behaviors, such as unprotected sex and illegal drug use, in Experiment 2. These experiments provide evidence that faster thinking induces greater risk taking.


Associations between Neurocardiovascular Signal Entropy and Physical Frailty.
In this cross-sectional study, the relationship between noninvasively measured neurocardiovascular signal entropy and physical frailty was explored in a sample of community-dwelling older adults from The Irish Longitudinal Study on Ageing (TILDA). The hypothesis under investigation was that dysfunction in the neurovascular and cardiovascular systems, as quantified by short-length signal complexity during a lying-to-stand test (active stand), could provide a marker for frailty. Frailty status (i.e., "non-frail", "pre-frail", and "frail") was based on Fried's criteria (i.e., exhaustion, unexplained weight loss, weakness, slowness, and low physical activity). Approximate entropy (ApEn) and sample entropy (SampEn) were calculated during resting (lying down), active standing, and recovery phases. There was continuously measured blood pressure/heart rate data from 2645 individuals (53.0% female) and frontal lobe tissue oxygenation data from 2225 participants (52.3% female); both samples had a mean (SD) age of 64.3 (7.7) years. Results revealed statistically significant associations between neurocardiovascular signal entropy and frailty status. Entropy differences between non-frail and pre-frail/frail were greater during resting state compared with standing and recovery phases. Compared with ApEn, SampEn seemed to have better discriminating power between non-frail and pre-frail/frail individuals. The quantification of entropy in short length neurocardiovascular signals could provide a clinically useful marker of the multiple physiological dysregulations that underlie physical frailty.


The molecular mechanism of thermal noise in rod photoreceptors.
Spontaneous electrical signals in the retina's photoreceptors impose a limit on visual sensitivity. Their origin is attributed to a thermal, rather than photochemical, activation of the transduction cascade. Although the mechanism of such a process is under debate, the observation of a relationship between the maximum absorption wavelength (λ(max)) and the thermal activation kinetic constant (k) of different visual pigments (the Barlow correlation) indicates that the thermal and photochemical activations are related. Here we show that a quantum chemical model of the bovine rod pigment provides a molecular-level understanding of the Barlow correlation. The transition state mediating thermal activation has the same electronic structure as the photoreceptor excited state, thus creating a direct link between λ(max) and k. Such a link appears to be the manifestation of intrinsic chromophore features associated with the existence of a conical intersection between its ground and excited states.


B Cell-Mediated Antigen Presentation through MHC Class II Is Dispensable for Atherosclerosis Progression.
Depletion of B cells attenuates plaque development and modulates T cell responses in mouse models of atherosclerosis, suggesting that Ag presentation by B cells may promote disease progression. Thus, we set out to determine the role of B cell-mediated MHC class II (MHC II) Ag presentation during atherosclerotic plaque development. We developed murine conditional MHC II deletion and expression systems under control of the B cell-restricted CD19 promoter in an experimental model of atherosclerosis. Mice lacking MHC II expression only on B cells exhibited systemic shifts in germinal center and marginal zone B cell populations, leading to a reduced Ab response compared with littermate control animals. However, all populations were present and normal cholesterol uptake was detected in the plasma following high-fat diet treatment. In a second model, in which conditional expression of MHC II is limited only to B cells, showed similar overall cellularity characteristics compared with mice with complete MHC II deficiency. High-fat diet feeding showed no major changes in atherosclerotic plaque size or plaque cellular content in either conditional deletion or conditional expression approaches, compared with control animals. By testing the necessity and sufficiency of MHC II on B cells in the progression of atherosclerosis, we determine that MHC II on B cells does not directly regulate lesion development in murine models.


Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.
Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT.


Insertion of Neurotransmitters into a Lipid Bilayer Membrane and Its Implication on Membrane Stability: A Molecular Dynamics Study.
The signaling molecules in neurons, called neurotransmitters, play an essential role in the transportation of neural signals, during which the neurotransmitters interact with not only specific receptors, but also cytomembranes, such as synaptic vesicle membranes and postsynaptic membranes. Through extensive molecular dynamics simulations, the atomic-scale insertion dynamics of typical neurotransmitters, including methionine enkephalin (ME), leucine enkephalin (LE), dopamine (DA), acetylcholine (ACh), and aspartic acid (ASP), into lipid bilayers is investigated. The results show that the first three neurotransmitters (ME, LE, and DA) are able to diffuse freely into both 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) membranes, and are guided by the aromatic residues Tyr and Phe. Only a limited number of these neurotransmitters are allowed to penetrate into the membrane, which suggests an intrinsic mechanism by which the membrane is protected from being destroyed by excessive inserted neurotransmitters. After spontaneous insertion, the neurotransmitters disturb the surrounding phospholipids in the membrane, as indicated by the altered distribution of components in lipid leaflets and the disordered lipid tails. In contrast, the last two neurotransmitters (ACh and ASP) cannot enter the membrane, but instead always diffuse freely in solution. These findings provide an understanding at the atomic level of how neurotransmitters interact with the surrounding cytomembrane, as well as their impact on membrane behavior.


[Taxation and tobacco control: the cases of Brazil and Mexico].
This study analyzes the achievements, obstacles and challenges related to cigarette taxes in Brazil and Mexico. Both countries have increased cigarette taxes in recent years and have included a specific tax, which allows maximizing the impact of tax increases on prices. However, it seems they have not taken full advantage of these measures. Three recommendations follow from these experiences: 1) specific taxes must represent a significant percentage of final prices; 2) specific taxes must be regularly adjusted to keep pace with cumulative inflation; and 3) specific taxes must be adjusted to compensate increases in personal income. It is also important to consider that taxes on legal substitutes of cigarettes must be similar to cigarette taxes. As for illegal substitutes, the issue is to reduce the incentives for illicit trade and to make illegal transactions more difficult. Modifications to national legislation and international cooperation constitute key elements to achieve this.


Self-terminating growth of platinum films by electrochemical deposition.
A self-terminating rapid electrodeposition process for controlled growth of platinum (Pt) monolayer films from a K(2)PtCl(4)-NaCl electrolyte has been developed that is tantamount to wet atomic layer deposition. Despite the deposition overpotential being in excess of 1 volt, Pt deposition was quenched at potentials just negative of proton reduction by an alteration of the double-layer structure induced by a saturated surface coverage of underpotential deposited H (H(upd)). The surface was reactivated for further Pt deposition by stepping the potential to more positive values, where H(upd) is oxidized and fresh sites for the adsorption of PtCl(4)(2-) become available. Periodic pulsing of the potential enables sequential deposition of two-dimensional Pt layers to fabricate films of desired thickness, relevant to a range of advanced technologies.


Quantitative Analysis of Supporting Cell Subtype Labeling Among CreER Lines in the Neonatal Mouse Cochlea.
Four CreER lines that are commonly used in the auditory field to label cochlear supporting cells (SCs) are expressed in multiple SC subtypes, with some lines also showing reporter expression in hair cells (HCs). We hypothesized that altering the tamoxifen dose would modify CreER expression and target subsets of SCs. We also used two different reporter lines, ROSA26 tdTomato and CAG-eGFP, to achieve the same goal. Our results confirm previous reports that Sox2 CreERT2 and Fgfr3-iCreER T2 are not only expressed in neonatal SCs but also in HCs. Decreasing the tamoxifen dose did not reduce HC expression for Sox2 CreERT2 , but changing to the CAG-eGFP reporter decreased reporter-positive HCs sevenfold. However, there was also a significant decrease in the number of reporter-positive SCs. In contrast, there was a large reduction in reporter-positive HCs in Fgfr3-iCreER T2 mice with the lowest tamoxifen dose tested yet only limited reduction in SC labeling. The targeting of reporter expression to inner phalangeal and border cells was increased when Plp-CreER T2 was paired with the CAG-eGFP reporter; however, the total number of labeled cells decreased. Changes to the tamoxifen dose or reporter line with Prox1 CreERT2 caused minimal changes. Our data demonstrate that modifications to the tamoxifen dose or the use of different reporter lines may be successful in narrowing the numbers and/or types of cells labeled, but each CreER line responded differently. When the ROSA26 tdTomato reporter was combined with any of the four CreER lines, there was no difference in the number of tdTomato-positive cells after one or two injections of tamoxifen given at birth. Thus, tamoxifen-mediated toxicity could be reduced by only giving one injection. While the CAG-eGFP reporter consistently labeled fewer cells, both reporter lines are valuable depending on the goal of the study.


Marine protected areas rescue a sexually selected trait in European lobster.
Marine protected areas (MPAs) are increasingly implemented worldwide to maintain and restore depleted populations. However, despite our knowledge on the myriad of positive responses to protection, there are few empirical studies on the ability to conserve species' mating patterns and secondary sexual traits. In male European lobsters (Homarus gammarus), the size of claws relative to body size correlates positively with male mating success and is presumably under sexual selection. At the same time, an intensive trap fishery exerts selection against large claws in males. MPAs could therefore be expected to resolve these conflicting selective pressures and preserve males with large claws. We explored this hypothesis by contrasting claw size of males and females in three pairs of MPAs and nearby fished areas in southern Norway. By finding that male lobsters have up to 8% larger claws inside MPAs compared to similarly sized males in fished areas, our study provides evidence that MPAs rescue a secondary sexual trait. Recovery from harvest selection acting on claws is the most likely explanation; however, the higher abundance of lobster inside MPAs does not rule out a plastic response on claw size due to increased competition. Regardless of the underlying cause, our study demonstrates (a) the value of protected areas as a management tool for mitigating fisheries-induced evolution and (b) that MPAs help maintaining the scope for sexual selection in populations with vulnerable life histories and complex mating system.


Do Young Adults Attend to Health Warnings in the First IQOS Advertisement in the U.S.? An Eye-Tracking Approach.
In October 2019, a heated tobacco product (HTP) IQOS debuted in the United States. This study examined young adults' attention and cognitions in response to an IQOS ad that carried two mandated textual health warnings (Surgeon General's warning and nicotine warning), and how their vaping and smoking status may interact with attention patterns to affect attitude and intention to use IQOS. In November 2019, college students (N = 164) viewed IQOS' first U.S. magazine ad and two distractor ads. Viewing patterns were recorded with eye-tracking. Masked recall and aided recognition, attitude and intention towards IQOS use were later assessed with self-report. Ordinary Least Squares (OLS) regressions and moderated mediation analyses examined the associations between visual attention and viewers' cognitions about IQOS use. Promotional content attracted significantly more attention compared to the warnings. Attention to the Surgeon General's warning but not to the nicotine warning was associated with recall and recognition of the warning's content. For ever-vapers, greater attention allocation to the promotional content in the IQOS ad was associated with more favorable attitude toward IQOS use, which was in turn positively associated with intention to use IQOS. Attention allocation to the warnings did not affect attitude or intentions, regardless of tobacco use status. The results revealed the effects of IQOS promotional content overshadowed the two health warnings in influencing young people's attitude and intention to use IQOS. Young adults who vaped were more vulnerable to HTP advertising with respect to future use and vaping may be a gateway to HTP use. This is the first eye-tracking study examining attention and cognitions associated with the new IQOS ad exposure among young adults. Promotional content in the ad attracted significantly more attention than the two warnings combined. Attention to the Surgeon General's warning but not to the nicotine warning was associated with recall and recognition of the warning's content. Greater attention allocation to the promotional content led to a more favorable attitude toward IQOS use which was associated with increased intention to use IQOS for ever-vapers. However, greater attention allocation to the warnings did not affect attitude or intentions to use IQOS.


Serotype-conversion in Shigella flexneri: identification of a novel bacteriophage, Sf101, from a serotype 7a strain.
Shigella flexneri is the major cause of bacillary dysentery in the developing countries. The lipopolysaccharide (LPS) O-antigen of S. flexneri plays an important role in its pathogenesis and also divides S. flexneri into 19 serotypes. All the serotypes with an exception for serotype 6 share a common O-antigen backbone comprising of N-acetylglucosamine and three rhamnose residues. Different serotypes result from modification of the basic backbone conferred by phage-encoded glucosyltransferase and/or acetyltransferase genes, or plasmid-encoded phosphoethanolamine transferase. Recently, a new site for O-acetylation at positions 3 and 4 of RhaIII, in serotypes 1a, 1b, 2a, 5a and Y was shown to be mediated by the oacB gene. Additionally, this gene was shown to be carried by a transposon-like structure inserted upstream of the adrA region on the chromosome. In this study, a novel bacteriophage Sf101, encoding the oacB gene was isolated and characterised from a serotype 7a strain. The complete sequence of its 38,742 bp genome encoding 66 open reading frames (orfs) was determined. Comparative analysis revealed that phage Sf101 has a mosaic genome, and most of its proteins were >90% identical to the proteins from 12 previously characterised lambdoid phages. In addition, the organisation of Sf101 genes was found to be highly similar to bacteriophage Sf6. Analysis of the Sf101 OacB identified two amino acid substitutions in the protein; however, results obtained by NMR spectroscopy confirmed that Sf101-OacB was functional. Inspection of the chromosomal integration site of Sf101 phage revealed that this phage integrates in the sbcB locus, thus unveiling a new site for integration of serotype-converting phages of S. flexneri, and determining an alternative location of oacB gene in the chromosome. Furthermore, this study identified oacB gene in several serotype 7a isolates from various regions providing evidence of O-acetyl modification in serotype 7a. This is the first report on the isolation of bacteriophage Sf101 which contains the S. flexneri O-antigen modification gene oacB. Sf101 has a highly mosaic genome and was found to integrate in the sbcB locus. These findings contribute an advance in our current knowledge of serotype converting phages of S. flexneri.


Synthesis and characterization of new Cr(III), Fe(III) and Cu(II) complexes incorporating multi-substituted aryl imidazole ligand: Structural, DFT, DNA binding, and biological implications.
Designing new metal-based molecular antibiotics is an efficient approach to overcome the growing threat of antimicrobial resistance. In this paper, novel Cr(III), Fe(III) and Cu(II) complexes comprising substituted aryl imidazole ligand (MSEB), namely (2-(1-(2-hydroxyethyl)-4,5-diphenyl-1H-imidazole-2-yl)(4-bromophenol)) have been synthesized and characterized using infra-red (IR), ultraviolet-visible (UV-Vis) and 1H, 13C NMR spectroscopic techniques, together with elemental (CHN) and thermogravimetric analyses, molar conductance, and magnetic susceptibility measurements. The combined results along with the DFT calculations revealed a 1:1 (M: L) stoichiometric ratio and the complexes adopted distorted-octahedral geometries to afford [Cr(MSEB)Cl2(H2O)2], [Fe(MSEB)(NO3)2(H2O)2] and [Cu(MSEB)Cl(H2O)3] respectively. Biological studies showed that all complexes exhibited powerful antimicrobial activity against various strains of bacteria and fungi, S. aureus (+ve), E. coli (-ve) and P. aeruginosa (-ve) bacteria and T. Rubrum, C. albicans, and A. flavus fungi. Moreover, the three metal-complexes showed high in vitro cytotoxicity against Colon (HCT-116), Breast (MCF-7), and hepatic cellular (HepG-2) carcinoma cell lines, with MSEBCu complex being the most cytotoxic one. Finally the binding interactions of the complexes with CT-DNA were explored using UV-Vis spectroscopy, viscosity and gel electrophoreses measurements.


Seemingly neutral polymorphic variants may confer immunity to splicing-inactivating mutations: a synonymous SNP in exon 5 of MCAD protects from deleterious mutations in a flanking exonic splicing enhancer.
The idea that point mutations in exons may affect splicing is intriguing and adds an additional layer of complexity when evaluating their possible effects. Even in the best-studied examples, the molecular mechanisms are not fully understood. Here, we use patient cells, model minigenes, and in vitro assays to show that a missense mutation in exon 5 of the medium-chain acyl-CoA dehydrogenase (MCAD) gene primarily causes exon skipping by inactivating a crucial exonic splicing enhancer (ESE), thus leading to loss of a functional protein and to MCAD deficiency. This ESE functions by antagonizing a juxtaposed exonic splicing silencer (ESS) and is necessary to define a suboptimal 3' splice site. Remarkably, a synonymous polymorphic variation in MCAD exon 5 inactivates the ESS, and, although this has no effect on splicing by itself, it makes splicing immune to deleterious mutations in the ESE. Furthermore, the region of MCAD exon 5 that harbors these elements is nearly identical to the exon 7 region of the survival of motor neuron (SMN) genes that contains the deleterious silent mutation in SMN2, indicating a very similar and finely tuned interplay between regulatory elements in these two genes. Our findings illustrate a mechanism for dramatic context-dependent effects of single-nucleotide polymorphisms on gene-expression regulation and show that it is essential that potential deleterious effects of mutations on splicing be evaluated in the context of the relevant haplotype.


Parenting Stress and Emotional/Behavioral Problems in Adolescents with Primary Headache.
Primary headache is a frequent and disabling disorder, common among children and adolescents, and it is a painful syndrome often accompanied by functional impairment and associated with emotional and behavior problems. The aim of this study was to investigate parenting stress and emotional/behavioral problems in adolescents affected by primary headache compared with healthy adolescents. The study population consisted of 35 adolescents and a control group of 23 healthy subjects. The assessment included the administration of clinical standardized scales such as Parent Stress Index-Short Form, Pediatric Migraine Disability Assessment Score Questionnaire, and Child Behavior Checklist (CBCL). Headache group and control group did not differ in terms of parenting stress (p = 0.29). On the contrary, headache group showed more internalizing problems (p = 0.023), affective problems (p = 0.01), anxious (p = 0.001), and somatic complaints (p < 0.001) compared with control group. In addition, we found a significant correlation between PSI domains and specific CBCL subscales in the headache group. The findings emphasize the need for expanded intervention in the clinical treatment of pediatric headache, a treatment that may also include the family members. Further research is needed.


Taking the long view: how well do patient activation scores predict outcomes four years later?
Patient activation is an important predictor of health outcomes and health care usage, yet we do not know how enduring the benefits of greater patient activation are. This study uses a large panel survey of people with chronic conditions (n = 4,865) to examine whether a baseline patient activation measure predicts outcomes 4 years later, and whether changes in patient activation measure scores are associated with changes in outcomes. The findings indicate that the benefits of health activation are enduring, yielding benefits in the form of better self-management, improved functioning, and lower use of costly health care services over time. Furthermore, the findings indicate that when activation levels change, many outcomes change in the same direction. Patient activation seems to be an important and modifiable factor for influencing chronic disease outcomes; health care delivery systems can use this information to personalize and improve care.


Early event-related potential changes during working memory activation predict rapid decline in mild cognitive impairment.
The conversion of mild cognitive impairment (MCI) to Alzheimer's disease is associated with substantial compromise of neocortical circuits subserving rapid cognitive functions such as working memory. Event-related potential (ERP) analysis is a powerful tool to identify early impairment of these circuits, yet research for an electrophysiological marker of cognitive deterioration in MCI is scarce. Using a "2-back" activation paradigm, we recently described an electrophysiological correlate of working memory activation (positive-negative working memory [PN(wm)] component) over parietal electrodes. Ours was a longitudinal study of 24 MCI patients with ERP analysis at inclusion and neuropsychological follow-up after 1 year. We used ERP waveform subtraction analysis between the n-back and control tasks. Analysis of variance (ANOVA) was used to compare electroencephalograph latencies between progressive MCI (PMCI) and stable MCI (SMCI), and univariate regression was used to assess the relationship between neuropsychological measures at baseline and clinical outcome. Thirteen (54%) MCI patients showed PMCI, and 11 (46%) remained stable (SMCI). In SMCI, a PN(wm) component with significantly larger density compared to baseline was identified when subtracting the detection task for both the 1- and 2-back tasks. In contrast, in PMCI, the PN(wm) component was absent in both 1-back and 2-back conditions. Neuropsychological variables and n-back test performance at inclusion did not predict cognitive deterioration 1 year later. In conjunction with recent functional imaging data, the present results support the notion of an early dysfunction of neural generators within the parietal cortex in MCI. They also reveal that the absence of the PN(wm) component may provide an easily applicable qualitative predictive marker of rapid cognitive deterioration in MCI.


The remote surveillance of forest fires.
The radiometric considerations for fifteen forest fire surveillance and detection systems are reviewed. The system response is optimized in the 3-6-micro spectral region. A formulation of system noise-equivalent temperature is presented in terms of operational performance requirements and start-of-the-art component parameters. The radiometric criteria are investigated for detection of incipient forest fires and mapping of terrain background. Obscuration of fire targets by timber canopies is discussed. A prototype fire detection system based on these considerations is being evaluated.


Cactin, a conserved protein that interacts with the Drosophila IkappaB protein cactus and modulates its function.
Rel transcription factors function in flies and vertebrates in immunity and development. Although Rel proteins regulate diverse processes, the control of their function is conserved. In a two-hybrid screen for additional components of the pathway using the Drosophila I-kappaB protein Cactus as a bait, we isolated a novel coiled-coil protein with N-terminal Arg-Asp (RD)- like motifs that we call Cactin. Like the other components of this pathway, Cactin is evolutionarily conserved. Over-expression of cactin in a cactus(A2) heterozygous background results in the enhancement of the cactus phenotype. Both the embryonic lethality and ventralization are strongly increased, suggesting that cactin functions in the Rel pathway controlling the formation of dorsal-ventral embryonic polarity.


Systematic characterization of myocardial inflammation, repair, and remodeling in a mouse model of reperfused myocardial infarction.
Mouse models of myocardial infarction are essential tools for the study of cardiac injury, repair, and remodeling. Our current investigation establishes a systematic approach for quantitative evaluation of the inflammatory and reparative response, cardiac function, and geometry in a mouse model of reperfused myocardial infarction. Reperfused mouse infarcts exhibited marked induction of inflammatory cytokines that peaked after 6 hr of reperfusion. In the infarcted heart, scar contraction and chamber dilation continued for at least 28 days after reperfusion; infarct maturation was associated with marked thinning of the scar, accompanied by volume loss and rapid clearance of cellular elements. Echocardiographic measurements of end-diastolic dimensions correlated well with morphometric assessment of dilative remodeling in perfusion-fixed hearts. Hemodynamic monitoring was used to quantitatively assess systolic and diastolic function; the severity of diastolic dysfunction following myocardial infarction correlated with cardiomyocyte hypertrophy and infarct collagen content. Expression of molecular mediators of inflammation and cellular infiltration needs to be investigated during the first 72 hr, whereas assessment of dilative remodeling requires measurement of geometric parameters for at least four weeks after the acute event. Rapid initiation and resolution of the inflammatory response, accelerated scar maturation, and extensive infarct volume loss are important characteristics of infarct healing in mice.


Amelioration of metformin-induced hypothyroidism by Withania somnifera and Bauhinia purpurea extracts in Type 2 diabetic mice.
An investigation was carried out to reveal the possible ameliorative role of two plant extracts on an antidiabetic drug-induced hypothyroidism in Type 2 diabetic animals. Dexamethasone (1.0 mg/kg, i.m.) administration caused hyperglycemia with a parallel increase in renal lipid peroxidation (LPO), relative risk ratio (RR), and the concentrations of serum insulin; total cholesterol (TC); low-density lipoprotein cholesterol (LDL-C); very low-density lipoprotein cholesterol (VLDL-C) and triglycerides (TG). It decreased serum triiodothyronine (T3), thyroxine (T4) and high-density lipoprotein cholesterol (HDL-C) levels as well as renal superoxide dismutase (SOD); catalase (CAT) and reduced glutathione (GSH) content. Administration with metformin (150 mg/kg, orally) to diabetic animals further reduced circulating T4 level and caused severe hypothyroidism. It also reduced renal LPO, RR, serum concentrations of insulin; glucose and LDL-C with a parallel increase in cellular antioxidants. While oral administration with either Withania somnifera (1.4 g/kg) or Bauhinia purpurea (2.5 mg/kg) extract along with dexamethasone and metformin elevated the concentrations of circulating T3 and T4 to euthyroid level. The plant extracts also corrected RR ratio and serum concentration of lipids. The findings of the present study, for the first time, reveal that the evaluated plant extracts have a potential to ameliorate metformin-induced hypothyroidism in Type 2 diabetic subjects.


Hemodynamic characterization of intracranial pressure plateau waves in head-injury patients.
Plateau waves of intracranial pressure (ICP) are often recorded during intensive care monitoring of severely head injured patients. They are traditionally interpreted as meaningful secondary brain insults because of the dramatic decrease in cerebral perfusion pressure (CPP). The aim of this study was to investigate both the hemodynamic profile and the clinical consequences of plateau waves. One hundred sixty head-injured patients were studied using continuous monitoring of ICP; almost 20% of these patients exhibited plateau waves. In 96 patients arterial pressure, ICP, and transcranial Doppler (TCD) blood flow velocity were studied daily for 20 minutes to 3 hours. Sixteen episodes of plateau waves in eight patients were recorded and analyzed. The dramatic increase in ICP was followed by a profound fall in CPP (by 45%). In contrast, flow velocity fell by only 20%. Autoregulation was documented to be intact both before and after plateau but was disturbed during the wave (p < 0.05). Pressure-volume compensatory reserve was always depleted before the wave. Cerebrovascular resistance decreased during the wave by 60% (p < 0.05) and TCD pulsatility increased (p < 0.05). Plateau waves did not increase the probability of an unfavorable outcome following injury. The authors have confirmed that the plateau waves are a hemodynamic phenomenon associated with cerebrovascular vasodilation. They are observed in patients with preserved cerebral autoregulation but reduced pressure-volume compensatory reserve.


Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement.
Astrocytes respond to neuronal activity and were shown to be necessary for plasticity and memory. To test whether astrocytic activity is also sufficient to generate synaptic potentiation and enhance memory, we expressed the Gq-coupled receptor hM3Dq in CA1 astrocytes, allowing their activation by a designer drug. We discovered that astrocytic activation is not only necessary for synaptic plasticity, but also sufficient to induce NMDA-dependent de novo long-term potentiation in the hippocampus that persisted after astrocytic activation ceased. In vivo, astrocytic activation enhanced memory allocation; i.e., it increased neuronal activity in a task-specific way only when coupled with learning, but not in home-caged mice. Furthermore, astrocytic activation using either a chemogenetic or an optogenetic tool during acquisition resulted in memory recall enhancement on the following day. Conversely, directly increasing neuronal activity resulted in dramatic memory impairment. Our findings that astrocytes induce plasticity and enhance memory may have important clinical implications for cognitive augmentation treatments.