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Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.
The disease caused by the influenza virus is a global public health problem due to its high rates of morbidity and mortality. Thus, analysis of the information generated by epidemiological surveillance systems has vital importance for health decision making. A retrospective analysis was performed using data generated by the four molecular diagnostic laboratories of the Mexican Social Security Institute between 2010 and 2016. Demographics, influenza positivity, seasonality, treatment choices and vaccination status analyses were performed for the vaccine according to its composition for each season. In all cases, both the different influenza subtypes and different age groups were considered separately. The circulation of A/H1N1pdm09 (48.7%), influenza A/H3N2 (21.1%), influenza B (12.6%), influenza A not subtyped (11%) and influenza A/H1N1 (6.6%) exhibited well-defined annual seasonality between November and March, and there were significant increases in the number of cases every 2 years. An inadequate use of oseltamivir was determined in 38% of cases, and the vaccination status in general varied between 12.1 and 18.5% depending on the season. Our results provide current information about influenza in Mexico and demonstrate the need to update both operational case definitions and medical practice guidelines to reduce the inappropriate use of antibiotics and antivirals.
Background: Greater than 80% of patient visits to emergency departments (EDs) are for a pain-related concerns. Approximately 38,000 patients per year have such complaints in our academic hospital ED. 3,300 (8.6%) of those visits are for musculoskeletal (MSK) pain (i.e. back or extremity injury/pain), which are typically triaged as low-acuity presentations, leading to longer times to clinician assessment. Delays to adequate analgesia result in unnecessary suffering, worse patient care and satisfaction, and increased patient complaints. Aim Statement: We aimed to reduce the time-to-analgesia (TTA; time from patient triage to receipt of analgesia) for patients with MSK pain in our ED by 55% (to under 60 minutes) in 9 months’ time (May 2018). Measures & Design: Our outcome measures were TTA (in minutes) and ED length of stay (LOS; in minutes). Process measures included nurses’ use of medical directive and rate of analgesia administration. Balancing measures included patient adverse events and time spent triaging for nurses. We utilized weekly data capture for the Statistical Process Control (SPC) chart, and we used Mann-Whitney U test for our before-and-after evaluation. Utilizing the Model for Improvement, we performed wide stakeholder engagement and root cause analyses, and we created a Pareto chart. This led to our Plan-Do-Study-Act (PDSA) cycles: 1) nurse-initiated analgesia (NIA) at triage; 2) new triage documentation aid for medication administration; 3) quick reference medical directive badge tag for nurses; 4) weekly targeted feedback of the project's progress at clinical team huddle. Evaluation/Results: TTA decrease from 129 minutes (n = 153) to 100 minutes (22.5%; n = 87, p < 0.05). ED LOS decreased from 580 minutes (n = 361) to 519 minutes (10.5%; n = 187; p = 0.77). Special cause variation was identified on the ED LOS SPC chart with eight consecutive points below the midline, after PDSA 1. The number of patients who received any analgesia increased from 42% (n = 361) to 47% (n = 187; p = 0.13). The number of patients who received medications via medical directives increased from 22% (n = 150) to 44% (n = 87; p < 0.001). Balancing measures were unchanged. Discussion/Impact: The significant reduction in the TTA and increase in the use of medical directives in the before-and-after analyses were likely due to our front-line focused improvements and deliberate nursing engagement. With continued success and sustainable processes, we are planning to spread our project to other EDs and broaden our initiative to all pain-related concerns.
Objectives: Children with acquired brain injury (ABI) can present with disruptive behavior, which is often a consequence of injury and parent factors. Parent factors are associated with child disruptive behavior. Furthermore, disinhibition in the child also leads to disruptive behavior. However, it is unclear how these factors interact. We investigated whether parental factors influence child disruptive behavior following ABI and how these factors interact. Methods: Parents of 77 children with ABI participated in the study. Parent factors (executive dysfunction, trait-anxiety), potential intervention targets (dysfunctional parenting practices, parental stress, child disinhibition), and child disruptive behavior were assessed. A hypothetical model based on the literature was tested using mediation and path analysis. Results: Mediation analysis revealed that child disinhibition and dysfunctional parenting practices mediated the association of parent factors and child disruptive behavior. Parents’ executive dysfunction mediated the association of dysfunctional parenting practices, parental stress and parent trait-anxiety. Parenting practices mediated the association of executive dysfunction and child disruptive behavior. Path analysis indices indicated good model adjustment. Comparative and Tucker-Lewis Index were >0.95, and the root mean square error of approximation was 0.059, with a chi-square of 0.25. Conclusions: A low level of parental trait-anxiety may be required to reduce dysfunctional parenting practices and child disinhibition. Impairments in child disinhibition can be exacerbated when parents present with high trait-anxiety. Child disinhibition is the major contributor of disruptive behavior reported by parents and teachers. The current study provides evidence of parent anxiety and child disinhibition as possible modifiable intervention targets for reducing child disruptive behavior. (JINS, 2019, 25, 237–248)
Completed suicide (CS) is a leading cause of death worldwide and its rates are available for most developed countries. On the other hand, attempted suicide (AS) is a risk factor for CS but there are limited data on its rates in various countries. In constructing a ratio for AS/CS rates, most would agree that for CS, the denominator should be the annual suicide rate (per 100 000). As for the ratio's numerator (AS) per 100 000, there are three possible calculations: (1) annual prevalence from population surveys, (2) annual prevalence from national clinical registers or (3) lifetime prevalence from population surveys. We think that the first possibility would probably be the best choice but, unfortunately, surveys providing the annual prevalence of AS are lacking for most countries. Annual prevalence from national registers is also lacking for most countries and is contaminated by under-reporting. Therefore, in this editorial, we are left with only the last option, a ratio for lifetime prevalence of AS (per 100 000) divided by annual rate of CS (per 100 000). This ratio for AS/CS rates appears to differ substantially across countries worldwide but presents no big regional differences other than two remarkable exceptions, one per continent. In Europe, Spain and France had greater ratios (174.4 and 152.5, respectively) than Italy (64.1). In Asia/Pacific, New Zealand has a higher ratio (345.9) compared with China (75.8) and Japan (76.9). The ratio for AS/CS rates could be a good index for implementing evidence-informed decision-making regarding suicidal behaviour (SB) among health service managers, and for helping them in the allocation of health resources for the prevention of SB.
Introduction: Treat and Release (T&R) patients are seen and discharged home from the emergency department (ED), and asked to return within 12-72 hours for follow-up care (e.g., ultrasound, repeat blood work). Our two academic teaching hospitals see approximately 2,000 T&R patients per year. Handover of care for T&R patientsdone through charting only and therefore dependent on the charts adequacy and completenessis crucial to the safety and quality of care they receive. An 18-month retrospective chart audit at our sites identified quality gaps, including suboptimal documentation that ultimately impedes patient disposition. Our projects aim was to reduce the time-to-disposition (TTD; time spent by patients between provider initial assessment and discharge from the ED) by a third (from 70min) in 6-months time (March 2017), a target felt to be both meaningful and realistic by our stakeholder team. Methods: Our primary outcome measure was the TTD (in minutes). Our process measure was the quality of documentation, using a modified version of QNOTE, a validated tool used to assess the quality of health-care documentation. PDSA cycles included: 1) Involvement of stakeholders for the creation and refinement of an improved T&R handover tool to cue more specific documentation; 2) Education of health-care providers (HCPs) about T&R patients; 3) Replacement of the previous T&R handover tool with a newly designed and mandatory tool (i.e. a forcing function); 4) Refinement of the process for T&R patients and chart hold-over. Results: Run charts for both the median TTD and median modified QNOTE scores over time demonstrate a shift (i.e., run chart rule) associated with the second and third clustered PDSA cycles. After the first three clusters of PDSA cycles (i.e., before-and-after), mean TTD was reduced by 40% (70min to 42min, p=0.005). The quality of documentation (mean modified QNOTE scores) was also significantly improved (all results p<0.0001): patient assessment from 81% to 92%, plan of care from 58% to 85% and follow-up plan from 67% to 90%. Conclusion: We reduced the time-to-disposition for T&R patients by identifying gaps in the quality of documentation of their chart. Using iterative PDSA cycles, we improved their time-to-disposition through improved communication between health-care providers and a new T&R handover tool working as a forcing function. Other centers could use similar assessment methods and interventions to improve the care of T&R patients.
A new species of Laeonereis from a shrimp farm associated with a subtropical coastal lagoon on the Mexican Pacific coast is described. The new species is characterized by a deep anterior groove on the prostomium, which is shared only with L. culveri. However, longer tentacular cirri extending back to the anterior margin of chaetiger two, the number of papillae of each group on the maxillary ring of the pharynx, and the relative size of the homogomph falcigers in the new species, allow us to separate the two species. Although the species has not been previously detected in the coastal lagoon surrounding the shrimp farm, we postulate that L. watsoni n. sp. is likely to be part of the invertebrate communities of the upper parts of similar coastal lagoons that are common along the tropical coasts of Mexico.
Since April 2015, whole genome sequencing (WGS) has been the routine test for Salmonella identification, surveillance and outbreak investigation at the national reference laboratory in England and Wales. In May 2015, an outbreak of Salmonella Enteritidis cases was detected using WGS data and investigated. UK cases were interviewed to obtain a food history and links between suppliers were mapped to produce a food chain network for chicken eggs. The association between the food chain network and the phylogeny was explored using a network comparison approach. Food and environmental samples were taken from premises linked to cases and tested for Salmonella. Within the outbreak single nucleotide polymorphism defined cluster, 136 cases were identified in the UK and 18 in Spain. One isolate from a food containing chicken eggs was within the outbreak cluster. There was a significant association between the chicken egg food chain of UK cases and phylogeny of outbreak isolates. This is the first published Salmonella outbreak to be prospectively detected using WGS. This outbreak in the UK was linked with contemporaneous cases in Spain by WGS. We conclude that UK and Spanish cases were exposed to a common source of Salmonella-contaminated chicken eggs.
The AMIGA project carries out a multiwavelength study of the largest catalogue of isolated galaxies from the Local Universe (CIG, Karachentseva 1973). Compared to any other sample —field galaxies included— and using highly strict isolation criteria (unperturbed for at least ~3 Gyr, Verdes-Montenegro et al. 2005), all the results show that these galaxies have the lowest values of the physical magnitudes expected to be enhanced by interactions. This strongly supports isolated galaxies as ideal laboratories for the study of galaxy formation and evolution. Despite CIG galaxies show the lowest HI integrated profile asymmetry level when compared to any other sample, some cases present up to 50% HI asymmetry (Espada et al. 2011b). We aim to shed light over the causes and sources of such asymmetries with our deep radiointerferometric and optical observations of CIG targets. Since major mergers are ruled out by the isolation criteria, in this work we are addressing whether minor mergers, internal processes or primordial gas accretion are responsible for such asymmetries.
Lolium rigidum L. (rigid ryegrass) is one of the most extensive and harmful weeds in winter cereal crops. A bioclimatic model for this species was developed using CLIMEX. The model was validated with records from North America and Oceania and used to assess the global potential distribution of L. rigidum under the current climate and under two climate change scenarios. Both scenarios represent contrasting temporal patterns of economic development and carbon dioxide (CO2) emissions. The projections under current climatic conditions indicated that L. rigidum does not occupy the full extent of the climatically suitable area available to it. Under future climate scenarios, the suitable potential area increases by 3·79% in the low-emission CO2 scenario and by 5·06% under the most extreme scenario. The model's projection showed an increase in potentially suitable areas in North America, Europe, South America and Asia; while in Africa and Oceania it indicated regression. These results provide the necessary knowledge for identifying and highlighting the potential invasion risk areas and for establishing the grounds on which to base the planning and management measures required.
Trajectory patterns of positive, disorganized and negative dimension symptoms during antipsychotic treatment in drug-naive patients with first-episode psychosis have yet to be examined by using naturalistic data.
This pragmatic clinical trial randomized 161 drug-naive patients with a first episode of psychosis to olanzapine, risperidone or haloperidol. Patients were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and Positive Symptoms (SAPS) at baseline and at the end of weeks 1, 2, 3, 4 and 6 of antipsychotic treatment. Censored normal models of response trajectories were developed with three dimensions of the SAPS-SANS scores (positive, disorganized and negative) in order to identify the different response trajectories. Diagnosis, cannabis use, duration of untreated psychosis (DUP), smoking and antipsychotic class were examined as possible predictive variables.
Patients were classified in five groups according to the positive dimension, three groups according to the disorganized dimension and five groups according to the negative dimension. Longer DUPs and cannabis use were associated with higher scores and poorer responses in the positive dimension. Cannabis use was associated with higher scores and poorer responses in the disorganized dimension. Only schizophrenia diagnosis was associated with higher scores and poorer responses in the negative dimension.
Our results illustrate the heterogeneity of short-term response to antipsychotics in patients with a first episode of psychosis and highlight markedly different patterns of response in the positive, disorganized and negative dimensions. DUP, cannabis use and diagnosis appeared to have a prognostic value in predicting treatment response with different implications for each dimension.
During seed germination, metabolism is reactivated, DNA is repaired and cell division is restarted in the meristems. The mechanisms that co-ordinate cell growth and division in maize embryonic axes during germination are not well understood. However, the presence of a factor similar to IGF (insulin-like growth factor) that accelerates germination has been reported. In the present work, the regulation of the cell-cycle restart by bovine insulin [which has been demonstrated to produce similar effects as insulin-like growth factor of maize (ZmIGF) in maize seeds] was studied in germinating embryonic axes. Our results showed that bovine insulin differentially stimulates growth, S6K phosphorylation, S6rp transcript accumulation on the polysomal fraction, as well as de novo DNA synthesis in the radicles and the coleoptiles of the embryonic axis. A stronger and earlier effect was observed in radicles compared to coleoptiles; therefore, the effect of insulin on the cell cycle of the root meristem was studied by flow cytometry. The G1–S transition was stimulated and cell proliferation was induced. Furthermore, it was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) that bovine insulin increased E2F and PCNA (proliferating cell nuclear antigen) transcription after 15 h of germination and PCNA de novo synthesis at 15 h of germination. These results show that bovine insulin preferentially stimulates growth in the radicles of germinating embryonic axes and suggest that its effect on the G1–S transition and the activation of cell proliferation is mediated by the induction of E2F and PCNA transcription.
Dietary non-digestible carbohydrates reduce the development of cows' milk allergy in mice. In the present study, the contribution of CD25+ regulatory T-cells (Treg) was investigated using in vivo Treg depletion and adoptive transfer studies. Mice were orally sensitised with casein and fed a diet containing 2 % short-chain galacto-, long-chain fructo- and acidic oligosaccharides (GFA) or a control diet. Donor splenocytes of mice sensitised with casein and fed the GFA or control diet were adoptively transferred to naive recipient mice, which were casein- or sham-sensitised and fed the control diet. In addition, in vivo or ex vivo CD25+ Treg depletion was performed using anti-CD25 (PC61). The acute allergic skin response upon intradermal casein challenge and casein-specific Ig were determined. Furthermore, T-helper (TH) 1 and TH2 cell numbers were analysed in the mesenteric lymph nodes. The oligosaccharide diet strongly reduced the development of the acute allergic skin response, which was abrogated by the in vivo anti-CD25 treatment. The diet enhanced the percentage of TH1 cells and tended to reduce the percentage of TH2 cells in casein-sensitised mice. Recipient mice were protected against the development of an acute allergic skin response when transferred with splenocytes from casein-sensitised GFA-fed donor mice before sensitisation. Ex vivo depletion of CD25+ Treg abrogated this transfer of tolerance. Splenocytes from sham-sensitised GFA-fed donor mice did not suppress the allergic response in recipient mice. In conclusion, CD25+ Treg contribute to the suppression of the allergic effector response in casein-sensitised mice induced by dietary intervention with non-digestible carbohydrates.
Biodiversity is the variability among living organisms, from genes to the biosphere. The value of biodiversity is multifold, from preserving the integrity of the biosphere as a whole, to providing food and medicines, to spiritual and aesthetic well-being.
One of the major drivers of biodiversity loss in Europe is atmospheric deposition of reactive nitrogen (Nr).
This chapter focuses on Nr impacts on European plant species diversity; in particular, the number and abundance of different species in a given area, and the presence of characteristic species of sensitive ecosystems.
We summarise both the scientific and the policy aspects of Nr impacts on diversity and identify, using a range of evidence, the most vulnerable ecosystems and regions in Europe.
Key findings/state of knowledge
Reactive nitrogen impacts vegetation diversity through direct foliar damage, eutrophication, acidification, and susceptibility to secondary stress.
Species and communities most sensitive to chronically elevated Nr deposition are those that are adapted to low nutrient levels, or are poorly buffered against acidification. Grassland, heathland, peatland, forest, and arctic/montane ecosystems are recognised as vulnerable habitats in Europe; other habitats may be vulnerable but are still poorly studied.
It is not yet clear if different wet-deposited forms of Nr (e.g. nitrate, NO3− versus ammonium, NH4+) have different effects on biodiversity. However, gaseous ammonia (NH3) can be particularly harmful to vegetation, especially lower plants, through direct foliar damage.
To compare food consumption during television (TV) viewing among adolescents who watched >2 h/d v. ≤2 h/d; and to examine the association between sociodemographic variables (age, gender and socio-economic status (SES)) and the consumption of energy-dense foods and drinks during TV viewing.
The data are part of the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional survey. Data on time watching TV, types of foods and drinks consuming during TV viewing and parental SES (parental education, parental occupation and family affluence) were measured by questionnaires completed by adolescents. Binary logistic regression tested the association between energy-dense foods and drinks and (i) sociodemographic variables and (ii) TV time.
Ghent (Belgium), Heraklion (Greece), Pecs (Hungary) and Zaragoza (Spain).
Girls (n 699) and boys (n 637) aged 12·5–17·5 years.
Boys reported more frequent consumption of beer and soft drinks whereas girls selected more fruit juice, water, herbal infusions and sweets (all P ≤ 0·05). Watching TV for >2 h/d was associated with the consumption of energy-dense foods and drinks. Girls whose mothers achieved the lowest education level had an adjusted OR of 3·22 (95 % CI 1·81, 5·72) for the consumption of energy-dense drinks during TV viewing v. those whose mothers had the highest educational level.
Excessive TV watching may favour concurrent consumption of energy-dense snacks and beverages. Adolescents from low-SES families are more likely to consume unhealthy drinks while watching TV.
We present a simplified model of electrons and phonons in a three-site cluster as a paradigm of a system exhibiting a lattice instability. We point out the utility of X-ray absorption fine structure (XAFS) in the study of materials where the coupling between electrons and phonons leads to the appearance of such lattice instabilities. As examples of these systems, we present X-ray absorption fine structure (XAFS) measurements on magnetic manganese oxide materials and II-VI semiconductors. Both of these systems exhibit local lattice instabilities which are reflected in the transport properties. In the case of the manganese oxide La0.67Ca0.33MnO3 we observe a change in the Mn-O local structure accompanying the ferromagnetic and metal-insulator transitions. For In doped CdTe we observe the appearance of a lattice distortion centered at the Cd atoms as the In concentration is increased. This distortion is associated with the trapping of free charge carriers, leading to the saturation of the conductivity as the In concentration increases.
Mony J. de Leon, Department of Psychiatry New York University School of Medicine New York, NY, USA,
Henry Rusinek, Department of Radiology New York University School of Medicine New York, NY, USA,
Wai Tsui, Department of Psychiatry New York University School of Medicine New York, NY, USA and Nathan Kline Institute Orangeburg, NY, USA,
Thomas Wisniewski, Department of Neurology New York University School of Medicine New York, NY, USA and Department of Developmental Neurobiology Institute for Basic Research Staten Island, NY, USA,
Jerzy Wegiel, Department of Developmental Neurobiology Institute for Basic Research Staten Island, NY, USA,
Ajax George, Department of Radiology New York University School of Medicine New York, NY, USA
This chapter offers a highly personal view of three-dimensional tomographic imaging related to Alzheimer's disease (AD). The age of structural imaging in AD began with X-ray computed tomography (CT). CT studies introduced the negative angulation acquisition plane to more efficiently reveal and measure temporal horn enlargement and incidentally found evidence for hippocampal atrophy. Structural imaging has been invaluable in anatomically defining the regional tissue vulnerability and atrophy correction as estimated by fluorodeoxyglucose positron emission tomography (FDG-PET) and amyloid imaging and other tracers. Structural imaging owes a great debt to pathology for the contributions made to understanding the lesions and pathologic anatomy of AD. Although magnetic resonance imaging (MRI) imaging has yet to deliver a specific marker of AD pathology, MRI has provided sensitive characterizations of the effects of AD pathology and the promise of new MR contrast agents for identifying amyloid plaque pathology.