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Inflammatory Type Focal Cerebral Arteriopathy of the Posterior Circulation in Children: A Comparative Cohort Study.
BACKGROUND
Inflammatory type focal cerebral arteriopathy (FCA-i) in the anterior circulation (AC) is well characterized, and the focal cerebral arteriopathy severity score (FCASS) reflects the severity of the disease. We identified cases of FCA-i in the posterior circulation (PC) and adapted the FCASS to describe these cases.
METHODS
In this comparative cohort study, patients from the Swiss NeuroPaediatric Stroke Registry with ischemic stroke due to FCA-i between January 2000 and December 2018 were analyzed. A comparison between PC and AC cases regarding pediatric National Institutes of Health Stroke Scale score and pediatric stroke outcome measure and FCASS was performed. We estimated infarct size by the modified pediatric Alberta Stroke Program Early Computed Tomography Score in children with AC stroke and the adapted Bernese posterior diffusion-weighted imaging score in the PC.
RESULTS
Thirty-five children with a median age of 6.3 (interquartile range, 2.7-8.2 [95% CI, 0.9-15.6]; 20 male; 57.1%) years with FCA-i were identified. The total incidence rate was 0.15/100 000/year (95% CI, 0.11-0.21). Six had PC-FCA-i. Time to final FCASS was longer in the PC compared with AC; the evolution of FCASS did not differ. Initial pediatric National Institutes of Health Stroke Scale score was higher in children with FCA-i in the PC with a median of 10.0 (interquartile range, 5.75-21.0) compared with 4.5 (interquartile range, 2.0-8.0) in those with AC-FCA-i. Different from the anterior cases, PC infarct volume did not correlate with higher discharge, maximum, or final FCASS scores (Pearson correlation coefficient [r], 0.25, 0.35, and 0.54).
CONCLUSIONS
FCA-i also affects the PC. These cases should be included in future investigations into FCA-i. Although it did not correlate with clinical outcomes in our cohort, the modified FCASS may well serve as a marker for the evolution of the arteriopathy in posterior FCA-i
Pediatric Patients with Eosinophilic Esophagitis and Their Parents Identify Symptoms as the Most Important Treatment Outcome.
INTRODUCTION
Given the lack of data, we aimed to explore which therapeutic endpoints pediatric patients with eosinophilic esophagitis (EoE) and their parents consider to be relevant.
METHODS
We created an educational brochure on EoE and a questionnaire, both of which were content-validated by pediatric patients and parents. Validated documents were sent to 112 patients and parents. They ranked the importance (5 levels) of short (during next 3 months) and long-term (≥1 year) treatment effect on symptoms, quality of life, endoscopic inflammation, stricture formation, histological inflammation, and fibrosis.
RESULTS
A total of 45 parents and 30 pediatric patients ≥11 years completed the questionnaires. Pediatric patients identified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (73% vs. 77%), QoL (53% vs. 57%), histologic inflammation (47% vs. 50%), histologic fibrosis (40% vs. 33%), endoscopic inflammation (47% vs. 40%), and strictures (33% vs. 40%). Parents of children ≥11 years old classified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (70% vs. 83%), QoL (63% vs. 80%), histologic inflammation (67% vs. 77%), histologic fibrosis (47% vs. 63%), endoscopic inflammation (77% vs. 80%), and strictures (40% vs. 53%). Agreement between caregiver and children on the short-term importance of treatment outcomes was as follows: symptoms (77%), QoL (40%), histologic inflammation and fibrosis (47% and 43%), endoscopic inflammation and strictures (50% and 40%).
CONCLUSION
Pediatric patients and parents attributed most importance to improvement in symptoms and QoL. Agreement between parents and patients regarding therapy goals is limited
Dominance and multi-locus interaction.
Dominance is usually considered a constant value that describes the relative difference in fitness or phenotype between heterozygotes and the average of homozygotes at a focal polymorphic locus. However, the observed dominance can vary with the genetic background of the focal locus. Here, alleles at other loci modify the observed phenotype through position effects or dominance modifiers that are sometimes associated with pathogen resistance, lineage, sex, or mating type. Theoretical models have illustrated how variable dominance appears in the context of multi-locus interaction (epistasis). Here, we review empirical evidence for variable dominance and how the observed patterns may be captured by proposed epistatic models. We highlight how integrating epistasis and dominance is crucial for comprehensively understanding adaptation and speciation
Climate Fluctuations and Settlement Dynamics in the Northern Alpine Foreland (3950–3200 BCE)
Since the dendrochronological revolution, we know that Neolithic lake and wetland settlements in the Northern Alpine Foreland were short-lived and their communities highly mobile. This was not in keeping with the expectations of sedentary agriculturalists in other regions or earlier periods of prehistoric Europe. Over time it became clear that the transience and mobility of lakeshore settlement communities was not forcefully only driven by climatic fluctuations, but first and foremost by sophisticated socio-economic forms of organization. However, the intensity of lakeshore settlements varied over time. Early on, it was suggested that climatic changes in environmental conditions – namely lake levels – led to the abandonment and re-settling of the settlement locations situated at the lakeshores. This hypothesis still needs further evaluation.
In this presentation we examine a dataset of dendrochronologically dated lakeshore settlements in the northern Alpine foreland and to test if climatic fluctuations were a central driving force to settlement dynamics. On the basis of a yearly precise sequence of contemporaneous lakeshore settlements, correlations with a number of climate proxies can be tested and interpreted. We put special emphasis on the first half of the 4th millennium BCE, as this is the initial phase of the so-called ‘lake-dwelling Neolithic’ in the Circum Alpine region and corresponds to the Michelsberg Culture. Preliminary results suggest correlations between climatic fluctuations and the (re-)settling and abandonment of lake shores in the Three-Lakes Region of western Switzerland and beyond. With our data, we aim to explore the resilience of local ‘wetland communities’ to changing climates and environments through their mobile lifestyles, and possible impulses for extending models of settlement dynamics in other regions and time periods
Reciprocal association between pain and quality of life after newly acquired spinal cord injury.
PURPOSE
Pain is highly prevalent in spinal cord injury (SCI) and a key determinant of quality of life (QoL). This is the first study to examine reciprocal associations between pain and QoL in patients undergoing their first inpatient rehabilitation after SCI.
METHODS
Longitudinal data, with three measurement time points (1 month and 3 months after SCI onset, and at discharge from inpatient rehabilitation) from the Inception Cohort of the Swiss Spinal Cord Injury Cohort Study. Participants were 381 individuals aged ≥ 16 years with a newly diagnosed traumatic or non-traumatic SCI. 75.1% were male and the average age was 53.2 years. Random intercept cross-lagged panel models were conducted to examine the reciprocal association between pain intensity and QoL, as measured with the International SCI QoL Basic Data Set three individual items (satisfaction with life, physical health, and psychological health) and total score (mean of the three individual items).
RESULTS
Both item and total QoL scores increased over time. 1 month: 5.3 (SD = 2.7), 3 months: 5.9 (SD = 2.3), discharge: 6.6 (SD = 2.0). Participants reported relatively low levels of pain intensity that remained stable over the course of inpatient rehabilitation. 1 month: 2.7 (SD = 2.3), 3 months: 2.6 (SD = 2.4), discharge: 2.7 (SD = 2.5). There were no significant cross-lagged associations between QoL and pain intensity across time.
CONCLUSION
Results indicate that pain intensity does not predict changes in QoL during first rehabilitation, and vice versa. Associations between pain intensity and QoL reported by previous studies may be attributable to individual characteristics and timely events that simultaneously influence pain and QoL
Impacts of preweaning colostrum feeding practices and health measures on dairy cow production, while accounting for genetic potential.
Calf management and health are essential for setting up the foundation of a productive cow. The objectives of this study were to estimate the impact of preweaning practices on milk production parameters while accounting for an animal's genetic potential in New Brunswick, Canada. A retrospective cohort study was performed on 220 heifer calves from eight herds born in 2014-2015. Preweaning practices and health data were recorded by producers and reviewed by the herd veterinarian for each calf. The herd veterinarian also visited the farms to collect serum samples from calves and frozen colostrum samples. The production outcomes assessed were milk, protein and fat yields, standardized to 305 d for the first lactation (L1) and a combined group of lactations two and three (L2 + 3). The genomic potential was determined as genomic parent averages (GPA) for the associated production parameters. Analysis was performed with multivariable linear (L1) and linear mixed (L2 + 3) regression models. In L1, for every 1.0 kg increase in weaning weight, milk, protein, and fat yield increased by 25.5 kg, 0.82 kg, and 1.01 kg, respectively (P 2 h produced greater yield outcomes of 68.2 kg to 72.6 kg for milk (P < 0.006), 2.06 kg to 2.15 kg for protein (P < 0.005), and 1.8 kg to 1.9 kg for fat (P < 0.045) for every one kg increase of weaning weight, respectively. The fit of all models was significantly improved with the inclusion of GPA. These results indicate that colostrum management and preweaning health measures impacted production parameters as adults. The inclusion of GPA significantly improved the accuracy of the models, indicating that this can be an important parameter to include in future studies
Neurologic changes induced by whole-brain synchrotron microbeam irradiation: 10 months behavioral and veterinary follow-up.
PURPOSE
Novel radiotherapy approaches have increased the therapeutic efficacy for malignant brain tumors over the last decades but the balance between therapeutic gain and radiotoxicity remains a medical hardship. Synchrotron Microbeam Radiation Therapy (MRT), an innovative technique, deposes extremely high (peak) doses in micron-wide, parallel microbeam paths, while the diffusing inter-beam (valley) doses lie in the range of conventional radiotherapy doses. In this study, we evaluated normal tissue toxicity of whole-brain microbeam irradiation (MBI) versus that of a conventional, hospital broad beam (hBB).
METHODS AND MATERIALS
Normal Fischer rats (n=6-7/group) were irradiated with one of the two modalities, exposing the entire brain to 0, 5/200, 10/400, 13/520, 17/680 or 25/1000 Gy MBI valley/peak dose, or to 7, 10, 13, 17 or 25 Gy hBB dose. Two additional groups of rats received 10 Gy MBI valley dose coupled with 7 or 15 Gy BB dose (groups MBI17* and MBI25*). Behavioral parameters were evaluated for 10 months post irradiation, combined with veterinary observations.
RESULTS
MBI peak doses of ≥680 Gy caused acute toxicity and death. Animals exposed to hBB or MBI dose-dependently gained less weight than controls; rats in the hBB25 and MBI25* groups deceased within 6 months post irradiation. Increasing doses of MBI caused hyperactivity but no other detectable behavioral alteration in our tests. Importantly, no health concerns were seen up to 17 Gy MBI valley dose.
CONCLUSIONS
While acute toxicity of microbeam exposures depends on very high peak doses, late toxicity mainly relates to delivery of high MBI valley doses. MBI seems to elicit low impact on normal rat behavior but further tests are warranted to fully explore this hypothesis. However, high peak and valley doses are well tolerated from a veterinary point of view. This normal tissue tolerance to whole-brain, high-dose MBI reveals a promising avenue for MRT, i.e., therapeutic applications of microbeams which are poised for translation to a clinical environment
Polypharmacy in psychiatry and weight gain: longitudinal study of 832 patients hospitalized for depression or schizophrenia, along with data of 3180 students from Europe, the U.S., South America, and China.
Epidemiologic data indicate that overweight and obesity are on the rise worldwide. Psychiatric patients are particularly vulnerable in this respect as they have an increased prevalence of overweight and obesity, and often experience rapid, highly undesirable weight gain under psychotropic drug treatment. Current treatment strategies in psychiatry are oriented towards polypharmacy, so that the information on drug-induced weight gain from earlier monotherapy studies is of very limited validity. We have analyzed the longitudinal data of 832 inpatients with ICD-10 diagnoses of either F2 (schizophrenia; n = 282) or F3 (major depression; n = 550) with the goal of ranking treatment regimens in terms of weight gain, side effects, and response to treatment. The patient data were complemented by the data of 3180 students aged 18-22 years, with which we aimed to identify factors that enable the early detection and prevention of obesity and mental health problems. After 3 weeks of treatment, 47.7% of F2 patients and 54.9% of F3 patients showed a weight gain of 2 kg and more. Major predictive factors were "starting weight" (r = 0.115), "concurrent medications" (r = 0.176), and "increased appetite"(r = 0.275). Between 11 and 30% of the observed variance in weight gain could be explained by these factors, complemented by sex and age. The comparison between monotherapy (n = 409) and polypharmacy (n = 399) revealed significant drawbacks for polypharmacy: higher weight gain (p = 0.0005), more severe side effects (p = 0.0011), and lower response rates (F2: p = 0.0008); F3: p = 0.0101). The data of 3180 students made it clear that overweight and obesity often begin early in life among those affected, and are interconnected with personality traits, while increasing the risk of developing psychosomatic disturbances, mental health problems, or somatic illnesses. Although the available data did not readily lead to a comprehensive, clinically applicable model of unwanted weight gain, our results have nevertheless demonstrated that there are ways to successfully counteract such weight gain at early stages of treatment