Letter from E. Van Unen to Waarde Broeder

A letter of E. van Unen to Waar de Broeder. A translated quote of the letter states: Dominee Van Raalte visited us on Thursday and it was especially uplifting. The worthy continues to visit us and displays his loyalty as a servant of the Evangelie and is not ashamed to show his bond/ties with us. The rest of the letter is about how they are often fined and then jailed but they continue to struggle forward.https://digitalcommons.hope.edu/vrp_1830s/1099/thumbnail.jp

Resuscitation with Valproic Acid Alters Inflammatory Genes in a Porcine Model of Combined Traumatic Brain Injury and Hemorrhagic Shock

Traumatic brain injury and hemorrhagic shock (TBI+HS) elicit a complex inflammatory response that contributes to secondary brain injury. There is currently no proven pharmacologic treatment for TBI+HS, but modulation of the epigenome has been shown to be a promising strategy. The aim of this study was to investigate whether valproic acid (VPA), a histone deacetylase inhibitor, modulates the expression of cerebral inflammatory gene profiles in a large animal model of TBI+HS. Ten Yorkshire swine were subjected to computer-controlled TBI+HS (40% blood volume). After 2?h of shock, animals were resuscitated with Hextend (HEX) or HEX+VPA (300?mg/kg, n?=?5/group). Six hours after resuscitation, brains were harvested, RNA was isolated, and gene expression profiles were measured using a porcine microarray. Ingenuity Pathway Analysis? (IPA), gene ontology (GO), Parametric Gene Set Enrichment Analysis (PGSEA), and DAVID (Database for Annotation, Visualization, and Integrated Discovery) were used for pathway analysis. Key microarray findings were verified using real-time polymerase chain reaction (PCR). IPA analysis revealed that VPA significantly down-regulated the complement system (p?Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140171/1/neu.2015.4163.pd

Fresh Frozen Plasma Resuscitation Provides Neuroprotection Compared to Normal Saline in a Large Animal Model of Traumatic Brain Injury and Polytrauma

We have previously shown that early treatment with fresh frozen plasma (FFP) is neuroprotective in a swine model of hemorrhagic shock (HS) and traumatic brain injury (TBI). However, it remains unknown whether this strategy would be beneficial in a more clinical polytrauma model. Yorkshire swine (42?50?kg) were instrumented to measure hemodynamic parameters, brain oxygenation, and intracranial pressure (ICP) and subjected to computer-controlled TBI and multi-system trauma (rib fracture, soft-tissue damage, and liver injury) as well as combined free and controlled hemorrhage (40% blood volume). After 2?h of shock (mean arterial pressure, 30?35?mm Hg), animals were resuscitated with normal saline (NS; 3?volume) or FFP (1?volume; n=6/group). Six hours postresuscitation, brains were harvested and lesion size and swelling were evaluated. Levels of endothelial-derived vasodilator endothelial nitric oxide synthase (eNOS) and vasoconstrictor endothelin-1 (ET-1) were also measured. FFP resuscitation was associated with reduced brain lesion size (1005.8 vs. 2081.9?mm3; p=0.01) as well as swelling (11.5% vs. 19.4%; p=0.02). Further, FFP-resuscitated animals had higher brain oxygenation as well as cerebral perfusion pressures. Levels of cerebral eNOS were higher in the FFP-treated group (852.9 vs. 816.4?ng/mL; p=0.03), but no differences in brain levels of ET-1 were observed. Early administration of FFP is neuroprotective in a complex, large animal model of polytrauma, hemorrhage, and TBI. This is associated with a favorable brain oxygenation and cerebral perfusion pressure profile as well as higher levels of endothelial-derived vasodilator eNOS, compared to normal saline resuscitation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140168/1/neu.2014.3535.pd

Fishery-Induced Selection for Slow Somatic Growth in European Eel

Both theoretical and experimental studies have shown that fishing mortality can induce adaptive responses in body growth rates of fishes in the opposite direction of natural selection. We compared body growth rates in European eel (Anguilla anguilla) from three Mediterranean stocks subject to different fishing pressure. Results are consistent with the hypotheses that i) fast-growing individuals are more likely to survive until sexual maturity than slow-growing ones under natural conditions (no fishing) and ii) fishing can select for slow-growing individuals by removing fast-growing ones. Although the possibility of human-induced evolution seems remote for a panmictic species like such as the European eel, further research is desirable to assess the implications of the intensive exploitation on this critically endangered fish

An extremely primitive halo star

The early Universe had a chemical composition consisting of hydrogen, helium and traces of lithium1, almost all other elements were created in stars and supernovae. The mass fraction, Z, of elements more massive than helium, is called "metallicity". A number of very metal poor stars have been found some of which, while having a low iron abundance, are rich in carbon, nitrogen and oxygen. For theoretical reasons and because of an observed absence of stars with metallicities lower than Z=1.5E-5, it has been suggested that low mass stars (M<0.8M\odot, the ones that survive to the present day) cannot form until the interstellar medium has been enriched above a critical value, estimated to lie in the range 1.5E-8\leqZ\leq1.5E-6, although competing theories claiming the contrary do exist. Here we report the chemical composition of a star with a very low Z\leq6.9E-7 (4.5E-5 of that of the Sun) and a chemical pattern typical of classical extremely metal poor stars, meaning without the enrichment of carbon, nitrogen and oxygen. This shows that low mass stars can be formed at very low metallicity. Lithium is not detected, suggesting a low metallicity extension of the previously observed trend in lithium depletion. Lithium depletion implies that the stellar material must have experienced temperatures above two million K in its history, which points to rather particular formation condition or internal mixing process, for low Z stars.Comment: Published on Nature, 2011 Volume 477, Issue 7362, pp. 67-6

Cognitive Behavioral Therapy versus Short Psychodynamic Supportive Psychotherapy in the outpatient treatment of depression: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Previous research has shown that Short Psychodynamic Supportive Psychotherapy (SPSP) is an effective alternative to pharmacotherapy and combined treatment (SPSP and pharmacotherapy) in the treatment of depressed outpatients. The question remains, however, how Short Psychodynamic Supportive Psychotherapy compares with other established psychotherapy methods. The present study compares Short Psychodynamic Supportive Psychotherapy to the evidence-based Cognitive Behavioral Therapy in terms of acceptability, feasibility, and efficacy in the outpatient treatment of depression. Moreover, this study aims to identify clinical predictors that can distinguish patients who may benefit from either of these treatments in particular. This article outlines the study protocol. The results of the study, which is being currently carried out, will be presented as soon as they are available.</p> <p>Methods/Design</p> <p>Adult outpatients with a main diagnosis of major depressive disorder or depressive disorder not otherwise specified according to DSM-IV criteria and mild to severe depressive symptoms (<it>Hamilton Depression Rating Scale </it>score ≥ 14) are randomly allocated to Short Psychodynamic Supportive Psychotherapy or Cognitive Behavioral Therapy. Both treatments are individual psychotherapies consisting of 16 sessions within 22 weeks. Assessments take place at baseline (week 0), during the treatment period (week 5 and 10) and at treatment termination (week 22). In addition, a follow-up assessment takes place one year after treatment start (week 52). Primary outcome measures are the number of patients refusing treatment (acceptability); the number of patients terminating treatment prematurely (feasibility); and the severity of depressive symptoms (efficacy) according to an independent rater, the clinician and the patient. Secondary outcome measures include general psychopathology, general psychotherapy outcome, pain, health-related quality of life, and cost-effectiveness. Clinical predictors of treatment outcome include demographic variables, psychiatric symptoms, cognitive and psychological patient characteristics and the quality of the therapeutic relationship.</p> <p>Discussion</p> <p>This study evaluates Short Psychodynamic Supportive Psychotherapy as a treatment for depressed outpatients by comparing it to the established evidence-based treatment Cognitive Behavioral Therapy. Specific strengths of this study include its strong external validity and the clinical relevance of its research aims. Limitations of the study are discussed.</p> <p>Trial registration</p> <p>Current Controlled Trails ISRCTN31263312</p

Development, Problem Behavior, and Quality of Life in a Population Based Sample of Eight-Year-Old Children with Down Syndrome

OBJECTIVE: Children with Down syndrome (DS) have delayed psychomotor development. We investigated levels of development, problem behavior, and Health-Related Quality of Life (HRQoL) in a population sample of Dutch eight-year-old children with DS. Developmental outcomes were compared with normative data of eight-year-old children from the general population. METHOD: Over a three-year-period all parents with an eight-year-old child with DS were approached by the national parent organization. Developmental skills were assessed by means of the McCarthy Scales of Children's Ability. To measure emotional and behavioral problems we used the Child Behavior Checklist. HRQoL was assessed with the TNO-AZL Children's Quality of Life questionnaire. Analyses of variance were applied to compare groups. RESULTS: A total of 337 children participated. Mean developmental age was substantially lower than mean calendar age (3.9 years, SD 0.87 and 8.1 years, SD 0.15 respectively). Mean developmental age was significantly lower among boys than girls (3.6 (SD 0.85) and 4.2 years (SD 0.82) respectively; p<0.001). Compared with the general population, children with DS had more emotional and behavioral problems (p<0.001). However on the anxious/depressed scale, they scored significantly more favorably (p<0.001). Significantly lower HRQoL scores for the scales gross motor skills, autonomy, social functioning and cognitive functioning were found (p-values<0.001). Hardly any differences were observed for the scales physical complaints, positive and negative emotions. CONCLUSION: Eight-year-old children with DS have an average developmental delay of four years, more often have emotional and behavioral problems, and have a less favorable HRQoL compared with children from the general population

Predicting glycated hemoglobin levels in the non-diabetic general population:Development and validation of the DIRECT-DETECT prediction model - a DIRECT study

AIMS/HYPOTHESIS: To develop a prediction model that can predict HbA1c levels after six years in the non-diabetic general population, including previously used readily available predictors. METHODS: Data from 5,762 initially non-diabetic subjects from three population-based cohorts (Hoorn Study, Inter99, KORA S4/F4) were combined to predict HbA1c levels at six year follow-up. Using backward selection, age, BMI, waist circumference, use of anti-hypertensive medication, current smoking and parental history of diabetes remained in sex-specific linear regression models. To minimize overfitting of coefficients, we performed internal validation using bootstrapping techniques. Explained variance, discrimination and calibration were assessed using R2, classification tables (comparing highest/lowest 50% HbA1c levels) and calibration graphs. The model was externally validated in 2,765 non-diabetic subjects of the population-based cohort METSIM. RESULTS: At baseline, mean HbA1c level was 5.6% (38 mmol/mol). After a mean follow-up of six years, mean HbA1c level was 5.7% (39 mmol/mol). Calibration graphs showed that predicted HbA1c levels were somewhat underestimated in the Inter99 cohort and overestimated in the Hoorn and KORA cohorts, indicating that the model's intercept should be adjusted for each cohort to improve predictions. Sensitivity and specificity (95% CI) were 55.7% (53.9, 57.5) and 56.9% (55.1, 58.7) respectively, for women, and 54.6% (52.7, 56.5) and 54.3% (52.4, 56.2) for men. External validation showed similar performance in the METSIM cohort. CONCLUSIONS/INTERPRETATION: In the non-diabetic population, our DIRECT-DETECT prediction model, including readily available predictors, has a relatively low explained variance and moderate discriminative performance, but can help to distinguish between future highest and lowest HbA1c levels. Absolute HbA1c values are cohort-dependent

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons