Radiation-Induced Cerebral Contrast Enhancements Strongly Share Ischemic Stroke Risk Factors.

PURPOSE: Radiation-induced cerebral contrast enhancements (RICE) are frequent after photon and particularly proton radiation therapy and are associated with a significant risk for neurologic morbidity. Nevertheless, risk factors are poorly understood. A more robust understanding of RICE risk factors is crucial to improve management and offer adaptive therapy at the outset and during follow-up. METHODS AND MATERIALS: We analyzed the comorbidities in detail of 190 consecutive adult patients treated at a single European national comprehensive cancer center with proton radiation therapy (54 Gy relative biological effectiveness) for LGG from 2010 to 2020 who were followed with serial clinical examinations and magnetic resonance imaging for a median 5.6 years. RESULTS: Classical vascular risk factors including age (≥50 vs <50 years: 1.6-fold; P = .0024), hypertension (2.7-fold; P = .00012), and diabetes (11.7-fold; P = .0066) were observed more frequently in the cohort that developed RICE. Dyslipidemia (2.1-fold), being overweight (2.0-fold), and smoking (2.6-fold), as well as history of previous stroke (1.7-fold), were also more frequently observed in the RICE cohort, although these factors did not reach the threshold for significance. Multivariable regression modeling supported the influence of age (P = .05), arterial hypertension (P = .01), and potentially male sex (P = .02), diabetes (P = .0008), and smoking (P = .001) on RICE occurrence over time, independent of each other and further vascular risk factors. If RICE occurred, bevacizumab treatment was 2-fold more frequently needed in the cohort with vascular risk factors, but RICE long-term prognosis did not differ between the RICE subcohorts with and without vascular risk factors. CONCLUSIONS: This is the first report in the literature demonstrating that RICE strongly shares vascular risk factors with ischemic stroke, which further enhances the nebulous understanding of the multifactorial pathophysiology of RICE. Classical vascular risk factors, especially age, hypertension, and diabetes, clearly correlated independently with RICE risk. Risk-adapted screening and management for RICE can be directly derived from these data to assist in clinical management.

The impact of adverse childhood experiences and posttraumatic stress symptoms on chronic pain.

Introduction: Chronic pain is a prevalent worldwide health condition. The current study aimed to extend previous research that investigated the dynamics between chronic pain, adverse childhood experiences (ACEs), and post-traumatic stress symptoms (PTSS). Method: Adult participants worldwide with chronic pain were recruited for this study (N = 199; 89% females). Three hypotheses were proposed: (a) a high ACEs score would result in more severe pain intensity and interference compared to no ACEs; (b) a low ACEs score would result in more severe pain intensity and interference compared to no ACEs; and (c) PTSS would fully mediate the ACEs-pain relationship. Results: Initially results indicated individuals with high ACEs reported more pain interference than those with no ACEs, although pain intensity did not differ between high and no ACEs. However, after controlling for age, socioeconomic status (SES), and pain duration, low and high ACEs were not significantly associated with pain intensity or interference compared to no ACEs. However, SES status was associated with pain intensity and interference, although not with pain interference after adding low and high ACEs to the model. Because of this the mediation exploration of PTSS was not viable. Discussion: Implications for practice, limitations and future research outcomes are outlined.

Corrigendum: The impact of adverse childhood experiences and posttraumatic stress symptoms on chronic pain.

[This corrects the article DOI: 10.3389/fpsyg.2023.1243570.].

TargetGeneReg 2.0: a comprehensive web-atlas for p53, p63, and cell cycle-dependent gene regulation.

In recent years, our web-atlas at www.TargetGeneReg.org has enabled many researchers to uncover new biological insights and to identify novel regulatory mechanisms that affect p53 and the cell cycle - signaling pathways that are frequently dysregulated in diseases like cancer. Here, we provide a substantial upgrade of the database that comprises an extension to include non-coding genes and the transcription factors ΔNp63 and RFX7. TargetGeneReg 2.0 combines gene expression profiling and transcription factor DNA binding data to determine, for each gene, the response to p53, ΔNp63, and cell cycle signaling. It can be used to dissect common, cell type and treatment-specific effects, identify the most promising candidates, and validate findings. We demonstrate the increased power and more intuitive layout of the resource using realistic examples.

Locus-specific expression analysis of transposable elements.

Transposable elements (TEs) have been associated with many, frequently detrimental, biological roles. Consequently, the regulations of TEs, e.g. via DNA-methylation and histone modifications, are considered critical for maintaining genomic integrity and other functions. Still, the high-throughput study of TEs is usually limited to the family or consensus-sequence level because of alignment problems prompted by high-sequence similarities and short read lengths. To entirely comprehend the effects and reasons of TE expression, however, it is necessary to assess the TE expression at the level of individual instances. Our simulation study demonstrates that sequence similarities and short read lengths do not rule out the accurate assessment of (differential) expression of TEs at the instance-level. With only slight modifications to existing methods, TE expression analysis works surprisingly well for conventional paired-end sequencing data. We find that SalmonTE and Telescope can accurately tally a considerable amount of TE instances, allowing for differential expression recovery in model and non-model organisms.

Worldwide variations in artificial skyglow.

Despite constituting a widespread and significant environmental change, understanding of artificial nighttime skyglow is extremely limited. Until now, published monitoring studies have been local or regional in scope, and typically of short duration. In this first major international compilation of monitoring data we answer several key questions about skyglow properties. Skyglow is observed to vary over four orders of magnitude, a range hundreds of times larger than was the case before artificial light. Nearly all of the study sites were polluted by artificial light. A non-linear relationship is observed between the sky brightness on clear and overcast nights, with a change in behavior near the rural to urban landuse transition. Overcast skies ranged from a third darker to almost 18 times brighter than clear. Clear sky radiances estimated by the World Atlas of Artificial Night Sky Brightness were found to be overestimated by ~25%; our dataset will play an important role in the calibration and ground truthing of future skyglow models. Most of the brightly lit sites darkened as the night progressed, typically by ~5% per hour. The great variation in skyglow radiance observed from site-to-site and with changing meteorological conditions underlines the need for a long-term international monitoring program.

Scrib:Rac1 interactions are required for the morphogenesis of the ventricular myocardium.

AIMS: The organization and maturation of ventricular cardiomyocytes from the embryonic to the adult form is crucial for normal cardiac function. We have shown that a polarity protein, Scrib, may be involved in regulating the early stages of this process. Our goal was to establish whether Scrib plays a cell autonomous role in the ventricular myocardium, and whether this involves well-known polarity pathways. METHODS AND RESULTS: Deletion of Scrib in cardiac precursors utilizing Scrib(flox) mice together with the Nkx2.5-Cre driver resulted in disruption of the cytoarchitecture of the forming trabeculae and ventricular septal defects. Although the majority of mice lacking Scrib in the myocardium survived to adulthood, they developed marked cardiac fibrosis. Scrib did not physically interact with the planar cell polarity (PCP) protein, Vangl2, in early cardiomyocytes as it does in other tissues, suggesting that the anomalies did not result from disruption of PCP signalling. However, Scrib interacted with Rac1 physically in embryonic cardiomyocytes and genetically to result in ventricular abnormalities, suggesting that this interaction is crucial for the development of the early myocardium. CONCLUSIONS: The Scrib-Rac1 interaction plays a crucial role in the organization of developing cardiomyocytes and formation of the ventricular myocardium. Thus, we have identified a novel signalling pathway in the early, functioning, heart muscle. These data also show that the foetus can recover from relatively severe abnormalities in prenatal ventricular development, although cardiac fibrosis can be a long-term consequence.

Coexistence of psoriasis and pemphigoid--only a coincidence?

It has previously been reported that pemphigoid coexists with psoriasis more frequently than it could be predicted on the basis of random distribution in the general population. In this study we present three psoriatic patients who developed tense blisters, which most likely were not provoked by anti-psoriatic treatment. Diagnosis of bullous pemphigoid in these cases was established by an overlay antigen mapping technique by laser confocal microscopy, immunoblotting and ELISA. In the context of these cases and the literature, we also discuss possible reasons for the coexistence of psoriasis and pemphigoid as well as selected aspects of diagnosis and therapy of patients simultaneously suffering from these two diseases.

Pediatric kidney stones: long-term outcomes.

OBJECTIVES: To determine the specific risks for recurrent stone disease and which initial evaluations resulted in an effective reduction of risk, we undertook a long-term follow-up study of children who had experienced upper tract urinary stones. METHODS: Identified patients were contacted and interviewed using a structured questionnaire. The patient data were subcategorized and analyzed. RESULTS: The results demonstrated that our population had a recurrence rate similar to the reported adult stone recurrence rates. No evidence was found of impaired growth or development. Our population of noncircumcised boys did not demonstrate a high risk of struvite stones. Surgical techniques have evolved. Anatomic and metabolic factors were not a predictor of an adverse risk of recurrence. Cystinuria may carry extra risk, although our numbers were not sufficient to be sure. CONCLUSIONS: Extensive metabolic screening of children with upper tract urinary stones is not supported by the data from our patients. Testing for cystinuria is justified. The principles of screening and surveillance should match the recommended care of adults with stone formation.

Reliable manual segmentation of the frontal, parietal, temporal, and occipital lobes on magnetic resonance images of healthy subjects.

BACKGROUND: It is a challenge to reliably measure the lobar volumes from magnetic resonance imaging (MRI) data. OBJECTIVE: Description of a landmark-based method for volumetric segmentation of the brain into the four cerebral lobes from MR images. METHOD: The segmentation method relies on a combination of anatomical landmarks and geometrical definitions. The first step, described previously, is a segmentation of the four lobes on the surface of the brain. The internal borders between the lobes are defined on the axial slices of the brain. The intra- and inter- rater reliability was determined from the MRI scans of a group of 10 healthy control subjects measured by 2 independent raters. RESULTS: The intra-rater relative error (and intra-class correlation coefficient) of the lobar volume measures ranged from 0.81% to 3.85% (from 0.97 to 0.99). The inter-rater relative error (and intra-class correlation coefficient) ranged from 0.55% to 3.09% (from 0.94 to 0.99). CONCLUSION: This technique has been shown to have high intra- and inter-rater reliability. The current method provides a method to obtain volumetric estimates of the 4 cerebral lobes.

The Canadian Enuresis Study and Evaluation--short- and long-term safety and efficacy of an oral desmopressin preparation.

OBJECTIVE: To evaluate the long-term (12 months) efficacy and safety of oral desmopressin (DDAVP). MATERIAL AND METHODS: A total of 256 healthy children (6-18 years old) with nocturnal enuresis with a frequency of > or = 10 wet nights during a 4-week observation period were eligible for inclusion in the study. Initially 0.2 mg of DDAVP was given for 14 nights. Those achieving a > 90% reduction in the number of wet nights over the observation period (full responders) began a 12-week continuous treatment period at this dose. The remaining children received 0.4 mg for an additional 14 nights. Those achieving a > or = 50% reduction in the number of wet nights (responders) commenced a 12-week continuous treatment period at this dose. Children with a < 50% reduction in the number of wet nights at this point were withdrawn from the study. Each 12-week treatment period was followed by a treatment-free period of 7-28 days. Children who remained dry during that period were assigned a full response and terminated the trial. Children with > or = 2 wet nights during that period immediately began a new 12-week treatment period at the previous dose. This was repeated for 12 months and thereafter the medication dose was tapered by halving over a 4-week period. RESULTS: A total of 117/236 children who completed the titration period (49.6%; 95% confidence interval 40-57%) responded (> 50% reduction over baseline). Throughout the study their response rate remained constant at approximately 74%. Continuous treatment reduced the median number of wet nights during the observation period from 5.75 to 1.00 per week. A total of 12.4% of children received the 0.2 mg dose and 87.6% the 0.4 mg dose. The proportion of full responses increased over the course of the study from 5.8% to 37.5%. DDAVP was well tolerated: the majority of reported adverse events were mild, although two adverse events leading to withdrawal were reported. CONCLUSIONS: Oral DDAVP provides an effective and well-tolerated means of providing long-term control in children with nocturnal enuresis. Long-term treatment increases the response rate.

Age transformation of combined hippocampus and amygdala volume improves diagnostic accuracy in Alzheimer's disease.

OBJECTIVE: The specificity of magnetic resonance imaging (MRI)-based hippocampal measurements in detecting Alzheimer's disease (AD) pathology is reduced by an age-related reduction of the hippocampus volume. We propose an adjustment for this age effect to increase the diagnostic accuracy of hippocampal volumes in AD. METHOD: Using an orthogonal rotational transformation of the coordinate system, values of MRI-determined volumes of hippocampus-amygdala formation (HAF) were transformed according to the age effect in 27 AD patients and 28 age- and sex-matched healthy control subjects. RESULTS: The age transformation increased the diagnostic accuracy of HAF volumes in the study sample and in an independent sample from the literature. The age-transformed HAF volume predicted AD in a subject with mild cognitive impairment (MCI) with later biopsy-confirmed AD. CONCLUSION: Age transformation may provide an easily applicable method to increase the clinical diagnostic accuracy of hippocampal measurements by considering the effect of aging on hippocampus volume.