Microstructure alterations in the Hypothalamus in cranially radiated Childhood Leukemia survivors but not in Craniopharyngioma patients unaffected by hypothalamic damage

Abstract

Objective

Metabolic complications are frequent in childhood leukemia (ALL) survivors treated with cranial radiotherapy (CRT). These complications are potentially mediated by damage to the hypothalamus (HT), as childhood onset (CO) craniopharyngioma (CP) survivors without HT involvement are spared overt obesity. Diffusion tensor imaging (DTI) shows brain tissue microstructure alterations, by fractional anisotrophy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). We used DTI to determine the integrity of the microstructure of the HT in ALL survivors.

Design

Case-control study.

Patients

Three groups were included: i) 27 CRT treated ALL survivors on hormone supplementation, ii) 17 CO-CP survivors on hormone supplementation but without HT involvement, and iii) 27 matched controls.

Measurements

DTI parameters of the HT were measured and body composition.

Results

Microstructural alterations in the HT were more severe in ALL survivors with a BMI ≥ 25 than with BMI < 25. Compared to controls, ALL survivors had reduced FA (P=0.04), increased MD (P<0.001), AD (P<0.001), and RD (P<0.001) in the right and left HT. In the right HT ALL survivors with a BMI ≥ 25 showed elevated MD (P=0.03) and AD (P=0.02) compared to ALL survivors with BMI < 25. In contrast, DTI parameters did not differ between CP survivors and controls.

Conclusions

Long-term follow up after CRT for ALL DTI measures were affected in the HT despite complete hormone replacement. The present data suggest that ALL survivors have demyelination and axonal loss in the HT.

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Longitudinal Changes in Serum 25-Hydroxyvitamin D in the Dallas Heart Study

Abstract

Context

While the prevalence of vitamin D deficiency is well described in various populations, limited data are available regarding longitudinal variation in serum 25-hydroxyvitamin D concentrations.

Objectives

To evaluate the temporal trends in serum 25(OH)D, prevalence of vitamin D deficiency, and factors influencing these trends.

Participants, Design and Setting

Adults enrolled in the Dallas Heart Study, a longitudinal, probability-based, multiethnic, population study in Dallas, Texas, USA.

Main Outcome Measures

Prevalence of vitamin D deficiency and predictors of change in serum 25(OH)D.

Results

2045 participants had serum 25(OH)D measured on two occasions (2000-2002 and 2007-2009) at a median interval of seven years. Serum 25(OH)D decreased (42.7 to 39.4 nmol/l, p<0.001) and the prevalence of vitamin D deficiency [25(OH)D < 50 nmol/l] increased significantly (60.6% to 66.4%, p<0.0001) despite vitamin D supplementation increasing over the interval (7.2% to 23.0%; p<0.0001). In a multivariable model adjusting for sex, race, BMI, age, season of blood draw, smoking, and exercise, a greater decline in serum 25(OH)D was noted in men compared with women (-8.0 vs. -3.5 nmol/l, p < 0.0001), in participants of Hispanic ethnicity vs. White and Black ethnicity (p<0.0001), in non-obese vs. obese participants (-7.2 vs. -4.0 nmol/l, p=0.005), and in non-users vs. users of vitamin D supplements (-5.7 vs. -1.7 nmol/l, p=0.032).

Conclusions

Despite increased vitamin D supplementation, serum 25(OH)D decreased in an ethnically diverse cohort of Dallas County residents between 2000-2002 and 2007-2009. Features most predictive of a decline in serum 25(OH)D include male sex, Hispanic ethnicity, and weight gain.

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Macrophage polarization differs between apical granulomas, radicular cysts, and dentigerous cysts

Abstract

Objectives

Apical periodontitis can appear clinically as apical granulomas or radicular cysts. There is evidence that immunologic factors are involved in the pathogenesis of both pathologies. In contrast to radicular cysts, the dentigerous cysts have a developmental origin. Macrophage polarization (M1 vs M2) is a main regulator of tissue homeostasis and differentiation. There are no studies comparing macrophage polarization in apical granulomas, radicular cysts, and dentigerous cysts.

Materials and methods

Forty-one apical granulomas, 23 radicular cysts, and 23 dentigerous cysts were analyzed in this study. A tissue microarray (TMA) of the 87 consecutive specimens was created, and CD68-, CD11c-, CD163-, and MRC1-positive macrophages were detected by immunohistochemical methods. TMAs were digitized, and the expression of macrophage markers was quantitatively assessed.

Results

Radicular cysts are characterized by M1 polarization of macrophages while apical granulomas show a significantly higher degree of M2 polarization. Dentigerous cysts have a significantly lower M1 polarization than both analyzed periapical lesions (apical granulomas and radicular cysts) and accordingly, a significantly higher M2 polarization than radicular cysts. Macrophage cell density in dentigerous cysts is significantly lower than in the periapical lesions.

Conclusions

The development of apical periodontitis towards apical granulomas or radicular cysts might be directed by macrophage polarization. Radicular cyst formation is associated with an increased M1 polarization of infiltrating macrophages. In contrast to radicular cysts, dentigerous cysts are characterized by a low macrophage infiltration and a high degree of M2 polarization, possibly reflecting their developmental rather than inflammatory origin.

Clinical relevance

As M1 polarization of macrophages is triggered by bacterial antigens, these results underline the need for sufficient bacterial clearance during endodontic treatment to prevent a possible M1 macrophage-derived stimulus for radicular cyst formation.

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Brain Sciences, Vol. 7, Pages 54: Neuronal Migration and AUTS2 Syndrome

Neuronal migration is one of the pivotal steps to form a functional brain, and disorganization of this process is believed to underlie the pathology of psychiatric disorders including schizophrenia, autism spectrum disorders (ASD) and epilepsy. However, it is not clear how abnormal neuronal migration causes mental dysfunction. Recently, a key gene for various psychiatric diseases, the Autism susceptibility candidate 2 (AUTS2), has been shown to regulate neuronal migration, which gives new insight into understanding this question. Interestingly, the AUTS2 protein has dual functions: Cytoplasmic AUTS2 regulates actin cytoskeleton to control neuronal migration and neurite extension, while nuclear AUTS2 controls transcription of various genes as a component of the polycomb complex 1 (PRC1). In this review, we discuss AUTS2 from the viewpoint of human genetics, molecular function, brain development, and behavior in animal models, focusing on its role in neuronal migration.

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Evaluation of the N-latex serum free light chain assay on the Siemens BNII analyzer and agreement with The Binding Site FreeLite assay on the SPAPlus

Publication date: Available online 13 May 2017
Source:Clinical Biochemistry
Author(s): Nicole M.A. White-Al Habeeb, Tammy Earle, Megan Spencer, Ivan M. Blasutig
ObjectivesTo evaluate the Siemens N-latex kappa free light chain (κFLC) and lambda FLC (λFLC) assays on the BNII nephelometer and assess agreement with The Binding Site Freelite FLC assays on the SPAPlus.Design and methodsOver 180 patient serum samples from routine analysis of κFLC and λFLC measured by the Freelite assay were collected for the study and measured with the N-latex κFLC and λFLC assays to assess precision, linearity, method comparison and dilutional effects.ResultsComplex precision showed coefficients of variation of 4.8–7.2% for the κFLC assay and 3.6–6.0% for the λFLC assay. Linearity assessment showed both assays were linear (κFLC, y=1.00x−0.09 and λFLC, y=1.050x−1.252). Qualitative method comparison showed 87.9% (116/132) agreement and Cohen's kappa of 80.4% between the κFLC assays and 72.6% (98/135) agreement and Cohen's kappa of 55.4% for the λFLC assays. Quantitative method comparison for κFLC<150mg/L was y=0.92x+2.21, R=0.661 and for λFLC<150mg/L was y=7.90x−137.96, R=0.526. Dilutional effects including antigen excess and non-linearity were also examined.ConclusionsThe N-latex assay showed good precision and linearity with reasonable agreement to the Freelite assay. However, the assays should not be used interchangeably to monitor patients.



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Batten disease

Batten disease: a rare, fatal genetic condition that typically begins in childhood. It is a form of a group of neurologic disorders called the neuronal ceroid lipofuscinoses, or NCLs. The term Batten disease is sometimes used to refer to all the NCL disorders. Early signs can be vision changes, seizures, clumsiness, or behavior changes. With time, neurologic deficits worsen, and the individual loses sight and motor skills. Cognitive abilities decline and dementia develops with time. The disease is often fatal by the teens or twenties. It is also known as Spielmeyer-Vogt-Sjögren-Batten disease. Batten disease is inherited in an autosomal recessive manner.

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Editorial Board

Publication date: July 2017
Source:Cellular Signalling, Volume 35





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