Extensive abnormality of brain white matter integrity in pathological gambling

Several magnetic resonance imaging (MRI) studies in substance use disorders have shown brain white matter integrity abnormalities, but there are no studies in pathological gambling, a form of behavioral addiction. Our objective was to investigate possible changes in regional brain gray and white matter volumes, and axonal white matter integrity in pathological gamblers compared to healthy controls. Twenty-four subjects (12 clinically diagnosed male pathological gamblers and 12 age-matched healthy male volunteers) underwent structural and diffusion weighted brain MRI scans, which were analyzed with voxel-based morphometry and tract based spatial statistics. In pathological gamblers, widespread lower white matter integrity (lower fractional anisotropy, higher mean diffusivity) was seen in multiple brain regions including the corpus callosum, the cingulum, the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the anterior limb of internal capsule, the anterior thalamic radiation, the inferior longitudinal fascicle and the uncinate/inferior fronto-occipital fascicle. There were no volumetric differences in gray or white matter between pathological gamblers and controls. The results suggest that pathological gambling is associated with extensive lower integrity of several brain white matter tracts. The diffusion abnormality closely resembles previous findings in individuals with substance addictions.     

Effects of growth and exercise on composition, structural maturation and appearance of osteoarthritis in articular cartilage of hamsters

Articular cartilage composition and structure are maintained and remodeled by chondrocytes under the influence of loading. Exercise‐induced changes in the composition, structure, mechanical properties and tissue integrity of growing and aging hamster articular cartilage were investigated. Articular cartilage samples (n = 191) were harvested from the proximal tibiae of hamsters aged 1, 3, 6, 12 and 15 months. The hamsters were divided into runners and controls. The runners had free access to a running wheel between 1 and 3 months (runner groups 3‐, 12‐ and 15‐month‐old hamsters) or 1 and 6 months (runner group 6‐month‐old hamsters) of age. Control animals were subjected to a sedentary lifestyle. Mechanical indentation tests and depth‐wise compositional and structural analyses were performed for the cartilage samples. Furthermore, the integrity of articular cartilage was assessed using histological osteoarthritis grading. Exercise affected the collagen network organization after a 5‐month exercise period, especially in the middle and deep zones. However, no effect on the mechanical properties was detected after exercise. Before the age of 12 months, the runners showed less osteoarthritis than the controls, whereas at 15 months of age the situation was reversed. It is concluded that, in hamsters, physical exercise at a young age enhances cartilage maturation and alters the depth‐wise cartilage structure and composition. This may be considered beneficial. However, exercise at a young age demonstrated adverse effects on cartilage at a later age with a significant increase in the incidence of osteoarthritis.     

Polymorphisms in the promoter region of <Emphasis Type="Italic">IL10</Emphasis> gene are associated with virus etiology of infant bronchiolitis

Background

Bronchiolitis is the most common infection leading to hospitalization in infancy. Interleukin-10 (IL-10) is an anti-inflammatory cytokine, and in our previous study, IL10 gene rs1800896 (??1082A/G) polymorphism was associated with viral etiology of infant bronchiolitis. The objective of this study was to evaluate the associations between IL10 single nucleotide polymorphisms (SNPs) at rs1800890 (??3575A/T), rs1800871 (??819C/T) or rs1800872 (??592C/A) either alone or combined with the SNP at rs1800896 (??1082G/A), and the etiology and severity of infant bronchiolitis.

Methods

Data on four IL10 SNPs were available from 135 full-term infants, hospitalized for bronchiolitis at age less than 6 months, and from 378 to 400 controls. Viral etiology was studied, and oxygen support, feeding support and the length of stay in hospital were recorded during bronchiolitis hospitalization.

Results

Infants with rhinovirus bronchiolitis had the IL10 rs1800890 variant AT or TT genotype less often (18.2%) than controls (63.3%, P?=?0.03), and likewise, had the IL10 rs1800896 variant AG or GG genotype less often (27.3%) than controls (65.5%, P?=?0.009). Twenty-eight infants with bronchiolitis had the variant–variant G_rs1800896T_rs1800890 haplotype, and none of them had rhinovirus infection. The IL10 rs1800871 or rs1800872 genotypes showed no associations with viruses. No association was found between any genotypes and bronchiolitis severity measures.

Conclusion

IL10 rs1800890 and rs1800896 polymorphisms differed between infants with rhinovirus bronchiolitis and controls, but not between infants with respiratory syncytial virus bronchiolitis and controls.

     

The role of DTNBP1, NRG1, and AKT1 in the genetics of schizophrenia in Finland

Several putative schizophrenia susceptibility genes have recently been identified. Significant associations between schizophrenia and neuregulin 1 (NRG1) and dysbindin (DTNBP1) were first reported in 2002 and studies in several populations have since independently reported positive associations to these gene regions. Further, both tentative functional and genetic data have implicated the role of AKT1 in the genetic background of this disorder. However, findings have not been consistent in all populations. We investigated the allelic diversity of these three genes NRG1, DTNBP1 and AKT1 in a representative nation-wide study sample of 441 Finnish schizophrenia families consisting of 865 affected individuals, in order to assess their role in one of the largest population-based study samples. DTNBP1 and AKT1 failed to show evidence of association, whereas two SNPs in the 3' region of the NRG1 gene yielded suggestive evidence of association (p=0.012 and p=0.048) in family-based association analyses. Thus, our study does not indicate that AKT1 or DTNBP1 play a role in the etiology of schizophrenia in the Finnish population. Furthermore, results do not support a major role for NRG1, but we cannot completely exclude a minor role of this gene in the Finnish population.     

Current state and future of pediatric allergology in Europe: A road map

The history of pediatric allergology (PA) in Europe is relatively youthful, dating back to 1984, when a small group of pediatricians founded the European Working Group on Pediatric Allergy and Immunology—later giving rise to ESPACI (European Society on Pediatric Allergology and Clinical Immunology). In 1990, the first dedicated journal, Pediatric Allergy and Immunology (PAI), was founded. There are striking differences across Europe, and even within European countries, in relation to the training pathways for doctors seeing children with allergic disease(s). In 2016, the EAACIClemens von Pirquet Foundation (CvP) organized and sponsored a workshop with the European Academy of Allergy and Clinical Immunology (EAACI) Pediatric Section. This collaboration focussed on the future of PA and specifically on education, research, and networking/ advocacy. The delegates representing many countries across Europe have endorsed the concept that optimal care of children with allergic diseases is delivered by pediatricians who have received dedicated training in allergy, or allergists who have received dedicated training in pediatrics. In order to meet the needs of children and families with allergic disease(s), the pediatric allergist is highly encouraged to develop several networks. Our challenge is to reinforce a clear strategic approach to scientific excellence to across our member base and to ensure and enhance the relevance of European pediatric research in allergy. With research opportunities in basic, translational, clinical, and epidemiologic trials, more trainees and trained specialists are needed and it is an exciting time to be a pediatric allergologist.     

Potential role for inhibition of protein phosphatase 2A tumor suppressor in salivary gland malignancies

The aetiology and pathogenesis of salivary gland malignancies remain unknown. To reveal novel molecular factors behind the development of salivary gland cancer, we performed gene expression analyses from Smgb‐Tag mouse salivary gland samples. The overall purpose was to apply these results for clinical use to find new approaches for both possible therapeutic targets and more accurate diagnostic tools. Smgb‐Tag mouse strain, in which salivary neoplasms arise through a dysplastic phase in submandibular glands, was investigated using genome‐wide microarray expression analysis, ingenuity pathway analysis, RT‐PCR, and immunohistochemistry. Thirty‐eight human salivary gland adenoid cystic carcinoma samples were investigated using immunohistochemistry for validation purposes. Our genome‐wide study showed that Ppp2r1b, a PP2A subunit encoding tumor suppressor gene, is underexpressed in submandibular gland tumors of Smgb‐Tag mice. mTOR signaling pathway was significantly enriched and mTOR linked PP2A subunit gene B55 gamma was significantly underexpressed in the analyses. Furthermore, parallel immunohistochemical analysis of three PP2A inhibitors demonstrated that two PP2A inhibitors, CIP2A and SET, are highly expressed in both dysplastic and adenocarcinomatous tumors of the Smgb‐Tag mice. In addition, all 38 investigated human salivary adenoid cystic carcinoma samples stained positively for CIP2A and most for SET. Finally, p‐S6 staining showed activation of mTOR pathway in human adenoid cystic carcinoma samples. Our results suggest that PP2A inhibition either via PP2A subunit underexpression or PP2A inhibitor overexpression play an important role in the formation of salivary gland malignancy, potentially due to mTOR signaling activation. © 2015 Wiley Periodicals, Inc.     

pH-triggered surface charge-reversal nanoparticles alleviate experimental murine colitis via selective accumulation in inflamed colon regions

In this study, we developed pH-triggered surface charge-reversal lipid nanoparticles (LNPs), loaded with budesonide, which could precisely deliver the drug to inflamed colon segments for the treatment of ulcerative colitis. Polyethyleneimine (PEI) was used to render LNPs cationic (PEI-LNPs), and Eudragit® S100 (ES) was coated on PEI-LNPs to obtain pH-triggered charge-reversal LNPs (ES-PEI-LNPs). ES coating avoided a burst drug release under acidic conditions mimicking the stomach and early small intestine environments and showed a sustained release in the colon. The surface charge of ES-PEI-LNPs switched from negative to positive under colonic conditions owing to pH-triggered removal of the ES coating. Bioimaging of the mouse gastrointestinal tract and confocal analysis of colon tissues revealed that ES-PEI-LNPs selectively accumulated in an inflamed colon. Furthermore, ES-PEI-LNPs mitigated experimental colitis in mice. These results suggest that the pH-triggered charge-reversal LNPs could be a promising drug carrier for ulcerative colitis therapy and other colon-targeted treatments.