Polymorphisms of IKBKE gene are associated with major depressive disorder and panic disorder

Background The immune system has been increasingly implicated in the development of mood and anxiety disorders. Inhibitor of kappa light polypeptide gene enhancer in B cells, kinase epsilon (IKBKE) gene encodes IKKε protein that is involved in innate immunity, predominantly antiviral response generation. It also bears pro‐inflammatory properties that could affect psychiatric outcomes. In order to investigate the possible role of IKBKE gene in major depressive disorder (MDD) and panic disorder (PD), we conducted a case–control genetic association study concerning these disorders. Methods In all, 14 SNPs of IKBKE gene were genotyped in groups of 391 patients with MDD and 190 patients with PD together with respective 389 and 371 healthy control individuals. The given groups were further divided by gender for additional analyses. Results Substantial genetic associations were revealed between IKBKE SNPs and MDD (multiple testing adjusted P 0.05). In addition, two SNPs that were only associated with PD among males, also displayed significantly different allele frequencies compared to PD females. This may indicate a specific role of these SNPs in male PD, but caution should be applied here due to the small size of the studied PD males group. Conclusions The results of this study confirm our initial findings and indicate a possible role of IKBKE gene in mood and anxiety disorders

Associations between LSAMP gene polymorphisms and major depressive disorder and panic disorder

The purpose of this case–control genetic association study was to explore potential relationships between polymorphisms in the limbic system-associated membrane protein (LSAMP) gene and mood and anxiety disorders. A total of 21 single-nucleotide polymorphisms (SNPs) from the LSAMP gene were analyzed in 591 unrelated patients with the diagnoses of major depressive disorder (MDD) or panic disorder (PD) and in 384 healthy control subjects. The results showed a strong association between LSAMP SNPs and MDD, and a suggestive association between LSAMP SNPs and PD. This is the first evidence of a possible role of LSAMP gene in mood and anxiety disorders in humans

Polymorphisms in the ATG16L1 Gene are associated with psoriasis vulgaris

Letter to the Edito

Wfs1 Is Expressed In Dopaminoceptive Regions Of The Amniote Brain And Modulates Levels Of D1-Like Receptors

During amniote evolution, the construction of the forebrain has diverged across different lineages, and accompanying the structural changes, functional diversification of the homologous brain regions has occurred. This can be assessed by studying the expression patterns of marker genes that are relevant in particular functional circuits. In all vertebrates, the dopaminergic system is responsible for the behavioral responses to environmental stimuli. Here we show that the brain regions that receive dopaminergic input through dopamine receptor D1 are relatively conserved, but with some important variations between three evolutionarily distant vertebrate lines–house mouse (Mus musculus), domestic chick (Gallus gallus domesticus) / common quail (Coturnix coturnix) and red-eared slider turtle (Trachemys scripta). Moreover, we find that in almost all instances, those brain regions expressing D1-like dopamine receptor genes also express Wfs1. Wfs1 has been studied primarily in the pancreas, where it regulates the endoplasmic reticulum (ER) stress response, cellular Ca2+ homeostasis, and insulin production and secretion. Using radioligand binding assays in wild type and Wfs1-/- mouse brains, we show that the number of binding sites of D1-like dopamine receptors is increased in the hippocampus of the mutant mice. We propose that the functional link between Wfs1 and D1-like dopamine receptors is evolutionarily conserved and plays an important role in adjusting behavioral reactions to environmental stimuli

Polymorphisms in Toll-like receptor genes are associated with vitiligo

Background: The members of Toll-like receptor (TLR) family are responsible for recognizing various molecular patterns associated with pathogens. Their expression is not confined to immune cells and have been detected in skin cells such as keratinocytes and melanocytes. As part of a generated response to pathogens, TLRs are involved in inducing inflammatory mediators to combat these threats. It is therefore not surprising that TLRs have been implicated in inflammatory skin diseases, including atopic dermatitis and psoriasis. Likewise, as key players in autoimmunity, they have been associated with a number of autoimmune diseases. Based on this, the role of TLRs in vitiligo could be suspected, but is yet to be clearly established. Methods: In order to conduct a genetic association analysis, 30 SNPs were selected from TLR1-TLR8 and TLR10 regions to be genotyped in Estonian case-control cohort consisting of 139 vitiligo patients and 307 healthy control individuals. The patients were further analyzed in subgroups based on sex, age of onset, occurrence of vitiligo among relatives, extent of depigmented areas, vitiligo progression activity, appearance of Köbner's phenomenon, existence of halo naevi, and incidence of spontaneous repigmentation. Results: The most notable finding came with SNP rs179020 situated in TLR7 gene, that was associated in entire vitiligo (Padj = 0.0065) and also several subgroup analyses. Other single marker and haplotype analyses pointed to TLR3, TLR4, and TLR10 genes. Conclusions: This study investigated the genetic regions of nine TLR genes in relation to vitiligo susceptibility. The main results were the associations of TLR7 SNPs with vitiligo, while several other associations were obtained from the remaining TLR gene regions. This suggests that in addition to other inflammatory skin diseases, TLRs affect the development of vitiligo, thus making them interesting targets for future research

Wfs1-deficient mice display altered function of serotonergic system and increased behavioral response to antidepressants

It has been shown that mutations in the WFS1 gene make humans more susceptible to mood disorders. Besides that, mood disorders are associated with alterations in the activity of serotonergic and noradrenergic systems. Therefore, in this study, the effects of imipramine, an inhibitor of serotonin (5-HT) and noradrenaline (NA) reuptake, and paroxetine, a selective inhibitor of 5-HT reuptake, were studied in tests of behavioral despair. The tail suspension test (TST) and forced swimming test (FST) were performed in Wfs1-deficient mice. Simultaneously, gene expression and monoamine metabolism studies were conducted to evaluate changes in 5-HT- and NA-ergic systems of Wfs1-deficient mice. The basal immobility time of Wfs1-deficient mice in TST and FST did not differ from that of their wild-type littermates. However, a significant reduction of immobility time in response to lower doses of imipramine and paroxetine was observed in homozygous Wfs1-deficient mice, but not in their wild-type littermates. In gene expression studies, the levels of 5-HT transporter (SERT) were significantly reduced in the pons of homozygous animals. Monoamine metabolism was assayed separately in the dorsal and ventral striatum of naive mice and mice exposed for 30 min to brightly lit motility boxes. We found that this aversive challenge caused a significant increase in the levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of 5-HT, in the ventral and dorsal striatum of wild-type mice, but not in their homozygous littermates. Taken together, the blunted 5-HT metabolism and reduced levels of SERT are a likely reason for the elevated sensitivity of these mice to the action of imipramine and paroxetine. These changes in the pharmacological and neurochemical phenotype of Wfs1-deficient mice may help to explain the increased susceptibility of Wolfram syndrome patients to depressive states

ESPRAS Survey on Continuing Education in Plastic, Reconstructive and Aesthetic Surgery in Europe

Background Specialty training in plastic, reconstructive and aesthetic surgery is a prerequisite for safe and effective provision of care. The aim of this study was to assess and portray similarities and differences in the continuing education and specialization in plastic surgery in Europe. Material and Methods A detailed questionnaire was designed and distributed utilizing an online survey administration software. Questions addressed core items regarding continuing education and specialization in plastic surgery in Europe. Participants were addressed directly via the European Leadership Forum (ELF) of the European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS). All participants had detailed knowledge of the organization and management of plastic surgical training in their respective country. Results The survey was completed by 29 participants from 23 European countries. During specialization, plastic surgeons in Europe are trained in advanced tissue transfer and repair and aesthetic principles in all parts of the human body and within several subspecialties. Moreover, rotations in intensive as well as emergency care are compulsory in most European countries. Board certification is only provided for surgeons who have had multiple years of training regulated by a national board, who provide evidence of individually performed operative procedures in several anatomical regions and subspecialties, and who pass a final oral and/or written examination. Conclusion Board certified plastic surgeons meet the highest degree of qualification, are trained in all parts of the body and in the management of complications. The standard of continuing education and qualification of European plastic surgeons is high, providing an excellent level of plastic surgical care throughout Europe

Male mice with deleted Wolframin (Wfs1) gene have reduced fertility

Background: Wolfram Syndrome (WS) is an autosomal recessive disorder characterised by non-autoimmune diabetes mellitus, optic atrophy, cranial diabetes insipidus and sensorineural deafness. Some reports have described hypogonadism in male WS patients. The aim of our study was to find out whether Wfs1 deficient (Wfs1KO) male mice have reduced fertility and, if so, to examine possible causes. Methods: Wfs1KO mice were generated by homologous recombination. Both Wfs1KO and wild type (wt) male mice were mated with wt female mice. The number of litters and the number of pups were counted and pregnancy rates calculated. The motility and morphology of the sperm and the histology of testes were analysed. Serum testosterone and FSH concentrations were also measured. Results: The pregnancy rate in wt females mated with Wfs1KO males was significantly lower than in the control group (15% vs. 32%; p < 0.05), but there was no significant difference in litter size. Analysis of male fertility showed that, in the Wfs1KO group, eight males out of 13 had pups whereas in the control group all 13 males had at least one litter. Sperm motility was not affected in Wfs1KO mice, but Wfs1KO males had less proximal bent tails (14.4 +/- 1.2% vs. 21.5 +/- 1.3 p < 0.05) and less abnormal sperm heads (22.8 +/- 1.8 vs. 31.5 +/- 3.5, p < 0.05) than wt males. Testes histology revealed significantly reduced number of spermatogonia (23.9 +/- 4.9 vs. 38.1 +/- 2.8; p < 0.05) and Sertoli cells (6.4 +/- 0.5 vs. 9.2 +/- 1.0; p < 0.05) in Wfs1KO mice. Serum testosterone and FSH concentrations did not differ between the two groups. Conclusion: The impaired fertility of Wfs1KO male mice is most likely due to changes in sperm morphology and reduced number of spermatogenic cells. The exact mechanism through which the Wfs1 gene influences sperm morphology needs to be clarified in further studies

Allergy from infancy to adolescence. A population-based 18-year follow-up cohort

<p>Abstract</p> <p>Background</p> <p>Anxious parents have many concerns about the future health of their atopic infants. Paediatricians and primary care practitioners need to seek knowledge on long-term outcomes in order to cope with the increasing caseload of suspected allergy and the concerns of parents. The aim of the study was to assess suspected and diagnosed allergy in infancy as predictors of allergy and asthma in adolescence.</p> <p>Methods</p> <p>Families expecting their first baby and making their first visit to a maternity health care clinic in 1986 were selected as the study population in a random sample. There were 1278 eligible study families. The data were provided of the children at the ages of 9 and 18 months and 3, 5, 12, 15 and 18 years by health care professionals, parents, and adolescents (themselves).</p> <p>Results</p> <p>At the age of 9 months, the prevalence of allergy suspicions was distinctly higher than that of allergy diagnoses. At the age of five years suspected allergy approaches were nil, and the prevalence of diagnosed allergy was about 9%. During the adolescence, the prevalence of self-reported allergy increases steadily up to the age of 18 years, and that of asthma remains at approximately 5%. Suspected allergy at the age of 9 or 18 months and at the 5 years of age does not predict allergy at adolescence. Compared with non-allergic children, children with definite allergy at the age of 5 were over 8 times more likely to have allergy and nearly 7 times more likely to have asthma in adolescence.</p> <p>Conclusion</p> <p>An early ascertained diagnosis of allergy, but not suspicions of allergy, predicts prevailing allergy in adolescence. Efforts need to be focused on accurate diagnosis of early childhood allergies.</p