Impact of sunlight on the age of onset of bipolar disorder

Bauer M, Glenn T, Alda M, Andreassen OA, Ardau R, Bellivier F, Berk M, Bjella TD, Bossini L, Del Zompo M, Dodd S, Fagiolini A, Frye MA, Gonzalez‐Pinto A, Henry C, Kapczinski F, Kliwicki S, König B, Kunz M, Lafer B, Lopez‐Jaramillo C, Manchia M, Marsh W, Martinez‐Cengotitabengoa M, Melle I, Morken G, Munoz R, Nery FG, O’Donovan C, Pfennig A, Quiroz D, Rasgon N, Reif A, Rybakowski J, Sagduyu K, Simhandl C, Torrent C, Vieta E, Zetin M, Whybrow PC. Impact of sunlight on the age of onset of bipolar disorder. Bipolar Disord 2012: 14: 654–663. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Although bipolar disorder has high heritability, the onset occurs during several decades of life, suggesting that social and environmental factors may have considerable influence on disease onset. This study examined the association between the age of onset and sunlight at the location of onset. Method: Data were obtained from 2414 patients with a diagnosis of bipolar I disorder, according to DSM‐IV criteria. Data were collected at 24 sites in 13 countries spanning latitudes 6.3 to 63.4 degrees from the equator, including data from both hemispheres. The age of onset and location of onset were obtained retrospectively, from patient records and/or direct interviews. Solar insolation data, or the amount of electromagnetic energy striking the surface of the earth, were obtained from the NASA Surface Meteorology and Solar Energy (SSE) database for each location of onset. Results: The larger the maximum monthly increase in solar insolation at the location of onset, the younger the age of onset (coefficient= ?4.724, 95% CI: ?8.124 to ?1.323, p = 0.006), controlling for each country’s median age. The maximum monthly increase in solar insolation occurred in springtime. No relationships were found between the age of onset and latitude, yearly total solar insolation, and the maximum monthly decrease in solar insolation. The largest maximum monthly increases in solar insolation occurred in diverse environments, including Norway, arid areas in California, and Chile. Conclusion: The large maximum monthly increase in sunlight in springtime may have an important influence on the onset of bipolar disorder.     

Relational job characteristics and well‐being: A study among Portuguese and Brazilian hospital nurses

Nurse well‐being is a crucial factor in the quality of care given to patients and in patient safety. The purpose of this study was to investigate the relationships between the psychological effects of relational job characteristics (PERJCs) and indicators of well‐being in hospital nurses. The data for this correlational study were collected from an online survey responded to by a sample of 620 hospital nurses (335 Portuguese and 285 Brazilian). Statistical procedures included structural equation modeling and multigroup analysis. A full mediation model was supported by data analysis, in which work‐related well‐being (i.e., engagement and burnout) explained the relationships between hospital nurses' perceived social worth and their context‐free well‐being. Moreover, in the Portuguese sample, the perceived social impact on client lives and the affective commitment to clients were indirectly related to the context‐free well‐being of nurses, through work engagement. Practical implications are presented in order to foster the PERJCs, thus contributing to nurse well‐being.     

Detection of regulatory T cell phenotypic markers and cytokines in patients with human papillomavirus infection

Infection with human papillomavirus (HPV) is the main cause of cervical cancer. Viral persistence is considered the main risk factor for neoplastic progression and evidence suggests that regulatory T cells (Treg) play an important role in the failure of viral elimination. The aim of this study was to detect phenotypic markers of Treg and cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β, in the cervical microenvironment of HPV-infected patients. One hundred and one samples of uterine cervix embedded in paraffin were analyzed. We used immunohistochemistry to examine the coexpression of the CD25/FOXP3 and CD4/TGF-β markers, and the expression of GITR and IL-10 in cells present in the cervical stroma. We detected a microenvironment composed of high proportions of CD25⁺FOXP3⁺, CD4⁺TGFβ⁺, IL-10⁺, and GITR⁺ cells in samples with high viral loads and severe lesions of HPV-infected patients. The abundance of these markers, indicative of the presence of Treg cells and immunosuppressive cytokines, was significantly associated with severe lesions and elevated viral loads in the examined samples. These results suggest that Treg cells may be involved in maintaining a microenvironment favorable for viral persistence and neoplastic progression. Our findings support those of previous studies that suggested that these markers could be used to predict HPV persistence and neoplastic progression, and as potential targets for immune response modulation.     

Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjects who did or did not commit suicide.

OBJECTIVE: Postmortem studies have indicated that suicide victims have greater serotonin receptor 2A (5-HTR2A) binding in prefrontal brain regions. However, there remains some controversy regarding the biological specificity of these findings. The authors hypothesized that the variance observed in brain 5-HTR2A binding is genetically mediated, at least in part. METHOD: Postmortem data from 56 subjects who had committed suicide and 126 normal comparison subjects were studied; brain tissue was available from 11 subjects who committed suicide and 11 comparison subjects. Homogenate binding assays were carried out with [3H]ketanserin. Variation at the 5-HTR2A gene (HTR2A) was investigated by means of two polymorphisms: T102C and A-1438G. RESULTS: 5-HTR2A binding was greater in the prefrontal cortex of the subjects who committed suicide. In addition, the findings suggest that HTR2A variation significantly affects 5-HTR2A binding. However, no interaction between suicidal behavior and this locus was observed. CONCLUSIONS: These results confirm previous reports of greater 5-HTR2A binding in subjects who committed suicide; they also provide preliminary evidence suggesting that the number of 5-HTR2A receptors is genetically mediated.     

Local immunosuppression induced by high viral load of human papillomavirus: characterization of cellular phenotypes producing interleukin‐10 in cervical neoplastic lesions

A specific immune response to human papillomavirus (HPV) in the cervical microenvironment plays a key role in eradicating infection and eliminating mutated cells. However, high‐risk HPVs modulate immune cells to create an immunosuppressive microenvironment, and induce these immune cells to produce interleukin 10 (IL‐10). This production of IL‐10, in conjunction with HPV infection, contributes to the appearance of cervical neoplastic lesions. We sought to characterize the IL‐10‐producing cellular phenotype, and investigate the influence of host and HPV factors upon the induction of an immunosuppressive microenvironment. Immunohistochemical analysis demonstrated an increase in IL‐10 production by keratinocytes, macrophages and Langerhans cells in high‐grade cervical lesions and cervical cancer. This increase was more pronounced in patients older than 30 years, and was also correlated with high viral load, and infection with a single HPV type, particularly high‐risk HPVs. Our results indicate the existence of a highly immunosuppressive microenvironment composed of different IL‐10‐producing cellular phenotypes in cervical cancer samples, and samples classified as high‐grade cervical lesions (cervical intraepithelial neoplasia stages II and III). The immunosuppressive microenvironment that developed for these different cellular phenotypes favours viral persistence and neoplastic progression.     

A genetic interaction of NRXN2 with GABRE,SYT1 and CASK in migraine patients: a case-control study

BackgroundMigraine is a multifactorial disorder that is more frequent (two to four times) in women than in men. In recent years, our research group has focused on the role of neurotransmitter release and its regulation. Neurexin (NRXN2) is one of the components of the synaptic vesicle machinery, responsible for connecting intracellular fusion proteins and synaptic vesicles.Our aim was to continue exploring the role and interaction of proteins involved in the control and promotion of neurotransmission in migraine susceptibility.MethodsA case-control study was performed comprising 183 migraineurs (148 females and 35 males) and 265 migraine-free controls (202 females and 63 males). Tagging single nucleotide polymorphisms of NRXN2 were genotyped to assess the association between NRXN2 and migraine susceptibility. The χ² test was used to compare allele frequencies in cases and controls and odds ratios were estimated with 95% confidence intervals. Haplotype frequencies were compared between groups. Gene-gene interactions were analysed using the Multifactor Dimensionality Reduction v2.0.ResultsWe found a statistically significant interaction model (p = 0.009) in the female group between the genotypes CG of rs477138 (NRXN2) and CT of rs1158605 (GABRE). This interaction was validated by logistic regression, showing a significant risk effect [OR = 4.78 (95%CI: 1.76–12.97)] after a Bonferroni correction. Our data also supports a statistically significant interaction model (p = 0.011) in the female group between the GG of rs477138 in NRXN2 and, the rs2244325''s GG genotype and rs2998250’s CC genotype of CASK. This interaction was also validated by logistic regression, with a protective effect [OR = 0.08 (95%CI: 0.01–0.75)]. A weak interaction model was found between NRXN2-SYT1. We have not found any statistically significant allelic or haplotypic associations between NRXN2 and migraine susceptibility.ConclusionsThis study unravels, for the first time, the gene-gene interactions between NRXN2, GABRE - a GABA_A-receptor - and CASK, importantly it shows the synergetic effect between those genes and its relation with migraine susceptibility.These gene interactions, which may be a part of a larger network, can potentially help us in better understanding migraine aetiology and in development of new therapeutic approaches.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01266-y.     

Accuracy and sensitivity of computed tomography‐guided percutaneous needle biopsy of pulmonary hilar lymph nodes

BACKGROUND:

Because of their proximity to the pulmonary artery or vein, hilar lymph nodes are routinely biopsied with endobronchial or endoscopic ultrasonography (EUS)‐guided fine‐needle aspiration biopsy (FNAB). Computed tomography (CT)‐guided percutaneous needle biopsy (PNB) allows the operator to acquire a larger core needle biopsy (CNB) when initial samples are inconclusive, when the suspected disease is not optimally diagnosed with FNAB, or when biomarkers are required. The purpose of this study was to retrospectively evaluate the sensitivity and accuracy of CT‐guided PNB in patients with hilar adenopathy.

METHODS:

The authors identified 80 patients who underwent 81 CT‐guided PNBs of pulmonary hilar lesions from October 2002 through December 2006 and retrospectively reviewed their medical and imaging records. The PNB sensitivity and accuracy were calculated in each case, and each case was reviewed for complications, including pneumothorax and subsequent thoracostomy tube insertion.

RESULTS:

PNB included FNAB and CNB in 81 (100%) and 14 (17%) procedures, respectively. Data on 69 PNB specimens (67 FNAB specimens and 13 CNB specimens) were available for statistical analysis. Overall, PNB had a sensitivity of 91.4% (95% confidence interval [CI], 81.0%‐97.1%) and an accuracy rate of 92.8% (95% CI, 83.9%‐97.1%). Pneumothoraxes occurred in 39 patients (48%), 26 (32%) of whom required thoracostomy tube insertion.

CONCLUSIONS:

CT‐guided PNB of pulmonary hilar lesions has high sensitivity and accuracy and represents a viable alternative for endobronchial ultrasound‐ or EUS‐guided FNAB when larger biopsy samples are required for diagnosis or biomarker analysis. However, the procedure can result in high rates of pneumothorax. Cancer 2010. © 2010 American Cancer Society.