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Increasing evidence documents turnover of the resting-state blood-oxygen-level dependent signal (TBOLD) as a key measure of local cortical brain status. Here we evaluated contemporaneous and lagged associations between TBOLD and cognitive function in 711 participants in the Human Connectome Project on Aging (HCP-A; 316 males and 395 females, age range 36-90 years). We found that TBOLD was negatively associated with Montreal Cognitive Assessment (MoCA) Total scores and with performance on 2 subscales, Delayed Recall and Visuospatial/Executive Function, controlling for sex, age, and handedness. This negative association was largely documented across brain areas and was significantly stronger in the left hemisphere compared to the right. In addition, analyses evaluating forward lagged crosscorrelations between TBOLD and cognitive performance demonstrated that TBOLD predicted decrements in future performance on MoCA Total score, Delayed Recall, and Visuospatial/Executive Function subscales, controlling for sex and handedness. Taken together, we found that increased TBOLD is associated with decreased cognitive performance contemporaneously and in the future. On the hypothesis that increased TBOLD is the outcome of neuroinflammatory processes, these findings provide a mechanism linking neuroinflammation with decreased cognitive performance. [ABSTRACT FROM AUTHOR]

Objective: Host immunogenetics (Human Leukocyte Antigen, HLA) play a critical role in the human immune response to melanoma, influencing both melanoma prevalence and immunotherapy outcomes. Beneficial outcomes hinge on the successful binding of epitopes of melanoma antigens to HLA Class I molecules for an effective engagement of cytotoxic CD8+ lymphocytes and subsequent elimination of the cancerous cell. This study evaluated the binding affinity and immunogenicity of HLA Class I to melanoma tumor antigens to identify alleles best suited to facilitate elimination of melanoma antigens. Methods: In this study, we used freely available software tools to determine in silico the binding affinity and immunogenicity of 2462 reported HLA Class I alleles to all linear nonamer epitopes of 11 known antigens expressed in melanoma tumors (TRP2, S100, Tyrosinase, TRP1, PMEL(17), MAGE1, MAGE4, CTA, BAGE, GAGE/SSX2, Melan). Results: We identified the following 9 HLA Class I alleles with very high immunogenicity and binding affinity against all 11 melanoma antigens: A*02:14, B*07:10, B*35:10, B*40:10, B*40:12, B*44:10, C*07:11, and C*07:13, and C*07:14. Conclusion: These 9 HLA alleles possess the potential to aid in the elimination of melanoma both by themselves and by enhancing the beneficial effect of immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Identification of early influences on cognitive decline is of paramount importance in order to stem the impacts of decrements in cognitive functioning and to potentially intervene. Thus, here we focused on 132 healthy adult women (age range 26-98 years) to (a) determine whether factors circulating in serum may exert neurotoxic effects in vitro, (b) evaluate associations between serum neurotoxicity and cognitive performance, and (c) assess the influence of human herpes virus (HHV) seroprevalence and other factors on apoptosis and cognitive performance. The results documented that the addition of serum from healthy adult women to neural cell cultures resulted in apoptosis, indicating the presence of circulating neurotoxic factors in the serum. Furthermore, apoptosis increased with age, and was associated with decreased cognitive performance. Stepwise regression evaluating the influence of 6 HHVs on apoptosis and cognitive function revealed that only HHV5 (cytomegalovirus; CMV) seropositivity was significantly associated with apoptosis and cognitive decline, controlling for age. These findings document neurotoxic effects of serum from healthy women across the adult lifespan and suggest a unique detrimental influence associated with CMV seropositivity. [ABSTRACT FROM AUTHOR]

Previous research has documented elevated risk of brain cancer in patients with multiple sclerosis (MS). Separately, human leukocyte antigen (HLA) has been implicated in protection or susceptibility for both conditions. The aim of the current study was to assess a possible role of shared immunogenetic influence on risk of MS and brain cancer. We first identified an immunogenetic profile for each condition based on the covariance between the population frequency of 127 high-resolution HLA alleles and the population prevalence of each condition in 14 Continental Western European countries and then evaluated the correspondence between MS and brain cancer immunogenetic profiles. Also, since each individual carries 12 HLA alleles (2 × 6 genes), we estimated HLA protection and susceptibility for MS and brain cancer at the individual level. We found that the immunogenetic profiles of MS and brain cancer were highly correlated overall (P <.001) and across all 6 HLA genes with the strongest association observed for DRB1, followed by DQB1 and HLA-A. These findings of immunogenetic overlap between MS and brain cancer are discussed in light of the role of HLA in the immune system response to viruses and other foreign antigens. [ABSTRACT FROM AUTHOR]

Impulsivity has been conceptualized as influencing the expression of suicidal behavior. Adolescence is a developmental period characterized both by a relatively high rate of suicide attempts and a high level of impulsivity. The current study examined two behavioral measures (delay reward and disinhibition) and one self-report measure of impulsivity among girls with suicide attempt histories. Girls with multiple suicide attempts performed more impulsively on measures of delayed reward, and had higher self-ratings of depression and aggression than girls with either one or no suicide attempts. The multiple attempter girls' preference for immediate gratification may directly increase vulnerability to suicidal acts in the context of distressing states or indirectly increase risk by creating poor life experience over time.

Psychiatric disorders characterized by disinhibition--substance use disorders, antisocial personality disorder (PD), and borderline PD--represent a serious risk to the safety and health of college students. The ability of researchers and clinicians to identify students most at risk for disinhibited disorders associated with campus crime, violence, and self-harm depends on measures with strong evidence of diagnostic efficiency, yet data on the diagnostic efficiency of screening measures in college populations are lacking. The authors addressed this need by examining the diagnostic efficiency of commonly used screening measures for disinhibited disorders in a sample of 2,085 students, 79 of whom also completed diagnostic interviews. Results suggest that the diagnostic efficiency (e.g., sensitivity, specificity) of screening measures for substance use disorders and antisocial PD in college samples can be increased by making simple adjustments in screening cutoff criteria. Similar adjustments did not increase the diagnostic efficiency of the screening measure for borderline PD, and this suggested that certain screeners may best be aimed at ruling out disorders. This type of information offers users flexibility with which to tailor the screening threshold to serve different objectives. (Contains 3 tables and 3 footnotes.)

The interpersonal-psychological theory of suicidal behavior (Joiner, 2005) proposes that the need to belong is fundamental; when met it can prevent suicide and when thwarted it can substantially increase the risk for suicide. We investigate one source of group-wide variation in belongingness among college students--changes in the social composition of college campuses across academic semesters--as an explanation for variation in suicidal ideation across the academic year. Our results indicate that in a sample of college students at a large southern state university (n = 309), suicidal ideation varied across academic semesters, with highest levels in summer compared to both spring and fall. Differences in suicidal ideation between summer and spring were, in large part, accounted for by belongingness. Theoretical, as well as practical, implications are discussed regarding mechanisms for seasonal variation in suicidal ideation.