Adversity specificity and life period exposure on cognitive aging.

This study set out to examine the role of different adversities experienced at different life course stages on cognitive aging (i.e., level and change). Data from the longitudinal study: Survey of Health, Ageing, and Retirement in Europe (SHARE) with the selection of participants over 60 years were used (N = 2662, Mdnage = 68, SDage = 5.39) in a Structural Equation Modeling. In early life, the experience of hunger predicted lower delayed recall (ß = - 0.10, p < 0.001) and verbal fluency (ß = - 0.06, p = 0.001) performance in older age, whereas financial hardship predicted lower verbal fluency (ß = - 0.06, p = 0.005) performance and steeper decline in delayed recall (ß = - 0.11, p < 0.001). In early adulthood, financial hardship and stress predicted better delayed recall (financial hardship: ß = 0.08, p = 0.001; stress: ß = 0.07, p = 0.003) and verbal fluency performance (financial hardship: ß = 0.08, p = 0.001; stress ß = 0.10, p < 0.001), but no adversities were associated with a change in cognitive performance. In middle adulthood, no adversities were associated with the level of cognitive performance, but financial hardship predicted lower decline in delayed recall (ß = 0.07, p = 0.048). This study highlights the importance of disentangling the period effect from the specific effect of the adversity experienced in the association between adversity and cognition in older age. Moreover, differential results for delayed recall and verbal fluency measures suggest that it is also important to consider the cognitive outcome domains examined.

Do executive functions explain older adults' health-related quality of life beyond event-based prospective memory?

Previous work has shown that event-based prospective memory (EBPM) predicted health-related quality of life (HrQoL). In the present study, we aimed to examine whether the relationship between EBPM and HrQoL extended to life satisfaction, and whether it persisted after controlling for other cognitive functions related to EBPM, namely executive functions and retrospective memory. We tested two models using structural equation modeling with latent variables in a sample of older adults. In the first model, we assessed whether EBPM predicted life satisfaction and HrQoL; in the second model, we controlled for retrospective memory and executive functions. The first model indicated that EBPM was related to HrQoL. However, in the second model, this relationship was eliminated by executive functions; life satisfaction was not related to any of the cognitive variables. Findings corroborated the link between HrQoL and EBPM, suggesting that such relationship stems from executive functions rather than retrospective memory.

Cumulative life course adversity, mental health, and cognition in the UK biobank.

The association between adversity and cognition varies according to the specific adversity, when the adversity was experienced, and the cognitive domains investigated. Disentangling the effect of adversity and the underlying mechanistic pathway is therefore difficult. The association between adversity (i.e., maltreatment) accumulated over the life course and cognitive flexibility, as well as two potential mediators (i.e., intra-individual variability in reaction time and depression) of this association, were investigated. Data stem from the baseline population of the UK Biobank study (N = 73,489, Mdnage = 56, SDage = 7.628, 55.740% of women). Cumulative life course adversity (specifically maltreatment) was measured with items based on the Childhood Trauma Questionnaire (CTS-5) and items adapted from the British Crime Survey. Depression was assessed with the Patient Health Questionnaire-9 (PHQ-9). Intra-individual variability in reaction time was measured with a reaction time test "snap game" and the Trail Making Test A and B were used as a measure of cognitive flexibility. A path analysis was performed on these data. Higher cumulative adverse experiences were associated with lower performance in cognitive flexibility (ß = .016, p < .001, 95% CI [0.009, 0.024]), and this effect was partly mediated by the level of depression (22.727% of the total effect of cumulative life course adversity on cognitive flexibility was mediated by depression (ß = .005, p < .001, 95% CI [0.004, 0.007])). No association between cumulative life course adverse experiences and intra-individual variability in reaction time was found, nor was any indirect association between cumulative life course adversity and performance in cognitive flexibility via intra-individual variability in reaction time. The association between cumulative life course adversity, depression, and performance in cognitive flexibility has been highlighted. In contrast, no indirect effect between cumulative life course adversity and performance in cognitive flexibility via intra-individual variability in reaction time was found, suggesting that it is not a potential mechanism underlying the association between cumulative life course adversity and executive function.

Online assessment of cognitive functioning across the adult lifespan using the eCOGTEL: a reliable alternative to laboratory testing.

As the population ages, risks for cognitive decline threaten independence and quality of life of older adults. Classically, psychological assessment tools that evaluate cognitive functioning are administered in face-to-face laboratory sessions, which are time- and resource-consuming. The present study set out to examine whether the eCOGTEL-an online adaptation of the Cognitive Telephone Screening Instrument (COGTEL; Kliegel et al. in J Psychol 141(2):147-170, 2007)-represents a reliable measure of cognitive performance in adulthood. Therefore, an age-stratified adult lifespan sample of 253 participants (aged 19-86 years) completed a face-to-face assessment in the laboratory and a self-administered online version, at their homes. A second, independent sample of 176 younger adults (aged 19-30 years) performed a test-retest assessment of the eCOGTEL. Results showed strong correlations between overall cognitive scores assessed online and in the laboratory, as well as a high test-retest reliability. Further, comparable data distributions between both assessment modes underline the feasibility of the eCOGTEL across the adult lifespan and particularly in older age. Our findings thereby indicate that the eCOGTEL can reliably measure cognitive performance across the lifespan at reduced costs, which may help detecting individuals at risk of developing age-related cognitive decline. Due to these strengths, the eCOGTEL represents a valuable contemporary approach for the resource-efficient online assessment of cognition, which may benefit a broad array of fundamental and applied research fields, such as clinical and organizational psychology. Supplementary Information: The online version contains supplementary material available at 10.1007/s10433-021-00667-x.

The Geneva Space Cruiser: a fully self-administered online tool to assess prospective memory across the adult lifespan.

The current study aimed to examine whether the Geneva Space Cruiser - a new online adaptation of the Cruiser - represents a valid, reliable and useful tool to assess prospective memory (PM) across the adult lifespan via fully self-administered online testing. Therefore, an adult lifespan sample of 252 adults (19-86 years old) performed the Geneva Space Cruiser in the laboratory and online, at home, and also performed a more traditional laboratory PM task. A second sample of 224 young adults (19-35 years old) participated in a test-retest online assessment of the Geneva Space Cruiser. Bayesian analyses showed that the Geneva Space Cruiser yielded similar results when administered in the laboratory versus online, both in terms of data distribution as well as of key outcome measures (i.e., PM performance and monitoring). Results further showed very good test-retest reliability and acceptable construct validity. Finally, the online tool was sensitive for detecting age-differences similar to those typically observed in laboratory studies. Together, our findings suggest that the Geneva Space Cruiser represents a rather valid, moderately to highly reliable, and generally useful tool to assess PM in online testing across wide ranges of the adult lifespan, with certain limitations for the oldest participants and for women.

Transscleral Optical Phase Imaging of the Human Retina.

In-vivo observation of the human retina at the cellular level is crucial to detect the first signs of retinal diseases and properly treat them. Despite the phenomenal advances in adaptive optics (AO) systems, clinical imaging of many retinal cells is still elusive due to the low signal-to-noise ratio induced by transpupillary illumination. We present a transscleral optical phase imaging (TOPI) method, which relies on high-angle oblique illumination of the retina, combined with AO, to enhance cell contrast. Examination of eleven healthy volunteer eyes, without pupil dilation, shows the ability of this method to produce in-vivo images of retinal cells, from the retinal pigment epithelium to the nerve fibre layer. This method also allows the generation of high-resolution label-free ex-vivo phase images of flat-mounted retinas. The 4.4°x 4.4° field-of-view in-vivo images are recorded in less than 10 seconds, opening new avenues in the exploration of healthy and diseased retinas.

Type I interferon: the ever unfolding story.

Since the discovery of interferon 50 years ago, the understanding of the mechanism of the virus-mediated induction of type I IFN and its function has been under intensive investigation. Remarkable progress has been made in recent years both in the identification of cellular receptors detecting the viral infection and in the understanding the signaling pathways resulting in the induction of interferon and interferon-induced genes. In this review of type I interferon, we aim to summarize not only the historical site of the interferon induction and its antiviral function, but also the complexity of the signals that lead to activation of expression of interferon genes and the expanding repertoire of this multifunctional protein.

[Complementary medicine and health legislation]. / Komplementärmedizin und Gesundheitsrecht.

This review begins by explaining the meaning and purpose of health law in general. While legal regulations pertinent to mainstream medicine are functioning well, this project focuses on the legal situation that developed in Switzerland as a consequence of the increasing availability and use of services in complementary medicine. There are obvious gaps and deficits in our legislation concerning medical and paramedical providers of services in complementary medicine. Main emphasis of this project, therefore, was placed on the regulations dealing with health professionals in complementary medicine, in particular on standards of training, on licenses to practice, and on the compensation by health insurance funds. The project achieved a comprehensive stock-taking of the great variety of the Swiss federal and the 26 cantonal laws and regulations. It also drew conclusions on the necessity to formulate generally applicable rules and regulations for the field of complementary medicine and finally submitted a list of practical recommendations.

Role of interferon-stimulated gene ISG-15 in the interferon-omega-mediated inhibition of human immunodeficiency virus replication.

Interferon-alpha (IFN-alpha) inhibits human immunodeficiency virus (HIV) replication in vivo and in vitro. In this study, we show that IFN-omega (IFN-omega) is also a potent inhibitor of HIV replication in vitro and that both laboratory and primary isolates of HIV-1 are more sensitive to IFN-omega than to IFN-alpha 2. Like IFN-alpha 2, IFN-omega inhibited proviral synthesis in acutely infected cells, but in contrast to IFN-alpha 2, IFN-omega did not alter the levels of HIV-1 unspliced messages. Yet, inhibition of HIV protein synthesis was greater in IFN-omega-treated than in IFN-alpha 2-treated cells. Whereas expression of IFN-stimulated genes was transient in IFN-alpha 2-treated cells, their expression was sustained in IFN-omega-treated cells. Expression of ISG-15 in particular was higher on treatment with IFN-omega than with IFN-alpha 2. Overexpression of ISG-15 in IFN-alpha 2-treated cells mimicked the effects of IFN-omega. In untreated cells, it resulted in the trapping of HIV unspliced RNA in the nucleus and a decrease in cytoplasmic HIV transcripts and HIV protein synthesis. These findings suggest that the sustained induction of IFN-stimulated genes by IFN-omega and that of ISG-15 in particular may confer a higher therapeutic index to IFN-omega in controlling HIV infection.

Identification of human immunodeficiency virus primary isolates resistant to interferon-alpha and correlation of prevalence to disease progression.

Human immunodeficiency virus (HIV) primary isolates, derived from donors at various stages of HIV infection, were assayed for their sensitivity to interferon (IFN)-alpha 2 in vitro. These isolates displayed a broad range of sensitivity to IFN-alpha 2. The prevalence of IFN-alpha 2 resistance was low in the absence of AIDS but dramatically increased once HIV infection progressed to AIDS. Although there was no linear correlation between the percentage of IFN-alpha 2 inhibition in vitro and the CD4 cell number in vivo or the level of endogenous IFN-alpha, serum IFN-alpha levels were higher in donors with AIDS and were associated with low CD4 cell numbers. Thus, circulating IFN-alpha appeared to either promote resistance or favor survival of IFN-alpha resistant variants. IFN-alpha 2 resistance was neither limited to a particular cell tropism nor enhanced by therapy with zidovudine. Sequential analysis indicated that reversion to IFN-alpha 2 sensitivity could occur during the course of infection.

[Complementary medicine and health policy regulations]. / Komplementärmedizin und Gesundheitsrecht.

A comprehensive approach to the broad field of complementary medicine must necessarily embrace the whole question of health policy rules. It is part of this approach to classify complementary medicine as belonging to the field of naturopathy and specific methods, on the grounds that naturopathic methods can, in most cases, be subjected to scientific evaluation. At the same time, however, specific methods such as homeopathy, acupuncture, and neuropathy should not be sidelined. On the contrary, experience gathered over a great many years has proven the efficacy of these methods, and this should be the criterion for official recognition by health insurance schemas. In other words, the conventional science-based approval procedures should be widened. It follows that changes to the approval procedures would have an impact on the providers of complementary medicine, as well as on hospitals. At present the individual cantons decide to what extent therapists who are not qualified doctors are permitted to practice complementary medicine. The question whether or not to standardize, simplify or tighten the rules for admission is left open here.

Identification of a novel human immunodeficiency virus strain cytopathic to megakaryocytic cells.

Impaired megakaryocytopoiesis may be a contributing factor to thrombocytopenia associated with human immunodeficiency virus (HIV) infection. Because HIV isolates differ in their host range and pathogenicity, we investigated whether HIV strains with demonstrable cell tropism and increased cytopathicity for megakaryocytes could be derived from the blood of thrombocytopenic HIV-infected individuals. We derived a strain, HIV-WW, from the peripheral blood of an individual with severe thrombocytopenia and found the virus to be highly and specifically cytotoxic to CMK and DAMI megakaryocytic cells. CMK and DAMI cells were not permissive for the virus and HIV-WW induced cytopathicity for these megakaryocytic cells did not depend on viral replication. The CD4 N-terminus-binding domain of the HIV gp120 envelope protein did not appear to be involved in determining the cytopathic phenomenon. HIV may impair megakaryocytopoiesis through interactions at the cell surface in some cases rather than through viral entry and intracellular replication.

Genetic evidence for involvement of vaccinia virus DNA-dependent ATPase I in intermediate and late gene expression.

To delineate the role of the vaccinia virus-encapsidated DNA-dependent ATPase I in the life cycle of the virus, we performed a detailed study of two temperature-sensitive mutants with lesions in the gene encoding the enzyme. Profiles of viral DNA and protein accumulation during infection showed the mutants to be competent for DNA synthesis but deficient in late protein synthesis, confirming their defective late phenotype (R. C. Condit and A. Motyczka, Virology 113:224-241, 1981: R. C. Condit, A. Motyczka, and G. Spizz, Virology 128:429-443, 1983). In vitro translation of viral RNA and S1 nuclease mapping of selected mRNAs demonstrated that the deficit in late protein synthesis stemmed from a defect in the transcriptional machinery. Intermediate and late gene expression appeared to be most affected. The transcriptional defect was of unequal severity in the two mutants. However, their phenotypes were indistinguishable and their respective lesions were mapped to the same 300 nucleotides at the 5' end of the gene. DNA sequence analysis assigned a single nucleotide and amino acid change to one of the mutants.

Evidence for protein kinase C in bovine adrenocortical membrane preparations using [35S] gamma-thio-ATP as a phosphate donor.

Thio-substituted ATP is a sensitive probe for detecting protein kinase C activity as demonstrated in bovine adrenocortical cell membrane preparations. A single endogenous protein substrate with a molecular weight of approximately 47 Kd was rapidly phosphorylated with [3 5S] gamma-thio-ATP as phosphate donor. Phosphorylation was significantly increased in 30 seconds and reached a plateau by 3 minutes. The activity of the endogenous membrane kinase was unaffected by ACTH, cAMP, calmodulin or trifluoperazine but was responsive to combinations of calcium (Ca), diolein and phosphatidyl serine (PS). In addition, the kinase was activated by the tumor promoting phorbol ester, 12-0-tetradecanoylphorbol-13-acetate, indicating that the membrane contains a protein kinase C and a single 47 Kd phosphorylatable protein substrate. The same substrate is phosphorylated by Ca/diolein/PS activated kinase in membrane preparations from a broad range of rat tissues. Attempts to identify the substrate indicate that it is neither the type I regulatory subunit of cAMP dependent protein kinase nor mitochondrial cytochrome P450.