The Effect of a 2-Year Intervention Consisting of Diet,Physical Exercise,Cognitive Training,and Monitoring of Vascular Risk on Chronic Morbidity—the FINGER Randomized Controlled Trial

Objective

To verify whether a multidomain intervention lowers the risk of developing new chronic diseases in older adults.

Annual banned-substance review: Analytical approaches in human sports drug testing 2019/2020

Analytical chemistry-based research in sports drug testing has been a dynamic endeavor for several decades, with technology-driven innovations continuously contributing to significant improvements in various regards including analytical sensitivity, comprehensiveness of target analytes, differentiation of natural/endogenous substances from structurally identical but synthetically derived compounds, assessment of alternative matrices for doping control purposes, and so forth. The resulting breadth of tools being investigated and developed by anti-doping researchers has allowed to substantially improve anti-doping programs and data interpretation in general. Additionally, these outcomes have been an extremely valuable pledge for routine doping controls during the unprecedented global health crisis that severely affected established sports drug testing strategies. In this edition of the annual banned-substance review, literature on recent developments in anti-doping published between October 2019 and September 2020 is summarized and discussed, particularly focusing on human doping controls and potential applications of new testing strategies to substances and methods of doping specified the World Anti-Doping Agency's 2020 Prohibited List.     

Ataxia telangiectasia-mutated and p53 are potential mediators of chloroquine-induced resistance to mammary carcinogenesis

The use of agents to prevent the onset of and/or the progression to breast cancer has the potential to lower breast cancer risk. We have previously shown that the tumor-suppressor gene p53 is a potential mediator of hormone (estrogen/progesterone)-induced protection against chemical carcinogen-induced mammary carcinogenesis in animal models. Here, we show for the first time a breast cancer-protective effect of chloroquine in an animal model. Chloroquine significantly reduced the incidence of N-methyl-N-nitrosourea-induced mammary tumors in our animal model similar to estrogen/progesterone treatment. No protection was seen in our BALB/c p53-null mammary epithelium model, indicating a p53 dependency for the chloroquine effect. Using a human nontumorigenic mammary gland epithelial cell line, MCF10A, we confirm that in the absence of detectable DNA damage, chloroquine activates the tumor-suppressor p53 and the p53 downstream target gene p21, resulting in G(1) cell cycle arrest. p53 activation occurs at a posttranslational level via chloroquine-dependent phosphorylation of the checkpoint protein kinase, ataxia telangiectasia-mutated (ATM), leading to ATM-dependent phosphorylation of p53. In primary mammary gland epithelial cells isolated from p53-null mice, chloroquine does not induce G(1) cell cycle arrest compared with cells isolated from wild-type mice, also indicating a p53 dependency. Our results indicate that a short prior exposure to chloroquine may have a preventative application for mammary carcinogenesis.     

Fat intake at midlife and cognitive impairment later in life: a population-based CAIDE study

OBJECTIVE: To investigate the association of midlife dietary fat intake to cognitive performance, and to the occurrence of clinical mild cognitive impairment (MCI) later in life in a non-demented population. DESIGN: A longitudinal population-based study. SETTING: Populations of Kuopio and Joensuu, Eastern Finland. PARTICIPANTS AND METHODS: Participants of the CAIDE study were derived from random, population-based samples studied at midlife (1972, 1977, 1982 or 1987). After an average follow-up of 21 years, a total of 1449 (72%) individuals aged 65-80 years participated in the re-examination in 1998. Altogether 82 (5.7%) people were diagnosed as having MCI. Dietary information was collected with a structured questionnaire and an interview at midlife. MAIN OUTCOME MEASURES: MCI, global cognitive and executive functions, episodic, semantic and prospective memory and psychomotor speed. RESULTS: Abundant saturated fat (SFA) intake from milk products and spreads at midlife was associated with poorer global cognitive function and prospective memory and with an increased risk of MCI (OR 2.36, 95% CI 1.17-4.74) after adjusting for demographic and vascular factors, other fats and ApoE. On the contrary, high intake of polyunsaturated fatty acids (PUFA) was associated with better semantic memory. Also frequent fish consumption was associated with better global cognitive function and semantic memory. Further, higher PUFA-SFA ratio was associated with better psychomotor speed and executive function. CONCLUSIONS: Our data suggests that dietary fat intake at midlife affects cognitive performance and occurrence of MCI later in life. The impact of dietary interventions needs to be tested in clinical trials.     

Spatial working memory function in twins with schizophrenia and bipolar disorder.

BACKGROUND: Family studies are in conflict as to whether schizophrenia and bipolar disorder have independent genetic etiologies. Given the relatively low prevalence (approximately 1%) of these disorders, the use of quantitative endophenotypic markers of genetic liability might provide a more sensitive strategy for evaluating their genetic overlap. We have previously demonstrated that spatial working memory deficits increase in a dose-dependent fashion with increasing genetic proximity to a proband among the unaffected co-twins of schizophrenic patients. Here, we evaluated whether such deficits might also mark genetic susceptibility to bipolar disorder. METHODS: The Wechsler Memory Scale-Revised Visual Memory Span and Digit Span subtests were administered to 46 schizophrenic patients, 32 of their unaffected co-twins, 22 bipolar patients, 16 of their unaffected co-twins, and 100 control twins, representing unselectively nationwide twin samples. RESULTS: Schizophrenic patients and their unaffected co-twins performed significantly worse than control subjects on the spatial working memory task, whereas only the schizophrenic patients performed significantly below the control subjects on the verbal working memory task. Neither bipolar patients nor their unaffected co-twins differed from control subjects on these measures. CONCLUSIONS: Our findings support the hypothesis that impairment in spatial working memory might effectively reflect an expression of genetic liability to schizophrenia but less clearly to bipolar disorder.     

Do schizotypal symptoms mediate the relationship between genetic risk for schizophrenia and impaired neuropsychological performance in co-twins of schizophrenic patients?

BACKGROUND: Neurocognitive deficits and symptoms of schizotypal personality disorder are both elevated in the first-degree relatives of schizophrenic patients, but their relationship to each other and their potential common genetic source remain unclear. METHODS: Fifty unaffected co-twins of schizophrenic patients and 123 control twins were assessed with a neuropsychological battery and structured clinical interviews. RESULTS: Working memory was influenced by genetic risk for schizophrenia but not schizotypal symptoms. Nearly all other domains were influenced by schizotypy symptoms but only in the co-twins of schizophrenic patients. Schizotypy symptoms in the absence of a family history did not seem to be related to impaired neurocognitive functioning. CONCLUSIONS: Schizotypy symptoms in those with genetic risk for schizophrenia are associated with increased risk for cognitive deficits. Some neurocognitive deficits might covary with subpsychotic symptoms due to a shared genetic factor. Community-ascertained schizotypal individuals might not be appropriate for modeling underlying genetic risk for schizophrenia.