Background
Evidence‐based interventions to improve the sleep–wake rhythm, mood and behaviour in older adults with intellectual disabilities (ID) are limited. Increasing light exposure has been shown ...to be effective in improving the sleep–wake rhythm, mood, and behaviour in other populations. The current study investigates the effect of installing environmental dynamic lighting in common living rooms of care facilities on sleep–wake rhythm, mood, and behaviour in older adults with ID.
Methods
A non‐randomised, non‐concurrent, multiple baseline study was performed from October 2017 to May 2018. Fifty‐four participants mean (SD) age of 63.42 (8.6) years, 65% female in six care facilities were included. All participants had three baseline measurements (Weeks 1, 5 and 9). Dynamic lighting was installed in Week 10, after which three intervention measurements took place (Weeks 12, 17 and 24). Sleep characteristics and the sleep–wake rhythm were assessed using actigraphy (GENEActiv). Mood was measured with the Anxiety, Depression and Mood Scale (ADAMS) and behaviour with the Aberrant Behaviour Checklist (ABC).
Results
Mixed‐effect regression analysis showed a worsening of the primary outcome interdaily stability (P = 0.001). This could be attributed to one care facility, whereas interdaily stability did not change in the other care facilities (P = 0.74). Dynamic lighting led to earlier mid‐sleep (P = 0.003) and sleep onset (P < .0001) and improved mood as indicated by lower scores on the ADAMS depression (−0.64 SD, P < 0.001) and social avoidance (−0.47 SD, P = 0.004) subscales. The prevalence of screening above cut‐off for depression decreased from 23 to 9.8% (OR = .16, P = 0.003). For behaviour, a decrease was seen in hyperactivity (−0.43 SD, P < 0.001), lethargy (−0.35 SD, P = 0.008) and irritability (−0.33 SD, P < .001) as measured with the ABC. No adverse effects were reported.
Conclusion
Installing dynamic lighting in common living areas for older adults with ID improved the mood and behaviour of the residents up to 14 weeks after placement. Integrated dynamic lighting is a promising, undemanding and potentially effective addition to improve mood and behaviour in care organisations for people with ID, but does not seem to do so by improving sleep or sleep–wake rhythms.
Background
There is no widely used instrument to detect frailty in people with intellectual disabilities (IDs). We aimed to develop and validate a shorter and more practical version of a published ...frailty index for people with IDs.
Method
This study was part of the longitudinal ‘Healthy Ageing and Intellectual Disability’ study. We included 982 people with IDs aged 50 years and over. The previously developed and validated ID‐Frailty Index consisting of 51 deficits was used as the basis for the shortened version, the ID‐FI Short Form. Content of the ID‐FI Short Form was based on statistics and clinical and practical feasibility. We evaluated the precision and validity of the ID‐FI Short Form using the internal consistency, the correlation between the ID‐FI Short Form and the original ID‐Frailty Index, the agreement in dividing participants in the categories non‐frail, pre‐frail and frail, and the association with survival.
Results
Seventeen deficits from the original ID‐Frailty Index were selected for inclusion in the ID‐FI Short Form. All deficits of the ID‐FI Short Form are clinically and practically feasible to assess for caregivers and therapists supporting people with ID. We showed acceptable internal consistency with Cronbach's alpha of 0.75. The Pearson correlation between the ID‐Frailty Index and the ID‐FI Short Form was excellent (r = 0.94, P < 0.001). We observed a good agreement between the full and short forms in dividing the participants in the frailty categories, with a kappa statistic of 0.63. The ID‐FI Short Form was associated with survival; with every 1/100 increase on the ID‐FI Short Form, the mortality probability increased by 7% (hazard ratio 1.07, P < 0.001).
Conclusion
The first validation of the ID‐FI Short Form shows it to be a promising, practical tool to assess the frailty status of people with ID.
There is currently considerable imprecision in the nosology of biomarkers used in the study of neuropsychiatric disease. The neuropsychiatric field lags behind others such as oncology, wherein, ...rather than using 'biomarker' as a blanket term for a diverse range of clinical phenomena, biomarkers have been actively classified into separate categories, including prognostic and predictive tests. A similar taxonomy is proposed for neuropsychiatric diseases in which the core biology remains relatively unknown. This paper divides potential biomarkers into those of (1) risk, (2) diagnosis/trait, (3) state or acuity, (4) stage, (5) treatment response and (6) prognosis, and provides illustrative exemplars. Of course, biomarkers rely on available technology and, as we learn more about the neurobiological correlates of neuropsychiatric disorders, we will realize that the classification of biomarkers across these six categories can change, and some markers may fit into more than one category.
Maes M, Kubera M, Leunis J‐C, Berk M, Geffard M, Bosmans E. In depression, bacterial translocation may drive inflammatory responses, oxidative and nitrosative stress (O&NS), and autoimmune responses ...directed against O&NS‐damaged neoepitopes.
Objective: Depression is accompanied by activation of immuno‐inflammatory and oxidative and nitrosative stress (IO&NS) pathways, and increased IgM/IgA responses to lipopolysaccharide (LPS) of gram‐negative commensal bacteria. The latter suggests that bacterial translocation has caused IgM/IgA responses directed against LPS. Bacterial translocation may drive IO&NS responses.
Method: To examine the associations between IgM/IgA responses to LPS and IO&NS measurements, including plasma/serum interleukin‐1 (IL‐1), tumor necrosis factor (TNF)α, neopterin, lysozyme, oxidized LDL (oxLDL) antibodies, peroxides, and IgM (auto)immune responses against malondialdehyde (MDA), azelaic acid, phophatidyl inositol (Pi), NO‐tryptophan and NO‐tyrosine in depressed patients and controls.
Results: We found significant positive associations between IgM/IgA responses to LPS and oxLDL antibodies, IgM responses against MDA, azelaic acid, Pi, NO‐tryptophan, and NO‐tyrosine. The IgA responses to LPS were correlated with lysozyme. There were no significant positive correlations between the IgM/IgA responses to LPS and IL‐1 and neopterin.
Conclusion: The findings show that in depression there is an association between increased bacterial translocation and lysozyme production, an antibacterial compound, O&NS processes, and autoimmune responses directed against O&NS generated neoantigenic determinants. It is suggested that bacterial translocation may drive IO&NS pathways in depression and thus play a role in its pathophysiology.
Drug-induced liver injury is a ubiquitous issue in clinical settings and pharmaceutical industry. Hepatotoxicity elicited by drugs may be intrinsic or idiosyncratic, both which are driven by ...different molecular mechanisms. Recently, a unifying mechanistic model of drug-induced liver injury has been introduced. According to this model, drug-induced hepatotoxicity relies on 3 consecutive steps, namely an initial cellular insult that leads to the occurrence of mitochondrial permeability transition, which in turn ultimately burgeons into the onset of cell death. Clinically, drug-induced liver injury can be manifested in a number of acute and chronic conditions, including hepatitis, cholestasis, steatosis and fibrosis. These pathologies can be diagnosed and monitored by addressing well-established physical, clinical chemistry and histopathological biomarkers. In the last few years, several novel read-outs of drug-induced liver injury have been proposed, involving genetic, epigenetic, transcriptomic, proteomic and metabolomic parameters. These new concepts and recent developments in the field of drug-induced liver injury are revised in the current paper.
BAX, a member of the BCL2 gene family, controls the committed step of the intrinsic apoptotic program. Mitochondrial fragmentation is a commonly observed feature of apoptosis, which occurs through ...the process of mitochondrial fission. BAX has consistently been associated with mitochondrial fission, yet how BAX participates in the process of mitochondrial fragmentation during apoptosis remains to be tested. Time-lapse imaging of BAX recruitment and mitochondrial fragmentation demonstrates that rapid mitochondrial fragmentation during apoptosis occurs after the complete recruitment of BAX to the mitochondrial outer membrane (MOM). The requirement of a fully functioning BAX protein for the fission process was demonstrated further in BAX/BAK-deficient HCT116 cells expressing a P168A mutant of BAX. The mutant performed fusion to restore the mitochondrial network. but was not demonstrably recruited to the MOM after apoptosis induction. Under these conditions, mitochondrial fragmentation was blocked. Additionally, we show that loss of the fission protein, dynamin-like protein 1 (DRP1), does not temporally affect the initiation time or rate of BAX recruitment, but does reduce the final level of BAX recruited to the MOM during the late phase of BAX recruitment. These correlative observations suggest a model where late-stage BAX oligomers play a functional part of the mitochondrial fragmentation machinery in apoptotic cells.
Exposure to organic forms of mercury has the theoretical capacity to generate a range of immune abnormalities coupled with chronic nitro-oxidative stress seen in children with autism spectrum ...disorder (ASD). The paper discusses possible mechanisms explaining the neurotoxic effects of mercury and possible associations between mercury exposure and ASD subtypes. Environmental mercury is neurotoxic at doses well below the current reference levels considered to be safe, with evidence of neurotoxicity in children exposed to environmental sources including fish consumption and ethylmercury-containing vaccines. Possible neurotoxic mechanisms of mercury include direct effects on sulfhydryl groups, pericytes and cerebral endothelial cells, accumulation within astrocytes, microglial activation, induction of chronic oxidative stress, activation of immune-inflammatory pathways and impairment of mitochondrial functioning. (Epi-)genetic factors which may increase susceptibility to the toxic effects of mercury in ASD include the following: a greater propensity of males to the long-term neurotoxic effects of postnatal exposure and genetic polymorphisms in glutathione transferases and other glutathione-related genes and in selenoproteins. Furthermore, immune and inflammatory responses to immunisations with mercury-containing adjuvants are strongly influenced by polymorphisms in the human leukocyte antigen (HLA) region and by genes encoding effector proteins such as cytokines and pattern recognition receptors. Some epidemiological studies investigating a possible relationship between high environmental exposure to methylmercury and impaired neurodevelopment have reported a positive dose-dependent effect. Retrospective studies, on the other hand, reported no relationship between a range of ethylmercury-containing vaccines and chronic neuropathology or ASD. On the basis of these results, we would argue that more clinically relevant research is required to examine whether environmental mercury is associated with ASD or subtypes. Specific recommendations for future research are discussed.
Due to steady increase in use and mass production carbon nanotubes (CNTs) will inevitably end up in the environment. Because of their chemical nature CNTs are expected to be recalcitrant and ...biotransform only at very slow rates. Degradation of CNTs within days has recently been reported, but excluding one study, conclusions relied solely on qualitative results. We incubated 13 different types of CNTs and subjected them to enzymatic oxidation with horseradish peroxidase and concluded that the analytical methods commonly employed for studying degradation of CNTs did not have the sensitivity to unequivocally demonstrate degradation of these materials. To obtain unambiguous results with regard to the biotransformability of CNTs in the horseradish peroxidase system we incubated: (a) 14C-labeled multiwalled CNTs, homologous to Baytubes CNTs; and (b) 13C-depleted single-walled CNTs, used in previous studies. Our results show that 14C–CO2 evolved linearly at a rate of about 0.02‰ per day, and at the end of the 30-day incubations the CO2 evolved amounted to about 0.5‰ of both initial substrates, the 14C-labeled multiwalled and 13C-depleted single-walled CNTs. These results clearly show that CNT material is oxidized in the horseradish peroxidase system but with half-lives of about 80 years and not a few days as has been reported before. Adequately addressing biotransformation rates of CNTs is key toward a better understanding of the fate of these materials in the environment.
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