Associations of bedroom PM2.5, CO2, temperature, humidity, and noise with sleep: An observational actigraphy study.

OBJECTIVE: Climate change and urbanization increasingly cause extreme conditions hazardous to health. The bedroom environment plays a key role for high-quality sleep. Studies objectively assessing multiple descriptors of the bedroom environment as well as sleep are scarce. METHODS: Particulate matter with a particle size <2.5 µm (PM2.5), temperature, humidity, carbon dioxide (CO2), barometric pressure, and noise levels were continuously measured for 14 consecutive days in the bedroom of 62 participants (62.9% female, mean ± SD age: 47.7 ± 13.2 years) who wore a wrist actigraph and completed daily morning surveys and sleep logs. RESULTS: In a hierarchical mixed effect model that included all environmental variables and adjusted for elapsed sleep time and multiple demographic and behavioral variables, sleep efficiency calculated for consecutive 1-hour periods decreased in a dose-dependent manner with increasing levels of PM2.5, temperature, CO2, and noise. Sleep efficiency in the highest exposure quintiles was 3.2% (PM2.5, p < .05), 3.4% (temperature, p < .05), 4.0% (CO2, p < .01), and 4.7% (noise, p < .0001) lower compared to the lowest exposure quintiles (all p-values adjusted for multiple testing). Barometric pressure and humidity were not associated with sleep efficiency. Bedroom humidity was associated with subjectively assessed sleepiness and poor sleep quality (both p < .05), but otherwise environmental variables were not statistically significantly associated with actigraphically assessed total sleep time and wake after sleep onset or with subjectively assessed sleep onset latency, sleep quality, and sleepiness. Assessments of bedroom comfort suggest subjective habituation irrespective of exposure levels. CONCLUSIONS: These findings add to a growing body of evidence highlighting the importance of the bedroom environment-beyond the mattress-for high-quality sleep.

In-vivo platelet activation and aggregation during and after acute atherothrombotic myocardial infarction in patients with and without Type-2 diabetes mellitus treated with ticagrelor.

INTRODUCTION: Patients with type-2 diabetes are twice as likely to suffer from acute myocardial infarction (AMI) and have a higher incidence of recurrent events than their non-diabetic counterparts. Ticagrelor is a platelet inhibitor known to reduce major adverse cardiovascular events (MACE) in AMI patients. This study measures the level and change in platelet activation and aggregation at the time of and following an AMI in patients with and without diabetes treated with ticagrelor. MATERIALS/METHODS: P2Y12 receptor inhibitor naïve patients presenting with AMI were prospectively enrolled. Blood collection occurred before coronary angiography (baseline: T0), 2, 4, 24, 48 h after baseline, and at a three-month follow-up. Ticagrelor was administered within five minutes of T0. We assessed platelet activation via measurements of surface P-selectin and platelet activated glycoprotein IIb/IIIa-1 (PAC-1) and assessed platelet aggregation via monocyte, lymphocyte, and granulocyte aggregates. We hypothesize that platelet activation and aggregation will be proportionally impacted to the same degree by ticagrelor, regardless of diabetes status. RESULTS: Ninety-seven patients were prospectively enrolled (diabetes, N = 33; no diabetes, N = 64). No difference was observed in the expression of P-selectin and PAC-1 at any given point between diabetes and non-diabetes groups (p > 0.05). No difference was observed in the percentage of platelet bound to leukocytes at any measured timepoint between patients with and without diabetes (p > 0.05). Platelet leukocyte aggregation was suppressed during the acute phase compared to quiescence equally among both groups. DISCUSSION: Ticagrelor demonstrated similar in-vivo effects on platelet activation and aggregation regardless of diabetes status in patients presenting with AMI.

Autophagy is essential for oligodendrocyte differentiation, survival, and proper myelination.

Deficient myelination, the spiral wrapping of highly specialized membrane around axons, causes severe neurological disorders. Maturation of oligodendrocyte progenitor cells (OPC) to myelinating oligodendrocytes (OL), the sole providers of central nervous system (CNS) myelin, is tightly regulated and involves extensive morphological changes. Here, we present evidence that autophagy, the targeted isolation of cytoplasm and organelles by the double-membrane autophagosome for lysosomal degradation, is essential for OPC/OL differentiation, survival, and proper myelin development. A marked increase in autophagic activity coincides with OL differentiation, with OL processes having the greatest increase in autophagic flux. Multiple lines of evidence indicate that autophagosomes form in developing myelin sheathes before trafficking from myelin to the OL soma. Mice with conditional OPC/OL-specific deletion of the essential autophagy gene Atg5 beginning on postnatal Day 5 develop a rapid tremor and die around postnatal Day 12. Further analysis revealed apoptotic death of OPCs, reduced differentiation, and reduced myelination. Surviving Atg5-/- OLs failed to produce proper myelin structure. In vitro, pharmacological inhibition of autophagy in OPC/dorsal root ganglion (DRG) co-cultures blocked myelination, producing OLs surrounded by many short processes. Conversely, autophagy stimulation enhanced myelination. These results implicate autophagy as a key regulator of OPC survival, maturation, and proper myelination. Autophagy may provide an attractive target to promote both OL survival and subsequent myelin repair after injury.

Blocking Autophagy in Oligodendrocytes Limits Functional Recovery after Spinal Cord Injury.

Autophagy mechanisms are well documented in neurons after spinal cord injury (SCI), but the direct functional role of autophagy in oligodendrocyte (OL) survival in SCI pathogenesis remains unknown. Autophagy is an evolutionary conserved lysosomal-mediated catabolic pathway that ensures degradation of dysfunctional cellular components to maintain homeostasis in response to various forms of stress, including nutrient deprivation, hypoxia, reactive oxygen species, DNA damage, and endoplasmic reticulum (ER) stress. Using pharmacological gain and loss of function and genetic approaches, we investigated the contribution of autophagy in OL survival and its role in the pathogenesis of thoracic contusive SCI in female mice. Although upregulation of Atg5 (an essential autophagy gene) occurs after SCI, autophagy flux is impaired. Purified myelin fractions of contused 8 d post-SCI samples show enriched protein levels of LC3B, ATG5, and BECLIN 1. Data show that, while the nonspecific drugs rapamycin (activates autophagy) and spautin 1 (blocks autophagy) were pharmacologically active on autophagy in vivo, their administration did not alter locomotor recovery after SCI. To directly analyze the role of autophagy, transgenic mice with conditional deletion of Atg5 in OLs were generated. Analysis of hindlimb locomotion demonstrated a significant reduction in locomotor recovery after SCI that correlated with a greater loss in spared white matter. Immunohistochemical analysis demonstrated that deletion of Atg5 from OLs resulted in decreased autophagic flux and was detrimental to OL function after SCI. Thus, our study provides evidence that autophagy is an essential cytoprotective pathway operating in OLs and is required for hindlimb locomotor recovery after thoracic SCI.SIGNIFICANCE STATEMENT This study describes the role of autophagy in oligodendrocyte (OL) survival and pathogenesis after thoracic spinal cord injury (SCI). Modulation of autophagy with available nonselective drugs after thoracic SCI does not affect locomotor recovery despite being pharmacologically active in vivo, indicating significant off-target effects. Using transgenic mice with conditional deletion of Atg5 in OLs, this study definitively identifies autophagy as an essential homeostatic pathway that operates in OLs and exhibits a direct functional role in SCI pathogenesis and recovery. Therefore, this study emphasizes the need to discover novel autophagy-specific drugs that specifically modulate autophagy for further investigation for clinical translation to treat SCI and other CNS pathologies related to OL survival.

Social exclusion of older people in deprived urban communities of England.

Addressing the causes and consequences of social exclusion represents a key theme in European social policy, reflecting growing awareness of the social costs which arise when individuals, families and communities become cut off from wider society. Conceptually, however, social exclusion remains underexplored in gerontology. The article suggests that exclusion represents a useful means of exploring the situation of older people in different environmental settings. Social exclusion in old age is conceptualised as a multi-dimensional phenomenon comprising of: exclusion from material resources; exclusion from social relations; exclusion from civic activities; exclusion from basic services; and neighbourhood exclusion. Drawing on a survey of 600 people aged 60 and over in deprived neighbourhoods of three English cities, the article develops indicators to represent each dimension of exclusion and seeks to assess the nature of social exclusion faced by older people in deprived neighbourhoods. Results reveal a considerable proportion of older people experiencing social exclusion in at least one form. The sample fell into three categories: 33% were not excluded on any of the five domains; 31% experienced exclusion on a single domain; 36% were vulnerable to the cumulative impact of multiple forms of exclusion. Multiple social exclusion was significantly correlated with respondents' ethnic origin, educational status, housing tenure, perceived health status and quality of life. It is concluded that social exclusion represents a useful means of depicting disadvantage experienced by older people living in deprived urban neighbourhoods, and that it would be useful to extend the analysis to other types of residential setting.