Alteration of EIF2 Signaling, Glycolysis, and Dopamine Secretion in Form-Deprived Myopia in Response to 1% Atropine Treatment: Evidence From Interactive iTRAQ-MS and SWATH-MS Proteomics Using a Guinea Pig Model.

Purpose: Atropine, a non-selective muscarinic antagonist, effectively slows down myopia progression in human adolescents and several animal models. However, the underlying molecular mechanism is unclear. The current study investigated retinal protein changes of form-deprived myopic (FDM) guinea pigs in response to topical administration of 1% atropine gel (10 g/L). Methods: At the first stage, the differentially expressed proteins were screened using fractionated isobaric tags for a relative and absolute quantification (iTRAQ) approach, coupled with nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) (n = 24, 48 eyes) using a sample pooling technique. At the second stage, retinal tissues from another cohort with the same treatment (n = 12, 24 eyes) with significant ocular changes were subjected to label-free sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics for orthogonal protein target confirmation. The localization of Alpha-synuclein was verified using immunohistochemistry and confocal imaging. Results: A total of 1,695 proteins (8,875 peptides) were identified with 479 regulated proteins (FC ≥ 1.5 or ≤0.67) found from FDM eyes and atropine-treated eyes receiving 4-weeks drug treatment using iTRAQ-MS proteomics. Combining the iTRAQ-MS and SWATH-MS datasets, a total of 29 confident proteins at 1% FDR were consistently quantified and matched, comprising 12 up-regulated and 17 down-regulated proteins which differed between FDM eyes and atropine treated eyes (iTRAQ: FC ≥ 1.5 or ≤0.67, SWATH: FC ≥ 1.4 or ≤0.71, p-value of ≤0.05). Bioinformatics analysis using IPA and STRING databases of these commonly regulated proteins revealed the involvement of the three commonly significant pathways: EIF2 signaling; glycolysis; and dopamine secretion. Additionally, the most significantly regulated proteins were closely connected to Alpha-synuclein (SNCA). Using immunostaining (n = 3), SNCA was further confirmed in the inner margin of the inner nuclear layer (INL) and spread throughout the inner plexiform layer (IPL) of the retina of guinea pigs. Conclusion: The molecular evidence using next-generation proteomics (NGP) revealed that retinal EIF2 signaling, glycolysis, and dopamine secretion through SNCA are implicated in atropine treatment of myopia in the FDM-induced guinea pig model.

Intergenerational relationships and depressive symptoms among older adults in urban China: The roles of loneliness and insomnia symptoms.

The prevalence of depressive symptoms in older Chinese adults has increased recently. Intergenerational relationships play an important role in the mental health conditions of older adults, especially in Chinese culture. Therefore, this study aims to unravel the complex connection between intergenerational relationships and depression, and to explore the potential mediating roles of loneliness and nighttime insomnia symptoms within that connection. A cross-sectional household survey was conducted in China with 2038 participants aged 65 years or above. Variables were measured using the Center for Epidemiologic Studies Short Depression Scale, the Intergenerational Relationship Quality Scale for Aging Chinese Parents (IRQS-AP), three nighttime insomnia symptoms extracted from the Insomnia Severity Index and the De Jong Gierveld Six-Item Loneliness Scale. The IRQS-AP includes four subdimensions: consensual-normative solidarity, structural-associational solidarity, affectual closeness and intergenerational conflicts. Path analyses were performed in Mplus to investigate regression coefficients and mediating effects. Results showed that three general intergenerational relationships (consensual-normative solidarity, affectual closeness and intergenerational conflicts) were significantly correlated with all mental health outcomes, including their symptoms of loneliness, insomnia and depression. A serial mediation model suggested that loneliness mediated the connection between those constructs of intergenerational relationships and depression, with an independent path to insomnia symptoms via loneliness. The proposed mediators fully mediated the effects of affectual closeness on depression. Nighttime insomnia symptoms alone mediated only the relationship between intergenerational conflicts and depression independently from paths involving depression. Removal of sleep item from CES-D did not affect the results of paths. Our findings highlight the importance of intergenerational relationships for mental health, especially for the mediating effects of loneliness and nighttime insomnia symptoms on the relationship between intergenerational relationships and depression. Effective mental health services for older adults can address their feelings of loneliness and sleep problems, especially for those who have a poor relationship with their adult children.

Cognitive Behavioral Therapies for Insomnia and Hypnotic Medications: Considerations and Controversies.

Insomnia is a costly health problem, where management has remained suboptimal despite advances in the understanding and treatment of the condition. This article provides an overview of the evidence-based treatment options of insomnia, looking at short-term and long-term therapeutic outcomes for cognitive behavioral therapies and pharmacologic therapies. Key issues of treatment delivery and implementation are highlighted at the patient and health system levels, and novel approaches for combining and sequencing treatment to maximize therapeutic outcomes for insomnia are discussed. The impact of recent updates of major clinical guidelines and future research directions for the field are discussed.

Integrative body-mind-spirit intervention for concurrent sleep and mood disturbances: sleep-specific daytime functioning mediates sleep and mood improvements.

Sleep disturbances and depressive symptoms are associated closely with daytime dysfunctions, yet few studies have investigated their temporal relationship in a randomized controlled trial. We investigated the inter-relationships among sleep, depressive symptoms and daytime functioning following an integrative body-mind-spirit (I-BMS) intervention. One hundred and eighty-five participants (mean age 55.28 years, 75.1% female) with co-existing sleep and depressive symptoms were randomized to I-BMS or waiting-list. Daytime functioning variables included the daytime dysfunction items of the Pittsburg Sleep Quality Index (PSQI-day), Somatic Symptom Inventory, Hospital Anxiety Depression Scale and Short Form Health Survey collected at baseline, post-treatment and 3-month follow-up. Sleep and depressive symptoms were measured by the sleep items of the PSQI (PSQI-night) and Center for Epidemiological Studies Depression Scale (excluding the sleep item) (CESD-M). Regression and path analyses were used to understand the role of daytime functioning in sleep and depressive symptoms. We found significant group and time effects on almost all daytime variables and significant group × time interactions on PSQI-day and somatic symptoms. The adjusted regression model showed that CESD-M was associated with all daytime variables. However, PSQI-night was associated only with PSQI-day. Path analyses indicated that PSQI-day bridged PSQI-night and CESD-M in a two-way direction after the I-BMS intervention. The conclusion was that, following I-BMS intervention, improvement in daytime functioning was related predominantly to improvement in depressive symptoms. Night-time sleep related only to daytime dysfunction that was specific to sleep disturbances. Therefore, 'sleep-specific daytime impairment' could be regarded as a major link from night-time sleep to depressive symptoms. More studies are required to understand the concept of 'sleep-specific daytime impairment'.

The interrelationship between sleep and depression: a secondary analysis of a randomized controlled trial on mind-body-spirit intervention.

OBJECTIVES: To conduct a secondary analysis of a randomized controlled trial (RCT) that aims to understand the mediating effects embedded in a mind-body-spirit intervention for sleep and mood disturbances. METHODS: 126 adults with mild to moderate depression and subjective sleep disturbance, defined as Center for Epidemiologic Studies Depression Scale (CESD) scores from 10 to 34 and Pittsburgh Sleep Quality Index (PSQI) score > 5, participated in a waitlist-controlled RCT of an integrative mind-body-spirit intervention (I-BMS). Holistic well-being scale (HWS), a measure of the state of affliction and equanimity in mind, body and spirit, was included as a possible mediator. Data was collected at baseline and three-month follow-up. Mediation analyses were adopted to examine the pathways leading to sleep and mood improvements. RESULTS: After adjustments of baseline severities, changes in depressive symptoms partially mediated the effect of I-BMS on nighttime symptoms of insomnia (95% CI: 0.12-0.96), while exerting a full mediating effect on daytime symptoms of insomnia (95% CI: 0.14-0.64). The effect of I-BMS on mood was mediated by daytime symptoms of insomnia and spiritual orientation, but not by nighttime symptoms of insomnia (95% CI: 0.93-4.62). CONCLUSION: A bidirectional relationship was found between sleep disturbances and depressive symptoms following a mind-body-spirit intervention. The relationship between daytime symptoms and depressive symptoms was especially strong. Of the HWS variables, spiritual orientation was the only significant mediator of mood improvement following I-BMS. Our findings suggest that efforts to optimize the treatment of comorbid sleep disturbances and depression are needed, especially the treatment of daytime impairments along with sleep and mood disruptions.

[Experimental study for thrombocytopenic purpura therapy by targeting macrophages in liver and spleen].

The study purpose was to explore whether dichloromethylene diphosphonate (Cl(2)MDP)-loaded gelatin particles can induce the depletion of macrophage in reticuloendothelial system of liver and spleen or can depress the immunity of macrophage in SD rat models of immune thrombocytopenic purpura (ITP) to treat the ITP rats. New Zealand rabbits were immunized with platelets of SD rats to prepare rabbit anti-rat platelet serum, and the serum was intravenously injected into SD rats to produce the ITP model. In experimental ITP models, 150 microl of anti-platelet serum was intravenously injected into SD rats per 24 hours. The platelet counts maintained pathological level and were persistently less than 50 x 10(9)/L in the models during experiment process. The MTT test of macrophage RAW264.7 was carried out by means of Cl(2)MDP-loaded gelatin particles in vitro. After intravenous injection of a group dose of Cl(2)MDP-gelatin particles, the platelet counts of the rats were measured at the time of 4 hours, 24 hours, 48 hours, 72 hours and 96 hours, respectively, and bleeding times were detected in 24 hours. The results showed that Cl(2)MDP-loaded gelatin particles increased the platelet counts of ITP models to mean of 180 x 10(9)/L, a physiological level in 24 hours after injection, and kept this platelet level through whole process of 120 hours. Furthermore, rats pre-treated with Cl(2)MDP-loaded gelatin particles avoided the decrease of platelet counts significantly when they were injected anti-platelet serum. It is concluded that Cl(2)MDP-loaded gelatin particles restrain multiplication of macrophage RAW264.7, and promptly, effectively restore platelet counts of ITP models to physiological level in a dose dependent manner. So, the targeting therapy of drug-loaded gelatin particles offers a new idea and approach to treat ITP, and this strategy is worthy of further studies.