A Systematic Review and Lived Experience Synthesis of Self-disclosure as an Active Ingredient in Interventions for Adolescents and Young Adults with Anxiety and Depression.

Self-disclosure, referring to the ability to communicate and share intimate personal feelings, has strong face validity for many young people as a way of improving anxiety and depression outcomes. The current review aimed to generate the first comprehensive evidence synthesis of self-disclosure interventions involving young people aged 14-24 years who are either disclosers or recipients of personal information about living with anxiety and/or depression. A systematic review of quantitative and qualitative data was combined with new insights from an adolescents and young adults lived-experience panel (n = 7) with the intention to combine rigorous systematic review methods and experiential knowledge. Six studies of variable quality were included in this review, five were quantitative and one was qualitative. Findings suggest that self-disclosure may be effective at reducing symptoms for adolescents and young adults with established depression; effects were not apparent when delivered as early prevention. No evidence for impacts on anxiety was found. The potential for negative effects like bullying or harassment was identified. Findings were limited by a small number of studies; low representation of peer-reviewed studies from low-or middle-income countries; and varied interventions in terms of format, participants' context, and nature of delivery. Self-disclosure may be of value in the context of interventions intended explicitly to reduce depression for those already showing symptoms. Delivery by non-specialists (such as peers and teachers) in addition to mental health professionals can help build capacity in community health systems. Self-disclosure may also be helpful at reducing stigma and stimulating help-seeking at earlier stages of mental health problems.

Inflammation and apoptosis, two key events induced by hyperglycemia mediated reactive nitrogen species in RGC-5 cells.

Nitrosative stress plays a critical role in retinal injury in high glucose (HG) environment of eye, but the mechanisms remain poorly understood. Here we tested the hypothesis that HG induced reactive nitrogen species (RNS) production acts as a key functional mediator of antioxidant depletion, mitochondrial dysfunction, biomolecule damage, inflammation and apoptosis. Our findings illustrated that exposure of cultured RGC-5 cells to HG significantly disrupts the antioxidant defense mechanism and mitochondrial machineries by increasing the loss of mitochondrial membrane potential (ΔÑ°M) and elevating mitochondrial mass. Furthermore, we used biochemical tools to analyze the changes in metabolites, sulfur amino acids (SAAs) such as L-glutathione (GSH) and L-cysteine (Cys), in the presence of HG environment. These metabolic changes were followed by an increase in glycolytic flux that is phosphofructokinase-2 (PFK-2) activity. Moreover, HG exposure results in a significant disruption of protein carbonylation (PC) and lipid peroxidation (LPO), downregulation of OGG1 and increase in 8-OHdG accumulations in RGC-5 cells. In addition, our results demonstrated that HG environment coinciding with increased expression of inflammatory mediators, cell cycle deregulation, decreased in cell viability and expression of FoxOs, increased lysosomal content leading to apoptosis. Pre-treatment of selective inhibitors of RNS significantly reduced the HG-induced cell cycle deregulation and apoptosis in RGC-5 cells. Collectively, these results illustrated that accumulated RNS exacerbates the antioxidant depletion, mitochondrial dysfunction, biomolecule damage, inflammation and apoptosis induced by HG exposure in RGC-5 cells. Treatment of pharmacological inhibitors attenuated the HG induced in retinal cells.

High glucose-induced ROS accumulation is a critical regulator of ERK1/2-Akt-tuberin-mTOR signalling in RGC-5 cells.

Hyperglycemia and oxidative stress are the primary stressors that elicit mitochondria specific cell stress in diabetes. Here we hypothesized that elevated level of ROS in high glucose (HG) environment, trigger mitochondrial stress by damaging mitochondrial DNA (mtDNA), altering inflammatory mediators, and neurodegenerative markers via stress signalling pathway in retinal ganglion cells (RGC-5). Mechanistically, our findings illustrated that the HG environment increases the ROS production in retinal cells leading to the disruption of antioxidant defence mechanism, and altering mitochondrial machinery such as an increase in loss of mitochondrial membrane potential (ΔΨm), increase in mitochondrial mass, and increase in mtDNA fragmentation. Furthermore, fragmented mtDNA escape from mitochondria into the cytosol, where it engaged with cyclic GMP-AMP synthase (cGAS) and stimulator of IFN gene (STING) phosphorylation and activate interferon regulatory factor 3 (IRF3) via ERK1/2-Akt-tuberin-mTOR dependent pathways. Our results further indicate that siRNA-mediated gene silencing of tuberin suppresses the strong downregulation of tuberin-mTOR-IRF3 activation. HG environment resulted in activation of IRF3, coinciding with the increased expression of inflammatory mediators and neurodegenerative markers. Pre-treatment of N-acetyl-l-cysteine (NAC) or ERK1/2 or phosphoinositide3-kinase (PI3-K)/Akt inhibitors in RGC-5 cells significantly reduced the HG-induced IRF3 expression and declined the expression of neurodegenerative markers. Collectively, our results demonstrates that HG-induced over production of ROS, disrupts the antioxidant defence mechanism and mitochondrial dysfunction, leading to alterations of inflammatory mediators and neurodegenerative markers through the ERK1/2-Akt-tuberin-mTOR dependent signalling pathway in RGC-5 cells.

CEES-induced ROS accumulation regulates mitochondrial complications and inflammatory response in keratinocytes.

Reactive oxygen species (ROS) is mainly produced as a by-product from electron transport chain (ETC) of mitochondria and effectively eliminated by cellular antioxidants. However, 2-chloroethyl ethyl sulfide (CEES) exposure to keratinocytes declined antioxidant capacity and increased accumulation of ROS triggered alteration of mitochondrial activity and apoptosis is lacking. Our findings demonstrated that the electron leakage from the impaired ETC, leading to the accumulation of ROS was gradually elevating with increasing concentration of CEES exposure, which decline the activity of superoxide dismutase (SOD), manganese SOD (MnSOD) and copper-zinc SOD (Cu-ZnSOD) in keratinocytes. Further, excess accumulation of ROS, decreased the mitochondrial membrane potential (ΔΨm) and increased the mitochondrial mass with increasing dose of CEES. CEES exposure provoked the decrease in expression of transcription factor A mitochondrial (TFAM), augmented mitochondrial DNA (mtDNA) damage and altered the mtDNA-encoded oxidative phosphorylation (OXPHOS) subunits. Moreover, fragmented mtDNA translocated into cytosol, where it activated cGAS-STING and interferon regulatory factor3 (IRF3), coinciding with the increased expression of inflammatory mediators and alteration of cell-to-cell communication markers. Pre-treatment of N-acetyl-l-cysteine (NAC) or L-Nω-nitroarginine methyl ester (NAME), hydralazine hydrochloride (Hyd·HCl) or ERK1/2 or phosphoinositide3-kinase (PI3-K)/Akt inhibitors in keratinocyte cells significantly restored the CEES effect. Our findings suggest that CEES-induced mitochondrial ROS production and accumulation leads to mitochondrial dysfunction and inflammatory response in keratinocytes. However, treatment of antioxidants or ERK1/2 or PI3-K/Akt inhibitors is a novel therapeutic option for the keratinocytes complication.

High glucose augments ROS generation regulates mitochondrial dysfunction and apoptosis via stress signalling cascades in keratinocytes.

Mitochondria are fascinating structures of the cellular compartments that generate energy to run the cells. However, inherent disorders of mitochondria due to diabetes can cause major disruption of metabolism that produces huge amount of reactive oxygen species (ROS). Here we study the elevated level of ROS provoked by high glucose (HG) environment triggered mitochondrial dysfunction, inflammatory response and apoptosis via stress signalling pathway in keratinocytes. Our results demonstrated that elevated glucose level in keratinoctes, increase the accumulations of ROS and decrease in cellular antioxidant capacities. Moreover, excess production of ROS was associated with mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential (ΔΨm), increase in mitochondrial mass, alteration of mitochondrial respiratory complexes, cytochrome c (Cyt c) release, decrease in mitochondrial transcription factor A (TFAM) and increase in mitochondrial DNA (mtDNA) fragmentation. Damaged mtDNA escaped into the cytosol, where it engaged the activation of ERK1/2, PI3K/Akt, tuberin and mTOR via cGAS-STING leading to IRF3 activation. Pre-treatment of pharmacological inhibitors, ERK1/2 or PI3K/Akt suppressed the IRF3 activation. Furthermore, our results demonstrated that activation of IRF3 in HG environment coinciding with increased expression of inflammatory mediators. Excess production of ROS interfered with decreased in cell viability, increased lysosomal content and expression of FoxOs, leading to cell cycle deregulation and apoptosis. Pre-treatment of N-acetyl-l-cysteine (NAC) significantly reduced the HG-induced cell cycle deregulation and apoptosis in keratinocytes. In conclusion, increased oxidative stress underlies the decrease in antioxidant capacities and mitochondrial dysfunction in HG environment correlate with inflammation response and apoptosis via ERK1/2-PI3K/Akt-IRF3 pathway in keratinoctes.

What are young Indians saying about mental health? A content analysis of blogs on the It's Ok To Talk website.

OBJECTIVES: This study used thematic content analysis to examine submissions to a youth mental health website, www.itsoktotalk.in, in India. SETTING: We considered submissions made to the It's OK to Talk web platform during the first year of its operation (April 2017-March 2018), focusing specifically on website users based in India. PARTICIPANTS: We analysed 37 submissions by 33 authors aged 19-31 years (mean age 22 years) from seven Indian cities (New Delhi, Lucknow, Bengaluru, Mumbai, Pune, Hyderabad and Haryana). Eligible submissions were English-language first-person accounts of self-identified mental health problems, submitted in any media format for online publication by authors aged 18 years or older and who were based in India. Eight study participants were additionally involved in a focus group who contributed to the coding process and preparation of the final manuscript. RESULTS: Four themes were identified: (1) living through difficulties; (2) mental health in context; (3) managing one's mental health and (4) breaking stigma and sharing hope. Overall, the participants expressed significant feelings of distress and hopelessness as a result of their mental health problems; many described the context of their difficulties as resulting from personal histories or wider societal factors; a general lack of understanding about mental health; and widespread stigma and other negative attitudes. Most participants expressed a desire to overcome mental health prejudice and discrimination. CONCLUSIONS: Personal narratives offer a window into young people's self-identified priorities and challenges related to mental health problems and recovery. Such insights can inform antistigma initiatives and other public awareness activities around youth mental health.

Oxidative stress, antioxidant capacity, biomolecule damage, and inflammation symptoms of sickle cell disease in children.

BACKGROUND: The phenotypic expression of sickle cell disease (SCD) is a complex pathophysiologic condition. However, sickle erythrocytes might be the cause for multiple sources of pro-oxidant processes with consequent linked to chronic and systemic oxidative stress. Herein, we explored the SCD phenomena could be the result in formation of oxidative stress as well as inflammation in children. MATERIAL AND METHODS: Blood samples of 147 SCD subjects were evaluated. A control group was formed of 156 individuals without SCD. Different oxidative stress markers and inflammatory mediators were measured by using various biochemical techniques. Plasma samples were collected from blood for the measurement of antioxidants and reactive oxygen species (ROS). RESULTS: The levels of plasma hydroxyl radical (HO•), and nitric oxide (NO) production were higher in SCD children in compared to control groups. The plasma antioxidants capacities such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) and protein thiol levels were significantly reduced in SCD children. The plasma lipid peroxidation, protein carbonylation, DNA damage markers were significantly altered in different age groups of SCD children. Further, our results showed that SCD children have chronic inflammatory disease due to persistent alteration of haemoglobin content, reticulocyte, total bilirubin, platelet, creatinine, leukocytes, and altered expression of inflammatory mediators in compared to control groups. CONCLUSION: SCD children have high oxidative stress, and conversely, decreased antioxidant activity. Decrease in antioxidant activity might explained the reduction in lipid peroxidation, protein carbonylation and increased inflammation, which in turn intensify the symptoms of SCD in children.

Prevalence of ocular morbidity among children aged 17 years or younger in the eastern India.

PURPOSE: Childhood ocular morbidity involves a spectrum of eye diseases that critically impact the mental development, future education and quality of life. However, there is limited evidence about the early detection and appropriate treatment of ocular morbidity in children <20 years. This study was aimed to assess the prevalence and make a comparison between the different types of ocular morbidity in children of both sexes in the age group of 6-17 years in the eastern India. METHODS: A cross-sectional survey of ocular morbidity among children <17 years of age who presented at the Department of Ophthalmology, Kalinga Institute of Medical Sciences, Bhubaneswar, and Vision Care Center for Retina, Bhubaneswar, in the eastern India between January 2015 and March 2018 was accomplished. Demographic information, visual acuity, type of eye injury, refractive errors and other detailed ophthalmic examination were screened. RESULTS: A total of 633 children (age 6-17 years) were examined in this study. The majority of cases were observed in children of age 12-17 years, accounting for almost close to half of all the cases. The prevalence of ocular morbidity was 45.92% in males and 53.97% in females. The most common ocular morbidity in children encountered was refractive error (54.62%), followed by congenital abnormalities (9%), allergic conjunctivitis (8.52%) and traumatic eye injury (7.1%). There was an increase in ocular morbidity with age, especially the refractive error and congenital abnormalities. CONCLUSION: A large number of ocular morbidity was observed in children of age <17 years. Since most of this morbidity was preventable or treatable, reasonable service for ocular morbidity and early age screening are effective methods to reduce this load. Moreover, health education for the prevention of childhood ocular morbidity and, at the same time, early presentation of children to ophthalmic hospitals for the treatment of eye disorders are essential.

Increasing NO level regulates apoptosis and inflammation in macrophages after 2-chloroethyl ethyl sulphide challenge.

Generation of nitric oxide (NO) in cellular compartments acts in a redox-dependent manner to counteract oxidative stress either by directly acting as an antioxidant through scavenging superoxide anions (O2-), to form peroxynitrite (ONOO-) or acting as a signaling molecule, altering gene expression that triggers various physiological processes. However, the molecular mechanisms of macrophage activation and NO production leads to apoptosis and inflammation after 2-chloroethyl ethyl sulphide (CEES) exposure remains unclear. We showed that CEES exposure in macrophages increased the O2- production. Also CEES exposure transiently increases the NO production and ONOO- accumulation via expression of inducible NO synthase (iNOS). Simultaneously, CEES exposure caused a significant reduction in cellular antioxidants and modulate lipid peroxidation (LPO), and protein carbonylation (PC) reactions, which was correlated with the increased level of NO and ONOO- accumulation. Mechanistic studies showed the DNA damage, 8-oxoGDNA glycosylase (OGG1) down regulation and 8-hydroxydeoxyguanosine (8-OHdG) accumulations in DNA, which was also confirmed by phosphorylation of ATM, ATR and H2A.X. Elevated levels of NO/ONOO- plays an important role in apoptosis, and alteration of cell cycle regulatory proteins in macrophages after CEES exposure. Moreover, CEES exposure to macrophage cells enhanced the transcriptional activities of inflammatory mediators such as TNFα, IL-1α, ICAM, CX3CL1, CCL8, and CXCL10, which were linked with NO/ONOO- accumulation. These results showed a mechanistic explanation of how NO/ONOO- cooperate to conduct apoptosis and inflammatory signals in macrophages after CEES challenged. Further, the protective effects of NO/ONOO- inhibitors may provide the basis for the development of a therapeutic strategy to counteract exposure to CEES.

Antimicrobial activity of iron oxide nanoparticle upon modulation of nanoparticle-bacteria interface.

Investigating the interaction patterns at nano-bio interface is a key challenge for safe use of nanoparticles (NPs) to any biological system. The study intends to explore the role of interaction pattern at the iron oxide nanoparticle (IONP)-bacteria interface affecting antimicrobial propensity of IONP. To this end, IONP with magnetite like atomic arrangement and negative surface potential (n-IONP) was synthesized by co-precipitation method. Positively charged chitosan molecule coating was used to reverse the surface potential of n-IONP, i.e. positive surface potential IONP (p-IONP). The comparative data from fourier transform infrared spectroscope, XRD, and zeta potential analyzer indicated the successful coating of IONP surface with chitosan molecule. Additionally, the nanocrystals obtained were found to have spherical size with 10-20 nm diameter. The BacLight fluorescence assay, bacterial growth kinetic and colony forming unit studies indicated that n-IONP (<50 µM) has insignificant antimicrobial activity against Bacillus subtilis and Escherichia coli. However, coating with chitosan molecule resulted significant increase in antimicrobial propensity of IONP. Additionally, the assay to study reactive oxygen species (ROS) indicated relatively higher ROS production upon p-IONP treatment of the bacteria. The data, altogether, indicated that the chitosan coating of IONP result in interface that enhances ROS production, hence the antimicrobial activity.