Dual‑Atom Nanozyme Eye Drops Attenuate Inflammation and Break the Vicious Cycle in Dry Eye Disease

Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual impairment.The incidence of DED is gradually increasing with the highfrequency use of electronic products.Although inflammation is core cause of the DED vicious cycle,reactive oxygen species(ROS)play a pivotal role in the vicious cycle by regulating inflammation from upstream.Therefore,current therapies merely targeting inflammation show the failure of DED treatment.Here,a novel dual-atom nanozymes(DAN)-based eye drops are developed.The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer.The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS,inhibiting NLRP3 inflammasome activation,decreasing proinflammatory cytokines expression,and suppressing cell apoptosis.Consequently,the DAN effectively alleviate ocular inflammation,promote corneal epithelial repair,recover goblet cell density and tear secretion,thus breaking the DED vicious cycle.Our findings open an avenue to make the DAN as an intervention form to DED and ROSmediated inflammatory diseases.

3-61 Mitochondrial Vicious Cycle Induced by Carbon Ions Supports the Long-lasting ROS Formation

As we all know ionizing radiation can promote the ROS formation in cells by water radiolysis instantly, whichexerts apoptosis in the tumors. Thus, increased production of ROS is one crucial mechanism for radiotherapy[1].However, the source of long-lasting ROS formation after radiation exposure is still not very clear.As the powerhouse of eukaryocyte, mitochondria is also a killer organelle equipped with death effectors incontrolling apoptosis, such as cyt-c and ROS, which are released when mitochondrial dysfunction[2;3]. The oxidativestress resulted from ROS generation and increase can injury mtDNA. The damages can elevate risks of mtDNAmutations, aggravate the mitochondrial dysfunction, and lead to more ROS production. Increased ROS results infurther increases in oxidative stress and increased rate of mtDNA damage, thus causing a mitochondrial viciouscycle, which ultimately culminates in cell death. During starting the vicious circle, mtDNA damage and ROSgeneration are two main factors.

Glymphatic system:a gateway for neuroinflammation

The glymphatic system is a relatively recently identified fluid exchange and transpo rt system in the brain.Accumulating evidence indicates thatglymphatic function is impaired not only in central nervous system disorders but also in systemic diseases.Systemic diseases can trigger the inflammatory responses in the central nervous system,occasionally leading to sustained inflammation and functional disturbance of the central nervous system.This review summarizes the current knowledge on the association between glymphatic dysfunction and central nervous system inflammation.In addition,we discuss the hypothesis that disease conditions initially associated with peripheral inflammation ove rwhelm the performance of the glymphatic system,thereby triggering central nervous system dysfun ction,chronic neuroinflammation,and neurodegeneration.Future research investigating the role of the glymphatic system in neuroinflammation may offer innovative therapeutic approaches for central nervous system disorders.

A qualitative exploration of Pakistan’s street children, as a consequence of the poverty-disease cycle

Background:Street children are a global phenomenon,with an estimated population of around 150 million across the world.These children include those who work on the streets but retain their family contacts,and also those who practically live on the streets and have no or limited family contacts.In Pakistan,many children are forced to work on the streets due to health-related events occurring at home which require children to play a financially productive role from an early stage.An explanatory framework adapted from the poverty-disease cycle has been used to elaborate these findings.Methods:This study is a qualitative study,and involved 19 in-depth interviews and two key informant interviews,conducted in Rawalpindi,Pakistan,from February to May 2013.The data was audio taped and transcribed.Key themes were identified and built upon.The respondents were contacted through a gatekeeper ex-street child who was a member of the street children community.Results:We asked the children to describe their life stories.These stories led us to the finding that street children are always forced to attain altered social roles because health-related problems,poverty,and large family sizes leave them no choice but to enter the workforce and earn their way.We also gathered information regarding high-risk practices and increased risks of sexual and substance abuse,based on the street children’s increased exposure.These children face the issue of social exclusion because diseases and poverty push them into a life full of risks and hazards;a life which also confines their social role in the future.Conclusion:The street child community in Pakistan is on the rise.These children are excluded from mainstream society,and the absence of access to education and vocational skills reduces their future opportunities.Keeping in mind the implications of health-related events on these children,robust inter-sectoral interventions are required.

Examination of the poverty-environmental degradation nexus in Sub-Saharan Africa

The relationship between environmental degradation and poverty has increasingly become the focus of national strategic decision-making in recent years.However,despite several theoretical explorations on the nexus,a dearth of empirical literature on the poverty-environmental degradation nexus,specifically on Sub-Saharan Africa(SSA),still exists.In this study,we investigated the poverty-environmental degradation nexus in SSA.We hypothesized that poverty is both a cause and effect of environmental degradation,and this relationship is explained as a vicious cycle.Unlike previous studies,we employed several alternative indicators of environmental degradation to examine the poverty-environmental degradation nexus in this study.We used data from 41 countries of SSA between 1996 and 2019 and employed the generalized method of moments(GMM)approach.The findings suggest a cyclical relationship between poverty and environmental degradation in SSA,which confirms that an increase in poverty leads to an increase in environmental degradation,especially in deforestation and PM2.5 emissions.Similarly,the increase in environmental degradation positively affects poverty in SSA.We also confirmed that exogenous conditioning factors such as population growth rate,education,industrialization,and income inequality,institutional quality indicators such as governance effectiveness,control of corruption,freedom ad civil liberty,and democracy,and endogenous factors including fossil fuel energy use,fuelwood energy use,household health expenditure,infant mortality rate,and agriculture productivity influence the nexus between poverty and environmental degradation.The findings on the relationship between poverty and environmental degradation in SSA are a testimonial evidence that both poverty and environmental degradation are significant issues in SSA.Hence,poverty alleviation policies in SSA should not lead to PM2.5 emissions and deforestation,which may as well force people into a poverty-environmental degradation trap.Instead,poverty reduction policies should simultaneously achieve environmental conservation.

Inflammation and dry eye disease——where are we?

The presence of inflammation in dry eye disease(DED)results in increased patient symptomatology,ocular surface damage and worsening tear dysfunction.It also affects the health of meibomian glands and their secretions which further aggravates ocular surface disease.This article reviews current knowledge regarding ocular surface inflammation in DED and explores the relationships between the vicious cycles of DED,inflammation and meibomian gland dysfunction(MGD).The clinical evaluation of eyes with such changes,markers that identify the presence of inflammation on the ocular surface and current treatment options are discussed.

Diabetic foot:Which one comes first,the ulcer or the contracture?

Diabetic foot is among the most common complications of patients with diabetes.One of the known causes of foot ulceration is ankle equinus,which increases the pressure on the plantar surface during ambulation.Conversely,equinus contracture can be caused by a complicated wound,and it may be due to prolonged immobilization.In this paper,we reviewed the pathogenesis of both conditions and their clinical considerations.Poor glycemic control in patients with diabetes may result in angiopathy and neuropathy as an underlying condition.An ulcer can be precipitated by an injury,improper foot care,or increased biomechanical loading as seen in elevated plantar pressure following equinus contracture.Equinus contracture may be a direct effect of hyperglycemia or can arise in combination with another pathway,for example,involving the activation of transforming growth factorβ.Static positioning resulting from any prior foot wound may develop fibrotic changes leading to contracture.Wound healing promoting factors can also result in overhealing outcomes such as hypertrophic scarring and fibrosis.The body’s repair mechanism during the healing cascade activates repair cells and myofibroblasts,which also serve as the main producers and organizers of the extracellular matrix.Considering this intricate pathogenesis,appropriate interventions are essential for breaking the vicious cycle that may disturb wound healing.

The Therapeutic Role of Guided Mental Imagery in Treating Stress and Insomnia: A Neuropsychological Perspective

Excessive distress and insomnia are much too common in the modern world and often lead to a myriad of detrimental effects including loss of cognitive ability and even physical ailments such as cancer. Current pharmaceutical treatments can be addictive, detrimental to health, and in the case of insomnia don’t produce naturalistic sleep. We present a viewpoint on a potential adjunctive treatment of distress and insomnia that harnesses specific mental imagery as a component of mind/body relaxation technique. Via our perspective on the modern nature of stress and insomnia, our theoretical perspective on how specific guided mental imagery can be used to treat these ailments, and our review on the current literature on treatment with mental imagery, we hope to stimulate further research into mental health treatment with mental imagery which has traditionally been neglected. This perspective on the pathology of insomnia and distress is founded in prevailing “dysevolution” and hyper-arousal theories. Hyper-arousal is characterized in part by a vicious cycle of chronic physiological and emotional stimulation/distress. We argue for spatially based mental imagery in the form of nighttime-sky imagery to attenuate such pathology by breaking one away from a vicious cycle of stimulation and distress and discuss neuropsychological bases for its potential treatment mechanisms which include the autonomic nervous system and a phenomenal foundation of conscious cognition.