The prognostic utility of temporalis muscle thickness measured on magnetic resonance scans in patients with intra-axial malignant brain tumours: A systematic review and meta-analysis.

Introduction: Sarcopenia is associated with worsened outcomes in solid cancers. Temporalis muscle thickness (TMT) has emerged as a measure of sarcopenia. Hence, this study aims to evaluate the relationship between TMT and outcome measures in patients with malignant intra-axial neoplasms. Method: We searched Medline, Embase, Scopus and Cochrane databases for relevant studies. Event ratios with 95% confidence intervals (CI) were analysed using the RevMan 5.4 software. Where meta-analysis was impossible, vote counting was used to determine the effect of TMT on outcomes. The GRADE framework was used to determine the certainty of the evidence. Results: Four outcomes were reported for three conditions across 17 studies involving 4430 patients. Glioblastoma: thicker TMT was protective for overall survival (OS) (HR 0.59; 95% CI 0.46-0.76) (GRADE low), progression free survival (PFS) (HR 0.40; 95% CI 0.26-0.62) (GRADE high), and early discontinuation of treatment (OR 0.408; 95% CI 0.168-0.989) (GRADE high); no association with complications (HR 0.82; 95% CI 0.60-1.10) (GRADE low). Brain Metastases: thicker TMT was protective for OS (HR 0.73; 95% CI 0.67-0.78) (GRADE moderate); no association with PFS (GRADE low). Primary CNS Lymphoma: TMT was protective for overall survival (HR 0.34; 95% CI 0.19-0.60) (GRADE moderate) and progression free survival (HR 0.23; 95% CI 0.09-0.56) (GRADE high). Conclusion: TMT has significant prognostic potential in intra-axial malignant neoplasms, showing a moderate to high certainty for its association with outcomes following GRADE evaluation. This will enable shared decision making between patients and clinicians.

Tlr4 Deletion Modulates Cytokine and Extracellular Matrix Expression in Chronic Spinal Cord Injury, Leading to Improved Secondary Damage and Functional Recovery.

Toll-like receptors (TLRs) play an important role in the innate immune response after CNS injury. Although TLR4 is one of the best characterized, its role in chronic stages after spinal cord injury (SCI) is not well understood. We examined the role of TLR4 signaling in injury-induced responses at 1 d, 7 d, and 8 weeks after spinal cord contusion injury in adult female TLR4 null and wild-type mice. Analyses include secondary damage, a range of transcriptome and protein analyses of inflammatory, cell death, and extracellular matrix (ECM) molecules, as well as immune cell infiltration and changes in axonal sprouting and locomotor recovery. Lack of TLR4 signaling results in reduced neuronal and myelin loss, reduced activation of NFκB, and decreased expression of inflammatory cytokines and necroptotic cell death pathway at a late time point (8 weeks) after injury. TLR4 null mice also showed reduction of scar-related ECM molecules at 8 weeks after SCI, accompanied by increase in ECM molecules associated with perineuronal nets, increased sprouting of serotonergic fibers, and improved locomotor recovery. These findings reveal novel effects of TLR4 signaling in chronic SCI. We show that TLR4 influences inflammation, cell death, and ECM deposition at late-stage post-injury when secondary injury processes are normally considered to be over. This highlights the potential for late-stage targeting of TLR4 as a potential therapy for chronic SCI.

Detection and isolation of wormhole nodes in wireless ad hoc networks based on post-wormhole actions.

The wormhole attack is one of the most treacherous attacks projected at the routing layer that can bypass cryptographic measures and derail the entire communication network. It is too difficult to prevent a priori; all the possible countermeasures are either too expensive or ineffective. Indeed, literature solutions either require expensive hardware (typically UWB or secure GPS transceivers) or pose specific constraints to the adversarial behavior (doing or not doing a suspicious action). The proposed solution belongs to the second category because the adversary is assumed to have done one or more known suspicious actions. In this solution, we adopt a heuristic approach to detect wormholes in ad hoc networks based on the detection of their illicit behaviors. Wormhole and post wormhole attacks are often confused in literature; that's why we clearly state that our methodology does not provide a defence against wormholes, but rather against the actions that an adversary does after the wormhole, such as packet dropping, tampering with TTL, replaying and looping, etc. In terms of contributions, the proposed solution addresses the knock-out capability of attackers that is less targeted by the researcher's community. In addition, it neither requires any additional hardware nor a change in it; instead, it is compatible with the existing network stack. The idea is simulated in ns2.30, and the average detection rate of the proposed solution is found to be 98-99%. The theoretical time to detect a wormhole node lies between 0.07-0.71 seconds. But, from the simulation, the average detection and isolation time is 0.67 seconds. In term of packet loss, the proposed solution has a relatively overhead of [Formula: see text] 22%. It works well in static and mobile scenarios, but the frame losses are higher in mobile scenarios as compared to static ones. The computational complexity of the solution is O(n). Simulation results advocate that the solution is effective in terms of memory, processing, bandwidth, and energy cost. The solution is validated using statistical parameters such as Accuracy, Precision, F1-Score and Matthews correlation coefficient ([Formula: see text]).

Cloud Digital Forensics: Beyond Tools, Techniques, and Challenges.

Cloud computing technology is rapidly becoming ubiquitous and indispensable. However, its widespread adoption also exposes organizations and individuals to a broad spectrum of potential threats. Despite the multiple advantages the cloud offers, organizations remain cautious about migrating their data and applications to the cloud due to fears of data breaches and security compromises. In light of these concerns, this study has conducted an in-depth examination of a variety of articles to enhance the comprehension of the challenges related to safeguarding and fortifying data within the cloud environment. Furthermore, the research has scrutinized several well-documented data breaches, analyzing the financial consequences they inflicted. Additionally, it scrutinizes the distinctions between conventional digital forensics and the forensic procedures specific to cloud computing. As a result of this investigation, the study has concluded by proposing potential opportunities for further research in this critical domain. By doing so, it contributes to our collective understanding of the complex panorama of cloud data protection and security, while acknowledging the evolving nature of technology and the need for ongoing exploration and innovation in this field. This study also helps in understanding the compound annual growth rate (CAGR) of cloud digital forensics, which is found to be quite high at ≈16.53% from 2023 to 2031. Moreover, its market is expected to reach ≈USD 36.9 billion by the year 2031; presently, it is ≈USD 11.21 billion, which shows that there are great opportunities for investment in this area. This study also strategically addresses emerging challenges in cloud digital forensics, providing a comprehensive approach to navigating and overcoming the complexities associated with the evolving landscape of cloud computing.

Performance analysis: Securing SIP on multi-threaded/multi-core proxy server using public keys on Diffie-Hellman (DH) in single and multi-server queuing scenarios.

The rapid replacement of PSTN with VOIP networks indicates the definitive phase-out of the PBX/PABX with smartphone-based VOIP technology that uses WLAN connectivity for local communication; however, security remains a key issue, regardless of the communication coverage area. Session initiation protocol (SIP) is one of the most widely adopted VOIP connection establishment protocols but requires added security. On the Internet, different security protocols, such as HTTPS (SSL/TLS), IPSec, and S/MIME, are used to protect SIP communication. These protocols require sophisticated infrastructure and some pose a significant overhead that may deteriorate SIP performance. In this article, we propose the following: i) avoid using Internet bandwidth and complex Internet protocols for local communication within an organization, but harness WLAN connectivity, ii) use multi-threaded or multicore computer systems to handle concurrent calls instead of installing hardware-based SIP servers, and iii) run each thread in a separate core. Cryptography is a key tool for securely transmitting confidential data for long- and short-range communication, and the Diffie-Hellman (DH) protocol has consistently been a popular choice for secret key exchanges. Primarily, used for symmetric key sharing, it has been proven effective in generating public/private key pairs, sharing public keys securely over public channels, and subsequently deriving shared secret keys from private/public keys. This key exchange scheme was proposed to safeguard VOIP communication within WLANs, which rely on the SIP for messaging and multimedia communication. For ensuring an efficient implementation of SIP, the system was rigorously analyzed using the M/M/1 and M/M/c queuing models. We analyze the behavior of SIP servers with queuing models with and without end-to-end security and increase users' trust in SIP security by providing a transparent sense of end-to-end security as they create and manage their private and public keys instead of relying on the underlying SIP technology. This research implements instant messaging, voice conversation, and secret key generation over DH while implementing and observing the role of multi-threading in multiqueue systems that serve incoming calls. By increasing the number of threads from one to two, the SIP response time improved from 20.23809 to 0.08070 min at an arrival rate of 4250 calls/day and a service rate of three calls/min. Similarly, by adding one to seven threads, the queue length was reduced by four calls/min. Implementing secure media streaming and reliable AES-based signaling for session confidentiality and integrity introduces a minor 8-ms tradeoff in SIP service performance. However, the advantages of implementing added security outweigh this limitation.

Association of serum testosterone with chronic obstructive pulmonary disease (COPD) in a nationally representative sample of White, Black, and Hispanic men.

BACKGROUND: The association between total testosterone (T) and chronic obstructive pulmonary disease (COPD), remains poorly understood. We aim to investigate this association and how it varies by smoking status, body fatness, and race/ethnicity in a nationally representative sample of American men. METHODS: Data included a full sample (NHANES 1988-1991, 1999-2004, 2011-2012) and subset sample (excluding 2011-2012, no estradiol and SHBG levels available) of 2748 and 906 men (≥20 years), respectively. COPD was measured by self-report or spirometry test. Total T (ng/mL) was measured among men who participated in a morning examination session. Weighted multivariable-adjusted logistic regression models were conducted. RESULTS: Low T was positively associated with self-reported COPD in the full sample (OR = 2.10, 95% CI = 1.18-3.74, Ptrend = 0.010), and when stratified by current smokers and body fatness. When examined across race and ethnicity strata, this association persisted among White men (OR = 2.50, 95% CI = 1.30-4.79, Ptrend = 0.002) but not among Hispanic or Black men. In the subset sample, low T was positively associated with self-reported COPD (OR = 1.42, 95% CI, 0.57,3.55, Ptrend = 0.04), including among smokers and White men, but not body fatness. No significant associations were observed with COPD defined with spirometry plus self-report. CONCLUSION: Low levels of T were associated with an increased prevalence of self-reported COPD in the full and subset samples. Similar associations were observed after stratifying by smoking status, body fatness, and race/ethnicity in the full sample and subset sample. Prospective studies are warranted to confirm these significant associations among understudied and underserved populations.

Financial Performance is Associated With PPE Shortages in Chain-Affiliated Nursing Homes During the COVID-19 Pandemic: A Longitudinal Study.

Many nursing homes operated at thin profit margins prior to the COVID-19 pandemic. This study examines the role of nursing homes' financial performance and chain affiliation in shortages of personal protection equipment (PPE) during the first year of the COVID-19 pandemic. We constructed a longitudinal file of 79 868 nursing home-week observations from 10 872 unique facilities. We found that a positive profit margin was associated with a 21.0% lower probability of reporting PPE shortages in chain-affiliated nursing homes, but not in non-chain nursing homes. Having adequate financial resources may help nursing homes address future emergencies, especially those affiliated with a multi-facility chain.

Alterations of neural activity in the prefrontal cortex associated with deficits in working memory performance.

Working memory (WM), a core cognitive function, enables the temporary holding and manipulation of information in mind to support ongoing behavior. Neurophysiological recordings conducted in nonhuman primates have revealed neural correlates of this process in a network of higher-order cortical regions, particularly the prefrontal cortex (PFC). Here, we review the circuit mechanisms and functional importance of WM-related activity in these areas. Recent neurophysiological data indicates that the absence of these neural correlates at different stages of WM is accompanied by distinct behavioral deficits, which are characteristic of various disease states/normal aging and which we review here. Finally, we discuss emerging evidence of electrical stimulation ameliorating these WM deficits in both humans and non-human primates. These results are important for a basic understanding of the neural mechanisms supporting WM, as well as for translational efforts to developing therapies capable of enhancing healthy WM ability or restoring WM from dysfunction.

UDHAVI Community Support During India's Second COVID-19 Wave: A Descriptive Study on a Tertiary Care Center's Pandemic Response Helpline.

BACKGROUND: In April 2021, during the peak of the second wave of the COVID-19 pandemic in India, hospitals overflowed with COVID-19 patients, and people hesitated to seek necessary care due to fear of contracting the disease. The UDHAVI helpline was set up by a tertiary care hospital in Vellore with the help of district administration, nongovernmental organizations, and various supporting agencies to provide general information, medical advice, counseling, and logistics support to the community. METHODS: This is a retrospective study of all the phone calls made to the UDHAVI helpline between mid-May and mid-June 2021 during the second wave of the COVID-19 pandemic. The calls were electronically captured as part of the process, and the information was subsequently retrieved and analyzed. RESULTS: In all, 677 calls were received. The lines for general information, medical advice, counseling, and logistics support received 168 (25%), 377 (56%), 15 (2%), and 117 (17%) calls, respectively. Home care kits, oxygen concentrators, and food were delivered by volunteers from local nongovernmental organizations and hospitals. CONCLUSION: We believe the details of our experience would be useful in the preparedness and mobilization of resources in the event of any public health emergency. As a result of this initiative, we propose an integrated partnership model for emergency response to any pandemic situation.

Autoclaving-induced dimensional changes of three-dimensional printed surgical guides: An in vitro study.

OBJECTIVES: Surgical guides are frequently used for dental implant placement. The aim of this study was to evaluate the impact of the 3D printing process itself and subsequent steam autoclaving on the dimensional stability of five different resin/printer combinations (RPCs). MATERIALS AND METHODS: Fifty identical surgical guides (10 per group) were produced consisting of five RPCs. Half of the guides (5 per group) were steam autoclaved with cycle 1 (121°C, 1 bar, 20.5 min) and the other half with cycle 2 (134°C, 2 bar, 5.5 min). All guides were scanned with a structured-light (SL) 3D scanner before (T0) and after (T1) autoclaving. Linear measurements along the x-, y-, and z-axes were performed at landmarks on the original STL file and on SL scans at T0 and T1, respectively. Wilcoxon signed-rank test, Kruskal-Wallis test, and linear mixed-effects models were performed, depending on the analysis. RESULTS: Three-dimensional printing was associated with significant dimensional alterations for all RPCs. Steam autoclaving using cycle 1 was associated with significant shrinkage in x- (1 RPC), y- (2 RPCs), and z-direction (2 RPCs), while cycle 2 was also associated with shrinkage in x- (2 RPCs), y- (1 RPC), and z-direction (1 RPC). One resin did not present any dimensional changes independently of the cycle. CONCLUSIONS: The majority of the guides presented minor but significant shrinkage due to 3D printing itself and both steam autoclaving cycles, the extent varied between different RPCs. Whether these changes compromise implant placement accuracy remains to be investigated.

Ferroptosis induces detrimental effects in chronic EAE and its implications for progressive MS.

Ferroptosis is a form of lipid peroxidation-mediated cell death and damage triggered by excess iron and insufficiency in the glutathione antioxidant pathway. Oxidative stress is thought to play a crucial role in progressive forms of multiple sclerosis (MS) in which iron deposition occurs. In this study we assessed if ferroptosis plays a role in a chronic form of experimental autoimmune encephalomyelitis (CH-EAE), a mouse model used to study MS. Changes were detected in the mRNA levels of several ferroptosis genes in CH-EAE but not in relapsing-remitting EAE. At the protein level, expression of iron importers is increased in the earlier stages of CH-EAE (onset and peak). While expression of hemoxygenase-1, which mobilizes iron from heme, likely from phagocytosed material, is increased in macrophages at the peak and progressive stages. Excess iron in cells is stored safely in ferritin, which increases with disease progression. Harmful, redox active iron is released from ferritin when shuttled to autophagosomes by 'nuclear receptor coactivator 4' (NCOA4). NCOA4 expression increases at the peak and progressive stages of CH-EAE and accompanied by increase in redox active ferrous iron. These changes occur in parallel with reduction in the antioxidant pathway (system xCT, glutathione peroxidase 4 and glutathione), and accompanied by increased lipid peroxidation. Mice treated with a ferroptosis inhibitor for 2 weeks starting at the peak of CH-EAE paralysis, show significant improvements in function and pathology. Autopsy samples of tissue sections of secondary progressive MS (SPMS) showed NCOA4 expression in macrophages and oligodendrocytes along the rim of mixed active/inactive lesions, where ferritin+ and iron containing cells are located. Cells expressing NCOA4 express less ferritin, suggesting ferritin degradation and release of redox active iron, as indicated by increased lipid peroxidation. These data suggest that ferroptosis is likely to contribute to pathogenesis in CH-EAE and SPMS.

Drug screening in zebrafish larvae reveals inflammation-related modulators of secondary damage after spinal cord injury in mice.

Prolonged inflammation after spinal cord injury is detrimental to recovery. To find pharmacological modulators of the inflammation response, we designed a rapid drug screening paradigm in larval zebrafish followed by testing of hit compounds in a mouse spinal cord injury model. Methods: We used reduced il-1ß linked green fluorescent protein (GFP) reporter gene expression as a read-out for reduced inflammation in a screen of 1081 compounds in larval zebrafish. Hit drugs were tested in a moderate contusion model in mice for cytokine regulation, and improved tissue preservation and locomotor recovery. Results: Three compounds robustly reduced il-1ß expression in zebrafish. Cimetidine, an over-the-counter H2 receptor antagonist, also reduced the number of pro-inflammatory neutrophils and rescued recovery after injury in a zebrafish mutant with prolonged inflammation. Cimetidine action on il-1ß expression levels was abolished by somatic mutation of H2 receptor hrh2b, suggesting specific action. In mice, systemic treatment with Cimetidine led to significantly improved recovery of locomotor behavior as compared to controls, accompanied by decreased neuronal tissue loss and a shift towards a pro-regenerative profile of cytokine gene expression. Conclusion: Our screen revealed H2 receptor signaling as a promising target for future therapeutic interventions in spinal cord injury. This work highlights the usefulness of the zebrafish model for rapid screening of drug libraries to identify therapeutics to treat mammalian spinal cord injury.

Ceruloplasmin-Deficient Mice Show Dysregulation of Lipid Metabolism in Liver and Adipose Tissue Reduced by a Protein Replacement.

Ceruloplasmin is a ferroxidase that plays a role in iron homeostasis; its deficiency fosters inter alia iron accumulation in the liver, which expresses the soluble form of the protein secreted into the bloodstream. Ceruloplasmin is also secreted by the adipose tissue, but its role in adipocytes has been poorly investigated. We hypothesized that ceruloplasmin might have a role in iron/lipid interplay. We investigated iron/lipid dysmetabolism in the liver and adipose tissue of the ceruloplasmin-deficient mouse (CpKO) model of aceruloplasminemia and evaluated the effectiveness of ceruloplasmin replacement. We found that CpKO mice were overweight, showing adipose tissue accumulation, liver iron deposition and steatosis. In the adipose tissue of CpKO mice, iron homeostasis was not altered. Conversely, the levels of adiponectin and leptin adipokines behaved opposite to the wild-type. Increased macrophage infiltration was observed in adipose tissue and liver of CpKO mice, indicating tissue inflammation. The treatment of CpKO mice with ceruloplasmin limited liver iron accumulation and steatosis without normalizing the expression of iron homeostasis-related proteins. In the CpKO mice, the protein replacement limited macrophage infiltration in both adipose and hepatic tissues reduced the level of serum triglycerides, and partially recovered adipokines levels in the adipose tissue. These results underline the link between iron and lipid dysmetabolism in ceruloplasmin-deficient mice, suggesting that ceruloplasmin in adipose tissue has an anti-inflammatory role rather than a role in iron homeostasis. Furthermore, these data also indicate that ceruloplasmin replacement therapy may be effective at a systemic level.

Current state of management and outcomes of facial nerve palsy in low-income and middle-income countries: a scoping review protocol.

INTRODUCTION: The aim of the protocol is to present the methodology of a scoping review that aims to synthesise up-to-date evidence on the management and outcomes of facial nerve palsy in low-income and middle-income countries (LMICs). METHODS AND ANALYSIS: The scoping review will be conducted per the Arksey and O'Malley's framework and the Joanna Briggs Institute Reviewers' Manual. The scoping review question, eligibility criteria and search strategy will be developed in accordance to the Population, Concept, and Context strategy. The search will be conducted in electronic bibliographic databases (Medline (OVID), Embase, WHO Global Index Medicus, Cochrane Library, Global Health, African Journals Online). The review will synthesise and report the findings with descriptive statistics and a narrative description of both quantitative and qualitative evidence. ETHICS AND DISSEMINATION: This scoping review does not require ethical approval. This protocol will describe the proposed scoping review that will map the evidence on the management and outcomes of facial nerve palsies in LMICs. The proposed review aims to collate and summarise published literature to inform policy-makers and healthcare organisations and governments and to identify knowledge gaps that will translate into future research priorities in LMICs.

Ferroptosis in Neurological Disease.

Iron accumulation in the CNS occurs in many neurological disorders. It can contribute to neuropathology as iron is a redox-active metal that can generate free radicals. The reasons for the iron buildup in these conditions are varied and depend on which aspects of iron influx, efflux, or sequestration that help maintain iron homeostasis are dysregulated. Iron was shown recently to induce cell death and damage via lipid peroxidation under conditions in which there is deficient glutathione-dependent antioxidant defense. This form of cell death is called ferroptosis. Iron chelation has had limited success in the treatment of neurological disease. There is therefore much interest in ferroptosis as it potentially offers new drugs that could be more effective in reducing iron-mediated lipid peroxidation within the lipid-rich environment of the CNS. In this review, we focus on the molecular mechanisms that induce ferroptosis. We also address how iron enters and leaves the CNS, as well as the evidence for ferroptosis in several neurological disorders. Finally, we highlight biomarkers of ferroptosis and potential therapeutic strategies.

A Survey on Wireless Wearable Body Area Networks: A Perspective of Technology and Economy.

The deployment of wearable or body-worn devices is increasing rapidly, and thus researchers' interests mainly include technical and economical issues, such as networking, interoperability, security, power optimization, business growth and regulation. To address these issues properly, previous survey papers usually focused on describing the wireless body area network architecture and network protocols. This implies that deployment issues and awareness issues of wearable and BAN devices are not emphasized in previous work. To defeat this problem, in this study, we have focused on feasibility, limitations, and security concerns in wireless body area networks. In the aspect of the economy, we have focused on the compound annual growth rate of these devices in the global market, different regulations of wearable/wireless body area network devices in different regions and countries of the world and feasible research projects for wireless body area networks. In addition, this study focuses on the domain of devices that are equally important to physicians, sportsmen, trainers and coaches, computer scientists, engineers, and investors. The outcomes of this study relating to physicians, fitness trainers and coaches indicate that the use of these devices means they would be able to treat their clients in a more effective way. The study also converges the focus of businessmen on the Annual Growth Rate (CAGR) and provides manufacturers and vendors with information about different regulatory bodies that are monitoring and regulating WBAN devices. Therefore, by providing deployment issues in the aspects of technology and economy at the same time, we believe that this survey can serve as a preliminary material that will lead to more advancements and improvements in deployment in the area of wearable wireless body area networks. Finally, we present open issues and further research direction in the area of wireless body area networks.

Lactobacilli and Cytokine Modifications during Menopause and Their Relation to Vulvar and Vulvovaginal Disorders.

OBJECTIVES: Female sexual and reproductive health is heavily influenced by the levels and ratios of Lactobacilli species and vaginal cytokines. Menopause marks a profound body change as it shifts to a natural and permanent non-reproductive state. Vulvovaginal diseases encompass a broad variety of sexual health conditions. Furthermore, both menopause and vulvovaginal diseases affect vaginal Lactobacilli and cytokine levels. Thus, this study aimed to investigate the correlation between menopause, vulvovaginal diseases, and vaginal Lactobacilli and cytokine levels. METHODS: Vaginal swab samples were collected as part of a prospective data bank creation to study vaginal conditions as approved by the Institutional Review Board of Texas Tech University Health Sciences Center, Lubbock, USA. This study utilized 38 samples in this database, which were assigned to the pre-menopausal with no vulvovaginal conditions (n = 20) and post-menopausal with vulvovaginal conditions (n = 18) groups. A real-time polymerase chain reaction was conducted to determine the relative concentration of Lactobacilli species, while cytokine analysis was performed using multiplex enzyme-linked immunosorbent assay immunoassay. The standardized mean difference, multivariate analysis of variance, and permutational unequal variance t test were used for the statistical analysis. RESULTS: Cytokines, interleukin (IL)-6, macrophage inflammatory protein-1α, IL-8, and Lactobacillus iners expression were significantly elevated in the control group compared to the study group (P = 0.03 for the cytokines, P = 0.0194 for Lactobacilli). CONCLUSIONS: The levels of vaginal cytokine and Lactobacillus profile were significantly different between the pre-menopausal and post-menopausal groups.

Utilising fluorescent reporters to probe the mode of action of norbornen-7-one CO releasing molecules.

The synthesis of the fluorescent organic carbon monoxide releasing molecules oCOm-57, oCOm-58, and oCOm-66 are reported. These oCOms are water soluble and exhibit a "turn-on" fluorescent behaviour when CO is released under physiological conditions. oCOm-66 also contains an additional nitro-naphthalimide moiety that functions as a fluorescent reporter. Delivery of CO released from these oCOms to the mitochondria of AC-16 cardiomyocytes was confirmed using confocal microscopy in conjuction with MitoTracker Red. While the neutral, PEGylated oCOm-57 was found to remain in the extracellular environment releasing CO to diffuse into the cellular compartments, the positively charged oCOm-58 and -66 are targeted to the mitochondria where they release CO. Notably, the use of the fluorescent oCOms in live cellular imaging, allows the intracellular CO delivery and oCOm localisation to be characterised. This cellular confocal study also shows that, subtoxic concentrations of CO released from these molecules preserved mitochondrial energetics as indicated by the membrane potential dependent MitoTracker Red.

Dysregulation of Iron Homeostasis in the Central Nervous System and the Role of Ferroptosis in Neurodegenerative Disorders.

Significance: Iron accumulation occurs in the central nervous system (CNS) in a variety of neurological conditions as diverse as spinal cord injury, stroke, multiple sclerosis, Parkinson's disease, and others. Iron is a redox-active metal that gives rise to damaging free radicals if its intracellular levels are not controlled or if it is not properly sequestered within cells. The accumulation of iron occurs due to dysregulation of mechanisms that control cellular iron homeostasis. Recent Advances: The molecular mechanisms that regulate cellular iron homeostasis have been revealed in much detail in the past three decades, and new advances continue to be made. Understanding which aspects of iron homeostasis are dysregulated in different conditions will provide insights into the causes of iron accumulation and iron-mediated tissue damage. Recent advances in iron-dependent lipid peroxidation leading to cell death, called ferroptosis, has provided useful insights that are highly relevant for the lipid-rich environment of the CNS. Critical Issues: This review examines the mechanisms that control normal cellular iron homeostasis, the dysregulation of these mechanisms in neurological disorders, and more recent work on how iron can induce tissue damage via ferroptosis. Future Directions: Quick and reliable tests are needed to determine if and when ferroptosis contributes to the pathogenesis of neurological disorders. In addition, there is need to develop better druggable agents to scavenge lipid radicals and reduce CNS damage for neurological conditions for which there are currently few effective treatments. Antioxid. Redox Signal. 37, 150-170.