A grazing crab drives saltmarsh carbon storage and recovery.

Consumers can directly (e.g., consumption) and indirectly (e.g., trophic cascades) influence carbon cycling in blue carbon ecosystems. Previous work found that large grazers have nuanced effects on carbon stocks, yet, small, bioturbating-grazers, which remove plant biomass and alter sediment properties, remain an understudied driver of carbon cycling. We used field-derived and remote sensing data to quantify how the purple marsh crab, Sesarma reticulatum, influenced carbon stocks, flux, and recovery in salt marshes. Sesarma caused a 40%-70% loss in carbon stocks as fronts propagated inland (i.e., ungrazed to recovered transition), with front migration rates accelerating over time. Despite latitudinal differences, front migration rate had no effect on carbon stocks, flux, or time to replacement. When we included Sesarma disturbance in carbon flux calculations, we found it may take 5-100 years for marshes to replace lost carbon, if at all. Combined, we show that small grazers cause a net loss in carbon stocks as they move through the landscape, and irrespective of migration rate, these grazer-driven impacts persist for decades. This work showcases the significant role of consumers in carbon storage and flux, challenging the classic paradigm of plant-sediment feedbacks as the primary ecogeomorphic driver of carbon cycling in blue carbon ecosystems.

Association of Electronic-Cigarette, Number of Cigarettes, and Marijuana Use with High-Risk Human Papillomavirus (HPV) Among Men and Women: A Cross-Sectional Analysis of a Nationally Representative Sample.

BACKGROUND: Smoking is associated with an increased risk of HPV infection. However, the use of e-cigarettes and marijuana, number of cigarettes, and serum cotinine concentrations in relation with HPV (6, 11, 16, 18) and high-risk HPV (16 or 18) infections in underserved and understudied populations remain poorly understood. METHODS: Data included 687 males and 664 females among whom 489 were White, 375 were Black and 342 were Hispanics from the NHANES 2013-2016 with HPV and high-risk HPV infections. Smoking history included current and past smokers, number of cigarettes, use of e-cigarettes, marijuana, and serum cotinine levels. Weighted multivariable-adjusted logistic regression models were conducted. RESULTS: High-risk HPV infection was associated with current smoking history plus ≥ 20 cigarettes/day (OR=1.92, 95% CI=1.09, 3.37) in the overall population. E-cigarettes use (5 days) was positively associated with high-risk HPV infection (OR=2.43, 95% CI=1.13, 5.22) in the overall population, with similar findings with e-cigarette (past 30 days) among women and Whites. CONCLUSION: High number of cigarettes, e-cigarette usage and marijuana were associated with HPV and high-risk HPV infections in the overall population. Most of these associations remained significant when stratified by gender and race/ethnicity. Increasing use of e-cigarettes and marijuana in these population warrants further investigation for the prevention of HPV infection and related cancers.

Leeches Predate on Fast-Escaping and Entangling Blackworms by Spiral Entombment.

We investigate how the Helobdella sp. freshwater leeches capture and consume Lumbriculus variegatus blackworms despite the blackworm's ultrafast helical swimming escape reflex and ability to form large tangled "blobs". We describe a spiral "entombment" predation strategy, where Helobdellid leeches latch onto blackworms with their anterior sucker and envelop them in a spiral cocoon. Quantitative analysis shows that larger leeches succeed more often in entombing prey, while longer worms tend to escape. The rate of spiral contraction correlates with entombment outcomes, with slower rates associated with success. These insights highlight the complex interactions between predator and prey in freshwater ecosystems, providing new perspectives on ecological adaptability and predator-prey dynamics.

Ferroptosis inhibitor improves outcome after early and delayed treatment in mild spinal cord injury.

We show that redox active iron can induce a regulated form of non-apoptotic cell death and tissue damage called ferroptosis that can contribute to secondary damage and functional loss in the acute and chronic periods after spinal cord injury (SCI) in young, adult, female mice. Phagocytosis of red blood cells at sites of hemorrhage is the main source of iron derived from hemoglobin after SCI. Expression of hemeoxygenase-1 that induces release of iron from heme, is increased in spinal cord macrophages 7 days after injury. While iron is stored safely in ferritin in the injured spinal cord, it can, however, be released by NCOA4-mediated shuttling of ferritin to autophagosomes for degradation (ferritinophagy). This leads to the release of redox active iron that can cause free radical damage. Expression of NCOA4 is increased after SCI, mainly in macrophages. Increase in the ratio of redox active ferrous (Fe2+) to ferric iron (Fe3+) is also detected after SCI by capillary electrophoresis inductively coupled mass spectrometry. These changes are accompanied by other hallmarks of ferroptosis, i.e., deficiency in various elements of the antioxidant glutathione (GSH) pathway. We also detect increases in enzymes that repair membrane lipids (ACSL4 and LPCAT3) and thus promote on-going ferroptosis. These changes are associated with increased levels of 4-hydroxynonenal (4-HNE), a toxic lipid peroxidation product. Mice with mild SCI (30 kdyne force) treated with the ferroptosis inhibitor (UAMC-3203-HCL) either early or delayed times after injury showed improvement in locomotor recovery and secondary damage. Cerebrospinal fluid and serum samples from human SCI cases show evidence of increased iron storage (ferritin), and other iron related molecules, and reduction in GSH. Collectively, these data suggest that ferroptosis contributes to secondary damage after SCI and highlights the possible use of ferroptosis inhibitors to treat SCI.

Could primary care records be used to identify women at risk of perinatal anxiety? A mixed-methods study.

BACKGROUND: Perinatal anxiety (PNA) occurs throughout the antenatal period or up to 1 year after childbirth, with a prevalence of 21%. AIM: To investigate if primary care records could be used to identify women at 'higher risk' of PNA. METHOD: Mixed-methods approach using quantitative and qualitative methods. Quantitative data analysis used Clinical Practice Research Datalink and IQVIA Medical Research Data to identify risk factors for PNA. Interviews explored the lived experiences of women with PNA about predisposing factors for PNA and acceptability of being informed of risk; and perspectives of primary healthcare professionals and Voluntary, Community, and Social Enterprise practitioners about risk communication. Interviews were conducted online, digitally recorded with consent, transcribed, and anonymised prior to analysis. Data were thematically analysed. Patient and clinical advisory groups informed each stage of the research. RESULTS: Women reflected on both positive and negative impacts of being identified at higher risk of PNA, a lack of understanding of how primary care records are used, and who has access to them. All interview participants suggested predisposing factors that would not be coded in primary care records. Quantitative analysis demonstrated that some predisposing factors for PNA can be identified in a woman's primary care records. Initial analysis suggests associations between PNA and infant health and healthcare use. CONCLUSION: While identification of higher risk of PNA may be acceptable, some factors that may contribute to PNA are not coded in primary care records. Identifying and managing PNA is needed to improve infant health.

Leeches Predate on Fast-Escaping and Entangling Blackworms by Spiral Entombment.

We investigate how the Helobdella spp. freshwater leeches capture and consume Lumbriculus variegatus blackworms despite the blackworm's ultrafast helical swimming escape reflex and ability to form large tangled 'blobs'. We describe our discovery of a unique spiral 'entombment' strategy used by these leeches to overcome the blackworms' active and collective defenses. Unlike their approach to less reactive and solitary prey like mollusks, where leeches simply attach and suck, Helobdella leeches employ this spiral entombment strategy specifically adapted for blackworms. Our findings highlight the complex interactions between predator and prey in freshwater ecosystems, providing insights into ecological adaptability and predator-prey dynamics.

Belief, knowledge, attitude and practices towards COVID-19 amongst residents of Abuja, Nigeria: implications for pandemic preparedness.

Introduction: coronavirus disease, (COVID-19), was a pandemic with high global morbidity and mortality, partly due to a lack of preparedness. People´s knowledge, belief, attitude, and perception of disease outbreaks may affect their response, and this may impact their health-related behavior. This study was designed to determine the pattern of belief, knowledge, attitude, and practices (BKAP) of residents of Abuja, Nigeria, towards the COVID-19 pandemic. The outcome of the study may help to make informed decisions on future pandemic preparedness. Methods: a cross-sectional study with data collected online about the local perceptions and common concerns, beliefs, misconceptions, attitudes, and conspiracy theories amongst residents of the FCT. A self-reported validated e-questionnaire prepared on Google Forms was used. The obtained data was downloaded on Excel sheet and then exported to SPSS for analysis. Results: there were one thousand eight hundred and seventy-three (1,873) respondents, 1017 (54.3%) females and 856 (45.7%) males. Participants were majorly knowledgeable, the majority (31.2%) were in the 41-50 years age group. Surprisingly, about 17% did not know that wearing a face mask could prevent COVID-19. About 25% still met in crowded places, and slightly more than 33% did not wear outdoor masks. The highest knowledge of COVID-19 was found among people in the age range 41-50 years, females, University graduates, married people, and healthcare personnel, particularly doctors. Conclusion: our study concludes that the overall population of Abuja had good knowledge and, a positive attitude, with pockets of poor attitudes and bad practices born out of misconceptions and infodemics.

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.

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]).

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.

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.

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.