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Ketone bodies (KBs), such as acetoacetate and β-hydroxybutyrate, serve as crucial alternative energy sources during glucose deficiency. KBs, generated through ketogenesis in the liver, are metabolized into acetyl-CoA in extrahepatic tissues, entering the tricarboxylic acid cycle and electron transport chain for ATP production. Reduced glucose metabolism and mitochondrial dysfunction correlate with increased neuronal death and brain damage during cerebral ischemia and neurodegeneration. Both KBs and the ketogenic diet (KD) demonstrate neuroprotective effects by orchestrating various cellular processes through metabolic and signaling functions. They enhance mitochondrial function, mitigate oxidative stress and apoptosis, and regulate epigenetic and post-translational modifications of histones and non-histone proteins. Additionally, KBs and KD contribute to reducing neuroinflammation and modulating autophagy, neurotransmission systems, and gut microbiome. This review aims to explore the current understanding of the molecular mechanisms underpinning the neuroprotective effects of KBs and KD against brain damage in cerebral ischemia and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. [ABSTRACT FROM AUTHOR]

Abstract Background The snake genera Atropoides, Cerrophidion, and Metlapilcoatlus form a clade of neotropical pit vipers distributed across Mexico and Central America. This study evaluated the myotoxic and neurotoxic effects of nine species of Atropoides, Cerrophidion, and Metlapilcoatlus, and the neutralising efficacy of the ICP antivenom from Costa Rica against these effects, in the chick biventer cervicis nerve-muscle preparation. Given the prominence of PLA2s within the venom proteomes of these species, we also aimed to determine the neutralising potency of the PLA2 inhibitor, varespladib. Results All venoms showed myotoxic and potential neurotoxic effects, with differential intra-genera and inter-genera potency. This variation was also seen in the antivenom ability to neutralise the muscle damaging pathophysiological effects observed. Variation was also seen in the relative response to the PLA2 inhibitor varespladib. While the myotoxic effects of M. mexicanus and M. nummifer venoms were effectively neutralised by varespladib, indicating myotoxicity is PLA2 mediated, those of C. godmani and M. olmec venoms were not, revealing that the myotoxicity is driven by non-PLA2 toxin types. Conclusions This study characterises the myotoxic and neurotoxic venom activity, as well as neutralisation of venom effects from the Atropoides, Cerrophidion, and Metlapilcoatlus clade of American crotalids. Our findings contribute significant clinical and evolutionary knowledge to a clade of poorly researched snakes. In addition, these results provide a platform for future research into the reciprocal interaction between ecological niche specialisation and venom evolution, as well as highlighting the need to test purified toxins to accurately evaluate the potential effects observed in these venoms.

Abstract Background Many older people from minority ethnic groups experience inequalities towards the end of life, including barriers to accessing palliative care. With levels of international migration increasing, there is a need to understand these differences and consider the needs of minority ethnic groups in healthcare policies. This review aimed to map evidence on how older people from minority ethnic groups access and utilise palliative and end of life care, preferences for palliative and end of life care, experiences of palliative and end of life care, and how this varies between minority ethnic groups in different countries, and with different health conditions. Methods Scoping review, following Joanna Briggs Institute (JBI) guidance. Searches of eight online databases (MEDLINE, Embase, Web of Science, CINAHL, PsycInfo, Assia, Scopus, and the Cochrane Library) and grey literature were undertaken in 2024. Qualitative sources that focused on older people from minority ethnic groups’ and carers’ access to and use of palliative and end of life care were included, as well as those focusing on healthcare professionals’ experiences. Results Twenty-three sources were included in the review, the majority of which were interview studies from the USA. Findings reflect a range of preferences, inequalities, facilitators and barriers to accessing palliative and end of life care, with themes relating to: (1) Knowledge of hospice and palliative care, (2) societal and structural issues, (3) language and health literacy, (4) migratory experiences, (5) trust in healthcare services and professionals, (6) religion and hope, and (7) cultural values. Conclusions This review identified areas for healthcare providers to consider developing more culturally appropriate palliative and end of life care practice, including building trust and improving communication, sharing information, reducing language barriers, addressing stigma, and, if relevant, acknowledging the importance of culture and religion. Further qualitative research from an intersectional perspective, such as geographical location or socio-economic status, rather than race, ethnicity, and culture alone, is needed in more diverse geographical settings and on specific health conditions.

The global increase in polyethylene terephthalate (PET)-based waste fiber poses a persistent environmental risk. While efforts have been made to repurpose waste fibers into bags, clothing, and building materials, the depolymerization process to extract pure raw materials for recycling remains underdeveloped. This study investigates the impact of normal hexane treatment on the purity of terephthalic acid (TPA) recovered from wastewater containing sodium terephthalate, ethylene glycol, and impurities generated during polyester fabric weight reduction or waste fiber recycling processes. Nuclear magnetic resonance analysis of the recovered TPA (rTPA) revealed a maximum purity of 99.81%, suggesting the effective removal of diverse contaminants such as adhesives and surfactants present in waste fibers through normal hexane and activated carbon treatments. This research contributes to the development of efficient and sustainable PET waste fiber recycling processes, highlighting the potential of normal hexane treatment in enhancing the purity of rTPA.

Abstract Background A dramatic decline in mental health of people worldwide in the early COVID-19 pandemic years has not recovered. In rural and remote Australia, access to appropriate and timely mental health services has been identified as a major barrier to people seeking help for mental ill-health. From 2020 to 2021 a care navigation model, Navicare, was co-designed with rural and remote communities in the Greater Whitsunday Region of Central Queensland in Australia. The Exploration, Preparation, Implementation and Sustainment (EPIS) framework was used to design and guide multiple aspects of a multisite study, The Bridging Study, to evaluate the implementation of Navicare in Australia. Methods A community-engaged hybrid effectiveness-implementation study design will focus on the tailored implementation of Navicare at three new sites as well as monitoring implementation at an existing site established since 2021. Study outcomes assessed will include sustained access as the co-primary outcome (measured using access to Navicare mental health referral services) and Proctor’s Implementation Outcomes of feasibility, acceptability, appropriateness, adoption, fidelity, implementation cost, and sustainability. Data collection for the implementation evaluation will include service usage data, community consultations, interviews, and workshops; analysed using mixed methods and guided by EPIS and other implementation frameworks. Pre-post effectiveness and cost-consequence study components are embedded in the implementation and sustainment phases, with comparison to pre-implementation data and value assessed for each EPIS phase using hospital, service, and resource allocation data. A scaling up strategy will be co-developed using a national roundtable forum in the final year of the study. Qualitative exploration of other aspects of the study (e.g., mechanisms of action and stakeholder engagement) will be conducted. Discussion Our study will use tailoring to local sites and a community-engaged approach to drive implementation of a mental health care navigation service in rural and remote Australia, with expected benefits to mental healthcare access. This approach is consistent with policy recommendations nationally and internationally as building blocks for rural health including the World Health Organization Framework for Action on Strengthening Health Systems to Improve Health Outcomes. Trial registration Prospectively registered on April 2, 2024, on the Australian New Zealand Clinical Trials Registry, no. ACTRN12624000382572. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386665&isReview=true .

Abstract Background With a median age at diagnosis of 70, lung cancer remains a significant public health challenge for older Americans. Surgery is a key component in treating most patients with non-metastatic lung cancer. These patients experience postoperative pain, fatigue, loss of respiratory capacity, and decreased physical function. Data on quality of life (QOL) in older adults undergoing lung cancer surgery is limited, and few interventions are designed to target the needs of older adults and their family caregivers (FCGs). The primary aim of this comparative effectiveness trial is to determine whether telephone-based physical activity coaching before and after surgery will be more beneficial than physical activity self-monitoring alone for older adults and their FCGs. Methods In this multicenter comparative effectiveness trial, 382 older adults (≥ 65 years) with lung cancer and their FCGs will be recruited before surgery and randomized to either telephone-based physical activity coaching or physical activity self-monitoring alone. Participants allocated to the telephone-based coaching comparator will receive five telephone sessions with coaches (1 pre and 4 post surgery), an intervention resource manual, and a wristband pedometer. Participants in the self-monitoring only arm will receive American Society of Clinical Oncology (ASCO) physical activity information and wristband pedometers. All participants will be assessed at before surgery (baseline), at discharge, and at days 30, 60, and 180 post-discharge. The primary endpoint is the 6-minute walk test (6MWT) at 30 days post-discharge. Geriatric assessment, lower extremity function, self-reported physical function, self-efficacy, and QOL will also be assessed. Discussion The trial will determine whether this telephone-based physical activity coaching approach can enhance postoperative functional capacity and QOL outcomes for older adults with lung cancer and their FCGs. Trial results will provide critical findings to inform models of postoperative care for older adults with cancer and their FCGs. Trial Registration ClinicalTrials.gov Identifier: NCT06196008.

Background: Despite an increased risk of visual impairment (V.I.) among adults from minority ethnic communities in the UK, limited research has explored their wider life experiences. Methods: A secondary analysis of V.I. Lives survey data explored priority issues among a sample of 46 Asian, 22 Black, and 77 White adults who have visual impairment A list of 24 issues were grouped into 10 life domains. Issue and domain mean importance scores were calculated for each to facilitate ranking of importance. Results: Kruskal–Wallis tests showed that there were statistically significant differences between the three groups for 7/10 domains and 19/24 issues. Post hoc comparisons showed that this largely reflected group differences between Asian and White participants. While there were no statistically significant differences between Asian and Black participants possibly due to small sample sizes, there were statistically significant differences between Asian and White participants in 7/10 domains and 14/24 issues. Additionally, there were significant differences between Black and White participants in 5/10 domains and 7/24 issues, specialist workplace equipment being the only issue with a significant difference between White and Black but not Asian participants. There were no group differences for confidence in ability to do everyday tasks and opportunities to take part in more sporting and leisure activities. Overall, White participants generally rated all issues as less important than Asian and Black participants. The top-three domains for Asian participants were ‘accessible environments’/‘finances’, ‘technology’, and ‘public attitudes’. The top-three issues were accessibility of public transport, employer attitudes, and reduction of street clutter. The top-three domains among Black participants were ‘employment’, ‘accessible environments’, and ‘emotional support’. The top-three issues were employer attitudes/specialised education for young people with V.I., specialist V.I. equipment in the workplace, and confidence in ability to do everyday tasks/accessibility of public transport. Conclusions: Differences in priorities between the groups suggest that the needs of individual communities may be lost when grouping culturally diverse communities together, highlighting the need for more research with different minority ethnic communities.

Abstract Background 5-Aminolevulinic acid (ALA) recently received much attention due to its potential application in many fields such as medicine, nutrition and agriculture. Metabolic engineering is an efficient strategy to improve microbial production of 5-ALA. Results In this study, an ALA production strain of Escherichia coli was constructed by rational metabolic engineering and stepwise improvement. A metabolic strategy to produce ALA directly from glucose in this recombinant E. coli via both C4 and C5 pathways was applied herein. The expression of a modified hemA RS gene and rational metabolic engineering by gene knockouts significantly improved ALA production from 765.9 to 2056.1 mg/L. Next, we tried to improve ALA production by RGMS-directed evolution of eamA gene. After RGMS, the ALA yield of strain A2-ASK reached 2471.3 mg/L in flask. Then, we aimed to improve the oxidation resistance of cells by overexpressing sodB and katE genes and ALA yield reached 2703.8 mg/L. A final attempt is to replace original promoter of hemB gene in genome with a weaker one to decrease its expression. After 24 h cultivation, a high ALA yield of 19.02 g/L was achieved by 108-ASK in a 5 L fermenter. Conclusions These results suggested that an industrially competitive strain can be efficiently developed by metabolic engineering based on combined rational modification and optimization of gene expression.

The Internet is the fastest and easiest way for one to collect and disseminate information to individuals regardless of their location. A number of educational institutions find that the Internet is an attractive method of delivering courses. This study was designed to identify elements of instruction formats that distinguish distance education (DE) methods from traditional face-to-face instruction with respect to instructors' experiences and opinions. The findings from this study should help explain instructors' willingness to participate in DE; and can be used to improve DE formats currently in use. Many students must juggle responsibilities other than academic ones (e.g., those of work and family), and instructional formats that facilitate their ability to do so will appeal to them. Content analysis indicated flexibility as one advantage of DE. Providing more resources for training and improving technology may encourage more instructors to become involved with DE. Instructors are an invaluable source of information with respect to the benefits and pitfalls of different delivery methods, and their feedback should be sought. (Contains 1 note.)

Background: Charles Bonnet syndrome (CBS) refers to the experience of visual hallucinations occurring secondary to sight loss. Although there is an increasing amount of research on this phenomenon, CBS remains a lesser-known outcome of visual impairment, with limited research into the impact on the patient. Objectives: To explore the experiences and opinions of visually impaired military veterans with CBS regarding the impact of visual hallucinations. Design: Semi-structured qualitative interviews. Methods: Forty-six telephone interviews were conducted with members of Blind Veterans UK, a charity for visually impaired ex-service men and women. One-hundred and fifteen individuals at the charity with CBS were identified and invited to a semi-structured interview (participation rate – 40%). Qualitative data was transcribed and analysed using thematic analysis. Results: Four overarching themes were identified: (1) impact of CBS (2) understanding and management of CBS (3) awareness of CBS (4) recommendations. Negative impact of CBS included feelings of fear, annoyance and disruptions to daily life and quality of life. Negative appraisal of CBS was not necessarily related to negative hallucination content. Participants expressed the value of increased awareness amongst patients and health care professionals. Knowledge and understanding of CBS provided reassurance and was considered an effective strategy to mitigate the negative impact of the condition. Conclusion: Regardless of hallucination content, CBS has a substantial impact on the lives of people with visual impairment. Increased awareness and information can help to support individuals to manage their CBS more effectively. However, the findings from this study cannot be generalized to people without a military background so further research is required to understand and optimize support for military veterans and civilians with CBS.

Next-generation 6G communication holds the potential to revolutionize data transfer, enabling the realization of eXtended Reality (XR) with enhanced sensory experiences. To achieve this, advanced components such as high-performance intensity/phase modulators, waveguides, multiplexers, splitters, combiners, and filters operating in terahertz (THz) regime, specifically within the frequency range of 0.1–1 THz, are essential. However, existing microwave equipment and vector network analyzers designed for this frequency range suffer from limitations in resolution, stability, and accuracy when evaluating the intensity and phase responses of critical 6G THz devices. In this comprehensive review, we delve into the critical device requirements and emerging trends in next-generation 6G communication, essential performance evaluation parameters, comparisons between microwave and nano/microphotonic devices for testing, and the application of high-resolution THz sensors in 6G Internet-of-Things (IoT) scenarios. Notably, a frequency comb in the photonic regime emerges as the prime candidate for achieving precision evaluations of 6G networks and devices. Consequently, this review highlights the latest research in frequency comb measurements in the 6G THz frequency regime, with a particular emphasis on nano/microphotonic devices and metamaterials. The integration of frequency comb measurements into 6G and THz photonic devices and networks promises to accelerate the realization of high-density next-generation 6G communication.

Intersubband transitions in semiconductor heterostructures offer a way to achieve large and designable nonlinearities with dynamic modulation of intersubband energies through the Stark effect. One promising approach for incorporating these nonlinearities into free space optics is a nonlinear polaritonic metasurface, which derives resonant coupling between intersubband nonlinearities and optical modes in nanocavities. Recent work has shown efficient frequency mixing at low pumping intensities, with the ability to electrically tune the phase, amplitude, and spectral peak of it. However, the spectral tunability of intersubband nonlinearities is constrained by the static spectral response of nanocavities. To overcome this limitation, we present nonlinear polaritonic metasurfaces for a broadband giant nonlinear response. This is achieved by combining a Stark tunable nonlinear response from a quantum-engineered semi-conductor heterostructure with arrays of three nanocavities with different resonant wavelengths. We experimentally demonstrate broadband second harmonic generation (SHG) and a shift in the peak SHG efficiency within the range of 8.9–10.6 μm by applying bias voltage. This work will provide a promising route for achieving broadband and electrically tunable nonlinearities in metasurfaces.

The Eastern Long-Nosed Viper (Vipera ammodytes meridionalis) is considered one of the most venomous snakes in Europe. However, it is unknown whether ontogenetic variation in venom effects occurs in this subspecies and how this may impact antivenom efficacy. In this study, we compared the procoagulant activities of V. a. meridionalis venom on human plasma between neonate and adult venom phenotypes. We also examined the efficacy of three antivenoms—Viperfav, ViperaTAb, and Inoserp Europe—across our neonate and adult venom samples. While both neonate and adult V. a. meridionalis venoms produced procoagulant effects, the effects produced by neonate venom were more potent. Consistent with this, neonate venom was a stronger activator of blood-clotting zymogens, converting them into their active forms, with a rank order of Factor X >> Factor VII > Factor XII. Conversely, the less potent adult venom had a rank order of FXII marginally more activated than Factor VII, and both much more so than Factor X. This adds to the growing body of evidence that activation of factors besides FII (prothrombin) and FX are significant variables in reptile venom-induced coagulopathy. Although all three examined antivenoms displayed effective neutralization of both neonate and adult V. a. meridionalis venoms, they generally showed higher efficacy on adult venom than on neonate venom. The ranking of antivenom efficacy against neonate venom, from the most effective to the least effective, were Viperfav, Inoserp Europe, ViperaTAb; for adult venom, the ranking was Inoserp Europe, Viperfav, ViperaTAb. Our data reveal ontogenetic variation in V. a meridionalis, but this difference may not be of clinical concern as antivenom was effective at neutralizing both adult and neonate venom phenotypes. Regardless, our results highlight a previously undocumented ontogenetic shift, likely driven by the documented difference in prey preference observed for this species across age classes