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Background: Climate change poses a significant threat to agricultural production worldwide, with developing countries being particularly vulnerable to its negative impacts. Agriculture, which is a crucial factor in ensuring food security and livelihoods, is particularly vulnerable to changes in climate patterns, such as increased temperatures, drought, and extreme weather events. One approach to addressing these challenges is by promoting the adoption of climate-smart agriculture (CSA) practices among farmers. CSA combines traditional agricultural practices with innovative techniques and technologies to adapt to and mitigate the impacts of climate change. infrastructure. By adopting CSA practices, farmers can enhance their resilience to climate variability and improve their productivity., Objectives: This review examines the effectiveness of interventions promoting CSA to enhance farmers' knowledge of the benefits of CSA approaches, subsequent adoption of CSA, and disadoption of harmful agricultural practices in low- and middle-income countries (LMICs)., Search Methods: We searched 39 academic and online databases, websites, and repositories and screened over 19,000 experimental and quasi-experimental publications to identify studies promoting CSA practices to women farmers. We conducted a citation tracking process on included studies and contacted experts to ensure a thorough search., Selection Criteria: The review focused on studies that included interventions promoting climate-smart agricultural approaches. Using EPPI Reviewer 4, two review authors independently screened the impact evaluation using a standardized screening tool., Data Collection and Analysis: Information about participant characteristics, intervention characteristics, control conditions, research design, sample size, bias risk, outcomes, and results were gathered. Data collection and quantitative analysis were conducted using standard Campbell Collaboration methods., Main Results: Eight impact evaluations were found (two randomized controlled trials) evaluating the effects of CSA practices on farmer's knowledge gains of the benefits of CSA practices and subsequent adoption. Knowledge dissemination approaches such as Farmer Field Schools and weather and climate information services were found to positively impact farmers' knowledge and adoption of specific CSA practices. However, the evidence supporting this claim is uncertain as a high risk of bias was assessed for five of the eight included studies. However, we found no effects on the disadoption of harmful practices such as pesticide overuse., Authors' Conclusions: The evidence base for studies promoting climate-smart agricultural approaches (CSA) to farmers in LMICs is small, and there is a lack of studies reporting sex-disaggregated data and studies explicitly targeting women farmers. The review suggests that knowledge dissemination techniques are significantly effective in improving CSA knowledge and adoption, including integrated pest management techniques and their benefits, adoption of climate-resilient rice seed varieties (STRVs), and use of botanical pesticides by farmers. More and better confidence studies are needed to inform policy and programming, including those that look at a wider range of interventions, including changing norms, values, and institutional arrangements., (© 2024 The Author(s). Campbell Systematic Reviews published by John Wiley & Sons Ltd on behalf of The Campbell Collaboration.)

Background: Value chain interventions have become widespread throughout the international development sector over the last 20 years, and there is a need to evaluate their effectiveness in improving women's welfare across multiple dimensions. Agricultural value chains are influenced by socio-cultural norms and gender dynamics that have an impact on the distribution of resources, benefits, and access to opportunities. While women play a critical role in agriculture, they are generally confined to the least-valued parts of the value chain with the lowest economic returns, depending on the local, social and institutional contexts., Objectives: The review assesses the effectiveness of approaches, strategies and interventions focused on women's engagement in agricultural value chains that lead to women's economic empowerment in low- and middle-income countries. It explores the contextual barriers and facilitators that determine women's participation in value chains and ultimately impact their effectiveness., Search Methods: We searched completed and on-going studies from Scopus, Web of Science Core Collection (Social Sciences Citation Index [SSCI], Science Citation Index Expanded [SCI-EXPANDED], Conference Proceedings Citation Index - Science [CPCI-S], Conference Proceedings Citation Index - Social Science & Humanities [CPCI-SSH], and Emerging Sources Citation Index [ESCI]), International Bibliography of the Social Sciences, EconLit, Business Source Premier, APA PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane, Database of Systematic Reviews, CAB Abstracts and Sociological Abstracts. We also searched relevant websites such as Consortium of International Agricultural Research Centers (CGIAR); the International Fund for Agricultural Development (IFAD); AgriProFocus; the Bill & Melinda Gates Foundation (BMGF); Donor Committee for Enterprise Development; the UN Food and Agriculture Organisation (FAO); the International Labour Organisation (ILO); the Netherlands Development Organisation; USAID; the Swiss Agency for Development and Cooperation; the International Food Policy Research Institute; World Agroforestry; the International Livestock Research Institute; the Foreign, Commonwealth & Development Office; the British Library for Development Studies (BLDS); AGRIS; the IMMANA grant database; the 3ie impact evaluation database; Innovations for Poverty Action (IPA); The Abdul Latif Jameel Poverty Action Lab (J-PAL); the World Bank IEG evaluations; the USAID Development Data Library; Experience Clearinghouse; the proceedings of the Agriculture, Nutrition and Health Academy conference; the proceedings of the Centre for the Study of African Economies (CSAE) Conference; the proceedings of the North East Universities Development Consortium (NEUDC) Conference; and the World Bank Economic Review. The database search was conducted in March 2022, and the website search was completed in August 2022., Selection Criteria: The review includes value chain interventions evaluating the economic empowerment outcomes. The review includes effectiveness studies (experimental and non-experimental studies with a comparison group) and process evaluations., Data Collection and Analysis: Two review authors independently assessed studies for inclusion, extracted data, critically appraised the studies, and synthesised findings., Results: We found that value chain interventions are successful in improving the economic conditions of their intended beneficiaries. The interventions were found to improve women's economic outcomes such as income, assets holdings, productivity, and savings, but these effects were small in size and limited by low confidence in methodological quality. The meta-analysis suggests that this occurs more via the acquisition of skills and improved inputs, rather than through improvement in access to profitable markets. The qualitative evidence on interventions points to the persistence of cultural barriers and other constraints. Those interventions implemented in Sub-Saharan Africa and South Asia are consistently more successful for all outcomes considered, although there are few studies conducted in other areas of the world., Conclusions: The review concludes that value chain interventions empower women, but perhaps to a lesser extent than expected. Economic empowerment does not immediately translate into empowerment within families and communities. Interventions should either moderate their expectations of empowerment goals, or they should be implemented in a way that ensures higher rates of participation among women and the acquisition of greater decision-making power., Competing Interests: Howard White is CEO of the Campbell Collaboration. As CEO he has no role in the editorial process., (© 2024 The Author(s). Campbell Systematic Reviews published by John Wiley & Sons Ltd on behalf of The Campbell Collaboration.)

Introduction: Monitoring, Evaluation and Learning (MEL) is an integral part of research, programme and policy development and implementation. However, MEL methods used to monitor and evaluate interdisciplinary research projects are often informal and under-reported. This article describes the MEL protocol of the UKRI GCRF Action Against Stunting Hub (AASH)., Methods and Analysis: The AASH conducts interdisciplinary research into childhood stunting in India, Indonesia and Senegal across 23 distinct work packages. Project-specific MEL framework and methods will be implemented. A logframe will be developed to monitor and evaluate the research activities across the field sites including the number of participants recruited, questionnaires, measurements and procedures completed. MEL dashboards using Tableau and Glasscubes will be used to track and report progress, milestones and outcomes of the project. Dashboard outputs will be reported as numbers and percentages, with additional graphs/charts for easy visualisation. A 'learning' framework will be developed to outline appropriate pipelines for the dissemination of the research findings. This includes a theory of change explicating the overarching ambitions of the project in influencing policy, practice and research, and strategic engagement of relevant stakeholders to evaluate knowledge, attitudes and best practices for impactful engagement and dissemination of the research findings., Ethics and Dissemination: Ethical approval was granted by the Ethics Committee of the London School of Hygiene & Tropical Medicine (17915/RR/17513); National Institute of Nutrition (ICMR)-Ministry of Health and Family Welfare, Government of India (CR/04/I/2021); Health Research Ethics Committee, University of Indonesia and Cipto Mangunkusumo Hospital (KET-887/UN2.F1/ETIK/PPM.00.02/2019); and the National Ethics Committee for Health Research (CNERS), Senegal (Protocole SEN19/78). Findings from this work will be published in peer-reviewed journals, presented in conferences and disseminated to policy makers and research communities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Sarcoidosis is a multi-system inflammatory disease of unknown origin with heterogeneous clinical manifestations varying from a single organ non-caseating granuloma site to chronic systemic inflammation and fibrosis. Gene expression studies have suggested several genes and pathways implicated in the pathogenesis of sarcoidosis, however, due to differences in study design and variable statistical approaches, results were frequently not reproducible or concordant. Therefore, meta-analysis of sarcoidosis gene-expression datasets is of great importance to robustly establish differentially expressed genes and signalling pathways., Methods: We performed meta-analysis on 22 published gene-expression studies on sarcoidosis. Datasets were analysed systematically using same statistical cut-offs. Differentially expressed genes were identified by pooling of p -values using Edgington's method and analysed for pathways using Ingenuity Pathway Analysis software., Results: A consistent and significant signature of novel and well-known genes was identified, those collectively implicated both type I and type II interferon mediated signalling pathways in sarcoidosis. In silico functional analysis showed consistent downregulation of eukaryotic initiation factor 2 signalling, whereas cytokines like interferons and transcription factor STAT1 were upregulated. Furthermore, we analysed affected tissues to detect differentially expressed genes likely to be involved in granuloma biology. This revealed that matrix metallopeptidase 12 was exclusively upregulated in affected tissues, suggesting a crucial role in disease pathogenesis., Discussion: Our analysis provides a concise gene signature in sarcoidosis and expands our knowledge about the pathogenesis. Our results are of importance to improve current diagnostic approaches and monitoring strategies as well as in the development of targeted therapeutics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 van Wijck, Sharma, Swagemakers, Dik, IJspeert, Dalm, van Daele, van Hagen and van der Spek.)

Background: Micronutrient deficiencies are widespread in India. Soil-transmitted helminth (STH) infections are acquired by interaction with soil and water contaminated by human feces and lead to blood loss and poor micronutrient absorption. The current recommendation for control of STH-related morbidity is targeted deworming, yet little is known about the effectiveness of deworming on micronutrient status in varying sanitation contexts. Ranging between 1% and 40% prevalence across Indian states, open defecation (OD) remains high despite India's investments at elimination by promoting community-wide sanitation. This variation provides an opportunity to study the relationship between deworming, micronutrient status, and OD at-scale., Methods and Findings: Cross-sectional datasets that were representative for India were obtained the Comprehensive National Nutrition Survey in 2016 to 2018 (n = 105,060 individuals aged 1 to 19 years). Consumption of deworming medication was described by age and community OD level. Logistic regression models were used to examine the relationship between deworming, cluster OD, and their interactions, with anemia and micronutrient deficiencies (iron, zinc, vitamin A, folate, and vitamin B12), controlling for age, sex, wealth, diet, and seasonality. These regression models further allowed us to identify a minimum OD rate after which deworming becomes ineffective. In sensitivity analyses, the association between deworming and deficiencies were tested in subsamples of communities classified into 3 OD levels based on statistical tertiles: OD free (0% of households in the community practicing OD), moderate OD (>0% and <30%), or high OD (at least 30%). Average deworming coverage and OD prevalence in the sample were 43.4% [IQR 26.0, 59.0] and 19.1% [IQR 0, 28.5], respectively. Controlling for other determinants of nutritional status, adolescents living in communities with higher OD levels had lower coverage of deworming and higher prevalence of anemia, zinc, vitamin A, and B12 deficiencies. Compared to those who were not dewormed, dewormed children and adolescents had lower odds of anemia (adjusted odds ratio 0.72, (95% CI [0.67, 0.78], p < 0.001) and deficiencies of iron 0.78, (95% CI [0.74, 0.82], p < 0.001) and folate 0.69, (95% CI [0.64,0.74], p<0.001)) in OD free communities. These protective effects remained significant for anemia but diminished for other micronutrient deficiencies in communities with moderate or high OD. Analysis of community OD indicated a threshold range of 30% to 60%, above which targeted deworming was no longer significantly associated with lower anemia, iron, and folate deficiency. The primary limitations of the study included potential for omitted variables bias and inability to capture longitudinal effects., Conclusions: Moderate to high rates of OD significantly modify the association between deworming and micronutrient status in India. Public health policy could involve sequencing interventions, with focus on improving deworming coverage in communities that have achieved minimum thresholds of OD and re- triggering sanitation interventions in high OD communities prior to deworming days, ensuring high coverage for both. The efficacy of micronutrient supplementation as a complementary strategy to improve nutritional outcomes alongside deworming and OD elimination in this age group needs further study., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chakrabarti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Environmental hygiene and food safety are important determinants of child stunting. This research aims to explore the relationship between child stunting and household hygiene practices and behaviours, including the availability of water, sanitation and hygiene (WASH) facilities; the use of safe food and good quality drinking water (especially when used for complementary feeding); hygienic practices in food transport, storage and preparation and the control of cross-contamination from animals, their produce and waste., Methods and Analysis: This study is part of a wider observational study which aims to investigate the interdisciplinary factors contributing to child stunting using a 'whole child' paradigm. The observational study recruits women during pregnancy in Hyderabad, India, Lombok, Indonesia and Kaffrine, Senegal, and dyads (ie, 500 mother-infant pairs per country) are followed longitudinally up to 24 months after birth. Within the interdisciplinary niche, the study here has developed tools to investigate the potential exposure pathways to environmental pathogen contamination of foods and water. Holistic WASH and food safety data collection tools have been developed to explore exposure pathways at the household level, including: (1) survey questionnaires; (2) spot-checks; (3) biological sampling of drinking water, food and domestic surfaces and (4) direct observation. An integrated analytical approach will be used to triangulate the evidence in order to examine the relationships between child stunting, WASH and food safety behaviours., Ethics and Dissemination: Ethical approval of the study was granted by the ethics committee of the LSHTM, RVC, ILRI, ICMR, IIPHG, SEAMEO-RECFON, University of Cheikh Anta Diop. Findings of the study will be disseminated through publication in peer-reviewed journals, relevant international conferences, public engagement events, and policy-maker and stakeholder events., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Neonatal sepsis is considered as alarming medical emergency and becomes the common global reason of neonatal mortality. Non-specific symptoms and limitations of conventional diagnostic methods for neonatal sepsis mandate fast and reliable method to diagnose disease for point of care application. Recently, disease specific biomarkers have gained interest for rapid diagnosis that led to the development of electrochemical biosensor with enhanced specificity, sensitivity, cost-effectiveness and user-friendliness. Other than conventional biomarker C-reactive protein to diagnose neonatal sepsis, several potential biomarkers including Procalcitonin (PCT), Serum amyloid A (SAA) and other candidates are extensively investigated. The present review provides insights on advancements and diagnostic abilities of protein and nucleotide based biomarkers with their incorporation in developing electrochemical biosensors by employing novel fabrication strategies. This review provides an overview of most promising biomarker and its capability for neonatal sepsis diagnosis to fulfil future demand to develop electrochemical biosensor for point-of-care applications.

Objectives: To evaluate the support from the available guidance on reporting of health equity in research for our candidate items and to identify additional items for the Strengthening Reporting of Observational studies in Epidemiology-Equity extension., Study Design and Setting: We conducted a scoping review by searching Embase, MEDLINE, CINAHL, Cochrane Methodology Register, LILACS, and Caribbean Center on Health Sciences Information up to January 2022. We also searched reference lists and gray literature for additional resources. We included guidance and assessments (hereafter termed "resources") related to conduct and/or reporting for any type of health research with or about people experiencing health inequity., Results: We included 34 resources, which supported one or more candidate items or contributed to new items about health equity reporting in observational research. Each candidate item was supported by a median of six (range: 1-15) resources. In addition, 12 resources suggested 13 new items, such as "report the background of investigators"., Conclusion: Existing resources for reporting health equity in observational studies aligned with our interim checklist of candidate items. We also identified additional items that will be considered in the development of a consensus-based and evidence-based guideline for reporting health equity in observational studies., Competing Interests: Declaration of Competing Interest Although Luis Gabriel Cuervo is an official of the Pan American Health Organization, the views expressed in this publication are his sole responsibility and do not necessarily represent the decisions or policies of the Pan American Health Organization (PAHO/WHO)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

A brief insight of Rigid Bronchoscopy and methodology in current times in a tertiary care centre and a series of 3 recent unusual encounters of foreign body removed through rigid bronchoscopy., (© Association of Otolaryngologists of India 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Non-randomized studies of intervention effects (NRS), also called quasi-experiments, provide useful decision support about development impacts. However, the assumptions underpinning them are usually untestable, their verification resting on empirical replication. The internal replication study aims to do this by comparing results from a causal benchmark study, usually a randomized controlled trial (RCT), with those from an NRS conducted at the same time in the sampled population. We aimed to determine the credibility and generalizability of findings in internal replication studies in development economics, through a systematic review and meta-analysis. We systematically searched for internal replication studies of RCTs conducted on socioeconomic interventions in low- and middle-income countries. We critically appraised the benchmark randomized studies, using an adapted tool. We extracted and statistically synthesized empirical measures of bias. We included 600 estimates of correspondence between NRS and benchmark RCTs. All internal replication studies were found to have at least "some concerns" about bias and some had high risk of bias. We found that study designs with selection on unobservables, in particular regression discontinuity, on average produced absolute standardized bias estimates that were approximately zero, that is, equivalent to the estimates produced by RCTs. But study conduct also mattered. For example, matching using pre-tests and nearest neighbor algorithms corresponded more closely to the benchmarks. The findings from this systematic review confirm that NRS can produce unbiased estimates. Authors of internal replication studies should publish pre-analysis protocols to enhance their credibility.

Neuropathic pain is associated with abnormal sensations and/or pain induced by non-painful stimuli, i.e., allodynia causing burning or cold sensation, pinching of pins and needles like feeling, numbness, aching or itching. However, no suitable therapy exists to treat these pain syndromes. Our laboratory explored novel potential therapeutic strategies using a suitable composition of neurotrophic factors and active peptide fragments-Cerebrolysin (Ever Neuro Pharma, Austria) in alleviating neuropathic pain induced spinal cord pathology in a rat model. Neuropathic pain was produced by constrictions of L-5 spinal sensory nerves for 2-10 weeks period. In one group of rats cerebrolysin (2.5 or 5 ml/kg, i.v.) was administered once daily after 2 weeks until sacrifice (4, 8 and 10 weeks). Ag, Cu and Al NPs (50 mg/kg, i.p.) were delivered once daily for 1 week. Pain assessment using mechanical (Von Frey) or thermal (Hot-Plate) nociceptive showed hyperalgesia from 2 weeks until 10 weeks progressively that was exacerbated following Ag, Cu and Al NPs intoxication in nerve lesioned groups. Leakage of Evans blue and radioiodine across the blood-spinal cord barrier (BSCB) is seen from 4 to 10 weeks in the rostral and caudal cord segments associated with edema formation and cell injury. Immunohistochemistry of albumin and GFAP exhibited a close parallelism with BSCB leakage that was aggravated by NPs following nerve lesion. Light microscopy using Nissl stain exhibited profound neuronal damages in the cord. Transmission electron microcopy (TEM) show myelin vesiculation and synaptic damages in the cord that were exacerbated following NPs intoxication. Using ELISA spinal tissue exhibited increased albumin, glial fibrillary acidic protein (GFAP), myelin basic protein (MBP) and heat shock protein (HSP 72kD) upregulation together with cytokines TNF-α, IL-4, IL-6, IL-10 levels in nerve lesion that was exacerbated following NPs intoxication. Cerebrolysin treatment significantly reduced hyperalgesia and attenuated BSCB disruption, edema formation and cellular changes in nerve lesioned group. The levels of cytokines were also restored near normal levels with cerebrolysin treatment. Albumin, GFAP, MABP and HSP were also reduced in cerebrolysin treated group and thwarted neuronal damages, myelin vesiculation and cell injuries. These neuroprotective effects of cerebrolysin with higher doses were also effective in nerve lesioned rats with NPs intoxication. These observations suggest that cerebrolysin actively protects spinal cord pathology and hyperalgesia following nerve lesion and its exacerbation with metal NPs, not reported earlier., (© 2023. The Author(s).)

Background: Addressing persistent and pervasive health inequities is a global moral imperative, which has been highlighted and magnified by the societal and health impacts of the COVID-19 pandemic. Observational studies can aid our understanding of the impact of health and structural oppression based on the intersection of gender, race, ethnicity, age and other factors, as they frequently collect this data. However, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline, does not provide guidance related to reporting of health equity. The goal of this project is to develop a STROBE-Equity reporting guideline extension., Methods: We assembled a diverse team across multiple domains, including gender, age, ethnicity, Indigenous background, disciplines, geographies, lived experience of health inequity and decision-making organizations. Using an inclusive, integrated knowledge translation approach, we will implement a five-phase plan which will include: (1) assessing the reporting of health equity in published observational studies, (2) seeking wide international feedback on items to improve reporting of health equity, (3) establishing consensus amongst knowledge users and researchers, (4) evaluating in partnership with Indigenous contributors the relevance to Indigenous peoples who have globally experienced the oppressive legacy of colonization, and (5) widely disseminating and seeking endorsement from relevant knowledge users. We will seek input from external collaborators using social media, mailing lists and other communication channels., Discussion: Achieving global imperatives such as the Sustainable Development Goals (e.g., SDG 10 Reduced inequalities, SDG 3 Good health and wellbeing) requires advancing health equity in research. The implementation of the STROBE-Equity guidelines will enable a better awareness and understanding of health inequities through better reporting. We will broadly disseminate the reporting guideline with tools to enable adoption and use by journal editors, authors, and funding agencies, using diverse strategies tailored to specific audiences., (© 2023. The Author(s).)

Military personnel are often exposed to hot environments either for combat operations or peacekeeping missions. Hot environment is a severe stressful situation leading to profound hyperthermia, fatigue and neurological impairments. To avoid stressful environment, some people frequently use methamphetamine (METH) or other psychostimulants to feel comfortable under adverse situations. Our studies show that heat stress alone induces breakdown of the blood-brain barrier (BBB) and edema formation associated with reduced cerebral blood flow (CBF). On the other hand, METH alone induces hyperthermia and neurotoxicity. These effects of METH are exacerbated at high ambient temperatures as seen with greater breakdown of the BBB and brain pathology. Thus, a combination of METH use at hot environment may further enhance the brain damage-associated behavioral dysfunctions. METH is well known to induce severe oxidative stress leading to brain pathology. In this investigation, METH intoxication at hot environment was examined on brain pathology and to explore suitable strategies to induce neuroprotection. Accordingly, TiO 2 -nanowired delivery of H-290/51 (150 mg/kg, i.p.), a potent chain-breaking antioxidant in combination with mesenchymal stem cells (MSCs), is investigated in attenuating METH-induced brain damage at hot environment in model experiments. Our results show that nanodelivery of H-290/51 with MSCs significantly enhanced CBF and reduced BBB breakdown, edema formation and brain pathology following METH exposure at hot environment. These observations are the first to point out that METH exacerbated brain pathology at hot environment probably due to enhanced oxidative stress, and MSCs attenuate these adverse effects, not reported earlier., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Concussive head injury (CHI) is one of the major risk factors in developing Alzheimer's disease (AD) in military personnel at later stages of life. Breakdown of the blood-brain barrier (BBB) in CHI leads to extravasation of plasma amyloid beta protein (ΑβP) into the brain fluid compartments precipitating AD brain pathology. Oxidative stress in CHI or AD is likely to enhance production of nitric oxide indicating a role of its synthesizing enzyme neuronal nitric oxide synthase (NOS) in brain pathology. Thus, exploration of the novel roles of nanomedicine in AD or CHI reducing NOS upregulation for neuroprotection are emerging. Recent research shows that stem cells and neurotrophic factors play key roles in CHI-induced aggravation of AD brain pathologies. Previous studies in our laboratory demonstrated that CHI exacerbates AD brain pathology in model experiments. Accordingly, it is quite likely that nanodelivery of NOS antibodies together with cerebrolysin and mesenchymal stem cells (MSCs) will induce superior neuroprotection in AD associated with CHI. In this review, co-administration of TiO 2 nanowired cerebrolysin - a balanced composition of several neurotrophic factors and active peptide fragments, together with MSCs and monoclonal antibodies (mAb) to neuronal NOS is investigated for superior neuroprotection following exacerbation of brain pathology in AD exacerbated by CHI based on our own investigations. Our observations show that nanowired delivery of cerebrolysin, MSCs and neuronal NOS in combination induces superior neuroprotective in brain pathology in AD exacerbated by CHI, not reported earlier., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Rationale: Spasticity develops in 80% of spinal cord injury cases and negatively affects the patents' quality of life. The most common method of surgical treatment for severe spasticity is a long-term intrathecal baclofen therapy (ITB). Long-term spinal cord stimulation is another possible treatment technique. This paper aims to evaluate the changes in quality of life for patients with spasticity who have been treated with neuromodulation (SCS or ITB) in 12 months after the surgery, as well to compare the changes in quality of life for patients who have been treated with spinal cord stimulation and those who received long-term intrathecal baclofen therapy., Materials and Methods: The influence of spasticity, experienced by the patients with a spinal cord injury, on their quality of life was analyzed before the surgery and 12 months after it. The severity of the spinal cord damage was determined with the scale of the American Spinal Injury Association (ASIA); spasticity was evaluated with the modified Ashworth scale, Penn Spasm Frequency Scale; pain levels were determined with visual analogue scale (VAS), anxiety and depression levels - with HADS. Functional activity of the patients was evaluated with the help of the Functional Independence Measure (FIM)., Results: The treatment results for 33 patients (25 men and 8 women), aged from 18 to 62, are presented. After the trial stimulation, the patients were randomly assigned to either SCS or ITB group (18 and 15 people respectively). The decrease of spasticity in both experimental groups caused lower levels of pain, less functional dependency on other people, lower stress and depression rates and, as a consequence, better quality of life and social adaptation. The obtained results for SCS and ITB groups are statistically similar., (Copyright © 2023. Published by Elsevier Inc.)

Stress is one of the most serious consequences of life leading to several chronic diseases and neurodegeneration. Recent studies show that emotional stress and other kinds of anxiety and depression adversely affects Parkinson's disease symptoms. However, the details of how stress affects Parkinson's disease is still not well known. Traumatic brain injury, stroke, diabetes, post-traumatic stress disorders are well known to modify the disease precipitation, progression and persistence. However, show stress could influence Parkinson's disease is still not well known. The present investigation we examine the role of immobilization stress influencing Parkinson's disease brain pathology in model experiments. In ore previous report we found that mild traumatic brain injury exacerbate Parkinson's disease brain pathology and nanodelivery of dl-3-n-butylphthalide either alone or together with mesenchymal stem cells significantly attenuated Parkinson's disease brain pathology. In this chapter we discuss the role of stress in exacerbating Parkinson's disease pathology and nanowired delivery of dl-3-n-butylphthalide together with monoclonal antibodies to alpha synuclein (ASNC) is able to induce significant neuroprotection. The possible mechanisms of dl-3-n-butylphthalide and ASNC induced neuroprotection and suitable clinical therapeutic strategy is discussed., Competing Interests: Conflict of interest There is no conflict of interest between any entity and/or organization mentioned here., (Copyright © 2023. Published by Elsevier Inc.)

Parkinson's disease (PD) in military personnel engaged in combat operations is likely to develop in their later lives. In order to enhance the quality of lives of PD patients, exploration of novel therapy based on new research strategies is highly warranted. The hallmarks of PD include increased alpha synuclein (ASNC) and phosphorylated tau (p-tau) in the cerebrospinal fluid (CSF) leading to brain pathology. In addition, there are evidences showing increased histaminergic nerve fibers in substantia niagra pars compacta (SNpc), striatum (STr), and caudate putamen (CP) associated with upregulation of histamine H3 receptors and downregulation of H4 receptors in human brain. Previous studies from our group showed that modulation of potent histaminergic H3 receptor inverse agonist BF-2549 or clobenpropit (CLBPT) partial histamine H4 agonist with H3 receptor antagonist induces neuroprotection in PD brain pathology. Recent studies show that PD also enhances amyloid beta peptide (AβP) depositions in brain. Keeping these views in consideration in this review, nanowired delivery of monoclonal antibodies to AβP together with ASNC and H3/H4 modulator drugs on PD brain pathology is discussed based on our own observations. Our investigation shows that TiO 2 nanowired BF-2649 (1 mg/kg, i.p.) or CLBPT (1 mg/kg, i.p.) once daily for 1 week together with nanowired delivery of monoclonal antibodies (mAb) to AβP and ASNC induced superior neuroprotection in PD-induced brain pathology. These observations are the first to show the modulation of histaminergic receptors together with antibodies to AβP and ASNC induces superior neuroprotection in PD. These observations open new avenues for the development of novel drug therapies for clinical strategies in PD., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Nasal hirudiniasis is uncommon in humans, where a leech invades through the nostrils, adhering to the nasal cavity mucosa. It is rare in urban areas, noted in endemic rural areas, but scarcely documented and, with urbanisation and ecological imbalance has become rarer still. It presents with recurrent epistaxis due to hirudin released by the leech while other symptoms are infinitesimal owing to an analgesic enzyme secreted. A thorough history-taking and examination is of utmost importance as respiratory complications may arise if the leech invades the airways. We present a case series of five patients, within a period of three years.

Neurorestorative treatments have been able to improve the quality of life for patients suffering from neurological diseases and damages since the concept of Neurorestoratology was proposed. The discipline of Neurorestoratology focuses on restoring impaired neurological functions and/or structures through varying neurorestorative mechanisms including neurostimulation or neuromodulation, neuroprotection, neuroplasticity, neuroreplacement, loop reconstruction, remyelination, immunoregulation, angiogenesis or revascularization, neuroregeneration or neurogenesis and others. The neurorestorative strategies of Neurorestoratology include all therapeutic methods which can restore dysfunctions for patients with neurological diseases and improve their quality of life. Neurorestoratology is different from regenerative medicine in the nervous system, which mainly focuses on the neuroregeneration. It also is different from Neurorehabilitation. Neurorestoratology and Neurorehabilitation share some functional recovering mechanisms, such as neuroplasticity, especially in the early phase of neurological diseases; but generally Neurorehabilitation mainly focuses on recovering neurological functions through making the best use of residual neurological functions, replacing lost neurological functions in the largest degree, and preventing and treating varying complications. Recently, there have been more advances in restoring damaged nerves by cell therapy, neurostimulation/neuromodulation and braincomputer interface (BCI), neurorestorative surgery, neurorestorative pharmaceutics, and other clinic strategies. Simultaneously related therapeutic guidelines and standards are set up in succession. Based on those advances, clinicians should consider injured and degenerated nervous disorders or diseases in the central nervous system as treatable or neurorestorative disorders. Extending and encouraging further neurorestorative explorations and achieving better clinical efficacy with stronger evidence regarding neurorestoratology will shed new light and discover superior benefits for patients with neurological disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Post-traumatic headache secondary to mild traumatic brain injury in patients has become an important factor in their prognosis. Due to the lack of effective pharmacological treatments, non-pharmacological interventions such as acupuncture are considered to have greater potential. However, the efficacy and safety of acupuncture treatment have not been clearly demonstrated. The purpose of this meta-analysis protocol is to investigate the effectiveness and safety of acupuncture in the treatment of headache secondary to mild traumatic brain injury., Methods and Analysis: Seven English and Chinese databases will be selected and searched according to their respective search methods, spanning the period from database creation to April 2022, and the languages will be limited to English and Chinese. Only randomized controlled trials will be included. Study selection, data collection, and risk of bias control will be performed by two independent investigators. Any disagreements will be referred to a third independent investigator for decision and documentation. Revman software will be used to complete our meta-analysis, and risk of bias assessment, subgroup analysis, and sensitivity analysis will be performed to correct the results. Finally we will assess the reliability of our final results using the Recommended Guidelines Development Tool for Assessment., Ethics and Dissemination: All data for this study will be obtained from published journals, so no ethical review will be required. The completed review will be published in a peer-reviewed journal and the findings will be further disseminated through presentation at an appropriate forum or conference., (Copyright © 2023. Published by Elsevier Inc.)

Environmental temperature adversely affects the outcome of concussive head injury (CHI)-induced brain pathology. Studies from our laboratory showed that animals reared at either cold environment or at hot environment exacerbate brain pathology following CHI. Our previous experiments showed that nanowired delivery of oxiracetam significantly attenuated CHI-induced brain pathology and associated neurovascular changes. Military personnel are the most susceptible to CHI caused by explosion, blasts, missile or blunt head trauma leading to lifetime functional and cognitive impairments affecting the quality of life. Severe CHI leads to instant death and/or lifetime paralysis. Military personnel engaged in combat operations are often subjected to extreme high or low environmental temperature zones across the globe. Thus, further exploration of novel therapeutic agents at cold or hot ambient temperatures following CHI are the need of the hour. CHI is also a major risk factor for developing Alzheimer's disease by enhancing amyloid beta peptide deposits in the brain. In this review, effect of hot environment on CHI-induced brain pathology is discussed. In addition, whether nanodelivery of oxiracetam together with neprilysin and monoclonal antibodies (mAb) to amyloid beta peptide and p-tau could lead to superior neuroprotection in CHI is explored. Our results show that co-administration of oxiracetam with neprilysin and mAb to AβP and p-tau significantly induced superior neuroprotection following CHI in hot environment, not reported earlier., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Military personnel during combat or peacekeeping operations are exposed to extreme climates of hot or cold environments for longer durations. Spinal cord injury is quite common in military personnel following central nervous system (CNS) trauma indicating a possibility of altered pathophysiological responses at different ambient temperatures. Our previous studies show that the pathophysiology of brain injury is exacerbated in animals acclimated to cold (5 °C) or hot (30 °C) environments. In these diverse ambient temperature zones, trauma exacerbated oxidative stress generation inducing greater blood-brain barrier (BBB) permeability and cell damage. Extracts of Ginkgo biloba EGb-761 and BN-52021 treatment reduces brain pathology following heat stress. This effect is further improved following TiO 2 nanowired delivery in heat stress in animal models. Several studies indicate the role of EGb-761 in attenuating spinal cord induced neuronal damages and improved functional deficit. This is quite likely that these effects are further improved following nanowired delivery of EGb-761 and BN-52021 with cerebrolysin-a balanced composition of several neurotrophic factors and peptide fragments in spinal cord trauma. In this review, TiO 2 nanowired delivery of EGb-761 and BN-52021 with nanowired cerebrolysin is examined in a rat model of spinal cord injury at cold environment. Our results show that spinal cord injury aggravates cord pathology in cold-acclimated rats and nanowired delivery of EGb-761 and BN-52021 with cerebrolysin significantly induced superior neuroprotection, not reported earlier., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Alzheimer's disease is one of the devastating neurodegenerative diseases affecting mankind worldwide with advancing age mainly above 65 years and above causing great misery of life. About more than 7 millions are affected with Alzheimer's disease in America in 2023 resulting in huge burden on health care system and care givers and support for the family. However, no suitable therapeutic measures are available at the moment to enhance quality of life to these patients. Development of Alzheimer's disease may reflect the stress burden of whole life inculcating the disease processes of these neurodegenerative disorders of the central nervous system. Thus, new strategies using nanodelivery of suitable drug therapy including antibodies are needed in exploring neuroprotection in Alzheimer's disease brain pathology. In this chapter role of stress in exacerbating Alzheimer's disease brain pathology is explored and treatment strategies are examined using nanotechnology based on our own investigation. Our observations clearly show that restraint stress significantly exacerbate Alzheimer's disease brain pathology and nanodelivery of a multimodal drug cerebrolysin together with monoclonal antibodies (mAb) to amyloid beta peptide (AβP) together with a serotonin 5-HT6 receptor antagonist SB399885 significantly thwarted Alzheimer's disease brain pathology exacerbated by restraint stress, not reported earlier. The possible mechanisms and future clinical significance is discussed., Competing Interests: Conflict of interest There is no conflict of interest between any entity and/or organization mentioned here., (Copyright © 2023. Published by Elsevier Inc.)

Blast brain injury (bBI) following explosive detonations in warfare is one of the prominent causes of multidimensional insults to the central nervous and other vital organs injury. Several military personnel suffered from bBI during the Middle East conflict at hot environment. The bBI largely occurs due to pressure waves, generation of heat together with release of shrapnel and gun powders explosion with penetrating and/or impact head trauma causing multiple brain damage. As a result, bBI-induced secondary injury causes breakdown of the blood-brain barrier (BBB) and edema formation that further results in neuronal, glial and axonal injuries. Previously, we reported endocrine imbalance and influence of diabetes on bBI-induced brain pathology that was significantly attenuated by nanowired delivery of cerebrolysin in model experiments. Cerebrolysin is a balanced composition of several neurotrophic factors, and active peptide fragment is capable of neuroprotection in several neurological insults. Exposure to heat stress alone causes BBB damage, edema formation and brain pathology. Thus, it is quite likely that hot environment further exacerbates the consequences of bBI. Thus, novel therapeutic strategies using nanodelivery of stem cell and cerebrolysin may further enhance superior neuroprotection in bBI at hot environment. Our observations are the first to show that combined nanowired delivery of mesenchymal stem cells (MSCs) and cerebrolysin significantly attenuated exacerbation of bBI in hot environment and induced superior neuroprotection, not reported earlier. The possible mechanisms of neuroprotection with MSCs and cerebrolysin in bBI are discussed in the light of current literature., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Concussive head injury (CHI) is one of the major risk factors for developing Parkinson's disease in later life of military personnel affecting lifetime functional and cognitive disturbances. Till date no suitable therapies are available to attenuate CHI or PD induced brain pathology. Thus, further exploration of novel therapeutic agents are highly warranted using nanomedicine in enhancing the quality of life of veterans or service members of US military. Since PD or CHI induces oxidative stress and perturbs neurotrophic factors regulation associated with phosphorylated tau (p-tau) deposition, a possibility exists that nanodelivery of agents that could enhance neurotrophic factors balance and attenuate oxidative stress could be neuroprotective in nature. In this review, nanowired delivery of cerebrolysin-a balanced composition of several neurotrophic factors and active peptide fragments together with monoclonal antibodies to neuronal nitric oxide synthase (nNOS) with p-tau antibodies was examined in PD following CHI in model experiments. Our results suggest that combined administration of nanowired antibodies to nNOS and p-tau together with cerebrolysin significantly attenuated CHI induced exacerbation of PD brain pathology. This combined treatment also has beneficial effects in CHI or PD alone, not reported earlier., Competing Interests: Conflict of interest There is no conflict of interest between any entity and/or organization mentioned here., (Copyright © 2023. Published by Elsevier Inc.)

Severe traumatic brain injury patients are in critical condition, and rapid rescue is very important for prognosis. Currently, the resuscitation process is complex and it is difficult to get to the operating room quickly to target treatment. We present a new strategy based on the Internet of Things system to integrate complex first aid procedures for efficient and comprehensive rescuing of patients with severe traumatic brain injury. This system includes three modules: human sign monitoring equipment, emergency transport equipment, and a network diagnosis and treatment progress control center. The system not only supports the streamlining of rescue procedures but also transmits the patient's status and optimal treatment strategies in real-time by using an advanced Internet of Things system. After deploying the system in a hospital, we conducted a validation study to evaluate its feasibility and superiority in clinical use. The preliminary results of the study show that this system can significantly shorten the treatment time, which may help the prognosis of severe traumatic brain injury patients., (Copyright © 2023. Published by Elsevier Inc.)

Neurorestorative cell therapies have been tested to treat patients with nervous system diseases for over 20 years. Now it is still hard to answer which kinds of cells can really play a role on improving these patients' quality of life. Non-randomized clinical trials or studies could not provide strong evidences in answering this critical question. In this review, we summarized randomized clinical trials of cell therapies for central nervous diseases, such as stroke, spinal cord injury, cerebral palsy (CP), Parkinson's disease (PD), multiple sclerosis (MS), brain trauma, amyotrophic lateral sclerosis (ALS), etc. Most kinds of cell therapies demonstrated negative results for stoke, brain trauma and amyotrophic lateral sclerosis. A few kinds of cell therapies showed neurorestorative effects in this level of evidence-based medicine, such as olfactory ensheating cells for chronic ischemic stroke. Some kinds of cells showed positive or negative effects from different teams in the same or different diseases. We analyzed the possible failed reasons of negative results and the cellular bio-propriety basis of positive results. Based on therapeutic results of randomized control trials and reasonable analysis, we recommend: (1) to further conduct trials for successful cell therapies with positive results to increase neurorestorative effects; (2) to avoid in repeating failed cell therapies with negative results in same diseases because it is nonsense for them to be done with similar treatment methods, such as cell dosage, transplanting way, time of window, etc. Furthermore, we strongly suggest not to do non-randomized clinical trials for cells that had shown negative results in randomized clinical trials., (Copyright © 2023. Published by Elsevier Inc.)

dl-3-n-Butylphthalide is a potent synthetic Chinese celery extract that is highly efficient in inducing neuroprotection in concussive head injury (CHI), Parkinson's disease, Alzheimer's disease, stroke as well as depression, dementia, anxiety and other neurological diseases. Thus, there are reasons to believe that dl-3-n-butylphthalide could effectively prevent Alzheimer's disease brain pathology. Military personnel during combat operation or veterans are often the victims of brain injury that is a major risk factor for developing Alzheimer's disease in their later lives. In our laboratory we have shown that CHI exacerbates Alzheimer's disease brain pathology and reduces the amyloid beta peptide (AβP) inactivating enzyme neprilysin. We have used TiO 2 nanowired-dl-3-n-butylphthalide in attenuating Parkinson's disease brain pathology exacerbated by CHI. Nanodelivery of dl-3-n-butylphthalide appears to be more potent as compared to the conventional delivery of the compound. Thus, it would be interesting to examine the effects of nanowired dl-3-n-butylphthalide together with nanowired delivery of neprilysin in Alzheimer's disease model on brain pathology. In this investigation we found that nanowired delivery of dl-3-n-butylphthalide together with nanowired neprilysin significantly attenuated brain pathology in Alzheimer's disease model with CHI, not reported earlier. The possible mechanism and clinical significance is discussed based on the current literature., Competing Interests: Conflict of interest There is no conflict of interest between any entity and/or organization mentioned here., (Copyright © 2023. Published by Elsevier Inc.)

Nicotine abuse is frequent worldwide leading to about 8 millions people die every year due to tobacco related diseases. Military personnel often use nicotine smoking that is about 12.8% higher than civilian populations. Nicotine smoking triggers oxidative stress and are linked to several neurodegenerative diseases such as Alzheimer's disease. Nicotine neurotoxicity induces significant depression and oxidative stress in the brain leading to neurovascular damages and brain pathology. Thus, details of nicotine neurotoxicity and factors influencing them require additional investigations. In this review, effects of engineered nanoparticles from metals Ag and Cu (50-60 nm) on nicotine neurotoxicity are discussed with regard to nicotine smoking. Military personnel often work in the environment where chances of nanoparticles exposure are quite common. In our earlier studies, we have shown that nanoparticles alone induces breakdown of the blood-brain barrier (BBB) and exacerbates brain pathology in animal models. In present investigation, nicotine exposure in with Ag or Cu nanoparticles intoxicated group exacerbated BBB breakdown, induce oxidative stress and aggravate brain pathology. Treatment with nanowired H-290/51 a potent chain-breaking antioxidant together with nanowired ondansetron, a potent 5-HT3 receptor antagonist significantly reduced oxidative stress, BBB breakdown and brain pathology in nicotine exposure associated with Ag or Cu nanoparticles intoxication. The functional significance of this findings and possible mechanisms of nicotine neurotoxicity are discussed based on current literature., (Copyright © 2023. Published by Elsevier Inc.)

Neurorestoratology constitutes a novel discipline aimed at the restoration of damaged neural structures and impaired neurological functions. This area of knowledge integrates and compiles all concepts and strategies dealing with the neurorestoration. Although currently, this discipline has already been well recognized by physicians and scientists throughout the world, this article aimed at broadening its knowledge to the academic circle and the public society. Here we shortly introduced why and how Neurorestoratology was born since the fact that the central nervous system (CNS) can be repaired and the subsequent scientific evidence of the neurorestorative mechanisms behind, such as neurostimulation or neuromodulation, neuroprotection, neuroplasticity, neurogenesis, neuroregeneration or axonal regeneration or sprouting, neuroreplacement, loop reconstruction, remyelination, immunoregulation, angiogenesis or revascularization, and others. The scope of this discipline is the improvement of therapeutic approaches for neurological diseases and the development of neurorestorative strategies through the comprehensive efforts of experts in the different areas and all articulated by the associations of Neurorestoratology and its journals. Strikingly, this article additionally explores the "state of art" of the Neurorestoratology field. This includes the development process of the discipline, the achievements and advances of novel neurorestorative treatments, the most efficient procedures exploring and evaluating outcome after the application of pioneer therapies, all the joining of a multidisciplinary expert associations and the specialized journals being more and more impact. We believe that in a near future, this discipline will evolve fast, leading to a general application of cell-based comprehensive neurorestorative treatments to fulfill functional recovery demands for patients with neurological deficits or dysfunctions., (Copyright © 2023. Published by Elsevier Inc.)

Military personnel are often victims of spinal cord injury resulting in lifetime disability and decrease in quality of life. However, no suitable therapeutic measures are still available to restore functional disability or arresting the pathophysiological progression of disease in victims for leading a better quality of life. Thus, further research in spinal cord injury using novel strategies or combination of available neuroprotective drugs is urgently needed for superior neuroprotection. In this regard, our laboratory is engaged in developing TiO 2 nanowired delivery of drugs, antibodies and enzymes in combination to attenuate spinal cord injury induced pathophysiology and functional disability in experimental rodent model. Previous observations show that histamine antagonists or antioxidant compounds when given alone in spinal cord injury are able to induce neuroprotection for short periods after trauma. In this investigation we used a combination of histaminergic drugs with antioxidant compound H-290/51 using their nanowired delivery for neuroprotection in spinal cord injury of longer duration. Our observations show that a combination of H3 receptor inverse agonist BF-2549 with H3 receptor antagonist and H4 receptor agonist clobenpropit induced neuroprotection is potentiated by antioxidant compound H-290/51 in spinal cord injury. These observations suggests that histamine receptors are involved in the pathophysiology of spinal cord injury and induce superior neuroprotection in combination with an inhibitor of lipid peroxidation H-290/51, not reported earlier. The possible mechanisms and significance of our findings in relation to future clinical approaches in spinal cord injury is discussed., Competing Interests: Conflict of interest There is no conflict of interest between any entity and/or organization mentioned here., (Copyright © 2023. Published by Elsevier Inc.)

Sleep deprivation is quite frequent in military during combat, intelligence gathering or peacekeeping operations. Even one night of sleep deprivation leads to accumulation of amyloid beta peptide burden that would lead to precipitation of Alzheimer's disease over the years. Thus, efforts are needed to slow down or neutralize accumulation of amyloid beta peptide (AβP) and associated Alzheimer's disease brain pathology including phosphorylated tau (p-tau) within the brain fluid environment. Sleep deprivation also alters serotonin (5-hydroxytryptamine) metabolism in the brain microenvironment and impair upregulation of several neurotrophic factors. Thus, blockade or neutralization of AβP, p-tau and serotonin in sleep deprivation may attenuate brain pathology. In this investigation this hypothesis is examined using nanodelivery of cerebrolysin- a balanced composition of several neurotrophic factors and active peptide fragments together with monoclonal antibodies against AβP, p-tau and serotonin (5-hydroxytryptamine, 5-HT). Our observations suggest that sleep deprivation induced pathophysiology is significantly reduced following nanodelivery of cerebrolysin together with monoclonal antibodies to AβP, p-tau and 5-HT, not reported earlier., Competing Interests: Conflict of interest There is no conflict of interest between any entity and/or organization mentioned here., (Copyright © 2023. Published by Elsevier Inc.)

Sleep deprivation induces amyloid beta peptide and phosphorylated tau deposits in the brain and cerebrospinal fluid together with altered serotonin metabolism. Thus, it is likely that sleep deprivation is one of the predisposing factors in precipitating Alzheimer's disease (AD) brain pathology. Our previous studies indicate significant brain pathology following sleep deprivation or AD. Keeping these views in consideration in this review, nanodelivery of monoclonal antibodies to amyloid beta peptide (AβP), phosphorylated tau (p-tau), and tumor necrosis factor alpha (TNF-α) in sleep deprivation-induced AD is discussed based on our own investigations. Our results suggest that nanowired delivery of monoclonal antibodies to AβP with p-tau and TNF-α induces superior neuroprotection in AD caused by sleep deprivation, not reported earlier., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

dl-3-n-butylphthalide (dl-NBP) is one of the potent antioxidant compounds that induces profound neuroprotection in stroke and traumatic brain injury. Our previous studies show that dl-NBP reduces brain pathology in Parkinson's disease (PD) following its nanowired delivery together with mesenchymal stem cells (MSCs) exacerbated by concussive head injury (CHI). CHI alone elevates alpha synuclein (ASNC) in brain or cerebrospinal fluid (CSF) associated with elevated TAR DNA-binding protein 43 (TDP-43). TDP-43 protein is also responsible for the pathologies of PD. Thus, it is likely that exacerbation of brain pathology in PD following brain injury may be thwarted using nanowired delivery of monoclonal antibodies (mAb) to ASNC and/or TDP-43. In this review, the co-administration of dl-NBP with MSCs and mAb to ASNC and/or TDP-43 using nanowired delivery in PD and CHI-induced brain pathology is discussed based on our own investigations. Our observations show that co-administration of TiO 2 nanowired dl-NBP with MSCs and mAb to ASNC with TDP-43 induced superior neuroprotection in CHI induced exacerbation of brain pathology in PD, not reported earlier., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Curcumin is a well-known antioxidant used as traditional medicine in China and India since ages to treat variety of inflammatory ailments as a food supplement. Curcumin has antitumor properties with neuroprotective effects in Alzheimer's disease. Curcumin elevates brain-derived neurotrophic factor (BDNF) and dopamine (DA) levels in the brain indicating its role in substance abuse. Methamphetamine (METH) is one of the most abused substances in the world that induces profound neurotoxicity by inducing breakdown of the blood-brain barrier (BBB), vasogenic edema and cellular injuries. However, influence of curcumin on METH-induced neurotoxicity is still not well investigated. In this investigation, METH neurotoxicity and neuroprotective effects of curcumin nanodelivery were examined in a rat model. METH (20 mg/kg, i.p.) neurotoxicity is evident 4 h after its administration exhibiting breakdown of BBB to Evans blue albumin in the cerebral cortex, hippocampus, cerebellum, thalamus and hypothalamus associated with vasogenic brain edema as seen measured using water content in all these regions. Nissl attaining exhibited profound neuronal injuries in the regions of BBB damage. Normal curcumin (50 mg/kg, i.v.) 30 min after METH administration was able to reduce BBB breakdown and brain edema partially in some of the above brain regions. However, TiO 2 nanowired delivery of curcumin (25 mg/kg, i.v.) significantly attenuated brain edema, neuronal injuries and the BBB leakage in all the brain areas. BDNF level showed a significant higher level in METH-treated rats as compared to saline-treated METH group. Significantly enhanced DA levels in METH-treated rats were also observed with nanowired delivery of curcumin. Normal curcumin was able to slightly elevate DA and BDNF levels in the selected brain regions. Taken together, our observations are the first to show that nanodelivery of curcumin induces superior neuroprotection in METH neurotoxicity probable by enhancing BDNF and DA levels in the brain, not reported earlier., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Military personnel are often exposed to silica dust during combat operations across the globe. Exposure to silica dust in US military or service personnel could cause Desert Strom Pneumonitis also referred to as Al Eskan disease causing several organs damage and precipitate autoimmune dysfunction. However, the effects of microfine particles of sand inhalation-induced brain damage on the pathophysiology of traumatic brain or spinal cord injury are not explored. Previously intoxication of silica nanoparticles (50-60 nm size) is shown to exacerbates spinal cord injury induces blood-spinal cord barrier breakdown, edema formation and cellular changes. However, the mechanism of silica nanoparticles-induced cord pathology is still not well known. Spinal cord injury is well known to alter serotonin (5-hydroxytryptamine) metabolism and induce oxidative stress including upregulation of nitric oxide synthase and tumor necrosis factor alpha. This suggests that these agents are involved in the pathophysiology of spinal cord injury. In this review, we examined the effects of combined nanowired delivery of monoclonal antibodies to neuronal nitric oxide synthase (nNOS) together with tumor necrosis factor alpha (TNF-α) antibodies and a potent antioxidant H-290/51 to induce neuroprotection in spinal cord injury associated with silica nanoparticles intoxication. Our results for the first time show that co-administration of nanowired delivery of antibodies to nNOS and TNF-α with H-290/51 significantly attenuated silica nanoparticles-induced exacerbation of spinal cord pathology, not reported earlier., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Hallmark of Alzheimer's disease include amyloid beta peptide and phosphorylated tau deposition in brain that could be aggravated following traumatic of concussive head injury. However, amyloid beta peptide or p-tau in spinal cord following injury is not well known. In this investigation we measured amyloid beta peptide and p-tau together with tumor necrosis factor-alpha (TNF-α) in spinal cord and brain following 48 h after spinal cord injury in relation to the blood-spinal cord and blood-brain barrier, edema formation, blood flow changes and cell injury in perifocal regions of the spinal cord and brain areas. A focal spinal cord injury was inflicted over the right dorsal horn of the T10-11 segment (4 mm long and 2 mm deep) and amyloid beta peptide and p-tau was measured in perifocal rostral (T9) and caudal (T12) spinal cord segments as well as in the brain areas. Our observations showed a significant increase in amyloid beta peptide in the T9 and T12 segments as well as in remote areas of brain and spinal cord after 24 and 48 h injury. This is associated with breakdown of the blood-spinal cord (BSCB) and brain barriers (BBB), edema formation, reduction in blood flow and cell injury. After 48 h of spinal cord injury elevation of amyloid beta peptide, phosphorylated tau (p-tau) and tumor necrosis factor-alpha (TNF-α) was seen in T9 and T12 segments of spinal cord in cerebral cortex, hippocampus and brain stem regions associated with microglial activation as seen by upregulation of Iba1 and CD86. Repeated nanowired delivery of cerebrolysin topically over the traumatized segment repeatedly together with monoclonal antibodies (mAb) to amyloid beta peptide (AβP), p-tau and TNF-α significantly attenuated amyloid beta peptide, p-tau deposition and reduces Iba1, CD68 and TNF-α levels in the brain and spinal cord along with blockade of BBB and BSCB, reduction in blood flow, edema formation and cell injury. These observations are the first to show that spinal cord injury induces Alzheimer's disease like symptoms in the CNS, not reported earlier., (Copyright © 2023. Published by Elsevier Inc.)

Asthma, COPD, COVID-19, EGPA, Lung cancer, and Pneumonia are major chronic respiratory diseases (or CRDs) affecting millions worldwide and account for substantial morbidity and mortality. These CRDs are irreversible diseases that affect different parts of the respiratory system, imposing a considerable burden on different socio-economic classes. All these CRDs have been linked to increased eosinophils in the lungs. Eosinophils are essential immune mediators that contribute to tissue homeostasis and the pathophysiology of various diseases. Interestingly, elevated eosinophil level is associated with cellular processes that regulate airway hyperresponsiveness, airway remodeling, mucus hypersecretion, and inflammation in the lung. Therefore, eosinophil is considered the therapeutic target in eosinophil-mediated lung diseases. Although, conventional medicines like antibiotics, anti-inflammatory drugs, and bronchodilators are available to prevent CRDs. But the development of resistance to these therapeutic agents after long-term usage remains a challenge. However, progressive development in nanotechnology has unveiled the targeted nanocarrier approach that can significantly improve the pharmacokinetics of a therapeutic drug. The potential of the nanocarrier system can be specifically targeted on eosinophils and their associated components to obtain promising results in the pharmacotherapy of CRDs. This review intends to provide knowledge about eosinophils and their role in CRDs. Moreover, it also discusses nanocarrier drug delivery systems for the targeted treatment of CRDs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: Effective and rapid actions are required to achieve global goals for climate change mitigation, and there is an opportunity to ensure that the actions taken are also positive for human health. However, little is known about the relative magnitude of the health co-benefits that can be achieved from mitigation actions, so robust and comprehensive syntheses of the evidence on the nature and effects of relevant actions are required. This paper presents a protocol for an interdisciplinary and cross-sectoral umbrella review of systematic reviews, synthesising modelled and empirical evidence on such actions., Methods: Nine bibliographic databases will be searched, capturing literature across a wide range of disciplines and sectors. Unique records retrieved by the searches will be screened by two independent reviewers. The quality of all the included systematic reviews will be assessed using A MeaSurement Tool to Assess Systematic Reviews (AMSTAR) 2 critical appraisal tool. Data will be extracted on methodological and thematic characteristics of the reviews, nature of the actions, and their effects on greenhouse gas emission reduction, health, and its determinants, as well as any other reported effects and interactions across different actions., Results: Narrative and quantitative synthesis methods will be used to create a typology of relevant actions, map pathways to their impacts on health, compare the magnitude of health and greenhouse gas (GHG) emission reduction impacts by selected characteristics of the actions and the nature of the evidence, as well as to identify gaps in evidence syntheses., Conclusion: This review will identify the most effective actions for global climate change mitigation and health based on the best available scientific evidence.   This protocol has been registered in PROSPERO, Reg No.: CRD42021239292., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Belesova K et al.)

This is the protocol for a Campbell systematic review. The objective of this systematic review is to assess the effectiveness of interventions with gender transformative approach (GTA) components in improving women's empowerment in low- and middle-income countries, and to curate evidence on the mechanisms through which GTA works to improve women's empowerment in agriculture., (© 2022 The Authors. Campbell Systematic Reviews published by John Wiley & Sons Ltd on behalf of The Campbell Collaboration.)