Development Of Strategies Research Articles

The Role of Alpha-7 Nicotinic Acetylcholine Receptors in Pain: Potential Therapeutic Implications.

Chronic pain represents a prevalent and costly medical challenge globally. Nicotinic acetylcholine receptors (nAChRs), one type of ligand-gated ion channels found extensively in both the central and peripheral nervous systems, have emerged as promising therapeutic targets for chronic pain. Although there are currently no FDA-approved analgesics specifically targeting nAChRs, accumulating preclinical and clinical evidence suggest that selective ligands for alpha 7 (α7) nAChRs show potential for treating chronic pain, boasting a reduced incidence of side effects compared with other nicotinic receptor types. The recent structural resolution of human α7 nAChRs has confirmed their negative association with heightened pain, providing a valuable foundation for the development of targeted medications. This review presents a comprehensive overview, encompassing insights into the roles of α7 nAChRs derived from structural and functional studies, recent advancements in pharmacology, and investigations into their involvement in the pathophysiology of chronic pain. Moreover, the review addresses the variability in analgesic effects based on the type of receptor agonist and highlights the current research limitations. As such, this review offers potential therapeutic approaches for the development of innovative strategies for chronic pain management.

Evaluating the efficacy of a phage cocktail against Pseudomonas fluorescens group strains in raw milk: microbiological, physical, and chemical analyses.

The objective of this study was to investigate the effectiveness of a phage cocktail against Pseudomonas fluorescens group and its effect on the microbial, physical and chemical properties of raw milk during different storage conditions. A phage cocktail consisting of Pseudomonas fluorescens, Pseudomonas tolaasii, and Pseudomonas libanensis phages was prepared. As a result, reductions in fluorescent Pseudomonas counts of up to 3.44 log units for the storage at 4°C and 2.38 log units for the storage at 25°C were achieved. Following the phage application, it is found that there was no significant difference in the total mesophilic aerobic bacteria and Enterobacteriaceae counts. However, it was observed that the number of lactic acid bacteria was higher in phage-treated groups. The results also showed that pH values in the phage added groups were lower than the others and the highest titratable acidity was obtained only in the bacteria-inoculated group. As a future perspective, this study suggests that, while keeping the number of target microorganisms under control in the milk with the use of phages during storage, the microbiota and accordingly the quality parameters of the milk can be affected. This work contributes to the development of effective strategies for maintaining the quality and extending the shelf life of milk and dairy products.

Enhancing the Evaluation of District Heating System Resilience: A Literature Review

Ensuring an uninterrupted supply of energy, electricity, and heat is becoming an increasingly pressing necessity. Energy provides both social and economic growth therefore, the energy systems should be resilient to different external conditions. Resilience is the ability of a system to recover from adversity [1] and in connection with the critical infrastructure - the ability to prepare for and adapt to changing conditions and withstand and recover rapidly from disruptions. Resilience includes the ability to withstand and recover from deliberate attacks, accidents, or naturally occurring threats or incidents. Several factors influence the resilience of the energy supply system: energy security, reliability, robustness, flexibility, and resilience. If energy resilience has not been well considered or even ignored in the planning, design, and operation stages in district energy communities can lead to system fragility and vulnerability. Therefore, the research assesses the different methods for resilience assessment in energy systems by focusing on district heating. During climate change mitigation and adaptation energy supply system resilience is unclear. Based on current studies, the energy resilience factor for most is considered in the context of the electricity transmission system, and the heat transmission resilience study is limited. During the research of the literature, it has been concluded that there is no consistent quantitative and quality approach to resilience because there is no consistent treatment of the concept of resilience. The available literature sources about energy resilience are limited in their scope and usability and hence are not amenable for use outside the scope where they have been developed. The metric and formula used for calculating resilience, if any, and the input data required for such calculations are also dependent on the research scope. There is a need for a fundamental generic quantitative and quality approach for resilience that would be usable and useful across various scopes or sectors in a consistent manner, which can be used for the development of resilient systems and effective resilience strategies for district heating systems.

Impact of EU Funding on Latvian Aquaculture: Productivity, Competitiveness and Perspectives

The eligibility period for the 2014-2020 Operational Programme of the EU's European Maritime and Fisheries Fund (EMFF) closed at the end of 2023. The allocation under the EMFF to the Latvian fisheries and aquaculture sector was more than €130 million, distributed in accordance with Latvia's Fisheries Development Action Programme 2014-2020. The primary objective of this research is to analyse the outcomes attained through the allocation of funding and ascertain the extent to which Latvian aquaculture productivity has augmented, alongside its competitive standing and sustainability across both domestic and global markets. This includes integrating technological advances and innovative practices into existing aquaculture companies, as well as providing funding for projects that stimulate the creation of new aquaculture companies, such as the promotion of community-led local development strategies and the collection and availability of sector-specific data that could indirectly contribute to the development of the sector. A cost-effectiveness analysis was conducted to ascertain the anticipated return on the EU funding provided and evaluate the amplified growth prospects within the aquaculture sector. The results show that the performance indicators and targets set for the aquaculture sector as part of the funding allocation are vague and consequently do not lead to a recognisable increase in aquaculture productivity or added value.

Determinants of physical activity promotion in primary care from the patient perspective of people at risk of or living with chronic disease: a COM-B analysis

BackgroundChronic disease (CD) accounts for more than half of the overall global disease burden and physical activity (PA) is an established evidence-based strategy for the prevention and management of CD. Global policy emphasises the value of embedding PA into primary healthcare, highlighting the positive effects on PA behaviour. However, there is limited implementation of PA protocols in primary care, and research is needed to guide its integration into routine practice. The voice of the patient is underrepresented in the literature, resulting in the absence of critical insights into determinants of PA promotion in primary care. The purpose of the research was to identify the perspectives of people at risk of or living with CD on the determinants of PA promotion in primary care and to map these determinants across the six COM-B constructs.MethodsSemi-structured interviews (n = 22), guided by the COM-B model were conducted with people aged 35–60 years, at risk of or living with CD and not meeting the PA guidelines. A hybrid analytic approach of thematic inductive and deductive analysis was applied to the participant transcripts guided by a COM-B informed coding framework.ResultsIn total, 37 determinants across constructs related to capability, opportunity and motivation were prominent, examples include; physical capability constraints, the conflation of exercise with weight management, credibility of the health services in PA advice, communication styles in PA promotion, expectations of tailored support for PA, social support, accessibility, and integration of PA into routine habits.ConclusionExploring the determinants of PA promotion through the lens of the COM-B model facilitated a systematic approach to understanding the primary care user perspective of the healthcare professional (HCP) broaching the topic of PA. Findings emphasise the value of HCPs being supported to broach the issue of PA in a therapeutic and patient-centred manner using diverse and flexible approaches, while highlighting the importance of tailored, accessible PA opportunities that build self-efficacy and foster social support. The research provides valuable learnings to support PA promotion and the development of strategies in primary care through encompassing the perspective of those living with or at risk of CD.

Using models and maps to inform Target Product Profiles and Preferred Product Characteristics: the example of Wolbachia replacement

Background The global prevalence of diseases transmitted by Aedes aegypti mosquitoes, such as dengue, Zika and Yellow Fever, is increasing, but development of promising new mosquito control technologies could reverse this trend. Target Product Profiles (TPPs) and Preferred Product Characteristics (PPCs) documents issued by the World Health Organization can guide the research and development pathways of new products and product combinations transitioning from proof of concept to operational use. Methods We used high resolution global maps of the case and economic burden of dengue to derive programmatic cost targets to support a TPP for Wolbachia replacement. A compartmental entomological model was used to explore how release size, spacing and timing affect replacement speed and acceptability. To support a PPC for a hybrid suppress-then-replace approach we tested whether Wolbachia replacement could be achieved faster, more acceptably or at a lower cost if preceded by a mosquito suppression programme. Results We show how models can reveal trade-offs, identify quantitative thresholds and prioritise areas and intervention strategies for further development. We estimate that for Wolbachia replacement to be deployable in enough areas to make major contributions to reducing global dengue burden by 25% (in line with 2030 WHO targets), it must have the potential for cost to be reduced to between $7.63 and $0.24 (USD) per person protected or less. Suppression can reduce the number of Wolbachia mosquitoes necessary to achieve replacement fixation by up to 80%. A hybrid approach can also achieve fixation faster and potentially improve acceptability, but may not justify their cost if they require major new investments in suppression technologies. Conclusions Here we demonstrate the value dedicated modelling can provide for interdisciplinary groups of experts when developing TPPs and PPCs. These models could be used by product developers to prioritise and shape development decisions for new Wolbachia replacement products.

An Analysis of Goldfish Hatchtery Business in the Situjaya Group of Situraja Village, Sumedang Regency, West Java

The purposes of this study were (1) To analyze the prospect of goldfish hatchery business in Situ Jaya Group, judged from the financial aspect. (2) To formulate any goldfish hatchery alternative strategy in Situjaya Group. The eligibility analysis criteria that is applied to analyze the business feasibility are Net Benefit Cost Ratio (Net B / C), and Payback Period (PP). Furthermore, the methods which are applied to identify the factors that influenced the business development using Internal Factor Evaluation (IFE) matrix, the EFE matrix, the Strategic Matrix, and the Matrix Strengths, Weaknesses, Opportunities and Threats (SWOT), on the final phase resulted in creating alternative development strategies. Data collection method was conducted by using census method. The number of respondents were 8 people in all members of the Situ Jaya Group. Based on the non-financial feasibility analysis, the hatchery business is still weak on all non-financial aspects. Based on the results of financial analysis, it yields worth 100%. The entire value of Net B / C that obtained is greater than 1, i.e. 1.67. All PP value that obtained is 6 years 11 months 27 days. Based on the Matrix Strategy analysis that can be applied is market penetration and product development. Based on the SWOT analysis, the strategy that needs to be done is aggressive strategy which means that the business is in steady and excellent condition so it is possible to continue to expand, enlarge the growth and achieve maximum progress. While the Alternative Strategy for business development is the application of Weaknesses-Opportunities Strategy.

ENT Manifestations of Sjögren’s Syndrome: A Comprehensive Narrative Review

Background: Sjögren's Syndrome (SjS) is a chronic autoimmune disorder predominantly affecting exocrine glands, leading to symptoms such as keratoconjunctivitis sicca and xerostomia. This review focuses on the ear, nose, and throat (ENT) manifestations of SjS, which significantly impact patient quality of life and pose diagnostic challenges. Aim: The review aims to consolidate current knowledge on the ENT manifestations of SjS, exploring pathophysiological underpinnings, clinical presentations, and treatment strategies, while addressing the diagnostic challenges associated with the disease. Review Summary: ENT manifestations in SjS include nasal dryness, recurrent sinusitis, otitis, and laryngeal dryness, which may precede other systemic manifestations, aiding in early diagnosis and management. This review highlights the importance of recognizing these symptoms for timely intervention, which can significantly improve disease prognosis. Future Implications: Understanding ENT manifestations can enhance multidisciplinary management approaches and foster development in diagnostic and therapeutic strategies, potentially improving patient outcomes and quality of life. Clinical Policy and Development: Enhanced awareness and training on the ENT aspects of SjS are recommended for healthcare professionals. Development of more sensitive diagnostic tools and personalized treatment plans could also address the variability in symptom presentation and response to treatment. Keywords: Sjögren's Syndrome, ENT Manifestations, Xerostomia, Keratoconjunctivitis Sicca, Multidisciplinary Management

Social support as a coping resource for psychosocial conditions in postpartum period: a systematic review and logic framework

PurposeThis review seeks to examine the current state of postpartum social support and psychosocial conditions among women around the world, as well as explore the relationship between these factors. Additionally, it aims to propose a logical framework for enhancing postpartum social support and psychosocial conditions in this population.MethodsFollowing the development of a search strategy, two databases, PubMed and Science Direct, were searched for studies published between January 2019 and May 2023. The search was conducted throughout the entire month of May 2023. The risk of bias in the included cross-sectional studies was assessed using the Newcastle–Ottawa Quality Assessment Scale, which was adapted for this specific study design. To determine if the main objective of the cross-sectional studies was to investigate the relationship between social support and postpartum psychosocial conditions, a review was conducted based on the AMSTAR checklist, PRISMA checklist and PRISMA flow diagram. Data extraction was performed with the consensus of two authors, and a narrative synthesis approach was chosen for data synthesis, following the guidelines provided by the Centre for Reviews and Dissemination (CRD).ResultsEleven cross-sectional studies were included in the final analysis. Our findings revealed that all reviewed studies provided evidence of a positive association between social support and healthy psychosocial conditions in postpartum period. However, due to the absence of standardized measurement indicators to identify and compare the outcomes of various studies, there was a need to develop a conceptual framework that could enhance our understanding of the postpartum psychosocial condition including anxiety, depression, unfavorable quality of life and social support status up to 24 month after child birth. This framework aimed to incorporate childbirth and motherhood as "stressful events," while considering social support as a crucial "coping resource." Furthermore, it acknowledged empowerment, help-seeking behavior, and peer support as important "coping actions," alongside implementing client-centered interventions. Lastly, it recognized postpartum mental health and optimal quality of life as significant "effects" of these factors.ConclusionsThe proposed conceptual framework could define postpartum women’s health as “the ability to adapt and self-manage.”

Brain health in preterm infants: importance of early-life pain and analgesia exposure.

"Everyday" exposures in the neonatal period, such as pain, may impact brain health in preterm infants. Specifically, greater exposure to painful procedures in the initial weeks after birth have been related to abnormalities in brain maturation and growth and poorer neurodevelopmental outcomes in preterm infants. Despite an increasing focus on the importance of treating pain in preterm infants, there is a lack of consensus of optimal approaches to managing pain in this population. This may be due to recent findings suggesting that commonly used analgesic and sedative medications in preterm infants may also have adverse effects of brain maturation and neurodevelopmental outcomes. This review provides an overview of potential impacts of pain and analgesia exposure on preterm brain health while highlighting research areas in need of additional investigations for the development of optimal pain management strategies in this population.

Advances in CAR-NK cell therapy for lung cancer: is it a better choice in the future?

Lung cancer remains one of the leading causes of cancer-related mortality worldwide necessitating the development of innovative therapeutic strategies. Chimeric antigen receptor (CAR) natural killer (NK) cell therapy represents a promising advancement in the field of oncology offering a novel approach to target and eliminate tumor cells with high specificity and reduced risk of immune-related adverse effects. This paper reviews the mechanism, potential targets, and recent advances in CAR-NK cell therapy for lung cancer, including the design and engineering of CAR-NK cells, preclinical studies, and the outcomes of early-phase clinical trials. We highlight the unique advantages of using NK cells, such as their innate ability to recognize and kill cancer cells and their reduced potential for inducing graft-versus-host disease (GvHD) and cytokine release syndrome (CRS) compared to CAR T-cell therapies. Results from recent studies demonstrate significant antitumor activity in lung cancer models with improved targeting and persistence of CAR-NK cells observed in vitro and in vivo. Finally, we discuss the challenges in optimizing CAR-NK cell therapies, including the potential resistance mechanisms. The paper concludes with an outlook on the future directions of CAR-NK cell research and its implications for lung cancer treatment emphasizing the importance of continued innovation and collaboration in the field.

Feline Leishmaniasis: Evidence-based Treatments and Challenges to be Solved.

Leishmaniasis is a neglected tropical disease caused by protozoa parasites from the Leishmania genus. Vertebrate hosts acquire the infection through the bite of a female sandfly, initiating a complex parasite development cycle. Contrary to previous beliefs regarding cats' resistance, these animals have recently been identified as potential reservoirs for leishmaniasis. Clinical symptoms in cats can manifest in diverse forms, including cutaneous, mucocutaneous, and visceral manifestations. The diagnosis of feline leishmaniasis is complicated by nonspecific symptoms and the relatively lower specificity of serological tests. The recommended treatment for feline leishmaniasis involves the administration of medications; however, success varies in each cat. This review aims to present cases of feline leishmaniasis, highlighting clinical symptoms, diagnostic methods, therapy schedules, and outcomes. Among the 24 cases documented in the available literature, 12 achieved successful treatment without relapses, resulting in a reduced parasite load and improved symptoms. Three cases responded well but presented persistent sequelae. Two feline leishmaniasis cases initially had treatment success but later experienced recurrences. Finally, no response was observed in seven cases, leading to the euthanasia of cats due to ineffectiveness or irregularities along the therapy. Conventional treatments, despite potential hepatotoxicity and nephrotoxicity, exhibit a high efficacy in reducing parasitic load, thereby improving clinical symptoms and increasing the life expectancy of affected cats. Nevertheless, consistent adherence is crucial, as interruptions may render the therapy ineffective and contribute to parasite resistance. Therefore, addressing the challenges associated with feline leishmaniasis treatment necessitates the development of new strategies to ensure a more effective and sustained approach.

The association between telomere length and blood lipids: a bidirectional two-sample Mendelian randomization study

BackgroundObservational studies suggest an association between telomere length (TL) and blood lipid (BL) levels. Nevertheless, the causal connections between these two traits remain unclear. We aimed to elucidate whether genetically predicted TL is associated with BL levels via Mendelian randomization (MR) and vice versa.MethodsWe obtained genetic instruments associated with TL, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) from large-scale genome-wide association studies (GWASs). The causal relationships between TL and BL were investigated via bidirectional MR, multivariable MR and mediation analysis methods. The inverse variance weighted (IVW) method was employed as the principal methodology, complemented by several other estimators to enhance the robustness of the analysis.ResultsIn the forward MR analyses, we identified significant positive correlation between genetically predicted TL and the levels of TG (β=0.04, 95% confidence interval [CI]: 0.01 to 0.06, p = 0.003). In the reverse MR analysis, TG (β=0.02, 95% CI: 0.01 to 0.03, p = 0.004), LDL-C (β=0.03, 95% CI: 0.01 to 0.04, p = 0.001) and ApoB (β=0.03, 95% CI: 0.01 to 0.04, p = 9.71×10–5) were significantly positively associated with TL, although this relationship was not observed in the multivariate MR analysis. The mediation analysis via two-step MR showed no significant mediation effects acting through obesity-related phenotypes in analysis of TL with TG, while the effect of LDL-C on TL was partially mediated by body mass index (BMI) in the reverse direction, with mediated proportion of 12.83% (95% CI: 0.62% to 25.04%).ConclusionsOur study indicated that longer TL were associated with higher TG levels, while conversely, higher TG, LDL-C, and ApoB levels predicted longer TL, with BMI partially mediating these effects. Our findings present valuable insights into the development of preventive strategies and interventions that specifically target TL-related aging and age-related diseases.

Interactive 360° media for the dissemination of endangered world heritage sites: the ancient city of Palmyra in Syria

Since the onset of conflict in Syria in 2011, several heritage sites have suffered partial or complete destruction. The ancient city of Palmyra, a UNESCO World Heritage Site since 1980, was placed on the List of World Heritage in Danger in 2013, alongside five other Syrian heritage sites. Between 2015 and 2017, Palmyra experienced the loss of nearly 40% of its historic buildings and landmarks. The site’s remote location and ongoing armed conflict pose additional challenges in accessing and preserving it.This paper introduces an interactive online platform employing 360° media to document and disseminate information about the world heritage site of Palmyra. The platform contributes to the safeguarding process of Palmyra, facilitating public engagement and interaction with the site. It also has potential applications for other sites in Syria and beyond. The platform allows users to explore both archival and current information of damaged historical monuments and buildings, revealing their layered histories before and after demolition. Employing interactive 360° media, similar to applications like Google Street View, the platform offers a reality-based digital environment. Users can virtually move into different buildings or follow specific pathways within the site, accessing archival information and documentation about particular monuments and buildings along their journey.This project serves as a unique informational resource for decision-makers and policy planners, aiding in the understanding of the site and the development of relevant strategies and recommendations. It also proves beneficial as an educational tool. The collective understanding fostered by this platform is expected to positively influence post-conflict restoration and reconstruction plans, making it an invaluable asset for research and educational purposes.

Cultivating Resilience: Multiple Case Study of School Heads’ Leadership in Integrated Senior High Schools

School leaders must be resilient in order to navigate the always shifting challenges in the field of education. This study employed a qualitative multiple case study, having three (3) distinct cases aimed to explore the perspectives of the school heads on resilient leadership in integrated senior high schools of Division of Davao de Oro. There were three (3) participants and six (6) informants underwent in-depth interviews. Participants were chosen through a purposive sampling technique. Each data was analyzed through thematic analysis and cross-case analysis. Case 1’s unique characteristics were resource management and optimization, hierarchical communication and strategic delegation, and crisis management and contingency planning. Participant experiences were complex stakeholder management, innovative problem-solving, and resilience amidst bureaucratic challenges. In times of challenges, the coping mechanism was structured decision-making processes delegation and team empowerment professional support networks. The policy recommendations were promotion of interpersonal communication skills, development of community engagement strategies, and investment in staff well-being programs. Further, Case 3’s unique characteristics were the following: strategic financial management and sustainability, stakeholder engagement and partnerships, brand differentiation and market positioning. The experiences were cultivating philanthropic relationships, navigating parental expectations, and ensuring financial sustainability. The coping mechanisms were strategic partnerships and fundraising initiatives, ethical leadership and values integration, and self-care and well-being practices while the policy recommendations were introduction of ethics and values integration policies, creation of leadership succession plans, and investment in infrastructure and technology. Moreover, cross-case analysis shows each case about distinct characteristics and commonalities such as strategic vision and planning, effective communication and collaboration, and resource management and optimization. Each case has distinct experiences, the common themes were resourcefulness and creativity, and community engagement and collaboration. Their coping mechanisms were effective leadership practices and ethical leadership and well-being. Their policy recommendations were leadership development policies and data-informed policies. This suggests that resilient leadership was crucial for school heads in managing and leading integrated senior high schools, despite the challenges and circumstances they faced in their workplace. Both teachers and learners benefit from the leadership styles promoted by the school heads.

Prevalence and Factors Associated With Willingness to Sustain Pandemic-Induced Digital Work in the General Population and Moderating Effects of Screen Hours: Cross-Sectional Study.

The pandemic has accelerated digital work transformation, yet little is known about individuals' willingness to sustain such digital modes and its associated factors. A better understanding of this willingness and its drivers is crucial for guiding the development of future digital work infrastructure, training programs, and strategies to monitor and prevent related health issues. This study aims to quantify the general population's willingness to sustain pandemic-induced digital work, identify its associated factors, and examine how screen time moderates these relationships. A cross-sectional study was conducted targeting Hong Kong residents aged ≥18 years who have increased engagement in digital work since the pandemic. Data were collected through self-reported, web-based surveys. Descriptive statistics determined prevalence rates, while structured multiphase logistic regression identified associated factors and explored the moderating effects of screen hour levels. This unfunded study enrolled 1014 participants from May 2 to June 24, 2022, and completed data analysis within 3 months after data collection. A total of 391 (38.6%; 95% CI 35.6%-41.6%) participants expressed willingness to sustain digital work. Positive factors associated with this willingness included being an employee (odds ratio [OR] 3.12, 95% CI 1.59-6.45; P=.001), being health professionals (OR 3.32, 95% CI 1.49-7.82; P=.004), longer screen hours (OR 1.09, 95% CI 1.03-1.15; P=.002), and higher depression levels (OR 1.20, 95% CI 1.01-1.44; P=.04). Conversely, negatively associated factors included older age (OR 0.87, 95% CI 0.81-0.94; P=.001), extroversion (OR 0.66, 95% CI 0.51-0.86; P=.002), higher eHealth literacy (OR 0.96, 95% CI 0.93-0.98; P<.001), perceived greater susceptibility to COVID-19 (OR 0.84, 95% CI 0.74-0.96; P=.009), residence in a high-severity COVID-19 community (OR 0.73, 95% CI 0.63-0.84; P<.001), having infected individuals in the immediate social circle (OR 0.64, 95% CI 0.46-0.88; P=.006), higher BMI (OR 0.94, 95% CI 0.90-0.99; P=.02), feelings of being out of control (OR 0.96, 95% CI 0.93-0.98; P=.002), and higher fear of COVID-19 (OR 0.96, 95% CI 0.94-0.98; P=.001). In addition, a moderating effect of screen hour level (high: >8 h/d; low: ≤8 h/d) influenced the association among 10 factors related to willingness to sustain pandemic-induced digital work, including age, education level, household size, needs for regular medical care, BMI, frequency of both vigorous and moderate physical activities, perceived COVID-19 severity, immediate social circle COVID-19 presence, and fear of COVID-19 (all P values for interaction <.05). The substantial willingness of the general population to sustain digital work after the pandemic highlights the need for robust telework infrastructure, thorough monitoring of adverse health outcomes, and the potential to expand telehealth services among this group. The identification of factors influencing this willingness and the moderating role of screen hours inform the development of personalized strategies to enhance digital work acceptance where needed.

Dynamics of acyl carrier protein in de novo fatty acid synthesis by Enterococcus faecalis based on NMR spectroscopy and molecular dynamics simulation

Fatty acid synthesis (FAS) is essential for the production of biological components such as cell membrane building blocks and metabolism-related compounds. There are two types of bacterial FAS: de novo FAS and FAS through the incorporation of external fatty acids. Enterococcus faecalis possesses two distinct acyl carrier proteins (ACPs), AcpA (EfAcpA) and AcpB (EfAcpB), which serve as cofactors in the two types of FAS. We previously showed through NMR spectroscopy that EfAcpA comprises only three long helices, while EfAcpB consists of four helices, including a short α3 helix, similar to other bacterial ACPs. An increase in melting temperature (Tm) from 64.0 to 76.1 °C confirmed that protein structural stability increased in the presence of calcium ions. Using NMR spectroscopy, two metal binding sites were identified in EfAcpA: site A was located at the start of the α2 helix while site B was situated near the α2 helix and α2α3 loop. To understand the importance of structural flexibility of EfAcpA in de novo FAS, we investigated its motional properties using backbone spin relaxation and molecular dynamics simulations. The α2α3 loop in EfAcpA displayed high flexibility, as indicated by low heteronuclear NOE values. The residues Val51, Glu54, and Gly58 exhibited significant R2 values, likely due to the movement of this loop. EfAcpA created a novel cavity towards the α1α2 loop, in contrast to conventional cavity formation in most bacterial ACPs. This unique behavior was attributed to the flexibility exhibited by the α2α3 loop. The structural and motional characteristics of EfAcpA confirmed that its conformational plasticity is a crucial factor influencing acyl chain transfers in de novo FAS. Given the increasing antibiotic resistance observed for E. faecalis in clinical settings, the findings of this study may contribute to the development of more effective pathogen management strategies targeting FAS.

The mechanisms of white matter injury and immune system crosstalk in promoting the progression of Parkinson’s disease: a narrative review

Parkinson’s disease (PD) is neurodegenerative disease in middle-aged and elderly people with some pathological mechanisms including immune disorder, neuroinflammation, white matter injury and abnormal aggregation of alpha-synuclein, etc. New research suggests that white matter injury may be important in the development of PD, but how inflammation, the immune system, and white matter damage interact to harm dopamine neurons is not yet understood. Therefore, it is particularly important to delve into the crosstalk between immune cells in the central and peripheral nervous system based on the study of white matter damage in PD. This crosstalk could not only exacerbate the pathological process of PD but may also reveal new therapeutic targets. By understanding how immune cells penetrate through the blood–brain barrier and activate inflammatory responses within the central nervous system, we can better grasp the impact of structural destruction of white matter in PD and explore how this process can be modulated to mitigate or combat disease progression. Microglia, astrocytes, oligodendrocytes and peripheral immune cells (especially T cells) play a central role in its pathological process where these immune cells produce and respond to pro-inflammatory cytokines such as tumor necrosis factor (TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6), and white matter injury causes microglia to become pro-inflammatory and release inflammatory mediators, which attract more immune cells to the damaged area, increasing the inflammatory response. Moreover, white matter damage also causes dysfunction of blood–brain barrier, allows peripheral immune cells and inflammatory factors to invade the brain further, and enhances microglia activation forming a vicious circle that intensifies neuroinflammation. And these factors collectively promote the neuroinflammatory environment and neurodegeneration changes of PD. Overall, these findings not only deepen our understanding of the complexity of PD, but also provide new targets for the development of therapeutic strategies focused on inflammation and immune regulation mechanisms. In summary, this review provided the theoretical basis for clarifying the pathogenesis of PD, summarized the association between white matter damage and the immune cells in the central and peripheral nervous systems, and then emphasized their potential specific mechanisms of achieving crosstalk with further aggravating the pathological process of PD.

Longer prostate stromal cell telomere length is associated with increased risk of death from other cancers

BackgroundTelomeres are located at chromosomal termini and function to maintain genomic integrity. Telomere dysfunction is a well-recognized contributor to aging and age-related diseases, such as prostate cancer. Since telomere length is highly heritable, we postulate that stromal cell telomere length in the tissue of a particular solid organ may generally reflect constitutive stromal cell telomere length in other solid organs throughout the body. Even with telomere loss occurring with each round of cell replication, in general, telomere length in prostate stromal cells in mid-life would still be correlated with the telomere length in stromal cells in other organs. Thus, we hypothesize that prostate stromal cell telomere length and/or telomere length variability is a potential indicator of the likelihood of developing future solid cancers, beyond prostate cancer, and especially lethal cancer.MethodsTo explore this hypothesis, we conducted a cohort study analysis of 1,175 men who were surgically treated for prostate cancer and were followed for death, including from causes other than their prostate cancer.ResultsIn this cohort study with a median follow-up of 19 years, we observed that longer prostate stromal cell telomere length measured in tissue microarray spots containing prostate cancer was associated with an increased risk of death from other solid cancers. Variability in telomere length among these prostate stromal cells was possibly positively associated with risk of death from other solid cancers.ConclusionStudying the link between stromal cell telomere length and cancer mortality may be important for guiding the development of cancer interception and prevention strategies.

Turmeric: from spice to cure. A review of the anti-cancer, radioprotective and anti-inflammatory effects of turmeric sourced compounds

Turmeric (Curcuma longa) has been extensively studied for its diverse pharmacological properties, including its potential role as an anticancer agent, antioxidant, and radioprotector. This review provides an overview of the chemical composition of turmeric, focusing on its main bioactive compounds, such as curcuminoids and volatile oils. Curcumin, the most abundant curcuminoid in turmeric, has been widely investigated for its various biological activities, including anti-inflammatory, antioxidant, and anticancer effects. Numerous in vitro and in vivo studies have demonstrated the ability of curcumin to modulate multiple signaling pathways involved in carcinogenesis, leading to inhibition of cancer cell proliferation, induction of apoptosis, and suppression of metastasis. Furthermore, curcumin has shown promising potential as a radioprotective agent by mitigating radiation-induced oxidative stress and DNA damage. Additionally, turmeric extracts containing curcuminoids have been reported to exhibit potent antioxidant activity, scavenging free radicals and protecting cells from oxidative damage. The multifaceted pharmacological properties of turmeric make it a promising candidate for the development of novel therapeutic strategies for cancer prevention and treatment, as well as for the management of oxidative stress-related disorders. However, further research is warranted to elucidate the underlying mechanisms of action and to evaluate the clinical efficacy and safety of turmeric and its bioactive constituents in cancer therapy and radioprotection. This review consolidates the most recent relevant data on turmeric’s chemical composition and its therapeutic applications, providing a comprehensive overview of its potential in cancer prevention and treatment, as well as in radioprotection.