Cholestasis is a hepatobiliary disorder characterized by the excessive accumulation of toxic bile acids in hepatocytes, leading to cholestatic liver injury (CLI) through multiple pathogenic inflammatory pathways. Currently, there are limited therapeutic options for the management of cholestasis and associated CLI; therefore, new options are urgently needed. Pirfenidone (PF), an oral bioavailable pyridone analog, is used for the treatment of idiopathic pulmonary fibrosis. PF has recently demonstrated diverse potential therapeutic activities against different pathologies. Accordingly, the present study adopted the α-naphthyl isothiocyanate (ANIT)-induced CLI model in mice to explore the potential protective impact of PF and investigate the underlying mechanisms of action. PF intervention markedly reduced the serum levels of ALT, AST, LDH, total bilirubin, and total bile acids, which was accompanied by a remarkable amelioration of histopathological lesions induced by ANIT. PF also protected the mice against ANIT-induced redox imbalance in the liver, represented by reduced MDA levels and elevated GSH and SOD activities. Mechanistically, PF inhibited ANIT-induced downregulated expressions of the farnesoid X receptor (FXR), as well as the bile salt export pump (BSEP) and the multidrug resistance-associated protein 2 (MRP2) bile acid efflux channels. PF further repressed ANIT-induced NF-κB activation and TNF-α and IL-6 production. These beneficial effects were associated with its ability to dose-dependently inhibit Wnt/GSK-3β/β-catenin/cyclin D1 signaling. Collectively, PF protects against ANIT-induced CLI in mice, demonstrating powerful antioxidant and anti-inflammatory activities as well as an ability to oppose BA homeostasis disorder. These protective effects are primarily mediated by modulating the interplay between FXR, NF-κB/TNF-α/IL-6, and Wnt/β-catenin signaling pathways.

The collection of papers in this Special Issue serves to extend the literature and evidence base for physical literacy (PL) research within child and youth populations. Currently, child and youth populations are increasingly sedentary, resulting in them spending less time engaging in daily physical activity (PA). Physical literacy serves as an attractive concept to help reframe and address physical inactivity and poor health and wellbeing, utilising a different and integrated approach to physical activity, health and wellbeing promotion. The studies presented in this Special Issue respond to previous calls in PL research for further empirical evidence, clarity around PL assessment, the utility of physical literacy with diverse populations including indigenous children and those with disabilities, the application of PL within early years, parental engagement and the role of physical education in the promotion of PL. These studies shed new light on the frontiers of PL research within child and youth populations.

This chapter of the New York City Panel on Climate Change 4 (NPCC4) report provides an overview of energy trends in New York City and the State of New York, as well as accompanying challenges and barriers to the energy transition-with implications for human health and wellbeing. The link between energy trends and their impact on health and wellbeing is brought to the fore by the concept of \"energy insecurity,\" an important addition to the NPCC4 assessment.

UNASSIGNED: Comprehensive oral care is a service centered around the patient, and individuals who need it the most often face limited access. Patient perception acts as a guide for enhancing quality, ensuring patients\' future intent to utilize the services and facilitating recommendations to others. The present study aimed to assess the patients\' perception of comprehensive dental services availed at a Primary Health Center (PHC).
UNASSIGNED: This qualitative study was based on a phenomenological interpretive approach, and judgment sampling method was employed. A validated interview guide, developed from relevant literature was employed in the local language to conduct interviews among adults visiting the PHC, gathering their views regarding the services provided. The interviews were audio recorded on a digital voice recorder, and files were password protected. Content saturation guided the determination of the final number of participants interviewed. After translating and transcribing the interviews, thematic analysis and coding were performed using ATLAS. ti 23 for Windows.
UNASSIGNED: A total of 12 participants were included in the study, following data saturation. Among them, there were 8(66.7%) female and 4(33.3%) male participants. Ten overarching main themes were discerned through the assigned codes, including positive views, neutral views, negative views, previous dental clinics visited, previous experience with dental treatment, treatments sought at the center, referrals, source of information about the dental center, subsequent visits and suggestions for improvement.
UNASSIGNED: The findings of this study revealed a positive patient perception of the comprehensive dental services offered at the PHC. Through insightful interviews, various strengths, and areas for improvement regarding the center and care provision were identified. These insights provide valuable suggestions that can be applied to elevate the utilization of dental services, ensuring continuous improvement in patient care.

UNASSIGNED: Understanding the pivotal interplay between systemic and oral health is paramount to ensuring holistic care, particularly among the aging demographic. Therefore, this review article aims to explore the emerging concept of Rapid Oral Health Deterioration (ROHD) by reviewing the current knowledge base among older adults and identifying knowledge gaps in this area of research.
UNASSIGNED: This scoping review was conducted in line with Arksey and O\'Malley\'s framework between December 2023 and March 2024 and reported while adhering to the PRISMA-ScR guidelines. A systematic database search was performed across three databases i.e. PubMed, Scopus, and EMBASE to collate the existing literature published in English between January 2013 and February 2024 addressing ROHD among older adults. After data charting, a critical appraisal of the selected studies was followed by qualitative thematic analysis.
UNASSIGNED: Among the 12 papers in this scoping review, 10 were cross-sectional studies, with one each of retrospective cohort and case-control studies. The qualitative thematic analysis of the selected articles resulted in the emergence of four main themes: risk factors for ROHD, attributes related to ROHD, challenges encountered in the management of ROHD, and management approaches for ROHD among older adults.
UNASSIGNED: This scoping review provides an overview of the rapid deterioration of oral health among older adults. Age-related dental disease harms the quality of life and overall health. To avoid dental disorders and to maintain and improve oral health in older adults, an integrated and multidisciplinary approach is essential. If ROHD is not treated, it may lead to poor health, a lower quality of life, and in severe cases, systemic infections that increase hospitalizations and possibly cause death.

APAP (Acetaminophen)-induced hepatic injury is a major public health threat that requires continuous searching for new effective therapeutics. KSG (Kaempferol-3-sophoroside-7-glucoside) is a kaempferol derivative that was separated from plant species belonging to different genera. This study explored the protective effects of KSG on ALI (acute liver injury) caused by APAP overdose in mice and elucidated its possible mechanisms. The results showed that KSG pretreatment alleviated APAP-induced hepatic damage as it reduced hepatic pathological lesions as well as the serum parameters of liver injury. Moreover, KSG opposed APAP-associated oxidative stress and augmented hepatic antioxidants. KSG suppressed the inflammatory response as it decreased the genetic and protein expression as well as the levels of inflammatory cytokines. Meanwhile, KSG enhanced the mRNA expression and level of anti-inflammatory cytokine, IL-10 (interleukin-10). KSG repressed the activation of NF-κB (nuclear-factor kappa-B), besides it promoted the activation of Nrf2 signaling. Additionally, KSG markedly hindered the elevation of ASK-1 (apoptosis-signal regulating-kinase-1) and JNK (c-Jun-N-terminal kinase). Furthermore, KSG suppressed APAP-induced apoptosis as it decreased the level and expression of Bax (BCL2-associated X-protein), and caspase-3 concurrent with an enhancement of anti-apoptotic protein, Bcl2 in the liver. More thoroughly, Computational studies reveal indispensable binding affinities between KSG and Keap1 (Kelch-like ECH-associated protein-1), ASK1 (apoptosis signal-regulating kinase-1), and JNK1 (c-Jun N-terminal protein kinase-1) with distinctive tendencies for selective inhibition. Taken together, our data showed the hepatoprotective capacity of KSG against APAP-produced ALI via modulation of Nrf2/NF-κB and JNK/ASK-1/caspase-3 signaling. Henceforth, KSG could be a promising hepatoprotective candidate for ALI.

BACKGROUND: The current study is a case study of a Māori (Indigenous people of New Zealand) organisation and their developmental processes in creating a kaumātua (older people) housing village for health and social wellbeing. This study identifies how a set of established co-design and culturally-centred principles were enacted when creating and developing the village.
METHODS: A mixed-method concurrent design was used in creating the case with interviews (n = 4), focus groups (N = 4 with 16 total participants) and survey questionnaires (n = 56) involving kaumātua and organisation members.
RESULTS: Survey results illustrate that suitable and affordable housing are associated with self-rated health, loneliness, and life satisfaction. The primary purpose of the housing village was to enable kaumātua to be connected to the marae (community meeting house) as part of a larger vision of developing intergenerational housing around the marae to enhance wellbeing. Further, key themes around visioning, collaborative team and funding, leadership, fit-for-purpose design, and tenancy management were grounded in cultural elements using te ao Māori (Māori worldview).
CONCLUSIONS: This case study illustrates several co-design and culturally-centred principles from a previously developed toolkit that supported the project. This case study demonstrates how one community enacted these principles to provide the ground for developing a housing project that meets the health and social wellbeing of kaumātua.

BACKGROUND: In Ghana, about 76% of households are at risk of drinking water polluted with faecal matter, hence, poor sanitation and unsafe water are responsible for 80% of all diseases in the country. Given this, some studies have been carried out concerning the factors that determine access and use of improved water among households in Ghana. However, although financial inclusion can make it easy for households to afford and hence, use improved water, it has received very little attention. This study, thus, examines the effect of financial inclusion on the use of improved water among households in Ghana.
METHODS: The Ghana Living Standards Survey round 7 (GLSS7) is used as the data source while the binary logit regression is employed as the main empirical estimation technique.
RESULTS: The results show that households with financial inclusion (employing an indicator which has not been disaggregated into formal and informal financial inclusion) have a higher likelihood of using improved water sources relative to those without financial inclusion. The results are robust using formal financial inclusion as well as a combined index of financial inclusion.
CONCLUSIONS: Enhancing financial inclusion, especially formal financial inclusion can be utilised as a major policy instrument towards increasing access and use of improved water sources among households in Ghana.

Objective: Climate change is recognised as the biggest threat to global health of the 21st century and impacts on health and wellbeing through a range of factors. Due to this, the need to take action in order to protect population health and wellbeing is becoming ever more urgent. Methods: In 2019, Public Health Wales carried out a comprehensive mixed-method Health Impact Assessment (HIA) of climate change. Unlike other risk assessments, it appraised the potential impact of climate change on health and inequalities in Wales through participatory workshops, stakeholder consultations, systematic literature reviews and case studies. Results: The HIA findings indicate potential impacts across the wider determinants of health and wellbeing. For example, air quality, excess heat/cold, flooding, economic productivity, infrastructure, and community resilience. A range of impacts were identified across population groups, settings, and geographical areas. Conclusion: These findings can inform decision-makers to prepare for climate change plans and policies using an evidence-informed approach. The work has demonstrated the value of a HIA approach by mobilising a range of evidence through a transparent process, resulting in transferrable learning for others.

The current study explored the protective potential of kaempferol 3-sophoroside-7-glucoside (KSG) against acute lung injury (ALI). Pre-treatment with KSG effectively secured mice from ALI and showed similar efficaciousness to dexamethasone. KSG markedly increased the survival rate and alleviated lung pathological lesions induced by lipopolysaccharide (LPS). Furthermore, KSG attenuated differential and total cell counts in BALF (bronchoalveolar lavage fluid) and MPO (myeloperoxidase) activity. KSG counteracted the NF-κB (nuclear factor-κB) activation and significantly ameliorated the downstream inflammatory cytokine, TNF-α (tumor necrosis factor-α). Simultaneously, KSG suppressed the over-expression of NLRP3 (NOD-like receptor protein 3), caspase-1, and pro-inflammatory cytokine interleukin IL-1β (interleukine-1β) and prohibited the elevation of the pyroptotic parameter GSDMD-N (N-terminal domain of gasdermin D) induced by LPS challenge. In addition, KSG significantly enhanced Nrf2 (nuclear-factor erythroid-2-related factor) and HO-1 (heme-oxygenase-1) expression. Meanwhile, KSG mitigated lipid peroxidative markers (malondialdehyde, protein carbonyl and 4-hydroxynonenal) and boosted endogenous antioxidants (superoxide dismutase/reduced glutathione/catalase) in lung tissue. In silico analyses revealed that KSG disrupts Keap1-Nrf2 protein-protein interactions by binding to the KEAP1 domain, consequently activating Nrf2. Specifically, molecular docking demonstrated superior binding affinity of KSG to KEAP1 compared to the reference inhibitor, with docking scores of -9.576 and -6.633 Kcal/mol, respectively. Additionally, the MM-GBSA binding free energy of KSG (-67.25 Kcal/mol) surpassed that of the reference inhibitor (-56.36 Kcal/mol). Furthermore, MD simulation analysis revealed that the KSG-KEAP1 complex exhibits substantial and stable binding interactions with various amino acids over a duration of 100 ns. These findings showed the protective anti-inflammatory and anti-oxidative modulatory efficiencies of KSG that effectively counteracted LPS-induced ALI and encouraged future research and clinical applications of KSG as a protective strategy for ALI.