Cervical cancer remains a leading cause of mortality among women worldwide, particularly in low- and middle-income countries, yet human papillomavirus (HPV) vaccination-the most effective method of prevention-faces variable uptake and acceptance. This study addresses the problem of suboptimal HPV vaccination by examining the factors associated with parental consent for HPV vaccination of adolescent girls in two distinct Peruvian cities, the capital city of Lima and a large city in the Peruvian Amazon, Iquitos. Cross-sectional survey data were collected in 2017 from 986 women attending public health centers, and the Capability, Opportunity, Motivation, Behavior model was applied to categorize behavioral factors associated with women's willingness to vaccine their daughters for HPV. Overall, 90.1% of women reported willingness to vaccinate their daughters, with higher support in Iquitos (94.2%) than in Lima (84.7%). Women who were willing to vaccinate tended to be younger and were more likely to believe the vaccine was safe (Capability), know that it was free and be willing to pay for it (Opportunity), and know someone who had been vaccinated (Motivation). This study contributes to the literature on parental willingness to vaccinate daughters against HPV in a Latin American context applying a validated behavioral framework. Findings provide insight into psychosocial and contextual factors associated with self-reported parental willingness to vaccinate daughters against HPV. The results have implications for public health research and practice by identifying modifiable barriers and facilitators that can inform targeted vaccine promotion strategies in Peru and similar settings, particularly in informing future vaccine promotion strategies in contexts where vaccine confidence may have shifted following the COVID-19 pandemic.
Most research on human milk donation and human milk banking has focused on mothers, while fathers' perspectives remain insufficiently explored. Although mothers may be willing to donate milk or use donor milk for their own infants, these decisions are often shaped by their spouses' viewpoints. This study aimed to explore fathers' views on human milk donation and human milk banking. This qualitative study used an inductive thematic analysis approach. Data were collected between August and December 2024 through semi-structured interviews with 20 fathers who brought their infants for routine checkups at a state hospital in Türkiye via semi-structured interviews and a descriptive form. Data were analyzed using thematic analysis. MAXQDA software was used during the analysis process. Five main themes with 10 subthemes were identified. Fathers' perspectives reflected a balance between perceived benefits of donor human milk for infants in need and concerns related to religious beliefs, milk kinship, hygiene, and trust. Acceptance of donor milk use for their own infants was conditional and depended on hygienic handling, professional supervision, and transparency regarding donor information. Fathers expressed divided opinions about allowing their wives to donate milk, and views on establishing human milk banks in Türkiye ranged from acceptance to conditional acceptance or rejection. Fathers' perspectives on human milk donation and milk banking are shaped by the interplay between infant benefits and religious, cultural, and hygiene concerns. Spouses' attitudes and approval regarding milk donation are important family factors influencing decisions about human milk donation.
To investigate the incidence and risk factors of endoscopic retrograde cholangiopancreatography (ERCP) post-ERCP pancreatitis (PEP) from the perspective of nursing practice, and to provide evidence for developing refined prevention and control strategies. A single-center retrospective study was conducted on 658 patients who underwent diagnostic or therapeutic ERCP between January 2020 and December 2025. Using a nested case-control design, 45 patients who developed PEP were assigned to the case group, and 180 patients without PEP were matched at a 1:4 ratio as the control group. Baseline characteristics, procedural variables, and perioperative nursing-related factors were collected. Multivariable logistic regression analysis was performed to identify independent risk factors, and a combined prediction model was constructed to evaluate its performance. The overall incidence of PEP was 6.8%, with mild cases accounting for 71.1%. The case group had significantly higher proportions of difficult cannulation and pancreatic duct opacification ≥ 3 times, but significantly lower proportions of receiving comprehensive nursing interventions and cooperation by a dedicated ERCP team. A higher proportion of patients in the case group were assessed as high risk preoperatively. Difficult cannulation (AOR = 6.70, 95% CI: 2.79-16.09, p < 0.001), pancreatic duct opacification ≥ 3 times (AOR = 3.38, 95% CI: 1.40-8.17, p = 0.007), and preoperative high-risk assessment (AOR = 3.98, 95% CI: 1.72-9.20, p = 0.001) were identified as independent risk factors, while comprehensive nursing interventions (AOR = 0.20, 95% CI: 0.09-0.47, p < 0.001) and dedicated ERCP team cooperation (AOR = 0.14, 95% CI: 0.05-0.37, p < 0.001) were protective factors. The combined prediction model showed good discriminative ability (AUC = 0.856) and model fit (Hosmer-Lemeshow test, p = 0.145). Comprehensive nursing interventions and dedicated ERCP team cooperation were associated with a lower risk of PEP in this retrospective study. These findings suggest that nursing-related factors may play a role in PEP prevention. We therefore recommend integrating nursing assessment and intervention into standardized ERCP management protocols to enhance overall procedural safety.
Human papillomavirus (HPV) and human immunodeficiency virus (HIV) co-infection exerts a substantial impact on women's health globally. This study enrolled confirmed HPV-infected women in Shanghai stratified by HIV status to compare the profiles of HPV genotype distribution and cervical lesions between two groups, and to identify the risk factors for cervical dysplasia among women with HIV-HPV co-infection. A total of 238 confirmed HPV-infected women who attended the Shanghai Public Health Clinical Center between January 2019 and July 2023 were enrolled in this cross-sectional study. All participants were divided into HIV-positive and HIV-negative groups. We compared the pathological distribution characteristics, high/low-risk HPV infection patterns and cervical cytological abnormalities between the two groups. Multivariate logistic regression was used to explore risk factors for cervical dysplasia in HIV-HPV co-infected women. Among the 238 HPV-positive patients, 47.9% (114/238) were HIV-HPV co-infected. The top five predominant HPV genotypes were HPV16, HPV52, HPV58, HPV53, and HPV18. The HIV-positive group had significantly higher rates of HR-HPV infection (χ²=4.537, p = 0.037) and multiple HR-HPV infections (χ²=15.878, p < 0.001) than the HIV-negative group. HPV33 and HPV66 were more prevalent in the HIV-positive group, and the positivity rates of HPV genotypes covered by 2-valent, 4-valent, and 9-valent HPV vaccines were all significantly higher in the HIV-positive group than in the HIV-negative group. HPV52 and HPV58 (13.10%, 11/84) were the most common genotypes in multiple HPV infections. The HIV-positive group had a significantly higher rate of cytological abnormalities (χ²=11.658, p < 0.001). Multivariate logistic regression analysis indicated that HIV RNA load > 1000 copies/µl was an independent risk factor (OR 9.845, 95%CI 1.324-73.202, p = 0.026) for cervical dysplasia in the HIV-positive group. Within the HPV-positive female population, HIV-positive women exhibit higher burdens of multiple HPV infection and cervical cytological abnormalities. Elevated HIV RNA load is a key independent risk factor for cervical dysplasia in this co-infected population. Immediate initiation of antiretroviral therapy, prioritized 9-valent HPV vaccination, and regular cervical cancer screening are recommended to reduce the risk of cervical lesions and alleviate the disease burden among HIV-HPV co-infected women.
Metabolic dysfunction-associated steatohepatitis (MASH) represents a severe form of metabolic dysfunction-associated steatotic liver disease (MASLD), largely due to metabolic dysregulation and sustained liver inflammation. TNF-α plays a pivotal role in MASH pathogenesis by inducing cell death, inflammation, and decreased insulin sensitivity. In this study we investigated the effects of TNF-α in human precision-cut liver slices (PCLS) under healthy or steatotic conditions, to provide insights into MASH pathogenesis. PCLS were prepared from human liver tissue and cultured in control (WEGG) and hyper-nutritive (GFIPO) mediums with or without TNF-α (50 ng/mL) for 96 h. Viability was assessed via ATP content, lipid accumulation by triglyceride (TG) assay, and transcriptomic changes through Next-Generation Sequencing. The protein levels of cytokines, chemokines, and fibrotic mediators released from PCLS were quantified using Luminex assay and ELISA. TNF-α significantly altered the transcriptional profiles in PCLS, inducing pro-inflammatory and pro-fibrotic signaling, and downregulating lipid metabolic processes in both WEGG and GFIPO media. TNF-α showed a trend in elevating intracellular TG in both conditions, albeit not statistically significant. On protein levels, TNF-α supplementation to WEGG medium induced the expression of IL8, CCL2, CCL19, PDGF-AB/BB, TGF-α, and MMP9. GFIPO medium alone induced inflammatory and fibrotic responses indicated by elevated levels of IL8, CCL2, and Pro-collagen 1A1. GFIPO medium with TNF-α supplementation further exacerbated the inflammatory and fibrotic responses, characterized by increased release of cytokines and growth factors. This human PCLS model effectively demonstrated the co-occurrence of key features of MASH, such as steatosis, inflammation, and fibrosis, highlighting the impact of metabolic stress and inflammatory cytokine TNF-α on these disease characteristics, and the potential of the PCLS model in exploring mechanism of MASH progression.
Rates of prediabetes are rising in the United States, especially within communities of color. Without adopting self-care behaviors and adhering to routine screenings, prediabetes is likely to progress to type 2 diabetes. This study examines factors associated with non-adherence to recommended blood glucose testing among non-Hispanic Black and Hispanic men ages ≥40 years with a history of prediabetes. Using an internet-delivered survey, data were collected from 769 Black (56.7%) and Hispanic (43.3%) men with a history of prediabetes. Chi-square tests and independent sample-tests were to identify differences across study variables by race/ethnicity and blood glucose testing adherence. A logistic regression model with backward stepwise entry was fitted to assess factors associated with blood glucose testing non-adherence, adjusted for sociodemographic factors, co-morbidities, healthcare interactions, social support, and lifestyle behaviors. Approximately 11% of participants did not receive a blood glucose test in the past 12 months, and 60.9% self-reported progression from prediabetes to diabetes. Men who self-reported progressing from prediabetes to diabetes were less likely to be non-adherent to blood glucose testing recommendations (Odds Ratio [OR]=0.51, P=0.006). Each additional year of age was associated with lower odds of being non-adherent to blood glucose testing (OR=0.97, P=0.018). On average, men who engaged more with healthcare providers during visits had lower odds of being non-adherent to blood glucose testing (OR=0.87, P<0.001). Men who reported reasons for medication non-adherence (OR=1.68, P=0.043) and used tobacco products (OR=2.39, P<0.001) were more likely to report blood glucose testing non-adherence. Findings suggest that disease progression, greater engagement with healthcare providers, and improved healthy behaviors may be associated with adherence to blood glucose testing among Black and Hispanic men with a history of prediabetes. Culturally tailored interventions and strategies are needed to improve adherence among male these sub-groups. Without adopting self-care behaviors and adhering to recommended screenings, prediabetes is likely to progress to type 2 diabetes. This study examined factors associated with non-adherence to recommended blood glucose testing among non-Hispanic Black and Hispanic men ages ≥40 years with a history of prediabetes. Findings highlight the importance of quality of patient-provider communication and improved healthy behaviors to increase adherence to blood glucose testing among Black and Hispanic men with prediabetes.
Metal and metalloid contamination from terrestrial and maritime human activities increasingly threatens coastal ecosystems, inducing ecotoxicological effects and potential risks to human health. Filter-feeding intertidal species such as Ruditapes spp. can bioaccumulate these contaminants and are therefore widely used for coastal environmental monitoring. For ecotoxicological purposes, seasonal and spatial concentrations of metals (Al, Cd, Cr, Co, Cu, Fe, Mn, Ni, Pb, V and Zn) and the metalloid As were analysed in sediments and clam tissues from the French English Channel and Atlantic coasts, using a multi-scale approach (local, regional and national). Spatial differences were mainly observed at local and regional scales, whereas no marked differences were detected at the national scale. Bioaccumulation in Ruditapes spp. was compared with Mytilus edulis and Crassostrea gigas, two other commonly used sentinel species. The species- and site-specific accumulation patterns suggested that employing multiple species could enhance environmental monitoring strategies. As showed the highest bioaccumulation values, followed by Zn, Cu, Ni and Co. Finally, environmental and human health risk assessments indicated that, among the studied elements, only As may raise concern in some sites, while risks associated with other metals remained low.
Controlled human infection (CHI) trials deliberately expose healthy participants to a pathogen. Although they share design features with phase I clinical trials, CHI trials may differ in participant burden and administrative burden. Literature on CHI participant motivations and trial experience compared to phase I participants is limited. We conducted a survey comparing motivation, decision-making, and ethical views among CHI and phase I participants, using a previously validated questionnaire. Descriptive and comparative analyses assessed motivational drivers and ethical attitudes. In total, 70 CHI and 98 phase I participants were included. Distribution of motivation was different for CHI compared to phase I participants, with reimbursement being a less prominent motivator, and more altruistic factors reported. CHI participants experienced more severe symptoms and reported symptoms as an important factor in the decision to participate. Views on key ethical principles such as reimbursement and burden of participation were similar between participant groups. Overall, findings suggest CHI participants experienced more symptoms than phase I participants, but that CHI participation was a well-informed decision, with symptom burden taken into account. This informs future CHI trial design and warrants further research on symptoms and participant experience in CHI trials.
Tissue Engineering (TE) represents an effective approach for addressing tissue or organ defects and functional impairments. Cells, scaffolds, and growth factors, as the three elements of TE, play an important role in tissue repair. In recent years, there has been growing interest in Wharton's Jelly (WJ), obtained from the umbilical cord of postpartum medical waste. Mesenchymal stem cells, extracellular matrix, and growth factors derived from WJ have been widely used in TE. WJ has shown the potential to treat a wide range of diseases in clinical applications. This review discusses the mechanisms of action of WJ, focusing on their applications in the field of tissue damage repair. We also highlight the advantages, current limitations, and future directions of WJ-based therapies, including challenges related to standardization, scalability, long-term safety, and clinical translation.
Preterm birth (PTB, < 37 weeks of gestation) is the leading cause of child mortality in the United States (U.S.) and worldwide, and has substantial short- and long-term health consequences for mothers and infants. Each year, > 350,000 infants in the U.S. are born preterm, and rates continue to rise in parallel with maternal risk factors such as hypertension, diabetes, anemia, asthma, and mental health conditions. Evidence-based interventions exist for many of these conditions and are associated with improved pregnancy outcomes, including low-dose aspirin for preeclampsia prevention in individuals with chronic hypertension or pregestational diabetes, inhalers for asthma, iron for anemia, and therapy or medication for mental health disorders, but fewer than half of eligible individuals receive them, reflecting persistent gaps in use. To address this, we developed the PTB Actionable Risk Index (PTB-ARIx), which leverages factors with known evidence-based interventions to identify individuals who are pregnant and are at increased risk for PTB. This study evaluates performance of the PTB-ARIx throughout pregnancy with respect to risk determination and characterization of actionable risk factors, including their combined contributions to PTB. A retrospective cohort study was conducted using linked data for 1.9 million singleton live births in California in 2016-2020, divided into training and testing sets. Poisson regression estimated associations between 18 candidate risk factors for PTB with evidence-based interventions spanning clinical, behavioral, and social risks, including preeclampsia risk composites (≥ 1 high-risk or ≥ 2 moderate-risk factors based on U.S. Preventive Services Task Force (USPSTF) criteria), maternal conditions (e.g., gestational hypertension, asthma), substance use, and social adversity. Beta coefficients were combined to construct the PTB-ARIx, evaluated by per-unit associations with PTB and by area under the receiver operating characteristic curve (AUC) overall, by early (< 32 weeks), late (32-36 weeks), spontaneous, and medically-indicated PTB, and by PTB co-occurring with preeclampsia. All risk factors were found to be associated with increased PTB risk. Having ≥ 1 high-risk or ≥ 2 moderate-risk factors for preeclampsia (based on composites) was most strongly related to PTB (relative risk (RR) 6.73, 95% confidence interval (CI) 6.57, 6.89). Each unit increase in PTB-ARIx was associated with > 60% higher PTB risk (RRs 1.66-1.72) across training and testing samples, with consistent findings across PTB and race/ethnicity-insurance subgroups. Model performance was modest for late PTB (AUC ≈ 0.63), stronger for early PTB (0.69-0.72), and especially high for early PTB with preeclampsia (AUCs up to 0.97). Over 70% of individuals with PTB-ARIx scores ≥ 3.00 experienced PTB or another adverse outcome such as low birth weight (< 2,500 grams). The PTB-ARIx is a well-performing metric for identifying individuals at increased risk for PTB and other adverse pregnancy outcomes. By centering on modifiable risks, the PTB-ARIx combines risk identification with opportunities for intervention. Demonstrating strong performance across subgroups, including for early PTB and PTB with preeclampsia, the PTB-ARIx provides a potential pathway to improve patient-provider communication and uptake of equitable, evidence-based care. Further validation, including integration with treatment data, is needed to confirm its potential to reduce PTB risk and rates.
Survivors of oesophageal and gastric cancer frequently experience persistent symptoms and functional limitations that affect their health-related quality of life (HRQL). Although self-care is increasingly recognised as a central component of survivorship care, little is known about what determines self-care engagement or whether engagement is associated with better HRQL. This study examined the sociodemographic and healthcare-related variables associated with self-care engagement and explored its association with global quality of life (QOL) in a nationwide cohort. A cross-sectional survey was conducted among individuals diagnosed with oesophageal or gastric cancer in Sweden between 2021 and 2023. Participants completed the EORTC QLQ-C30 and a study-specific questionnaire assessing symptoms and self-care. Self-care engagement was operationalised as the ratio of self-care strategies used to the number of symptoms experienced and categorised into no, moderate, and high. Factors associated with self-care engagement were analysed using multinomial logistic regression, and the association between self-care engagement and global QOL was assessed using linear regression, adjusting for sociodemographic and clinical confounders. Of the 432 respondents, 422 reported at least one symptom and were included in the self-care analysis. One-third of the participants reported no self-care engagement, whereas two-thirds reported moderate or high engagement. Across all models, university education was the strongest and only consistent variable associated with self-care engagement (high vs. no self-care engagement: odds ratio 2.83, 95% confidence interval 1.48-5.42). Neither assignment of a designated contact nurse nor proximity to the treating hospital was associated with self-care engagement. Participants with high self-care engagement had substantially better global QOL than those with moderate or no self-care engagement, with mean differences exceeding 10 points on a 0-100 scale. Global QOL did not differ between the moderate and no self-care groups. Self-care engagement varies widely among oesophageal and gastric cancer survivors and appears to be influenced by educational level. High self-care engagement is associated with clinically meaningful improvements in global QOL, whereas no or moderate self-care appears insufficient to confer benefits. These findings suggest an equity gap in survivorship care, and future research should explore the development of structured and accessible interventions to enhance self-care capabilities among patients with lower educational attainment.
Worldwide, the incidence, prevalence, disability, and mortality associated with Parkinson's disease (PD) have increased substantially, placing an immense strain on healthcare systems across countries of all income levels, prompting the use of the term "Parkinson pandemic" to emphasize the urgent need for coordinated strategies to address its worldwide impact. This narrative review explores the regional differences in the dramatic increase in PD burden, along with its genetic, environmental, and socioeconomic determinants worldwide. Furthermore, it discusses the healthcare access in different regions and proposes strategies to combat this pandemic. The rising burden of PD is largely driven by population aging, increased life expectancy, and potentially by greater exposure to by-products of industrialization-such as pesticides, air pollution and heavy metals- and declining smoking rates, which vary across world regions. Differences in prevalence, demographic, genetic and lifestyle factors, the impact of urbanization and environmental risk factors, as well as inequality and disparities in access to care and healthcare services, have been outlined, mandating the development of tailored and region-specific strategies to mitigate the pandemic and reduce its burden globally and regionally. These strategies include exploring relevant genetic and environmental determinants, promoting research, increasing public awareness, facilitating early diagnosis and optimal management, improving access to healthcare services, supporting caregivers, encouraging the adoption of protective lifestyle factors, ensuring the availability of essential medications and controlling environmental exposures such as toxicants. Global Burden of Parkinson's Disease worldwidePlain language summaryMapping the global burden of Parkinson's diseaseThe global burden of PD is increasing over the past decades worldwide, with estimated that about 12 million had PD in 2021 and might exceed 25 million by 2025. This global rise places an immense strain on healthcare systems across all countries, prompting the use of the term Parkinson Pandemic to emphasize the urgent need for coordinated strategies to address its worldwide impact. However, considerable regional variability in its burden exists, attributed to differences in prevalence, underlying genetic and environmental risk factors and its interaction, variable population aging and growth, life expectancy, lifestyle factors, awareness and early diagnosis as well as inequality and disparities in access to care and healthcare services. This review recognizes the determinants of PD pandemic and their variations across continents and discusses proposed strategies to combat this growing global challenge.Regional differences of PD prevalence are well recognized. High-income countries reported high prevalence, while low-middle-income countries showed a greater increase over recent decades. Understanding genetic variations among populations might explain the variability of PD prevalence, explore disease pathogenesis and tailor future therapies. Additionally, environmental risk factors for PD show marked global variation, reflecting differences in industrialization, agricultural practices and regulatory frameworks, with higher risk in areas with intensive agriculture, industrial emissions, and heavy air pollution.Comprehensive strategies to combat this pandemic include exploring relevant genetic and environmental determinants, promoting research, increasing public awareness, facilitating early diagnosis and optimal management, improving access to healthcare services, supporting caregivers, encouraging the adoption of protective lifestyle factors, ensuring the availability of essential medications and controlling environmental exposures such as toxicants.
Human papillomavirus (HPV) can cause six cancer types but can be prevented with timely vaccination in early adolescence. However, despite the wide availability of the HPV vaccine, uptake remains suboptimal among US adolescents. School nurses are invaluable resources to students and their families regarding adolescent immunization needs. As part of the All for Them vaccination program, we assessed the impact of the continued nurse education (CNE) intervention on school nurses' HPV vaccine communication with parents. Seventy-two school nurses and nurse administrators in Texas participated in the study. Using a single-arm study design, we measured participants' potential barriers to and self-efficacy for recommending the HPV vaccine, and knowledge about HPV and the vaccine. Data were collected between November 2021 and May 2023. We evaluated differences in survey responses using paired t-test and McNemar-Bowker chi-square test. Participants' uncertainty about HPV vaccine efficacy was significantly reduced at follow-up (P < .001). More participants indicated that their HPV knowledge (P = .003) and understanding of the recommended dosing schedule for the vaccine (P = .003) were not barriers at all at follow-up. Participants' confidence to communicate with parents about HPV vaccination significantly increased across six self-efficacy variables at follow-up (P < .001). The CNE intervention appeared to improve nurses' HPV and HPV vaccine-related knowledge and increased their self-efficacy to communicate about HPV vaccination with parents, while lessening their perceived barriers to do so. The CNE can be a key resource to support school nurses' professional practice, facilitating their high-quality HPV vaccine recommendations to adolescents and parents.
Microbial small RNAs (sRNAs) can regulate human genes. Higher plasma concentrations of microbial tRNA-derived RNA-1 (tDR-1) were previously associated with lower rheumatoid arthritis (RA) disease activity. This study examined whether tDR-1 concentrations differ in anti-cyclic citrullinated peptide-3 positive (CCP3+) at-risk individuals (ARI) based on who later develops clinical RA and discriminate later conversion status beyond established risk factors, and whether tDR-1 has in vitro effects. Plasma tDR-1 concentrations were measured in CCP3+ ARI. Group differences in log-transformed tDR-1 were assessed by lognormal Welch's t-test and logistic regression. Area under the receiver operating characteristic curve (AUROC) was used to evaluate discriminatory ability. Human THP-1 monocyte-derived macrophages were treated with tDR-1 versus scramble control and gene expression was assessed by NanoString Immunology panel. Among 60 CCP3+ ARI, 25 later developed clinical RA ("converters") over a mean of 2.2 years, while 35 did not ("non-converters") over a mean of 5.3 years. Baseline plasma tDR-1 concentrations were significantly higher (5.4-fold) in non-converters versus converters, even after adjustment for additional RA risk factors (shared epitope, smoking, rheumatoid factor) (P=5.1x10-4). The AUROC improved from 0.722 for these risk factors alone to 0.902 with the addition of tDR-1 (P=0.003). In vitro, tDR-1 significantly downregulated many type 1 interferon response genes in THP-1 cells. Higher plasma tDR-1 concentrations were associated with non-conversion to clinical RA in CCP3+ ARI. tDR-1's reducing type 1 interferon response gene expression suggests a potential mechanism by which microbes, and tDR-1, could affect RA development.
The human papillomavirus (HPV) vaccine is one of the most powerful tools in cancer prevention and is central to global efforts to eliminate cervical cancer as a public health problem. Yet worldwide uptake remains suboptimal. Our 2025 Cochrane qualitative evidence synthesis - comprising 71 studies from diverse geographic and socioeconomic settings - provides the most comprehensive global understanding to date of caregivers' and adolescents' views and practices regarding HPV vaccination, and the reasons why some are reluctant to receive the vaccine. Our review found HPV vaccine decision-making to be influenced by a complex web of socio-cultural, political and trust-related factors, beyond awareness or a simple evaluation of vaccine benefits and risks. We synthesized these factors into eight overarching themes. Together these provide a novel conceptual framework of the multi-level, interacting influencing factors, distinguishing it from more narrow, individual HPV vaccination acceptance frameworks. In this commentary we describe this conceptual framework and propose how it might be used to inform strategies for improving HPV vaccine uptake in ways that are more person-centered, equitable and ultimately effective. As countries worldwide aim to upscale and optimize HPV vaccination programs, incorporating insights from this review into HPV vaccination policy, program design and service delivery is essential and urgent.
In this research, we examine the determinants of citizens' beliefs about the severity of criminal and administrative sanctions attached to violations of COVID-19 mitigation laws in Russia, as well as extrajudicial sanctions employed in other parts of the world. Although criminological research has identified many predictors of punitive attitudes toward traditional criminal offenses, less is known about how citizens evaluate punishments for violations of newly introduced rules adopted under emergency conditions. The key explanatory variables in our study include beliefs in attribution of human behavior, self-commitment to compliance with COVID-19 mandates, trust in government, and the fear of COVID-19 infection. Data for the study come from 508 respondents from St. Petersburg, Russia's second-largest city, who participated in an online survey during the first wave of the pandemic in May 2020. Findings suggest that citizens who believe in the free-will explanations of human nature and those who are more likely to comply with pandemic-mitigating laws feel that the punishments imposed for violating the pandemic-related laws were not severe enough. Additionally, those who trust the government's effectiveness and integrity in controlling COVID-19 are more punitive, a finding contrary to crime-related punitiveness research. Together, these findings indicate that support for sanctioning pandemic-related violations is closely tied to rule-related evaluations, including responsibility attribution, institutional trust, and personal commitment to compliance. The study contributes to criminological research by showing that established explanations of punitive attitudes may operate differently when applied to newly institutionalized crisis rules. How People Judge Punishments for Breaking Emergency RulesThis study looks at how people decide whether punishments for breaking COVID-19 rules are too harsh or not harsh enough. We focus on people in Russia and examine both formal punishments, such as fines or legal penalties, and informal responses seen in other countries. Past research has identified many factors that shape opinions about punishment for traditional crimes, however, we know less about how people judge punishments for new rules introduced during emergencies like the pandemic. In this study, we focus on several key factors: whether people believe individuals are responsible for their actions, how willing they are to follow COVID-19 rules themselves, how much they trust the government, and how worried they are about getting infected. The study is based on an online survey of 508 people in St. Petersburg, conducted during the first wave of the pandemic in May 2020. The findings show that people who believe individuals have control over their actions, and those who are more willing to follow COVID-19 rules themselves, are more likely to think that punishments were not strict enough. We also find that people who trust the government to manage the pandemic tend to support stronger punishments. This is different from what we usually see in studies of crime, where higher trust in government is often linked to less support for harsh punishment. Overall, the results suggest that support for punishing pandemic-related rule-breaking is closely tied to how people think about responsibility, their trust in institutions, and their own commitment to following the rules. The study shows that ideas we use to explain attitudes toward punishment may work differently when applied to new rules created during a crisis.
Carbon dioxide (CO2) can regulate blood flow and is applied therapeutically in intensive care units to treat brain injury, as well as in balneotherapy for peripheral arterial disease (PAD) and diabetic angiopathy; however, its mode of action remains unclear. The vasoactive CO2 effects were tested in arteries of healthy C57BL/6J mice, hypertensive apolipoprotein E-deficient mice, and soluble guanylyl cyclase (sGC) knockout mice in a small vessel myograph with and without pharmacologically intervening in endothelium- and/or vascular smooth muscle-mediated vasodilation. CO2-based Near Infrared Spectroscopy (NIRS-CO2) was developed to assess vasoreactivity of the skin microcirculation to CO2 in healthy individuals, PAD and coronary artery disease (CAD) patients, and was compared with flow-mediated dilation (FMD). We identified CO2 as a triple vasodilator mimicking the actions of endothelium-derived relaxing factor (nitric oxide, NO), endothelium-derived hyperpolarization factor (EDHF), and direct myogenic vasodilators. CO2 engaged endothelial NO/sGC, endothelial small-/intermediate-conductance calcium-activated potassium channels (SKCa/IKCa), and myogenic voltage-gated (KV) and IKCa potassium channels, respectively, acting as a triple vasodilator. CO2-evoked vasodilator responses were blunted and delayed in diseased human and murine arteries. In the human cohort, the NIRS-CO2-derived time-to-intersection (TTI) of the HbO2 and HHb curves, capturing the delay phenotype, showed a strong association with PAD/CAD status and, in exploratory analyses, also distinguished young individuals with cardiovascular risk factors, supporting NIRS-CO2 as a physiological readout that integrates endothelial and myogenic components of microvascular reactivity. Duration and extent of CO2 vasodilation were coupled to tissue metabolism through vascular carbonic anhydrases (CAs), providing a mechanism for vasculometabolic coupling and one for clinically approved CA inhibitors. NIRS-CO2 provides a feasible readout of CO2-evoked microvascular responsiveness and shows disease-associated alterations in our PAD/CAD cohort. Larger studies will validate generalizability across vasculopathies and clarify the relative contributions of NO-sGC versus K+ channel-linked mechanisms for future therapeutic translation.
Unhealthy dietary patterns are increasingly recognized as important modifiable factors associated with cognitive decline and Alzheimer's disease (AD). Diets characterized by high intake of saturated fats, refined sugars, and ultra-processed foods are consistently linked to metabolic dysfunction, systemic inflammation, and impaired brain health. Epidemiological and interventional studies suggest that these dietary patterns are associated with poorer cognitive outcomes, whereas adherence to nutrient-rich dietary patterns such as the Mediterranean, MIND, and DASH diets is linked to improved metabolic profiles and slower cognitive decline. Several biological mechanisms have been proposed to explain these associations, including insulin resistance, oxidative stress, neuroinflammation, vascular dysfunction, and alterations in gut-brain axis signaling; however, much of the current human evidence remains observational, limiting definitive causal inference. Emerging research also indicates that individual susceptibility to diet-related AD risk may be modified by genetic background, metabolic status, and sex-specific biological factors. Despite variability in study findings, the overall body of evidence supports a biologically plausible relationship between dietary quality and key processes implicated in AD pathogenesis. Future research should prioritize long-term, biomarker-driven randomized controlled trials, alongside life-course approaches that consider early- and mid-life dietary exposures, to better clarify causal pathways and inform targeted nutritional strategies for AD risk reduction.
The integrity of the human genome is continuously challenged by diverse endogenous and exogenous threats that damage DNA and disrupt its replication. When the replication machinery encounters such obstacles, including lesions or non-canonical DNA structures, it may stall, initiate repair, or activate specialized pathways to bypass the impediment. Maintaining replication progression requires a coordinated and dynamic assembly of numerous nucleoprotein complexes that recognize, process, and resolve DNA damage and replication stalling structures. This chapter highlights how proliferating cell nuclear antigen (PCNA), poly(ADP-ribose) polymerase 1 (PARP1), and non-canonical DNA structures are integrated into higher-order supramolecular complexes that stabilize, remodel, or resolve stalled or damaged replication forks. The molecular events carried out by these supramolecular complexes are essential for preserving genomic integrity in human cells. Moreover, many of the factors involved emerge as attractive therapeutic targets for diseases driven by genome instability, including cancer.
Higher prevalence of hepatocellular carcinoma (HCC) in men is largely attributed to the sex hormones and behavioral risk factors. This study investigated the effects of male (testosterone) and female (estradiol) hormones on Aurora-A/B kinases, GATA-3, and microRNAs (miR-3941, miR-4500, miR-4742) in HepG2 and Huh-7 cell lines. In this study, two human hepatocellular carcinoma cell lines, HepG2 (with a differentiated phenotype) and Huh-7 (with more aggressive tumorigenic behavior), were treated with the sex hormones β-estradiol and testosterone. Hormonal effects were evaluated using the MTT assay (to assess cytotoxicity), flow cytometry (for cell cycle analysis), RT-qPCR (to quantify the expression of target genes and miRNAs, including Aurora-A, Aurora-B, GATA-3, miR-3941, miR-4500, and miR-4742), and western blotting (to assess protein levels of Aurora-A/B kinases and GATA-3). In HepG2 cells, estradiol and testosterone decreased Aurora-A/B kinase expression and increased GATA3, causing G0/G1 and G2/M cell cycle arrest and reduced DNA synthesis. Conversely, in the more aggressive Huh7 cell line, these hormones accelerated G1-S transition and led to late cell cycle accumulation. Both cell lines exhibited inverse miRNA regulation (miR-3941 and miR-4500 upregulated; miR-4742 downregulated), suggesting a post-transcriptional mechanism affecting cell division genes. Multivariate regression indicated Aurora-A/B independently regulated G0/G1-S transition in HepG2, while temporal factors predominated in Huh7 cell cycle control. A simultaneous comparison of female and male sex hormones in two HCC cell models-one less aggressive (HepG2) and one highly aggressive (Huh-7)-demonstrated that the direction of hormonal effects (inhibitory or stimulatory) depends not on hormone type but on cellular phenotype, and downstream regulatory networks. This duality of response was similar for both hormones within each cell line. This paradox may be attributed to the predominance of distinct signaling pathways-protective in HepG2 versus proliferative in Huh-7 cells.