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PMC11276901_p29
|
PMC11276901
|
sec[3]/p[7]
|
4. Results
| 2.439453 |
biomedical
|
Study
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The significant effects ( p < 0.001) of the interactions suggest that the combination of activity intensity, frequency, and accessibility to quality suitable UGSs has a substantial impact on individuals’ mental well-being.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276901_p30
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PMC11276901
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sec[4]/p[0]
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5. Discussion
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biomedical
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Study
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Our study aimed to explore the relationship between nature engagement (activity intensity, duration, frequency), mental well-being (depression, anxiety, and stress), and accessibility to suitable UGSs. The findings underscore the critical role of UGS suitability in maximizing the mental well-being benefits of nature engagement, corroborating recent studies that have provided further insights into this relationship. For instance, a systematic review by Nguyen et al. highlighted that UGSs contribute significantly to mental health by providing environmental benefits, promoting outdoor activity, and enhancing social cohesion.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
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PMC11276901_p31
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PMC11276901
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sec[4]/p[1]
|
5. Discussion
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biomedical
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Study
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Similarly, a study conducted during the post-COVID-19 era emphasized the importance of perceived UGSs for youth mental health, showing a negative correlation between UGSs and anxiety among youth, although the effect on depression was less pronounced . This aligns with our findings that more intense, longer, and frequent activities in high-quality green spaces are associated with lower depression and anxiety scores, as indicated by our multiple regression analysis. Additionally, UGS suitability showed a significant negative coefficient, suggesting that the quality of nearby green spaces plays an important role in reducing depression scores. These results are consistent with the findings of Dadvand et al. , who reported that access to green spaces positively impacts general health by reducing mental health issues through increased physical activity and social support. Houlden et al. found that the perceived quality of green spaces was more important than their quantity in predicting mental health outcomes in urban settings. In turn, Van den Berg et al. highlighted that individuals who spent more time in high-quality green spaces reported lower levels of stress and better overall well-being.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276901_p32
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PMC11276901
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sec[4]/p[2]
|
5. Discussion
| 3.710938 |
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Study
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Regarding anxiety scores, more intense, longer, and more frequent activities are also associated with lower levels of anxiety. Moreover, UGS suitability showed a significant negative coefficient, reinforcing the importance of high-quality green spaces. These outcomes suggest that urban interventions promoting frequent and intense use of high-quality green spaces can be effective in reducing anxiety among urban residents. This is supported by a review by Liu et al. , which found that different types of UGS impact residents’ mental health through various mediators, including stress reduction and emotional stabilization. Marselle et al. also found that the frequency of visits to green spaces was positively associated with lower levels of anxiety and stress, particularly when the spaces were well-maintained and provided opportunities for physical activity.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276901_p33
|
PMC11276901
|
sec[4]/p[3]
|
5. Discussion
| 4.035156 |
biomedical
|
Study
|
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As with depression and anxiety, significant negative coefficients indicate that more intense, longer, and more frequent activities are associated with lower stress levels. However, UGS suitability was not significant for stress, suggesting that other factors beyond UGS suitability may moderate the effects of stress. These results suggest that promoting physical activities in green spaces can be an effective strategy for reducing stress, but the quality of green spaces may need additional improvements to maximize their benefits. This is echoed in the findings of a recent study that examined the role of UGS suitability on stress, which emphasized the need for well-maintained and accessible green spaces to achieve optimal mental health benefits . Moreover, White et al. also support this finding, suggesting that while green space suitability is important, the specific features and quality of these spaces significantly impact their effectiveness in reducing stress. Their study emphasizes that factors such as the presence of water features, biodiversity, and facilities for physical activities play crucial roles in maximizing the stress-reducing benefits of UGSs. The significant effects revealed by the ANOVA results also emphasize the need for urban policies that promote not only the presence of green spaces but also their suitability, ensuring they are suitable for nature engagement.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276901_p34
|
PMC11276901
|
sec[4]/p[4]
|
5. Discussion
| 3.769531 |
biomedical
|
Study
|
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These findings confirm the research hypothesis that higher nature engagement is associated with better mental health outcomes and these positive effects are moderated by the quality of nearby green spaces. Therefore, simply having green space in the neighborhood is not enough to make a significant difference in mental well-being outcomes. While the presence of UGS is important, their suitability plays a crucial role in maximizing benefits. Therefore, urban planning policies should focus not only on increasing the quantity of green spaces but also on improving their suitability. Even in an emerging country like Brazil, with high tax rates, Bressane et al. found significant willingness among the population to pay for the maintenance and improvement of UGS, driven by the recognition of health benefits. High-quality green spaces that are accessible, safe, and well-maintained can significantly enhance residents’ mental well-being by promoting more frequent and intense use for recreational and physical activities.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276901_p35
|
PMC11276901
|
sec[4]/sec[0]/p[0]
|
5.1. Insights for the Design of Healthy Cities
| 3.917969 |
biomedical
|
Study
|
[
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Table 4 provides key insights for the design of healthy cities based on the study results. Each theme identifies a specific aspect of UGS, highlighting the associated study findings and providing actionable insights for urban planners and policymakers. These insights are aimed at optimizing the design, maintenance, and accessibility of green spaces to enhance the mental health and well-being of city residents. The integration of these recommendations into urban planning strategies can significantly contribute to creating more resilient, inclusive, and health-promoting urban environments. This study has demonstrated that high-intensity activities in green spaces, such as running and cycling, are linked to reduced levels of depression, anxiety, and stress. To promote high-intensity activities, urban planners should consider designing specific areas within green spaces. This can be achieved by allocating certain paths specifically for cycling and others for jogging, with clear signage and mile markers. Additionally, installing outdoor fitness equipment such as pull-up bars, balance beams, and outdoor gyms that cater to various fitness levels allows for circuit training or high-intensity interval training (HIIT) sessions. Hosting regular fitness-related events or classes, such as yoga, or Tai Chi, can attract more visitors and encourage engagement in high-intensity activities.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276901_p36
|
PMC11276901
|
sec[4]/sec[0]/p[1]
|
5.1. Insights for the Design of Healthy Cities
| 1.357422 |
other
|
Other
|
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[
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Our results also showed that the duration and frequency of engagement with nature are also important for mental well-being. To facilitate longer and more frequent interactions with nature, providing comfortable amenities, such as benches, shaded areas, water fountains, restrooms, and Wi-Fi hotspots, can make long stays more comfortable. Educational and engaging signage can encourage visitors to explore different parts of the park, extending the duration of their visits. Scheduling regular educational and recreational programs, such as bird watching tours, nature walks, or art sessions, can also encourage repeated and prolonged visits.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276901_p37
|
PMC11276901
|
sec[4]/sec[0]/p[2]
|
5.1. Insights for the Design of Healthy Cities
| 1.570313 |
other
|
Other
|
[
0.1407470703125,
0.002079010009765625,
0.857421875
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[
0.007175445556640625,
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The UGS suitability for various activities was identified as an extremely important factor in moderating the mental health benefits. Designing varied landscapes in green spaces, such as open fields for team sports, quiet wooded areas for meditation or reading, and interactive playgrounds for children, can cater to diverse preferences. Maintaining high standards of upkeep, ensuring pathways are clear, lawns are mowed, and facilities are in good repair, is essential. Increasing the sense of safety with adequate lighting, visible security presence, and emergency call stations enhances usability at different times of the day.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276901_p38
|
PMC11276901
|
sec[4]/sec[0]/p[3]
|
5.1. Insights for the Design of Healthy Cities
| 1.170898 |
other
|
Other
|
[
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Accessibility to high-quality green spaces is crucial, especially in urban areas where natural spaces are limited. Improving public transportation links to green spaces, providing ample parking, and ensuring pedestrian pathways leading to these areas are safe and well-maintained is fundamental. Involving community members in the planning process helps identify the most needed improvements and preferred features in green spaces. Strategically developing new green spaces in underserved areas ensures balanced accessibility across the city.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276901_p39
|
PMC11276901
|
sec[4]/sec[0]/p[4]
|
5.1. Insights for the Design of Healthy Cities
| 1.621094 |
other
|
Other
|
[
0.322509765625,
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[
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The quality of UGSs can significantly enhance the mental health benefits derived from nature activities. Implementing strategies that incorporate a variety of plant species can increase biodiversity, which has been shown to enhance psychological well-being. Including elements like ponds, streams, or fountains can provide calming soundscapes and visual interest, thus increasing the quality of the green space. Integrating environmental art that encourages interaction and engagement provides aesthetic value and promotes mental relaxation.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276901_p40
|
PMC11276901
|
sec[4]/sec[0]/p[5]
|
5.1. Insights for the Design of Healthy Cities
| 1.279297 |
other
|
Other
|
[
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[
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By focusing on these detailed strategies, urban planners and community leaders can maximize the mental health benefits of green spaces, making them more than just places to relax but vital components of urban public health infrastructure.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276901_p41
|
PMC11276901
|
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|
5.2. Limitations and Future Directions
| 3.347656 |
biomedical
|
Study
|
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While our findings underscore the critical role of UGS suitability in maximizing the mental well-being benefits of nature engagement, we acknowledge the potential bidirectional nature of this relationship. It is possible that individuals with better mental health are more likely to engage in outdoor activities and utilize green spaces. This bidirectional relationship is a common challenge in cross-sectional studies, which limits our ability to infer causality definitively. Therefore, we recommend that future research employ longitudinal designs to establish causal links between nature engagement and mental health improvements.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276901_p42
|
PMC11276901
|
sec[4]/sec[1]/p[1]
|
5.2. Limitations and Future Directions
| 3.919922 |
biomedical
|
Study
|
[
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The study did not account for potential confounding variables such as pre-existing mental health conditions, lifestyle factors (e.g., physical activity outside of nature engagement), or environmental stressors (e.g., noise pollution) that could influence mental health outcomes. Future research should control for these factors to isolate the effects of nature engagement more effectively. Furthermore, the study’s focus on depression, anxiety, and stress, as measured by the DASS-21, may overlook other dimensions of mental well-being, such as resilience, social connectedness, and overall life satisfaction. Future studies should incorporate a broader range of mental health indicators.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276901_p43
|
PMC11276901
|
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|
6. Conclusions
| 3.947266 |
biomedical
|
Study
|
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[
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This study aimed to elucidate whether the quality of nearby green spaces modulates the mental well-being benefits derived from nature engagement. The findings confirmed the research hypothesis, demonstrating that higher intensity and longer duration of nature activities correlate with reduced scores of depression, anxiety, and stress. Therefore, we conclude that the mere presence of green spaces in urban environments is insufficient to elicit substantial health benefits. Instead, the suitability and quality of these spaces are paramount. Urban planning strategies should prioritize the development and maintenance of high-quality green spaces that are accessible, safe, and conducive to various nature activities. By doing so, urban areas can better support the mental well-being of their residents, promoting healthier and more sustainable city living.
|
[
"Adriano Bressane",
"Maria Eduarda Guedes Ferreira",
"Ana Júlia da Silva Garcia",
"Líliam César de Castro Medeiros"
] |
https://doi.org/10.3390/ijerph21070937
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
38906364_p0
|
38906364
|
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|
Who and when
| 3.404297 |
biomedical
|
Other
|
[
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[
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Another huge barrier to the improvement of quality and safety in Brazil and South American LMICs is the model of healthcare delivery: The role of the physician is often the central point of care underestimating the real requirement of other well-trained healthcare professionals. The practice of anesthesia is no different, the physician plays a pivotal role in decision-making and the care provision is delivered in a system based on hierarchy. Opposed to that, in high-income countries, the healthcare system has evolved to embrace a multidisciplinary approach and collaborative teamwork, where responsibilities are shared among professionals such as anesthesiologists, nurses, and respiratory specialists.
|
[
"Anelise Schifino Wolmeister",
"Tom G. Hansen",
"Thomas Engelhardt"
] |
https://doi.org/10.1016/j.bjane.2024.844525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
38906364_p1
|
38906364
|
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|
Who and when
| 3.792969 |
biomedical
|
Other
|
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[
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This comprehensive model of care ensures safety, especially in the context of the pediatric population, where the tasks are more complex and time-critical due to the higher fragility of the patients. Even though Europe and North America have different structured healthcare systems, the overall practice of anesthesia relies heavily on the expertise of the non-medical personnel. Anesthesia is either provided directly by a physician or supervised by a physician in most of the European countries while in the US nurse anesthetists may provide direct care medical guidance. In both, trained nurse anesthetists or anesthesia technicians work together with the physicians, assuming different levels of independence, and focusing on providing excellent clinical care. 10
|
[
"Anelise Schifino Wolmeister",
"Tom G. Hansen",
"Thomas Engelhardt"
] |
https://doi.org/10.1016/j.bjane.2024.844525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
38906364_p2
|
38906364
|
sec[0]/p[2]
|
Who and when
| 1.982422 |
biomedical
|
Other
|
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[
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This huge discrepancy among the anesthesia workforce worldwide is well documented by the World Federation of Societies of Anesthesiologists (WFSA). For example, the workforce in the US has more than 33,000 nurse anesthesia providers as well as almost 2,000 other anesthesia providers while in Brazil there are no nurse anesthesia providers or other supporting professionals. 11
|
[
"Anelise Schifino Wolmeister",
"Tom G. Hansen",
"Thomas Engelhardt"
] |
https://doi.org/10.1016/j.bjane.2024.844525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
38906364_p3
|
38906364
|
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|
Who and when
| 1.889648 |
biomedical
|
Other
|
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Certainly, the transition to a decentered and multidisciplinary system is a difficult task, yet it is based on a fundamental principle: shared expertise leads to improved safety and quality of care.
|
[
"Anelise Schifino Wolmeister",
"Tom G. Hansen",
"Thomas Engelhardt"
] |
https://doi.org/10.1016/j.bjane.2024.844525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
38906364_p4
|
38906364
|
sec[1]/p[0]
|
How
| 2.333984 |
biomedical
|
Other
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There is no doubt that pediatric anesthesia care for sicker and younger children at a tertiary specialized pediatric center improves patient outcomes. Unfortunately, there is a mismatch between individual patient needs and available clinical resources in LMICs. Nonetheless, any center providing pediatric care must always have staff with expertise in pediatric resuscitation available. In addition, reciprocal relationships need to be in place for the provision of a higher level of care if transfer is deemed necessary. 12
|
[
"Anelise Schifino Wolmeister",
"Tom G. Hansen",
"Thomas Engelhardt"
] |
https://doi.org/10.1016/j.bjane.2024.844525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
38906364_p5
|
38906364
|
sec[1]/p[1]
|
How
| 3.839844 |
biomedical
|
Other
|
[
0.95751953125,
0.03704833984375,
0.005413055419921875
] |
[
0.01070404052734375,
0.94580078125,
0.041107177734375,
0.00222015380859375
] |
The development of partnerships between LMIC-LMIC and HIC-LMIC gave rise to the Global Initiative for Children's Surgery (GICS), responsible for the identification of the priorities for surgical children and the development of guidelines for Optimal Resources for Children's Surgery (OReCS). 13 Based on their recommendations, first-level hospitals have the infrastructure and workforce to admit healthy children for common surgical procedures, resuscitation, and emergency surgical care. Sicker children and/ or younger than 1 year old requiring more complicated surgical procedures should receive perioperative treatment in higher levels of care unless emergent. The most experienced available anesthesia providers should be in charge. Secondary and tertiary-level hospitals must have specialists with pediatric experience in anesthesia for the comprehensive care of more complex cases and children with comorbidities. These recommendations are aligned with the World Federation of Societies of WFSA and the Association of Anaesthetists to enhance the quality of children's care by providing training in LMICs.
|
[
"Anelise Schifino Wolmeister",
"Tom G. Hansen",
"Thomas Engelhardt"
] |
https://doi.org/10.1016/j.bjane.2024.844525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
38906364_p6
|
38906364
|
sec[1]/p[2]
|
How
| 3.216797 |
biomedical
|
Other
|
[
0.9228515625,
0.0711669921875,
0.005992889404296875
] |
[
0.002777099609375,
0.99365234375,
0.00170135498046875,
0.0017261505126953125
] |
Programs such as SAFE Paeds – a branch of the Safer Anaesthesia Education (SAFE) initiative have led to improvement in the knowledge, skills, and behavior of anesthesia providers. Opportunities for advanced training in pediatric anesthesia to develop future pediatric anesthesia leaders and educators should be encouraged. The goal is to guarantee that any hospital admitting a pediatric patient has a team of anesthesia providers led by at least one anesthesiologist appropriately trained. 8 Academic training centers, mostly represented by tertiary referral centers, should be staffed with experienced pediatric anesthetists to ensure the quality of education training.
|
[
"Anelise Schifino Wolmeister",
"Tom G. Hansen",
"Thomas Engelhardt"
] |
https://doi.org/10.1016/j.bjane.2024.844525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
38906364_p7
|
38906364
|
sec[2]/p[0]
|
Where and who
| 2.382813 |
biomedical
|
Other
|
[
0.90771484375,
0.0204925537109375,
0.0718994140625
] |
[
0.0083160400390625,
0.990234375,
0.0011320114135742188,
0.0005035400390625
] |
Unfortunately, in Brazil pediatric anesthesia encounters challenges based on the lack of either educational or financial incentives for healthcare professionals to pursue additional training. First, there is little or no movement of local staff from smaller institutions to seek additional training at specialized centers. Second, remuneration in pediatric anesthesia is shamefully inferior in comparison with other areas of anesthesia effectively placing the importance, needs, and well-being of children below most. It is important to notice that, most of the time, anesthesia practice occurs in the context of a mixed population varying from geriatric patients to infants in the same hospital on the same operating list. Children are commonly not pooled or cared for in a pediatric friendly environment.
|
[
"Anelise Schifino Wolmeister",
"Tom G. Hansen",
"Thomas Engelhardt"
] |
https://doi.org/10.1016/j.bjane.2024.844525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
38906364_p8
|
38906364
|
sec[2]/p[1]
|
Where and who
| 3.984375 |
biomedical
|
Study
|
[
0.99755859375,
0.0019330978393554688,
0.0003669261932373047
] |
[
0.93994140625,
0.02294921875,
0.036163330078125,
0.0009179115295410156
] |
It is well described that caseload and clinical experience are crucial to improve safety in pediatric anesthesia and the number of years of practice being the most common factor influencing the quality of care. Each year of anesthesia experience reduces 1% of respiratory events and 2% of cardiovascular events. 5 , 14 The dedication of pediatric anesthesia performance of less than 73 days per year is an independent risk factor for the number of cardiac arrests in the operating and postoperative recovery room. 14 In this way, not only the lack of adequate training but also the scarce maintenance of required skills exposes the children in need of anesthesia to suboptimal care in Brazil and in the majority of LMICs in South America.
|
[
"Anelise Schifino Wolmeister",
"Tom G. Hansen",
"Thomas Engelhardt"
] |
https://doi.org/10.1016/j.bjane.2024.844525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
38906364_p9
|
38906364
|
sec[2]/p[2]
|
Where and who
| 4.070313 |
biomedical
|
Study
|
[
0.99853515625,
0.0009751319885253906,
0.0003266334533691406
] |
[
0.95263671875,
0.002777099609375,
0.04437255859375,
0.0003643035888671875
] |
In HICs, the economic pressure, time constraints, and demands of enhanced productivity conflict with the possibility of healthcare providers prioritizing education. This situation is even more challenging in LMIC. 15 Data from the APRICOT study showed a variable incidence and management of severe perioperative critical events across Europe, raising concerns about pediatric anesthesia training, teams’ experience with higher-risk children, resources, and infrastructure. 5 A sub‐analysis of the APRICOT, exploring the differences between Scandinavian data (Denmark, Finland, Norway, and Sweden) and the rest of Europe, indicated better outcome regarding the incidence and nature of perioperative critical events. 16 This is not surprising given the unique practice and training in pediatric anesthesia in Scandinavia: the use of medications, anesthetic techniques, and training are uniform, there are always two anesthesia‐trained professionals, and in the pediatric recovery room, patients are accompanied by recovery‐trained and registered nurses. Aligned with this high standard of care, the Scandinavian countries have had a consistent training program in pediatric anesthesia and intensive care running for over 20 years. There is no doubt that all these factors continue to result in a safer perioperative outcome. 17
|
[
"Anelise Schifino Wolmeister",
"Tom G. Hansen",
"Thomas Engelhardt"
] |
https://doi.org/10.1016/j.bjane.2024.844525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
38906364_p10
|
38906364
|
sec[3]/p[0]
|
Future directions
| 3.175781 |
biomedical
|
Other
|
[
0.921875,
0.039031982421875,
0.03887939453125
] |
[
0.005214691162109375,
0.9931640625,
0.001129150390625,
0.0005249977111816406
] |
Without changes in the investment in extra years of specific pediatric anesthesia training, either by providing financial funding or by standardizing and regulating pediatric anesthesia competencies, the current mixed anesthesia system will continue to disadvantage children in Brazil. In addition to organizing local pediatric specialized care, administrative strategies are necessary to guarantee and optimize the delivery of excellent care. The creation of specific guidelines and flowsheets related to referral criteria are essential, permitting objective decision making. Such strategies should be based on hospital infrastructure and equipment, population age, urgency of the procedure, complexity of anesthesia, postoperative care needs, pain management availability, and the experience of the anesthesia, surgical, and nursing teams involved.
|
[
"Anelise Schifino Wolmeister",
"Tom G. Hansen",
"Thomas Engelhardt"
] |
https://doi.org/10.1016/j.bjane.2024.844525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
38906364_p11
|
38906364
|
sec[3]/p[1]
|
Future directions
| 3.945313 |
biomedical
|
Review
|
[
0.99462890625,
0.004489898681640625,
0.000972747802734375
] |
[
0.05328369140625,
0.1510009765625,
0.79345703125,
0.002010345458984375
] |
Technological and pharmacological advances in anesthesia play an important role in the reduction of morbidity and mortality in perioperative settings worldwide. Adequate and well-functioning equipment is an elementary requirement for safe anesthesia in children and is extensively described by the World Federation of Societies of Anesthesiologists (WFSA) and the World Health Organization (WHO) Safe Surgery Checklist. 18 Even though access to new technologies is variable in LMICs, improvement of care should not only focus on acquiring equipment but guaranteeing the proper use of the basic equipment by training personnel and maintenance of competence. 15 Gaps in the preparation of appropriately sized pediatric equipment and monitors remain a major obstacle despite the availability of perioperative pediatric anesthesia equipment. 19
|
[
"Anelise Schifino Wolmeister",
"Tom G. Hansen",
"Thomas Engelhardt"
] |
https://doi.org/10.1016/j.bjane.2024.844525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
38906364_p12
|
38906364
|
sec[3]/p[2]
|
Future directions
| 2.373047 |
biomedical
|
Other
|
[
0.97412109375,
0.00945281982421875,
0.0163116455078125
] |
[
0.0112457275390625,
0.96875,
0.0188140869140625,
0.0013055801391601562
] |
Investing in infrastructure alone will not solve these challenges, developing an institutional competence does. 20 In the pre-pandemic era, the Global Initiative for Children's Surgery stated that the delivery of safe, effective surgical care to children was already critical and neglected. The pandemic has aggravated this scenario posing unprecedented challenges to the healthcare system worldwide. Even though the adult population bore the brunt of the pandemic as reflected in the number of deaths, the impact on the pediatric population cannot be underestimated. 21 The fear of reaching the hospitals resulted in diagnostic as well as therapeutic delays and preventable complications. 22
|
[
"Anelise Schifino Wolmeister",
"Tom G. Hansen",
"Thomas Engelhardt"
] |
https://doi.org/10.1016/j.bjane.2024.844525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
38906364_p13
|
38906364
|
sec[3]/p[3]
|
Future directions
| 2.609375 |
biomedical
|
Other
|
[
0.9609375,
0.0160980224609375,
0.0230712890625
] |
[
0.00662994384765625,
0.99072265625,
0.002002716064453125,
0.0005269050598144531
] |
Longer surgical waiting lists and diseases that are more advanced have an even bigger impact on pediatric anesthesia practice, exacerbating the existing surgical backlogs and delays for elective, urgent, and emergent cases. 23 Brazil and other South American LMICs need urgent mobilization of resources and focus on strategies to mitigate the already overwhelmed healthcare provision for children. The exponential growth in pediatric surgical need will increase the ratio between mixed-practice anesthetists and pediatric patients. Nonetheless, special efforts must be made to provide long-term strategies to guarantee pediatric anesthesia care.
|
[
"Anelise Schifino Wolmeister",
"Tom G. Hansen",
"Thomas Engelhardt"
] |
https://doi.org/10.1016/j.bjane.2024.844525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
38906364_p14
|
38906364
|
sec[3]/p[4]
|
Future directions
| 2.011719 |
biomedical
|
Other
|
[
0.79541015625,
0.164306640625,
0.040069580078125
] |
[
0.0009489059448242188,
0.99658203125,
0.0006861686706542969,
0.0017242431640625
] |
The morbidity and mortality in the pediatric population undergoing surgery can be significantly improved by implementing simple strategies. As anesthetists, we should ask ourselves uncomfortable questions: Are we able to provide appropriate care for these children needing surgery? and When will we be ready to put safety into practice? In addition, most importantly: Are we ready to respect the right of the child to enjoy the highest attainable standard of health?
|
[
"Anelise Schifino Wolmeister",
"Tom G. Hansen",
"Thomas Engelhardt"
] |
https://doi.org/10.1016/j.bjane.2024.844525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
38906364_p15
|
38906364
|
sec[4]/p[0]
|
Declaration of Competing Interest
| 0.866699 |
other
|
Other
|
[
0.057525634765625,
0.002864837646484375,
0.939453125
] |
[
0.0114288330078125,
0.98486328125,
0.00243377685546875,
0.0014019012451171875
] |
The authors declare no conflicts of interest.
|
[
"Anelise Schifino Wolmeister",
"Tom G. Hansen",
"Thomas Engelhardt"
] |
https://doi.org/10.1016/j.bjane.2024.844525
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276939_p0
|
PMC11276939
|
sec[0]/p[0]
|
1. Introduction
| 4.011719 |
biomedical
|
Review
|
[
0.9814453125,
0.004180908203125,
0.01416778564453125
] |
[
0.10223388671875,
0.1920166015625,
0.705078125,
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] |
Accessibility is one of the five main characteristics required to achieve optimal access to care. Access to healthcare services is defined as the ability of the population to receive and utilize health services when needed , and it reflects a set of more specific dimensions describing the fit between the patient and the health care provider or system. These dimensions are grouped into five As of access to care: affordability, availability, accessibility, accommodation, and acceptability . Accessibility is ascertained by the geographic accessibility, and defined as how easily the client can physically reach the provider’s location, in other words, accessibility refers to the distance and time traveled to reach the facility . Optimal access to healthcare services is essential for establishing a high quality of life in every community; however, equal access to healthcare services can be difficult to achieve due to multiple impediments. These impediments include but are not limited to a lack of awareness to the spatial distribution of healthcare services, challenging opportunities for private healthcare investors, and inadequate understanding of geographic variations and the saturation of the population.
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11276939_p1
|
PMC11276939
|
sec[0]/p[1]
|
1. Introduction
| 3.955078 |
biomedical
|
Study
|
[
0.99951171875,
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] |
[
0.984375,
0.0016613006591796875,
0.013671875,
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] |
The prevalence of dental diseases is significantly high in the Kingdom of Saudi Arabia (KSA). The prevalence of dental caries among Saudi children aged 5–7 years and 12–15 years was estimated at 84% and 72%, respectively . Alhabdan et al. reported that the prevalence of dental caries among children in Riyadh was 83% (95% CI: 79.7–86.0%) . Disease prevention at multiple levels is critical and many oral and dental diseases may be screened and treated during the early stages to hamper progression and further complications. Although dental caries is a disease that can be prevented easily, a lack of accessibility may contribute to its increasing prevalence. Enhancing accessibility to dental care services may encourage regular screening, aiding in early detection and more efficient management. Also, ease of access to dental care services in Riyadh may increase patients’ awareness and enhance their knowledge about the risk factors associated with dental caries and other oral diseases, hence, reducing the risk of developing such diseases.
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276939_p2
|
PMC11276939
|
sec[0]/p[2]
|
1. Introduction
| 1.84375 |
other
|
Other
|
[
0.461181640625,
0.003421783447265625,
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] |
[
0.01418304443359375,
0.98486328125,
0.0005621910095214844,
0.00022804737091064453
] |
To address accessibility challenges to dental care, a thorough understanding of the distribution of dental healthcare facilities is needed. Mapping the distribution of all facilities in Riyadh city in relation to the population density may help in illustrating saturated areas and thus guide authorities to target areas that are in greater need of dental care services. Moreover, it may benefit future dentists and investors planning to establish new practices by directing attention to the unserved/underserved areas in Riyadh to meet demands with less competition.
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276939_p3
|
PMC11276939
|
sec[0]/p[3]
|
1. Introduction
| 4.09375 |
biomedical
|
Study
|
[
0.99755859375,
0.0005660057067871094,
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] |
[
0.99951171875,
0.00016891956329345703,
0.0002541542053222656,
0.00004178285598754883
] |
Previous studies reported some insightful information regarding the distribution of dental care facilities around the world. A study conducted in Japan found that even though there has been a significant improvement in the distribution of dental care facilities over the past years, 21% of municipalities with a population of 5000 or fewer still lack dental clinics . More relevantly, studies conducted in Al Madina city and the Jazan region were consistent in finding that accessibility to dental care is challenging, particularly in rural areas . In 2016, Alsalleeh and his co-workers conducted an interesting general analysis of private dental clinics in Riyadh city and reported that private dental clinics were not evenly distributed in Riyadh city; however, they only determined the number of clinics in each sub-municipality without mapping out the detailed spatial distribution. Nonetheless, there are insufficient studies in the literature that address the spatial distribution of dental healthcare facilities in KSA and a gap needs to be filled specifically in Riyadh city. Therefore, this study aimed to evaluate the spatial distribution of PDHFs in Riyadh city, determine the saturation of PDHFs using PDHFs to population ratios, and investigate correlations between the number of PDHFs and other variables, such as area, total population, and mean monthly individual income. This makes the study the first of its kind in Riyadh city and may help in shedding light on possible gaps and disparities and point out overserved/underserved areas, thus benefiting health authorities and investors to target underserved or less saturated areas in Riyadh city for the better well-being of the residents.
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276939_p4
|
PMC11276939
|
sec[1]/p[0]
|
2. Materials and Methods
| 2.115234 |
biomedical
|
Study
|
[
0.9580078125,
0.001697540283203125,
0.04022216796875
] |
[
0.99072265625,
0.00894927978515625,
0.00019538402557373047,
0.000247955322265625
] |
Data collection for this study was conducted in August 2023. The study proposal was exempted from Institutional Review Board (IRB) review since it did not include human subjects or relevant data. Also, the data used were anonymous. Official approval was obtained from the research office at King Abdullah International Medical Research Center (#RSS23R/015). Riyadh city is the capital and highest populated city in KSA; it covers an area of 1973 km 2 and its municipality includes 16 sub-municipalities . This study analyzed the spatial distribution of private dental healthcare facilities (PDHFs) within these sub-municipalities. Moreover, the districts within these sub-municipalities were analyzed individually to calculate PDHFs per person.
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276939_p5
|
PMC11276939
|
sec[1]/sec[0]/p[0]
|
2.1. Location of PDHFs
| 2.005859 |
biomedical
|
Study
|
[
0.96484375,
0.005191802978515625,
0.0301055908203125
] |
[
0.95947265625,
0.039337158203125,
0.000507354736328125,
0.0007843971252441406
] |
The current information regarding the number, location, and operability of PDHFs in Riyadh city was obtained from the Ministry of Health (MOH). All operating PDHFs were included: dental clinics, dental and dermatology polyclinics, and dental care departments located in hospitals. Whereas dental schools, mobile dental clinics, and government healthcare facilities were excluded. A total of 632 PDHFs were included in this study excluding 98 non-operating facilities or those with expired licensure.
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
PMC11276939_p6
|
PMC11276939
|
sec[1]/sec[1]/p[0]
|
2.2. Geographic Integration
| 1.575195 |
other
|
Other
|
[
0.362548828125,
0.0013151168823242188,
0.63623046875
] |
[
0.21240234375,
0.7861328125,
0.0008311271667480469,
0.0008730888366699219
] |
Ain el Abd/UTM zone 38N was used for coordinate referencing. The precise geographic location (GPS coordinates) of each sub-municipality and district was exported from the Riyadh region municipality website map to Quantum Geographic Information System (QGIS) software (version 3.32.1, Essen, Germany), which was used to visualize, analyze, and interpret the geographic data.
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276939_p7
|
PMC11276939
|
sec[1]/sec[2]/p[0]
|
2.3. Mapping
| 3.197266 |
biomedical
|
Study
|
[
0.97998046875,
0.0007238388061523438,
0.0192718505859375
] |
[
0.9990234375,
0.0009169578552246094,
0.00008654594421386719,
0.00005269050598144531
] |
All residential (15) sub-municipalities were included and analyzed in this study. The location of each PDHF was converted to longitude and latitude using Google Earth (version 10.52.0.0, Google, Sunnyvale, CA, USA) . Then, each PDHF location was plotted on QGIS and treated as a central point. Four levels (radii) of buffer zones were determined as the covering range around each central point, with the difference between the levels being the distance from the central point. In other words, four levels of buffer zones—1 km, 3 km, 5 km, and >5 km—were determined to analyze the coverage of each private dental healthcare facility. The coverage of each facility was based on the area covered in square kilometers (km 2 ).
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276939_p8
|
PMC11276939
|
sec[1]/sec[3]/p[0]
|
2.4. Population Statistics
| 1.405273 |
other
|
Other
|
[
0.3984375,
0.0016918182373046875,
0.60009765625
] |
[
0.05157470703125,
0.94677734375,
0.0010519027709960938,
0.0005931854248046875
] |
The population statistics and mean monthly individual income per district were gathered from the Zadd.910ths website, which is a governmental website that provides an interactive map with updated statistics .
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276939_p9
|
PMC11276939
|
sec[1]/sec[4]/p[0]
|
2.5. Statistical Analysis
| 2.814453 |
biomedical
|
Study
|
[
0.99462890625,
0.00048542022705078125,
0.005031585693359375
] |
[
0.99169921875,
0.0078887939453125,
0.00028443336486816406,
0.0001354217529296875
] |
The area of each district and sub-municipality was calculated in square kilometers (km 2 ) using QGIS. Descriptive statistics were determined using Microsoft Excel (version 16.0, Microsoft, Redmond, WA, USA). Pearson’s correlation test was performed to evaluate the strength of the association between continuous variables. RStudio software (version 4.1.3, Posit Software, PBC, Boston, MA, USA) was used to create the Lorenz curve.
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
PMC11276939_p10
|
PMC11276939
|
sec[2]/p[0]
|
3. Results
| 2.330078 |
biomedical
|
Study
|
[
0.904296875,
0.0011692047119140625,
0.0946044921875
] |
[
0.982421875,
0.017059326171875,
0.00013065338134765625,
0.00019228458404541016
] |
Riyadh city consists of 16 sub-municipalities with a population of 6,500,000 residents . More than a third of these residents (35.4%, 2,225,665) reside mainly in three sub-municipalities: Rawdah (15.4%, 968,565), Alorayjah (10.4%, 653,600), and North Riyadh (9.6%, 603,500) ( Table 1 ). A total of 632 PDHFs were geocoded by QGIS. Graphical data representation was used to show the distribution of PDHFs in Riyadh city. Figure 1 shows the population densities and private dental healthcare facilities’ spatial distribution in Riyadh city. Coverage areas of the dental facilities were mapped out and delineated by four buffer zones: 1 km, 3 km, 5 km, and >5 km, with each PDHF being a centroid .
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276939_p11
|
PMC11276939
|
sec[2]/p[1]
|
3. Results
| 3.382813 |
biomedical
|
Study
|
[
0.931640625,
0.0007352828979492188,
0.067626953125
] |
[
0.9990234375,
0.0010213851928710938,
0.00013124942779541016,
0.000039696693420410156
] |
Almost half of the PDHFs (48.3%, 305/632) were clustered in only three sub-municipalities: Rawdah (17.6%, 111/632), Olaya (16.8%, 106/632), and North Riyadh (13.9%, 88/632); however, these three sub-municipalities have about one-third of total Riyadh population (32.6%, 2,056,028/6,500,000). Furthermore, although Olaya had the second-highest number of PDHFs, it was not one of the most populated sub-municipalities, ranked fifth regarding total population. North Riyadh and Alorayjah had similar total populations; however, the number of PDHFs in North Riyadh (88) was almost twice of that located in Alorayjah (45) ( Table 1 ). On the other hand, Alshemaisi (1.1%, 7/632), Alsulay (1.9%, 12/632), and Alsharq (2.4%, 15/632) sub-municipalities had the lowest numbers of PDHFs. Looking at the districts’ level, Thrh Labn (3.79%, 24/632), Olaya (3.16%, 20/632), and Alnaseem Algharbi (3%, 19/632) districts had the highest numbers of PDHFs while there were 42 districts that did not have any PDHFs, mostly located in Albathaa (10 districts), Alshemaisi (8 districts), and Alsulay (5 districts) sub-municipalities ( Table 1 ).
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276939_p12
|
PMC11276939
|
sec[2]/p[2]
|
3. Results
| 2.089844 |
biomedical
|
Study
|
[
0.8427734375,
0.0024280548095703125,
0.1549072265625
] |
[
0.8095703125,
0.1893310546875,
0.000507354736328125,
0.00058746337890625
] |
The overall private dental healthcare facility-to-population ratio in Riyadh city was one PDHF per 9958 residents. Looking at the ratios of each sub-municipality, Olaya and Maather sub-municipalities had the largest PDHF-to-population ratios: and , respectively. This may indicate the oversaturation of PDHFs in these two sub-municipalities as Olaya was not the most populated sub-municipality and Maather was the third least populated. On the contrary, Alshemaisi had the smallest PDHF-to-population ratio (1:41,004), followed by Alsulay (1:25,490) and Albathaa (1:21,353) .
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276939_p13
|
PMC11276939
|
sec[2]/p[3]
|
3. Results
| 2.298828 |
other
|
Study
|
[
0.2247314453125,
0.0010309219360351562,
0.7744140625
] |
[
0.9755859375,
0.0238494873046875,
0.0002956390380859375,
0.0002105236053466797
] |
Looking at the covered areas in square kilometers (km 2 ) using the four buffer zones around each PDHF, the majority of (86.7%) of Riyadh city total area was located within 5 km of a PDHF, and almost three-quarters (72.5%) of the total area was within 3 km while only a little above one third (36.3%) was within 1 km buffer zones. The sub-municipalities that had the highest coverage within 1 km buffer zones were Alnaseem (78.6%), Maather (73.9%), and Olaya (69.7%). All the districts of the Alnaseem sub-municipality had at least half (50%) of the area located within 1 km from a PDHF, with the Alrawabi district having complete (100%) coverage within 1 km . Moreover, the districts with the highest coverage in the Maather sub-municipality were Olaya and Almuhamadeyah, with complete (100%) coverage within 1 km buffer zones, while other districts had at least 50% coverage within 1 km buffer zones except for the King Saud University area (42.6%). Half of the districts located in the Olaya sub-municipality (7/14) were completely (100%) covered within 1 km buffer zones: Altaawuon, Olaya, Almaseef, Alworood, King Fahad, Alnuzhah, and Almorouj districts, while the remaining districts had at least 60% coverage within 1 km buffer zones except for the King Abdulaziz district (8.1%) that had the least coverage, followed by the King Abdullah district (44.9%). On the other hand, some sub-municipalities were underserved in Riyadh city. The sub-municipalities that had the least coverage within the 1 km buffer zones were Alsulay (11.1%), Alsharq (13.4%), and Nmar (19.9%). Moreover, these three sub-municipalities had the largest percentages of areas located out of 5 km buffer zones: Alsharq (33.2%), Nmar (30.2%), and Alsulay (29.7%) .
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276939_p14
|
PMC11276939
|
sec[2]/p[4]
|
3. Results
| 4.117188 |
biomedical
|
Study
|
[
0.99267578125,
0.00046133995056152344,
0.007068634033203125
] |
[
0.99951171875,
0.0002532005310058594,
0.00019943714141845703,
0.00003081560134887695
] |
Pearson’s test showed an overall weak positive correlation between the number of PDHFs and total area of each sub-municipality (r = 0.29). However, there was a stronger overall positive correlation between the number of PDHFs and the total population in each sub-municipality (r = 0.74), indicating an increase in the number of PDHFs as the population increases; however, this does not necessarily mean the increase was even or followed a consistent proportion. Furthermore, the correlation between the mean individual income and number of PDHFs per district was negative in nine sub-municipalities: Alnaseem (r = −0.90), Alsharq (r = −0.72), Arqh (r = −0.47), North Riyadh (r = −0.44), Alshemaisi (r = −0.44), Olaya (r = −0.25), Nmar (r = −0.21), Maather (r = −0.16), and Rawdah (r = −0.05), while it was positive in the other six sub-municipalities: Aziziah (r = 0.69), Alsulay (r = 0.51), Albathaa (r = 0.38), Alorayjah (r = 0.23), Almalaz (r = 0.23), and Alshefa (r = 0.22). The Lorenz curve and Gini coefficient were determined to evaluate the distribution of PDHFs. The density of PDHFs corresponding to the area in square kilometers (km 2 ) was estimated. The Lorenz curve was plotted with the cumulative proportion of PDHFs on the x-axis and proportions of mean income and area on the y-axis . The curve in blue color represents the distribution of PDHFs in Riyadh city corresponding to the area with a Gini coefficient of 0.357, indicating a moderate level of disparity in the distribution of PDHFs corresponding to the area. The curve in red color represents the distribution of PDHFs corresponding to the mean income with a Gini coefficient of 0.207, indicating almost equality in the distribution of PDHFs in Riyadh city corresponding to the mean income.
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276939_p15
|
PMC11276939
|
sec[3]/p[0]
|
4. Discussion
| 2.083984 |
biomedical
|
Study
|
[
0.84619140625,
0.0023212432861328125,
0.151611328125
] |
[
0.9619140625,
0.037261962890625,
0.0005412101745605469,
0.0004374980926513672
] |
Accessibility to dental healthcare is a key factor affecting the utilization of dental services, in addition to financial reasons, attitudes toward dental care , and the availability of high-quality dental services . Enhancing access to healthcare is one of the goals of the Saudi Vision 2030, and the private healthcare sector is an essential partner to help in achieving this important goal. The dental healthcare private sector in Riyadh city has been growing rapidly over the past few years. However, there is a lack of information regarding the spatial distribution of PDHFs and a need for a more comprehensive analysis and details about the saturation of PDHFs. The distribution of PDHFs in Riyadh city is an important topic as it sheds light on the accessibility to dental healthcare services. Therefore, this study was conducted.
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276939_p16
|
PMC11276939
|
sec[3]/p[1]
|
4. Discussion
| 1.911133 |
biomedical
|
Study
|
[
0.833984375,
0.0018463134765625,
0.1639404296875
] |
[
0.958984375,
0.040313720703125,
0.00037384033203125,
0.0004229545593261719
] |
As of August 2023, there were 632 operating PDHFs registered in MOH. A Geographical Information System (GIS)-based approach was utilized in this study. The project started with analyzing the map of Riyadh city, its sub-municipalities, and districts. According to the governmental website of Riyadh Municipality Portal, Riyadh city is divided into 16 sub-municipalities. Fifteen sub-municipalities were included and analyzed in this study . Alhayer sub-municipality was excluded due to the lack of population statistics and the absence of registered PDHFs, which could be explained by the fact that it included mainly non-residential areas.
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276939_p17
|
PMC11276939
|
sec[3]/p[2]
|
4. Discussion
| 4.082031 |
biomedical
|
Study
|
[
0.994140625,
0.0005841255187988281,
0.0054168701171875
] |
[
0.99951171875,
0.00021064281463623047,
0.00012934207916259766,
0.000032961368560791016
] |
Each PDHF was treated as a central point and buffer zones were created around each one. Four levels of buffer zones were selected for this study with 1 km being the smallest as shown in Figure 2 . One kilometer represents the shortest straight-line distance (radius) around each PDHF and may not represent the actual route, which would likely be longer driving a car considering road obstacles and traffic. In addition, Riyadh is a metropolitan area and the capital city with significant traffic congestion (traffic congestion index = 21.98) . There is no universally approved distance for access to care. Riyadh city is considered the most congested city in Saudi Arabia with a peak vehicle speed of 46.7 km/h during morning and afternoon periods . Thus, the levels of buffer zones were set at 1 km, 3 km, 5 km, taking into consideration the time to travel to the nearest dental healthcare facility in each district and the relative saturation of PDHFs in Riyadh. Several sub-municipalities in Riyadh city showed multiple shared patterns of PDHFs distribution and PDHF-to-population ratios. For instance, Olaya, Maather, North Riyadh, and Rawdah sub-municipalities had the largest PDHF-to-population ratios at 1:4566, 1:4828, 1:6858, 1:8726, respectively. The percentages of the areas covered within 1 km buffer zones were Maather (73.9%), Olaya (69.7%), Rawdah (47.6%), and North Riyadh (39.4%). A total of 347 PDHFs (54.9% of included PDHFs) were located within these four sub-municipalities. This may indicate significant clustering of PDHFs in these sub-municipalities. On the other hand, less than 50% of the areas of Alshefa, Alsharq, Nmar, Aziziah, and Alsulay sub-municipalities were within 1 km from 92 facilities . The PDHF-to-population ratios in these sub-municipalities were 1:11,924, 1:12,289, 1:16,659, 1:18,127, and 1:25,490.25, respectively. This may demonstrate an uneven distribution of PDHFs with an inadequate number of facilities to serve these highly populated sub-municipalities. In Alnaseem, Almalaz, Alorayjah, and Albathaa sub-municipalities, there were 157 PDHFs distributed over 51 districts, with more than 50% of the area of these sub-municipalities being within 1 km of PDHFs . However, the PDHF-to-population ratios in these sub-municipalities were relatively low, precisely equal to 1:10,208, 1:11,102, 1:14,524, and 1:21,353, respectively, indicating the number of PDHFs might not be sufficient to serve the entire population in these sub-municipalities although the spatial distribution of PDHFs seemed relatively even . A more unique pattern of distribution was noticed in two sub-municipalities: Arqh and Alshemaisi. Arqh sub-municipality had the third largest PDHF-to-population ratio ; however, only 26.8% of the total areas were within 1 km of 29 PDHFs. This may demonstrate that although the number of PDHFs seemed quite adequate to serve the population, the facilities were not evenly distributed across these two sub-municipalities. In contrast, Alshemaisi sub-municipality had only seven PDHFs with the lowest PDHF-to-population ratio (1:41,004), and only 28.1% of the area was within a 1 km range of PDHFs, indicating a lack of private facilities in this sub-municipality. This could be explained by the presence of a large governmental healthcare facility, King Saud Medical City. In general, the findings of the present study showed a tendency of significant clustering of PDHFs in northern, central, and northeastern parts of Riyadh city.
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276939_p18
|
PMC11276939
|
sec[3]/p[3]
|
4. Discussion
| 3.955078 |
biomedical
|
Study
|
[
0.99658203125,
0.0003750324249267578,
0.0031337738037109375
] |
[
0.99755859375,
0.0005769729614257812,
0.0017843246459960938,
0.00005441904067993164
] |
Previous studies were conducted to analyze the distribution of dental services in KSA. Shubayr and his co-workers reported that there was an uneven distribution of dental services in the Jazan region, although there was a positive correlation between the distribution of dental clinics and population density across Jazan region, which is in agreement with the findings of this study. The overall dental clinics-to-population ratio reported in the Jazan region was one PDHF per 6279 residents, which is more favorable than the ratio found in the present study . This could be explained by the fact that Riyadh city is more densely populated, being the capital city, and that Shubayr and his co-workers included both public and private dental clinics in their analysis. On the contrary, a study conducted in 2020 reported a ratio of one dental clinic per 13,647 residents in Al Madina city, which is much lower although both public and private dental clinics were included . A study conducted in 2016 reported that the overall dental clinic-to-population ratio in Malaysia was 1:9000; 1:38,000 for public dental clinics and 1:13,000 for private facilities; however, the clinics were unevenly distributed across the country .
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276939_p19
|
PMC11276939
|
sec[3]/p[4]
|
4. Discussion
| 3.460938 |
biomedical
|
Study
|
[
0.99462890625,
0.0008320808410644531,
0.004741668701171875
] |
[
0.99853515625,
0.0009403228759765625,
0.0004200935363769531,
0.00007051229476928711
] |
Alsalleeh and his co-workers investigated the number of private dental clinics and the number of dentists in Riyadh city. They reported that private dental clinics were not evenly distributed in Riyadh city, which is in agreement with the present study. However, they determined the number of clinics in each sub-municipality without mapping out the exact distribution. Mapping the clinics in GIS should give further details regarding the facilities’ distribution, saturation, and accessibility in each district. The number of dental clinics included in their study was obtained from the Ministry of Health (MOH)—a total of 236 registered dental clinics. Comparing the number of dental clinics registered in 2016 to the number collected in this study shows that the number of dental healthcare facilities has tripled, signifying the rapid expansion of this sector over the past few years. Their results showed that Olaya and Rawdha had the highest number of dental clinics, 49 and 45, respectively, which aligns with the results found in the present study, 106 and 111, respectively. Alsalleeh and his co-workers collected information about the number of dentists and available specialties; however, almost one third of (31.4%, 74/236) the dental clinics refused to be enrolled.
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276939_p20
|
PMC11276939
|
sec[3]/p[5]
|
4. Discussion
| 3.34375 |
other
|
Study
|
[
0.18017578125,
0.0005183219909667969,
0.8193359375
] |
[
0.97802734375,
0.019805908203125,
0.0020904541015625,
0.0001951456069946289
] |
The Lorenz curve and Gini coefficient are essential tools in economics that provide insight into income distribution within a population. The Lorenz curve is a graphical representation of income distribution, plotting the cumulative percentage of income against the cumulative percentage of the population . In an ideal egalitarian society, the Lorenz curve would be a diagonal line indicating perfect income equality. However, in reality, it usually curves away from the diagonal line, reflecting varying degrees of income inequality. The Gini coefficient, derived from the Lorenz curve, is a numerical measure that quantifies this inequality which was introduced by the Italian statistician Corrado Gini in his work ‘ Variability and Mutability ’ published in Italian in 1912 . It ranges from 0 to 1, where 0 indicates perfect equality, and 1 indicates extreme inequality. The current study used a similar concept to explain the geographical distribution of PDHFs in Riyadh city and showed that there was a moderate level of disparity in the distribution of PDHFs corresponding to the area (Gini coefficient = 0.357). To further illustrate this, as the number of PDHFs increases, the Lorenz curve shifts towards the upper-right portion of the graph. In other words, a greater proportion of PDHFs is concentrated in a smaller proportion of the area as the number of PDHFs increases. However, there was almost equality in the distribution of PDHFs in Riyadh city corresponding to the mean income (Gini coefficient = 0.207). In other words, as the number of PDHFs increases, the Lorenz curve shifts towards the upper-left portion of the graph. This movement signifies an improvement in the mean income according to the increase in the number of PDHFs.
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276939_p21
|
PMC11276939
|
sec[3]/p[6]
|
4. Discussion
| 3.994141 |
biomedical
|
Study
|
[
0.9931640625,
0.0007405281066894531,
0.0059661865234375
] |
[
0.99951171875,
0.0002237558364868164,
0.0001537799835205078,
0.00004082918167114258
] |
This study is the first to evaluate the distribution of private dental healthcare facilities in Riyadh city using GIS and showed significant findings. However, in order to achieve optimal access to healthcare services, multiple factors in addition to the spatial distribution of PDHFs need to be analyzed, such as the actual number of dental chairs per facility, number of dentists and dental auxiliaries or clinicians’ full time equivalent (FTE) per facility, and the available dental specialties and types of services provided. In other words, the number of PDHFs may not accurately represent the exact capacity (number of dental chairs or dentists); therefore, obtaining additional information about the actual number of dental chairs and dental staff and analyzing it with regard to the spatial distribution is recommended for future studies, which may help in reaching a more detailed view of the supply and demand in dental health care services. The findings of the present study established a foundation for the spatial distribution of PDHFs in Riyadh city. One of the limitations of this study is that it did not include the governmental dental healthcare facilities, which are considered a significant sector in providing healthcare services in Saudi Arabia in general and Riyadh city in particular. It would be beneficial to also map out and integrate the governmental facilities in Riyadh city to attain a more comprehensive perspective. Another limitation is having data collected from a single point in time. In other words, Riyadh city is rapidly developing, and new dental healthcare facilities are continually being established.
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276939_p22
|
PMC11276939
|
sec[4]/p[0]
|
5. Conclusions
| 1.711914 |
other
|
Other
|
[
0.336181640625,
0.004611968994140625,
0.6591796875
] |
[
0.01123046875,
0.98779296875,
0.0004858970642089844,
0.00030422210693359375
] |
There was an uneven distribution of PDHFs in Riyadh city. Some areas were underserved while others were overserved in several sub-municipalities. This highlights the need for improving the distribution and accessibility of dental healthcare facilities in Riyadh city. It is fundamental to ensure that residents have optimal access to care. Policy-makers and investors are encouraged to target underserved areas rather than areas with significant clustering to improve access and quality of care.
|
[
"Najla S. Alrejaye",
"Faisal H. Alonazi",
"Zaid M. Alonazi",
"Rahf S. Alobaidi",
"Asma B. Alsaleh",
"Alanoud A. Alshami",
"Sultan A. Alshamrani",
"Seena T. Kaithathara"
] |
https://doi.org/10.3390/ijerph21070959
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276951_p0
|
PMC11276951
|
sec[0]/p[0]
|
1. Introduction
| 4.445313 |
biomedical
|
Review
|
[
0.9951171875,
0.0028209686279296875,
0.0023021697998046875
] |
[
0.02288818359375,
0.0025768280029296875,
0.97412109375,
0.000637054443359375
] |
Atopic dermatitis (AD) is a chronic, hereditary, recurrent, inflammatory skin disease that is clinically manifested by rashes, erythema, exudates, epidermal peeling, edema, and papules on the skin . The disease occurs at all stages of life, with a higher prevalence among women than men in adulthood . Modern medical research has shown that when various external factors (including exposure to hot and cold stimuli, chemicals, pollen and dust, infection) interact with various internal factors of the immune system (including family genetics, mental state, skin dysfunction), it triggers an abnormal response of the immune system, which ultimately leads to the development of AD . The pathogenesis of AD is often accompanied by inflammation and oxidative stress responses, which produce a large number of free radicals, further aggravating skin damage . The course of AD is divided into an acute phase and a chronic phase. The acute phase is the immune response mainly by T helper 2 cells (Th2), which manifests as Th2 cell infiltration, and the levels of interleukin (IL)-4, IL-5, and IL-13 were increased. The chronic phase is an immune response dominated by Th1 cells, manifested by delayed hypersensitivity through interferon-γ (IFN-γ) and IL-2 responses and excessive collagen accumulation, inducing skin thickening and tissue remodeling . There is no good cure for this disease in Western medicine. Glucocorticoids and immunosuppressants are used to treat AD, which can temporarily alleviate the related symptoms, but the long-term effect is not ideal, and there are more adverse reactions . Therefore, further development of drugs from traditional Chinese medicine is needed to effectively treat AD.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276951_p1
|
PMC11276951
|
sec[0]/p[1]
|
1. Introduction
| 4.289063 |
biomedical
|
Study
|
[
0.99951171875,
0.0003821849822998047,
0.000274658203125
] |
[
0.7255859375,
0.005550384521484375,
0.268310546875,
0.00079345703125
] |
Sinomenine (SIN, C 19 H 23 NO 4 ) is the main component of the Chinese herb Sinomenium acutum (Thunb.) Rehder & E.H. Wilson. Because of the poor water solubility of SIN, the pharmaceutical industry mostly uses its sinomenine hydrochloride (SINH) as the water-soluble salt form of SIN. Experiments have proved that SINH has many biological activities such as anti-oxidation, anti-inflammation, immunomodulation, and improving microcirculation . The existing clinical formulations of SINH are mainly used for rheumatoid arthritis and cardiac arrhythmias . The mechanisms of action of SINH include regulating the balance of Th17/Treg cells, increasing the level of IL-10 (mainly secreted by Treg cells), and decreasing the level of IL-17A mainly secreted by Th17 cells ; decreasing the activity of antigen-presenting cells and affecting the nuclear factor κB (NF-κB) pathway ; inhibiting the production of serum pro-inflammatory cytokines IL-1β and IL-6; and suppressing the expression of matrix metalloproteinases (MMP)-2 and MMP-9 proteins . In addition, SINH is able to inhibit the inflammatory response by reducing oxidative stress . Therefore, SINH has the potential to treat AD.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276951_p2
|
PMC11276951
|
sec[0]/p[2]
|
1. Introduction
| 4.191406 |
biomedical
|
Study
|
[
0.99951171875,
0.0004973411560058594,
0.0001608133316040039
] |
[
0.9990234375,
0.0004901885986328125,
0.0005388259887695312,
0.0001175999641418457
] |
In view of the problems of SINH with a short half-life, low oral bioavailability, and gastrointestinal irritation caused by high blood concentrations , this study aimed to explore a new sinomenine hydrochloride delivery system—SINH-liposome-hydrogel (SINH-L-H) system. SINH loaded into liposomes and evenly dispersed in hyaluronic acid colloidal hydrogel take advantage of their excellent biocompatibility and high hydration capacity, enabling the drug to remain on the surface of the skin for a longer period of time , improving the bioavailability of the drug and providing benefits for the treatment of atopic dermatitis. Due to their structural properties, the liposomes-in-hydrogel not only act as carriers but also achieve slow drug release and keep the affected area moist, which is crucial for the treatment of dry, inflammatory skin diseases such as AD. In addition, SINH-L incorporated into colloidal hydrogel provided the dual effect of enhanced drug permeability and sustained release to reduce skin lesions and provide antioxidant and anti-inflammatory effects . Therefore, this paper will construct a mouse model of atopic dermatitis, observe and evaluate the therapeutic effect of the SINH-L-H system on atopic dermatitis, explore the mechanism of action of the SINH-L-H system in the treatment of atopic dermatitis, and verify the effectiveness of the SINH-L-H system in the treatment of atopic dermatitis.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276951_p3
|
PMC11276951
|
sec[1]/sec[0]/p[0]
|
2.1. Molecular Docking of SIN as the Active Structure of SINH
| 4.132813 |
biomedical
|
Study
|
[
0.99951171875,
0.00018739700317382812,
0.0003561973571777344
] |
[
0.99951171875,
0.00036597251892089844,
0.00018548965454101562,
0.000054955482482910156
] |
The computer software Discovery Studio 4.5 was used to predict the interactions between the components of the formula. Through software screening, the three-dimensional structure of proteins IL4 and IL2 combined with SIN was selected, and the results showed that SIN had a good docking effect with IL4 and IL2. There are pi-alkyl and carbon-hydrogen bonds between SIN and IL4 . There are van der Waals forces, pi-alkyl, and carbon-hydrogen bonds between SIN and IL2, and there is also a pi-pi stacked interaction between molecules . In the same space, there are carbon-hydrogen bonds and bump interactions between SIN, cholesterol, and phospholipid in different conformations . There is also a bump interaction between SIN and hydrogel .
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276951_p4
|
PMC11276951
|
sec[1]/sec[1]/p[0]
|
2.2. Basic Characteristics of SINH-L-H
| 4.164063 |
biomedical
|
Study
|
[
0.99951171875,
0.0002199411392211914,
0.00023496150970458984
] |
[
0.99951171875,
0.00039124488830566406,
0.0002206563949584961,
0.00006574392318725586
] |
The absorbance of SINH was measured by an ultraviolet spectrophotometer; SINH at 10–60 μg/mL concentration is proportional to their absorbance , and the linear relationship is good . The SINH-loaded liposomes-in-hydrogel (SINH-L-H) is a creamy white, homogeneous, and fine hydrogel with no viscous lumps and low fluidity, remaining colloidal hydrogel at room temperature . The liposomes in SINH-L-H were spherical and uniformly dispersed in the hyaluronic acid hydrogel (HA) via Cyro-EM ; the size of the SH-L is about 133.8 ± 14.5. Viscosity measurements showed the viscosity of SINH-L-H was 9.83 ± 0.11 mPa·s at 25 °C, and its pH was 7.27 ± 0.01. The encapsulation rate of SINH-L is 72.27%.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276951_p5
|
PMC11276951
|
sec[1]/sec[1]/p[1]
|
2.2. Basic Characteristics of SINH-L-H
| 4.128906 |
biomedical
|
Study
|
[
0.99951171875,
0.0002923011779785156,
0.0003211498260498047
] |
[
0.99951171875,
0.0003478527069091797,
0.0003230571746826172,
0.000059604644775390625
] |
Stability measurements showed that SH-L-H did not change significantly when stored for 30 days under refrigeration at 4 °C. The appearance and viscosity of SH-L-H did not differ from day 0, indicating that SH-L-H was stable under these conditions. SH-L-H is more variable when stored at ambient conditions: for the first 14 days, the SH-L-H was similar to the initial preparation, creamy white, homogeneous, and fine in texture; on the 21st day, the color of the SH-L-H changed from creamy white to yellowish and the viscosity decreased; on the 30th day, the color of the SH-L-H continued to deepen to yellow, and there was stratification and a decrease in viscosity. The above indicates that SH-L-H is unstable when stored under these conditions and that the drug is easily released from the liposomes and oxidized and discolored ( Table 1 ).
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276951_p6
|
PMC11276951
|
sec[1]/sec[2]/p[0]
|
2.3. In Vitro/Ex Vivo Dialysis Diffusion Dialysis
| 2.597656 |
biomedical
|
Study
|
[
0.99462890625,
0.0007176399230957031,
0.004459381103515625
] |
[
0.98095703125,
0.0178680419921875,
0.0008020401000976562,
0.0003409385681152344
] |
The in vitro and ex vivo release profiles of SINH, SINH-L, SINH-H, and SINH-L-H are shown below . It can be seen that the sample from the upper diffusion pool gradually penetrates into the lower diffusion pool as the release time increases.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276951_p7
|
PMC11276951
|
sec[1]/sec[2]/p[1]
|
2.3. In Vitro/Ex Vivo Dialysis Diffusion Dialysis
| 4.179688 |
biomedical
|
Study
|
[
0.99951171875,
0.0003006458282470703,
0.00028777122497558594
] |
[
0.99951171875,
0.00021779537200927734,
0.00026416778564453125,
0.00005793571472167969
] |
In the in vitro diffusion experiment, the release rate of the SH group was greater than the other three groups during the first 11 h. After 11 h, the release rate of SINH in SINH-H began to exceed that of the SINH group, which indicates that the hydrophilic porous structure of SINH-H promoted the release of SINH, so that SINH rapidly passed through the dialysis membrane into the lower diffusion pool, and the release rate of SINH in SINH-H did not show a large change with the increase in time, and the release curve showed that it entered the plateau period at about 12 h, and the final release degree could reach about 77%; the largest amount of SINH released by SINH-L-H occurs at 96 h, up to about 55%, this may be due to the fact that SINH-L-H possesses the three-dimensional mesh structure of HA hydrogels and the phospholipid bilayer of liposomes, and thus SINH is tightly bound in it and cannot be easily released.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276951_p8
|
PMC11276951
|
sec[1]/sec[2]/p[2]
|
2.3. In Vitro/Ex Vivo Dialysis Diffusion Dialysis
| 4.183594 |
biomedical
|
Study
|
[
0.99951171875,
0.0002930164337158203,
0.0003063678741455078
] |
[
0.99951171875,
0.00024390220642089844,
0.0003237724304199219,
0.00005632638931274414
] |
In the ex vivo diffusion experiment, the total diffusion rate was SINH-L > SINH-L-H > SINH-H > SINH, and SINH-L reached the highest permeation efficiency of about 46% at 96 h, while the release rate of SINH only reached 30% at this time, and the liposomes contained phospholipids similar to skin tissues, which were “similarly compatible”. Therefore, the release of SINH in SINH-L is the greatest, while SINH is in the free state and less compatible with the skin, so the amount and speed of penetration through the skin are smaller. SINH-L-H contains phospholipids and HA, which are also contained in skin tissues, and although it can contact a larger area of skin, it also takes time to cross the three-dimensional structure of the phospholipid bilayer and hydrogel, so the diffusion rate of SINH in SINH-L-H is lower than that of SINH-L; the amount and rate of release of SINH in SINH-H with the help of HA is slightly higher than that of SINH.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276951_p9
|
PMC11276951
|
sec[1]/sec[2]/p[3]
|
2.3. In Vitro/Ex Vivo Dialysis Diffusion Dialysis
| 4.136719 |
biomedical
|
Study
|
[
0.99951171875,
0.0002694129943847656,
0.00023043155670166016
] |
[
0.99951171875,
0.0002663135528564453,
0.00032806396484375,
0.00005453824996948242
] |
Comparing the release profiles of in vitro and ex vivo diffusion, we found that the speed of SINH through the dialysis membrane was faster and the amount of transmission was greater in each group, while the transdermal speed of the drug in each group showed irregularities and significant differences. Dialysis membrane is a homogeneous porous membrane of organic polymers that mainly relies on the osmotic pressure generated by the different concentration gradients on both sides of the membrane to promote the flow of solutes, so the speed and amount of SINH passage mainly depend on the osmotic pressure on both sides of the membrane. The skin includes the dermis and epidermis with abundant cells and blood vessels, and it will take more time for the drug to pass through the skin. The principle of similar compatibility between liposomes and cell membranes means that more SINH in SINH-L and SINH-L-H is deposited in the skin.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276951_p10
|
PMC11276951
|
sec[1]/sec[3]/sec[0]/p[0]
|
2.4.1. The Scavenging Rate on Hydroxyl Radicals
| 4.140625 |
biomedical
|
Study
|
[
0.99951171875,
0.00019371509552001953,
0.000308990478515625
] |
[
0.9990234375,
0.0004591941833496094,
0.00022900104522705078,
0.000058710575103759766
] |
In the Fenton reaction, hydroxyl radicals react with salicylic acid to generate 2,3-dihydroxybenzoic acid, which exhibits a special absorption at 510 nm . SINH had antioxidant activity in the reaction system and could reduce the production of hydroxyl radicals. Therefore, the generation of 2,3-dihydroxybenzoic acid in the reaction system decreased, and the color became lighter. It was indicated that the clearance rate of SINH for 2,3-dihydroxybenzoic acid was directly proportional to the concentration of SINH in the concentration range of 0.2 to 1.0 mg/mL. The IC 50 of SINH for scavenging hydroxyl radicals was about 0.7034 mg/mL.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276951_p11
|
PMC11276951
|
sec[1]/sec[3]/sec[0]/p[1]
|
2.4.1. The Scavenging Rate on Hydroxyl Radicals
| 4.148438 |
biomedical
|
Study
|
[
0.99951171875,
0.00025463104248046875,
0.00022161006927490234
] |
[
0.99951171875,
0.0002467632293701172,
0.00040078163146972656,
0.00006276369094848633
] |
In the antioxidant reaction experiment, the drugs in SINH-L-H were surrounded by liposomes and hydrogels, and SINH was difficult to release. However, because of the synergistic effect of the antioxidant capacity of liposomal hydrogel and SINH itself, the clearance rate of SINH-L-H was higher than that of SINH. At the concentration of 0.2 mg/mL, the scavenging rates of SINH, SINH-L, SINH-H, and SINH-L-H on hydroxyl radicals were about 0.42 ± 0.1%, 6.73 ± 1.7%, 7.98 ± 3.4%, and 3.36 ± 1.5%, respectively. The clearance rate of SINH was lower than that of the same concentration formulation . In the Fenton reaction, the removal effect of SINH-L-H was lower than that of SINH-L and SINH-H but higher than that of SINH. This showed that SINH-L-H had better stability and durability while maintaining the sinomenine’s effect so that the drug could work in the body for a longer time.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11276951_p12
|
PMC11276951
|
sec[1]/sec[3]/sec[1]/p[0]
|
2.4.2. The Inhibitory Rate on ABTS Radicals
| 3.728516 |
biomedical
|
Study
|
[
0.998046875,
0.00032639503479003906,
0.00151824951171875
] |
[
0.62255859375,
0.375244140625,
0.0015010833740234375,
0.0007710456848144531
] |
The 1:1 mixture reaction of ABTS and K 2 S 2 O 8 produced stable cationic free radicals ABTS + . The maximum absorption wavelength of ABTS + is 734 nm, and the reaction between antioxidants and ABTS + will cause the solution to fade . The stronger the antioxidant capacity, the lighter the color of the solution, and the higher the free radical scavenging rate.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276951_p13
|
PMC11276951
|
sec[1]/sec[3]/sec[1]/p[1]
|
2.4.2. The Inhibitory Rate on ABTS Radicals
| 4.1875 |
biomedical
|
Study
|
[
0.99951171875,
0.0002551078796386719,
0.0003223419189453125
] |
[
0.99951171875,
0.00022029876708984375,
0.0003211498260498047,
0.00005716085433959961
] |
The scavenging ability of SINH on ABTS + was directly proportional to the concentration between 0.001 and 0.02 mg/mL, and the higher the concentration, the stronger the scavenging ability. The IC 50 value of SINH was about 0.0115 mg/mL. The reaction steps of SINH, SINH-L, SINH-H, and SINH-L-H with the same concentration of 0.001 mg/mL have clearance rates of 11.33 ± 4.21%, 5.76 ± 0.32%, 6.96 ± 0.41%, and 5.74 ± 0.36% for ABTS + , respectively . The clearance rate of ABTS + in the preparations was lower than that of SINH. The clearance of ABTS + was lower than that of SINH. This was because SINH was encapsulated in the liposomal hydrogel, and the release rate of SINH was slow. For a certain period of time, the free radical scavenging ability of SINH-L-H was weaker than that of SINH. But SINH-L-H had a slow release effect, which made it have a long-term effect. Therefore, SINH-L-H had the ability for long-term, slow release.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276951_p14
|
PMC11276951
|
sec[1]/sec[4]/sec[0]/p[0]
|
2.5.1. Measurements Results of Skin Irritation of SINH-L-H
| 4.15625 |
biomedical
|
Study
|
[
0.9990234375,
0.000583648681640625,
0.00025653839111328125
] |
[
0.99951171875,
0.00034928321838378906,
0.0002827644348144531,
0.0000852346420288086
] |
In the single-dose skin irritation test, no mice in the B-L-H and SINH-L-H groups showed any skin changes within 72 h after administration ( Table 2 ). In multiple skin irritation experiments, the mice in the B-L-H (Blank-loaded liposomes-in-hydrogel) and SINH-L-H groups did not show any erythema or edema within 7 days after administration, indicating that the formula matrix we selected was safe and non-toxic ( Table 3 ). In terms of scoring results, B-L-H and SINH-L-H were safe because of no irritation to intact mouse skin.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276951_p15
|
PMC11276951
|
sec[1]/sec[4]/sec[1]/p[0]
|
2.5.2. General Condition of Mice and Manifestation of Skin Lesions
| 4.136719 |
biomedical
|
Study
|
[
0.99951171875,
0.0004572868347167969,
0.0002033710479736328
] |
[
0.99951171875,
0.0002377033233642578,
0.0004031658172607422,
0.0000852346420288086
] |
The establishment of the AD mouse model and the time point of drug administration according to Figure 5 A. The body weight and skin thickness of each group of mice are shown in Figure 5 B, and the skin healing is shown in Figure 5 C. The mice in the blank group showed an increasing trend in body weight and skin thickness, with smooth hair, good condition, and no abnormal behavior; the ears were red and transparent, with an intact appearance and clearly visible blood vessels. The body weight of mice in the other groups peaked on the fourth day and decreased thereafter, among which the body weight of mice in the positive control group with ointment decreased more rapidly, presumably due to the side effects caused by dexamethasone as a kind of glucocorticoids. After 2,4-dinitrochlorobenzene (DNCB) excitation twice, erythema appeared on the dorsal skin of mice in each group and gradually thickened and dried, with scabs appearing, and mice scratched frequently and became agitated. On the 4th day, the erythema and thickening of the skin of the mice in each group were gradually reduced, and the skin of the mice in the positive control group was obviously thinner, with slight folds and erythema and no hair growth at the excitation site. As shown in Figure 5 D, compared with the model group, the skin injury scores of mice in the model group were significantly higher than those in the normal control group, and the skin scores of mice in the positive control group were significantly lower than those in the SINH-L-H group.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276951_p16
|
PMC11276951
|
sec[1]/sec[4]/sec[2]/p[0]
|
2.5.3. Ear Swelling in Mice
| 3.621094 |
biomedical
|
Study
|
[
0.9990234375,
0.00046706199645996094,
0.0007162094116210938
] |
[
0.99853515625,
0.001190185546875,
0.0003159046173095703,
0.00010913610458374023
] |
Except for the blank group, the ears of mice in the other groups showed swelling and crusting after excitation, and the symptoms significantly improved after SINH-L-H administration. Compared with the blank group, the swelling and crusting status of the remaining groups increased to varying degrees, with the most significant change in mice’s status in the model group. Compared with the model group, the mice were administered to the SINH-L-H group with the most significant ear changes .
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11276951_p17
|
PMC11276951
|
sec[1]/sec[4]/sec[3]/p[0]
|
2.5.4. Mouse Organ Index
| 4.050781 |
biomedical
|
Study
|
[
0.99951171875,
0.00026535987854003906,
0.00020813941955566406
] |
[
0.99951171875,
0.00023818016052246094,
0.0004296302795410156,
0.00006371736526489258
] |
The effect of SINH-L-H on AD was initially evaluated by organ indices, including the spleen index and thymus index, and the results are shown in Figure 6 C. Compared with the blank group, the spleen index and thymus index of mice in the model group increased, and the differences were statistically significant; compared with the model group, the spleen index and thymus index of mice using SINH, SINH-L, SINH-H, and SINH-L-H decreased, and the effect of using SINH-L-H was almost similar to that of using dexamethasone, indicating that SINH and its three preparations all have good efficacy on AD.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276951_p18
|
PMC11276951
|
sec[1]/sec[4]/sec[4]/p[0]
|
2.5.5. Malondialdehyde (MDA) in Mouse Organ
| 4.082031 |
biomedical
|
Study
|
[
0.99951171875,
0.0002415180206298828,
0.00022685527801513672
] |
[
0.99951171875,
0.00018584728240966797,
0.0002987384796142578,
0.00005644559860229492
] |
MDA, one of the products of lipid peroxidation, is one of the important indexes to measure the degree of oxidative damage. The content of MDA in each mouse tissue is shown in Figure 6 D,E. Compared with the blank group, the content of MDA in the skin and liver of mice in the model group increased with significant differences, and the content of MDA in the kidney also increased. All MDA levels in the skin, liver, and kidney of mice in the SINH, SINH-L, SINH-H, and SINH-L-H groups also decreased, with the most pronounced decrease in mice in the SINH-L-H group, indicating that SH-L-H was the most effective in AD among these three groups.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276951_p19
|
PMC11276951
|
sec[1]/sec[4]/sec[5]/p[0]
|
2.5.6. HE Staining
| 4.136719 |
biomedical
|
Study
|
[
0.99951171875,
0.00044846534729003906,
0.00020611286163330078
] |
[
0.99951171875,
0.00021982192993164062,
0.00035762786865234375,
0.00008058547973632812
] |
The results of HE staining of the dorsal skin of mice in each group are shown in Figure 6 F. Compared with the blank group, the dorsal skin of the model mice showed obvious hyperplasia, significant thickening of the epidermal layer, intracellular and intercellular edema, and a large amount of inflammatory infiltration around the blood vessels in the dermis, showing a severe inflammatory state overall. In the control group, the structure of each layer was more complete with clear borders; the epidermis was not obviously keratinized; the spiny layer was mildly hyperplastic; there was mild intracellular and intercellular edema; and the inflammatory infiltrate around the blood vessels in the dermis was mild. The rest of the administered groups were less symptomatic than the model group, showing varying degrees of epidermal layer thickening, intracellular and intercellular edema, and vascular inflammatory infiltration, with the SINH-L-H group producing the mildest manifestations .
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276951_p20
|
PMC11276951
|
sec[2]/p[0]
|
3. Discussion
| 3.642578 |
biomedical
|
Study
|
[
0.99951171875,
0.00019371509552001953,
0.0002758502960205078
] |
[
0.99609375,
0.0026378631591796875,
0.0010776519775390625,
0.00018703937530517578
] |
AD is a common skin disease that can have a serious impact on a patient’s life. It is currently considered to have a strong correlation with susceptibility genes, epidermal barrier dysfunction, and immune dysfunction. The AD model was established by DNCB, leading to epidermal barrier dysfunction, and the therapeutic effect of SINH-L-H on AD was studied.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276951_p21
|
PMC11276951
|
sec[2]/p[1]
|
3. Discussion
| 4.09375 |
biomedical
|
Study
|
[
0.99951171875,
0.00019824504852294922,
0.0001653432846069336
] |
[
0.9990234375,
0.00025153160095214844,
0.000583648681640625,
0.00005823373794555664
] |
Liposomes were reported to be an excellent drug carrier, which could load drugs for the treatment of skin injuries, and hydrogels could clear wound exudates, provide a moist environment, and stimulate and guide tissue regeneration, which could be used as external materials for wounds . In this study, hyaluronic acid was selected for the colloidal hydrogel matrix. Hyaluronic acid itself is a polysaccharide and has additional characteristics that make it very suitable for drug delivery systems, such as biocompatibility, antiviral, antibacterial, and anti-tumor properties. The combination of liposomes and hyaluronic acid to load drugs could form an excellent delivery system to enable the drug to be delivered to its target. The successful preparation of SINH-L-H had the characteristics of a slow and controlled release. In addition, SINH-L-H prepared in the study had stable properties, good dispersion, and an excellent dermal penetration effect, which was in line with the expected effect.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276951_p22
|
PMC11276951
|
sec[2]/p[2]
|
3. Discussion
| 4.496094 |
biomedical
|
Review
|
[
0.99853515625,
0.000789642333984375,
0.0007548332214355469
] |
[
0.305908203125,
0.0038967132568359375,
0.689453125,
0.0007643699645996094
] |
The onset of AD could be caused by multiple factors. Abnormal Notch signaling pathways can induce the development of severe AD, while normal Notch signaling pathways can inhibit the production of thymic stromal lymphopoietin (TSLP) in keratinocytes and alleviate the pathogenesis of AD . Pro-inflammatory cytokines can promote the occurrence of AD, including TSLP, IL-25, and IL-33 . Th2 cells are derived from the immune differentiation of T cells and serve as pro-inflammatory mediators in AD. Activate Th2 cells, promote specific cytokine-related inflammation (IL-4, IL-5, IL-13), an increase in eosinophils, and the production of immunoglobulin E (IgE) . B cells participate in T cell activation and Th2 production and differentiate into cytokine-producing cells that may alter the differentiation of effector T cells . One of the main signs of AD is an increase in serum total IgE levels. Activated Th2 cells release IL-4 and IL-13, which promote B cells to produce IgE antibodies through the signal transducer and transcriptional activator (STAT) pathway . The various pathogenic factors mentioned above can serve as targets for the treatment of AD.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276951_p23
|
PMC11276951
|
sec[2]/p[3]
|
3. Discussion
| 4.109375 |
biomedical
|
Study
|
[
0.99951171875,
0.00018918514251708984,
0.00019180774688720703
] |
[
0.9990234375,
0.00025343894958496094,
0.000579833984375,
0.00006115436553955078
] |
In order to better predict the target of action between AD and SIN, we used Genecards (GeneCards—Human Genes|Gene Database|Gene Search ( https://www.genecards.org/ ), retrieved from 15 January 2023) to screen out the target of disease and drug action and created a Venn diagram to find the intersection of the target of action . DIVID (DAVID Functional Annotation Bioinformatics Microarray Analysis ( ncifcrf.gov ), retrieved from 16 January 2023) was used to find the relevant pathways of the intersection genes, and bioinformatics ( bioinformatics.com.cn ) was used to enrich the pathways and find the best pathway . At the same time, use STRING (STRING: functional protein association networks ( string-db.org ), retrieved from 17 January 2023) to create a Protein-Protein interaction network (PPI) graph of the intersecting genes and identify the genes that have the most significant impact . Finally, the most relevant gene targets were extracted from the screened pathways and rescreened with significant genes in STRING. IL2 and IL4 were selected as the predicted targets for SIN treatment of AD.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276951_p24
|
PMC11276951
|
sec[2]/p[4]
|
3. Discussion
| 4.003906 |
biomedical
|
Study
|
[
0.99951171875,
0.0001888275146484375,
0.00014448165893554688
] |
[
0.9658203125,
0.0127105712890625,
0.021270751953125,
0.00040793418884277344
] |
Studies have shown that there is an excess of reactive oxygen species in the skin of atopic dermatitis patients, and these reactive oxygen species can cause high oxidative stress, resulting in oxidative damage to skin cell DNA and proteins, further aggravating skin inflammation and damage . SINH, SINH-L, SINH-H, and SINH-L-H are able to remove reactive oxygen species, which helps reduce oxidative damage to cells due to the accumulation of reactive oxygen species. By reducing the accumulation of reactive oxygen species, SINH-L-H may help reduce oxidative damage to skin cells and improve skin barrier function, thereby relieving the symptoms of atopic dermatitis. Therefore, SINH-L-H is a potential drug for the treatment of AD.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276951_p25
|
PMC11276951
|
sec[3]/sec[0]/p[0]
|
4.1. Materials
| 1.585938 |
biomedical
|
Other
|
[
0.9833984375,
0.0012722015380859375,
0.01541900634765625
] |
[
0.04669189453125,
0.951171875,
0.0009393692016601562,
0.0013856887817382812
] |
Sinomenine hydrochloric (≥98%, China), cholesterol (AR, Sinopharm Chemical Reagent Co., Ltd., Shanghai, China), soy lecithin (Shanghai Jinsong Industry Co., Ltd., Shanghai, China), absolute ethanol (AR, Shanghai RichJoint Chemical Reagents Co., Ltd., Shanghai, China), hyaluronic acid (HA, 99%, Shandong Xiya Reagents Co., Ltd., Linyi, China), 1,1-diphenyl-2-picrylhydrazyl (DPPH, 98%, Shanghai Yuanye Biology Science and Technology Co., Ltd., Shanghai, China), H 2 O 2 (AR, Shanghai SuYi Chemical Reagent Co., Ltd., Shanghai, China), FeSO 4 ·7H 2 O (AR, Sinopharm Chemical Reagent Co., Ltd., Shanghai, China), thiobarbituric acid (TBA, 98%, Shanghai Yuanye Biology Science and Technology Co., Ltd., Shanghai, China), trichloroacetic acid (TCA, AR, Tianjin Damao Chemical Reagent Factory, Tianjin, China), 2,4-dinitrochlorobenzene (DNCB, Shandong Xiya Reagents Co., Ltd., Linyi, China), 2,2′-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS, 98%, Shanghai Macklin Biochemical Technology Co., Ltd., Shanghai, China), K 2 S 2 O 8 (99.5%, Macklin Biochemical Technology Co., Ltd., Shanghai, China), phosphate buffered saline (PBS).
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276951_p26
|
PMC11276951
|
sec[3]/sec[1]/p[0]
|
4.2. Animals
| 2.298828 |
biomedical
|
Study
|
[
0.99755859375,
0.0007138252258300781,
0.0017499923706054688
] |
[
0.595703125,
0.3994140625,
0.002689361572265625,
0.0024471282958984375
] |
Healthy Kunming mice (female, 20 ± 2 g) were provided by the Animal Experimental Center of the Anhui University of Traditional Chinese Medicine (Hefei, China). All animal experiments conform to the guidelines approved by the Ethics Committee of the Anhui University of Traditional Chinese Medicine (Hefei, China). Animals are kept under constant environmental conditions (25 ± 2 °C, 40–70% relative humidity), and provided with unlimited supplies of food and water.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276951_p27
|
PMC11276951
|
sec[3]/sec[2]/p[0]
|
4.3. Preparation SINH-L, SINH-H, and SINH-L-H
| 4.109375 |
biomedical
|
Study
|
[
0.99951171875,
0.00022423267364501953,
0.00025463104248046875
] |
[
0.9990234375,
0.0007724761962890625,
0.00024378299713134766,
0.00006473064422607422
] |
The synthesis of SINH-L, SINH-H, and SINH-L-H was adopted from our previous work as cited . Took 0.3 g of phospholipids and 0.1 g of cholesterol in a rotary evaporation flask, added the appropriate amount of absolute ethanol to dissolve, fixed the flask on a rotary evaporator to rotated and evaporated to form a thin film, set the temperature at 70 °C, vacuum pressure at 70 kPa, speed at 100 r/min until the absolute ethanol evaporated completely. Then, 10 mL of 2 mg/mL of SINH solution was added to the film and rotated and hydrated for 30 min to form a milky white suspension. The suspension was sonicated for 10 min and filtered across the 0.22 μm microporous membrane three times to obtain SINH-L. 0.1 g HA was added to the prepared 10 mL SINH-L suspension and stirred at the speed of 100 rpm for 12 h with a magnetic stirrer till HA naturally swelled to form a uniform hydrogel (SINH-L-H). 0.1 g of HA was also added to 10 mL of SINH solution, and the same was used to form SINH-H. In addition, blank liposomes (B-L) with PBS instead of SINH solution, blank liposome hydrogels (B-L-H) with B-L instead of SINH-L, and blank HA hydrogels (B-H) with PBS instead of SINH solution were prepared.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276951_p28
|
PMC11276951
|
sec[3]/sec[3]/sec[0]/p[0]
|
4.4.1. Appearance and Morphology of Cryo-EM
| 2.861328 |
biomedical
|
Study
|
[
0.994140625,
0.0004181861877441406,
0.005428314208984375
] |
[
0.94580078125,
0.053314208984375,
0.0005803108215332031,
0.00035953521728515625
] |
The prepared SINH-L suspension was placed in a transparent glass test tube to observe its appearance. An appropriate amount of prepared SINH-L was mixed with a turbine apparatus, and the morphological characteristics of SINH-L were observed with cryo-EM.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276951_p29
|
PMC11276951
|
sec[3]/sec[3]/sec[1]/p[0]
|
4.4.2. Particle Size and Zeta Potential
| 4.027344 |
biomedical
|
Study
|
[
0.9990234375,
0.0001989603042602539,
0.0009751319885253906
] |
[
0.99951171875,
0.0004131793975830078,
0.0001310110092163086,
0.00003618001937866211
] |
First, we applied the Malvern potential particle simeter ( n = 3) to measure the particle size of SINH-L and the electrophoretic mobility of SINH-L in electric fields. The electrophoretic mobility was then converted to the Zeta potential value according to the Smoluchowski equation.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276951_p30
|
PMC11276951
|
sec[3]/sec[3]/sec[2]/p[0]
|
4.4.3. Encapsulation Rate and Drug Load
| 4.128906 |
biomedical
|
Study
|
[
0.99951171875,
0.0002789497375488281,
0.00023365020751953125
] |
[
0.99951171875,
0.00046133995056152344,
0.0001862049102783203,
0.000059664249420166016
] |
In this experiment, the drug amount of free sinomenine hydrochloride in SH-L suspension was obtained by the high-speed centrifugal method, and the drug amount of total sinomenine hydrochloride in SINH-L suspension was obtained by the ethanol demulsification method: 1 mL SINH-L suspension was precisely measured and diluted by adding an appropriate amount of PBS solution. After centrifugation at 15,000 RPM for 10 min, the supernatant was taken to measure the dosage of free SINH ( W 1 ) at 262 nm. In addition, 1 mL SINH-L suspension was precisely measured and placed in a 10 mL volumetric bottle; anhydrous ethanol was added to the scale line, and the volumetric bottle was placed in a CNC ultrasonic cleaner for 30 min for ultrasonic demulsification. An appropriate amount of demulsified solution was taken and measured at 262 nm to measure the dosage of total SINH ( W 2 ). Calculate the EE of SINH-L according to the following Equation: E E = W 2 − W 1 × 100 % W 2
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276951_p31
|
PMC11276951
|
sec[3]/sec[3]/sec[2]/p[1]
|
4.4.3. Encapsulation Rate and Drug Load
| 2.568359 |
biomedical
|
Study
|
[
0.9892578125,
0.0004482269287109375,
0.0103302001953125
] |
[
0.75048828125,
0.2471923828125,
0.00160980224609375,
0.0006427764892578125
] |
Among them, W 1 represents the amount of free SINH in liposome suspension, and W 2 represents the amount of total SINH in liposome suspension.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276951_p32
|
PMC11276951
|
sec[3]/sec[4]/p[0]
|
4.5. Molecular Docking
| 4.089844 |
biomedical
|
Study
|
[
0.99951171875,
0.0001952648162841797,
0.000148773193359375
] |
[
0.9990234375,
0.0004036426544189453,
0.00034999847412109375,
0.00006783008575439453
] |
The 2D molecular structures of SIN, hyaluronic acid hydrogel, phospholipid, and cholesterol were obtained from PubChem. They were imported into Discovery Studio 4.5 and exported as small-molecule compound files in SDF format. Then, we downloaded the core target proteins IL4 and IL6 from the UniProt database and selected the appropriate protein structure. Finally, after ligand extraction, hydrogenation, and water extraction, the docking program of Discovery Studio 4.5 was used for docking between small molecules and therapeutic targets. A molecular docking pattern diagram was achieved.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276951_p33
|
PMC11276951
|
sec[3]/sec[5]/p[0]
|
4.6. Ex Vivo/Ex Vivo Dialysis Diffusion Dialysis of SH-L-H
| 4.125 |
biomedical
|
Study
|
[
0.99951171875,
0.0002663135528564453,
0.00019633769989013672
] |
[
0.9990234375,
0.0007305145263671875,
0.000286102294921875,
0.00006914138793945312
] |
We performed this experiment using the Franz diffusion cell. For in vitro diffusion: first fill each diffusion cell with diffusion solution (PBS) and add a stirrer of appropriate size. A dialysis membrane of appropriate size was fixed in the middle of the upper and lower cells of the diffusion cell, and 1 mL of SH, SH-L, SH-L-H, and their corresponding blanks were added to the upper cell, respectively. At 5 min, 30 min, 60 min, 120 min, … 720 min, 1440 min, 2160 min, and 2880 min, 2 mL of samples were aspirated and immediately supplemented with the same volume of PBS solution. The absorbance was measured at 262 nm using a UV spectrophotometer and the corresponding cumulative drug release rates were calculated according to the Equation.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276951_p34
|
PMC11276951
|
sec[3]/sec[5]/p[1]
|
4.6. Ex Vivo/Ex Vivo Dialysis Diffusion Dialysis of SH-L-H
| 4.15625 |
biomedical
|
Study
|
[
0.99951171875,
0.00021266937255859375,
0.00022470951080322266
] |
[
0.9990234375,
0.00079345703125,
0.00026106834411621094,
0.00006103515625
] |
For the ex vivo skin dialysis experiments, we used the dorsal skin of Kunming mice, and the other operations were the same as for dialysis membrane diffusion. R % = C n × V n + ∑ i = 1 n − 1 C i × V Q t × 100 % where “ R ” is the cumulative drug release rate of SH at the different sampling points, “ C n ” is the mass concentration of SH at the nth time point (μg/mL), “ V n ” is the volume of the solution sampled at the nth time point (mL), “ C i ” is the mass concentration of SH in the receiving solution at the sampling point ( i ≤ n − 1) (μg/mL), “ V ” is the total volume of the lower cells (mL), and “ Q t ” is the theoretical drug content .
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276951_p35
|
PMC11276951
|
sec[3]/sec[6]/sec[0]/p[0]
|
4.7.1. The Scavenging Rate on Hydroxyl Radicals
| 4.125 |
biomedical
|
Study
|
[
0.9990234375,
0.0003478527069091797,
0.0004372596740722656
] |
[
0.9990234375,
0.0007462501525878906,
0.0001571178436279297,
0.000053882598876953125
] |
SINH (0.2, 0.4, 0.6, 0.8, and 1.0 mg/mL) was added to the Fenton reaction system with salicylic acid. The experimental operation was as follows: in the sample group, add 1 mL FeSO 4 solution, 1 mL salicylic acid solution, and 1 mL H 2 O 2 solution into 1 mL SINH successively to measure the absorbance ( A 1 ); in the control group, add 1 mL of salicylic acid and 2 mL water to 1 mL SINH to measure the absorbance ( A 2 ); in the blank group, add 1 mL FeSO 4 solution, 1 mL salicylic acid solution and 1 mL H 2 O 2 solution into 1 mL water to measure the absorbance ( A 3 ). The solution of each group was mixed evenly and reacted in a 37 °C water bath for 30 min. The absorbance at a wavelength of 510 nm was measured. The same operation was used for SINH-L-H, SINH-H, and SINH-L of 0.2 mg/mL as SINH mentioned above. E % = A 3 − A 1 − A 2 A 3 × 100 %
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276951_p36
|
PMC11276951
|
sec[3]/sec[6]/sec[0]/p[1]
|
4.7.1. The Scavenging Rate on Hydroxyl Radicals
| 3.462891 |
biomedical
|
Other
|
[
0.998046875,
0.00042557716369628906,
0.00162506103515625
] |
[
0.474609375,
0.5234375,
0.0013275146484375,
0.0007390975952148438
] |
Calculate the clearance rate and IC50 of SINH and its preparations on hydroxyl radicals based on changes in the absorbance.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276951_p37
|
PMC11276951
|
sec[3]/sec[6]/sec[1]/p[0]
|
4.7.2. The Inhibitory Rate on ABTS Radicals
| 4.089844 |
biomedical
|
Study
|
[
0.998046875,
0.0007801055908203125,
0.0009822845458984375
] |
[
0.88232421875,
0.1162109375,
0.0009670257568359375,
0.00043320655822753906
] |
Mix the ABTS aqueous solution and K 2 S 2 O 8 solution (1:1) evenly, and react in a dark place for 12 h. Dilute the ABTS mixture 30 times so that the absorbance of the solution at 734 nm is within the range of 0.7–0.8. Take 0.5 mL of SINH with different concentrations (0.001, 0.005, 0.01, 0.02, 0.03 mg/mL) and place it in a reaction vessel. Add 2 mL of the 30 times diluted ABTS mixture as the sample group ( A S ) and react in the dark at room temperature for 5 min. Then measure the absorbance at 734 nm. The control group ( A C ) added 2 mL of PBS to SINH, while the blank group ( A 0 ) added 2 mL of ABTS mixture to 0.5 mL of PBS, and then measured the absorbance using the same procedure. E % = A 0 − A S − A C A 0 × 100 %
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276951_p38
|
PMC11276951
|
sec[3]/sec[6]/sec[1]/p[1]
|
4.7.2. The Inhibitory Rate on ABTS Radicals
| 2.638672 |
biomedical
|
Other
|
[
0.99365234375,
0.0013332366943359375,
0.005218505859375
] |
[
0.137939453125,
0.8603515625,
0.0007529258728027344,
0.0009083747863769531
] |
SINH-L, SINH-H, and SINH-L-H with a concentration of 0.001 mg/mL, replace the SINH position with formulations and perform the same operation. Finally, based on the measurement results, calculate IC 50 and the clearance rate of the samples.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276951_p39
|
PMC11276951
|
sec[3]/sec[7]/sec[0]/p[0]
|
4.8.1. Skin Irritation of SINH-L-H
| 2.373047 |
biomedical
|
Study
|
[
0.9970703125,
0.001155853271484375,
0.0019130706787109375
] |
[
0.92919921875,
0.0682373046875,
0.0011625289916992188,
0.0014324188232421875
] |
Forty healthy Kunming mice (20 ± 2 g) were provided by the Experimental Animal Center of Anhui University of Chinese Medicine under license No. SYXK (SU): 2020-0009. This research protocol has been approved by the Animal Care and Use Committee of Anhui University of Traditional Chinese Medicine . The mice were randomly divided into a single-dosing test group and a multiple-dosing test group.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276951_p40
|
PMC11276951
|
sec[3]/sec[7]/sec[0]/p[1]
|
4.8.1. Skin Irritation of SINH-L-H
| 3.648438 |
biomedical
|
Study
|
[
0.9970703125,
0.0023975372314453125,
0.0004162788391113281
] |
[
0.98583984375,
0.01319122314453125,
0.0004801750183105469,
0.0005192756652832031
] |
The back hair of the mice was removed before the experiment began. The mice were divided into three groups, one group was evenly applied with 0.3 mL of B-L-H, one group was evenly applied with 0.3 mL of SINH-L-H, and the other group was not treated as a control group. After application, cover the affected area with gauze and secure it with medical pressure-sensitive tape. The erythema and edema, pigmentation, bleeding, and skin roughness were observed at 1 h, 24 h, 48 h, and 72 h after removal of the gauze.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276951_p41
|
PMC11276951
|
sec[3]/sec[7]/sec[0]/p[2]
|
4.8.1. Skin Irritation of SINH-L-H
| 3.695313 |
biomedical
|
Study
|
[
0.99853515625,
0.0005578994750976562,
0.0007023811340332031
] |
[
0.974609375,
0.0245208740234375,
0.0005402565002441406,
0.00026535987854003906
] |
The skin irritation test after multiple doses was administered in a similar manner to the single dose, with the exception that it required 1 week of continuous dosing at the same site for the same duration and amount of dose each time. The gauze and medical pressure-sensitive tape were also removed 6 h after administration and the site was washed with gauze soaked in warm water. Observe the skin condition of the mice 1 h after each removal of the gauze. Score according to Table 4 and Table 5 , (at the same time do the individual project score and then do the comprehensive score).
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276951_p42
|
PMC11276951
|
sec[3]/sec[7]/sec[1]/p[0]
|
4.8.2. Establishment of AD Model and Administration
| 4.097656 |
biomedical
|
Study
|
[
0.99951171875,
0.0004830360412597656,
0.00019824504852294922
] |
[
0.9990234375,
0.0006937980651855469,
0.00023627281188964844,
0.00008243322372436523
] |
The healthy Kunming mice were domesticated in a specific pathogen-free environment for 3 days. One day before the experiment, shave skin hair with an area of about 2 cm × 2 cm on the back. The shaved back skin was treated with 100 μL 5% DNCB solution (a mixture of acetone:olive oil = 3:1 as solvent) on the first and second days, and the blank group was replaced with the same volume of acetone/olive oil mixture after sensitization. After the first induction, the mice were fed normally with an interval of 5 days. The second sensitization, the skin of the ear was applied with a 0.5% DNCB solution every 3 days, for a total of 3 times. The treatment group was treated with SINH, SINH-L, SINH-H, and SINH-L-H, respectively, starting on the 4th day (if sensitized on the same day, dosed 2 h before sensitization) for 12 days, and the mice of the blank and model groups were treated with equal amounts of PBS, while DXM group was treated with dexamethasone (DXM) as a positive control. The mice were fasted for 12 h after the final administration. The ear pieces, spleen, serum, and dorsal skin of the mouse were collected for subsequent tests after execution .
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276951_p43
|
PMC11276951
|
sec[3]/sec[7]/sec[2]/p[0]
|
4.8.3. Degree of Skin Lesion Score (EASI Score) in AD Mice
| 4.097656 |
biomedical
|
Study
|
[
0.99951171875,
0.00027751922607421875,
0.00019109249114990234
] |
[
0.99951171875,
0.0002551078796386719,
0.0002963542938232422,
0.00006324052810668945
] |
During the modeling process, the mice were observed for changes in their physiological status, including activity, body weight, changes in skin thickness, fur color, diet, and water intake. Skin thickness is measured using a sebum thickness meter (also known as a skin fold caliper) to measure the thickness of the skin and underlying adipose tissue by picking up skin folds. The mice were scored 12 h after the last administration according to the Eczema Severity Index (EASI) scale. The scoring criteria included erythema, papules, desquamation, crusting, and exudate, each of which was divided into three degrees of mild, moderate, and severe and expressed in different data. The scoring criteria were as follows, and the total score was the mouse skin lesion score ( Table 6 ). Based on this scale, the establishment of the AD model and the intervention of SINH, SINH-L, SINH-H, and SINH-L-H on this model were obtained.
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276951_p44
|
PMC11276951
|
sec[3]/sec[7]/sec[3]/p[0]
|
4.8.4. Determination of Ear Swelling Rate in Mice
| 3.947266 |
biomedical
|
Study
|
[
0.99951171875,
0.00022733211517333984,
0.0002694129943847656
] |
[
0.9951171875,
0.004215240478515625,
0.0004413127899169922,
0.00011813640594482422
] |
After the mice were executed, the right and left ear pieces (about 8 mm) were immediately removed with a punch and weighed on an analytical balance, and the ear swelling rate of the mice was calculated according to the following formula. Ear swelling rate % = Right ear mass − Left ear mass Left ear mass × 100 %
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11276951_p45
|
PMC11276951
|
sec[3]/sec[7]/sec[4]/p[0]
|
4.8.5. Measurement of Organ Index in Mice
| 3.716797 |
biomedical
|
Study
|
[
0.99951171875,
0.0001888275146484375,
0.0004329681396484375
] |
[
0.9873046875,
0.01171112060546875,
0.0005941390991210938,
0.0001678466796875
] |
After the mice were executed, the thymus and spleen tissues were separated and quickly weighed, and the thymus (spleen) index was calculated according to the formula as follows: Spleen thymus index = Spleen thymus mass mg Body mass mg
|
[
"Xue Chen",
"Yang Wu",
"Ruoyang Jia",
"Yuqing Fang",
"Keang Cao",
"Xinying Yang",
"Xiaobo Qu",
"Hongmei Xia"
] |
https://doi.org/10.3390/ijms25147676
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
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