The Cancer Spectrum Theory.

SUMMARY: Biological characteristics of tumors are heterogeneous, forming spectra in terms of several factors such as age at onset, anatomic spatial localization, tumor subtyping, and the degree of tumor aggressiveness (encompassing a neoplastic property spectrum). Instead of blindly using dichotomized approaches, the application of the multicategorical and continuous analysis approaches to detailed cancer spectrum data can contribute to a better understanding of the etiology of cancer, ultimately leading to effective prevention and precision oncology. We provide examples of cancer spectra and emphasize the importance of integrating the cancer spectrum theory into large-scale population cancer research.

Regional determinants of quality of care for sick children: A multilevel analysis in four countries.

Background: The limited impact of increased access to care on improvements in health outcomes during the Millennium Development Goal era has been attributed, in part, to inadequate quality of care. We identified regional factors associated with health service quality for sick child care in low-income countries and examined whether provider factors interact with regional factors to affect the quality of care. Methods: We conducted cross-sectional random intercept four-level linear regression using the most recent Service Provision Assessment and Demographic Health Survey data from four countries (467 from the Democratic Republic of Congo 2018, 2425 from Afghanistan 2018, 2072 from Nepal 2015, and 813 from Senegal 2017). The outcome variable was the service quality score for sick child care, which was measured as the percentage of clinically recommended tasks completed in the integrated management of childhood illness (ranging from 0 to 100). Regional factors were selected based on the High-Quality Health System Framework. Results: The service quality score was found to be positively associated with the proportion of large facilities (ß = 8.61; P = 0.004) and the proportion of providers ranked in the top fifth for service quality score (ß = 30.15; P < 0.001) in the region. We identified significant cross-level interactions between provider qualifications (ß = -16.6; P < 0.001) or job descriptions (ß = 12.01; P = 0.002) and the proportion of providers in the top fifth for service quality scores within the region. As the proportion of top-performing providers in a region increased, the increase in the service quality score was more pronounced among providers who were nonmedical doctors or did not have job descriptions than among their counterparts. Conclusions: Our findings indicate that the quality of care for sick children in a region improves with a greater proportion of high-performing providers or larger facilities. Providers who are not medical doctors, or those who have specific job descriptions, tend to benefit more from the presence of these top-performing providers.

User-reported quality of care: findings from the first round of the People's Voice Survey in 14 countries.

High-quality care is essential for improving health outcomes, although many health systems struggle to maintain good quality. We use data from the People's Voice Survey-a nationally representative survey conducted in 14 high-income, middle-income, and low-income countries-to describe user-reported quality of most recent health care in the past 12 months. We described ratings for 14 measures of care competence, system competence, and user experience and assessed the relationship between visit quality factors and user recommendation of the facility. We disaggregated the data by high-need and underserved groups. The proportion of respondents rating their most recent visit as high quality ranged from 25% in Laos to 74% in the USA. The mean facility recommendation score was 7·7 out of 10. Individuals with high needs or who are underserved reported lower-quality services on average across countries. Countries with high health expenditure per capita tended to have better care ratings than countries with low health expenditure. Visit quality factors explained a high proportion of variation in facility recommendations relative to facility or demographic factors. These results show that user-reported quality is low but increases with high national health expenditure. Elevating care quality will require monitoring and improvements on multiple dimensions of care quality, especially in public systems.

Health system quality and COVID-19 vaccination: a cross-sectional analysis in 14 countries.

The social and behavioural determinants of COVID-19 vaccination have been described previously. However, little is known about how vaccinated people use and rate their health system. We used surveys conducted in 14 countries to study the health system correlates of COVID-19 vaccination. Country-specific logistic regression models were adjusted for respondent age, education, income, chronic illness, history of COVID-19, urban residence, and minority ethnic, racial, or linguistic group. Estimates were summarised across countries using random effects meta-analysis. Vaccination coverage with at least two or three doses ranged from 29% in India to 85% in Peru. Greater health-care use, having a regular and high-quality provider, and receiving other preventive health services were positively associated with vaccination. Confidence in the health system and government also increased the odds of vaccination. By contrast, having unmet health-care needs or experiencing discrimination or a medical mistake decreased the odds of vaccination. Associations between health system predictors and vaccination tended to be stronger in high-income countries and in countries with the most COVID-19-related deaths. Access to quality health systems might affect vaccine decisions. Building strong primary care systems and ensuring a baseline level of quality that is affordable for all should be central to pandemic preparedness strategies.

Angelica gigas extract inhibits acetylation of eNOS via IRE1α sulfonation/RIDD-SIRT1-mediated posttranslational modification in vascular dysfunction.

Angelica gigas NAKAI (AG) is a popular traditional medicinal herb widely used to treat dyslipidemia owing to its antioxidant activity. Vascular disease is intimately linked to obesity-induced metabolic syndrome, and AG extract (AGE) shows beneficial effects on obesity-associated vascular dysfunction. However, the effectiveness of AGE against obesity and its underlying mechanisms have not yet been extensively investigated. In this study, 40 high fat diet (HFD) rats were supplemented with 100-300 mg/kg/day of AGE to determine its efficacy in regulating vascular dysfunction. The vascular relaxation responses to acetylcholine were impaired in HFD rats, while the administration of AGE restored the diminished relaxation pattern. Endothelial dysfunction, including increased plaque area, accumulated reactive oxygen species, and decreased nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) Ser1177 phosphorylation, were observed in HFD rats, whereas AGE reversed endothelial dysfunction and its associated biochemical signaling. Furthermore, AGE regulated endoplasmic reticulum (ER) stress and IRE1α sulfonation and its subsequent sirt1 RNA decay through controlling regulated IRE1α-dependent decay (RIDD) signaling, ultimately promoting NO bioavailability via the SIRT1-eNOS axis in aorta and endothelial cells. Independently, AGE enhanced AMPK phosphorylation, additionally stimulating SIRT1 and eNOS deacetylation and its associated NO bioavailability. Decursin, a prominent constituent of AGE, exhibited a similar effect in alleviating endothelial dysfunctions. These data suggest that AGE regulates dyslipidemia-associated vascular dysfunction by controlling ROS-associated ER stress responses, especially IRE1α-RIDD/sirt1 decay and the AMPK-SIRT1 axis.

What are the determinants of variation in caretaker satisfaction with sick child consultations? A cross-sectional analysis in five low-income and middle-income countries.

OBJECTIVES: The objective of this study was to explore determinants of variation in overall caretaker satisfaction with curative care for sick children under the age of 5 in five low-income and middle-income countries. DESIGN: A pooled cross-sectional analysis was conducted using data from the Service Provision Assessment. SETTING: We used data collected in five countries (Afghanistan, Democratic Republic of the Congo, Haiti, Malawi and Tanzania) between 2013 and 2018. PARTICIPANTS: Respondents were 13 149 caretakers of children under the age of 5 who consulted for a sick child visit. PRIMARY OUTCOMES MEASURED: The outcome variable was whether the child's caretaker was very satisfied versus more or less satisfied or not satisfied overall. Predictors pertained to child and caretaker characteristics, health system foundations and process of care (eg, care competence, user experience). Two-level logistic regression models were used to assess the extent to which these categories of variables explained variation in satisfaction. The main analyses used pooled data; country-level analyses were also performed. RESULTS: Process of care, including user experience, explained the largest proportion of variance in caretaker satisfaction (13.8%), compared with child and caretaker characteristics (0.9%) and health system foundations (3.8%). The odds of being very satisfied were lower for caretakers who were not given adequate explanation (OR: 0.56, 95% CI 0.46 to 0.67), who had a problem with medication availability (OR: 0.31, 95% CI 0.27 to 0.35) or who encountered a problem with the cost of services (OR: 0.57, 95% CI 0.48 to 0.66). The final model explained only 21.8% of the total variance. Country-level analyses showed differences in variance explained and in associations with predictors. CONCLUSIONS: Better process of care, especially user experience, should be prioritised for its benefit regarding caretaker satisfaction. Unmeasured factors explained the majority of variation in caretaker satisfaction and should be explored in future studies.

Factors predicting different times for brushing teeth during the day: multilevel analyses.

BACKGROUND: The most effective and simple intervention for preventing oral disease is toothbrushing. However, there is substantial variation in the timing of brushing teeth during the day. We aimed to identify a comprehensive set of predictors of toothbrushing after lunch and after dinner and estimated contextual (i.e., geographic) variation in brushing behavior at different times of the day. METHODS: We constructed a conceptual framework for toothbrushing by reviewing health behavior models. The main data source was the 2017 Community Health Survey. We performed a four-level random intercept logistic regression to predict toothbrushing behavior. (individual, household, Gi/Gun/Gu, and Si/Do). RESULTS: Individuals under 30 years of age had higher likelihood of brushing after lunch, while brushing after dinner was higher among those aged 40-79 years. People engaged in service/sales, agriculture/fishing/labor/mechanics, as well as student/housewife/unemployed were 0.60, 0.41, and 0.49 times less likely to brush their teeth after lunch, respectively, compared to those working in the office, but the gap narrowed to 0.97, 0.96, 0.94 for brushing after dinner. We also found significant area-level variations in the timing of brushing. CONCLUSIONS: Different patterns in association with various factors at individual-, household- and Si/Gun/Gu-levels with toothbrushing after lunch versus toothbrushing after dinner suggests a need for tailored interventions to improve toothbrushing behavior depending on the time of day.

The Role of Reactive Oxygen Species, Inflammation, and Endoplasmic Reticulum Stress Response in the Finasteride Protective Effect against Benign Prostate Hyperplasia.

PURPOSE: Benign prostate hyperplasia (BPH) is a common age-related chronic condition. Its pathogenesis involves androgen imbalance, inflammation, oxidative stress, and endoplasmic reticulum (ER) stress. This study aims to assess the protective effect of finasteride, a 5α-reductase inhibitor, against testosterone propionate (TP)-induced BPH in rats and explore its potential mechanism of action. MATERIALS AND METHODS: TP-induced BPH rats received either saline or finasteride (1 mg/kg) orally once a day for 7 weeks. Prior to sacrificing the animals, blood samples were collected. After sacrifice, prostate and tissue around the prostate were dissected from seminal vesical for further analysis. Body weight, prostate weight, dihydrotestosterone (DHT), 5α-reductase type 2 (5-AR2), and prostate-specific antigen (PSA) levels were measured. In addition, HIF-1α, VEGF, MMP-2 expressions in prostate, oxidative stress, inflammation, and ER stress responses were analyzed to understand the mechanism of action of finasteride. RESULTS: Finasteride administration inhibited prostate enlargement, DHT, 5-AR2, and PSA levels in BPH rats. Additionally, finasteride inhibited angiogenesis markers such as HIF-1α, VEGF, and MMP-2. Moreover, components of oxidative stress, inflammation, and ER stress responses were significantly regulated by finasteride treatment. CONCLUSIONS: This study suggests that finasteride prevents BPH-associated symptoms by regulating angiogenesis, reactive oxygen species, ER stress responses, and inflammation, another mechanism to explain the effect of the 5α-reductase against BPH.

Occupational and Psychological Factors Associated With Burnout in Night Shift Nurses.

OBJECTIVE: Providing inpatient nursing care inevitably involves night shift work. However, night shift work nurses often face psychiatric health problems such as burnout. If night shift work is an essential work type for nurses, it is necessary to select personnel suitable for night shift work or establish improvement measures such as psychiatric intervention through psychiatric evaluation. The objective of this study was to identify factors that could be interventional among factors affecting burnout in shift-working nurses. METHODS: A total of 231 night shift female nurses participated in this study. A questionnaire survey was given to assess their general characteristics. To assess burnout, the Maslach Burnout Inventory-General Survey Korean version was adopted. In addition, several mental health scales were used to identify individual psychological characteristics. To identify variables associated with the presence of burnout, odds ratios were calculated using a logistic regression model taking three dimensions of burnout as a dependent variable after adjusting for psychological and occupational factors. RESULTS: High resilience was a significant preventive factor in the three dimensions of burnout. Regarding occupational factor, the longer the duration of employment, the higher depersonalization, but the professional efficacy was good. CONCLUSION: Our results indicate that resilience and social support could be prevention factors for burnout. This study is meaningful in examining items that require active intervention and support for burnout targeting night shift nurses who are indispensable for patient care.

Combined Treatment of Mori folium and Mori Cortex Radicis Ameliorate Obesity in Mice via UCP-1 in Brown Adipocytes.

Mori Folium (Morus alba leaf, MF) and Mori Cortex Radicis (Morus alba root cortex, MR) have been studied for their anti-obesity effects by enhancing the browning process and inhibiting adipogenesis. However, important aspects of their protective mechanisms have not been thoroughly investigated, which could aid in developing functional food. Thus, this study aims to determine the synergistic effects of MF and MR against obesity and its associated mechanisms. In an in vitro cell culture model of brown adipocytes, a 1:1 mixture of MF and MR showed a synergistic effect on the expression of brown adipocyte-specific genes, including Ucp-1, Ppargc1a, Cbp/p300-interacting transactivator (Cited), Prdm16, Tbx1, and Fgf21 compared with either MF- or MR-treated conditions. Moreover, they demonstrated the involvement of cAMP and Ca2+ in induction of brown adipocyte-specific genes. In an in vivo model using HFD-fed mice, MF/MR significantly inhibited weight gain, plasma cholesterol, LDL, TG content, fat mass, and adipocyte size. Furthermore, MF/MR inhibited morphological alteration and the expressions of fatty acid synthesis genes such as Srebp1 and Fasn in the white adipose tissue. Thermogenesis genes were recovered in the brown adipose tissue with MF/MR supplementation, indicating that MF/MR regulated adipocytic dysmetabolism where AMPK signaling is involved. In conclusion, these results suggested that MF/MR regulates brown and beige adipocyte processes, providing one of the preventive functional food/herbal medicines against obesity and its associated metabolic diseases.

Ixeris dentata and Lactobacillus gasseri media protect against periodontitis through Nrf2-HO-1 signalling pathway.

Periodontitis is an infectious inflammation in the gums characterized by loss of periodontal ligaments and alveolar bone. Its persistent inflammation could result in tooth loss and other health issues. Ixeris dentata (IXD) and Lactobacillus gasseri media (LGM) demonstrated strong antioxidant activity, which may prevent oxidative and inflammatory periodontitis. Here, IXD and LGM extracts were investigated for antioxidative activity against oral discomfort and evaluated for their synergistic effect against oxidative and inflammatory periodontitis in a mouse model. IXD/LGM suppressed pro-inflammatory cytokines like interleukin (IL)-1ß, IL-6, and TNF-α. Additionally, it reduced pro-inflammatory mediators, nitric oxide, iNOS (inducible nitric oxide synthase), and COX-2 (cyclooxygenase-2) and enhanced AKT, Nrf2, and HO-1 activation. Similarly, IXD/LGM treatment elevated osteogenic proteins and mRNAs; alkaline phosphatase, collagen type 1 (COL1), osteopontin (OPN), and runt-related transcription factor 2 (RUNX2). Hematoxylin and Eosin (H&E) staining and micro-CT analysis confirm the positive impact of IXD/LGM on the periodontal structure and its associated inflammation. These findings demonstrate that IXD/LGM inhibits oxidative stress, periodontal inflammation, and its resultant alveolar bone loss in which Akt (also known as protein kinase B)-nuclear factor-erythroid 2-related factor 2 (Nrf2)-hemoxygenase-1 (HO-1) signaling is involved. Thus, IXD/LGM is a potential candidate against oxidative/inflammatory stress-associated periodontitis.

Combination of Panax ginseng and Diospyros kaki Leaf Inhibits White Adipocyte Differentiation and Browning Process through AMP-Activated Protein Kinase (AMPK) Activation In Vitro and In Vivo.

Activating brown adipose tissue (BAT) and stimulating white adipose tissue (WAT) browning is a prospective obesity treatment method. Dietary components derived from plants are the most effective approach to activate BAT and promote WAT browning in rodents. This study investigated the synergistic effects of Panax ginseng (PG) and Diospyros kaki leaf (DKL) extract on adipocyte differentiation and browning, as well as the molecular mechanism underlying their beneficial effects. The administration of PG and DKL to HFD-induced obese mice significantly decreased body weight and epididymal and abdominal adipose tissue mass. In in vitro, PG inhibited the adipogenesis of 3T3-L1 adipocytes by regulating the expression of key adipogenic regulators, such as peroxisome proliferator-activated receptor (PPAR)γ and CCAAT/enhancer-binding protein (C/EBP)-α. In contrast, DKL negligibly influenced the adipogenesis of 3T3-L1 adipocytes but greatly increased the protein expression of UCP-1, PGC-1α, and PPARα in BAT and/or WAT. Moreover, PG and DKL inhibited adipogenesis synergistically and activated white adipocyte browning via AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) pathways. These results suggest that a combination of PG and DKL regulates adipogenesis in white adipocytes and browning in brown adipocytes by activating AMPK/SIRT1 axis. The potential use of PG and DKL may represent an important strategy in obesity management that will be safer and more effective.

Standardized Suicide Prevention Program for Gatekeeper Intervention of North Korean Defectors in South Korea.

OBJECTIVE: North Korean defectors (NKDs) have experienced substantial difficulties during the migration and settlement in South Korea. They have a high prevalence of depression, post-traumatic stress disorder, and suicidal behaviors. The high prevalence of mental disorders among NKDs can lead to a high suicide rate. However, there are no suicide prevention programs for NKDs. This study aims to customize a suicide prevention program with content suitable for NKDs' particular circumstances. METHODS: A multidisciplinary research team developed this program based on domestic and international gatekeeper training programs for suicide prevention and articles related to suicide prevention. RESULTS: We developed a multi-part gatekeeper training program, "Suicide CARE for NKDs." In the "Introduction," trainees learn about the need for the program and its importance. In "Careful observation," trainees learn to recognize linguistic, behavioral, and situational signals of suicide risk. In "Active listening," trainees learn how to ask about suicidal thoughts and to listen empathetically. In "Risk evaluation and expert referral," trainees learn to evaluate suicide risk and to connect NKDs with institutes or services. CONCLUSION: We expect this program to become useful for training gatekeepers to prevent suicide among NKD. A future follow-up study is needed to confirm the efficacy of the program.

Nationwide trends in the prevalence and incidence of depressive disorders and their correlates among adults with disabilities in Korea from 2006 to 2017.

BACKGROUND: Evidence suggests that people with disabilities are more likely to suffer from depression. Previous studies have focused on depressive disorders in specific disability types or age groups using small-scale cross-sectional samples. We investigated longitudinal trends in the prevalence and incidence of depressive disorders according to disability types and severity levels in the entire Korean adult population. METHODS: The age-standardised prevalence and incidence of depressive disorders were investigated using National Health Insurance claims data from 2006 to 2017. The odds of depressive disorders by type and severity were examined using logistic regression after adjusting for sociodemographic characteristics and comorbidities based on merged 2006 to 2017 data. RESULTS: Both the incidence and prevalence of depressive disorders were higher among the disabled than the non-disabled, with the prevalence gap being larger than the incidence gap. In regression analyses, adjusting for sociodemographic characteristics and comorbidities considerably reduced the odds ratios, particularly for incidence. The severity of disabilities was inversely associated with the incidence of depressive disorders. Brain injury and disabilities in major internal organs were associated with lower odds of developing depressive disorders than in non-disabled individuals. CONCLUSIONS: A significant proportion of depressive disorders in disabled individuals are caused by financial hardships or comorbidities rather than disabilities themselves. We must pay special attention to those who cannot access healthcare services due to severe disabilities and those whose depressive disorders are misdiagnosed as intellectual disabilities. More research is required to elucidate the causal mechanisms underlying depressive disorders in people with various types and severities of disabilities.

Impact of community health interventions on maternal and child health indicators in the upper east region of Ghana.

BACKGROUND: This paper reports on results of a health system strengthening implementation research initiative conducted the Upper East Region of northern Ghana. Transformative interventions to accelerate and strengthen the health delivery were implemented that included empowering community leaders and members to actively participate in health delivery, strengthening the referral systems through the provision of community transport systems, providing basic medical equipment to community clinics, and improving the skills of critical health staff through training. METHODS: A mixed method design was used to evaluate the impact of the interventions. A quantitative evaluation employed a flexible research design to test the effects of various component activities of the project. To assess impact, a pre-versus-post randomized cluster survey design was used. Qualitative research was conducted with focus group data and individual in depth interviews to gauge the views of various stakeholders associated with the implementation process. RESULTS: After intervention, significant improvements in key maternal and child health indicators such as antenatal and postnatal care coverage were observed and increases in the proportion of deliveries occurring in health facilities and assisted by skilled health personnel relative to pre-intervention conditions. There was also increased uptake of oral rehydration salts (ORS) for treatment of childhood diarrhoea, as well as marked reductions in the incidence of upper respiratory infections (URI). CONCLUSIONS: A pre-and post-evaluation of impact suggests that the programme had a strong positive impact on the functioning of primary health care. Findings are consistent with the proposition that the coverage and content of the Ghana Community-based Health Planning and Services programme was improved by program interventions and induced discernable changes in key indicators of health system performance.

Effect of Home-based Self-administered Transcranial Direct Stimulation in Patients with Mild to Moderate Major Depressive Disorder: A Single-arm, Multicentral Trial.

Objective: Although the effects and safety of transcranial direct current stimulation (tDCS) treatment in depressive patients are largely investigated, whether the self-administration of tDCS treatment at patient's home is comparable to clinic-based treatment is still unknown. Methods: In this single-arm, multi-center clinical trial, 61 patients with mild to moderate major depressive disorder were enrolled. tDCS treatment was delivered at the patient's home once a day, 5 to 7 times a week for 6 weeks, and each session lasted for 30 minutes. The primary outcome was a total Beck-Depression Inventory-II score, and no concurrent antidepressants were used. Results: The remission rates in both Full-Analysis (FA) (n = 61) and Per-Protocol (PP) (n = 43) groups were statistically significant (FA: 57.4% [0.44-0.70], PP: 62.8% [0.47-0.77]; percent [95% confidence interval]). The degree of depression- related symptoms was also significantly improved in 2, 4, and 6 weeks after the treatment when compared with baseline. There was no significant association between treatment compliance and remission rate in both FA and PP groups. Conclusion: These results suggest that acute treatment of patient-administered tDCS might be effective in improving the subjective feeling of depressive symptoms in mild to moderate major depressive disorder patients.

Ramie leaf Extract Alleviates Bone Loss in Ovariectomized Rats-The Involvement of ROS and Its Associated Signalings.

Ramie leaf (Boehmeria nivea L.) has been traditionally used to treat gynecological and bone-related disorders. This study aims to evaluate the effect of Ramie leaf extracts (RLE) against osteoporosis in ovariectomized (OVX) rats. Female SD rats aged seven weeks were randomly assigned into five OVX and a sham-operated (sham) group. OVX subgroups include OVX, vehicle-treated OVX group; E2, OVX with 100 µg/kg 17ß-estradiol; and RLE 0.25, 0.5, and 1, OVX rats treated with 0.25, 0.5, and 1 g/kg/day RLE, respectively. Two weeks into the bilateral ovariectomy, all the rats were orally administered with or without RLE daily for 12 weeks. OVX rats administered with RLE showed higher bone density, relatively low tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and lower reactive oxygen species (ROS) within bone tissues compared to vehicle-treated OVX rats. Furthermore, supplementation of RLE improved bone mineral density (BMD) and bone microstructure in the total femur. RLE prevented RANKL-induced osteoclast differentiation and expression of osteoclastogenesis-related genes such as Cal-R, MMP-9, cathepsin K, and TRAP in RANKL-induced RAW264.7 cells. Moreover, RLE administration lowered the intracellular ROS levels by reducing NADPH oxidase 1 (NOX-1) and 4-hydroxynonenal (4HNE). These results suggest that RLE alleviates bone mass loss in the OVX rats by inhibiting osteoclastogenesis, where reduced ROS and its associated signalings were involved.

BMI trajectory and inflammatory effects on metabolic syndrome in adolescents.

BACKGROUND: Various life course factors can affect susceptibility to diseases during adolescence and adulthood, and those relationships are complex. However, few studies have assessed the potential mediating factors. Therefore, we assessed the mediating effects of factors related to growth and inflammation between perinatal factors and metabolic syndrome risk during adolescence. METHODS: The study was conducted on adolescents who participated in the follow-up in the Ewha Birth and Growth Cohort. We considered the ponderal index (PI) as a perinatal factor and the continuous metabolic syndrome score (cMetS) as the outcome and confirmed the mediating effects of body mass index (BMI) trajectory pattern in childhood and inflammation levels by using the PROCESS macro for SAS. RESULTS: Although the direct effect of BMI trajectory on the relationship between PI and cMetS was not significant (0.545), the indirect effect was significant (1.044). In addition, the indirect effect was statistically significant in the pathways mediating the BMI trajectory pattern and inflammation (ß = 1.456). CONCLUSIONS: The direct and indirect effects on the relationship between PI and cMetS suggest that childhood factors related to growth may be involved in disease susceptibility. Therefore, appropriate interventions for the management of obesity during the growth phase are necessary. IMPACT: Unlike other existing studies, this study assessed multiple mediating effects by considering the BMI trajectory pattern and inflammatory indexes as mediating factors between the ponderal index and the continuous metabolic syndrome score during adolescence. We found significant indirect effects of the BMI trajectory between PI and cMetS, and also significant indirect effects in the pathways mediating the BMI trajectory and hs-CRP. The significant indirect mediating effects support that childhood factors related to growth may be involved in disease susceptibility.