Background: Endometriosis is a common nonfatal gynecological disease, and infertility is one of its main dangers. Endometriosis-related infertility causes serious damage to women’s health and places a burden on women of reproductive age. The aim of this study was to describe the current burden of endometriosis-associated infertility and to analyze its spatiotemporal trends. Methods: Age-standardized prevalence rate (ASPR) data from 1990 to 2019 for Endometriosis-related primary infertility (ERPI) and secondary infertility (ERSI) were obtained from the Global Burden of Disease Study (GBD) 2019. These data spanning three decades cover the global, sociodemographic index (SDI) regions, GBD regions, and 204 countries and territories. Spatiotemporal trends were analyzed by calculating the estimated annual percentage change (EAPC) and using a time–period–cohort model. Results: Globally, the ASPR of ERPI and ERSI showed a weak downward trend from 1990 to 2019, with EAPCs of −1.25 (95% CI: −1.39 to −1.11) and −0.6 (95% CI: −0.67 to −0.53), respectively. The spatiotemporal trends in ERPI and ERSI varied substantially between regions and age groups. When endometriosis-related infertility burden was linked to SDI values, a strong negative correlation was observed between the ASPR of ERSI and its EAPC and SDI values. When modeling with age–period–cohort, ERPI burden was found to be highest at ages 20–25 years, while ERSI burden was persistently higher at ages 20–45 years. Using 2000–2004 as the reference period, both ERPI and ERSI burden decreased with each year among women. Significant variability in burden between regions was found for the birth cohort factor. Conclusions: The global burden of endometriosis-related infertility declined minimally from 1990 to 2019. However, this burden varied considerably across regions, age groups, periods, and birth cohorts. The results of this study reflect spatiotemporal trends in the burden of endometriosis-related infertility over the study period and may be used to help improve health management, develop timely and effective prevention and control strategies, and provide epidemiologic theoretical evidence for reducing the burden for endometriosis-related infertility. Endometriosis is a common, nonfatal chronic disease manifested by the presence of endometrial-like tissue outside the uterus that has an insidious onset, inadequate detection of the disease, and a lack of noninvasive diagnostic methods, leading to delays and often misdiagnosis, delaying the patient’s access to optimal treatment ,2. EndomThe Global Burden of Disease Study (GBD) 2019 is an international comprehensive statistical measure of disease and the associated impairments. The last brief assessment of the global burden of endometriosis was based on GBD 2017 . In the https://ghdx.healthdata.org/gbd-2019, accessed on 10 February 2023) covers a wide range of population health and demographic data from across the globe obtained from census data, surveys, registries, indicators and estimates, administrative health data, and health-related financial data. Disease and impairment data and 95% uncertainty interval (UI) from 1990 to 2019 were obtained from the GBD 2019 public database (accessed on 10 February 2023). Our analysis focused on the burden of endometriosis-related infertility, including endometriosis-related primary infertility (ERPI) and endometriosis-related secondary infertility (ERSI). ASPR data were used to evaluate the burden for endometriosis-related infertility. For analysis of age-specific data on the burden of endometriosis, health data from the GBD 2019 were used for women aged 15 to 54 years, grouped by five years each. The GBD 2019 provided infertility data for women aged 15–49 years, also grouped by the five years, to assess the age-specific burden of endometriosis-associated infertility. Data for each region were provided by GBD 2019. Based on the SDI values, the 204 countries were divided into five regions with different SDI levels.The GBD 2019 database  is a comprehensive assessment of national and regional per capita income, years of schooling, and fertility rates for women under 25 years of age, and allows for the classification of all countries and regions into five classes.In our study, we first restricted the disease to endometriosis and then focused on infertility as an impairment to obtain ERPI and ERSI data. Consequently, women aged 15–49 years with endometriosis-related infertility were successfully acquired.ASPR from 1990 to 2019 were used to assess burden of endometriosis-related infertility. Temporal trends in burden over three decades are captured by the estimated annual percentage change (EAPC). EAPC and its 95% confidence interval (CI) are obtained from the formula EAPC = 100 ∗ (exp (β) − 1), where β is the annual change in ln (ASPR). A positive value of EAPC and its 95% CI represents an upward trend; if both values are negative, it is a downward trend; otherwise, we consider it relatively stable.The age–period–cohort model is based on a Poisson distribution and was used to assess independent estimates of the effects of age, period, and birth cohort on the burden of endometriosis-related infertility globally and in five SDI-level regions.p-value of no more than 0.05 indicates a statistical difference. The longitudinal age curve is used to assess changes in disease burden due to age effects. Period rate ratios (RR) and cohort RR show period effects and birth cohort effects, with RR greater than 1 representing a higher relative risk of disease compared with the reference cohort and RR less than 1 representing a lower risk.The age–period–cohort model is based on a Poisson distribution and was used to assess independent estimates of the effects of age, period, and birth cohort on the burden of endometriosis globally and in five SDI-level regions. The R packages “magrittr” and “dplyr” are used to construct the model. Here, the age factor is determined by the loading of aging factors. Period factors refer to changes in the load of anthropogenic factors in a given epoch. The variation of the cohort factor is attributed to the different exposure conditions of the population in different birth periods. In this case, the age, period, and birth cohort are each 5 years apart. The net drift represents the overall time trend, and a Correlations between statistics, SDI, and EAPC were determined using Pearson correlation. The age–period–cohort model was evaluated by the Wald test. All data could be obtained free of charge from GBD 2019 except those specifically mentioned. All statistical analyzes and plots were generated using GraphPad Prism8 or R Studio (4.1.0).Infertility is considered the main impairment posed by endometriosis. We analyzed the prevalence of primary and secondary endometriosis-related infertility . In 1990At the SDI region level, for ERPI, ASPR was consistently lowest in the High-middle SDI region and consistently highest in the Low SDI region over the 30-year period. For ERSI, ASPR is lowest in the High SDI region and, as expected, consistently highest in the Low SDI region from 1990 to 2019. The burden of endometriosis-related infertility trended downward in all SDI regions, including ERPI and ERSI. Over the three decades, the burden has declined fastest in the Low-middle SDI region, with EAPCs in ASPR for total endometriosis-related infertility, ERPI, and ERSI of −1.38 (95% CI: −1.43 to −1.33), −2.18 (95% CI: −2.45 to −1.91), and −1.07 (95% CI: −1.19 to −0.96), respectively.At the GBD level, the highest ASPR for ERPI was attributed to North Africa and the Middle East in both 1990 and 2019. In 1990, the ASPR for ERSI peaked in Oceania , whereas in 2019 it trended upward in North Africa and the Middle East . Over the 30-year period, the ASPR of ERPI tended to increase in Eastern Europe and the ASPR of ERSI increase in Eastern Europe and Andean Latin America, remained essentially flat in Western Europe, and was lower in all other regions.Of the 204 countries and territories with endometriosis-related infertility, both primary and secondary, Yemen provided the highest ASPR in 1990. Regarding ERPI, Yemen had the highest ASPR in 1990, while Iran (Islamic Republic of) had the highest in 2019. Over the three decades, the burden of ERPI declined in a total of 186 of 204 countries, with Liberia showing the most significant decline in burden with an EAPC = −3.85 (95% CI: −4.38 to −3.33). A total of 12 countries showed an increasing trend in the ASPR of ERPI, with Sweden showing the highest value with EAPC = 2.02 (95% CI: 1.57 to 2.48). The ASPR was stable in the other countries. For ERSI, Taiwan (Province of China) had the highest ASPR in both 1990 and 2019. A total of 162 countries showed a decreasing ASPR of ERSI from 1990 to 2019, with Pakistan showing the most significant decrease in ASPR with EAPC = −3.43 (95% CI: −3.74 to −3.12). Nineteen countries showed an increased ASPR, led by Peru with EAPC = 1.86 (95% CI: 0.95 to 2.79).GBD 2019 counted women aged 15 to 49 years with endometriosis-related infertility. We analyzed the age-specific burden for ASPR of ERPI and ERSI according to age groups, respectively . The higWe were also made aware of the association between sociodemographic changes and the prevalence of endometriosis-related infertility A. For EROur objective was to further understand the change in prevalence burden of ERPI and ERSI using the age–period–cohort model. The overall risk of impairment during the study period was lower in the ERPI population with a net drift = −1.22 (95% CI: −1.37 to −1.06) . The ageFor ERSI, an overall decreasing trend in prevalence risk was observed at the global level, with a net drift of −0.84 (95% CI: −1.01 to −0.67), which was statistically significant. As for the age factor, prevalence tended to increase with age and then decreased, peaking at 25–29 years. Regarding SDI regions, although they all showed a general trend of first increasing and then decreasing with age, the vast majority of regions had the highest prevalence risk at age 25–29 years. However, the areas with high SDI peaked at age 40–44 years, showing a significant delay in the age peak of prevalence risk. Regarding period effects, the period RR tends to decrease over time, with 2000–2004 as the reference period. For the birth cohort with 1970 as the reference year, greater variability is seen at the global level. At the global level, the rate of increase in ERSI burden slows with increasing birth year for women born before 1970 and decreases each year for women born between 1970 and 1982, whereas the burden of ERSI increases again for women born in subsequent years. The birth cohort effect of ERSI shows a remarkably high degree of variability within SDI regions. In the high SDI region, results show that ERSI burden decreases with birth year for both women born before 1950 and women born after 1970; whereas, the opposite is true for women born between 1950 and 1970. In other SDI regions, the most consistent observation is that ERSI burden increases with birth year, a phenomenon that began to reverse in the 1970 birth cohort.Endometriosis is now considered a systemic disease and is not limited to the pelvis . It can In our study, the prevalence burden of endometriosis-related infertility showed a weak downward trend over three decades at the global level and in all SDI regions. Notably, the overall trend for ERPI and ERSI showed the same trend. However, the different SDI regions showed a split in prevalence burden, i.e., the burden was higher in the lower SDI regions and the prevalence burden was lower in the higher SDI regions. This differential status was particularly evident for ERSI, suggesting regional differences. Nevertheless, in the regions with lower SDI, the decline in burden was most rapid, indicating efforts in controlling endometriosis-related infertility. However, this rapid decline in disease burden may have a false-positive element. In short, our study spans three decades. During the past three decades, as medical care has advanced, so have the criteria for diagnosing endometriosis. This is what compels us to wonder whether overdiagnosis due to low-quality ultrasound technology may have occurred thirty years ago. In addition, we found that the prevalence burden of ERPI was hardly negatively correlated with SDI, except for SDI values of 0.3–0.5, which reflected a relatively high burden, and a slight lower burden for SDI values above 0.8. In contrast, the ASPR for ERSI showed a sensitive decline with increasing SDI values. This suggests that ERSI may be the major decreasing burden when SDI increases with social development and SDI. A favorable social environment may contribute to more comprehensive management and prevention of women’s health, including stricter control of the ERSI burden. In addition, the emergence of this phenomenon may be related to the quality of care. Countries and regions with rapid social development are often matched with better health care systems, such as assisted reproductive technology or laparoscopic techniques, which make it possible for infertility not to become a major problem. However, in poorer countries and regions, it can still be a huge problem. We also observed a negative sinusoidal trend in the EAPC of ASPR with SDI values in ERPI, which reflected a reversion in the EAPC in the range of SDI values 0.75–0.85, suggesting a potential risk of burden rebound. This change was not seen in secondary infertility.The prevalence of endometriosis-associated infertility varies by age group. The highest prevalence of ERPI is between 20 and 24 years of age, with the burden decreasing with age. Regional differences are also seen in younger women, with higher prevalence in areas with lower SDI. These differences become negligible with increasing age. In ERSI, all women aged 20 to 44 years had a high prevalence burden, and regional differences continued to exist, manifested by a negative correlation between SDI level and burden. The age–period–cohort model showed a decline in the risk of endometriosis-related infertility from 1990 to 2019, with a rebound risk for ERSI prevalence in high SDI areas in recent years. The age effect had a greater impact on infertility risk for ERPI and was most pronounced among younger women. For ERSI, prevalence risk was consistently higher among young and middle-aged women, particularly in the high SDI region that had a delayed age peak in prevalence. This suggests that the potentially advanced aging burden of endometriosis-related infertility may be a major problem in the future, for which we need to start addressing. For the cohort effect, the early birth cohort had a relatively high risk of infertility. However, for ERSI, women born after 1995 also suffered a high risk, as was most evident in the low–middle SDI regions. These data remind us that prevention and control of endometriosis-related infertility is an ongoing struggle, requiring consideration of the impact of social context and population age.Overall, these results suggest that global efforts to combat endometriosis-related infertility have been reasonably successful. However, the age-related and spatially uneven distribution of the endometriosis-related infertility burden may undermine this progress. Although higher SDI areas currently appear to reflect a lower burden, there is a risk that the burden will rise again if efforts remain inadequate. In addition, efforts to curb the burden of endometriosis-related infertility must be aligned with actual health needs and social environments, taking into account disease background, regional culture, and age composition to be effective in reducing the burden of disease. The GBD 2019 study takes into account influencing factors such as social context and population age on the changing global burden of disease landscape to inform disease and impairment prevention and control strategies.Several limitations provide room for further development of this study. First, data on endometriosis and associated infertility in some countries and regions need further refinement to provide a more accurate and reasonable estimate of disease burden. The burden of disease and harms do not currently cover the entire age range, which will lead to the absence of a significant amount of important data. Because our study spanned three decades, the criteria for diagnosis and confirmation of disease have evolved over those three decades, which may lead to inevitable over- or underdiagnosis. We had to account for some of the resulting false-positive or false-negative results. Second, infertility data are controversial. This is because in some surveys only married women were interviewed, but the final prevalence estimates suggest infertility among couples. In such cases, it is unrealistic to determine which partner is the cause of infertility as soon as possible. At the same time, there is no complete guarantee at the time of the survey that infertility is caused by endometriosis. These two limitations may have led to a different view from other studies available to date. Third, this study lacks data on factors that influence endometriosis, such as environment, diet, lifestyle, or metabolism. These additional data would help to address the burden of endometriosis. Medical technologies such as laparoscopy and advances in ultrasound diagnostics may contribute to the diagnosis and treatment of endometriosis-related infertility. This is a direction that could be explored in depth in the future. Finally, this study only runs through 2019 and does not consider the potential impact of COVID-19 on endometriosis and related infertility. This could have a significant impact on the landscape for global disease and impairment, as lack of health monitoring, inadequate diagnosis, and limited treatment options could reduce global efforts to combat endometriosis and related infertility.In summary, the GBD 2019 study provides a comprehensive, high-quality estimate of the burden of disease for endometriosis-related infertility. Over the past three decades, the burden of endometriosis-related infertility has declined more or less significantly in a concerted worldwide effort. However, global estimates of the burden of endometriosis-related infertility vary widely, highlighting disparities in the global burden, particularly in less developed regions. In addition, age differences show disparities in disease burden, and the potential risk of disease aging must be taken seriously. Public health leaders should develop more complex responses based on specific social contexts and age distribution characteristics, actively promote women’s health knowledge, call for attention to endometriosis, and improve medical care in order to fundamentally reduce the burden of endometriosis-related infertility and regional disparities to advance women’s health.


Ultra-processed foods (UPF) consumption may affect the risk of PCAD through affecting cardio metabolic risk factors. This study aimed to evaluate the association between UPFs consumption and premature coronary artery disease (PCAD).A case–control study was conducted on 2,354 Iranian adults (≥ 19 years). Dietary intake was assessed using a validated 110-item food frequency questionnaire (FFQ) and foods were classified based on the NOVA system, which groups all foods according to the nature, extent and purposes of the industrial processes they undergo. PCAD was defined as having an stenosis of at least single coronary artery equal and above 75% or left main coronary of equal or more than 50% in women less than 70 and men less than 60 years, determined by angiography. The odds of PCAD across the tertiles of UPFs consumption were assessed by binary logistic regression.After adjustment for potential confounders, participants in the top tertile of UPFs were twice as likely to have PCAD compared with those in the bottom tertile . Moreover, those in the highest tertile of the UPFs consumption had more than two times higher risk for having severe PCAD than those in the first tertile . In addition, there was a significant upward trend in PCAD risk and PCAD severity as tertiles increased .Higher consumption of UPFs was related to increased risk of PCAD and higher chance of having severe PCAD in Iranian adults. Although, future cohort studies are needed to confirm the results of this study, these findings indicated the necessity of reducing UPFs intake. Coronary artery disease (CAD) is the most frequent cardiac complication of chronic diseases in developing countries . In geneThere are various food classifications based on the level of processing amongst them the NOVA system is the most common . AccordiDue to the fact that UPFs have a long shelf life, are tasty, ready to use, and most importantly are not expensive  the tendAlthough there are several studies on the relationship between UPFs and CVD, so far, no study has been done specifically on PCAD. Also, due to differences among lifestyle, dietary habits and the average consumption of UPFs in each population, there may be contradictions between the results of different studies. Therefore, this study aims to investigate the association between UPFs consumption and the PCAD in a multi-centric study of Iranians.via convenient sampling from reference hospitals in 16 cities of Iran. This study was reviewed and approved by the Ethics Committee of Isfahan University of Medical Sciences (IR.MUI.REC.1396.2.055). We obtained a written informed consent from all patients and the Declaration of Helsinki was considered.This case–control study was conducted using the data from IRAN Premature Coronary Artery Disease study (IPAD) . IPAD isTrained healthcare professionals completed questionnaires and collected data regarding demographics characteristics, personal and family history of illnesses and medications. A demographic questionnaire was used to collect marital status and level of education. The height of patients was measured by a wall-fixed stadiometer with a sensitivity of 0.1 cm while participants were barefoot, and weight was obtained while participants were minimally clothing and recorded to the nearest 0.1 kg. Body mass index (BMI) was calculated by dividing weight in kilogram by height squared in meter. Waist circumference (WC) was measured with a tape measure between the lowest rib and iliac crest to the nearest 0.1 cm . Systolivia a validated and reliable 110-item semi-quantitative food frequency questionnaire (FFQ)  . The FFQre (FFQ) , 28.Ultra-processed foods were determined according to the NOVA classification system . NOVA clBlood samples were collected after a fasting period of 12 h to measure fasting blood sugar (FBS), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Serum lipids and glucose were measured using the enzymatic method, based on calorimetry, utilizing commercial kits  with an automatic device . Based on the definition of the National Cholesterol Education Program (NCEP) TG ≥ 150 mg/dl, TC ≥ 240 mg/dl, LDL ≥ 160 mg/dl, and HDL-C < 40 in men and < 50 mg/dl in women, were considered as hypertriglyceridemia, hypercholesterolemia, raised LDL-C and low HDL-C, respectively .p-values were reported and statistical significance was considered p < 0.05. Kolmogorov Smirnov test was used to explore the normality of the distribution for quantitative variables. The tertiles of UPFs were determined based on the overall range of UPFs consumption in the whole population. General characteristics of participants across the tertiles of UPFs were compared by one-way analysis of variance (ANOVA) for continuous variables such as BMI, age and WC and Chi-square test for categorical variables. The independent-sample Student t-test was used to distinguish means of continuous variables between cases and controls. For comparing the distribution of participants in categorical variable levels between cases and controls, the chi-square test was run. The association between UPFs consumption and PCAD was assessed by binary logistic regression in different models. The crude model remained unadjusted. Model 1 was adjusted for age, sex, and daily energy intake. Model 2 was additionally adjusted for smoking, level of education, different ethnicities and family history of CVD. Model 3 was additionally adjusted for the Mediterranean dietary score. BMI in model 4, and WC in model 5 were additionally and separately adjusted as mediators. Due to the small sample size of some subgroups of ethnicities, the association between UPFs consumption and PCAD in different ethnicities was assessed by binary logistic regression in just one adjusted model for age, sex, and daily energy intake.All analyses were performed using SPSS Statistics 26.0 software . Two-tailed p-value < 0·001), hypertriglyceridemia  and hypertension . The average of FBS and SBP levels were significantly higher in cases than that of in controls . In comparison to controls, cases showed lower LDL-C, HDL-C and TC mean values . Assessing participants’ characteristics across the tertiles of UPFs consumption revealed that individuals in the top tertile of UPFs consumption were younger , more educated  more frequently current smokers  and had lower TC levels .General characteristics of cases and controls across the tertiles of UPFs consumption are presented in p-value: < 0·001), cholesterol , dairy products , cake and cookies, soft drinks, sweets, processed meats and mayonnaise and dressings  than that of in control group. Total fat , protein , Fruits and Vegetables , monounsaturated fatty acids  and polyunsaturated fatty acids  dietary intakes of controls were significantly higher than cases. Evaluating dietary intakes of participants across the tertiles of UPFs consumption showed that individuals in the highest tertile of UPFs consumption had higher intake of total energy, SFAs, PUFAs , cholesterol, cake and cookies, soft drinks, sweets, processed meats and mayonnaise and dressings  than participants in the first tertile. Bread, sodium , protein and fiber intake of those in the third tertile of UPFs consumption was significantly lower than whom in the first tertile .Dietary intakes of cases and controls across the tertiles of UPFs consumption are indicated in p trend < 0.001 for all models).Multivariable-adjusted ORs (95% CI) for PCAD across the tertiles of UPFs consumption are provided in p trend < 0.001 for all models).Multivariable-adjusted ORs (95% CI) for PCAD severity across the tertiles of UPFs consumption are provided in -Balouch and Arab and Qashqaei, 2-Fars and 3-Kord) had statistically significant higher chance of PCAD than those in the lowest tertile .Multivariable-adjusted ORs (95% CI) for PCAD severity in different ethnicity across the tertiles of UPFs consumption are provided in In this multi-centric case-control study, a significant direct relationship was obtained between UPFs consumption and the risk of PCAD. This is the first study that examined the relation between UPFs and PCAD in a population with different ethnicities. We found 2.3 times higher risk of PCAD in the 3rd tertile of UPFs consumption. Although the share of UPFs in daily energy intake in this population was substantially lower than Western populations [6.5 vs. 60% in United Kingdom  and in tGlobal interest for consuming UPFs is rapidly increasing. UPFs are high-calorie dense products which are usually consumed in large portion sizes. Due to this fact, higher consumption of UPFs is associated with lower intake of fruits, vegetables, olive oil, nuts and legumes which are high in fiber, PUFAs, anti-oxidants and anti-inflammatory properties which all are cardio-protective , 35. SimHigh amount of salt , trans fBeyond the nutritional composition of UPFs, other harmful components and mechanisms may play a role. Additives, stabilizers and colors used in UPFs are special concerns for CVD. Phosphate, a known UPFs additive, is usually used in order to enhance appearance, and shelf life . InorganThis study comes with some limitations. Due to the nature of case–control study, establishing a causal relationship between UPFs and PCAD was not possible. In addition, in the case of using FFQ, recall bias and misclassification of individuals across tertiles of the UPFs are likely. This study also presents important strengths. First, this is the first study which examined the relationship between UPFs and PCAD. Second, using a relatively large sample size from different parts of the country with multiple ethnicities increases the external validity of our findings and therefore our results can be generalized to different populations of Iranians. Third, using the NOVA food classification which is a valid tool for nutrition epidemiologic studies.In conclusion, we found that higher consumption of UPFs was related to increased risk of PCAD and higher chance for having severe PCAD in different ethnicities of Iranian adults. Although, future cohort studies are warranted to confirm the results of this study, our findings can increase people’s awareness about the risk of UPFs consumption on cardiovascular health and the necessity to reduce UPFs intake.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Medical Ethics Committee in Isfahan, Iran. The patients/participants provided their written informed consent to participate in this study.ShA and FH contributed to the concept. FaN contributed to data entry, managing, and cleaning. KT, NM, and FSh contributed to data interpreting. ShA, FH, and NM contributed to manuscript drafting. NM and NiS contributed to study design. SM analyzed the data. EZ, SM, FeN, HA, TK, NA, NS, KS, ML, SG, EJ, AS, MD, MC, AA, HH, SN, SS, ShSh, and RM contributed to the data collection. All authors contributed to the article and approved the submitted version.This study has been funded by the Research and Technology Department, Iran Ministry of Health and Medical Education and the Iranian Network of Cardiovascular Research (296055).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Vitis vinifera L.) is mostly important for wine production in Mediterranean countries, and the variety Tempranillo is one of the most cultivated in Spain and Portugal. Drought decreases yield and quality and causes important economic losses. As full irrigation has negative effects on quality and water is scarce in this region, deficit irrigation is often applied. In this research, we studied the effects of two deficit irrigation treatments, Sustained Deficit Irrigation (SDI) and Regulated Deficit Irrigation (RDI), on the transcriptome of grape berries at full maturation, through RNAseq. The expression of differentially regulated genes (DEGs) was also monitored through RT-qPCR along berry development. Most transcripts were regulated by water stress, with a similar distribution of up- and down-regulated transcripts within functional categories (FC). Primary metabolism was the more severely affected FC under water stress, followed by signaling and transport. Almost all DEGs monitored were significantly up-regulated by severe water stress at veraison. The modulation of an auxin response repression factor, AUX22D, by water stress indicates a role of this gene in the response to drought. Further, the expression of WRKY40, a TF that regulates anthocyanin biosynthesis, may be responsible for changes in grape quality under severe water stress.Climate change in the Mediterranean area is making summers warmer and dryer. Grapevine ( Abiotic stresses are a foremost restricting factor impairing grapevine growth, yield, productivity, and long term survival in traditional Mediterranean climate areas and in new production regions. Drought is one of the most critical environmental factors affecting plant water uptake, and short and long-term adaptation of grapevine varieties to climate change .In regions with hot and dry summer seasons, major adaptations of plant metabolism are required to cope with those adverse environmental conditions. Such adaptations include regulation of transcription and gene expression, and wide transcriptome reprogramming as a response to the stress . TherefoGrapevine is one of the most important crops worldwide and the wine industry is one of the most globalized and competitive. Impending global climate change stands to severely impact the wine industry and the economy of southern Europe, through decreases in yield and grape quality ,9. EpisoWith that challenge in mind, we set out to comprehend the impact of different levels of deficit irrigation (Sustainable Deficit Irrigation and Regulated Deficit Irrigation) on the berry transcriptome of the widely cultivated grapevine variety Tempranillo. The modulation of expression of key transcripts related to the drought-induced defense mechanisms were also monitored in key phenological stages, to characterize its response to stress.PD reaching values lower than −0.7 MPa on several days between veraison and full maturation.The values of pre-dawn leaf water potential along the season in both deficit irrigation treatments  are depicted in To determine the number of transcripts exclusive to each irrigation strategy, a Venn diagram was built. At full maturation (M), 22,844 transcripts were identified, in RDI and SDI a. A totaThe ratio RDI/SDI reflects a differential regulation of expression in genes belonging to various functional categories that is modulated by water stress. The percentage of genes up- and down-regulated per functional category was plotted and is shown in The functional categories signaling and transcription factors were analyzed in more detail . In the The ten genes with the highest and lowest levels of expression are shown on sHSPs and AAE1, while two ERFs, WRKY40 and 2βDIOX were down-regulated at veraison, when compared to green pea stage. At full maturation, only AAE1 and HSP17.9B were significantly up-regulated. In SDI, all DEGs were significantly down-regulated at veraison, and most kept a down-regulation pattern through maturation, except for AAE1 and ERD4, significantly up-regulated . The only significantly down-regulated DEG at full maturation in RDI was HSP18.2C  under two different deficit irrigation conditions, SDI  and RDI (severe water stress). To achieve this goal, global gene expression was obtained by RNA-Seq at full maturation and target gene expression was monitored in the three developmental stages using RT-qPCR.In a global first analysis, a common feature of the distribution graphs of the transcripts into functional classes in SDI and RDI is the fact that the Primary Metabolism category represents the highest percentage of the graph, occupying about 50%. One of the main explanations for this result is the fact that the Primary Metabolism category involves many processes of extreme importance for the survival of the plant, such as the metabolism of carbohydrates, lipids, nitrogen, sulfur, carbon fixation, among others. Of these processes, carbohydrate metabolism tends be down-regulated, since the decrease in basic metabolism processes is typical in stress conditions ,15, as tERF gene expression. In the case of auxins, when under severe water stress (RDI), the plant activated genes within this category, which differs from the results reported by Zhang et al. [The response to water stress, as to any other type of stress factor, is mediated by plant hormones ,17. A tyg et al. , and by g et al. , where tg et al. . Howeverg et al. .Our results also show that there is a high number of transcripts encoding kinases that are activated when the plant is under severe water stress, certainly because these proteins are the main components of intracellular signaling and are responsible for rapid responses to changes in the environment . In planMYB and Zinc Finger families had several up-regulated genes in RDI, which is in line with the literature [C2H2 and C3HC3, are induced by several types of abiotic stress, including drought [AtMYB88, which increased the tolerance to abiotic stress when overexpressed in Arabidopsis, restricting the divisions that occur at the end of the stomatal cell line [As transcription factors are mediators between the appraisal of environmental signals and the expression of stress response genes, they act as switches of regulatory transcription cascades enabling the adaptation of plants to environmental changes ,30. In tterature ,32. Stud drought ,34. The  drought , with elell line .In a more detailed analysis, using RT-qPCR, two main families of genes were studied in detail, those coding for Heat shock proteins (HSP) and Ethylene Responsive Factors (ERF), along with other genes that are also associated with responses to abiotic stress. In Tempranillo at veraison, all the genes studied had significantly higher levels of expression in RDI than in SDI, while at full maturation, the differences were atoned. This result differs from the one obtained in Touriga Nacional under equivalent experimental conditions , and wheAUX22D significantly decreased throughout berry development. This decrease was modulated by water stress level, with the control decreasing to significantly lower levels than the severe water stress.During the first two weeks of berry development, its size increases markedly, as auxins directly promote cell division and growth ,39. HoweHSP are predominantly induced during ripening [HSPs analyzed would have increased their expression in RDI at full maturation, as they did at veraison, but in fact, they decreased to levels significantly lower than before the application of stress (at the green pea stage).The HSP family responds to a wide range of abiotic stresses , conferrripening ,45 due tripening , but theripening . For theERF family genes studied would be up-regulated during water stress. However, the ERFs studied accumulated significantly in response to drought only at veraison. At full maturation, only two isoforms of ERF105 were significantly up-regulated by drought. These intriguing profiles suggest that different ethylene signaling pathways can be induced at different phases of berry development, possibly also in response to stress [WRKY40, which had the same pattern of expression as both isoforms of ERF105. In fact, in Vitis amuriensis, one such relation was described in the response to cold stress, where VaERF092 regulates the expression of VaWRKY33 [WRKY40 is described as controlling anthocyanin biosynthesis in red apple [The ERF family TFs confer plants’ tolerance to stress through different mechanisms, such as inducing the expression of genes associated with resistance to stress , hormonao stress . In factVaWRKY33 . WRKY40 ed apple  and coulBerry samples were collected during the growing season in grapevine plants of the variety Tempranillo, in an experimental field located at Herdade do Esporão, Reguengos de Monsaraz . The plants were subjected to two irrigation strategies, Sustainable Deficit Irrigation (SDI), corresponding to 36% potential crop Evapotranspiration (ETc), as the control, and Regulated Deficit Irrigation (RDI), the deficit irrigation treatment, at 24% ETc. Water stress levels were monitored regularly along the season  through RNA extraction was performed with Spectrum Plant Total RNA kit , according to the manufacturer’s instructions. After the extraction, RNA samples were treated with RNase-free DNase I  according to the manufacturer’s protocol. RNA was quantified through spectrophotometry in a Synergy HT Multiplate Reader  with a Take3 Multi-Volume Plate (BioTek), with Gene5 software (BioTek). Sample quality and integrity were assessed through the A260/A280 ratio and through visual analysis on 2% agarose electrophoresis, respectively. Only samples with a ratio between 1.8 and 2.1 and with the two ribosomal RNA bands clearly visible were used for RNA-sequencing (RNA-seq).https://cpt.univr.it/en/genomics-and-transcriptomics-platform/, accessed on the 14 September 2016), as described in Carvalho et al. [Sequencing was performed in the Genomics and Transcriptomics Platform, University of Torino, Italy , as described in Carvalho et al. [In all samples, the number of Reads per Kilobase transcript per Million reads (RPKM) was individually calculated, and it matched the cleaned reads library from each sample to the reference transcriptome  were strong, the data contained in the replicates were merged and the average of the replicates was used for further analyses.RStudio R i386 3.3.2  was usedhttps://genomes.cribi.unipd.it/grape/, accessed on the 14 September 2016) by matching the transcript ID, and submitted to a blastn [Arabidopsis Thaliana Genome Database , as this database is more complete than CRIBI.In all transcripts the value of RPKM in the RDI treatment was divided by the RPKM measured in SDI (here used as the control) to assess how the expression levels of the transcripts changed in RDI relatively to SDI . A cut oa blastn  on TAIR,Venn Diagrams were used to assess the transcripts that were exclusively present in each sample, using the function venn.diagram from package VennDiagram (1.6.17) . The tracDNA was prepared using oligo-dT primers  and the kit RevertAid Reverse Transcriptase , according to the manufacturer’s instructions, using 0.5 µg RNA. The cDNA thus obtained was stored at –20 °C until further analysis.−1), and Mili-Q H2O to obtain a final volume of 20 µL. The PCR program was the following: initial denaturation at 95 °C for 2 min; 50 cycles of denaturation at 95 °C, annealing at 60 °C for 30 s and elongation at 72 °C for 45 s, with a reading of fluorescence at the end of each cycle, followed by a final elongation at 72 °C for 5 min.The transcripts used for qPCR were within functional categories of interest, such as response to stress, hormones, signaling, metabolism, and regulation, and were significantly regulated in the RNAseq analysis. Primers were designed with Beacon designer 4  Software. The sequences used were retrieved from the RNA-seq experiment, and the levels of expression in that experiment and the primer sequences used for RT-qPCR are indicated in Actin 2 (ACT), Vitis vinifera translation initiation factor 3 subunit G (TIF), and Vitis vinifera translation initiation factor eIF-2B subunit alpha (TIF-GTP). These genes were chosen due to their stability under abiotic stress conditions [The baseline subtracted logarithmic amplification plot of the fluorescence signal (ΔRn) was obtained with the readings gathered between cycles 5 and 17. The Rn threshold was set at 50 to obtain Cq values, that were exported to excel, for quantification. The ΔΔCq method  was usednditions .p-value < 0.05.Significant variations of gene expression in RDI (using SDI as control) were considered if |log2 (gene expression level)| > 2. The same rule was used in the comparison along berry development, with the phenological stage green pea as control. Variations between veraison and maturation in RDI; and between RDI and SDI in each phenological stage were assessed through Student’s t-test  for In conclusion, primary metabolism was the functional category most affected under severe water stress, followed by signaling and transport. Almost all the genes selected to be studied by RT-qPCR experienced significant increases in expression at veraison, the developmental stage that was most affected by water stress, and a pattern that appears variety-specific. At full maturation, as Tempranillo berries responded to water stress with a down-regulation of general metabolism, gene expression decreased to a minimum, with increases of the genes associated with pathways that confer tolerance to stress.HSPs. In Tempranillo berries, however, they were relevant in the response to stress at veraison, but not at full maturation. The response to water stress at late developmental stages may fall under the regulation of auxins, as the modulation of the expression of an auxin response repression factor, AUX22D, by water stress, indicates. Further, ERF105 may play a role in the regulation of the expression of WRKY40, a TF that controls anthocyanin biosynthesis, and that could be responsible for changes in Tempranillo grape quality under severe drought stress. This response suggests an interplay between ethylene signaling pathways and anthocyanin production, which may have consequences in wine quality.One of those stress response mechanisms is the induction of


Children in both groups improved their locomotor, object control, and overall physical competence (p < 0.05) over the 12-week intervention. There was a significant intervention effect for locomotor and overall physical competence (p < 0.05). Interestingly, parents did not perceive these changes in physical competence (p > 0.05). However, teachers perceived improved physical competence for children in the intervention. Our physical literacy intervention improved the physical competence of children in kindergarten and grade one.Increasing children’s physical activity engagement has short- and long-term health benefits. Developing physical competence is a key component of children’s engagement in physical activity. The purpose of our study was to assess if a 12-week home, school, and community-based physical literacy intervention improved the physical competence of children in kindergarten and grade one. Four schools were either assigned to receive the intervention (n = 2 schools) or continue with their usual practice (control sites) (n = 2 schools). Physical competence was evaluated pre- and post-intervention in 103 intervention  and 83 usual practice  children using PLAY Fun. PLAY Parent and PLAY Coach tools measured parent and teacher perspectives of children’s physical competence, respectively. The intervention effect was assessed with repeated measures MANOVA to evaluate change in physical competence, with alpha set at  Physical activity is beneficial to the health and wellness of children ,2,3, andOne way to improve physical activity engagement is through the development of physical literacy. Physical literacy is defined as “the motivation, confidence, physical competence, knowledge, and understanding to value and take responsibility for engagement in physical activities for life” . ComponeChildren 7 years of age with low physical competence continue to have low physical competence 5 years later compared to their peers . These dWhile our intuition may lead us to believe sport participation or time spent in sport are the most important, Engström  found thDespite the importance of sport, 26% of Canadian children 5 to 17 years of age do not participate in organized sport , so unstFor children in kindergarten and grade one, two of the most important settings that provide opportunities for the development of physical competence are the home and school. These settings are crucial since the family has the greatest and longest impact on a child’s behavior towards physical activity . FurtherInterventions in schools focused on improving physical competence have yielded improvements after the intervention ,31,32,33This study assessed the effect of a 12-week physical literacy intervention on the physical competence of children in kindergarten and grade one using a repeated measures cluster randomized control trial. Two hundred and seventeen  kindergarten and grade one students were recruited from two cities. In each city, the local Catholic School Divisions selected one school to act as an intervention site and another school to continue their usual practice (control site). In total four schools, matched for neighborhood demographics , participated in the project . The study received ethical approval from the University of Saskatchewan’s Behavioural Ethics Review board (BEH#16-66) and permission from the participating Catholic School Divisions. In one city, the participating school division requested that the research team use passive consent. Thus, children were automatically involved in the study unless their parents chose to opt out. In the other city, parents provided written informed consent; all children at both sites provided verbal assent prior to data collection.Physical competence was assessed using the Physical Literacy Assessment for Youth (PLAY) Tools: specifically, PLAY Fun, PLAY Parent, and PLAY Coach. PLAY Fun assessed running, locomotor, object control, and balance skills . PLAY PaSince PLAY Fun was designed for children aged 7 and up , modificIn order to facilitate the PLAY Fun assessment, a team of assessors (n = 5) was formed consisting of researchers and graduate students experienced in movement analysis with children to properly apply the PLAY Fun criterion to motor skills. Assessors were trained by a leader in physical literacy assessment (ALS) and practiced by watching a film of PLAY Fun skills and assessing them based on the criteria with feedback from the facilitator. The study’s data collection followed the recommended PLAY Fun procedures . For exaThe 12-week intervention targeted home, school, and community settings. At the home level, children were provided with a backpack that contained equipment and instructional cards or physical literacy practice at home . The actTwenty grade-specific physical literacy-focused lesson plans were developed by a physical education specialist to be taught during physical education classes . The lesFinally, at the community level, five two-hour community nights were held in the school gymnasium where families could come with their children and be involved in different physical literacy opportunities with other community members. All families in the participating classes were invited to the community nights. Additionally, families were encouraged to bring their other children. The community nights were led by the facilitator and members of the research team . The goal of the community nights was to offer parents and children an opportunity to play together and develop physical competence. The community nights involved physical literacy activities, generally in the form of games that could be easily implemented by the participants outside of the organized setting. Unfortunately, compliance was not measured in any setting during the intervention.To summarize, our intervention focused on a variety of skills, progressive challenges, collaboration with peers, individual achievement, and fun, which are key aspects for developing physical literacy ,20,46,47p-value was set at 0.05.Descriptive statistics were run to describe the sample, including demographics such as grade and the number of males and females in each group. To evaluate the effectiveness of the intervention, a repeated measure MANOVA was used to assess the intervention effect pre- and post-intervention in each of the 10 skills, the domains, and overall physical competence. Separate repeated measures MANOVAs were used to assess the intervention effect on PLAY Parent and PLAY Coach values. All statistics were performed using SPSS version 28, and the Two hundred and seventeen children from kindergarten and grade one participated and were measured at baseline; 31 children  were removed from the analysis because they did not have follow-up data. Thus, 186 children with complete pre- and post-intervention PLAY Fun assessments were included in the current analyses. PLAY Parent and PLAY Coach were obtained in one of the two cities and thus are presented as a sub-sample of the total study population. p < 0.000; 95% CI, 32.5–35.3) and usual practice groups . At follow-up, children in the intervention group (33.9 ± 6.6) had greater overall physical competence than children in the usual practice group .Differences in overall physical competence are presented in p < 0.000; 95% CI, 36.6–42.5), gallop , hop , jump , throw , catch , kick , and balance . However, they displayed a decrease in their run there and back . Children in the usual practice group improved their jump , throw , catch , kick , and balance , while their run there and back  also decreased.PLAY Fun scores at baseline and follow-up for each skill are shown in p < 0.000; ηp2 = 0.290), gallop , kick , and balance   and greater jump  and throw  at follow-up.At follow-up, children in the intervention group had higher physical competence for skip (= 0.111) . In contp = 0.010; 95% CI, 99.1–111.9) but improved in the locomotor  and object control domains . Children in the usual practice group demonstrated no change in the run domain  and improved their locomotor  and object control domains . No group differences were found in the run and object control domains. Children in the intervention scored higher in the locomotor domain post-intervention (p < 0.001).p > 0.05).PLAY Parent results are shown in p = 0.001; ηp2 = 0.139), object control competence , locomotor competence , and overall physical competence  at baseline. No group differences were found at follow-up (p > 0.05).PLAY Coach physical competence domain scores are presented in The aim of this study was to assess if a 12-week multi-setting  intervention could improve the physical competence of children in kindergarten and grade one. We found improvements in locomotor, object control, and overall physical competence for both students in the intervention and usual practice. However, children in the intervention group had greater locomotor and overall physical competence post-intervention. Surprisingly, children in the intervention decreased their physical competence in the running domain.For specific skills, children in the intervention group significantly improved their skip, gallop, hop, jump, throw, catch, kick, and balance physical competence. Children in the usual practice group improved their jump, throw, catch, kick, and balance physical competence. Additionally, children in the intervention group had higher skip, gallop, kick, and balance physical competence, while the usual practice group had higher jump and throw physical competence post-intervention. The improvements observed for children in the usual practice group could be from involvement in sports that are developing those skills  or a greater focus on those skills by their teachers in physical education. There were no differences in parental perceptions of children’s physical competence between parents of children in the intervention and usual practice groups. Teachers of children in the intervention perceived that their students had lower physical competence compared to teachers in the usual practice group before the intervention, but no differences in teacher perception of physical competence existed after the intervention.The improvements in physical competence are not surprising since physical literacy interventions have the strongest effect on physical competency outcomes . When coFor specific skills, similar results have been reported for gallop, hop, throw, catch , skip, kThe results from the PLAY Coach measurement indicated that teachers of children in the intervention group perceived their students’ physical competence as improving over time compared to teachers of children in the usual practice group. While this result is positive, because teachers of the intervention students were present for the physical literacy-enriched lessons and were asked to teach one of the lesson plans introduced that week to their class, they were aware of their students’ involvement in the intervention. This awareness could have influenced them to score these students more favorably after the intervention. However, teachers were not provided with the pre-scores they assessed their students; therefore, they would have had to remember what they scored their students’ 12-weeks previously. Additionally, given the fact that teachers in the intervention group scored their students lower at baseline compared to teachers in the usual practice group, the teachers in the intervention group may have perceived that their students lacked physical competence, and the intervention decreased the gap between the two groups.The length of the intervention likely influenced our results; other interventions of a similar duration have also found benefits ,49, suggThe multi-setting approach used in the current study may be more beneficial than solely a school-based intervention by providing ample opportunities for children to practice these skills at school, at home, and at community nights. Additionally, by design, the intervention was non-competitive and non-comparative, which may have been advantageous as these environments have been suggested to make children more willing to engage in new motor skills . Thus, iA limitation of the current study is the lack of compliance measures for the intervention in the home and community settings. While students returned their backpacks weekly to be given new equipment and physical literacy cards, and the facilitator reminded students to practice the new skills at home, we did not measure how often they were using the equipment and practicing at home. Having a compliance measure would have informed how often the children were engaging in motor development in each setting, providing more insight into how the different settings impacted physical competence. Another limitation was the need to adapt the PLAY Fun tool to be more age-appropriate. Removing skills deemed developmentally inappropriate could have affected the validity of the tool; however, the skills retained covered all the movement domains, and only the criteria for evaluating balance was altered, which may have helped to protect the integrity of the tool. Finally, since the PLAY Coach has not been validated, considerations need to be taken when interpreting the results.Having multiple assessors could have led to interpersonal reliability issues; however, all assessors were well trained, and previous studies have reported that the PLAY Fun tool has good to excellent inter-rater reliability ,44. AddiIn conclusion, a 12-week multi-setting intervention was found to be effective at improving the physical competence of children in kindergarten and grade one. Teachers of children in the intervention group perceived these changes, while parents did not. We found significant improvements in physical competence for both children in the intervention and usual practice, with a significant intervention effect. Future studies should investigate the benefits of employing multi-setting physical literacy interventions. Since physically literate children should be able to engage in a variety of motor skills in different environments  and settings , conducting an intervention in one setting may not assist in the development of certain aspects of their physical literacy.


This study aimed to investigate the impact of the different domains of intrinsic capacity (IC) and chronic disease burden on health-related quality of life (HRQoL) and domain-specific HRQoL in Chinese community-dwelling older adults.A cross-sectional observational study of a community-based cohort.n = 429, mean age, 72.91 ± 7.014 years; female proportion, 57.30%).We evaluated Chinese older adults  and psychosocial  dimensions. Low HRQoL (HRQoL score or subscores in the highest quintile) was used as a dependent variable in logistic regression analyses adjusted for demographic, health-related, and psychological confounders.IC contains five domains, namely locomotion, vitality, cognition, psychological, and sensory capacity. Locomotion dysfunction was defined as grip and/or gait decline. Vitality decline was defined if two of the following three parameters were present: fatigue, physical inactivity, and weight loss or overweight. Cognition was classified into normal cognition, pre-mild cognitive impairment (pre-MCI), and MCI according to the normative Sensory impairment was an independent determinant of senses, and locomotion impairment was significantly associated with overall HRQoL, independent living, and pain in the physical dimension of HRQoL. Cognition was an independent determinant of the senses. Vitality was independently associated with overall HRQoL, senses, and pain in the physical dimension and mental health and relationships in the psychological dimension of HRQoL. The psychological domain of IC was independently associated with overall and domain-specific HRQoL apart from senses after adjustment for all confounders. The number of multimorbidities mainly had a significant impact on independent living after adjustment for all confounders.IC domains and chronic disease burden had heterogeneous influences on overall and domain-specific HRQoL. The impairment of sensory and locomotion domains had a synergistic impact on the overall and physical dimensions of HRQoL. The vitality and psychological domains of IC had more profound effects on HRQoL. Older people with high morbidity might have a higher risk of poor independent living. Healthy aging is the process of developing and maintaining functional ability and wellbeing in old age, regardless of the presence or absence of diseases  of ≤23 kg/m2, ≤17.3 kg with a BMI between 23.1 and 26.0 kg/m2, ≤18 kg with a BMI between 26.1 and 29.0 kg/m2, and ≤21 kg with a BMI of >29.0 kg/m2. Sensory impairment of IC was diagnosed when the individual was with hearing and/or visual impairment. Hearing impairment was assessed according to the pure-tone average (PTA) based on 0.5-, 1-, 2-, and 4-kHz thresholds using pure-tone audiometry. Individuals with a PTA of ≤25 dB experiencing tinnitus in the better ear were defined as having a hearing impairment. Vision referred to the participant's eyesight with glasses or corrective lenses if they were used regularly. Visual impairment was measured using a self-reported question asking participants to rate each sense on a 5-item Likert scale as excellent, very good, good, fair, or poor  self-report questionnaire, which contains three physical  and five psychosocial  dimensions  was set to reject H0 and accept Ha. The continuous variables were expressed as medians and quartiles. A bivariate correlation was analyzed using Pearson's test for normally distributed variables and Spearman's test for non-normal distribution variables and X2 for categorical variables. The difference among the four groups based on sensory and locomotion impairment for continuous variables was tested using univariate ANOVA analysis. When the homogeneity of variances was inappropriate, the Mann–Whitney U-test was employed to analyze the univariate correlation. The association between the different domains of IC or the number of multimorbidities with low overall HRQoL scores, and each low subscore of domain-specific HRQoL was further assessed using multiple logistic regression analyses adjusted for age, sex, and education levels (Model 1), adjusted for covariates in Model 1 and other health covariates, including smoking, drinking, multimorbidities, vitality, and cognitive performance (Model 2), and adjusted for covariates in Model 2, and GDS scores (Model 3). A P-value of < 0.05 was considered statistically significant, and all statistical analyses were performed using the SPSS software (version 18.0).The null hypothesis (H0) of the study was that there is no effect of IC domains on overall and domain-specific cognitive performance. Accordingly, the alternative hypothesis (Ha) was that there is a significant effect of IC domains on overall and domain-specific cognitive performance. The alpha level  is indicated in Among the three physical domains, compared to those with sensory and locomotion impairment, individuals with a lack of sensory and locomotion impairment had better independent living and senses after being adjusted for confounders in Model 1 , Model 2 , and Model 3 , respectively, and they also experienced less pain  in Model 1. Individuals with sensory impairment had better independent living in Model 1  and Model 3  and experienced less pain in Model 1 . Individuals with locomotion impairment had better senses after being adjusted for confounders in Model 1 , Model 2 , and Model 3 .Apart from older age, low education level significantly increased the odds of adverse influence in the senses  and pain  domains of HRQoL after being adjusted for confounders in Model 3. Multiple logistic regression analysis of the association of other domains of IC, and chronic burden with HRQoL indicated that the cognitive impairment, vitality, and psychological domains of IC, and chronic burden had different influences on HRQoL and the physical dimension of HRQoL . IndividMultiple logistic regression analysis indicated that chronic disease burden had different effects on HRQoL and the physical dimension of HRQoL . Those wThe capacity decline of the IC cognitive domain (no more than MCI level) did not affect the psychological dimension of HRQoL and the reserve decline in vitality and psychological domains of IC, and chronic burden had a domain-specific influence on the psychosocial dimension of HRQoL. Compared to those with low vitality, individuals with high reserve showed a significantly higher likelihood of better mental health in Model 2  and Model 3 , more happiness in Model 2 , and better relationships in Model 2  and Model 3 . Those with lower capacity of IC psychological domain (higher GDS score) had a low likelihood of better mental health , more happiness , higher self-worth , less coping , and better relationships  after being adjusted for all confounders in Model 3.Multiple logistic regression analysis indicated that chronic disease burden had a significant influence on mental health, coping, relationships, and the psychosocial dimension of HRQoL . CompareIn this cross-sectional study, we found that IC domains had different influences on HRQoL and domain-specific HRQoL. Individuals with sensory impairment indicated low HRQoL in senses of physical dimensions. Those with locomotion impairment had significantly low HRQoL in independent living and pain in the physical dimension. The combined effects of sensory and locomotion domains in IC indicated low HRQoL in all three domains of the physical dimension . ParticiLow IC reserve has been verified to be associated with worse physical, mental, and total QoL , may be objective to assess vitality  of physical dimension, and mental health and relationships and happiness (in Model 2) in the psychological dimension. Compared with IC, chronic disease burden mainly had a profound impact on HRQoL in the physical dimension and some domains in the psychological dimension. Participants with more multimorbidities had a higher likelihood of worse independent living and pain in the physical dimension and a significantly higher likelihood of worse HRQoL in coping and relationships in the psychosocial dimension after adjusting for all confounders, and mental health after adjustment for demographic and health-related confounders in Model 2. The vitality domain reflects the energy metabolic capacity for the maintenance of an individual's optimal homeostasis level . The patients/participants provided their written informed consent to participate in this study.QR and ZY conceived and designed the manuscript. QR wrote the manuscript. JC, ZB, ZY, and QR revised the manuscript. XH, JR, JC, ZB, QR, and WZ conducted the investigation and data analysis. All authors contributed to the article and approved the submitted version.


Depression in diabetes patients is caused by their own disease or the surrounding social environment. How to cope with changes in mentality and adjust psychological stress responses, especially under China’s dynamic zero COVID-19 policy, is worth further discussion. The researchers constructed a moderated mediation model to test the effect of psychological resilience during dynamic zero COVID-19 on depression in diabetes patients and the mediating role of stigma and the moderating effect of medication burden.From June to September, 2022, data were collected in Jinghu District, Wuhu City, Anhui Province, by multi-stage stratified sampling. Firstly, we selected a tertiary hospital randomly in Jinghu District. Secondly, departments are randomly chosen from the hospital. Finally, we set up survey points in each department and randomly select diabetes patients. In addition, we used the Connor-Davidson Elasticity Scale (CD-RISC) to measure psychological resilience of patients, and used the Stigma Scale for Chronic Illness (SSCI) to measure stigma, medication burden was measured by the Diabetes Treatment Burden Scale (DTBQ), and depression was assessed by the Patient Health Questionnaire-9 (PHQ-9). We used SPSS (version 23.0) and PROCESS (version 4.1) for data analysis.(1) Psychological resilience was negatively correlated with stigma, medication burden, and depression. Stigma was positively associated with medication burden and depression. Medication burden and depression are positively correlated, (2) The mediation analysis showed that psychological resilience had a direct predictive effect on depression, and stigma partially mediated the relationship, and (3) Medication burden moderates the direct pathway by which psychological resilience predicts depression; Medication burden moderates the first half of “psychological resilience → stigma → depression.”Under the mediating effect of stigma, psychological resilience can improve depression. Medication burden has a moderating effect on the relationship between psychological resilience and depression, and it also has a moderating effect on the relationship between psychological resilience and stigma. These results facilitate the understanding of the relationship mechanisms between psychological resilience and depression. The polGlobally, depression is the second leading cause of disability, characterized by loss of happiness, depressed mood and suicidal behaviors . DepressMany factors can affect depression, including psychological resilience. Psychological resilience (PR) plays an important role in adapting to the changes brought about by a pandemic and seeking to restore psychological well-being in people with diabetes . PR refeThe long-term medication burden of diabetes increases the burden of self-experience for patients, who are left in a state of chronic stress and loss of control, triggering stress reactions including depression, anxiety, stigma and other diabetes-related psychological problems . OriginaMedication burden (MB) is one of the key components of treatment burden. Xin et al.  defined Therefore, we hypothesized the following: (1) PR is negatively associated with depression in diabetes patients, (2) Stigma mediates the relationship between PR and depression, and (3) MB plays a moderating role in the relationship between PR, stigma, and depression in diabetes patients .2.2.1.Participants were recruited from a tertiary hospital in the Wuhu City (China) by multi-stage sampling. The inclusion criteria were as follows: (i) All patients should meet the diagnostic criteria for DM established by the American Diabetes Association, (ii) Patients are conscious and have full mobility and cognitive ability, and (iii) Patients are willing to cooperate and complete the questionnaire. Exclusion criteria are as follows: (i) presence of severe mental impairment or intellectual problems, (ii) severe diabetic complications or inability to care for themselves, (iii) other serious illnesses such as severe cardiovascular disease, severe infectious diseases, cancer, visual and hearing impairment due to complications of DM, and (iv) pregnancy or other specific diabetes. To reduce errors, relevant personnel was trained before the investigation to clarify communication skills and scoring standards. After obtaining the informed consent of the diabetic, the questionnaire was issued, and the patients answered by themselves. For illiterate patients, the investigators asked face-to-face and then filled out the questionnaire. All methods are implemented following the declaration of Helsinki.2.2.From June to September 2022, this study used a multi-stage sampling method and random number table method to collect data from tertiary hospitals in Jinghu District, Wuhu City, Anhui Province. Firstly, the First Affiliated Hospital of Wannan Medical College was randomly selected from all tertiary hospitals in Wuhu, Anhui Province. Secondly, four departments were strategically selected from this hospital: endocrinology, geriatrics, traditional Chinese medicine, and dermatology. Thirdly, survey points were set up in each department, and diabetes patients were strategically selected for questionnaire surveys. Based on the criteria proposed by Kendall (5 ~ 10 times the number of items and expanded by at least 10% to ensure an adequate sample size), we need at least 228 samples. Eventually, a total of 334 questionnaires were distributed and 329 valid questionnaires were returned, with a valid return rate of 95.85%.2.3.2.3.1.The Conner-Davidson Resilience Questionnaire (CD-RISC) was developed by psychologists Professors Conner and Davidson in 2003 . The CD-2.3.2.The Stigma Scale for Chronic Illness (SSCI) was an instrument developed by Rao to measure stigma in people with chronic illnesses . It cons2.3.3.The Diabetic Treatment Burden Questionnaire (DTBQ) was compiled by Professors Ishii H and Shin K in 2018 , and it 2.3.4.The Patient Health Questionaire-9 (PHQ-9) was derived from the depression part in the Patient Health Questionnaire (PHQ) compiled by Spitzer in 1999 . PHQ-9 w2.4.SPSS23.0 was used to conduct all statistical analyses. Harman single factor test was used for exploratory factor analysis of all the questionnaire items. The results showed that there were 25 factors with eigenvalues greater than 1. The first factor explained only 18.913% of the variance, which was less than 40% critical standard, suggesting that there was no common methodological bias.We used SPSS 23.0 to accomplish all the statistical analyses. Firstly, we calculated general and controlled variables for descriptive statistics and bivariate correlations. Secondly, we used Hayes’ PROCESS (2013) macro (model 4) to evaluate the mediating effect of stigma. Finally, we analyzed the moderator–mediator model with Hayes’s PROCESS macro (model 8) (2013). All the continuous variables were standardized, and the interaction terms were calculated from these standardized scores. The bootstrap method produces 95% bias-corrected CIs for these effects from 5,000 re-sample of the data. CIs that do not contain zero indicate a significant effect.2.5.Approval for this study was given by the medical ethics committee of Wannan Medical College . All the participants were informed that they would bear no penalty for refusal to participate in the study and would be allowed to withdraw at any time without affecting their treatments. Informed consents were obtained before questionnaires were administered to participants.3.3.1.3.2.r = −0.325, p < 0.01) and MB , as well as depression .The stigma was positively correlated with MB  and depression . MB was positively correlated with depression .The mean, standard deviation, and correlation between variables are shown in 3.3.β = −0.069, p < 0.001), and PR explained a total of 41.2% of depression . PR was associated negatively with stigma . Stigma was associated positively with depression . We examined the indirect effect  and direct effects  of PR on depression by testing 95% CIs based on 5,000 bootstrapped samples, indicating stigma partially mediated the relationship between PR and depression  proposed by Hayes, after controlling for the variables of monthly income and SMBG demographics . The respression . The ind3.4.To examine H2 and H3, we adopted PROCESS macro (Model 8) proposed by Hayes to examine the moderated mediation. Specially, we estimated parameters for two models. In Model 1, we estimated the moderating effect of MB on the relationship between PR and depression. In Model 2, we estimated the moderating effect of MB on the relationship between depression and stigma.β = −0.272, SE = 0.594, 95%CI = ), which was moderated by MB . Model 2 revealed a major impact of PR on depression , which was moderated by MB . And it revealed a major impact of stigma on depression , which was not moderated by MB . Hence, hypothesis 2 and 3 were partially supported. The final moderated mediation model was shown in As shown in Z = −1), depression has a significant downward trend with the increase of PR , PR increased by one standard deviation, and the total score of depression decreased by 0.049 standard deviations, that is, the higher the level of PR, the lower the degree of depression; For diabetes patients with high-level MB (Z = 1), With the increase of stigma, the degree of depression also showed a significant downward trend , and the downward trend was higher than that of diabetes patients with low MB.Z = −1), stigma decreased significantly with the increase of PR . One standard deviation increase in psychological resilience was associated with a 0.363 standard deviation decrease in stigma. The higher the PR, the lower the degree of stigma; For diabetes patients with high-level MB (Z = 1), with the increase in PR, the decline of stigma was also significant . One standard deviation increase in psychological resilience was associated with a 0.639 standard deviation reduction in stigma, slightly higher than in diabetes patients with a lower MB.4.In this study, the results showed that PR was negatively associated with depression in older patients with diabetes, and this relationship was mediated by stigma. Furthermore, the moderating effect suggests that MB moderated these relationships during the COVID-19 policy. And, consistent with our hypothesis about the moderating effect, we found that MB moderated the association between PR and depression, and moderated the effect of PR on stigma. At the same time, the study results showed that only 7.9% of older diabetic patients did not have depression, up to 56% of patients had mild to moderate depression, and 36.1% had moderate to severe depression. This phenomenon indicates that the incidence of depression in older diabetic patients in China is high during COVID-19. Overall, our findings broaden our understanding of PR and depression and contributed to research linking depression to PR.Older people with diabetes were at high risk for increased depression associated with dangerous public health emergencies. Our results were consistent with previous studies , 52, andOur results showed that PR was negatively correlated with stigma and depression, which was consistent with previous findings . Thus, PModeling predictors of depression had identified PR as a protective factor in young people and stigma as a precipitator of depression. This finding highlighted the importance of monitoring stigma in older diabetics. In our study, stigma was found to mediate between PR and depression, suggesting that older diabetics who experience the shame of their illness and the blame of others reduce perceived PR and thus increase depression in the context of COVID-19. These findings were consistent with previous research on depression , 62. OurMany studies , 65 suppIn this study, we constructed and tested a hypothetical model based on the results of previous research and theory to determine whether PR might be a protective factor for depression. We also examined the mediating role of stigma and investigated whether MB moderated the mediation model in the context of the COVID-19 pandemic. Clearly, the model shows that older diabetics can maintain their mental health during the COVID-19 pandemic if they have good high levels of mental resilience and pay attention to managing stigma and MB. Resilience is associated with the ability of individuals to manage stress . At the The current study suggested that stigma and MB mediate the relationship between PR and depression, a finding that may have useful clinical implications. Our study suggested that the relationship between PR and depression can be partially affected by more frequent stigma in older diabetics. In addition, we found that MB not only moderated the relationship between PR and depression, but also the effect of PR on stigma. Therefore, risk factors such as stigma and MB increased the risk of depression among older Chinese patients with diabetes during the COVID-19 pandemic. These findings suggested that governments and educational institutions should work together to address the deterioration of mental health in older people with diabetes and provide timely and effective services to promote adaptive and positive mental health in this age group. Together, our findings shed light on the relationship between PR and depression and broaden our understanding of how to use protective factors, such as resilience, to formulate public health interventions during the COVID-19 pandemic, especially in the older adult population with diabetes.4.1.There are several limitations to this study. Firstly, due to the study’s cross-sectional design, we could not make any causal inferences about the observed associations. Future research should use longitudinal studies to better define the pathways in our theoretical model. Secondly, although self-reporting has been widely used in the literature, this data collection method has inherent disadvantages, such as being highly subjective, inevitably leading to some bias in the data. Future research should include multiple data collection methods to cross-check and obtain more objective and accurate data. Finally, future research should explore the mechanisms of influence of different psychological factors to obtain more accurate findings. Further investigations should not only use a more representative sample and validate the findings, but also focus more on the different mechanisms by which resilience and depression affect others, and clearly measure the impact that the COVID-19 pandemic may have on variables . As a result, future research may involve more psychological structures, such as social anxiety, social support, and self-esteem, to better understand how individuals cope with the adverse consequences of COVID-19 and possibly respond more adaptive in future pandemics.5.This is the first time we have established a moderating mediation model between PR and depression. Our findings showed that stigma played a mediating role in the association between PR and depression. MB plays a role in regulating the relationship between PR and depression. Specifically, with the increase of PR, depression decreased, and the decreasing trend of depression in patients with high MB was greater than that in patients with low MB; In addition, MB also played a moderating role between patient stigma and depression. As patients’ PR increased, stigma decreased, with a slightly greater tendency to decrease in patients with high MB than in those with low MB. Therefore, we should be fully aware of patients’ PR levels and intervene in a timely manner to improve their psychological status. At the same time, MB as an influencing factor needs to be considered with a view to better protecting patients’ psychological well-being. Medical professionals should give regular public lectures on stigma and depression prevention and control measures to achieve early screening, diagnosis, and intervention. Patients should also be regularly questioned about their medication in order to understand the presence of MB and intervene in a timely manner.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by medical ethics committee of Wannan Medical College. The patients/participants provided their written informed consent to participate in this study.LZ conceived and designed the research. YM wrote the paper. YM and LZ analyzed the data. YM, LZ, XY, YL, JG, XZ, YW, and CL revised the paper. YM, XY, JG, YL, XZ, YW, WC, MC, CL, and LZ reviewed the manuscript. All authors contributed to the article and approved the submitted version.The research was supported by the Support Program for Outstanding Young Talents from the Universities and Colleges of Anhui Province for LZ (gxyqZD2021118); The study was supported by the Research on the Creation of International Rules for China’s Participation in Global Health Governance and Path Selection” (21yjcgjw006); The study was supported by the National Innovation and Entrepreneurship Training Program for College Students (202210368016); The study was supported by the Research Practice of Elderly Nursing (2021shsjkc030).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Sleep bruxism in preschool children has a higher prevalence in boys and is more frequently expressed from 5 years of age. Open bite, overbite, and crossbite should be considered factors associated with parafunction.The prevalence of bruxism in the preschool population varies according to different investigations. The aim of this study was to investigate the prevalence of sleep bruxism and its relationship with social and orofacial factors in children aged 3 to 5 years. Three hundred forty-three preschool children were divided into two groups, one with nocturnal bruxism, as reported by parents, and another without this disorder. Questionnaires were distributed to the parents to determine the children’s family social status and parafunctional habits at the time of the study. The clinical inspection confirmed the presence of certain parafunctional habits and the children’s occlusal characteristics. The data obtained were analysed using descriptive statistics such as frequency chi-square tests to identify the influence of qualitative variables. Of the total sample, 28.9% of preschoolers presented sleep bruxism. The highest prevalence was observed in boys (61.6%) at the age of 5 years (41.4%). Characteristics associated with this pathology were lip incompetence, open bite, crossbite, and overbite, with  Bruxism is a non-functional and repetitive involuntary activity of the masticatory muscles . Its prePaediatricians must be trained to issue presumptive diagnoses in children and educate parents to prevent complications that affect oral and systemic health . The thrThe therapeutic management of child bruxism at the dental level is complicated. Some therapeutic options include kinesitherapy, massage, infrared, and low-intensity laser therapy . The useDrug treatments with hydroxyzine, trazodone, flurazepam, occlusal splints, and orthodontic and psychological therapies are therapeutic options for adults .The factors predisposing individuals to this parafunction are still a topic of debate; because of this, it is essential to develop research in this field. Thus, the main aim was to determine the prevalence of sleep bruxism and its relationship with family social class, parafunctional habits, and occlusal characteristics in the preschool population as possible factors associated with bruxism.A descriptive, observational, cross-sectional, and epidemiological study was designed. It was carried out under the statutes and approval of the Ethics Committee of the European University of Madrid and the Clinical Research Ethics Committee of the Insular-Maternal and Child University Hospital Complex (CEIC-CHUIMI-2015/807).Data collection was performed before the declaration of a state of alarm due to coronavirus in the municipality of Arrecife .The sample size was calculated considering a total population of 2108 users, an expected proportion of 30% [p < 0.05 was determined for the minimum number of 283 patients with a power of 80%. Meanwhile, 343 patients in total were chosen for the final sample.A significance level of This study included healthy patients aged 3 to 5 years with a Canarian health card who attended paediatric consultations in Arrecife and whose parents signed the consent form allowing them to participate in all study phases. Patients without personal and complete medical data, negative behaviour , and mixed dentition were excluded .The lead researcher in the primary care paediatric office performed the data collection three days a week with a simple random sampling technique.After obtaining the informed consent and the affiliation and medical data, the questionnaire was completed via a guided interview with the parents, where information was collected on breastfeeding and parafunctional and non-nutritive habits such as time of use of the bottle and pacifier, presence of the digital sucking habit, onychophagia, mouth breathing, or lip incompetence. The diagnosis of bruxism was based on the information reported by the parents. Finally, the family’s social status data were collected , consideThe average time spent on the interview was approximately 5 min per participant.The recommended methodology by the WHO was followed. A previously trained and calibrated researcher conducted the examination in the dental chair (Fedesa JS 500 Spanish manufacturing) with the preschoolers in semi-fowler position and the neck in extension. The intraoral examination was performed with a mouth mirror without magnification while the examiner stood .The presence of habits such as oral breathing was confirmed by observing the lack of lip seal and the presence of adenoid facies and lower lip incompetence. Finger sucking and onychophagia were verified via visual inspection of the child’s fingers.The presence of primary teeth and interdental spaces were recorded, along with the occlusal characteristics in the three anatomical planes . In the It was considered that an occlusal alteration was present when the child exhibited an overjet, a long mesial step, a distal step, and a mixed component, as well as an overbite of 2/3 and 3/3, open bite, and crossbite. The time used in the examination per patient was approximately 10 min.To evaluate intra-observer reliability, a second clinical examination was conducted on 10% of the sample one week after the first inspection. The obtained kappa value was 0.9, indicating a significantly high level of agreement.p < 0.05 was established.SPSS IBM version 26.0 for Windows was utilised for the statistical analyses. Descriptive statistics, such as frequencies, were employed to represent the qualitative variables of the sample. Contingency tables and the chi-square test were utilised for inferential statistics to assess the independence or influence between two qualitative variables. Furthermore, the prevalence ratio was employed to measure the association, 95% confidence intervals were calculated, and a significance level of p = 0.017) and preschool age (p = 0.05).The initial population consisted of 361 patients. However, the final sample size for this study was 343, as participants were excluded due to non-attendance of the medical appointment, and thirteen were excluded due to lack of cooperation from the preschool. Of all the preschoolers included, 99 (28.9%) were reported by their parents as having bruxism. The distribution of the sample is presented in Among the parents of the total number of preschoolers, 29.7% were semi-skilled manual workers, the distribution of the presence or absence of bruxism in each family social class is presented in When analysing the association between registered parafunctional habits and possible bruxism in preschoolers, significance was only found in the variable of lip incompetence, as shown in Several occlusal factors are significantly associated with the habit of bruxism, such as occlusal alterations in the vertical and transverse planes. These factors are presented in The diagnosis of sleep bruxism in young children is commonly based on the report of family members seeking advice due to the annoying grinding sound. Access to polysomnographic records is limited, and clinical manifestations of bruxism are not as evident as in adults, particularly children aged 3–5. Therefore, most studies in this age group have been conducted based on possible diagnoses. This underscores the need for further investigation to enhance our knowledge of the condition in this population and develop effective diagnostic and therapeutic strategies ,29The prevalence of sleep bruxism in early childhood shows great variability according to the scientific literature. Bulanda et al.  determinAccording to Clementino et al. , the habOther studies, such as Ghafournia et al. , observeThe results of other researchers indicate a higher prevalence. According to Alencar et al. , 32.8% op = 0.034). Similarly, Clementino et al. [p = 0.020). However, this study found a statistically significant difference, with the male group being the most prevalent, possibly due to unconsidered factors such as personality traits or anxiety [p = 0.097; p = 0.393). Similarly, De Alencar et al. [In this regard, a consensus has yet to be reached. Alves et al.  reportedo et al.  identifi anxiety , as well anxiety , Simões- anxiety , Gomes e anxiety , Massign anxiety , and Nah anxiety  also fair et al.  and Ferrr et al.  did not Similar to the sex variable, there is no consensus on social factors. Perhaps the age of the children studied may influence this aspect, as their emotional development can influence managing family dynamics derived from the social aspect. Some researchers suggest a significant relationship between high and medium socioeconomic status . HoweverIn this context, parents’ social status may serve as a proxy for various bruxism-related factors, including lifestyle factors resulting from occupation, work engagement, and psychological traits. An in-depth understanding of these potential factors may facilitate a better comprehension of the aetiology of bruxism in children. It may contribute to the development of effective prevention and intervention strategies.p = 0.112). Simões-Zenari et al. [p = 0.036), lip biting (p < 0.001) and onychophagia (p = 0.028). Regarding pacifier use, children with this habit are seven times more likely to have bruxism. Children who bite their lips are five times more likely to be bruxists. In the present research, the presence of onychophagia (27.3%) and oral breathing (14.1%) and their relationship with sleep bruxism were insignificant. Research with populations of higher age ranges (8 to 10 years) indicates that children with sleep bruxism more frequently have a history of onychophagia (62.3%), lip sucking (63.2%), handkerchiefs (48.4%), and fingers (63%). However, these results are not statistically significant except for sucking on objects (p = 0.001) [p < 0.001), who are 2.71 times more likely to be bruxists.The highest prevalence in our sample was associated with bottle use ≥24 months (51.5%) and pacifier use <24 months (62.6%). DaCosta et al.  found sii et al.  observed= 0.001) . Lamenha= 0.001)  reportedEmodi-Perlman et al. have reported that habits such as pacifier use and onychophagia increase the likelihood of a child developing sleep bruxism. Therefore, healthcare professionals are advised to be vigilant in identifying clinical signs of bruxism in children who exhibit or have a history of pacifier use and nail-biting . These hp = 0.023) as well as the mesial step (p = 0.001) in preschool children aged 3–6 years. Considering the discrepancies between these investigations, it is necessary to consider the peculiarities of masticatory function rather than solely focusing on occlusal characteristics since an abnormal mandibular function can lead to bruxism regardless of the child’s occlusion type. In this present study, bruxist preschoolers exhibit crossbite (17.2%) and open bite (5.1%), which are statistically significant occlusal characteristics, unlike other investigations [p = 0.002). Although, according to Gomes et al. [p = 0.226). Once again, this reinforces the idea that the masticatory function is relevant.According to Da Costa et al. , childreigations . Nahás-Sigations  also fous et al. , malocclp = 0.656). In a similar line of research, Hazar Bodrumlu et al. [There has not been found research that indicates the presence or absence of diastemas as a factor associated with sleep bruxism. Although this characteristic indicates the degree of maxillary bone development based on the observed results, it is not a statistically significant factor concerning bruxism. (u et al.  found thu et al. .Using questionnaires to diagnose bruxism in preschool children is a reliable and cost-effective method. However, parents sometimes need to be made aware of parafunctional behaviours, partially because children sleep separately from their parents, which could lead to underestimating the prevalence using this diagnostic method. In addition, at these ages, the clinical manifestations related to bruxism are mild and can easily go unnoticed.Paediatric sleep bruxism serves as an indicator of adverse health status and highlights the need for early intervention. Multiple etiological factors in a child increase the probability of bruxism. Therefore, the findings from this research could help the paediatrician and dentist guide the anamnesis and inform parents about the risks associated with increased levels of masticatory muscle activity in their child. However, further studies with similar sample ranges are recommended to more accurately assess the relationship between age, sex, orofacial and social factors, and bruxism.The prevalence of sleep bruxism in preschool children aged 3 to 5 years was 28.9%. Factors associated with this habit include age, sex, open bite, and increased overbite and crossbite.Early diagnosis and treatment are crucial, Considering the long-term effects of this habit on the child’s overall health status. We strongly recommend that paediatricians and other health professionals identify and inform parents about parafunctional behaviours, emphasising the multidisciplinary approach and the necessity of managing its development.The primary and noticeable symptom of bruxism in children is grinding. The unpleasant, repetitive sound that occurs during sleep serves as a clear indication of non-functional tooth contact. It is also valuable for parents to be aware of the risk factors and factors associated with bruxism. Its multifactorial aetiology necessitates treatments that extend beyond dental care and encompass various aspects of human well-being.