Diabetes and prediabetes ) are adverse health effects associated with exposure to pesticides. However, there are few epidemiological studies on the relationship between pesticide use and the incidence of AGR. We examined the causal relationship between pesticide use and AGR incidence in a rural population using data from a Korean Farmers’ Cohort study of 1076 participants. Poisson regression with robust error variance was used to calculate the relative risks (RR) and 95% confidence intervals (CI) to estimate the relationship between pesticide exposure and AGR. The incidence of AGR in the pesticide-exposed group was 29.1%. Pesticide use increased the RR of AGR . We observed a low-dose effect related to exposure of pesticides to AGR and a U-shaped dose–response relationship in men. Pesticide exposure is related to the incidence of AGR, and the causal relationship differs between men and women. Pesticides are toxic substances used to kill living organisms for various purposes , and agrIt is well known that diabetes increases the mortality rate of affected patients, causes complications when not properly treated, reduces the quality of life of patients, and causes socioeconomic problems ,13. The Rapid urbanization and increasingly sedentary lifestyles in several countries have contributed in part to the increase in the prevalence of insulin-resistant diabetes . TherefoTherefore, our objective was to investigate the risk of AGR—including diabetes and prediabetes—using a detailed pesticide exposure questionnaire and population-based longitudinal data from the general population living in rural areas. Few studies have attempted to determine the causal relationship between cumulative exposure to pesticides and AGR, including prediabetes. Most previous studies on the association between pesticide exposure and diabetes, which did not include prediabetes, were cross-sectional studies. Additionally, previous studies that evaluated pesticide exposure by measuring pesticide metabolites by biomarker measurements are somewhat unreasonable for reflecting long-term chronic exposure to pesticides other than organochlorine pesticides that may remain in the human body . TherefoThis study used data from a cohort study of Korean farmers. This rural cohort study aimed to elucidate the prevalence, incidence, and risk factors of chronic diseases such as hypertension, diabetes, and cardiovascular disease. Participants lived in the rural areas of Wonju and Pyeongchang, Gangwon-do, Republic of Korea and were between 39 and 72 years of age . The InsBaseline and follow-up examination were carried out between November 2005 and January 2008, and between April 2008 and August 2012, respectively. At baseline, 5178 subjects were chosen, of which 2568 participated in an additional survey of pesticide exposure. In this study, to determine the link between pesticide exposure and AGR, pesticide exposure or pesticide use was limited to occupational pesticide use, and did not include indirect exposure to the surrounding environment or pesticide ingestion through food or water. We excluded 217 participants with insufficient data on pesticide exposure, 603 participants who were lost to follow-up, and 672 participants with suspected diabetes or prediabetes detected on blood tests. Ultimately, 1076 participants were included in the study. The mean follow-up period was 2.64 years.Continuous variables such as age, fasting blood glucose level, glycated hemoglobin (HbA1c), and body mass index (BMI) were expressed as mean ± standard deviation (SD), and categorical variables were expressed as counts with percentages (%). Smoking status was divided into three groups . Alcohol use was divided into two groups according to current alcohol consumption (no/yes). Physical activity was divided into two groups according to regular exercise (no/yes). Patients were divided into two groups according to the monthly income of 1,500,000 Korean Won , divided into two groups according to the highest educational qualification , and divided into two groups according to the marital status (married or other status). N = 91). Data from this pilot sample were not used in subsequent analyses. The target respondents were adults between 39 and 72 living in rural areas. The pesticide exposure group was defined as those who sprayed pesticides occupationally (including those who owned farms or farm workers). The study was conducted through face-to-face interviews, after each participant provided written informed consent. The interviews were conducted in the local language, and participants were asked to provide detailed information on their use of pesticides. They were asked to state whether they had ever used pesticides and if they had mixed or applied any pesticides. The sum of years of pesticide use and the average number of days per year of pesticide use were also assessed. To collect data on pesticide exposure, we used a revised standardized questionnaire developed by the Agricultural Health Study (AHS) in a baseline survey. AHS, a study conducted by the National Cancer Institute, developed a quantitative method to estimate long-term pesticide exposure in a large prospective cohort study of more than 58,000 pesticide sprayers in North Carolina and Iowa . In 2005Although the types of pesticides were not considered in the questionnaire, among the possible pesticides to which our study subjects were exposed, the following pesticides have been reported to have a high probability of causing health effects; paraquat (quaternary ammonium herbicides), organophosphate insecticides, organophosphate herbicides, pyrethroid insecticides, carbamate insecticides, organochloride insecticides, and phenoxy herbicides . In KoreExposure to pesticides can occur during transport, mixing, application of pesticides, or cleaning and repair of equipment. Based on these factors, the intensity of pesticide exposure and the cumulative exposure index (CEI) were calculated as follows :*IntensiPesticides were divided into three groups according to the mixing status , which were further divided into six groups . The repair status was a two-level variable based on whether the equipment was repaired personally . For using PPE, participants were scored according to using protective equipment and divided into eight groups  . Years oThe outcome was the incidence of AGR. The classification of AGR was based on standard cutoffs for FPG and HbA1c, as defined by ADA ,32. Normt-test was initially used to calculate the number of participants and percentiles based on each continuous variable. A chi-square test was performed for each categorical variable to estimate the difference in the incidence of AGR according to the covariates and calculate the p-value. For common events such as the occurrence of AGR, the odds ratio can overestimate the relative risk (RR) [p-value of <0.05. All analyses were performed with the SPSS statistical software package .To examine the relationship between pesticide exposure and AGR, a isk (RR) . Poissonisk (RR) . Therefop = 0.32). For HbA1c, the mean fasting glucose was 5.21% (SD ± 0.01) in the group without pesticide use and 5.28% (SD ± 0.10) in the group with pesticide use (p <0.0001). There were also statistically significant differences in age and BMI between the groups without and with pesticide use. Furthermore, sex, smoking status, alcohol use, regular exercise, monthly income, education, and marital status were significantly different between groups.The descriptive and baseline information of the study population at enrollment is listed in p < 0.001). AGR was observed in 23.1% and 29.1% of patients in the groups without pesticide use and with pesticide use, respectively . The incThe incidence of AGR was significantly higher in participants with pesticide use than in those with no pesticide use . The incIn p-value = 0.026). We also confirm the relationship between pesticide exposure and the resulting occurrence of AGR . Furthermore, when CEI, an indicator of cumulative exposure to pesticides, was the first quartile, second quartile, third quartile, and fourth quartile, the RR were 1.46 (95% CI 0.93–2.31), 1.31 (95% CI 0.89–1.94), 1.29 (95% CI 0.85–1.95), and 1.63 (95% CI 1.18–2.27), respectively (In this study, the occurrence of AGR in the pesticide use group was 29.1%, which was higher than 23.1% in the pesticide non-use group (ectively . This inIn our study, the incidence of AGR was 29.1% during a 2.64-year follow-up period. As most diabetic diseases occur after prediabetes , the shoA study by Duzguner et al., which dealt with neonicotinoid pesticides and neurological and hepatotoxicity in rats, also suggested that oxidative stress and inflammation may participate in the development of diabetes . ParticiIn a previous study, we confirmed that exposure to pesticides was related to the development of metabolic syndrome , and diaIn this study, the risk of occurrence of AGR was shown to increase even when individuals were exposed to low concentrations of pesticides. Therefore, it is necessary to actively wear PPE even if the pesticide application period or frequency of application is small. This can also be improved through farmers’ pesticide education. For example, an agricultural council could encourage farmers to use pesticides responsibly by providing intensive training that includes information on the importance of using pesticides correctly, such as wearing protective gear and using pesticides in the right amount . In addiConversely, in a situation where the prevalence of diabetes and the burden thereof increase, prevention of new diabetes and prediabetes caused by exposure to pesticides may reduce some of these burdens. The nanotechnology related to pesticides is expected to play an important role. One of the goals of nanotechnology in agriculture is to reduce the use of toxic chemicals. Incorporated nanoformulations with herbicides have also been reported to reduce the environmental toxicity and genotoxic effects of agricultural products. As a result, the use of these nanoformulations can reduce the farmer’s cumulative exposure to pesticides and can be expected to have a preventive effect on various health effects, such as decreased insulin function due to exposure to pesticides .Our study has some limitations. First, total pesticide exposure was calculated using the method described by Dosemeci et al. . AlthougDespite these limitations, our study had several advantages. This is the first study to consider the causal link between pesticide use and AGR, including diabetes and prediabetes. Additionally, to our knowledge, the risk of AGR occurrence was calculated in relative detail according to the level of pesticide exposure. Based on this, the possibility of a low-dose toxic action as a mechanism for the occurrence of AGR by exposure to pesticides was presented for the first time in an epidemiological study. Finally, we included more than 1000 participants in the analyses, which is one of the strengths of this cohort study. On the contrary, most of the studies evaluating pesticide exposure by measuring serum biomarkers were small or cross-sectional. There were prospective studies that did not include pre-diabetes and self-reported incident diabetes as the primary outcome. Therefore, we think that our study has the advantage of defining the status of AGR through blood tests .Exposure to pesticides can lead to more pronounced health effects related to insulin resistance in men than in women. Although several well-known factors affect insulin resistance in adults, exposure to pesticides may be related to the pathophysiology of diabetes. Therefore, it may be helpful to emphasize reducing pesticide exposure as much as possible, especially in diabetes prevention education for farmers or people living in countries with high pesticide use.


The present study advances our knowledge of the mindfulness reperceiving theory, and thus provides a new explanation for the inhibition of negative emotions from the perspective of resilience, internal locus of control, and self-esteem.The present study aimed to explore the roles of resilience, internal locus of control, and self-esteem in the link between mindfulness and benign/malicious envy (BE/ME). Nine hundred ninety-one participants  completed a survey that assessed mindfulness, internal locus of control, resilience, self-esteem, and BE/ME. The results suggest that resilience, internal locus of control, and self-esteem independently mediate the relationship between mindfulness and BE/ME. Additionally, “internal locus of control → resilience” and “self-esteem → resilience” play chain mediating roles in the relationship between mindfulness and BE/ME. Namely, mindfulness is positively associated with resilience  Mindfulness is generally defined as an individual's purposeful and uncritical focus on their current internal and external experiences, including emotions, cognition, physical feelings, and sensory stimuli . The tenResilience is an ability or trait by which people effectively adapt to adversity , 17. As Internal locus of control is defined as a person's belief that they control their own life . People Some studies have also proposed that the internal locus of control should be understood to consist of perceived control . PerceivFurthermore, self-esteem is defined as an individual's general sense of their own value . AccordiAdditionally, research has demonstrated a link between self-esteem and BE/ME . People Based on the above literature and the mindfulness reperceiving theory, we proposed four hypotheses: (1) Mindfulness is indirectly related to BE/ME through the mediating role of internal locus of control. (2) Mindfulness is related to BE/ME through the chain mediating mechanism of “internal locus of control → resilience”. (3) Mindfulness is indirectly related to BE/ME through the mediating role of self-esteem. (4) Mindfulness is related to BE/ME through the chain mediating mechanism of “self-esteem → resilience”.m =19.05, sd = ±1.54). They completed hardcopy informed consent forms and received compensation of 30 yuan after completing all questionnaires. This study was approved by the ethics committee of the author's university. Two exclusion criteria were used. First, a survey was excluded if more than 2/3 of the questions were not filled out. Second, a questionnaire was excluded if all the questions had the same answer, as this indicated that the participant did not answer them carefully. based on these two exclusion criteria, 64 questionnaires were excluded. Moreover, for power = 0.95, the required sample size for this study is 400. The sample size of this study was 991  meeting the requirement. It should noted that the data for the current study were from an ongoing project named “Philosophy and Social Science Project of Hunan Province of China”, some of the data have been used in previous studies  were selected from the eastern and coastal regions of china by random sampling and cluster sampling. participants' ages ranged from 17 to 26 , the Connor-Davidson Resilience Scale (CD-RISC), the Rosenberg Self-Esteem Scale (RSES), and the Benign and Malicious Envy Scale (BEMAS). The participants completed all the questionnaires in about 40 min. Numerous studies have proven the effectiveness of this procedure –40.almost always, 6 = almost never), with higher scores meaning higher levels of mindfulness. Studies have shown this scale to be highly reliable with Chinese participants . Higher scores indicate higher levels of BE/ME. Many studies have demonstrated the validity of this scale for Chinese participants . Higher scores indicate stronger resilience. Xiang et al. . Higher scores indicate a higher internal locus of control. Studies have confirmed its reliability with Chinese participants . Higher scores indicate higher levels of self-esteem. Kong and You  was analyzed. Second, a measurement model was established to determine whether the observed variables represent the latent variables well. Prior studies have shown that when using a structural equation model to construct a measurement model, the items can be packaged to divide the factor loadings . SpecifiGiven that this study was based on a questionnaire survey method, Harman's single factor test was used to measure CMB . The com2 = 157.950, p < 0.001; RMSEA = 0.040; SRMR = 0.028; CFI = 0.985; AIC = 243.950; ECVI = 0.246]. Furthermore, all variables were significantly related; M (mean), SD (standard deviation), and correlations of mindfulness, resilience, internal locus of control, self-esteem, and BE/ME.Latent variables in the measurement model included mindfulness, resilience, internal locus of control, self-esteem, and BE/ME; there were 14 observed variables. The results showed that the data were suitable for the established models , self-esteem , internal locus of control , or BE /ME . The gender difference in resilience was significant , with men scoring higher than women.The independent sample p < 0.001]. Meanwhile, all fitting indicators of the model reached the standard of fitness  and internal locus of control → resilience . Meanwhile, there were no significant differences in the structural paths of all other variables .The results showed that there was a significant gender difference in the structure paths of mindfulness → resilience , so that they can avoid the painful experience of envy, especially malicious envy, and feel more satisfied with their lives . MeanwhiThis research investigated the underlying mechanisms by which mindfulness is linked to BE/ME from the perspective of the mindfulness reperceiving theory. Why does mindfulness effectively inhibit ME and promote BE? A possible explanation is that mindful reperceiving enhances resilience, internal locus of control, and self-esteem. Future research can design mindfulness interventions and improve resilience from the view of internal locus of control and self-esteem to inhibit ME and promote BE.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by the paper was Ethics Committee of the Hunan Normal University. All procedures carried out in this study involving human participants were in accordance with the ethical standards of the Helsinki Declaration. All participants provided informed consents before completing the questionnaires, and were paid after completing the whole questionnaires. The patients/participants provided their written informed consent to participate in this study.XD: paper writing, paper revising, and data analysis. XL and XJ: paper revising. YX: study design and paper revising. All authors contributed to the article and approved the submitted version.This work was supported by the Philosophy and Social Science Project of Hunan Province of China (18YBA324).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.


The calculated cut-off value was 0.067, and there were no differences in the results of tests that utilized positive and negative sera (p < 0.05). The characteristics of two diagnostic tests were evaluated using a conditional dependent and one-population Bayesian model. The Se value of an in-house indirect ELISA were almost similar to ELISA test kit. On the other hand, the Sp value of the in-house ELISA test was lower than that of the commercial ELISA test with the median values of 89% (95% PPI = 75.9–99.3%) and 91.4% (95% PPI = 85.3–95.5%), respectively. A posterior estimate for the prevalence was 66.9% (95% PPI = 60.8–83.3%) and higher than initially expected.Lumpy skin disease (LSD) is a contagious disease among cattle and buffalo worldwide. Currently, an enzyme-linked immunosorbent assay (ELISA) has been recognized as an efficient diagnostic tool that is less time-consuming and easier than the viral neutralization test to measure the antibody levels. In the present study, an in-house method of indirect ELISA was developed to detect the bovine antibodies against Lumpy skin disease virus (LSDV) and its performance was assessed using field samples. This in-house method has been compared with the commercial ELISA test kit for detection of bovine antibodies against LSDV. The sensitivity (Se) and the specificity (Sp) of the test were estimated using a Bayesian latent class model. Checkerboard titration was performed using the naturally LSDV-infected bovine sera and colostrum-deprived calf sera. The LSDV antigen concentrations (1 TCID LSDV is a double-stranded DNA virus containing around 150 kilobase pairs (kbp) enclosed in a lipid envelope. It is relatively large (230–260 nm). In addition to LSDV, the genus Capripoxvirus also consists of the sheeppox virus (SPV) and the goatpox virus (GPV) exhibiting a high nucleotide identity (97%) , whereas the median value of the posterior estimate for Sp of the test was 89.8% (95% PPI = 75.9–99.3%) as is shown in For the purposes of convergence testing, the model exhibited proper convergence and autocorrelation was eliminated by burning out one every ten iterations. With regard to sensitivity analysis, no major changes (change in median or 95% probability percentiles >25%) were observed in the posterior estimates of the Se of the commercial ELISA test and disease prevalence when non-informative distributions were used as prior values for any of the parameters. This was interpreted as evidence of the robustness of the model. However, changes in the posterior estimates for the Sp of the commercial ELISA test were observed with a lower estimated posterior specificity (from 91.4% to 59.1%) .4The ELISA method has been empolyed as diagnostic tool to evaluate the immunity response against LSDV in several studies ,14,31,32The use of a specific antigen is crucial for the ELISA test because of its specificity to antibody detection. Thus the search for an appropriate coating antigen is very important. Previous studies have been conducted to identify a suitable antigen to be coated onto the ELISA plate. Consequently, an inactivated sucrose gradient-purified SPPV , a maturA Bayesian latent class analysis has been performed for the estimation of accuracy of a diagnostic test and has been used to evaluate the values of Se and Sp of various diagnostic techniques in veterinary medicine, especially with regard to the development of a novel diagnostic test ,11,13,15The posterior estimates for disease prevalence were higher than the prior values, which had been inferred using the outcomes of a single study conducted in the northeastern part of Thailand in conjunction with the opinions of an expert. This outcome might be explained by the fact that all samples were collected from infected herds and were considered to be high prevalence samples. Moreover, the results might suggest that the prevalence of the LSD in this region was higher than the northeastern region by what had initially been expected. With regard to the model sensitivity analysis, there were no major changes in the posterior estimates when non-informative prior distributions were applied in the model with the exception of the posterior estimates for the Sp of the commercial ELISA test. This would suggest that the prior values of this parameter did have a stronger influence on the results of the model. Thus, there may have been a strong effect of the prior selections on the posterior estimates, and further studies with larger populations ideally including more prior information are needed in order to verify the results from this study.550/well, a sample serum at a dilution of 1:500, and HRP-conjugated goat anti-bovine IgG at a dilution of 1:10,000. The calculated cut-off value was 0.067. The posterior estimates for the Se and Sp values of an in-house ELISA  developed in this study were notably higher than the Se value of the commercial ELISA kit. However, the Sp value was lower than the commercial ELISA kit of the commercial ELISA kit . From these results, we can conclude that our in-house ELISA produced higher sensitivity levels along with decreases in specificity levels than those of the commercial test kit. Furthermore, the commercial ELISA kit in conjunction with the method described herein, will assist local laboratories in establishing an in-house diagnostic tool for the monitoring of an antibody to LSDV.An in-house ELISA method has been successfully developed in this study. Our method used a local strain of an inactivated whole LSDV particle as a coating antigen at 1 TCIDThis study was conducted according to the guidelines of and approved by the Animal Care and Use Committee (FVM-ACUC) approval number S26/2563, Faculty of Veterinary Medicine, Chiang Mai University and Chiang Mai University Institutional Biosafety Committee (CMU-IBC) approval number CMUIBC A-0764012.Nattawooti Sthitmatee, DVM,MS,PhD: Conceived and designed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.Pallop Tankaew, M.T.,M.S: Performed the experiments; Contributed reagents, materials, analysis tools or data.Wittawat Modethed, DVM; Paramintra Vinitchaikul, DVM,MS,PhD: Conceived and designed the experiments; Performed the experiments.Amarin Rittipornlertrak, DVM,PhD; Anucha Muenthaisong, BS.,MS; Nisachon Apinda, DVM; Pongpisid Koonyosying, BS.,MS; Boondarika Nambooppha, DVM,PhD; Paweena Chomjit, BS; Kanokwan Sangkakam, BS: Performed the experiments.Tawatchai Singhla, DVM,MS,PhD: Conceived and designed the experiments; Performed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.Kittikorn Boonsri, DVM.,MS; Kidsadagon Pringproa, DVM,MS,PhD: Conceived and designed the experiments.Verrasak Punyapornwithaya, DVM,MS,PhD; Khwanchai Kreausukon, DVM,MS,Dr.med.vet: Conceived and designed the experiments; Analyzed and interpreted the data.National Research Council of Thailand (NRCT) [Grant No: FF66/021], Chiang Mai University [R000029530] and Faculty of Veterinary Medicine, Chiang Mai University [08/2566].This work was supported by the No data was used for the research described in the article.The authors declare no competing interests.


Leptomantella tonkinae  was 15,527 bp in length and contained 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, and one control region. The gene arrangement of mt genome of L. tonkinae was identical to the primitive mantis. The overall AT content of the mt genome was 74%. In ML and BI phylogenetic analyses, the monophyly of Leptomantellidae was robustly supported and the clade of Leptomantellidae is a sister clade to the group of (Gonypetidae+(Leptomantellidae+(Amorphoscelidae+Nanomantidae))).The complete mitochondrial (mt) genome of  Leptomantellidae is originally included in Iridopterygidae as a genus (Leptomantella), which has recently been promoted to a new family that included four genera  was available in NCBI  (Mantodea: Leptomantellidae). The mt genome was deposited in GenBank with accession no. OK480879. The BI and ML phylogenetic trees were constructed by using the 13 PCGs of mt genomes, which aimed to discuss the phylogenetic relationship of Leptomantellidae.Praying mantises are a major group of predatory insects, with over 2500 species/subspecies in 29 families and 60 subfamilies according to the website  Ehrmann . Leptoma Ehrmann . HoweverLeptomantella tonkinae is not a protected insect species, so no permission for scientific research in China is needed. Our sample (GXJX20170714-1) was collected from Jinxiu Yao Autonomous County, Guangxi Zhuang Autonomous Region, China . Based on the taxonomic system of Otte, the sample was identified as L. tonkinae by its morphometric features and was stored at −40 °C in the Animal Specimen Museum, College of Chemistry and Life Sciences, Zhejiang Normal University, China. Whole genomic DNA was extracted from leg muscle tissue using an Ezup Column Animal Genomic DNA Purification Kit  and stored at Zhang’s lab . The mt genome was amplified with several universal primers as described in Zhang et al. , 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs), and one control region (681 bp). The nucleotide composition of L. tonkinae was shown to be A: 37.9%, C: 15.7%, G: 10.3%, and T: 36.1%, with an overall AT% content of 74%. Furthermore, the AT-skew and GC-skew of the mt genome were 0.025 and −0.207, respectively, which was similar to the published mt genome of L. albella  and two termites, Termes hospes (Dietrich and Brune 2016) and Macrotermes barneyi . According to the results of Schwarz and Roy (Leptomantella to the family level. This was consistent with previous studies that supported the monophyly of the families Nanomantidae, Toxoderidae, and Mantidae (Zhang et al. To discuss the phylogenetic position of  and Roy , they suAll authors were involved in the conception and design, or analysis and interpretation of the data; Lin YJ, Zhao YY, Yang YM, Jin WT, and Cai LN were involved in the drafting of the paper; Storey KB, Zhang JY, and Yu DN were involved in revising it critically for intellectual content; and all authors were involved in the final approval of the version to be published; and that all authors agree to be accountable for all aspects of the work.


The purpose of this study was to objectively evaluate the degree of damage to Holstein cows in Korea caused by summer heat stress. It was also established that the milk and rumen characteristics changed under heat stress depending on the difference in the Holstein cows’ parity. As a result of the study, it was confirmed that the summer weather in Korea adversely affects the milk yield, milk fat, milk protein, somatic cells, rumen activity, and rumen temperature of Holstein cows. Additionally, a correlation was found between the degree of heat stress experienced by Holstein cows based on parity. With AMSs and rumen biosensors, this study could provide farms with advice on improving milk yields in Holstein dairy cows. The results of this study suggest that the metabolic mechanisms of each of these factors are needed in Korea to understand how they contribute to the maximum improvements in milk yield and characteristics.p < 0.05), and milk fat increased (p < 0.05) at all farms during the summer, from July to August, when the temperature and humidity were high (THI = 72–79). Milk yields were the highest in the fifth, sixth, seventh, and eighth parities, and the lowest in the fourth (p < 0.05). Milk fat concentration was the highest in the fourth parity and the lowest in the first parity (p < 0.05). In the first parity, the highest levels of milk protein and lactose were seen . However, milk protein concentration was the lowest in the third parity, and the lactose concentration was the lowest in the fifth, sixth, seventh, and eighth parities. According to the rumen sensor, the rumen temperature of the dairy cows at the two farms also continued to increase (p < 0.05) from July to August, and then decreased (p < 0.05) in September. However, the activity in the rumen was increased (p < 0.05) from July to September. In the second parity, the highest rumen temperature (39.02 °C) was observed, while the lowest value (38.28 °C) was observed in the third parity. The highest value of rumen activity (12.26 mg) was observed in the second parity and the lowest value (11.31 mg) in the fourth parity. These data, taken together, confirm that a high THI during summer conditions negatively affects milk yield, milk protein content, and rumen temperature and activity in lactating Holstein cows. It is also demonstrated that various parities affect milk characteristics and the rumen environment in the summer season. This survey investigated, using robotic milking and rumen sensors, the effects of an adjusted temperature–humidity index (THI) in different geographical areas on milk yield, fat and protein, rumen temperature, and activity in lactating Holstein cows. We additionally explored the effect of parity on milk and rumen temperature and activity under different THI levels during the summer. From January to September 2020, four farms (276 dairy cows) were subjected to the use of robot milking machines, and two farms (162 dairy cows) to the use of rumen sensors. For the temperature and humidity data, the THI was calculated on the basis of the data from the Korea Meteorological Administration (KMA). The data were analyzed using the GLM procedure of SAS. Milk yield and milk protein decreased ( Smart farming  has the potential to reduce the impact of the environment, such as workers, ration, and seasons, on livestock production quality . Many faBiosensors are becoming increasingly important in the livestock sector . They caOptimizing the rumen environment can help improve milk production and milk characteristics, both of which are considered critical to achieving farm profitability, and are highly desired by the vast majority of farmers who use automatic milking systems and rumen sensors ,4. HowevTherefore, the objectives of this study were (1) to investigate, using robotic milking and rumen sensors, the influence of an adjusted THI in different geographical areas on milk yield, milk fat and protein, somatic cells, rumen temperature, and rumen activity in lactating Holstein cows, and (2) to compare the milk and rumen performance of dairy cows triggered by parity numbers during summer in Korea.This survey did not require the approval of the local ethical committee, in accordance with applicable law. It was routine for the herd’s activities to follow all of the procedures included in this survey. We studied 276 Holstein Friesian cows that were subjected to the use of robot milking machines, and 162 Holstein Friesian cows that were subjected to the use of rumen sensors in tie stall barns located in different geographical areas in Korea. Animal breeding environments were met , and total mixed ration (TMR) was fed. All farms had identical TMR compositions, which included forage to concentrate ratios of 60:40, and 14–15% crude protein in diets. An additional concentrated mixture was offered to cows individually in the milking box according to their daily milk yield. We chose farms with comparable housing conditions, so the housing system was the same. From January to September 2020, four farms (two farms in Pocheon (Farms A and B), one in Pyeongtak (Farm C), and one in Hwaseong (Farm D); a total of 276 dairy cows) were subjected to the Lely-Astronaut A4 automatic milking system , and two farms  were subjected to a sensor  inserted in the rumen. The cows had free access to fresh water at all times.db is the dry bulb temperature (°C) and RH is the relative humidity (%). We subjected the dairy cow to THI conditions, which change based on temperature and humidity, including Stress Threshold: 68~71 THI, Mild–Moderate Stress: 72~79, Moderate–Severe Stress: 80~89 THI, Severe Stress: 90~98. In response to the refusal of visits to the robot, basic descriptive statistics were provided for both milk yield and composition. In the original data set, 276 Holstein cows were observed from January to September 2020. The milk yield, milk protein and fat, and somatic cell counts (SCCs) were measured each day by adding up all the milk collected over two milking activities a day (a 24 h period). The milk composition determined from the AMS was calculated using the 24 h average of milk yield at the time of the corresponding milking. On the days on which milk yield was recorded, the AMS software automatically retrieved information on milking frequency by counting the number of events for the previous 24 h. Using the starting and end times of the milking event, the length of time between two consecutive milkings was computed, and the daily average interval between milking was obtained. Because just a few parameters, such as fat, protein, and the SCC in the available data set were monitored, we discuss a limited number of milk characteristics. The 3.5% fat-corrected milk (FCM) and energy-corrected milk (ECM) yields were calculated using the following equation: 3.5% FCM: (0.4324 × milk yield) + (16.216 × milk fat yield), ECM: (0.327 × milk yield) + (12.95 × milk fat yield) + (7.2 × milk protein yield). With regard to the rumen temperature and activity, we recorded the sum of consecutive measurements taken over a 24 h period as the sum of the daily rumen temperature and activity, as suggested by Ramunas et al. [n = 77), 2 (n = 70), 3 (n = 64), 4 (n = 29), and ≥5 (n = 35).Daily milk yield and milk composition were measured by the robot milking system twice a day. The rumen biosensor was implanted by qualified veterinarians through the mouth, and data on rumen activity and temperature were collected using a software program . Temperature and humidity were set based on the Korea Meteorological Administration . Two datp-value was less than 0.05, and to have a significant trend tendency when the values were between 0.05 and 0.10. The standard error of the mean is reported. The correlation coefficients for the milk characteristics and rumen environment were calculated on the basis of Pearson’s correlation coefficients.The GLM procedure of SAS was used to conduct the statistical analysis . The analysis incorporated repeated measurements of properties such as milk yield, milk price, milk protein, milk fat, somatic cell, rumen temperature, and activity; and animal distribution into treatment was regarded as a random effect. The covariance structure of each variable was examined using four elements . The mean value for each trait was compared using the covariance structure with the lowest Akaike information criterion. The difference between the means of the data was considered statistically significant when the p < 0.05; p < 0.05; p < 0.05; p < 0.05; The study shows that in the summer, when the temperature and humidity were high, from July to September, the milk yield decreased (3/mL).According to parity number, The levels of milk fat were the highest (4.28%) in the fourth parity and the lowest (3.76%) in the first parity. The milk protein and lactose levels were the highest  in the first parity. However, milk protein was the lowest (3.05%) in the third parity, and lactose was the lowest (4.77%) in the fifth, sixth, seventh, and eighth parities.p < 0.05). At Farm A, milk yield was strongly and positively correlated with MPY, MFY, 3.5% FCM, and ECM , and moderately correlated with milk protein (0.345). However, MPY and milk protein showed a positive correlation , and MFY, 3.5% FCM, and ECM showed a negative correlation . At Farms A and B, milk yield was moderately and negatively correlated with milk fat . There was a strong positive correlation between milk yield, milk protein, and MPY.There is a correlation matrix in Tables 7 and 8 for the traits considered for milking. Statistical significance was determined for all correlation coefficients (p < 0.05) from July to August, and then decreased (p < 0.05) in September (p < 0.05) from July to September (At the two farms where the rumen sensors were being used, the rumen temperatures continued to increase (eptember . The acteptember .As shown in According to the cluster patterns observed over the last 20 years, research has tended to focus on animal-related issues and process implementation . SeveralDue to seasonal variables, the quality of milk produced by dairy cows might fluctuate over time . For theIn the livestock sector, it is becoming increasingly important to use rumen biosensors. Rumen sensors can measure a variety of variables, including physiological, immunological, and behavioral data . The useThe rumen activity in ruminant animals can be a reliable early indicator of certain metabolic diseases, such as ruminant acidosis . RecentlThe findings of this study provide insights into the effects of high THI during summer conditions on milk yield, milk fat and protein contents, rumen temperature, and rumen activity in lactating Holstein cows. Using a robot milking system and rumen sensor, it was possible to confirm monthly changes in milk compositions and rumen function due to HS. It was also demonstrated that milk characteristics and the rumen environment are different under the same HS, depending on the difference in the parity of dairy cows. Although rumen temperature changed with monthly changes in the THI, continual HS in July and August may have reduced milk yield and protein in September, decreasing income from milk for farmers. We suggest that robot milking systems and rumen sensors be used to improve our understanding of summer HS effects on lactating cows. This study could be used as a benchmark to advise farms on how high milk yields can be achieved in Holstein dairy cows using AMSs and rumen biosensors. It is important to further investigate the molecular mechanisms of each of these factors and how they contribute to the maximum milk yield in Holstein dairy cows in Korea, and possibly in other parts of the world.


Public health issues related to chronic pain management and the risks of opioid misuse and abuse remain a challenge for practitioners. Data on the prevalence of disorders related to the use of prescribed opioids in patients suffering from chronic pain remains rather patchy, in particular because of the absence of a gold standard for their clinical assessment. We estimated the prevalence of prescription opioid misuse (POM), using a specific and validated opioid misuse scale , in adults with chronic non-cancer pain. Nine-hundred-fifty-one (951) patients with opioids prescription and followed-up in pain clinics and addictology centers for chronic non-cancer pain (CNCP) completed the survey interview. The results suggest that 44.4% of participants have POM, accompanied by overuse (42.5%), use of opioids for effects other than analgesia (30.9%), withdrawal syndrome (65.7%), and craving (6.9%). The motivations cited for POM, apart from pain relief, were to calm down, relax and improve mood. POM was shown to be related to male sex (OR 1.52), young age (OR 2.21) and the presence of nociplastic pain (OR 1.62) of severe intensity (OR 2.31), codeine use (OR 1.72) and co-prescription of benzodiazepines (OR 1.59). Finally, despite the presence of three subgroups of misusers, no factor was associated with the intensity of misuse, reinforcing the view that distinguishing between strong and weak opioids is not appropriate in the context of use disorder. Almost half of patients with CNCP misuse their prescribed opioid. Practitioners should be attentive of profiles of patients at risk of POM, such as young, male patients suffering from severe nociplastic pain, receiving prescription for codeine and a co-prescription for benzodiazepine. We encourage French-speaking practitioners to use the POMI-5F scale to assess the presence of POM in their patients receiving opioid-based therapy.Clinical Trial Registrationclinicaltrials.gov, identifier NCT03195374 Chronic pain is a common problem, affecting approximately 20%–31% of the general adult population, depending on the country . The manThe pharmacological class of opioid analgesics includes all the natural and synthetic derivatives of the poppy, of which morphine is the foremost. They have in common that they bind to opioid receptors, the source of both their undesirable and desired effects. Their usual indications are moderate-to-severe nociceptive pain . Due to their several adverse effects  and doubts about their efficacy against chronic non-cancer pain (CNCP), their long-term administration should not be recommended . NeverthBased on reports of Analgesic, Anesthetic, and Addiction Clinical Trials, Translations, Innovations, Opportunities, and Networks  and the According to a review by Vowles, among the US patients suffering from chronic pain and taking opioids, about 21%–29% developed a misuse . A FrencComité de Protection des Personnes Sud-Est VI, Clermont-Ferrand, France) on 21 July 2016 (ref: AU1263), the French personal data protection authority  and registered on Clinicaltrials.gov (NCT03195374). The research was conducted in accordance with the World Medical Association Declaration of Helsinki .The study was approved by the Research Ethics Committee (http://project-redcap.org/) possesses the authorization of the French personal data protection authority.Study data were managed using REDCap  electronThis cross-sectional and multicenter study was offered to all adult patients suffering from CNCP for at least 6 months, treated by opioids for at least 3 months, and followed-up in pain clinics and addictology centers. Only patients with sufficient comprehension of French to answer the questionnaires and who volunteered to participate were included in the study.The study was systematically proposed to eligible patients during an addictology or chronic pain consultation as part of their usual care with the investigator. An information form was given to each patient, summarizing the objectives of the study and the strictly confidential aspect of the treatment of their medical data. Patients were free to accept or not to participate in this study, without impact on the quality of care and the relationship with their physician in the case of refusal. In the case of acceptance of participation, the patients had to fill in the paper form  on site and return it to the investigator. At the end of the study, all the patient forms were sent by mail to the University Hospital of Clermont-Ferrand and the data were entered twice and compared by two clinical research assistants in the REDCap database for statistical analysis.The primary objective of the study was to estimate the prevalence of POM in a population of patients with CNCP followed-up in pain clinics and addictology centers. To achieve this objective, the POMI scale, previously translated and validated in French for 154 patients , was useThe secondary objectives were: 1) to investigate the relationship between the presence of POM and type of opioids; 2) to characterize misuser profiles and the modalities of POM; and 3) to identify factors associated with the presence of POM. To address our secondary objectives, a home-made questionnaire  describing all analgesic treatments (including opioids), patient sociodemographic data, clinical data , misuse and associated behavior  was completed.A withdrawal syndrome was confirmed when the patient answered “YES” to at least one of the possible answers to the following question: Have you ever experienced one or more of these symptoms when your opioid medication(s) was/were delayed or in the hours before usual intake or when the dose was decreased or when it was stopped suddenly? .Craving was confirmed when the patient answered “YES” to the following question: Have you ever felt an uncontrollable urge to use your opioid medication(s) in a non-painful setting? Finally, use for other effects  was analyzed with at least one “YES” response to the following question: Have you ever taken this/these pain medication(s) for the following reasons? .This cross-sectional study conducted on a sample should make it possible to generalize the results to the entire target population. A margin of error on the estimate is defined to estimate the number of participants required, in addition to the expected proportion of chronic pain subjects with misuse. Thus, according to the literature, for an expected proportion of misuse subjects of about 40% , the incCategorical parameters were expressed as frequencies and associated percentages, and continuous data as mean ± standard deviation or as median , according to statistical distribution. The assumption of normality (Gaussian) distribution was assessed using the Shapiro-Wilk test.t-test or the Mann-Whitney test if the assumptions of the t-test were not met. The equality of variances was analyzed by the Fisher-Snedecor test. The relationships between POMI-5F score (<2 versus ≥2) and opioid use for non-analgesic effects and type of withdrawal symptoms were also described with the aforementioned statistical tests.The prevalence of a POMI-5F score ≥2 of patients with CNCP was presented with a 95% confidence interval (CI) calculated by an exact binomial distribution. The comparisons according to the POMI-5F score  were conducted using Chi-squared or Fisher’s exact tests for categorical data. For continuous data, the comparisons were performed with Student’s Then, in order to determine factors associated with the POMI-5F score ≥2, a multivariable logistic regression model was run using the stepwise approach (backward and forward) on covariates fixed according to univariate results and to clinical relevance. Particular attention has been paid to the study of multicollinearity and interactions between covariates: 1) studying the relationships between the covariates, and 2) assessing the impact of adding or deleting variables in the multivariable model. Furthermore, variance inflation factor, a measure of the amount of multicollinearity, was also calculated with collin command from Stata. The results were expressed as odds-ratios and 95% CI.Finally, to determine patterns on patients at risk of POM, a multiple correspondence analysis (MCA) followed by a mixed unsupervised classification  were proposed to: 1) study the relations between the modalities of the variables, and 2) determine the profiles of the participants . MCA can be used to perform cross tabulations and can be considered as a useful tool for revealing the relationships among categorical variables. The significance of association as tested by Chi-squared or Fisher’s exact tests provides no information regarding significant individual associations between row-column pairs. On the contrary, factorial analyses such as MCA show how the variables are related, and not just if a relationship exists. This approach enables handling a large amount of data in order to unfold hidden patterns. For these analyses, the variables were chosen according to univariate results, clinical relevance and statistical distribution . Only individuals without missing data were included in this analysis.http://cran.r-project.org/). All the tests were two-sided, with a Type I error set at 0.05. Particular attention was given to the magnitude of differences expressed with effect-sizes, in addition to inferential statistical tests expressed using p-values without Type I error correction.Statistical analyses were performed using Stata software  and R 3.3.3 . Nine hundred and fifty-one patients were analyzable for the primary objective. The first patient was enrolled on 24 August 2018, and the last patient on 09 July 2019.Participating patients were mostly middle-aged women, in a couple and having a professional activity. Among patients in professional activities, 16.3% were in work stoppage and 42.6% were in disability due to their CNCP. Moreover, a majority of patients elicited comorbidities such as sleep and anxiety disorders for about half of them while 29.0% of them had depressive disorders.Regarding the characterization of pain disorders and their opioid treatments, patients suffered mainly from nociplastic pain (64.0%), with a duration longer than 5 years for more than 60.0% of them, and most of them (about 90.0%) had a moderate to severe pain intensity. Finally, opioid treatments used by patients were mainly tramadol (44.2%) followed by oxycodone (20.0%). The median percentage of pain relief by opioids declared by the patient, was 50.0%. In parallel, other concomitant analgesic treatments were prescribed  reported a POMI-5F score ≥2, meaning the presence of POM. The majority reported having withdrawal symptoms when stopping or delaying opioid treatment (81.5%), as well as taking higher doses than prescribed for lack of sufficient pain relief (72.4%). In addition, 45.5% of them reported taking their opioid treatment for something other than pain relief. The different purposes of using their opioids for non-analgesic effects, correlated with the presence of a POM, was to improve mood and to calm-down/to relax (see p = 0.02), with professional activity, suffering from severe nociplastic pain, depressive and sleep disorders (Characterization of the participants was performed according to the POMI-5F score (<2 versus ≥2). Our results from univariate analysis highlighted certain factors that could be associated with POM: younger patient, male sex  shows almost similar populations with a slightly higher proportion of women (p = 0.037) and a slightly lower proportion of neuropathic pain (p = 0.034) in the multivariate analysis population (data not shown). The MCA of the POM population was conducted for 377 patients (377/422 = 89.3%) who had no missing data for the variables included in the analysis, and 45 were removed. These two samples were similar in all assessed criteria (data not shown). The MCA showed the presence of three clusters of patients. The clusters differed mainly in age, type of pain, pain intensity, and type of opioid (weak or strong). Clusters 1 and 3, which were quite similar , differed from each other by the type of pain and their opioid treatment. Cluster 1 included mostly patients with nociplastic pain and weak opioids, whereas cluster 3 included mostly patients with different types of chronic pain and treated with strong opioids. We also noticed that cluster 3 tended to have more depressive disorders and co-prescription of benzodiazepines . Cluster 2 differed from the other clusters in that it corresponded to elderly, retired patients with mild to moderate various chronic pain.From an exploratory perspective, we performed a multivariable analysis to determine associated factors with the presence of POM  and a clCurrently, only the POMI scale  is used et al.  showed a prevalence from 43% to 52% , 26.5% iet al.  also asset al. .et al. study , age (about 50 years old), and marital status (about 35% single) with the studies mentioned previously. It is noteworthy that in the German study, the patients were older (61.8 years old), and we have fewer unemployed patients (32.9%) compared to the studies of l. study . The stuConcerning the characteristics of our patients considered as misusers (POMI-5F score ≥2), we were able to determine POM-related factors and profiles using multivariable analysis. The results obtained show that young male patients, patients suffering from severe nociplastic pain, codeine prescription and a co-prescription of benzodiazepine were associated with a POM. These characteristics are also mainly found as associated factors for misuse, addiction and/or OUD in the literature . InteresLastly, we were able to separate our POM population into three subgroups differentiated mainly by age (cluster 2 = patients aged +60 years) and type of opioid . Interestingly, the clusters did not differ on the POMI-5F score and OUD symptoms . Moreover, there was no difference in the intensity of misuse (POMI score) between the weak versus strong opioid cluster (1 and 3 respectively). This reinforces the fact that the distinction between weak and strong opioids is not appropriate for use disorders, in line with the recent recommendations of the French National Health Authority on opioid drugs  Bon usa. Our thrOur study has certain limitations, such as a measurement bias, which occurs frequently in observational studies . NeverthThe updated prevalence of POM in French patients with CNCP remains high, with almost half of the patients concerned. In view of all our results, certain factors should draw the attention of practitioners to the profile of patients at risk of POM, such as: young age, male, suffering from severe nociplastic pain, having a codeine prescription and a co-prescription of benzodiazepine. Nevertheless, because of the cross-sectional design of this study, further longitudinal studies are required to assess the findings. Our study also highlights that distinguishing between strong and weak opioids is not appropriate in the context of use disorder. Finally, we encourage French-speaking practitioners to use the POMI-5F scale to assess the presence of OUD in their patients receiving opioid-based therapy.Debbah Abdelouahab, Peyre Alexandre, Simon Anna, Defeuillet Catherine, Wiart Catherine, Sureau Christophe, Vulser Cristofini Claire, Bouhassira Didier, Touchard Emmanuelle, Collin Elisabeth, Serra Eric, Perez-Varlan Evelyne, Mohy Frédérique, Peyriere Hélène, Le Borgne Jean-Marie, Poinsignon Jean Paul, Micallef Joëlle, Dy Lénaïg, Amilhaud Marlène, Venard Maria, Dorsner-Binard Marie, Berrier Oui Marie, Martial Maud, Feuillet Maryline, De Rijk Pablo, Ginies Patrick, Kieffert Patrick, Giraud Pierric, Aerts Raluca, Le Boisselier Reynald, Cauchin Sonia, Pouplin Sophie, Corand Virginie, Perier Yannick, Poujol Yves.


To assess the effectiveness of endoscopic retrograde appendicitis therapy (ERAT) as a new technique and method for chronic fecalith appendicitis complicated by active ulcerative colitis. A 46-year-old male patient was admitted with right iliac fossa pain, tenderness, and raised inflammatory markers. A computed tomography (CT) scan of his abdomen confirmed a dilated appendix, which is considered chronic fecalith appendicitis combined with active ulcerative colitis. He was treated with an endoscopic retrograde appendicitis therapy procedure. The patient recovered well after the ERAT procedure and was discharged from the hospital in two days. On follow-up one year later, there was no recurrence of pain in his abdomen. In conclusion, ERAT could be seen as a different approach and be favored as a safer and more effective option in treating UC patients with appendicitis, especially those who are later in the course of the disease. Because of the ERAT procedure, such cases can avoid surgery and surgery-related complications. More research and issues must be addressed to demonstrate the efficacy and effectiveness of ERAT in appendicitis combined with UC. A 46-year-old Chinese male patient was admitted because of right lower abdominal pain for over two years that had been aggravated for one month. An abdominal CT scan revealed appendicitis and ulcerative colitis, which were suspected at a local hospital. As a result, the patient was referred to our hospital for further treatment. The patient denied a history of hypertension, coronary heart disease, cerebrovascular diseases, diabetes, and hyperthyroidism. During the physical examination, the temperature was 38.1°C, the abdomen was soft, there was positive tenderness, and there was no rebound pain. The auxiliary examination after admission showed that the white blood cells (WBC) were 13.8×109/L; hemoglobin was 111 g/L; C-reactive protein (CRP) was 90 mg/L (8 mg/L); the neutrophil percentage was 81.5%; and the procalcitonin was 0.55 ng/ml (0.5). Our hospital CT scan showed that the appendix was locally thickened and enhanced, chronic fecal appendicitis was suspected, and multiple small lymph nodes were displayed in the ileocecum area Figure 1The orifice of the appendix was thickened, so it was challenging to insert the guide wire into the appendiceal orifice Figure 3Ulcerative colitis (UC) is a chronic colon inflammation that has a variable clinical course . AlthougERAT is a different approach and is favored as a safer and more effective option in treating UC patients with appendicitis, especially those later in the course of the disease. Because of the ERAT procedure, such cases can avoid surgery and surgery-related complications. Follow-up one year later, the patient has no recurrent episodes of appendicitis. More research and issues must be addressed to demonstrate the efficacy and effectiveness of ERAT in appendicitis combined with UC.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.Written informed consent was obtained from the patient for publication of this case report and accompanying images.MZ and GC drafted the manuscript. GC and HH performed the ERAT procedure and designed the study. LG, SF, FL, LL and WX revised the manuscript. and HA is responsible for the collection of data and analysis. All authors contributed to the article and approved the submitted version.


After adulthood, as a person grows older, the secretion of sex hormones in the body gradually decreases, and the risk of periodontitis increases. But the relationship between sex hormones and periodontitis is still controversial.We investigated the association between sex hormones and periodontitis among Americans over 30 years old. 4,877 participants containing 3,222 males and 1,655 postmenopausal females who had had periodontal examination and detailed available sex hormone levels, were included in our analysis from the 2009-2014 National Health and Nutrition Examination Surveys cycles. We applied multivariate linear regression models to estimate the connection between sex hormones and periodontitis after converting sex hormones into categorical variables through tertile. Additionally, to ensure the stability of the analysis results, we carried out a trend test, subgroup analysis, and interaction test. After fully adjusting the covariates, estradiol levels were not associated with periodontitis in both males and females with a P for trend = 0.064 and 0.064, respectively. For males, we found that sex hormone-binding globulin was positively associated with periodontitis . Congruously, free testosterone , bioavailable testosterone , and free androgen index  was found to be negatively associated with periodontitis. Moreover, subgroup analysis of age found a closer relationship between sex hormones and periodontitis in those younger than 50 years.Our research suggested that males with lower bioavailable testosterone levels affected by sex hormone-binding globulin were at a higher risk of periodontitis. Meanwhile, estradiol levels were not associated with periodontitis in postmenopausal women. By 2100, the global population of those older than 65 years is anticipated to reach 2.37 billion according to the Global Burden of Disease Study . ManagemPeriodontitis is a chronic, microbial-associated, host-mediated inflammatory disease of the oral cavity . The infSex hormones are important endocrine substances in the human body that are related to many functions, such as growth, reproduction, and differentiation. Testosterone (T) is a primary male sex hormone synthesized from cholesterol in Leydig cells in males, and estradiol (E2), another of the sex hormones, is mainly derived from the ovaries in females. But E2 is also derived from the conversion of androgens by aromatase in adipose tissue in males and adrenal glands and ovaries also produce T in females. Low T and E2 are connected with a series of medical disorders including obesity, metabolic syndrome, diabetes, cardiovascular disease, and osteoporosis –18. Sex The prevalence estimate of periodontitis depends on the case definition of periodontitis and methods of periodontal surveillance . There avia questionnaires and examinations in a two-year cycle, with the aim of establishing a database of the health and nutritional status of the US population. As a cross-sectional survey with a complex, multistate, probabilistic sampling design, the NHANES ensures that nationally representative data are available. The National Center for Health Statistics (NCHS) institutional Review Board examines and gives permission to the study and each participant in the survey signs the appropriate written permission. More elaborate information on the methods and protocol of the NHANES is available on the CDC’s official website.The data that we used for the analysis were derived from the NHANES. The Centers for Disease Control and Prevention (CDC) conducts the NHANES in the United States 30,468 participants from the 2009-2010, 2011-2012, and 2013-2014 cycles were selected. The study population was restricted to participants with detailed sex hormone levels and a diagnosis of periodontitis. Considering the dramatic changes in hormone levels during the female physiological cycle, we chose only postmenopausal women who answered “no” to the question “Have you had at least one menstrual period in the past 12 months?” and answered “hysterectomy” or “menopause/life changes” to the question “What is the reason why you have not had a period in the last 12 months?” in the self-reported reproductive health questionnaire . Finallyvia a photomultiplier tube after binding to SHBG with immuno-antibodies  and E2 levels were measured using an isotope dilution high-performance liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) in the NHANES, while the concentrations of sex hormone-binding globulin (SHBG) were quantified using chemo-luminescence measurements of the reaction products tibodies . Accorditibodies  and the tibodies  through tibodies .The FMPE that included clinical attachment loss (AL) and probing depth (PD) was used for the periodontal examination from 2009 to 2014. The dental examiner used the HU-Friedy periodontal probe to perform the assessment. AL and PD were assessed at six positions per tooth using a perioprobe for a maximum of up to 28 teeth . Cases oCovariates associated with periodontitis and T were collected, including some demographic information such as age, race, ratio of family income to poverty, educational level, and civil state. All demographic data could be obtained from questionnaire data and they were converted into the corresponding categorical variables. Smoking status was classified as never, former, and current, respectively, and alcohol intake per day was classified as never, moderate, and heavy, respectively. Time of venipuncture, BMI, diabetes, and hypertension were also potential confounding factors. White blood cells (WBC), which partly reflect inflammation in an individual’s body, were also adjusted in the analysis –37.http://www.Rproject.org,theRFoundation) and Empower (R) to carry out all the analysis, and a p-value of ≤ 0.05 was required to be statistically significant. In the data analysis, continuous variables and categorical variables were denoted by mean ± SD/Median (Q1-Q3) and proportions, respectively. A sample weight was assigned to each participant because of the multistate, probabilistic sampling design  guidelines recommend two measurements due to intra-individual and diurnal variations of serum T . ThirdlyOur research suggested that males with lower bioavailable testosterone levels affected by SHBG were at a higher risk of periodontitis. But we need to carry out a large, carefully designed prospective study for clarifying the causal association between sex hormones and periodontitis due to mechanism complexity.The original contributions presented in the study are included in the article/Author contributions are as follows: KJ, SQ, QW, and LY contributed equally by conceiving and designing the study. XS, KJ, and SQ organized and analyzed the data. XZ and XS wrote the paper. LY, XC, XZ, ZZ, CZ, YL, MY, XH, and SX revised the manuscript critically for important intellectual content. MY and XH helped to complete the design and evaluation of the statistical methodology in this study. All authors contributed to the article and approved the submitted version.


Prior studies have consistently revealed that a combination of physical activity with caloric restriction results in a reduction in body weight in the general population. Both overweight and drug abuse are risk factors for poor physiological health, and poor mental health has been associated with drug abuse and unhealthy body mass index (BMI). However, the effects of low-carbohydrates diet (LC) combined with mind-body exercise intervention on improving anthropometric characteristics, lipid metabolism, quality of life, and craving among overweight people who struggle with drug addiction have yet to be clarified.n = 18), the Baduanjin intervention group , and the Baduanjin combined with LC intervention group . We compared the anthropometric characteristics, blood biochemical parameters, quality of life, and drug craving responses between the three groups at baseline (week 0), week 4, and week 8.Fifty-four eligible male patients were randomly assigned to the control group . There was no significant difference in the HDL-C level observed among the BA and LC groups at 8 weeks (P > 0.05); however, there was an overall upwards trend. A significant change in trends in the quality of life scale score was determined in the three groups (P < 0.001). The three groups showed reductions in visual analog scale score distribution over time (P < 0.05).After repeated measurements in the general linear model, both the BA and LC groups exerted significant effects on decreasing waist circumference, BMI, body weight, hip circumference, body fat percentage, total cholesterol level, and triglyceride level (Either Baduanjin or an 8-week Baduanjin combined with LC can significantly reduce anthropometric characteristics and body composition, enhance the quality of life, and reduce craving in overweight/obese patients. Baduanjin combined with LC is particularly effective in improving lipid metabolism. Drug addiction is a type of mental illness that affects a significant number of people, with an estimate of nearly 1.4 million in China . Drug-seAlthough various drug-dependent treatments have been developed, including pharmacological, psychological, and sociological interventions, their efficacy is limited. The side effects of pharmacological therapy on the physical and psychological health of users should be noted. Other non-pharmacological treatments have been developed, such as contingency management, cognitive–behavioral therapy, and repetitive transcranial magnetic stimulation . In addiIn our previous survey, we found that 1 year after rehabilitation in DRC, more than 1/3 of addicts were overweight, and there was an upwards trend, although early studies have found that more than 60% of patients have multiple nutritional deficiencies . OverweiAs one of the traditional Chinese health-promoting exercises , Baduanjin has eight simple postures and movements, which makes it readily accessible to a variety of people . PreviouTraditional Chinese health-promoting exercise, as an exercise intervention for drug addiction, can promote the physical and mental health of people with drug addiction. Collectively, the combination of LC and exercise training seems to also be beneficial for this special population. Hence, to fill this knowledge gap, we aimed to investigate the safety, effectiveness, and craving among overweight people who struggle long-term with drug addiction practicing Baduanjin and who have adopted LC. Thus far, no research has been conducted on the effect of Baduanjin and nutritious diet on the health-related outcomes . We also attempted to explain the relationships between overweight and drug abuse and offer practical strategies in exercise intervention and health management of rehabilitation for drug addiction. With these basic considerations in mind, we conducted a randomized controlled trial for 8 weeks to compare the effects of (i) 8 weeks of Baduanjin and (ii) Baduanjin with LC on anthropometric assessments and body composition, blood biochemical parameters, quality of life, and craving response in overweight patients. Based on the reviewed literature, the following hypotheses will be tested: as an intervention, Baduanjin combined with LC among overweight people who struggle with drug addiction was assumed to induce a more significant loss in body weight (BW), BMI, BFP and craving response and better QOL and lipid metabolism outcome than Baduanjin alone.Before recruitment, the sample size was calculated using GPower (Version 3.1). With a 20% potential dropout rate considered, the goal was to recruit 54 participants in total for three groups . A sample size of 18 participants for each group was necessary.2; (4) no cognitive impairment and ability to complete the questionnaire independently; (5) no serious diseases that prevent participation in physical activities; (6) not undergoing psychotropic drug treatment; and (7) no medical or neurological diseases or trauma of the central nervous system.We preliminarily evaluated 60 male patients in a DRC in China between December 2021 and February 2022. All participants had stayed in the DRC for more than six months within the study period. The inclusion criteria were as follows: (1) age 18–60 years; (2) illegal drug-dependent use (assessed by the Chinese version of the Addiction Severity Index) ; (3) BMIn = 20), (ii) Baduanjin intervention , and (iii) Baduanjin combined with LC intervention . Six participants dropped out because of schedule conflicts or personal reasons. Ultimately, 54 participants completed the project, and all pre- and postmeasurements were included in the final data analysis . Participation in the study was entirely voluntary, and informed consent was obtained from each qualified participant. To ensure that the sample would be significantly representative and to reduce statistical error, we adopted a stratified sampling methodology to collect the relevant data. In the first sampling stage, we stratified all samples according to age, type of drug, and drug use duration. Then, the participants were randomly assigned to three groups in a 1:1:1 ratio by using PASW software : (i) general physical activity  and Baduanjin intervention (BA) in metabolic equivalents (METs). General physical activity is categorized as light-intensity activity with an average of 2.7 METs; Baduanjin with ~4.8 METs is considered moderate-intensity activity.Participants in the BA and LC groups underwent training for Baduanjin . The training was conducted under the supervision of two trained coaches for 8 weeks . Each training session consisted of eight movements: (1) Double Hands Hold Up the Heavens, (2) Left–Right Opening the Bow, (3) Single Lift, (4) Five Weaknesses and Seven Injuries, (5) Sway the Head and Swing the Tail to Get Rid of the Heart Fire, (6) Two Hands Hold the Feet, (7) Screw the Fist with Fiery Eyes, and (8) Seven Disorders and Hundreds of Illnesses Disappear . The coaIn this study, only participants in the LC group underwent the 8-week Baduanjin with LC intervention. The daily calorie intake before and after the intervention was ~2,000–2,700 kcal. The nutritional requirements of LC adopted that fats, proteins, and carbohydrates comprised ~65, 25, and 10% of their daily energy intakes, respectively. Carbohydrates were limited to 70–130 g/day. All participants in the CON and BA groups consumed a nutritionally balanced diet of 1,800–2,400 kcal/day  during the study.To support treatment fidelity, Baduanjin intervention focused on improving physical function and mental health, and LC intervention focused on reducing body weight. Each participant will be given a Baduanjin manual with exercise instructions and safety information. Participants in the LC group received dietary recommendation flyers according to the guidelines of the China Society for Nutrition to reduce their body weight. Questions from participants about dietary methods were immediately answered by the researchers throughout the experiment. The coaches and researchers passed fidelity assessment prior to starting the exercise intervention and diet intervention for the current study and maintained fidelity for the duration of the study.Outcome measures were obtained at baseline (week 0) and after weeks 4 and 8 to evaluate changes in anthropometric characteristics, blood biochemical parameters, quality of life, and drug craving response among overweight male patients from the three intervention groups.2), and the values were accurate to 0.1 cm and 0.1 kg, respectively. BFP was determined using body composition analysers. Each index  was measured within the same morning and evaluated by the same researchers before and after the intervention. Overweight and obesity were identified as BMI 24–28 kg/m2 and BMI equal to or over 28 kg/m2, respectively, according to the Working Group on Obesity in China (WGOC) (Waist circumference (WC) between the rib frame and the ilium was measured as the participant exhaled gently. WC was measured with an inelastic tape on bare skin, accurate to 0.1 cm between the lowest ribs and the upper edge of the iliac crest. Hip circumference (HC) was measured over the widest part of the buttocks. BMI was calculated as weight (kg) divided by height squared , high-density lipoprotein-cholesterol (HDL-C), and triglyceride (TG) levels, were collected .The Quality of Life Scale for Drug Addiction (QOL-DA) was developed by Chonghua Wan in 1997 for drug-dependent patients in China to measure their quality of life . The scaThe Visual Analog Scale (VAS) of cravings was used to evaluate the participants' current level of drug cravings. The VAS was denoted by a line segment, with two ends set to 0  and 10 (the strongest craving in the imagination). The research subjects were required to mark the corresponding position of the line segment according to the subjective craving of the participants during the investigation. The distance between the site and Point 0 was the craving score ; the higpost hoc SIDAK correction. Statistical significance was set at P < 0.05.Statistical data were analyzed using PASW software . Pearson's chi-squared test was applied for demographic  variables. Normal distribution tests were employed for continuous variables. The repeated-measures analysis of continuous numerical variables was conducted using the general linear model repeated measures. Two classified variables were analyzed using a generalized estimating equation (GEE), and a paired chi-square test was used to assess the predictive accuracy of the model. The time point  was the within-group factor, the groups  were the intergroup factors, and the type of drug  was the covariate. The effects of intervention, drug type, and time point on the outcome indexes  were determined. If the time point–group interaction was significant, the simple effect between the time point and the intervention was further investigated with the n = 60) were randomly assigned to the control (n = 20), BA (n = 20) and LC (n = 20) groups. A total of 54 participants ultimately completed the 8-week experiment and thus were included in the data analysis; the dropout rate was 10%. The demographic characteristics of the included participants and the data comparison between the three groups at baseline are listed in 2. There were no significant differences in age, BW, WC, HC, BFP, TC level, HDL-C level, TG level, marital status, educational level, occupation, type of drug, or drug use duration among the three groups (P > 0.05). A significant difference in BMI (P < 0.05) was reported. BMI was included as a main effect term in all GEE models to control for its confounding effect.All eligible participants , BMI , and BFP . However, no significant differences in BW and HC were found . Relative to those of the CON group from baseline to weeks 4 and 8, both the BA and LC groups showed modest reductions in BW, WC, BMI, and BFP (P < 0.05). No significant differences in group–time interaction analyses of BW, WC, BMI, and BFP were found between the groups (P < 0.05). This finding indicates that the changing trends in BW, WC, BMI, and BFP varied depending on the intervention. The BW, WC, BMI, and BFP were significantly reduced after intervention in the BA and LC groups. However, no significant differences in BW and HC existed , whereas no changes in the TC and TG levels occurred in the CON group , suggesting that the changing trend in QOL-DA scores varied depending on the intervention . The QOL-DA scores of the LC group were slightly lower than those of the BA group at week 8  or type of drugs (P > 0.05) existed between the three groups. The efficiency improved over time, and the craving decreased significantly at weeks 4 (P = 0.002) and 8 (P < 0.001). The predictive accuracy of the model was 72.84% (118/162).With VAS scores distributed as the dependent variable , if score <5 points, it was considered effective—that is, the craving was reduced . The intNo adverse events were reported in this trial.Our study shows that for overweight patients, 4–8 weeks of Baduanjin intervention or Baduanjin intervention with LC can reduce body weight, BMI, and WC over time, indicating that both interventions can prevent the development of central obesity (WC ≥85 cm). These interventions can also improve the quality of life of patients in DRCs. We further found that compared with the Baduanjin intervention, the combined LC intervention provided additional benefits and thus more effectively reduced HC, BFP, TG, and TC levels. However, in DRCs, the Baduanjin intervention and general physical activity reduced drug craving, which was not relevant to the intervention measures. No adverse events were reported during the experiment. The data obtained show that Baduanjin, a mild physical and mental exercise, could be combined with LC diet therapy, effectively reducing BMI, controlling central obesity, reducing drug cravings, and improving the quality of life of patients. This study may contribute new ideas for our follow-up and other experiments related to exercise and diet control, healthy lifestyle promotion, and integrity maintenance among people who struggle with drug addiction .The results of the present study show that after an 8-week intervention, the BW, BMI, WC, HC, and BFP of the BA and LC groups decreased. However, no change was observed in the CON group, suggesting that general physical activity was ineffective in weight loss. These findings are consistent with previous studies; the abdominal circumference of the Baduanjin group was also significantly improved after weeks 12 and 24 of the intervention . Study rGiven that reports have demonstrated and discussed the beneficial effects of Baduanjin on enhancing various health outcomes , 37, theA good fit and dietary habits are essential to overall health. Recent studies have shown that failure to maintain a healthy weight disrupts the metabolic–immune axis of the body, increasing the risk of deadly diseases such as COVID-19 and other infectious diseases . New eviHowever, no significant changes in HDL-C were detected in our study, and the reasons for the differences have yet to be determined. A study in Korea revealed that HDL-C levels are affected by genetic factors and socioeconomic status  . Emergin2 dopamine receptors in the ventral striatum  and psychological (craving) returns from the intervention. The application of neuroimaging tools  or Electroencephalography can also be used to measure brain activity of drug addicts, and help deepen the understanding of the beneficial effects of the integrated program  and regular Baduanjin intervention may not only enhance anthropometric characteristics and body composition in overweight patients but may also positively affect other aspects, such as quality of life and mental health. Compared with Baduanjin exercise only, Baduanjin with LC intervention can more effectively reduce body fat and improve lipid metabolism and is equally safe. It may still be worth considering for patients undergoing LC interventions and continued rehabilitation after returning to society. In addition to practicing Baduanjin, patients should also learn to control their weight and maintain a healthy lifestyle. Moreover, the long-term safety and effectiveness of LC combined with regular exercise require further research.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by Ethics Committee of Zhejiang Police Vocational College. The patients/participants provided their written informed consent to participate in this study.DJ participated in the research design and coordination, conducted the experiments, and analyzed and interpreted the data. YX helped draft the manuscript. All authors have read and agreed to the published version of the manuscript.This work was supported by the 2022 Soft Science Research Program of Zhejiang Province (2022C35056).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.