Sorbate and benzoate are important preservatives in food products, but these compounds can also have genotoxic effects, causing health risks to consumers. In this regard, this study aims to determine the mass fractions of sorbate and benzoate in Brazilian samples of mustard, ketchup and tomato sauce using an adequately validated sub-minute capillary electrophoresis method.In this study, sorbate and benzoate were evaluated in sauce samples by capillary electrophoresis using a simple sample preparation procedure. Previously, the method was validated according to Eurachem guidelines, and its greenness was assessed by Eco-Scale.The fitness for purpose of the method, as well as its suitability for the analysis of the studied matrices and its agreement with the principles of green chemistry were checked and confirmed. Also, according to our findings, among the 30 commercial samples assessed, six of them presented some mislabeling or non-compliance with European or Brazilian legislation, reinforcing the constant need for quality assessment and surveillance of food products.So far, there have been few studies related to investigating the preservatives such as sorbate and benzoate in mustard, ketchup and tomato sauce, highlighting the significance and contribution of the obtained results to the knowledge in the field. Sorbic and benzoic acids and their salts play a significant role as preservatives in the food industry. Due to their capacity to inhibit yeasts, molds and bacteria, these additives are widely used in foods and beverages such as bread, sauces, soft drinks, cheese, juice and fermented products  determine sorbate and benzoate mass fractions in Brazilian mustard, ketchup and tomato sauce using a sub-minute capillary zone electrophoresis method, (ii) validate the method for these food matrices, and (iii) determine the greenness of the method using the Eco-Scale.In this context, this study aims to: (The reagents Tris(hydroxymethyl)aminomethane (TRIS), 2-hydroxyisobutyric acid (HIBA), and sorbic, benzoic and salicylic acids were purchased from Sigma-Aldrich, Merck . The stock solutions of TRIS and HIBA (components of the background electrolyte) were prepared in ultrapure water  at the concentration of 100 and 125 mmol/L, respectively. The stock solutions of sorbic, benzoic and salicylic acids were prepared in methanol (Merck) at the concentration of 1000 mg/L and kept under refrigeration ((5±2) °C) until the analysis, when they were diluted to obtain the working concentrations.The analyses were performed in a capillary electrophoresis (CE) system  equipped with a diode array detector. The data acquisition and treatment software were supplied by the manufacturer (HP ChemStation®).et al. (The electrophoretic separations were performed according to Costa N=10), ketchup (N=10), and tomato sauce (N=10) from different brands were purchased in a local supermarket of Florianopolis, Santa Catarina state, Brazil.A total of 30 samples of mustard  containing 250 µL chloroform (extraction solvent) were added. The mixture was homogenized for 2 min and centrifuged at 1784×g for 10 min. The sediment phase was quantitatively placed into another test tube and evaporated with nitrogen gas. The residue was redissolved in 100 µL mobile phase for high-performance liquid chromatography (HPLC) analysis. In the present study, a simple sample preparation based only on aqueous dilution was employed as follows: samples ((1.00±0.05) g) were weighed into polypropylene tubes, and 10 mL of ultrapure water were added. The tubes were sealed, and the resulting solution was stirred with a vortex  for 1 min and centrifuged for 5 min at 9861×g . The supernatant was filtered through syringe filters  and diluted in the proportion of 5:1 (V/V) with salicylate  at the concentration of 120 mg/L before being injected at the CE system. Subsequent dilutions were performed when necessary. For all experiments  the corrected peak area  and the corrected migration time /tm) were considered.The sample preparation procedure was modified from that proposed by Javanmardi All samples were prepared in three independent replicates and analyzed before the expiration date.et al.  method proposed by Costa This method allowed the separation of both ions and the salicylate in just 28 s. The total analysis time of the method, which includes flushing, vial permutation, injection and separation, was experimentally determined and took about 1.3 min, achieving an analytical throughput of approx. 40 samples per hour. Moreover, the high throughput of the CE method is noteworthy compared to chromatographic methods such as NMKL  method 124  and three independent replicates, and randomly injected in the CE system.Two matrix calibration curves were prepared, one for mustard and another one for ketchup, both prepared by standard addition to blank samples. Due to the similarities in the composition of ketchup and tomato sauce, we assume that the interfering is comparable and, therefore, just one curve was built for ketchup to represent all styles of tomato-based sauces. In order to reproduce accurately the presence of possible interfering of the matrix, the blank samples used were obtained under the extraction and dilution conditions described in the sample preparation paragraph of Materials and Methods section.versus concentration, and all curves had coefficient of regression R2>0.99. Residual plots were assessed by visual inspection, and no lack of linearity or heteroscedasticity was verified. The assumptions of normality  t-test bi-caudal. The presence of matrix effect was observed for the ions of sorbate (p=0.0002) and benzoate (p=0.01) in ketchup and sorbate in mustard (p=0.006). In this regard, all quantifications were performed using matrix calibration curves.The matrix effect was assessed by comparing the slopes obtained for the standard solution and matrix calibration curves (mustard and ketchup). Differences were considered statistically significant at the 5% level (p<0.05) through the The selectivity was evaluated experimentally by injecting the analytes  and the possible interferent (ascorbic acid) under the separation conditions. After the injection, the electropherogram was visually inspected, and the capacity of the method to accurately separate the analytes in the presence of the interferent was confirmed.The parameter repeatability (intra-day) was assessed using three consecutive injections of a standard solution of the analytes . At the same time, the intermediate precision (inter-day) was determined by injecting this standard solution three times for three consecutive days. The method precision was confirmed since the results for both intra- and inter-day precision were lower than 2.60% relative standard deviation .The accuracy was established by recovering blank samples fortified at three concentrations . The results for sorbate and benzoate in mustard ranged from 99.0 to 101.1% and 98.8 to 101.6%, respectively, while in ketchup, they ranged from 91.6 to 98.8% for sorbate and 94.2 to 104.2% for benzoate . TherefoThe scientific community has shown a growing interest in the development of environmentally sustainable analytical methods. Several authors name their methods as ’environmentally friendly’, however, this affirmation often comes from an empirical denomination, since there is no clear evidence to support it. Recently, some approaches have been proposed to quantitatively determine this claim in analytical procedures. Some examples are the National Environmental Methods Index (NEMI) labeling, Analytical Greenness Calculator (AGREE), white analytical chemistry (WAC) and Eco-Scale  red principles are scope of application, sensitivity (LOD and LOQ), precision, and accuracy; (ii) green principles are toxicity of reagents, amount of reagents and waste, energy consumption, and impact on human and animal health; and (iii) blue principles are cost-benefit, time-efficiency, requirement of personnel and infrastructure, and simplicity of operation.The 12 principles of WAC are grouped into 4 red, 4 green and 4 blue principles: , it has limits of detection and quantification consistent with the level of the analytes in the samples, and it has good precision and accuracy. Most of the reagents used are non-hazardous, and the hazardous one (methanol) was used at a minimum amount; the sample preparation and the CE method were developed in order to obtain a minimum consumption of reagents and waste generation. The energy consumption of the CE method is low, and by using correct disposal protocols the impact on the environment, humans and animals can be avoided. The cost-benefit of the method is great, the time of analysis is considerably short, allowing the analysis of several samples per hour. Besides, laboratory infrastructure requirement is low. The only aspect of the WAC that the CE method may not satisfy properly is the last blue principle, which recommends miniaturization and portability, a point of potential improvement in the future to make this method even more complete.The validated method was applied for the analysis of sorbate and benzoate in 30 commercial samples of mustard, ketchup and tomato sauce from different manufacturers. The results are shown in Among the analyzed samples, six of them declared ’no preservatives’ on the label, and this claim was confirmed experimentally. Also, of the thirty evaluated samples, seven showed some kind of non-compliance. Significant problems involving mislabeling and non-compliance with the Brazilian legislation were found in the ketchup samples, where four out of ten assessed samples had some irregularity.The Brazilian legislation only allows the addition of sorbic acid and its salts at the maximum mass fraction of 1000 mg/kg in ketchup  contained benzoate, an analyte that is not allowed in this product by Brazilian legislation, at a mass fraction higher than 1000 mg/kg. Therefore, these aspects highlight the need for this kind of assessment, especially by using fast and reliable methods.


Polycystic ovary syndrome (PCOS) and irritable bowel syndrome (IBS) share similar clinical and psychosocial features. We aimed to investigate the clinical characteristics of IBS in women with PCOS, and its relationship with obesity, metabolic and hormonal profiles, as well as sleep and psychiatric disorders.2. Anthropometric measurements, metabolic, hormonal profiles, and psychosocial morbidities were compared.This is a cross-sectional case-control study of 431 untreated women with PCOS and 259 healthy volunteers. All participants were assessed with a comprehensive clinical evaluation and two questionnaires: the Athens Insomnia Scale (AIS) and the Brief Symptom Rating Scale (BSRS-5). IBS was diagnosed using the Rome III criteria. Obesity was defined as a BMI ≥30 kg/mvs 5.8%, p=0.029) and obesity  than healthy volunteers. Mixed-type IBS (IBS-M) was the most common subtype (74%) among patients with PCOS and IBS. There was a higher prevalence of psychiatric morbidities  in women with PCOS than in healthy women . Women with PCOS and IBS were more likely to have sleep difficulties  and psychiatric morbidities  than those without IBS. Anthropometrics, metabolic and hormonal profiles were similar between PCOS women with and without IBS. Among women with PCOS, those with both IBS and obesity had the highest risk of developing sleep difficulties  and psychiatric distress  than those without.Women with PCOS were more likely to have IBS (10.7% Women with PCOS have increased IBS, obesity, sleep and psychiatric disturbances. The presence of IBS in PCOS women is associated with sleep and psychiatric disorders. The coexistence of obesity and IBS exacerbates sleep difficulties and psychiatric distress. Screening and management of IBS and obesity might be warranted to improve sleep and psychiatric disturbances in women with PCOS. Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women of early reproductive age. It is characterized by chronic anovulation (oligomenorrhea or amenorrhea), clinical or biochemical hyperandrogenism, and the presence of polycystic ovaries . Women wWomen with PCOS are also more likely to present with psychological disorders such as depression, anxiety, sexual dysfunction, and psychosocial problems, affecting their health-related quality of life (QOL) –5. One sIrritable bowel syndrome (IBS) is characterized by chronic or recurrent abdominal pain or discomfort associated with altered bowel habits in the absence of structural or biochemical abnormalities . The preWe conducted this case-control study at the National Taiwan University Hospital (NTUH), a tertiary medical center. This study was approved by the institutional ethics committee (No. 201907101RINC). All participants provided their written informed consent before they were enrolled in the study. Consecutive women aged older than or equal to 20 years, with a confirmed diagnosis of PCOS and a chief complaint of irregular menstrual cycles, clinical hyperandrogenism, or both, were eligible for enrolment and were approached by the attending physicians in the reproductive endocrinology clinic. The diagnosis of PCOS was made using the Rotterdam criteria, and the enrolment inclusion and exclusion criteria we used for patients with PCOS have previously been described in detail . BrieflyWe assessed participants using a validated symptom questionnaire and diagnosed IBS using the Rome III criteria. Diagnosis is based on the presence of recurrent abdominal pain or discomfort, at least 3 days/month, for the last three months with symptom onset for at least six months, combined with at least two of the following conditions: symptoms associated with a change in the frequency of defecation or form of the stool and improvement of pain or discomfort following defecation . ParticiAll participants completed the validated Chinese version of the Athens Insomnia Scale (AIS) and the Brief Symptom Rating Scale (BSRS-5) to evaluate their sleep difficulties and stress levels. The AIS is a brief self-assessment instrument that consists of eight items: difficulty of sleep induction, awakening during the night, final awakening, total sleep duration, overall sleep quality, well-being, functioning capacity, and sleepiness during the day. It is a validated instrument for diagnosing insomnia . The firThe BSRS-5 is a five-item screening tool for identifying common psychiatric morbidities such as anxiety, depression, and related disorders . Each itt-tests. Categorical variables are expressed as a percentage and were analyzed using chi-squared or Fisher’s exact tests as appropriate. First, we compared the demographic characteristics, anthropometrics, prevalence rates of IBS, and scores for the sleep and mental health questionnaires between women with PCOS and healthy volunteers. Second, to explore the pathophysiology of IBS in PCOS, we compared the anthropometrics and metabolic and hormonal profiles of PCOS patients with and without IBS. Finally, to explore the role of obesity in the association between PCOS, IBS, and psychiatric or sleep disorders, we stratified women with PCOS based on obesity (BMI ≥ 30 kg/m2 or < 30 kg/m2) and presence of IBS. We compared the groups and used the Mantel–Haenszel test to assess the linear trend. Patients with PCOS but without IBS or obesity were considered the reference group. We calculated the 95% confidence interval (CI) and odds ratios for the other three groups. A p-value of < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS 16 .For the sample size estimation, we planned to enroll 500 women with PCOS and 500 healthy volunteers in a 1:1 ratio based on the earlier pilot study by Mathur et al. . Neverthvs 48.4 ± 10.5, p < 0.001) and had a higher BMI  and larger waist circumference  than women in the control group. There was also a higher prevalence of obesity  and central obesity  in women with PCOS than in healthy women (p < 0.001) and more hard or lumpy stool (p < 0.001) than the control group. In the PCOS group, the overall prevalence of IBS was 10.7%, which was significantly higher than in the control group . Mixed-type IBS (IBS-M) was the most common subtype in both groups , suggesting higher psychosocial stress levels. Additionally, the prevalence of psychiatric morbidity, defined as a total BSRS-5 score of ≥ 10, was higher in the PCOS group .Women with PCOS had lower scores than the control group for the AIS items ‘awakening during the night’ and ‘early awakening’, but higher scores for ‘sleepiness during the day’ Table 2.p < 0.001). Patients with PCOS and IBS also had higher scores for all five BSRS-5 items and higher total scores  in patients with PCOS and IBS. Other clinical characteristics  were similar in the two groups.We compared the demographics, metabolic profiles, hormone profiles, and sleep and psychological characteristics of PCOS women with and without IBS Table 3.2 and those with a BMI < 30 kg/m2  women with PCOS have a higher prevalence of IBS, as diagnosed using the Rome III criteria, and obesity than healthy controls; (2) women with PCOS and IBS are more likely to have sleep difficulties and psychiatric morbidities; and (3) obesity may increase the impact of IBS to exacerbate sleep and psychiatric disorders in women with PCOS. To our knowledge, this is the first study to report the complex relationship of IBS and obesity in women with PCOS—a population that is increasing continuously—and its relationship with sleep and mental health.vs 3.4%) (vs Rome III) and the populations studied. The Rome I criteria did not categorize IBS into subtypes, but using the Rome III criteria we found that mixed-type IBS was the most common subtype in both groups of our study population. This result is consistent with the latest systematic meta-analysis  is consistent with a nationwide questionnaire survey based on the Rome III criteria that was conducted in Taiwan in 2005–2008. The authors of that study reported an overall prevalence of IBS in the general population of 4.4%, and the prevalence was significantly higher in women than in men (5.4% vs 3.4%) . Our resvs 3.4%) , 12. How% is consPrevious studies have consistently shown that IBS is more common in women than in men . The preIn the present study, we used the Rome III criteria rather than the more recent Rome IV criteria because they remain the most widely used and well-validated diagnostic criteria in the literature. In addition, the Rome IV criteria include ‘abdominal pain’ and exclude ‘abdominal discomfort’, and also include more stringent frequency criteria. The use of the Rome IV criteria has greatly reduced the prevalence of reported IBS, so this system may be less suitable for an epidemiological survey such as this one , 19.via the inhibition of RhoA signaling, cholecystokinin (CCK) and CCK(A) receptor activation   transit and are more prone to constipation than men. However, previous studies have obtained contradictory findings regarding the effect of the various sex hormones on GI motility –27. A re (MLC20) . These fSeveral studies have highlighted the association between the abundance of gut microbiota and PCOS in humans –31. AnotPsychosocial distress is common in both patients with IBS and patients with PCOS, and could also play a bidirectional role in the development of IBS in women with PCOS . A recen2) than those with PCOS but no IBS (30.3 ± 1.6 kg/m2) (2) than in Western studies, suggesting that obesity alone may not play a significant role in the development of IBS in women with PCOS. However, obesity has been associated with increased psychiatric disorders and sleep disturbances in previous studies (Obesity is an important feature of PCOS. Previous studies have found that women with PCOS and IBS had a higher BMI (32.9 ± 2.0 kg/m6 kg/m2) . Althoug studies , 46. In  studies . Similar studies . This asThis study’s strengths include a relatively large sample of women with PCOS and a complete clinical assessment, including anthropometric measurements and hormonal assays, which allowed for a comprehensive subgroup analysis. In addition, we recruited the control group from the general population who attended the routine health check-up. The in-person interviews and physical examination by gynecologist as well as detailed laboratory and imaging studies to exclude any organic lesions which may interfere the manifestations of IBS symptoms and psychosocial comorbidities. However, our study also has several limitations. First, it was designed as a cross-sectional case-control study, and as such it cannot explain the cause–effect relationship between PCOS and IBS. Second, women with PCOS were younger and more obese than the control group, and age and BMI may be confounding factors in interpreting the higher prevalence of IBS in women with PCOS. However, the fact that our study had mostly younger women reflects the real-world situation, and further this aspect is consistent with two similar studies , 12. FutIn conclusion, our study shows that women with PCOS have increased IBS, obesity, sleep and psychiatric disturbances. The presence of IBS in women with PCOS is highly associated with presence of sleep and psychiatric disorders. The coexistence of obesity and IBS exacerbates sleep difficulties and psychiatric distress in women with PCOS. Screening and management of IBS and overweight/obesity might be warranted to improve sleep and psychiatric disturbances in women with PCOS.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 National Taiwan University Hospital (NTUH) Research Ethics Committee (REC). The patients/participants provided their written informed consent to participate in this study.P-HT, H-MC, C-HT, and M-JC: drafting the manuscript. P-HT, H-MC, and M-JC: study concept and design. P-HT, H-MC, and M-JC: acquisition of data, analysis, and interpretation of data. M-SW, H-NH, and M-JC: critical revision of the manuscript for important intellectual content. P-HT and M-JC: statistical analysis. P-HT, M-SW, and M-JC: obtained funding. M-SW, H-NH, and M-JC: study supervision. All authors have seen and approved the submission of this version of the manuscript and take full responsibility for the manuscript. All authors have given final approval of the version submitted, and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.This study was supported by research grants from the National Taiwan University Hospital (NTUH. 106-003411) and the Ministry of Science and Technology, Taiwan . The funders had no role in the study design, data collection and analysis, decision to publish, or manuscript preparation.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.


Background: To determine the possible risk factors of recurrent tracheoesophageal fistula (rTEF) after Gross type C esophageal atresia (EA) and tracheoesophageal fistula (TEF) repair.Methods: The medical records of 343 pediatric patients with Gross type C EA/TEF who underwent surgical repair were retrospectively analyzed. The patients were retrospectively divided into two groups according to whether they had rTEF. Univariate and multivariable logistic regression analysis were performed to identify risk factors for rTEF.Results: After the diagnosis of EA/TEF, 343 patients (221 boys) underwent primary repairs after birth. According to the follow-up results , 259 patients (257 survived and two died after rTEF repair) were included in the analysis. rTEF occurred in 33 patients , with a median onset time to recurrence of 3.8  months. Multivariate analysis showed that closing the original TEF with ligation and hospital stay ≥ 28.5 days were significant risk factors of rTEF with OR of 4.083  and 3.228 .Conclusions: Surgical closure technique of original TEF and the length of initial stay could influence the occurrence of rTEF after Gross type C EA/TEF repair. Esophageal atresia (EA) and tracheoesophageal fistula (TEF) is one of the most common congenital malformations of the esophagus, with an incidence of 1/2500 – 1/4500 . Understn = 195) and from January 2013 to January 2020 at The Affiliated Children's Hospital of Nanchang University (n = 148) were retrospectively analyzed. The primary operations were performed via thoracoscopic or open approach. Demographic information, preoperative assessments, surgical notes, and information pertaining to surgical complications were extracted from the electronic medical records and analyzed. The symptoms that led to diagnosis of rTEF were recurrent pneumonia, coughing during feeding, or both. Diagnostic investigations for rTEF included bronchoscopy and esophagram. Bronchoscopy was used to measure the distance between the fistula and the tracheal carina and the glottis. The patients were retrospectively divided into two groups according to whether they had rTEF. Patients with missed diagnosis of the proximal TEF during the initial operation were excluded in this study. All patients in the rTEF group received surgical repair. This retrospective study was approved by the Medical Ethics Committee of the Beijing Children's Hospital (2019-k-333), and the patient informed consent requirements were waived.The medical records of 343 pediatric patients with Gross type C EA/TEF who underwent surgical repair from January 2007 to January 2020 at Beijing Children's Hospital , VACTERL syndrome (n = 19), chromosome abnormality (n = 2), and other syndromic diagnosis (n = 1).In this study, 343 patients were included (221 boys and 122 girls). These patients had a median gestational age of 38.1 weeks (range: 30–44 weeks) and a median birth weight of 2,850 g . Two hundred and seventy-four patients were found to have congenital diseases, including non-syndromic anomalies  or open (n = 129) approach.After the diagnosis of EA/TEF, all patients underwent primary repairs after birth. The primary operations were performed After a median follow-up of 16 months (range: 0 months to 163 months), 257 patients survived, 42 died and 44 patients were lost to follow-up. Among the 42 who died, parents of 21 patients had refused further treatment after surgical repair of EA/TEF. Thirteen patients died in hospital after surgical repair of EA/TEF, two died after rTEF surgery, one died of perforation after dilation procedure, and one died of cardiac abnormalities. The reason for death in the remaining four patients was unknown.P = 0.044) and the length of hospital stay (P = 0.009) was associated with rTEF after the primary repair of Gross type C EA/TEF. There were no differences between the two groups for other clinical characteristics .According to the follow-up results, 259 patients (257 survived and two died after rTEF repair) were included in the analysis of risk factors of rTEF. rTEF occurred in 33 patients , with a median onset time to recurrence of 3.8  months. In order to find the risk factors for rTEF, we conducted a multivariate analysis. As shown in rTEF is a serious complication after EA/TEF repair, with an incidence of 3–14% . ComplexPatients with rTEF usually present with choking and recurrent pneumonia. However, these symptoms may also appear due to other complications after the operation of EA/TEF, such as esophageal stricture or gastroesophageal reflux. It is difficult to diagnose rTEF by symptoms alone and it is usually necessary to rely on auxiliary examinations such as bronchoscopy, esophagography, and esophageal gastroscopy to form a diagnosis , 5. RepaFew studies have reported the influencing factors of rTEF. According to previous reports, rTEF may be associated with premature delivery, low birth weight , anastomn = 4) or sutures (n = 80) to close the fistula. Ligation is used to ligate, and suture is used to transfix the tracheal end of the fistula, both of which occur before eventually cutting the fistula off. For thoracoscopic surgery, we use ligation (n = 86), ham-lock clips (n = 70), or sutures (n = 10) to close the fistula. The use of ligation and sutures is the same as during thoracotomy. The Ham-lock clip is used to clip and close the fistula near the trachea before cutting it off. We found that separating the fistula after ligation was an important risk factor for recurrence. In early EA/TEF repair, the fistula was simply ligated and an esophagus end-to-side anastomosis was performed, but it was believed that the fistula may be recanalized after surgery . Finally, the free part of the prevertebral fascia is placed between the two ends of the fistula to isolate the ends, which is known to prevent re-recurrence of the fistula. At present, it is generally believed that it is very important to choose a suitable tissue liner between the incised TEF during the rTEF operation to improve the success rate and avoid recurrence. Whether the application of this technique can reduce the occurrence of rTEF is still worthy of future research.Basing on this is a retrospective study, surgical procedures and details, and perioperative management will change over time, and access to surgical details and postoperative complications information is also limited. Surgery performed by different surgeons and the respective follow-up time is different, resulting in a certain degree of heterogeneity in the results. Due to the small sample size of the two centers, the conclusions cannot be verified externally. We need to prospectively recruit more patients for regular and longer follow-up and obtain more detailed surgery and perioperative records to further understand the long-term prognosis of these patients and analyze risk factors for rTEF.In conclusion, using transfixing suture to close TEF is an important protective factor for rTEF. We should avoid simply ligating the fistula during primary repair of EA/TEF. Furthermore, patients with long postoperative hospital stay (≥ 28.5 days) and postoperative complications should be highlighted for the possibility of rTEF during follow-up.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the Medical Ethics Committee of the Beijing Children's Hospital. Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.JH, SY, and SiL: study conception and design. ZY, JL, KH, and YG: data acquisition. YZhan, YZhao, and ShL: analysis and data interpretation. SY and SiL: drafting of the manuscript. All authors contributed to the article and approved the submitted version.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.


At present, chemotherapy is still the primary treatment for advanced biliary tract carcinoma, but it is challenging to balance the efficacy and side effects. Network meta-analysis (NMA) is a better way to identify the protocol, and the advantage is that it can be combined with direct and indirect evidence to judge the best treatment regimens. Therefore, we conducted NMA on the searched randomized controlled trials (RCTs).NMA was conducted regarding the searched RCTs by comparing progression-free survival (PFS), overall survival (OS), objective remission rates (ORRs), and adverse events (AEs) of different chemotherapy protocols.We screened 24 studies that met the inclusion criteria for further analysis. Compared with other regimens, the best supportive care (BSC) or FUFA protocol has a worse OS. Folfox4, GEMOX+erlotinib, and C+GEMOX can improve patients’ PFS compared with BSC. Patients receiving GP+cediranib protocol have higher ORRs. There was reduced neutropenia grade ≥3 when adopting GP+cediranib, GS, C+GEMOX, RAM+GP, and MER+GP than when using FUFA protocol. The probability of vomiting of XELOX is lower than that of GEM+XELOX. There is a lower diarrhea incidence of XELOX than that of GEMOX+erlotinib. The results of cluster grade analysis illustrated that GEMOX+erlotinib owned a higher ORR and a higher surface under the cumulative ranking (SUCRA) of neutropenia and vomiting but also had a lower SUCRA of diarrhea and fatigue. Meanwhile, both GEMOX and C+GEMOX have a better ORR and a higher AE SUCRA.The NMA demonstrated that chemotherapy combined with targeted therapy has better efficacy and lower incidence of AEs than chemotherapy alone. Biliary tract carcinoma (BTC) can be divided into intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), gallbladder carcinoma, and ampullary cancer according to the position of disease occurrence, in which ECC can be further divided into hepatic portal cholangiocarcinoma and distal cholangiocarcinoma. BTC is a malignant tumor originating in the bile duct epithelium, accounting for 3% of all digestive tract tumors , 2. The Currently, based on the results of randomized controlled ABC-02 and JCOG1113/FUGA-BT in period III, gemcitabine combined with cisplatin or gemcitabine combined with tegafur, gimeracil, oteracil potassium capsules is recommended for the first-line treatment of advanced BTC . Based oTargeted drugs and immune checkpoint inhibitors (ICIs) have been explored in BTC treatment, and there is no evidence of adjuvant therapy. In terms of the first-line treatment of advanced BTC, the combination of ICIs with chemotherapy or targeted drugs is still in the clinical trial stage. Hence, at present, chemotherapy is still the primary treatment for advanced BTC, but it is challenging to balance the efficacy and side effects, and the evidence-based medical evidence for drugs used in advanced BTC therapy is still less. The efficacy and safety of many chemotherapy regimens are still controversial. Additionally, the evidence-based medical evidence for medications used in advanced BTC therapy is still inadequate.Network meta-analysis (NMA) is a better way to identify the protocol. The advantage is that it can be combined with direct and indirect evidence to judge the best treatment plan instead of relying solely on direct head-to-head comparisons of the two drugs. Therefore, we conducted NMA on the searched randomized controlled trials (RCTs). Progression-free survival (PFS), overall survival (OS), objective remission rates (ORRs), and adverse events (AEs) of different chemotherapy protocols were compared to find the best treatment strategy for the first-line treatment of advanced BTC in these clinical studies .We have retrieved all articles published before August 10, 2020, in PubMed, EMBASE, and Cochrane Library. The combination of subject words and free words was adopted for retrieval with the following MeSH terms: “Bile Duct Neoplasms”, “Cholangiocarcinoma”, “Gallbladder Neoplasms,” “advanced”, “unresectable”, “randomized”.The literature should meet the following criteria: (1) study type: published RCT of II/III period; (2) subjects: advanced BTC confirmed by histology; (3) patients with advanced BTC receiving first-line chemotherapy; (4) the primary outcome indicators: reported PFS, OS, and ORR; the secondary outcome indicators: the probability of neutropenia level ≥3, vomiting, diarrhea, and fatigue. The exclusion criteria are as follows: (1) letters, reviews, case reports, non-human studies, and articles that do not provide raw data; (2) non-English articles; (3) non-randomized controlled single-arm studies; (4) research includes a comparison of chemotherapy with adjuvant or neoadjuvant treatment; (5) the study only included patients with specific gene mutations.Data were extracted independently by two researchers, and the following information was recorded in the Microsoft Excel spreadsheet: study number, first author, year of publication, country, pathological diagnosis, patient’s tumor stage and Eastern Cooperative Oncology Group (ECOG) score, patient’s sex, age, sample size of each group, sample size, treatment plan, usage of test group and control group, hazard ratio (HR) and 95% CI of PFS and/or OS, and occurrence of the probability of neutropenia grade ≥3, vomiting, diarrhea, and fatigue.Two researchers independently assessed the quality of all included literature based on RCT Cochrane Reviewer bias risk assessment criteria: (1) generation of random sequences; (2) allocation concealment or not; (3) blind method or not; (4) complete results or not; (5) selective reporting or not; (6) other biases. These key points are divided into three levels: low risk, high risk, and unclear risk. Differences between investigators are resolved through discussion.vice versa.HR and its 95% CI were adopted to express outcome indicators of time–event variables (PFS and OS); OR and corresponding 95% CI were applied to represent the outcome indicators of binary variables (ORR and adverse reactions). Engauge4.1 was used to estimate the HR and its 95% CI if only survival curves were provided. Stata14.0 software was adopted to make an evidence relationship diagram of NMA, generating network diagram for different protocols. R software gemtc installation package and gemtc software were applied to conduct NMA based on Bayesian framework. Considering the heterogeneity between the studies, the random-effects consistency model was used for all data analyses. The parameters of R software are as follows: four simulated chains, 400,000 simulated iterations, 50,000 adjustment iterations, 10 refinement iterations. The 95% CI was adopted as a criterion judging whether the difference was statistically significant: When 95% CI was over 1, it prompts P < 0.05, the difference was not statistically significant, and 2 statistic and p-value within a visual forest plot to time–event variables. p > 0.05 is considered to have no inconsistency. With I2 values below 25%, between 25% and 50%, and above 50%, the heterogeneity is deemed to be low, moderate, or high, respectively. For binary variables, we used node-splitting analysis to assess heterogeneity and inconsistency. We investigated the inconsistency factor (IF) among studies in each closed loop. If the 95% CIs of IF values include zero, it indicates no significant inconsistency. The τ2 = 0 and p > 0.05 are considered to have no inconsistency and low heterogeneity. A funnel plot evaluated the publication bias.We assessed heterogeneity and inconsistency between studies using the IWithin the Bayesian framework, the overall ranking of treatments was estimated through NMA by calculating the ranking probability of each method. We calculate the surface under the cumulative ranking (SUCRA) within the framework of frequency science to estimate the overall ranking of treatment. Cluster rank analysis was conducted on the ORR of each intervention and the corresponding reported SUCRA of AEs .We searched a total of 1,668 records in the database and removed 701 duplicate documents. After reading the title and abstract, we preliminarily screened 967 papers. The title/summary and the full text were screened based on inclusion and exclusion criteria. Finally, we screened 24 studies that met the inclusion criteria for further analysis. The flowchart of literature screening is shown in OS and PFS –25, 27 wA total of 21 studies reported ORR –27 of alBased on all the studies, we selected four mostly reported AEs for subgroup analysis: neutropenia grade ≥3, vomiting, diarrhea, and fatigue. The comparison of the four AEs of each protocol obtained from Bayesian NMA is shown in Based on the above NMA results, cluster rank analysis was conducted on the ORR of each intervention and the corresponding reported SUCRA of AEs . The result demonstrated in -2 = 0%) or low heterogeneity in half of all comparisons. The high heterogeneity was detected in OS in comparisons of GS and GEMOX regimens (I2 = 59.8% vs. 48.4%). There was no severe heterogeneity, inconsistency analysis, and bias in the PFS, ORR, and AEs of each regimen (τ2 = 0 and p > 0.05).We analyze the heterogeneity and inconsistency of the results; the forest plot and funnel plot of the offset results were generated in This paper comprehensively compared in an NMA the efficacy and safety in advanced BTC of the most commonly used first-line BTC therapies to the best of our knowledge. The results showed that in terms of patients’ OS, the above protocols own a better efficacy to prolong patients’ OS than BSC does. There is no statistical difference between the other protocols through pairwise comparison, but it could be found that gemcitabine+sorafenib had a better effect than gemcitabine alone. XELOX and GEMOX performed better in prolonging patients’ PFS than other protocols. The three chemotherapy protocols GP +cediranib, GEMOX+erlotinib, and C+GEMOX combined with targeting can improve patients’ ORR compared with different protocols. At the same time, there were fewer occurrences of AEs in GEMOX+erlotinib and C+GEMOX. As a result, chemotherapy combined with targeting has better efficacy and lower AE incidence than chemotherapy alone. Critical headway has been made in targeted therapy acting on single or multiple targets in the treatment of advanced BTC.KRAS mutations and epidermal growth factor receptor (EGFR) overexpression have been reported in many investigations studying advanced BTC , 29. StuMeanwhile, we also found that GEMOX+erlotinib was better than the protocol fluorouracil+folic acid in OS, PFS, and ORR. Both previous NMAs also suggested that protocol gemcitabine was superior to protocol fluorouracil , 39. CedNotably, according to the SUCRA, we found that sorafenib appeared to perform better in improving patients’ OS. When analyzing the AIO study , we founBy using NMA, we compare the effectiveness and security of some protocols. NMA can reach the direct and indirect comparisons in RCTs, and our RCTs account for a large proportion, thus obtaining a more complete outcome data. A previous NMA has proven no statistically significant difference in toxicity between chemotherapy combined with targeted therapy and chemotherapy alone . By clusNMA also has limitations in this paper. Most of the studies included did not provide detailed information. Besides, there are inevitable errors in software calculation. Some studies have failed to offer specific pathological types, and clinical stages were unable to do subgroup analysis on the subtypes or stages of BTC. Since RCT studies on cholangiocarcinoma are the minority, there are not many available data. If one of the studies is excluded for sensitivity analysis, it may prevent the NMA from forming a closed loop, thus affecting the estimation. So the possibility of bias or heterogeneity is not ruled out. We will further improve the sensitivity analysis to test the robustness of the results when more RCTs are added in the future. At the same time, tumor therapy has entered the era of immunotherapy, which has achieved amazing efficacy in lung cancer, liver cancer, and other tumors. Since many RCTs on immunotherapy have not yet published complete results, the NMA in this paper is not included in immunotherapy-based protocols. Today, there are many studies on ICIs for the treatment of advanced BTC, such as pembrolizumab, nivolumab, and other drugs combined with targeting or chemotherapy, whose efficacy remains to be seen. We look forward to an NMA on the effectiveness and safety of ICIs for patients with advanced BTC.By using NMA, which involves more drugs in advanced BTC first-line therapy, we hope that our study can be used as a reference for clinical treatment. Also, we hope that more research and treatment drugs can be included in the future to carry out a more detailed analysis to obtain more comprehensive results, thereby selecting the optimal treatment plan for patients.Our meta-analysis revealed that chemotherapy combined with targeted therapy has better efficacy and lower incidence of AEs than chemotherapy alone. This finding may facilitate the effective treatment of patients with cancer.The original contributions presented in the study are included in the article/YJ and JM contributed to the conceptualization. YJ and JQ contributed to the methodology. YJ and JT contributed the software. YL and NM contributed to the validation. YJ and JZ contributed to the formal analysis. ZZ and LD contributed to the data curation. YJ contributed to writing–original draft preparation. ZZ contributed to writing–review and editing. YJ and CL contributed to the visualization. All authors contributed to the article and approved the submitted version.This research was supported by the Guangxi Natural Science Foundation (2018GXNSFAA281126).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.


Objective: This study examined how best to identify modifiable protective and risk factors for burnout in healthcare workers in the face of the COVID-19 pandemic. Individual, occupational, organizational and social factors were investigated. The study also assessed the impact of these factors on post-traumatic stress disorder (PTSD), anxiety, and depression.Methods: Healthcare workers in the Quebec (Canada) healthcare system were recruited between May 21 to June 5, 2020. Participants answered an electronic survey 3 months after the COVID-19 epidemic outbreak began in Canada. Using the Maslach Burnout Inventory, PTSD Checklist for DSM-5, and Hospital Anxiety and Depression Scale, we studied the prevalence of burnout, PTSD, anxiety and depression in this cohort. Multivariable logistic or linear regression models including resilience, social and organizational support, workload and access to mental health help, simulation techniques and protective personal equipment (PPE) as well as perception of PPE security were conducted for each outcome.Results: In mid-June 2020, 467 participants completed the survey. We found that half (51.8%) of the respondents experienced burnout characterized by emotional exhaustion and/or depersonalization at least once a week. In total, 158 healthcare workers (35.6%) displayed severe symptoms of at least one of the mental health disorders . Resilience  and perceived organizational support  were significantly associated with burnout and other outcomes. Social support satisfaction, perception of PPE security, work type and environment, mental health antecedents and reassignment were associated with PTSD and/or anxiety and/or depression, but not burnout.Conclusion: Future studies should address primarily resilience and perceived organizational support to promote mental health and prevent burnout, PTSD, anxiety and depression. Healthcare workers are at high risk of contracting SARS-CoV2  after the start of the COVID-19 epidemic outbreak in Quebec, Canada (March 2020).The Montreal Health Innovations Coordination Center (MHICC) specifically developed the web platform for the present study. The system used the MHICC extranet portal with secure access to web pages by a Transport Layer Security (TLS) certificate, using standard encryption technology  and an auto logoff function in the event of a sustained period of inactivity. The data collected using this platform was sent and saved to the MHICC for a period of 10 years. Each participant only had access to their own data, and in no case had access to the data of other participants. The platform was accessible in French and in English via a smartphone, a tablet or a computer.Between May 21st and June 5th 2020, the study team recruited healthcare workers from across Quebec's healthcare system, including those in long-term care centers (in French: Centres d'hébergement de soins de longue durée [CHSLD]). To do so, we shared a newsletter explaining the objectives of the study through study collaborators' social media accounts, Quebec health professional organizations and association's networks, and conventional media. The newsletter directed the interested healthcare workers to a web page that served as an initial screening for eligibility for participation. All participants were required to have access to an e-mail address and the Internet, had to be age 18 or over and had to work as one of the listed health care work types . After reading the information and consent form, the users could sign it, if desired, to become participants in the study. In addition to the survey, we asked participants if they wanted to be contacted by the research team for (1) a post-survey follow-up to collect their comments and/or questions and/or (2) feedback on their individual results if the questionnaires indicated risks of developing PTSD, anxiety or depression . In addition, all participants could contact the research team by phone or e-mail if they had any questions related to the research project or if they needed either psychology referral, or referral to any other mental health organizations. It should be noted that we did not use the snowball sampling technique here since the subjects who consented to participate were not invited to continue recruiting among their affiliation , 36.In mid-June 2020, study coordinators sent one to three e-mails to invite participants to complete the 3-month online survey. Participants had 1 week to respond and partially completed surveys were accepted.The main features of the tools used are presented here, but additional details about the surveyed measures are described in Resilience, self-compassion, social and organizational support were measured with the Connor-Davidson Resilience Scale [α = 0.85 ], the SeWe calculated the sample size based on a simple logistic regression model with resilience as the single independent variable of interest. Then, we made a correction based on the correlation between the variable of interest and the model's other independent variables. The expected overall burnout rate at 3 months was 50% . Using ap-value lower than 0.2 in univariate models were then identified and entered in the previous model including all independent variables (which were forced in the model) using the stepwise procedure. The criteria for an adjustment variable to stay in the final multivariable model was a significance level of 0.05. For each endpoint, an exploratory analysis was conducted by adding the self-compassion variable to the final multivariable model identified above. Adjusted odds ratio for logistic regressions and adjusted coefficients for linear regressions were calculated with 95% confidence intervals.Study characteristics were summarized using counts and percentages for categorical variables and mean ± SD for continuous variables. To identify the survey response rate, we divided the number of participants who completed the survey by the total number of participants who consented to participate in the study and then multiplied by 100 to obtain a percentage. For each efficacy endpoint , a multivariable logistic (or linear) regression model including all the pre-specified independent variables of clinical interest  was fit first. No variable selection was done at this stage and all independent variables were included. The pre-specified adjustment variables  showing a Scores for each questionnaire were calculated according to the formulas provided in the Of the 564 participants, 467 (83%) respondents completed the 3-month survey. Two (0.4%) participants have withdrawn, one before and one after completing the 3-month survey.Centres locaux de services communautaires [CLSC]), clinics and CHSLD. About a quarter of participants worked in another environment such as rehabilitation centers or child and youth protection centers. Ninety-one percent of the respondents perceived they had access to psychological resources if needed. Concerning the PPE, 67% of the respondents always had access to it, with a majority feeling either “pretty” or “totally safe” using it. Twenty-two percent of respondents participated in COVID-related simulation-type practices, the last simulation round having occurred 1–2 months ago for 50% of these participants. Seventy percent of the respondents had been tested for SARS-CoV2 and <5% of them had received a positive status. Close to 40% of respondents were involved in direct COVID care and 33% were reassigned either to another practice area or establishment  and perceived organizational support  were the only two variables significantly associated with burnout, in an inverse relationship. In other words, there is a 31% decrease in the odds of burnout for each SD (6) increase on the resilience scale; and there is a 25% decrease in the odds of burnout for each SD (12) increase on the perceived organizational support scale.Multivariable linear regression analyses were performed for PTSD, anxiety, and depression symptoms –6. Tablep = 0.04) and anxiety symptoms .For the exploratory analyses, only the PTSD and anxiety models are presented, as they are the two models that have retained the self-compassion variable (SD = 3.74) in their regression models see , 9. TherThree months after the start of the COVID-19 pandemic, we surveyed the psychological health of 467 workers of Quebec's healthcare system. Among them, 52% met the cutoff score for burnout, much higher than pre-pandemic periods [which was estimated at ~30%   . In anotctively) , 65 showBecause self-compassion is a less recognized and studied variable in healthcare compared to resilience, we studied it as part of an exploratory analysis. Our results show that it has a protective effect on anxiety and PTSD, which is consistent with the general population literature , 72. SelConcerning the limits of our survey study, we cannot establish causal effects, given that we measured our outcome and factors at the same time, making the temporal relationship impossible to assess . Also, wOur study differs from previous ones by covering a wide range of variables often treated separately. Notably, this study addresses both organizational and individual psychological health outcomes and considers a combination of factors arising from individual, social and organizational psychology. In addition, our study includes medical workers, but also non-medical health workers facing this pandemic. Our results reinforce the relevance of targeting individuals –79 and oIn accordance with the ethical consent provided by participants, the data underlying this article cannot be shared publicly to preserve their privacy.The studies involving human participants were reviewed and approved by Research Ethics and New Technology Development Committee (CÉRDNT), Montreal Heart Institute, Montréal, Canada. The patients/participants provided their written informed consent to participate in this study.JB, M-FM, J-CT and SG: conceptualization. SC, M-JM, CR, and JB: data curation. CR and M-CG: formal analysis. JB: investigation, project administration, resources, and supervision. SC, M-CG, and JB: methodology. CR and JB: validation. SC, M-JM, and JB: visualization. CR, M-CG, CG, and JB: roles/writing—original draft. All authors recruitment, funding acquisition, and writing—review and editing.J-CT reported grants from Amarin, grants and personal fees from Astra Zeneca, grants, personal fees, and other from Dalcor, grants from Esperion, grants from Ionis, grants from Pfizer, grants and personal fees from Sanofi, grants and personal fees from Servier, personal fees from HLS Therapeutics, outside the submitted work; In addition, J-CT had a patent Genetic markers for predicting responsiveness to therapy with hdl-raising or hdl mimicking agent pending, and a patent Methods for using low dose colchicine after myocardial infarction with royalties paid to Invention assigned to the Montreal Heart Institute. The remaining 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.


Diet and social determinants influence the state of human health. In older adults, the presence of social, physical and psychological barriers increases the probability of deprivation. This study investigated the relationship between social deprivation and eating habits in non-institutionalized older adults from Southern Italy, and identified foods and dietary habits associated with social deprivation.We recruited 1,002 subjects, mean age 74 years, from the large population based Salus in Apulia Study. In this cross-sectional study, eating habits and the level of deprivation were assessed with FFQ and DiPCare-Q, respectively.n = 441) included slightly more females, who were slightly older and with a lower level of education. They consumed less fish (23 vs. 26 g), fruiting vegetables (87 vs. 102 g), nuts (6 vs. 9 g) and less “ready to eat” dishes (29 vs. 33 g). A Random Forest (RF) model was used to identify a dietary pattern associated with social deprivation. This pattern included an increased consumption of low-fat dairy products and white meat, and a decreased consumption of wine, leafy vegetables, seafood/shellfish, processed meat, red meat, dairy products, and eggs.Deprived subjects (The present study showed that social factors also define diet and eating habits. Subjects with higher levels of deprivation consume cheaper and more readily available food. Together with the quality of diet and eating habits, social determinants influence the welfare of a population –3. An unWrezinski defines deprivation as “the lack of safety, like a job, enabling individuals and families to assume professional, family and social responsibilities and to enjoy basic rights” . In the The presence of social, physical and psychological barriers, such as loss of appetite, an impaired sense of smell and taste, difficulty in finding and preparing food, age-related diseases, reduced mobility, and social isolation, not only make states of deprivation more frequent in older adults than in younger ones, but also result in inevitable changes of lifestyle and eating habits. Many age-related physical, clinical, economic and social factors can compromise previously existing healthy dietary habits. In qualitative and quantitative terms, several studies have highlighted that nutrition in older people is influenced by age, gender, and socio-economic conditions , 20. In www.istat.it).According to the data reported by the National Institute of Statistics (ISTAT), about 22.8% of the entire Italian population is aged over 65 years of age, and the aging population trend is continually rising  older people of the United Kingdom . The pren = 4,537), enrolled from 2014 to 2019 in Castellana Grotte, Southern Italy. The sample is representative of the entire population of older people (age > 65 years) of Castellana Grotte at 2014, as described elsewhere (http://www.stard-statement.org/). The manuscript was organized according to the “Strengthening the Reporting of Observational Studies in Epidemiology-Nutritional Epidemiology” (STROBE-nut) guidelines (https://www.strobe-nut.org/).This cross-sectional population-based study involved 1,002 subjects aged over 64 years, representing a sub-sample from the “Salus in Apulia Study” . The signs of deprivation, perceived and self-reported, allow possible states of social distress to be identified. DiPCare-Q is a structured self-administered questionnaire consisting of 16 questions about social status, level of education, source of income, and poverty level. This questionnaire assesses three distinct dimensions of deprivation: material (eight items), social (five items), and health (three items), each of which corresponds to a sub-index . Sub-indGlobal cognitive performance was assessed by the Mini-Mental State Examination (MMSE), a measure that includes 10 items determining spatial and temporal orientation, attention, memory, language, and visuospatial functions .2. Height and weight measurements were performed using a Seca 220 stadiometer and a Seca 711 scale. Blood was collected from the subjects in the morning after an overnight fast and, among other parameters, Interleukin-6 (IL-6), Tumor Growth Factor-α(TNF-α), C-Reactive Protein (CRP) were measured, using standard automated enzymatic colorimetric methods , under strict quality control.Lifestyle and anthropometric assessments were evaluated by a physician during an interview at the study center. Smoking status was assessed with the single question, “Are you a current smoker?.” The level of education was expressed as years of schooling. Body mass index (BMI) was calculated as kg/mDiet and eating habits were assessed with a validated food frequency questionnaire (FFQ) used in previous studies , 28. TheSubject characteristics are reported as Mean ± Standard Deviation (M ± SD) for continuous variables and as frequencies and percentages (%) for categorical variables.Comparisons of a categorical variable between two independent groups were performed by Chi-square test and Wilcoxon rank-sum (Mann-Whitney) test to assess the statistically significant differences between groups in relation to a continuous variable based on mean rank scores.A logistic regression model was used to evaluate the associations of Social Deprivation with age, gender, education and the single Food-Group examined and to obtain the z-score to evaluate the ratio of the coefficient estimate divided by standard error of the estimator, i.e., the point estimate of the coefficient, with 95% Confidence Intervals (95% C.I.). The Random Forest (RF) method , is a maThe “forest” it builds is an ensemble of decision trees, usually trained with the “bagging” method. The general idea of the bagging method is that a combination of learning models increases the overall result.We examined which variables best predict variance in the intervention effects by ranking the covariates in order of importance. The ranking is calculated as the sum of how often a given covariate is split at each depth of the forest. The sum is weighted so that early splits (low forest depth) are more important than late splits. Variables are considered “more important” if the variable is more frequently used for the first splits across all decision trees that are grown in the random forest.The parameter used for ranking was the importance score variable, calculated by adding up the improvement in the objective function given by the splitting criterion over all internal nodes of a tree and across all trees in the forest, separately for each predictor variable. The importance score variable was normalized by dividing all scores over the maximum score (100%).Variables with a high importance  were drivers of the outcome and their score values have a significant impact on the outcome, in this case social deprivation. When testing the null hypothesis of no association, the probability level of error at two tails was set at 0.05. All statistical computations were made using StataCorp. 2021. Stata Statistical Software: Release 17. College Station, TX: StataCorp LLC.n = 1,002), belonging to the “Salus in Apulia Study” population, the female sex was slightly predominant, accounting for 51%.In the participants examined in the present study  subjects included people with a deprivation index value of 0 and 1, while the group of “more deprived” (MD) people had a deprivation index value ranging between 2 and 5.p: 0.01; TNF-α: 2.84 μg/ml ± 4.08 vs. 3.04 μg/ml ± 4.29, p: 0.40; CRP: 0.54 mg/dl ± 0.71 vs. 0.60 mg/dl ± 0.90, p: 0.30). They had lower scores of MMSE than LD participants .p: 0.01), fruiting vegetables , nuts  and less “ready to eat” dishes , compared to LD subjects.A Random Forest (RF) model was used to identify a dietary pattern associated with social deprivation. This analysis underlined that 8 of the 28 food groups  were associated with this outcome: leafy vegetables, seafood/shellfish, processed and red meat, eggs, white meat, dairy and low-fat dairy products . In partIn our study of 1,002 older adults, we identified some foods able to rank subjects according to social deprivation. A higher consumption of low-fat dairy products, white meat and seafood/shellfish and a lower consumption of leafy vegetables, dairy products, processed meat, red meat and eggs was associated with a higher level of social deprivation.https://www.istat.it/it/files//2021/03/BES_2020.pdf accessed September 2021).Age was one of the factors most significantly associated with social deprivation. Older adults are generally more deprived than young subjects due to the various barriers, social and otherwise, that typically affect this age group. In our study sample, the average age of the more socially deprived (MD) group was 75 years while less socially deprived (LD) subjects were slightly younger, with an average age of 73 years, supporting the concept that age is positively associated with social deprivation. The level of education also contributes to define a more or less deprived subject. Although we could not identify any study that directly assessed the relationship between social deprivation and level of education, Prattley et al. found that fewer years of schooling predict higher levels of social exclusion in later life . EducatiIt was of great interest to note that the prediction power of education level in our study population is not as important as that of diet for social deprivation, although our study sub-sample had an average of only about 7 years of school . This rewww.bda-ieo.it). To confirm this data, longitudinal data are needed.In our sample, in the light of the data shown in The concept of deprivation is vast; social deprivation is currently distinguished from material deprivation, even if the two are really intimately linked: people are considered deprived if they lack the material standards of diet, clothing, housing, household facilities, working, environmental and locational conditions and facilities which are ordinarily available in their society, and do not participate in or have access to the forms of employment, occupation, education, recreation and family and social activities and relationships which are commonly enjoyed or accepted . The achThe present study evaluated the association between diet and social deprivation in older Italian adults. This is its main strength because to our knowledge no study has yet analyzed these aspects in similar populations. Another strength was the identification of a dietary pattern associated with deprivation through a strong machine learning approach. The dietary pattern associated with social deprivation is to be understood as an association ranking of certain food groups with a certain outcome . However, some limitations must also be taken into account. One of these is the nature of the study which was cross-sectional, and does not allow a clear directionality of an association to be discerned. A further limitation is the FFQ as a dietary assessment method. It is memory-based and thus considered prone to measurement error, limiting the ability to study small diet-disease relationships, in particular . In addiIn conclusion, eating habits, diet quality, and composition are influenced by several factors, including age, socioeconomic, cultural, and educational status. The results of our study are in line with Townsend's idea of social deprivation, in the sense that not only economic but also social, physical, psychological and nutritional conditions influence the state of health. The present results showed that older subjects with a low educational level were more deprived, and ate a diet based on foods that are generally cheaper and more easily available. The dietary pattern associated with social deprivation identified by the current study includes white meat and low-fat dairy products, that were positively associated with deprivation, while wine, leafy vegetables, seafood/shellfish, eggs, dairy, processed and red meat were negatively associated. Reducing the level of deprivation in older subjects could have a positive impact on their eating habits, their dietary quality and hence on their overall state of health during aging.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 the IRB of IRCCS Saverio de Bellis. The patients/participants provided their written informed consent to participate in this study.LL and RS: conceptualization and methodology. FC, RZ, IB, SD, GC, and DL: investigation. RD: formal analysis. RT and LL: writing—original draft preparation. RS and LV: writing—review and editing. FP, ML, GD, and HB: supervision. RS and GG: project administration. GG: funding acquisition. All authors have read and agreed to the published version of the manuscript.This study was funded by the Italian Ministry of Health with the Ricerca Corrente 2019 Grant. The work reported in this publication was granted by the Italian Ministry of Health, under the Studies on Aging Network, at Italian Research Hospitals (IRCCS).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.


Being female was the only predictor of changes in MVPA . Being female  and perceived family affluence  were predictors of changes in SB. As such, PA was less, while SB was more during the early stages of the pandemic. With the progress of the pandemic stages, health behaviors in young adults have been gradually improved. Sex and perceived family affluence were two important factors in predicting health behaviors. Our results can inform efficient policies or interventions in the COVID-19 era and future similar public health events.Though we know physical activity (PA) decreased while sedentary behavior (SB) increased compared to that before the COVID-19 pandemic, little is known about subsequent changes in PA and SB throughout one year in the post-pandemic era. This study aimed to examine the changes in PA and SB in a sample of Chinese young adults using a four-wave repeated-measure design during the pandemic. A total of 411 participants provided self-reported data of sociodemographic characteristics , PA, and SB. Nonparametric tests and generalized estimating equations were conducted. Results revealed significant changes in moderate to vigorous PA (MVPA), light PA (LPA), and SB. The MVPA of Wave 1, 2, and 3 was significantly less than that of Wave 4 ( The risks of insufficient physical activity (PA) and excessive sedentary behavior (SB) on the health burden have been well documented in the previous literature ,4,5,6,7.As a concept related to PA, but less explored, SB is characterized by low energy expenditure  in a sitting or reclined posture during waking hours . It has Nevertheless, while most existing longitudinal studies compared levels of PA and SB between two time points (pre and during the pandemic), few studies have adopted a more intensive longitudinal design to observe the changes in PA and SB during the pandemic. However, the pandemic has been predicted to last for a long time, suggesting that we will have to coexist with COVID-19 for a long period. In the real world, this expectation has been true, as many countries are suffering from the COVID-19, and a large number of cities or communities are switching the status between lockdowns starting and ending repeatedly. This scenario informs that previous studies focusing on changes in PA and SB at two survey points may inhibit researchers to obtain a more comprehensive understanding of changes in PA and SB during the pandemic. Tracking how PA and SB change in a longer period with more repeated measurements can help to depict a more accurate profile of movement changes, and thus can better inform behavioral changes plan for health promotion. However, to our knowledge, there is no study investigating changes in PA and SB throughout one year. Hence, the current study aims to fill the literature gaps and adds to evidence about seasonal changes in PA and SB in young adults during the COVID-19 era.Moreover, to better understand behavior changes in young adults, sociodemographic correlates of PA and SB during the COVID-19 pandemic were needed to be identified. Demographic factors  and physical characteristics  have been shown to be associated with changes in PA and SB during the COVID-19 pandemic ,33. ThroCollectively, the primary aim of this survey study was to examine between-season variation in PA (MVPA and LPA) and SB in a sample of Chinese university students during the pandemic period; additionally, this study aimed to examine sociodemographic correlates  of PA and SB during the COVID-19 pandemic. The results of this study may assist in designing efficient strategies to cope with healthy movement behaviors during the present and next quarantine periods.This study used data from a four-wave one-year longitudinal study conducted during the pandemic , aiming to understand changes in lifestyle behaviors and mental health among Chinese university students in the context of the COVID-19 pandemic. Initially, a convenient sampling method was taken in the current study. Study participants were mainly recruited using an online social network, by positing our research protocol through social media platforms . The inclusion criteria were to be a college student in China, willing to participate in the study and be able to communicate in Chinese. Participants who provided consent to be included in our research were sent a survey link to an online questionnaire that required around 20 min to complete. In Wave 1, 1365 Chinese college students participated in our survey.f = 0.10), a margin of error of 5%, and power of 80%. The calculated required sample size is 222. The final sample (n = 411) goes beyond this, which is sufficient to meet the excepted statistical requirements. Study participants’ recruitment and data collection procedures, as well as details of research protocol, were informally approved by the Human Research Ethics Board (No: 2020005) at Shenzhen University. More details of the study survey methodology can be found elsewhere ) at different survey time points. To examine the sex difference in age, BMI, and perceived family affluence, Mann-Whitney U test was used to achieve the related aims; then, a Chi-square test was performed to test sex differences in residence location. A nonparametric test  with repeated measures was used to examine the changes in MVPA, LPA, and SB. In this regard, the Durbin-Conover post-hoc test was used to report the differences in MVPA, LPA, and SB at different survey time points. To examine if sociodemographic factors had effects on these behaviors, sex, residence, age, BMI, and perceived family affluence were entered as fixed factors. Generalized Estimating Equations (GEE) with a Gamma Positive Link function were used to analyze the changes in MVPA, LPA, and SB during the COVID-19 pandemic and their associated predictors (based on control variables). The level of significance was set at p = 0.489). The mean BMI was 21.8 (SD = 6.6), with a statistically significant sex difference (p< 0.001). As for perceived family affluence, the mean of the study sample was 4.9 (SD = 1.3) without sex difference (p = 0.130). For residence, more than 50% of study samples lived in urban areas and more females lived in urban areas than males (p = 0.027). p < 0.001), Wave 2 (p < 0.001), and Wave 3 (p < 0.001) were significantly less than that of Wave 4.p < 0.001) and Wave 2 (p < 0.001) was significantly less than that of Wave 4.Changes in LPA during the survey period were shown in p = 0.019).Changes in SB during the survey period can be observed in Prior research on the differences in movement behaviors between before and after the COVID-19 pandemic has revealed PA decreased while SB increased in different countries or regions because of quarantine caused by the COVID-19 ,40,41. WOur study found that PA (MVPA and LPA) in the early stages were significantly lower and SB was significantly higher than that in the later remission period. Echoing that research compared the levels of PA or SB between during and before the pandemic, findings of this study also revealed the negative impact of COVID-19 on individuals’ health by observing less PA and more SB observed in the early pandemic stage. Numerous studies have suggested that the COVID-19 has led to impacts on people’s health behaviors, especially on movement-related activities  ,42,43. TWhen looking at predictors of changes in PA and SB, some interesting findings are worthy of further interpretation. As for MVPA, compared with males, females were more likely to report less time spent in MVPA. This finding was consistent with much previous relevant literature concerning health behaviors during the pandemic ,46,47,48This study found that sex and perceived family affluence were predictors of changes in SB in young adults, a research finding that is consistent with some previous studies ,33,49. CThe obvious strength of this study was using an intensive longitudinal design with four repeated measurements. On the basis of previous relevant studies that have investigated differences of PA and SB between before and during the COVID-19 pandemic, our study, in another perspective, further verified the negative impacts of the pandemic on people’s health behaviors. Further, we measured MVPA, LPA, and SB concurrently, which is another advantage of this study compared to other studies. However, some study limitations must be acknowledged. One of the limitations is that the sample size was relatively small (<500), which may reduce the generalizability of research findings. Second, the sampling technique this study used was not a random sampling, and accordingly, the representativeness of the sample was restricted. Third, owing to the social distancing caused by COVID-19, device-based assessments cannot be achieved, and the current study used a self-reported questionnaire to collect data. Fourth, compared with some studies that investigate the levels of PA and SB before COVID-19, our study merely had data on PA and SB during the pandemic, which limited a comprehensive understanding of changes in PA and SB. Future studies are encouraged to consider longer tracks of PA and SB in young adults from pre-lockdowns to later periods, which can produce more insightful information for public health promotion. Fifth, all of our study participants came from Guangdong Province (Southern China); thus, research findings based on our study could not be extended into other regions with different cultural, socioeconomic, and societal characteristics. Moreover, concerning the predictors of PA and SB, owing to limited availability of the measures, only some simple sociodemographic factors  were considered in our analysis, which may inhibit our understanding of correlates of PA and SB in young adults during the pandemic. Finally, in our study, the distribution of males (about one-third) and females (about two-thirds) was not equal. Future studies are encouraged to address these limitations.This study investigated the changes in PA (MVPA and LPA) and SB during the COVID-19 pandemic and further provides evidence of the impacts of the pandemic on populations using a sample of Chinese college students. Moreover, as seen during the studied year of the COVID-19 pandemic, in order to promote PA in young adults for health promotion, it is necessary to pay attention to female young adults; while targeting female young adults and those with a lower family affluence can be helpful in reducing excessive SB during quarantine.


The increased thrombotic risk in patients with acute coronary syndrome (ACS) and diabetes highlights the need for adequate antithrombotic protection. We aimed to compare the 6-month clinical outcomes between ticagrelor and clopidogrel in patients with ACS and diabetes. n = 133) and the clopidogrel group (n = 133) , but the incidence of bleeding events in the ticagrelor group was higher than that in the clopidogrel group .  The study was a single-center, prospective, randomized, open-label, blinded endpoint, and controlled registry trial. A total of 270 ACS patients with diabetes were randomly assigned in a 1 : 1 ratio to either the ticagrelor group or the clopidogrel group. Follow-up was performed for 6 months, and the data on efficacy outcomes and bleeding events were collected. At 6 months, complete follow-up data were available for 266 (98.5%) of 270 patients, and 4 were lost to follow-up. There was no significant difference in the survival rate of the effective endpoints between the ticagrelor group  criteria in Chinese patients with ACS and diabetes during the 6-month follow-up compared with clopidogrel. Acute coronary syndrome (ACS) is one of the major lethal and disabling diseases that affect millions of people worldwide . Followi12 receptor inhibitor is recognized as a standard treatment for patients after ACS. An impaired response to clopidogrel that occurs in 5% to 44% of patients with diabetes has been reported in multiple pharmacodynamic studies [12 inhibitors, circumvent the clinical limitations of clopidogrel, such as liver metabolism, drug interactions, and polymorphisms in genes encoding platelet receptors, thereby exerting faster and stronger antiplatelet aggregation properties, which suggests their usefulness in patients with ACS and diabetes [Inhibition of platelet aggregation with dual antiplatelet therapy (DAPT) consisting of low-dose aspirin and a P2Y studies . Prasugrdiabetes , 9. Exisdiabetes , 11; howdiabetes , which m12 inhibitors (such as ticagrelor). Therefore, we aimed to compare the 6-month clinical outcomes between ticagrelor and clopidogrel in patients with ACS and diabetes and hopefully provide valuable data in an Asian population.Ticagrelor has been demonstrated to reduce the composite of ischemic events without increasing the overall risk of major bleeding compared with clopidogrel in ACS patients . HoweverThe study was a single-center, prospective, randomized, open-label, blinded endpoint, and controlled registry trial carried out at the Institute of Cardiovascular Medicine, the Second Affiliated Hospital, Army Medical University in China. We consecutively enrolled 270 patients with ACS and diabetes. For the study patients, ACS was determined based on the diagnosis of unstable angina or acute MI. Unstable angina pectoris was defined as a patient with symptoms of myocardial ischemia but no increase in troponin, with or without ischemic changes in the electrocardiogram, such as ST-segment depression or new T wave inversion. Acute MI was defined as ST elevation MI or non-ST elevation MI. Each patient underwent percutaneous coronary intervention in the study. Type 2 diabetes was defined as individuals with fasting blood glucose ≥ 126 mg/dL (7.0 mmol/L) or random blood glucose ≥ 200 mg/dL (11.1 mmol/L) or patients with a known history of diabetes who were undergoing hypoglycemic therapy. Fasting was defined as no calorie intake for ≥8 hours. The main exclusion criteria were any contraindications to antiplatelet drugs, the need for oral anticoagulation therapy, the simultaneous use of potent inhibitors or inducers of cytochrome P450 3A, and the combination of chronic infections, malignant tumors, and autoimmune diseases.http://www.chictr.org.cn (ChiCTR1800015104). The study was conducted in accordance with the Declaration of Helsinki following the Good Clinical Practice Guidelines. Fifty-seven patients refused to enter after reading the informed consent form, and ultimately, informed consent forms from 270 eligible participants were obtained. This report complied with the Consolidated Standards of Reporting Trial (CONSORT) statement.This randomized controlled trial is aimed at evaluating the effectiveness and safety of two different antiplatelet strategies. The protocol  was performed in a conventional manner. All patients were given antiplatelet drugs before the intervention, with aspirin and clopidogrel or ticagrelor, according to the principle of randomization.Follow-up was performed for 6 months by phone interview or personal contact, and data on efficacy  and safety (bleeding events) outcomes were collected. MI was defined according to the fourth universal definition proposed in 2018. Target vessel revascularization was defined as percutaneous revascularization or bypass surgery for the target lesion or any arterial segment containing the target lesion. Rehospitalization was defined as hospitalization for unstable angina. Ischemic stroke was characterized by the onset of neurological dysfunction caused by focal brain, spinal cord, or retinal infarction. The Bleeding Academic Research Alliance (BARC) standards were used to evaluate bleeding events.n (%). As appropriate, the Mann-Whitney U test, Pearson's χ2 test, the continuity correction test, or Fisher's exact test was used to compare the differences between the ticagrelor group and the clopidogrel group. Binary logistic regression models were employed to identify the independent risk factors. Cox proportional hazards regression analysis was used to explore the correlation between the different antiplatelet regimens and clinical outcomes. Variables considered to be clinically relevant or that showed statistically univariate significance with clinical outcomes (p < 0.20) were included in the multivariate regression model. To ensure the simplicity of the final model, the variables were carefully selected based on the number of available events, and co-linearity was avoided. The odds ratio (OR) or hazard ratio (HR) was used to clarify the relations between risk factors and clinical outcomes. p < 0.05 was considered statistically significant. Statistical analyses were performed using SPSS software version 20 . Statistical power calculations were performed using PASS software, version 11 .Continuous variables are represented by the median , and categorical variables are represented by n = 135) and the ticagrelor group (n = 135). At 6 months, 266 (98.5%) of the 270 patients had complete follow-up data available, and 4 patients (2 in the ticagrelor group and 2 in the clopidogrel group) were lost to follow-up due to missing phone numbers or their own reasons  and the ticagrelor group (n = 133) were well balanced in almost all baseline characteristics (p = 0.038). There seemed to be more patients in the ticagrelor group with chronic kidney disease, but the difference was not significant (p = 0.053).A total of 270 ACS patients with diabetes were enrolled in the current study between October 2017 and March 2019. The 6-month follow-up period ended in September 2019. The recruited patients were randomly divided into the clopidogrel group . For the safety outcome, the total number of bleeding events defined by BARC in the ticagrelor group was slightly more than that in the clopidogrel group, although there was no significant difference ; particularly in the BARC type 2 group, the bleeding risk in the ticagrelor group showed a tendency to increase   .p = 0.006)  were potential influencing factors for the composite effectiveness endpoint  . The sam= 0.006) .p = 0.002) and eGFR (p = 0.026) were found to be independent factors influencing the survival of the effectiveness endpoints  (p = 0.049)  , but the= 0.049) .The study was conducted to compare the 6-month clinical outcomes between the clopidogrel and ticagrelor groups in Asian patients with ACS and diabetes. The main findings of our study on a Chinese population were that ticagrelor did not improve the survival rate of efficacy outcomes  but increased the prevalence of bleeding events defined by BARC criteria in patients with ACS and diabetes compared to clopidogrel.Diabetes has a clear negative impact on the clinical outcome of ACS patients . AlthougAt present, the results of studies on optimized dual antithrombotic regimens for patients with ACS and diabetes are controversial. The PLATO study shows that compared with clopidogrel, ticagrelor treatment significantly reduced the risk of major adverse cardiovascular events (MACEs) in patients with ACS and played an effective role in antithrombosis without significantly increasing the risk of major bleeding . A substn = 1000) did not improve the composite of cardiac death, recurrent MI, or stroke but significantly increased the number of major bleeding events compared with clopidogrel treatment (n = 2985) [However, some studies have different conclusions. Spoendlin et al. conducted a cohort study using United States commercial claims data (2009–2015) in ACS patients with diabetes and revealed that the prasugrel group had better cardiovascular outcomes despite a higher risk of short-term bleeding. No significant difference was found in two different comparisons between the ticagrelor and clopidogrel groups or between the prasugrel and ticagrelor groups . Data fr = 2985) . Additio = 2985) .Furthermore, in the current study, age, hypertension, liver insufficiency, hemoglobin, and eGFR were found to be potential influencing factors for the composite effectiveness endpoint in patients with ACS and diabetes in univariate logistic regression model analysis, and liver insufficiency was an independent risk factor that affected the effectiveness outcomes in the multivariate model for calibration analysis. In addition, there are many factors that may affect the prognosis of patients who underwent PCI, including their own conditions, the types and specifications of implanted devices, and the choices and timing of medications. A meta-analysis of 64 randomized controlled trials and 102 735 patients after approximately 20 months of follow-up showed that the type of stent implanted seems to have a partial impact on the risk of adverse events in patients and that different treatment durations of DAPT are also related to bleeding risk .Atherothrombosis is a highly complex process , and a cThis study has several limitations. First, although our study is based on prospective, randomized, open-label, blinded endpoints, and controlled registries, it is a small-scale, single-center study, and the small sample size may limit the power to detect differences in clinical outcomes. Second, we did not include information on the lifestyle of the patients regarding the type of diet and frequency of exercise per week or the frequencies of drinking and smoking. This lack of information seems slightly rudimentary in terms of lifestyle surveys. Third, middle-aged and elderly heart disease patients usually have other diseases, such as diabetes, hypertension, and gout, which causes them to take multiple drug treatments. Actually, the impact of polypharmacy with the varied disease backgrounds and other complications the patients have made it difficult to arrive at a definitive conclusion of the study. Fourth, the duration of follow-up was limited, and it is possible that a longer follow-up period could have displayed significantly different outcomes between the ticagrelor and clopidogrel groups of ACS patients with diabetes.Our study shows that ticagrelor did not improve the composite of nonfatal MI, target vessel revascularization, rehospitalization, stroke, and death from any cause; however, ticagrelor significantly increased the number of bleeding events defined by the BARC criteria in Chinese patients with ACS and diabetes during the 6-month follow-up compared with clopidogrel. These results seem to suggest the need to transform antiplatelet strategies for the treatment of ACS patients with diabetes from “one guideline suitable for all races” to “racially differentiated antiplatelet therapy,” but more dedicated studies in East Asian populations are required.