Sumac fruit is an antioxidant and reduces serum triglyceride (TG) and cholesterol (CHOL) levels. Therefore, this study aimed to investigate the effect of sumac fruit on serum lipids and body mass index (BMI) of hemodialysis (HD) patients. N = 40), 3-gram sumac (N = 40), and placebo (N = 40) by nonprobability consecutive sampling and stratified block randomization method based on inclusion criteria. Serum lipids and BMI were measured at the beginning of the study and also at the end of the sixth and the twelfth weeks. The physical activity and 24-hour dietary recall questionnaires were used to collect data.  This triple-blind randomized clinical trial study was conducted for 12 weeks on HD patients. Participants were randomly divided into three groups of 2-gram sumac (P > 0.05), physical activity (P=0.159), and BMI (P=0.718) of patients in the three groups before and after the intervention. However, the difference in serum low-density lipoprotein (LDL) levels in each studied group was significant over time (P < 0.001). The difference was not statistically significant between the groups before the intervention, 6 and 12 weeks after the intervention (group effect), and between the study groups over time (time-group interaction). No statistically significant difference was observed between the mean levels of TG (P=0.875), CHOL level (P=0.969), LDL level (P=0.998), high-density lipoprotein (HDL) level (P=0.136), and BMI (P=0.608) in the groups over time.  No significant difference was found between the level of nutrient and micronutrient intake ( Consumption of sumac fruit significantly changed the LDL level over time. Although BMI and serum lipids changed in HD patients, these changes were not significant. Future studies are needed to determine the effective dose of sumac and any dose increase should take toxicity into account and consider a larger sample size and longer intervention and follow-up times. L-carnitine during HD [2), overweight (BMI ≥ 25–30 kg/m2), and obese (BMI ≥30 kg/m2) [Today, 10% of the world's population suffers from chronic renal failure (CRF) . Up to turing HD . HD pati0 kg/m2) .Renal dysfunction is also associated with many disorders in the metabolism of lipoproteins, which leads to disorders of blood fat and its accumulation. The dysregulated fat metabolism that leads to dyslipidemia is often unrecognized, but almost universal. Dyslipidemia is a common nutritional and metabolic disorder in patients with CRF, which leads to deposition and misplaced distribution of fat in some organs including the kidney, heart, and skeletal muscle, which accelerates inflammation and peripheral diseases. In renal failure, triglycerides (TG), very low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) levels increase and high-density lipoprotein (HDL) decreases . StudiesL-carnitine are used to treat hyperlipidemia, modulate patients' weight, and reduce their BMI [However, therapies such as statin compounds, vitamin B6, and heir BMI , 19. Butheir BMI . This tyheir BMI , 21. In heir BMI . Sumac iheir BMI , hyperteheir BMI , cancer,heir BMI , CHOL, aheir BMI , 27. It heir BMI , antioxiheir BMI , 29, antheir BMI , hypoglyheir BMI . Sumac cheir BMI . The hypheir BMI . Howeverheir BMI . In geneBy adjusting the baseline serum lipid values, there is a significant difference between the serum lipid level changes in the groups receiving sumac 2 g, sumac 3 g, and placeboBy adjusting the baseline BMI values, there is a significant difference between BMI changes in the groups receiving sumac 2 g, sumac 3 g, and placeboThe present study is a triple-blind randomized controlled clinical trial (IRCT20180407039214N1) with three groups that was conducted between July and August 2018.The study setting included the educational and medical centers in Khorramabad and Rasoul Akram Hospital in Javanrood, Iran.The study population included all patients undergoing HD at the educational and medical centers in Khorramabad and Rasoul Akram Hospital in Javanrood, Iran.n = 40 in each group) using the Altman nomogram and considering the test power of 80% and standard deviation of 0.5, taking into account a 10% sample drop. 4 people due to death (1 person in 2 g sumac group and 3 people in 3 g sumac group), 3 people due to transplant (2 people in 2 g sumac group and 1 person in 3 g sumac group) and 8 people due to noncooperation in taking sumac  were excluded from the study and statistical analysis was done on 105 people , and being available for assessment three months after the study.Exclusion criteria included; death of the patient within the study period, migration, unwillingness of the patient or his/her companion to continue the study, occurrence of allergies during the study period, undergoing kidney transplantation during the study, having cold nature (by patient's statement and examination by a researcher based on a questionnaire), receiving more than one lipid-lowering drug , having regular and intense exercise, having allergies to sumac fruit and its products, having sensitivity to gluten and celiac disease , having mental disorders, experiencing acute pain and illness, having excessive weight loss and morbid obesity (19 ≤ BMI ≤ 40), adherence to weight loss diets under the supervision of a nutritionist, having history of obstructive and inflammatory bowel disease, having severe constipation, being pregnant and lactation, smoking and alcohol consumption, using supplementation and antioxidants during research, participating in other research and programs to prevent cardiovascular disease, and nonregular consumption of sumac and placebo (one day a week according to weekly follow-up).Sumac fruit was prepared from the mountainous region of Zagros in western Iran. A botanist identified specimens of sumac fruit. Sumac fruit was packaged in Dana Kasian Pharmaceutical Company in Khorramabad, Iran, in 2-gram and 3-gram sachets. Since the literature review showed that consuming more than 5 g of sumac fruit a day causes gastrointestinal problems, we have used only 2 g and 3 g sachets of sumac in this study after consulting with an herbalist .A, B and C, respectively, by the research assistant without the researchers' knowledge, participants, and biostatistics experts, and then were provided to the samples.Placebo sachets filled with wheat powder were prepared by the laboratory of the Faculty of Pharmacy, Khorramabad, Iran. Sachets of 2-gram, 3-gram sumac powder, and wheat powder were secretly named sachet A, two to group B, and two to group C. We randomly selected a number from the table and, moving from the top to the bottom, numbers 0–24, 25–49, and 75–99 were allocated to group A, B, and C, respectively. After determining the blood lipids and the BMI levels, group randomization was carried out. Also, the effect of BMI was matched with statistical modeling.We performed the sampling by a sequential nonprobability method. In this study, subjects were entered from a time point, and sampling was continued until the sample size was sufficient. A stratified block randomization method was used for the random assignment of eligible individuals into three experimental groups. Within each block of 6, two people were assigned to group First, the purpose and method of the study were explained to the patients, and their informed consent was obtained. Eligible patients were matched by gender, age, baseline lipid levels, and medications. Also, the effect of BMI was matched with statistical modeling. Each participant completed a demographic questionnaire containing questions about age, gender, education level, marital status, place of residence, and underlying diseases during the first visit. Also, to assess physical activity, the International Physical Activity Questionnaire (IPAQ), and nutritional behaviors, the 24-hour dietary recall questionnaire was completed by the participant with the help of a researcher. The collected data were analyzed and interpreted by a nutritionist. The weight and height of the participants were measured by the researcher and recorded in the relevant checklists. Individuals' weight was measured and recorded by using a Ska scale with an accuracy of 0.5 kg, and their height was measured using a height gauge installed on the same scale with an accuracy of 0.1. Then, BMI was calculated and recorded based on Adolen's formula (a division of weight in kilograms by height squared in millimeters). Necessary training was given to the subjects one week before the beginning of the study during an introductory session. Subjects were asked to fast for 12 hours before the intervention and at the sixth and twelfth weeks for blood sampling . On the first day, when the participants received the sachets, they were examined for rash, urticaria, and anaphylactic symptoms and then were recommended to report any problems. Patients were instructed to consume one sachet dissolved in a glass of cool boiled water a day after lunch. Sachets were given to patients at the beginning of the study and in the sixth and twelfth weeks. A physician also visited the patients at the time of dialysis for clinical, laboratory, and possible complications. At the end of each week, patients were reminded how to take the medication and get information about any problems and side effects such as constipation, stomach pain, allergies, etc. They were also reminded that they would be excluded from the study if not take the drugs one day a week.The demographic information form included personal information , underlying diseases, medical history of dyslipidemia disorders, and laboratory test results. Intravenous blood samples were taken from the cubital vein at a rate of 5 ccs, then analyzed using a Pars testing kit and BT3000 device. Before the intervention, subjects were instructed to fast for 12 hours, and the venous blood sample was taken by the researcher and placed into sealed tubes without citrate to evaluate lipid, TG, serum CHOL, serum LDL level, and serum HDL level, and then were sent to the laboratory environment of the studied hospitals. The kit and device of all three centers were similar, and all tests were performed automatically. It is worth noting that before taking the blood sample, people were seated to rest for a few minutes. Then, in the shortest possible time, 5 cc of blood was taken from their cubital vein by the researcher and collected in a citrate-free tube in the same package, and then, it was auto-analyzed within one hour using a Pars testing kit BT3000 device.IPAQ was used to assess physical activity. In this questionnaire, the researcher asked about the time of physical activity during the last week. The amount of physical activity is calculated in metabolic equivalent (MET), –37. The N4) software, and the obtained values were analyzed by SPSS software. The validity and reliability of this questionnaire were confirmed in the study of Isfahani and colleagues. The correlation coefficient of this tool was 0.51 for men and 0.59 for women after adjusting the effect of age and energy intake, which indicated its acceptable validity and relative reliability [The 24-hour dietary recall questionnaire was used to assess food intake. In this questionnaire, to evaluate the diet, the mentioned values of each food were converted to grams using a home scale , 42. Theiability .t-test was used to compare the scores of each group before and after the intervention, and one-way analysis of variance with repeated measures (ANOVA), Kruskal–Wallis statistical test, Chi-square, and covariance with adjustment of confounding variable were used to compare the mean scores between the groups before and after the intervention. A significant level of 0.05 was considered in all tests.Data were analyzed by SPSS software version 22, using descriptive statistics (frequency distribution tables and mean and standard deviation). Paired The Research Ethics Committee approved this research of the Lorestan University of Medical Sciences with the code “IR.LUMS.REC.1396.399.” Patients were also randomly assigned to one of the control or intervention groups. The treating physician prescribed routine lipid-lowering drugs, and patients were not deprived of their routine treatment. In addition, the confidentiality of individuals' information, the possibility of withdrawing from the study, making the study results available to patients, and financing the project were other ethical considerations that were observed in this study.There was no statistically significant difference between the study groups regarding gender, marital status, place of residence, and education level, and the groups were homogenous . Also, aP=0.676) and mean age (P=0.253), Amount of energy, carbohydrates, fats, CHOL, saturated fatty acids, unsaturated fatty acids, sodium, potassium, calcium, phosphorus, fiber, soluble fiber, insoluble fiber, crude fiber and fermented fiber received by patients in three groups before the intervention (P > 0.05). The results of the Kruskal-Wallis statistical test also showed no statistically significant difference between the 2-gram sumac, 3-gram sumac, and placebo groups in terms of physical activity (P > 0.05). Also, according to the chi-square test, the difference in the intensity of physical activity between the three groups was not statistically significant (P > 0.05).The one-way analysis of variance showed no significant difference in mean BMI (P=0.1). Also, the difference in total serum CHOL levels between the groups in each period (group effect) (P=0.299), as well as time-group interaction, which is the difference in mean serum CHOL between groups over time, was not statistically significant (P=0.969)  (P=0.969) .P < 0.001). But the difference in serum LDL levels between groups in each period (group effect) (P=0.525) and also between groups over time (time-group interaction) was not statistically significant (P=0.988)  (P=0.988) .P=0.85), although a slight change was observed. Also, between groups in each of the periods before the intervention, six weeks after the intervention, and 12 weeks after intervention (P=0.851), as well as the time-group interaction effect, which is the difference in mean HDL serum levels between groups over time was not statistically significant (P=0.136).According to P=0.059), although slight changes were observed. Also, the difference between groups in each period (group effect) (P=0.459) and time-group interaction was not significant. In the sense that no statistically significant difference was observed over time between serum TG levels in the study groups (time-group interaction effect) (P=0.875).According to the results of P > 0.05)  .According to the results, following the consumption of sumac in the study groups, there was no significant difference between BMI and serum lipid level changes in the groups receiving 2-gram sumac, 3-gram sumac, and placebo over time. However, a significant decrease was observed in serum LDL levels in each group over time (time effect).In the study of Haj Mohammadi et al., which examined the effect of sumac on 80 patients with hyperlipidemia, no significant difference was observed in LDL levels . The stuOn the other hand, isoflavones in sumac reduce CHOL levels by increasing the activity of LDL receptors and LDL catabolism in the liver . In addiBacillus subtleties and Bacillus licheniformis. On the other hand, these organisms can synthesize the enzymes esterase (which converts fatty acids in a different form from the structure of TG in the intestine) and lipase (which reduces the absorption of TG) [The results of this study also showed that long-term consumption of sumac reduces serum TG levels, but there was no significant change between the groups in each of the periods and over time. These findings are similar to the results of a systematic review and meta-analysis by Akbari Fakhrabadi et al., which examined the effect of sumac on blood lipids . It is pn of TG) , 54.B, nitrate, nitrite, fibrinogen, seven-factor, and liver enzymes in rabbits are also not in line with the results of this study [In addition, the results of the present study showed that total serum CHOL levels in HD patients in each group over time (time effect) and between groups did not change significantly in each period (group effect) and over time (time-group interaction). The study of Akbari Fakhrabadi et al. also showed no significant difference between intervention and control groups . But theis study . In thisis study  which isis study . Until nThe statistical analysis results showed that time did not significantly affect the mean level of HDL. However, in the 2 g sumac group, HDL cholesterol levels were slightly increased between the beginning and end of the sixth and twelfth weeks. However, no significant change in serum HDL levels was observed between the groups at any period and over time. This study revealed that after adjusting the effect of diet and physical activity, the highest and lowest increase in serum HDL levels were observed in the 2 g sumac and placebo groups, respectively, from the sixth to the twelfth week. However, these changes were significant. The study of Salimi et al., which examined the effect of sumac extract on blood glucose and serum lipids in diabetic rats, showed that changes in serum HDL levels were not significant in the groups treated with the sumac extract compared to the control group . Also, iThe present study results showed that sumac fruit has no significant effect on patients' BMI. In contrast, the results of Haj Mohammadi et al. study showed that the consumption of sumac has reduced obesity and its complications . Also, iIn general, in this study, consumption of sumac fruit in the studied groups significantly decreased serum LDL levels over time. However, no significant change was observed in serum LDL levels between the groups in each period and over time. According to research, the water-soluble part of sumac inhibits the enzyme xanthine oxidase and collects superoxide radicals in the body, preventing CHOL increases. However, the lack of effect of sumac on LDL levels between groups is probably related to the method of consumption and the dose consumed, which could increase the antioxidant capacity. Also, the isoflavones in sumac might not have been high enough to increase the activity of LDL receptors, which lowers CHOL levels. The strengths of this study include its human samples that consisted of patients with CRF, the use of two different doses, and the existence of a control group.This research had some limitations. Although the researchers tried to implement the research protocol by continuously monitoring the patients, some patients might not have followed the protocols. Patients might have taken medication, eaten food, or done strenuous activities without telling us which have affected lipid and BMI levels but such things have not been reported. Due to the inflexibility of the research environment, it was impossible to match the type of dialysis machine and the type of coil used for the patients. Other limitations were the impossibility of selecting a large number of samples as well as the inability of assessing the dry weight of HD patients.Consumption of sumac fruit decreased LDL levels over time. However, changes in BMI and serum lipids levels were not significant in patients undergoing HD due to the minimum dose of sumac used in this study regardless of dry weight . Also, t


Common Yoga Protocol (CYP) is a standardized yoga protocol authored by experts from all over the world under the aegis of the Ministry of AYUSH, Ayurveda, Yoga and Naturopathy, Unani, Siddha, Sowa Rigpa and Homeopathy (AYUSH). The potential of CYP can be determined as a cost-effective lifestyle modification to prevent the risk of developing cardiovascular diseases (CVD).In this prospective trial, we compared the effect of CYP at baseline and after 1 month. A total of 374 yoga-naïve participants performed CYP under the supervision of experienced trainers. Physiological , biochemical (fasting blood glucose and lipid profile), and neurocognitive parameters were measured before and after the intervention.At day 30 of yoga practice, serum levels of low-density lipoprotein (LDL), total cholesterol (TC), and high-density lipoprotein (HDL) were found significantly improved as compared to the baseline levels observed at the time of enrollment. Similarly, the lipid profile was also obtained from experienced trainers and found to be significantly different from those of yoga-naïve volunteers. When the intervention was compared between the healthy yoga-naïve participants with yoga-naïve participants suffering from medical issues, it was found that cholesterol profile improved significantly in the healthy-naive group as compared to the diseased group .These results highlight the need for further research to better understand the effects of yoga on the primary prevention of CVD. Cardiovascular disease (CVD) is the leading cause of mortality in India as well as across the globe , 2. AccuA systematic review conducted in 2017 revealed that 50% of the people suffering from type-2 diabetes mellitus (T2DM) died due to CVD . Among tYoga has already been proven an effective and affordable means of intervention in health care and it may reduce the burden of CVD as well. Numerous studies have reported the effects of yoga on biochemical parameters such as glucose , uric acAshtanga Yoga.This is the first study conducted to assess the effectiveness of the AYUSH yoga protocol which does not belong to any particular yoga school. This is a consensus protocol evolved after the Delphi round of discussions comprising all major schools of Yoga in India, inspired by research data obtained for various components of Yoga .Group 1: healthy participants who did not perform any yoga (Yoga-naïve); Group 2: comorbid group; Group 3: trainer participants without a history of any comorbidity. A healthy control group was determined by normal vital parameters duly assessed by clinical colleagues as well as by self-disclosure of participants regarding health status. Individuals who have performed yoga for at least 15 days were included in the respective groups.Participants were recruited during the International Yoga Day (IYD)-2016  program organized by the Ministry of AYUSH at the Panjab University, Chandigarh, India. There were three groups: The recruited participants had given informed written consent as per the ethical guidelines before being included in the study. Physiological and biochemical parameters of the yoga-naïve group , comorbid group, and trainer group were obtained before and after 30 days of yoga practice. Socio-demographic details of participants were obtained before participation in the study.n = 34) and female (n = 52) subjects in good health, with an age range of 18–55 years, and who had not performed yogic practices in the past 6 months were included in the “naïve group” . The collected blood samples were subjected to centrifugation at 2,500 rpm for 20 min and an upper layer  was collected in the vial for further biochemical investigations.Fully-automated clinical chemistry analyzer (Spectra Pro M) was used for biochemical analysis. Investigation of triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) levels were carried out as per the manufacturer's instructions.For attention, Digit Span (DS) Test was performed. This test is a subtest of Wechsler Memory Scale (WMS)-III India, which is a measure of auditory attention and working memory. It includes two components, DS forward (DSF) and DS backward (DSB) tests. In the DSF test, the individual was presented with a series of digits and was asked to repeat them in the same order. In the DSB test, an individual was asked to repeat the digits in the reverse order of presentation. The score was based on the maximum number of digits recalled correctly. Similarly, a six-letter cancellation test (SLCT) was also administered for measuring attention. This test comprised of a sheet containing six target letters to be canceled. A working section comprised of 22 rows and 14 columns of randomly arranged letters that participants were asked to cancel as many as possible, at least six target letters in 90 s. To assess the executive functions, the Trail Making Test-A and Test-B were performed (TMT A and B). Part A dealt with visual attention. In this part, the subject was asked to connect a set of 25 circles with numbers (1-2-3) as quickly as possible while maintaining accuracy, on the other hand, part B measured cognitive flexibility and task switching. It contained both numbers and alphabets which had to be connected (1 a 2 b 3 c) as quickly as possible. The time needed to complete each test was noted at the end 26. For information processing speed, the coding test, which is also known as the digit symbol substitution test (DSST) from Wechsler's Adult Intelligent Scale, was performed. It is a test of visuomotor coordination, motor persistence, sustained attention, and responds to speed. This test consists of a sheet in which the numbers 1–9 are randomly arranged in 7 rows of 20 squares each. The subject was instructed to substitute a symbol for a corresponding digit with the given key. Scoring was as per the time taken to complete the task and errors were also noted.The raw data and attendance of trainers, trainees, and staff were recorded in notebooks and digitized in Excel spreadsheets. These data were also validated independently to reduce bias and to preserve individuals' privacy. Immediately after collection, all blood samples were blinded with a master code and transported to a testing facility. The trainers documented participants' attendance and participation, and the protocol was video-recorded and/or still photographed daily. The trainer-to-participant ratio was 1:5.t-tests and Wilcoxon signed ranks tests were utilized based on the distribution. Post-hoc analysis was also performed to measure the changes after 1 month of CYP in various groups, including trainer groups. Pearson's correlation analysis and scatter-plot matrix (through R stat) were performed to analyze the correlation of age and yoga experience with both anthropometric and biochemical parameters. The details of the dietary profile could not be obtained and hence did not correlate with the lipid profile of the participants. We have compared the baseline parameters of naïve participants with themselves (as they were not having a prior history of any exercise or yoga practice) after yoga intervention. Importantly, the naïve participant's data were further compared with comorbid and yoga practitioners' groups to understand the response of yogic practices to different physiological conditions and also to define the period of yoga exposure to bring homeostatic changes. The statistical significance threshold was set at p < 0.05.Statistical Package for the Social Sciences (SPSS) version 16 was used for statistical analysis. The normality of data was determined by using the Kolmogorov–Smirnov test and an appropriate test was employed based on the normality of data. Paired A total of 374 participants were recruited for the study. Of these participants, 86 were assigned to the “healthy” yoga-naïve group. After the exclusion of 195 comorbid participants, 179 participants were found to be fit for the naïve group. However, 93 participants (out of 179) were excluded based on their compliance during the camp (minimum 15 days of yoga practice). Hence, the final analysis was carried out on 86 naïve participants. Additionally, 81 yoga trainers were also enrolled for comparison. Comparing pre- and post-levels after 1 month of practice, the yoga-naïve, and healthy participant group demonstrated a significant decrease in systolic blood pressure, pulse rate, and BMI . There wAnthropometric and lab testing were performed on trainers on day 30. Controlling for age differences between yoga-naïve and trainer groups at day 30, the trainer's group had significantly higher percent oxygen saturation and lower BMI as compared to the yoga-naïve group . HoweverTo estimate a temporal correlation between age and yoga experience, we analyzed the effect of age with physiological and biochemical parameters by scatter-plot matrix. This showed a significant positive correlation of age with blood pressure, BMI, TG, TC, and VLDL . PearsonAnalysis based on various age groups in naïve and trainer participants has also revealed significant alteration parameters of physiological  as well as lipid metabolism . Results suggest that adoption of these practices could show a better effect after the age of >30 years .Moreover, gender-based analysis in naïve and trainer participants also showed alterations in various physiological  and biochemical parameters  which suggest a differential effect of these practices on male and female participants .p = 0.015) in the naïve participants after the yoga duration of 1 month. This result indicated an improvement in the psychomotor speed. Improvements in the TMT B test results were also observed though statistically non-significant. Improvements in tests related to attention and information processing speed  were also observed after performing a 1-month yoga protocol , diastolic blood pressure (p = 0.013), and weight (p = 0.003) when the comorbid yoga group and healthy yoga group were compared, signifying the effectiveness of yoga in healthy participants as compared to the comorbid group. However, a significant increase in percent oxygen saturation (POR) was observed in both healthy and comorbid groups (p ≤ 0.001), TG (p = 0.030), and VLDL (p = 0.026) showed significant differences between healthy and comorbid groups after a 1-month of practice (2 saturation (p ≤ 0.001), systolic blood pressure (p ≤ 0.001), diastolic blood pressure p ≤ 0.001), weight (p ≤ 0.001), TG (p = 0.018), HDL (p ≤ 0.001), LDL (p = 0.002), VLDL (p = 0.009), ratio (p ≤ 0.001), but pre- and post-intervention comparison of the comorbid group revealed significant differences only in O2 saturation (p ≤ 0.001) and HDL (p ≤ 0.001), TC/HDL ratios (p = 0.016)  .via the parasympathetic activation of the vagal nerve, reducing coronary atherosclerosis with an improvement in the lipid profile, cholesterol levels, and body weight. Yoga has its effects on cardio-respiratory efficiency and physical fitness , showed significant improvement in the mean arterial blood pressure, blood glucose, and cholesterol after 3 months of practice . An investigation performed on cardiac patients revealed that the patient number visiting the clinics reduced to a much greater extent when they practiced yoga . Yoga an fitness . For car fitness . A studypractice . These spractice –30. Sevepractice –33. ThisNadishodhana, Pranav, and Savitrikapalabhati) and fast Pranayama which included Bhastrika and Kukkuriya on the cognitive function of the healthy individuals. Both aspects have been covered in the yoga-based CYP. Results of inter-group comparison have shown that both types of Pranayama are beneficial for cognitive function, but a rapid Pranayama technique has additional effects on the executive function of manipulation in auditory working memory, central neural processing, and sensory-motor performance  and blood pressure after 1 month of CYP practice is consistent with previous studies that indicate yoga practice lowers blood pressure –48. DecrCYP can be argued as a preventive and protective measure for a developing country like India whose health budgets are fast escalating. POR has been found to have a significant difference in both the groups, even though another arm of the sham or general exercise group was not available. In this study, we report increased POR in practitioners which is concomitant with the increase in blood glucose levels in most yoga practice groups. Similarly, triglycerides and VLDL levels were also increased after one month of yogic practices. Though, the levels were not go beyond the recommended values for both biomolecules. After yoga practices, both results have indicated that aerobic conditions can increase the cellular metabolic processes and also maintenance of pH of the body by regulating the respiratory processes. Mindfulness rejuvenating effect is ascribed to breathing exercises centered around forced breathing.In this study, we report an increased percentage of saturation of oxygen in yoga practitioners. Our study showed statistically significant improvement in TC/HDL ratios. High TC/HDL ratios are correlated with the risk of heart disease. A study by Balaji et al.  and TangOur study was limited by low numbers of healthy yoga-naïve participants. Therefore, there is a high risk of type one error, in that, a statistical significance of some outcomes might have been seen with higher numbers of participants. Another limitation of our study was that it was a short-term study and was not randomized. Also, the healthy group was comprised of people aged 18–55, while the comorbid group was comprised of a heterogeneous group including healthy individuals over age 55 and younger individuals with medical issues. This did not allow us to separately analyze the effect of the CYP on a healthy older population.We have not undertaken any classification as reported in references , 47 and Our results showed that Common Yoga Protocol improved the key metabolic and physiological processes in the yoga intervention group. Healthy yoga-naïve participants showed greater improvement than yoga-naïve participants with comorbidities. The results from these comparisons indicate that yoga is useful for maintenance of good health parameters. However, the length of the study was shorter and we were not able to evaluate if the effects last after leaving yoga practice. Whether CYP holds any potential effect in the treatment of hyperlipidemia can only be confirmed by a randomized control study.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Institutional Ethical Committee of the Post-graduate Institute of Medical Education and Research, Chandigarh, India (INT/IEC/2016/2565). The patients/participants provided their written informed consent to participate in this study.AA: conceptualization and principal investigator. KS, NS, and RT: collection of sample, data and writing of the initial manuscript, and analysis of data. IB-R, AV, DK, MS, and VP: writing, copy editing, and repeated revision based on data. SB, SM, PB, PK, and VB: collection of samples and data and sample processing. AG, DP, KJ, VGa, BM, NT, and AC: compilation and electronic entries of the data. NK and PM: assistance in yoga follow up. KB, VP, and AB: data from medical parameters. AB, MM, GS, and SS: assistance in conceptualization of study design. VGu: assistance in providing the medical staff and equipments. NM, RM, and RKu: yoga training to the volunteers and arrangement of the space and other accessories for yoga participants. DM: writing and revision of the manuscript. MM and HA: neuropsychology analysis of the volunteers. RKa provided chemicals used in sample processing. SS: statistical analysis of the data. 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.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.


Tuberculosis is the leading cause of mortality from lung infectious disease worldwide in recent years, and its incidence has re-emerged in large cities in low-incidence countries due to migration and socioeconomic deprivation causes. Diabetes mellitus and tuberculosis are syndemic diseases, with diabetes being considered a risk factor for developing tuberculosis.To investigate whether diabetic patients were at increased risk of tuberculosis living in an inner-district of a large city of northeastern Spain.Observational matched retrospective cohort study based on clinical records from the population of the lowest socioeconomic status in Barcelona (Ciutat Vella district). A cohort including patients with type 1 and type 2 diabetes mellitus in 2007 and new cases until 2016 (8004 subjects), matched 1:1 by sex and age with a non-diabetic cohort. Follow-up period was until December 31st 2018. We evaluated the risk of developing tuberculosis in diabetic patients compared to non-diabetic patients during the follow up period. We used time-to-event analysis to estimate the incidence of tuberculosis, and competing risks regression by clusters and conditional Cox regression models to calculate the hazard ratio (HR) and its 95% confidence intervals (CI).Among the 16,008 included subjects, the median follow-up was 8.7 years. The mean age was 57.7 years; 61.2% men and 38.8% women in both groups. The incidence of tuberculosis was 69.9 per 100,000 person-years in diabetic patients, and 40.9 per 100,000 person-years in non-diabetic patients . After adjustment for the country of origin, chronic kidney disease, number of medical appointments, BMI, alcoholism and smoking, the risk remained higher in diabetic patients (1.66: CI 0.99–2.77). Additionally, subjects from Hindustan or with a history of alcohol abuse also showed a higher risk of developing tuberculosis .People with diabetes mellitus were at higher risk of developing tuberculosis in a large cohort recruited in an inner-city district with a high incidence for this outcome, and low socioeconomic conditions and high proportion of migrants. This risk was higher among Hindustan born and alcohol abusers. Tuberculosis (TB) is a contagious airborne disease that has become the leading cause of mortality worldwide in recent years. The poorest countries and the most disadvantaged populations in developed countries are especially affected. According to the World Health Organization (WHO), in 2020, 10 million people developed this disease, causing 1,3 million deaths, 214,000 additional deaths in HIV-infected people. Two-thirds of TB cases worldwide are concentrated in 8 countries: India, China, Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh and South Africa  is considered by the WHO as one of the most prevalent chronic diseases and one of the main risk factors for developing active TB . The gloM. tuberculosis  is two times higher in diabetic patients . Also, dThe aim of our study was to determine the risk of TB in diabetic patients compared to a non-diabetic population in an inner-city district with a high TB incidence.We designed an observational matched retrospective cohort study . The recruitment period was between January 1st 2007 and December 31st 2016, with a follow-up period of two more years, until December 2018.https://jrealgatius.github.io/TBC_ANALISIS/codi/shiny/DashBoard_TB.html.The inclusion date was January 1st 2007 for prevalent diabetic participants, and the date of diagnosis for incident diabetic subjects during the recruitment period. For each DM case, a non-DM control matched by sex, year of birth, and time of inclusion was selected (ratio = 1:1), using a density sampling approach  see moreThe study was carried out in Ciutat Vella, a district in Barcelona (Northeastern Spain), which has been recently characterized by a high percentage of immigrants  and a low socioeconomic level, with a population of 108,000 inhabitants .All diabetic patients over the total attended population in Ciutat Vella were selected, and finally 8,004 of them were matched .People younger than 18 years old or without any appointment registered in their Primary Health Care Centre during the study period were excluded.All data was treated as confidential according to the ethical principles of the Helsinki Declaration of 1964, revised by the World Medical Organization in Edinburgh in 2000, and the Spanish Organic Law 3/2018 of Data Protection. Clinical characteristics and specific data on DM were extracted from the Primary Care medical record database from Barcelona. Specific data on TB were obtained from the Barcelona TB Prevention and Control program. Both sources were linked through an anonymized unique identifier. Because data was collected on a routine basis following the Spanish law about mandatory notification diseases, no informed consent was required. The data collection took place during 2019.The primary outcome was defined as the occurrence and date of a TB diagnosis during the follow-up period in DM and non-DM patients.We obtained the following information on the subject at baseline:  demograpAs Ciutat Vella is a district with a high percentage of migrants (50.1%), mostly from South-East Asia  , we grouWe identified diabetic patients if they had an ICE 0.10 diagnostic code for DM in their medical record (E10–E14), or if they were taking any anti-diabetic drug other than metformin (sometimes used in other conditions). We also recorded glycated hemoglobin, DM duration, treatment , and microvascular complications: neuropathy, nephropathy or retinopathy.A person was considered to have TB if they had a maintained anti-TB drug prescription according to the Barcelona TB Program; the program has an active epidemiological surveillance system with a good follow-up of patients. TB cases and their characteristics such as diagnostic procedure , location (pulmonary or extrapulmonary), treatment and socioeconomic deprivation index (MEDEA) were collected. This index classifies the subject by living area: values have an average of 0 and a standard deviation of 1, and higher values indicate a more unfavorable socioeconomic situation .Baseline characteristics of both groups were evaluated to examine homogeneity in comorbidities and demographic and clinical characteristics, and were described by frequencies (n) and percentages (%), continuous and count variables were described using mean and standard deviation (SD), using compareGroups R Package . A complp-values were computed with robust standard errors to account for the matched sample. A sensitivity analysis of different fitted models was performed including different adjusted variables using a Cox proportional hazard model by clusters. The models were adjusted by origin and clinical characteristics with known clinical association with TB and DM. Statistical significance was established as a p-value < 0.05.We conducted a time-to-event analysis to estimate the incidence of TB by group, and to examine the association between DM condition and risk of TB. To examine time-related incidence curves and differences between groups, we performed competing risks regression for clustered data using crrSC R package version 1.1 . Risk fuhttps://github.com/jrealgatius/TBC_ANALISIS.Finally, we performed a descriptive analysis of the cases of TB in DM and non-DM subjects. Data management and analysis was done with the R version 3.6.3 package (R Core Team 2020). The R data analysis scripts can be consulted at: Initially we started from a potential population from Ciutat Vella (Barcelona) of 85,919: 10,065 diabetic subjects  and 75,854 potential non-diabetic subjects. Of these, 8,004 diabetics and 8,004 controls of the same age and sex were matched .Regarding the sample demographic characteristics , the aveIn the DM cohort, the mean DM duration was 3.2 years (SD 5.8), and 45.3%  had a glycated hemoglobin value above 7% .At follow-up , 73 new The result of sensitivity analysis taking into account different adjusting variables and different approaches  did not materially change the results in terms of the direction of the risk .The forest plot for different HRs of each analyzed variable related to TB  is shown in Finally, we analyzed the differences between diabetic and non-diabetic patients who presented with a first episode of TB. Demographic and clinical data, including country of origin, smoking status, alcohol use, homelessness, unemployment, death, site of TB and tuberculin skin test, did not significantly differ between both groups. However, patients with TB from the two groups had a different socioeconomic deprivation index according to the Medea classification . RegardiOur work showed a 1.90-fold higher risk of developing TB in DM patients. After adjusting for country of origin, chronic kidney disease, number of medical visits, BMI, alcohol abuse and smoking, the risk remained higher at 1.66 for DM patients. By analyzing other variables related to TB, our analysis revealed that subjects of a Hindustani origin and history of alcohol abuse were at higher risk for developing TB. As the use of alcohol is really frequent in our context , we consIn the model 4, when adjusting by all covariables, the confidence interval remains in the limit of statistical significance, probably due to a lower statistical power or a risk of overadjustment. Hindustan origin and alcohol abuse are expected risk factors for developing TB because are also related to poor socioeconomic conditions in this context, and they are considered risk factors independently of having or not diabetes.The inner-city district of Ciutat Vella is characterized by the lowest socioeconomic level in Barcelona and a high percentage of immigrants. Half of them are migrants from Asia , Oceania  and Central and South America . In 2017Our results showing a higher risk of developing TB in DM patients are in line with several other studies performed in different countries, with elevated estimated risk ratios being 1.77 times (CI: 1.41–2.24) for active TB in DM patients in China , 1.9 CI, and 6 tThe higher incidence of TB in immigrant populations may be due to migrants coming from countries with a high incidence of TB. However, socioeconomic deprivation  and living conditions  may also increase exposure to TB. Indeed, in a study in people with TB from across Barcelona (2000–2013), autochthonous people had a higher risk of developing DM . In contInterestingly, an independent study conducted in 2008 in the same district, showed that Hindustani young people had up to 3 times more cases of type 2 DM than autochthon population, albeit having a lower average BMI . The notOur data also showed that DM patients with TB had more pulmonary involvement. This result is consistent with previous reports , 34. In Because of the large number of subjects affected worldwide by both diseases, and that they exacerbate each other and increase the burden when they appear together, we can probably define this as a syndemic. Their interaction is a priority issue in global public health. TB is often related to poor living conditions and overcrowding, poverty and immigration. At the same time, these conditions are also related to poor nutritional habits, obesity and, in case of DM, poor glycemic control.In contrast to DM, the contribution of obesity to TB is controversial. Although it is considered a risk factor for DM, it has been reported as a protective factor against TB development . An inteWe believe that our work may be important to study the association of the two diseases and make specific strategic plans in areas of high TB concentration even in low-incidence countries.As with chronic complications of the disease, glycemic control in DM patients probably influences both the risk  and the Some limitations can be found in our study. One of them is the retrospective and observational nature of the study design. All studies done with databases depend directly on the quality of the data record, which may be more worrisome in retrospective studies. In addition, retrospective studies may have more difficulty establishing a correct temporal relationship, and they have more selection and information biases, but we have tried to minimize these biases with a careful methodology and creating dynamic cohorts. Working with a population at risk of social exclusion may imply a risk of underreporting in key clinical factors. The 60.3% of DM without anti-DM treatment could be explained by a missing data in the databases or a lack of adherence to treatments. Moreover, some of the cases were incident DM; therefore, with the exception of cases with a highly elevated glycated hemoglobin, diet and exercise alone would have been recommended. However, the incidence rate shown was similar to the rates reported in independent studies . The meaOur work has also a number of strengths. Among these, the population database for a city area with an extremely high incidence of TB, and a long follow-up period of 10 years. Both sources of information are large and they provided important high quality information. Moreover, our results were consistent with the literature published elsewhere.Further studies are required to investigate the interaction of both diseases, the contribution of optimization of glycemic control, and to consider whether screening for both diseases in specific areas could be cost effective.This large retrospective cohort study showed that in an inner-city district with high TB incidence and a high percentage of migrants, DM was associated with an increased risk of developing the disease. It is possible that the higher incidence was coupled with a higher TB transmission. Besides, TB in migrants can also be due to the reactivation of old infections, especially in people coming from Hindustan, where this disease is highly prevalent. Moreover, alcohol abuse was also identified as a risk factor for TB. In view of these results, we advocate for screenings to control diabetes-associated TB in the inner districts of high-income countries where the proportion of migrant people is high and characteristics such as low socioeconomic level further contribute to increase the risk.Prevention of DM and TB are two of the WHO's main objectives. Changes in lifestyle, unhealthy diets, globalization, a greater access to diagnosis and a longer life expectancy could probably explain the increase of DM in countries where the burden of TB is greater.We strongly recommend TB screening in DM patients in areas with a high TB incidence. According to the CDC's guidelines for the diagnosis of LTBI , Tubercuhttps://jrealgatius.github.io/TBC_ANALISIS/codi/shiny/DashBoard_TB.html. The data analysis code is shown at https://github.com/jrealgatius/TBC_ANALISIS.Publicly available datasets were analyzed in this study. This data can be found here: The studies involving human participants were reviewed and approved by Ethics Committee of the Primary Healthcare University Research Institute IDIAP-Jordi Gol (P16/023). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.VA-A, JC, JF-N, JR, ÀO, and AM-M participated in the study design. ÀO, JD, and JR worked on data collection. JR, VA-A, EN, RP, and JF-N performed all statistical work. VA-A, JF-N, and JC were major contributors in writing the manuscript. MM-C, DM, JJ, JM, JB, and AM-M reviewed and corrected the manuscript. BV contributed to prepare the manuscript according to the journal policies. All authors contributed to the article and approved the submitted version.This work was supported by two grants given by the Instituto de Salud Carlos III PI16/01751 (Spanish Ministry of Economy) and the Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina  PREDOC_ECO-19/2. JJ was recipient of a Miguel Servet contract (CPII18/00004) .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.


Diseases caused by necrotrophic fungi, such as the cosmopolitan Sclerotinia sclerotiorum and the Diaporthe/Phomopsis complex, are among the most destructive diseases of sunflower worldwide. The lack of complete resistance combined with the inefficiency of chemical control makes assisted breeding the best strategy for disease control. In this work, we present an integrated genome-wide association (GWA) study investigating the response of a diverse panel of sunflower inbred lines to both pathogens. Phenotypic data for Sclerotinia head rot (SHR) consisted of five disease descriptors . Two disease descriptors (DI and DS) were evaluated for two manifestations of Diaporthe/Phomopsis: Phomopsis stem canker (PSC) and Phomopsis head rot (PHR). In addition, a principal component (PC) analysis was used to derive transformed phenotypes as inputs to a univariate GWA (PC-GWA). Genotypic data comprised a panel of 4269 single nucleotide polymorphisms (SNP), generated via genotyping-by-sequencing. The GWA analysis revealed 24 unique marker–trait associations for SHR, 19 unique marker–trait associations for Diaporthe/Phomopsis diseases, and 7 markers associated with PC1 and PC2. No common markers were found for the response to the two pathogens. Nevertheless, epistatic interactions were identified between markers significantly associated with the response to S. sclerotiorum and Diaporthe/Phomopsis. This suggests that, while the main determinants of resistance may differ for the two pathogens, there could be an underlying common genetic basis. The exploration of regions physically close to the associated markers yielded 364 genes, of which 19 were predicted as putative disease resistance genes. This work presents the first simultaneous evaluation of two manifestations of Diaporthe/Phomopsis in sunflower, and undertakes a comprehensive GWA study by integrating PSC, PHR, and SHR data. The multiple regions identified, and their exploration to identify candidate genes, contribute not only to the understanding of the genetic basis of resistance, but also to the development of tools for assisted breeding. Helianthus annuus var. macrocarpus, Asteraceae: Heliantheae) is nowadays the fourth most important oilseed crop in the world, with approximately 57 million tons of seeds produced in 2021 [S. sclerotiorum (Lib) de Bary and the Diaporthe/Phomopsis complex, are among those with the highest latent risk [Originally from North America, sunflower . It co weeds, ). The hio weeds, . In factjectives . In recejectives ,12,13,14S. sclerotiorum, diseases caused by Diaporthe/Phomopsis have historically had a great, but localized, impact. This way, since its initial report, it has been a major problem in Europe, where the first efforts were made to characterize the pathogen and identify sources of resistance [The Diaporthe/Phomopsis complex comprises multiple species involved in disease development in sunflower, with Diaporthe helianthi being the most widespread and the first to be reported ,16. Of tsistance ,20,21. Isistance . In factsistance  reportedsistance  and Canasistance . In Argesistance ). Howevesistance . A recensistance .S. sclerotiorum, head rot (SHR) has the greatest damage potential, determined not only as yield reduction, but also as a decrease in the quality of the oil. As mentioned before, PSC is the most frequent disease of the Diaporthe/Phomopsis complex, although head rot (PHR) is becoming more common, at least in Argentina [S. sclerotiorum and Diaporthe/Phomopsis-associated diseases [Despite their different prevalence and distribution history, the two pathogens have common characteristics that make them comparable to some extent. Both pathogens generate a primary infection in the plant, caused by ascospores, existing as a strong environmental component in epidemic development. In addition, both pathogens are able to infect different parts of the plant  and cause different diseases ,29. In trgentina . In bothrgentina . Biparendiseases ,28. On tdiseases ,28,31. IIn this work, we conduct a genome-wide association mapping (GWA) study for SHR, PSC, and PHR based on the association mapping population (AMP) of the INTA, Argentina . In addiOur AMP includes 135 inbred lines of sunflower developed and preserved by the Active Germplasm Bank of the Instituto Nacional de Tecnología Agropecuaria, Argentina (INTA). These inbred lines were selected to achieve a balance between genetic diversity ,32,34 anInformation on the SHR response data used here can be found in Filippi et al. . BrieflyThe response of the AMP inbred lines against SHR was estimated as disease incidence (DI), disease severity (DS), area under the disease progress curve for disease incidence (AUDPCI) and disease severity (AUDPCS), and incubation period (IP). It should be noted here that Filippi et al.  also conTo estimate the response of the AMP inbred lines to Diaporthe/Phomopsis infection, two successive FTs were conducted in naturally infested fields containing a range of Diaporthe/Phomopsis populations. In addition, inoculum titer was increased by aggregates of infected crop debris in the V2 stage. These FTs, consisting of a randomized complete block design with two blocks and no irrigation, were conducted in General Pico  in 2017 (sowing date 30 October 2017) and 2018 (sowing date 21 October 18) growing seasons. This location was selected based on reports of high incidence of the disease. The experimental unit was a row of 0.52 m in length and 5 m wide, with a planting distance of 0.52 m. Two manifestations of the disease were evaluated: Phomopsis head rot (PHR) and Phomopsis stem canker (PSC). In PHR, the symptoms are brown, rotten areas affecting the receptacles and achenes (discolored seeds), necrotic bracts, and expanded V-shaped necrosis pointing toward the peduncles. In PSC, the symptoms on the stems are pale brown cankers that develop around petiole insertions. For each of these diseases, both DI  and DS  were visually registered, at the R7-R8 sunflower stage , on at lSpearman rank correlation analyses of the standardized adjusted means of all phenotypic variables, as well as the correlation plot, were performed using corrplot v0.92 , while phttp://github.com/cfilippi/GWAS_Han.The ddRADseq sequencing data generated by Filippi et al.  for the The association between SNPs and phenotypes was evaluated using statgenGWAS v1.0.9  in R 4343, folloTo investigate the existence of epistatic interactions between significant and non-significant SNPs, we relied on the WISH-R package v1.0 , which iManhattan plots and marker effect plots were depicted using statgenGWAS v1.0.9  and ggplGenes in linkage disequilibrium with the associated SNPs  were rep < 0.05) were observed between inbred lines. The PSC susceptible accession HA89, used as a control in other studies , showedp < 0.05). Again, this correlation was positive for all recorded traits except PI, which was negative. This can be observed in both As expected, the correlation between traits recorded for the same disease was stronger than the correlation between traits for different diseases. Thus, the different traits associated with SHR showed a strong and significant correlation , whereas DI and DS were strongly correlated in PHR and PSC. No correlation was observed for DI between PSC and PHR, but the correlation was significant for DS between PSC and PHR. This suggests that, although the incidence to both Diaporthe/Phomopsis diseases may be uncoupled, once the disease is established, the severity is subject to similar responses. Overall, the traits associated with SHR showed a weak but significant correlation with the response to PHR and PSC . After initial filtering, a total of 16,705 SNPs were considered for population analysis, as PCA (to control population structure) and kinship estimation. The first PCs did not explain a high percentage of genotypic variance  epistatic interactions emerged as candidates for further studies . As an eExamination of the 200 Kb region around each significantly associated SNP allowed the identification of 364 physically close genes. Gene enrichment analysis showed that biological processes, such as hydrogen peroxide signaling pathways, response to molecules of fungal origin, response to molecules of bacterial origin, and others, were significantly enriched in the 364 genes physically closest to the associated markers . The GO In addition, prediction of disease resistance genes using DRAGO2  revealedS. sclerotiorum, and the re-emerging Diaporthe/Phomopsis complex are currently the necrotrophic fungi with the greatest impact on global sunflower production. Although natural variability is observed, the lack of complete resistance combined with the inefficiency of chemical control has made assisted breeding the best disease control strategy. In this work, we present an integrated study of the response of a diverse panel of sunflower inbred lines, the AMP of the INTA (Argentina), to both fungal pathogens.The devastating and cosmopolitan Diaporthe/Phomopsis were erratic and tended to be low for both DI and DS. This fact reflects the differences in the way the FTs were conducted. SHR FTs were conducted with irrigation and assisted inoculation to support conditions for ideal infection. Indeed, traits evaluated after artificial inoculation usually show higher heritabilities than those obtained in semi-natural infection conditions [Diaporthe/Phomopsis FTs were performed in naturally infested fields. One of the major drawbacks of relying on non-assisted infection is the high dependence not only on the availability of a viable inoculum, but also on the occurrence of climatic conditions that allow the disease to establish and develop [Disease levels achieved for SHR were consistent across field trials (FTs). In contrast, disease levels for nditions . In the  develop .Diaporthe/Phomopsis benefits from abundant moisture and temperatures between 23–25 °C during the growing stage [Diaporthe/Phomopsis involve inoculation with fungal mycelium. While these methods allow the study of the kinetics of symptom development, they cannot reveal the resistance to penetration by ascospores.ng stage  for PSC ng stage . This alng stage . On the Analysis of the genotypic matrix revealed the importance of hard filtering SNP data for good data quality. Here, only ~5.7% of the original SNP matrix was considered for marker–phenotype association testing . The main reasons for filtering out the markers were the high percentage of missing data, low MAF, and the presence of strongly linked markers. This was not unexpected as the strategy used for data generation, ddRADseq, typically results in a high percentage of missing data . FurtherDiaporthe/Phomopsis, with CHR05, CHR10, and CHR15 having the highest number of associated loci. No common markers were found for the response to the two pathogens studied. This is not unexpected considering the complex genetic base of the resistance, the size of our AMP , and the weak correlation between phenotypic SHR and PSC traits. The observed correlation values are comparable to those reported by Bert et al. [S. sclerotiorum and Diaporthe/Phomopsis phenotypic traits (r~0.20). In an independent work, Talukder et al. [r = 0.52). However, the GWA study conducted on the basis of Talukder’s phenotypic data, and using > 200,000 SNPs as genotypic data, found only a single common associated region for SHR and PSC [Diaporthe/Phomopsis in sunflower.The GWAS analysis revealed 24 unique marker–trait associations for SHR and 19 unique marker–trait associations for t et al.  for S. sr et al.  reported and PSC . These wAs a complementary approach, a GWAS using PC scores as dependent variables was performed. The effectiveness of PC-GWAS relies on (a) the ability of this strategy to decrease the type I error rate ; (b) theWhile each SNP associated via GWA is expected to have a significant effect in determining a phenotypic trait, non-significant markers interacting with these associated SNPs could also have an influence on such traits . ConsideS. sclerotiorum and/or Diaporthe/Phomopsis on this chromosome  genes using a tool developed specifically for this purpose  yieldedomosome  in sunflower. The combined evaluation of phenotypic data obtained for PSC and PHR, together with data previously generated for SHR [Diaporthe/Phomopsis species causing PHR and PSC at our screening site over the years . We anticipate that these studies will have a concrete application in the near future.This paper presents the first simultaneous large-scale evaluation of two manifestations of  for SHR , allowedS. sclerotiorum and the Diaporthe/Phomopsis complex is evidenced by the multiple associated SNPs found, in addition to the identification of epistatic interactions. Although no common SNPs were found to be associated with resistance to both pathogens, the study of epistatic interactions allowed the identification of two markers significantly associated with the response to S. sclerotiorum and Diaporthe/Phomopsis. The posterior search for genes physically linked to the associated SNPs revealed in all cases pathogenesis-related genes, mainly of the “receptor-like kinase” class. In-depth analysis of these genes may help to dissect the underlying mechanism of resistance to both pathogens in sunflower. It is expected that the associated regions, and the identified sources of resistance, will contribute to the development of tools for assisted breeding in crops.The complex nature of the genetic basis of sunflower resistance to diseases caused by


Anthracyclines play an important role in the treatment of breast cancer (BC) and other malignant tumors. However, accompanied side-effects are non-ignorable. The purpose of this meta-analysis is to determine the risk factors for anthracycline-induced cardiotoxicity (ACT), so as to identify high-risk patients.The search for literature was conducted in PubMed, The Cochrane Library, Embase and Web of science. Records were selected with inclusion criteria and exclusion criteria. The newcastle-ottawa scale (NOS) was used to assess the quality of literature, and Review Manager 5.3 software was used for meta-analysis.p < 0.00001), cumulative dose of anthracyclines , hypertension , diabetes mellitus (DM) , tumor metastasis  and coronary heart disease (CAD) . In addition, our analysis revealed that body mass index (BMI) had no effect on ACT .Thirteen studies met the inclusion criteria. Meta-analysis indicated that risk factors for ACT were use of trastuzumab (odds ratio [OR]: 2.84, 95% confidence interval [CI]: 2.49-3.22, Patients with high risk for ACT can be identified by these factors. For such patients, a higher level of monitoring and protection for the cardiac function should be performed by clinicians.INPLASY, identifier INPLASY202250140. Anthracyclines play an important role, even when targeted therapy and immunotherapy are emerging. Anthracyclines are broad-spectrum, effective and widely used in the treatment for solid tumors and hematological malignancies, including breast cancer (BC), gastric cancer , ovarianThis meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) . The seaInclusion criteria: (1) The source of the case was BC patients diagnosed by medical institutions and received adjuvant treatment with anthracyclines. (2) The type of design was a case-control study or cohort study. (3) Relevant studies on the influencing factors for ACT were included (influencing factors for ACT were mentioned in at least three literature). (4) Odds ratio (OR)/hazard ratio (HR) and 95% confidence interval (CI) were provided in the results, or sufficient data could be provided for calculation.Exclusion criteria: (1) Repeated publication of literature. (2) Unable to obtain the full text, incomplete data, or incorrect statistical methods. (3) Reviews, meta-analyses, conferences, comments, case reports and animal experiments. (4) Newcastle-ottawa scale (NOS) score < 6. (5) The definition of risk factors was significantly different from general standards or most studies.After searching the literature in the database, we firstly excluded repetitive literature. Secondly, we excluded outmoded literature published before the year of 2000. Then we eliminated the meta-analyses, reviews, case reports, meetings, comments and animal experiments. Next, we deleted the articles that did not conform to the research by reading the title and abstract. Finally, we downloaded the full texts of left-behind studies, and retained the clinical studies that conformed the intention and inclusion criteria.Two researchers extracted the relevant data from the included literature: author, year of publication, country, type of study, number of patients and risk factors for ACT (mentioned in at least three articles).This Meta-analysis used the NOS recommended by the Cochrane Collaboration for quality assessment. The NOS is mostly used in cohort studies or case control studies and includes selection, comparability and outcome/exposure, with a total eight items. A study can be awarded a maximum of one star for each numbered item within the selection and outcome/exposure categories. A maximum of two stars can be given for comparability. Stars range from zero to nine, and six stars and above are considered high-quality literature . The NOS2 were used to analyze the heterogeneity among studies. When p > 0.1 and 2I < 50%, it indicated that there was no statistical heterogeneity and fixed effect model was used for data analysis. If there was statistical heterogeneity and the degree of heterogeneity was acceptable, we would choose the random effect model for analysis. Otherwise, we should conduct a sensitivity analysis to evaluate the source of heterogeneity. After excluding the literature that had an obvious effect on heterogeneity, if heterogeneity did not exist, we would continue to use the fixed effect model for meta-analysis. The final results were shown by forest plot, and the publication bias was analyzed by funnel plot.Review Manager 5.3 software was used for data analysis. Cochrane Q test and Ip < 0.05), while BMI was not related to ACT (p = 0.08)  were deleted. After the screening of 1521 irrelevant records, the remaining 46 were read in full text and carefully evaluated. Finally, 13 articles  were inc = 0.08) Table 3.2I = 69%, p = 0.001). Therefore, we continued the sensitivity analysis and found that Edward 2017 and Elise ‘ 2019 were the main causes of heterogeneity. After deletion, meta-analysis was performed again, and the results were shown in 2I = 39%, p = 0.13). A fixed effect model was selected for meta-analysis. It was concluded that trastuzumab use was a risk factor for ACT . The risk of ACT among BC patients who use trastuzumab was 2.84 times higher than those who did not use trastuzumab.A total of nine articles –24, 26 s2I = 77%, p = 0.01). Therefore, a random effect model was selected for analysis and the result showed that BMI was not a risk factor for ACT .Based on the data of three articles , 19, 25,2I = 86%, p < 0.1). The analysis of data from five studies (p < 0.0001). Compared with people who did not suffer from hypertension, BC patients with hypertension were more likely to develop ACT . So we used the fixed effect model for meta-analysis. The result revealed that DM was an influence factor for ACT . We found that BC patients with DM were 1.39 times more likely to develop ACT than those who without DM , and the random effect model was chosen. Finally, CAD was a risk factor for ACT in our results     (p < 0.00001).Four articles , 26, 27 As the number of articles included in the above factors was limited, we took the funnel plot of trastuzumab as an example. The seven studies , 24, 26 Anthracyclines play an irreplaceable role in the BC treatment. Cardiotoxicity, as the most serious side-effect of anthracyclines, is of concern to clinicians for its mechanism, risk factors, monitoring and prognosis. In terms of mechanism, some conclusions have been achieved with doubts remaining. It was generally believed that cardiotoxicity was related to the damage of oxygen free radicals and TOP II , 29.2) and 146 for overweight (25kg/m2 ≤ BMI ≤ 29.9kg/m2) and concluded that obesity was significantly associated with a higher risk of cardiotoxicity by multivariate analysis. Likewise, Charles et al.  before initial use of anthracyclines to effectively prevent the ACT. DRZ is also the only cardioprotective agent approved by Food and Drug Administration for anthracyclines. In addition, a meta-analysis showed that prophylactic use of angiotension converting enzyme inhibitors (ACEI) could also reduce the clinical or subclinical cardiotoxicity, thus improving the survival of BC patients . WittayaWe identified the risk factors for ACT, whether we could consider using the model of score to assess the cardiotoxicity of these patients and develop a more comprehensive treatment before adjuvant chemotherapy or neoadjuvant chemotherapy. However, the specific weight of each risk factor is unknown. We are able to construct an ACT prediction model based on the selected risk factors, which is conducive to making clinical decisions. In addition, based on these risk factors, we can identify high-risk patients with ACT, fully assess the patient’s condition, and formulate an individualized treatment plan for BC patients. For high-risk patients of ACT, cardiac function should be monitored and followed up early to avoid the interruption of chemotherapy due to cardiotoxicity and other reasons, so as to ensure the continuity and safety throughout treatment. Regular follow-up is also necessary for BC patients who have completed all treatment. The literature suggests that ACT may occur within one year after chemotherapy, and early detection and aggressive treatment can achieve better efficacy .Although this meta-analysis was carried out strictly conforming with the PRISMA, there were some limitations. In this study, due to the strict inclusion and exclusion criteria, the number of articles included was limited, leading to the unavoidable heterogeneity in our results. Some risk factors could not be analyzed for publication bias. Hence, it was suggested that multicenter and prospective studies should be carried out in the future to provide more scientific evidence for taking targeted measures.This meta-analysis showed that trastuzumab use, cumulative dose of anthracyclines, hypertension, DM, tumor metastasis, and CAD were risk factors for ACT. High-risk patients are identified easily in the clinic by these risk factors. We can formulate more precise and individualized treatments for BC patients at different clinical stage who need chemotherapy. It is crucial to administer cardioprotective measures in time and conduct heart monitoring during the treatment, with the purpose of reducing the occurrence of ACT and ensuring a better prognosis for BC survivors.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.FJ and AZ were the directors for the fund and conceived this study. MZ collected medical records and drafted manuscript. HY and CX assisted in revising the manuscript. All authors contributed to the article and approved the submitted version.This project was supported by the National Natural Science Foundation of China (82073282), Natural Science Foundation of Liaoning Province (2021-BS115) and China Postdoctoral Science Foundation (2020M681018).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.


It is urgent to explore new ways to protect endangered wild animals and develop sustainable animal husbandry on the Qinghai–Tibet Plateau due to its fragile ecological environment. Ruminants, raised in captivity and free-range, have important niches in the Plateau and are the best models to analyze the effects of different feeding modes on their health. In this study, two ruminants, yaks and goats in free-range and captive modes, respectively, were selected to study the relationship between gut microbes and ruminant health. The results showed that the gut microbial diversity of free-range ruminants was higher than those of captive ruminants. Principal co-ordinates analysis (PCoA) showed that there were significant differences in the gut microbial communities in different breeding modes. Both the captive ruminants enriched the Succinivibrionaceae family, which had a strong potential to synthesize lipopolysaccharide, and the low exercise amount of the captive animals was significantly related to this function. Meanwhile, free-range ruminants enriched Oscillospiraceae, which had the potential to degrade benzoic acid, and this potential had a significant positive correlation with resistance to parasitic infections. We offer other possibilities, such as adding benzoic acid to feed or increasing the exercise time of captive ruminants to make them healthier. The Qinghai–Tibet Plateau, known as the “Third Pole” of the world, has the significant climatic characteristics of low pressure, low oxygen, low temperature, and intense ultraviolet radiation. Its ecological environment is fragile, and its space for human and animal survival and development is limited. In recent years, due to global warming and artificial overgrazing, the ecosystem of the Qinghai–Tibet Plateau has become more sensitive . Yaks arOvis orientalis musimon) and blue sheep (Pseudois nayaur) are two kinds of wild goats who are crucial for the ecosystem of the Qinghai–Tibet Plateau. The European mouflon , a subspecies of O. orientalis and a member of the Bovidae family, is a wild ruminant native to the Mediterranean basin [Pseudois nayaur) is a species of Bovidae and is mainly distributed throughout Bhutan, China’s Qinghai–Tibet Plateau and its surrounding mountains, Northern India, and Nepal. Their habitats are generally alpine areas 4000 m above sea level. From 1991 to 2002, the number of blue sheep on the Qinghai–Tibet Plateau sharply declined, and they were listed as a second-class National Protected and endangered species. Currently, it is challenging to observe blue sheep populations in nature. Captive breeding can achieve benign and sustainable development of animal populations under limited space and animal populations, so it is considered an effective method to protect endangered animals [In addition, endangered wild animals, such as European mouflons  whose living environment is similar with those of European mouflons and blue sheep for the samples for follow-up research on free-range goats. The mountain goat, a species of Bovidae, is currently distributed throughout the mountains of North America. Phylogenetic analysis based on eight genes showed that blue sheep, the European mouflon, and the mountain goat clustered in the 92% bootstrap confidence level (BCL) value . TherefoThis paper explored the differences in the gut microbial community structures, diversity, and functions between free-range and captive groups of ruminants under different living conditions, aiming to provide some feasible methods for improving the health of captive animals, promoting their adaptation to environmental changes, and preventing disease and parasite outbreaks.Five samples of grazing yaks were collected from the Qinghai Lake grazing area , and four samples of captive yaks were from Datong Hui and Tu Autonomous County  from 2 July 2020 to 28 July 2020. All selected adult female yaks (3–4 years old) looked similar in size and received similar immunization procedures and were free of any illness. The dietary data of yaks in the captive and grazing group are given in the ® Soil DNA Kit [® 9700 PCR thermocycler . PCR amplification of the 16S rRNA gene was performed as follows [Microbial community genomic DNA was extracted from fecal samples using an EZNA DNA Kit  , Beijing Institute of Genomics (BIG), Chinese Academy of Sciences, under the accession number, CRA006829 (7 May 2022).Purified amplicons were pooled in equimolar and paired-end sequenced on an Illumina MiSeq PE300 platform/NovaSeq PE250 platform  according to the standard protocols outlined by the Majorbio Bio-Pharm Technology Co. Ltd. . The raw sequencing data from this study were deposited in the genome sequence archive in the BIG data center  [The whole-genome sequences of r (KAAS) . KAAS prData reflecting the ruminant health status and behavioral activities of yaks and goats from the Plateau with similar living conditions were collected ,42,43,44A total of 1,553,209 high-quality reads were produced from 17 fecal samples  and were classified into 2612 ASVs after a quality control of 97% similarity. Rarefaction curves  approachp < 0.05). Overall, the gut microbial diversity and richness of free-range ruminants were higher than those of captive ruminants. Alpha diversity analysis was performed on yaks and goats with different breeding methods. The abundance-based coverage estimator (ACE) index was used to analyze microbial richness, and the Simpson index was used to analyze microbial diversity. Next, Bray–Curtis distance was used for the PCoA analysis of yaks and goats with different breeding methods. The distance between the samples reflected the degree of differences. We compared and annotated all ASVs with the silva-138-99 database. A Venn diagram and the relative abundance of microbes in the two ruminants are presented in The correlation network between the groups was drawn using Pearson’s correlation coefficient at the family level on MicrobiomeAnalyst. LDA was employed to determine the significantly different taxa between the groups from the different breeding methods. Oscillibacter valericigenes, the most abundant bacteria of Oscillospiraceae, and Ruminobacter amylophilus, the most abundant bacteria of Succinivibrionaceae, were used as biomarkers for free-range and captive ruminants, respectively. To explore the special functions of the two bacteria, Roseburia intestinalis, Clostridium bornimense, and Intestinibacter bartlett from both captive and free-range ruminants were selected as controls. All the five bacteria mentioned above were annotated with KAAS [Oscillibacter valericigenes was significantly enriched in the enzymes of both the butanoate metabolism pathway and benzoate degradation pathway, while Ruminobacter amylophilus was significantly enriched in the enzymes of the lipopolysaccharide-synthesis pathway. Other pathways showed no significant differences.ith KAAS , and theOscillibacter valericigenes, it can be seen from Oscillibacter valericigenes had five enzymes in the butyrate metabolism pathway that generated methyl butyrate from acetyl-CoA, among which EC: 2.8.3.8, EC: 4.2.1.17, EC: 1.1. 1.157, and EC: 2.3.1.9 were all annotated, and only EC: 1.3.1.44 and EC: 1.1.1.86 were not annotated. The pathway integrity was 80%, and we speculate that they could cooperate with other bacteria to produce butyric acid. At the same time, six enzymes in the metabolic pathway generated acetyl-CoA from 3-Oxopimeloyl-CoA, among which EC: 2.3.1.16, EC: 7.2.4.5, EC: 4.2.1.17, EC: 1.1.1.157, and EC: 2.3.1.9 were all annotated, and only EC: 1.3.99.32 was not annotated. The pathway integrity was 83%. In the lipopolysaccharide-synthesis pathway of Ruminobacter amylophilus , hemoglobin concentration (HGB), hematocrit (HCT), mean corpuscular volume (MCV), parasite infection rate, rumination time, eating time, and breaking and resting time corresponding to different groups  were usep > 0.05) or even increases in the microbial diversity of captive mammal populations [p < 0.05) in α diversity in captive ruminant populations, which was consistent with the findings of this study. These diversities may be mainly due to the differences in the food composition of the two groups.Several studies have discovered no changes  in the microbiota composition of captive and wild mountain goats [Compared with wild animals, which mainly eat a variety of plants that are high in fiber but low in energy and more difficult to digest, captive animals mainly eat fixed high-energy food. Therefore, free-range ruminants need a more diverse set of gut microbes to help them digest a variety of plants. Theoretically, the high diversity of gut microbial communities is beneficial for the animals to resist external environmental changes . A recenin goats . The reain goats , and it Ruminobacter amylophilus, we found that it had a strong potential to synthesize LPS. The correlation analysis showed that this phenomenon was likely significantly related to the low exercise levels of captive animals (p < 0.05). Previous studies also found that disturbed gut microbiota could lead to increased gut permeability, resulting in the entry of LPS into the plasma to trigger an immune response [This study found that the dominant microbiome family of captive ruminants was Succinivibrionaceae, which belongs to the phylum Proteobacteria . Proteobresponse , while mresponse , and modresponse . CombineOscillibacter valericigenes, which was the most abundant type of Oscillospiraceae, we found that it had the potential to synthesize butyric acid and degrade benzoic acid, which had a significant positive correlation with ruminants’ resistance to parasitic infections (p < 0.05). For herbivorous animals, ingested benzoic acid was combined with glycine to produce hippuric acid within 24 h under the catalysis of enzymes, and then excreted in the urine in the form of hippuric acid (95–100%) [The dominant family of bacteria in free-range ruminants is Oscillospiraceae, which belongs to Firmicutes . Firmicu95–100%) . Because95–100%) . TherefoHowever, the understanding of the health effects of both captive and free-range farming methods on ruminants in this study was limited. This study only focused on the effects of gut microbes on host health under different farming methods, and did not consider the impact of breeding methods on the hosts themselves. Moreover, due to the lack of extensive research on the gut microbes of plateau ruminants, the sample size used in this study was not sufficient, and follow-up research should continue to be carried out on other plateau ruminants to update the database. In addition, although the collecting of sample environmental factors was strict in this study, and the data analysis method was relatively rigorous, the speculation that benzoic acid could reduce the infection rate of intestinal parasites in ruminants should also be verified in follow-up studies. Oscillibacter valericigenes. This representative species of Oscillospiraceae had the potential to synthesize butyric acid and degrade benzoate, which had a significant positive correlation with the resistance to parasitic infections of ruminants, and Ruminobacter amylophilus, a representative bacteria of Succinivibrionaceae, had a strong potential to synthesize lipopolysaccharide. This function was significantly correlated with disease susceptibility in captive animals. Therefore, we concluded that adding an appropriate amount of benzoic acid in the feed and increasing the amount of exercise for the captive animals were beneficial for decreasing their intestinal parasites and improving their health. Taken together, we established a model of the effects of breeding methods on ruminant health (In general, by comparing the differences between the two types of ruminants, yaks and goats, under captive and free-range conditions, we found that the composition of gut microbes in captive and free-range ruminants was significantly different. The dominant family shared by captive yaks and goats was Succinivibrionaceae; the dominant family shared by free-range goats and yaks was Oscillospiraceae, t health .