Patients with simple obesity suffer from poor quality of life, as well as high risk of hypertension, diabetes, cardiovascular, and cerebrovascular accidents. Lots of Clinical trials suggested that acupuncture is beneficial for simple obesity, and it aims to gather solid evidence in order to provide reliable reference in establishing guidelines for acupuncture treatment of simple obesity in this study.Relevant databases including Cochrane Library, PubMed, Cochrane Central Register of Controlled Trials, Medline University Resource Center, Chinese Biomedical Literature Service System, and China National Knowledge Infrastructure will be retrieved from January 1950 to November 2018. Two authors will screen studies independently according to the inclusion and exclusion criteria and extract the data in a form of sheet. Quality evaluations and bias risk assessments will be performed for the methodology of included studies. Dichotomous data will be analyzed using odds ratio (OR), and continuous data using mean differences. Network meta-analysis will be conducted by using Stata 14.0. The Development and Evaluation approach will be used to rate the certainty of the evidence of estimates derived from meta-analysis. The primary outcome is body mass index (BMI), and the secondary outcomes are triglycerides, total cholesterol, low-density lipoprotein-cholesterol, effective rate, adverse effects, and recurrence rate. Trial registration number is CRD42019117387.Based on current evidence, this review will rank the efficacy and safety of the various acupuncture regimen in decreasing BMI, triglycerides, total cholesterol of patients with simple obesity, and to summarize a prioritization regimen.This evidence may be useful for clinicians, patients, and guideline-makers to select the optimum proposal of acupuncture for the simple obesity treatment. Today, obesity has been the 2nd largest public health concern, and its prevalence has dramatically increased over the past 30 years. According to surveys, more than 1.9 billion adults worldwide were overweight in the year of 2016, and among these, over 650 million adults were obese. A raised of weight is significantly correlated with the risk of various diseases, such as hypertension, diabetes, cardiovascular, and cerebrovascular accidents.–8 It is widely acknowledged that obesity kills more people than underweight does. Weight loss is an effective measure to reduce all kinds of adverse risks, which can be achieved by diet management and exercise, medication, and surgical treatment. Although diet and exercise have been playing an essential role in the weight management, their precise mode of action remains controversial. The management of diet and exercise can be a great challenge for some people, which require a firm will and a proper planning. Various weight loss attempts result in weight regain and poor long-term results. Pharmacological drugs for obesity, including sibutramine and orlistat (FDA-approved), could not be widely accepted due to side effects and lacking of long-term safety assurance.–14Simple obesity, the most common type of obesity, is characterized by the absence of metabolic disorder and is described as a chronic disease. There is increasing scientific evidence suggests that acupuncture is beneficial for simple obesity as well as its complications.–21 In the past decade, the number of randomized clinical trials for acupuncture has escalated gradually, and the treatment regimen of simple obesity has been increasingly diversified. Acupuncture can reduce weight through regulating glucose-inhibited neurons, inducing UCP1 expression, remodeling white adipose tissues to brown adipose tissue, and inhibiting appetite. After the literature searching of meta-analysis in acupuncture and related therapies for managing weight, the results showed positive. A study suggested that ear acupuncture could reduce the body weight (BM) and body mass index (BMI). However, the quality of acupuncture researches is variable and some meta-analyses have been produced, the guideline for acupuncture treatment of simple obesity has not yet been developed. Evidence strength of relative studies is somewhat inadequate in guiding the treatment of simple obesity. Therefore, evidence need to be collected and analyzed for the formulation of a prioritization regimen of acupuncture for simple obesity.Traditional Chinese medicine (TCM) especially acupuncture has been an effective treatment for simple obesity.2This study has been registered with PROSPERO, and registration number was CRD42019117387. It will be reported following the Preferred Reporting Items for Systematic Review.2.12.1.1There are no limitations on the language of randomized controlled trials, which baseline information were statistically balanced between each group.2.1.2), no organic diseases, and the ability to complete the trial independently. No restrictions on gender, age, race, education level, or economy.The criteria for participants are as follows: patients with obesity , moxibustion, or acupoint catgut embedding as a monotherapy will be included in this study. The interventions in control group can be exercises , pharmaceutical drug, placebo (sham needle or sham acupoint), sham, or waitlist. Comparisons investigated are given in Figure 2.1.4The primary outcome is BMI, which is an evaluation index of obesity degree, and the calculation of BMI is weight (kg) divided by the square of height (m). The secondary outcomes are including BM, body fat percentage, waist, hip, waist hip rate, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, BM reducing rate, adverse effect, and recurrence rate. Total cholesterol, triglycerides, and low-density lipoprotein-cholesterol will be assessed for various vascular accidents associated with obesity. The characteristic information of included studies is shown in Table 2.22.2.1We plan to collect all studies comprehensively that meet the inclusion criteria. Subject retrieval will be performed for Medline University Resource Center and China National Knowledge Infrastructure in first step to develop a retrieval strategy. According to retrieval strategy, we will search the following databases from January 1950 to November 2018: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Medline University Resource Center, Chinese Biomedical Literature Service System, China National Knowledge Infrastructure, VIP Database, and Wanfang Data. The search strategy is presented in Table 2.2.2We will also search some related journals by manual including “Journal of Traditional Chinese Medicine,” “Chinese Acupuncture & Moxibustion,” “Shanghai Journal of Acupuncture and Moxibustion,” “Journal of Clinical Acupuncture and Moxibustion,” “New Chinese Medicine,” “Journal of Guangzhou University of Chinese Medicine,” and paper dissertation library in Guangzhou University of Chinese Medicine, Southern Medical University, Jinan University and Guangzhou Medical University.2.32.3.1 If there are divisions in the screening process, the authors will discuss together and seek advice from a third party. Details of the selection process will be presented in the PRISMA flow chart  will review the studies independently according to the inclusion criteria. The consistency of the result will be examined by Kappa value.art Fig. .[27]2.3.2A data extraction sheet will be conducted for the including study, involving information on details of the first author, year of publication, study design, sample capacity, characteristics of participants, intervention, comparator, outcomes, follow-up, and adverse events.2.3.3Cochrane Handbook.5.1.0 (The Cochrane Collaboration's tool for assessing risk of bias) will be adopted to conduct quality evaluation and risk assessment of the included study methodology. The main contents include: Correctness of stochastic; Concealment of allocation; The setup of blind method; Baseline comparison; Result data integrity; Selective report results; Description of lost visit and exit; and Other sources of bias. The result of the evaluation will be input in RevMan 5.3 to generate bias and risk proportional diagram.The standards from 2.42.4.1Cochrane Handbook.5.1.0, to calculate the standard deviation of d-value.  This review will extract data from the outcomes of each study and combine all effects of the same interventions. We will summarize the data using odds ratio (OR) with 95% confidence intervals (CIs) for dichotomous data, and using mean difference with 95% CI for continuous outcomes. If the research only provides the mean and standard deviation before and after treatment, we can use the formula, which is offered by E baseline: Baseline measures; SDE final: Final measures; Corr: Correlation coefficient.)SD2.4.22 and I2 test to estimate heterogeneity of both OR and mean difference. If I2 < 50% and P > .10, fixed-effect model will be used to interpret the results as low heterogeneity, whereas a random-effect model will be used.We will use χ2.4.3Dichotomous and continuous data will be transformed into the format as shown in Table 2.4.4 Triangular  loops will be assessed to confirm local inconsistency between direct and indirect evidence. Those closed loops formed by more than 3 treatments will be divided into several triangular loops. Inconsistency factor (IF) will be calculated as the absolute difference (with 95% CIs and a z-test) between direct and indirect estimates for each paired comparison in the loop. The IF is the logarithm of the ratio of 2 ORs from direct and indirect evidence in the loop; IF close to 0 or ratio of 2 ORs close to 1 indicates that the 2 sources are in agreement.We plan to evaluate the consistency assumption for the entire network using the design-by-treatment interaction model.2.4.5,31 An inconsistency will be used to conduct network-meta analysis if inconsistency is statistically significant, whereas a consistency model will be used. We regard inconsistency as remarkable when P < .05 .The center group of evidence network will be chosen as the reference group. Based on the hypothesis of no heterogeneity between interventions, we will fit consistency and inconsistency model to assess the differences between 2 models’ results, and examine the inconsistency by Wald test.2.4.6Based on design-by-treatment interaction, we intend to calculate the surface under the cumulative ranking curve of all interventions and then sort the effects of network-meta analysis according to the cumulative ranking curve value.2.4.7 Therefore, we plan to use a funnel plot to assess publication among included studies.Publication bias may decrease the evidence intensity of systematic evaluation.2.4.8If the necessary data are available, subgroup analyses will be conducted based on baseline weight status of participants ; within each class, we also plan to do a subgroup analysis by gender  or age . This is a qualitative synthesis and while subgroup analyses may be undertaken, it is not possible to decide the groups in advance.2.4.9We will undertake statistical analysis by using Stata 14.0 software. If the data cannot be combined in a network meta-analysis, we will provide a narrative synthesis of the findings of included studies, structured around the type of intervention, target population characteristics, and type of outcome. The synthesis of the findings will be presented along with tables and figures to aid in data presentation where appropriate.2.4.10We will evaluate the quality of evidence of the included studies through the Grading of Recommendations Assessment, Development and Evaluation system. The limitations of the study, inconsistencies, indirect evidence, inaccuracies, and publication bias will also be considered. Four levels of quality of evidence will be used: high, moderate, low, or very low.3 Studies include clinical and meta-analysis have showed the positive effect in some diseases: Luo et al reported that acupuncture has effect on primary dysmenorrhea in a network meta-analysis; Raul et al researched that acupuncture on Hegu point could reduce pain level tested by fNIRS; Wang et al reported that acupuncture is effective and safety for erectile dysfunction; and Jade and Seung researched that acupuncture has effect on women's sex hormone changes.Acupuncture as a main technique of TCM has been accepted for managing many kinds of disorders in the whole world, and high interest is showing among doctors and patients.,39–41: remodel white adipose tissue, regulate central nervous system and metabolic factor, and improve insulin resistance and leptin resistance. The effects of acupuncture have been proven on animal experiments and in clinical practice. Nowadays, there are a variety of acupoint combinations in treating simple obesity. Based on the complex network analysis, it is found that,43 frequently used meridians include the Stomach Meridian, Conception Vessel, and Bladder Meridian. Frequently used acupoints include Tianshu (ST 25), Zusanli (ST 36), and Sanyinjiao (SP 6), which play a significant role in treating simple obesity. Tianshu and Zusanli are both located on stomach meridian, and Sanyinjiao is on Spleen meridian. Those 3 acupoints always used together for controlling the function of stomach and spleen. In TCM, stomach and spleen have great relationship with dietary metabiloc, and obesity could be occurred when dietary metabiloc is disorder.Research on the mechanism of acupuncture in treating simple obesity is still indefinite, while some possible functions of acupuncture have been partly elucidatedHowever, the guideline for acupuncture treatment of simple obesity has not yet been developed; so acupuncturists may use variable plans depend on their own experience, which may result in different effects. The evidence strength of relative studies is somewhat inadequate. This study will provide a detailed review on the efficacy and safety aspects of various acupuncture therapies for simple obesity. Solid evidence will be obtained to formulate a prioritization regimen for the treatment of simple obesity, which can be useful for clinicians, patients, and guideline-makers to select an optimum proposal of acupuncture in the simple obesity treatment.4This evidence may be useful for clinicians, patients, and guideline-makers to select the optimum proposal of acupuncture for the simple obesity treatment.Conceptualization: Rui Zhou, Zhijie Wang, Lixing Zhuang.Data curation: Chushuan Huang, Chang Liu, Lixing Zhuang.Formal analysis: Wanwei Chen, Xiaoyan Xie.Funding acquisition: Zhijie Wang, Lixing Zhuang.Investigation: Haidu Hong.Methodology: Rui Zhou, Zhijie Wang.Project administration: Chushuan Huang.Resources: Wanwei Chen, Xiaoyan Xie.Software: Rui Zhou.Supervision: Chang Liu, Lixing Zhuang.Validation: Lixing Zhuang.Visualization: Haidu Hong.Writing – original draft: Rui Zhou, Zhijie Wang, Wanwei Wang.Writing – review & editing: Zhijie Wang, Lixing Zhuang.


Carcharodon carcharias (white sharks) and a baited target in the presence of a commercially available electric anklet shark deterrent, the Electronic Shark Defense System (ESDS). The stereo-camera system enabled accurate assessment of the behavioural responses of C. carcharias when approaching an ESDS. We found that the ESDS had limited meaningful effect on the behaviour of C. carcharias, with no significant reduction in the proportion of sharks interacting with the bait in the presence of the active device. At close proximity (< 15.5 cm), the active ESDS did show a significant reduction in the number of sharks biting the bait, but this was countered by an increase in other, less aggressive, interactions. The ESDS discharged at a frequency of 7.8 Hz every 5.1 s for 2.5 s, followed by an inactive interval of 2.6 s. As a result, many sharks may have encountered the device in its inactive state, resulting in a reduced behavioural response. Consequently, decreasing the inactive interval between pulses may improve the overall effectiveness of the device, but this would not improve the effective deterrent range of the device, which is primarily a factor of the voltage gradient rather than the stimulus frequency. In conclusion, given the very short effective range of the ESDS and its unreliable deterrent effect, combined with the fact that shark-bite incidents are very rare, it is unlikely that the current device would significantly reduce the risk of a negative interaction with C. carcharias.Personal shark deterrents offer the potential of a non-lethal solution to protect individuals from negative interactions with sharks, but the claims of effectiveness of most deterrents are based on theory rather than robust testing of the devices themselves. Therefore, there is a clear need for thorough testing of commercially available shark deterrents to provide the public with information on their effectiveness. Using a modified stereo-camera system, we quantified behavioural interactions between  As human populations increase, more people continue to enter the ocean for leisure, resulting in an increase in human-shark interactions globally , 2. AlthPrevious research suggests that there are a variety of methods that could be used to deter sharks from an area, based purely on manipulation of their sensory cues –21. PersCarcharodon carcharias (white shark) from biting stationary bait presented in the water column [Some electric shark deterrents have been shown to effectively deter r column , 25, andr column . Specifir column , 30. Thir column –28, 34. C. carcharias, the Shark Shield was shown to be an effective deterrent [In field tests with eterrent –25 capabeterrent . The mineterrent  observedeterrent , therefoC. carcharias based on the known electrosensory deterrent threshold of this species [C. carcharias. In addition, we aimed to behaviourally test the effective deterrent radius of the ESDS by measuring the closest distance that C. carcharias would approach a bait protected by the active device compared to a visually-identical  control. Overall, this study aimed to determine the effectiveness of the ESDS, and provide more information on the electric field characteristics necessary to deter white sharks.In the present study, we set out to test the effectiveness of another commercially available electric shark deterrent, the Electric Shark Defense System (ESDS), which is known to utilise different electric field characteristics to the Shark Shield. We aimed to measure the electric field gradient and frequency of the ESDS to determine if, in theory, it would be capable of deterring  species . This woThis project was approved by The University of Western Australia Animal Ethics Committee (Permit No. RA/3/100/1193), and by the South African Department of Environmental Affairs: Biodiversity and Coastal Research, Oceans and Coasts Branch (Permit No. RES2014/91). All work was carried out in strict accordance with the guidelines of the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes (8th Edition 2013).C. carcharias periodically throughout the year [Experiments were conducted on consecutive days in July 2014 off Seal Island, Mossel Bay, in the Western Cape region of South Africa . This sithe year . TestingStereo-video recordings were made using a modified Baited Remote Underwater Video System (BRUVS) called a Remote Monitoring Research Apparatus (ReMoRA). Stereo-BRUVS have been used extensively to characterise fish assemblages and allow for the recording of events at precise distances . The desThe source of the electric deterrent in this study was the commercially available Electronic Shark Defense System (ESDS). The ESDS is a portable electronic device, patented by Wilson Vinano , 40, whiTo estimate the electric field gradient that a shark experienced when encountering an active ESDS, a voltage gradient probe was constructed and connected to an oscilloscope to record the electric field gradient at set distances, and angles, relative to an active ESDS, following the same protocol outlined by Kempster, Egeberg . MeasureEach ReMoRA was deployed with either an inactive ESDS (control treatment) or an active ESDS (active treatment). As the ESDS automatically activates upon contact with water, we used a device with no charge for the control treatment. Each rig was suspended from the surface via a large float, with the bait positioned at approximately 4 m depth (1 m below the cameras), and anchored to the seabed at approximately 20 m depth . Four Rewww.oceans-research.com). Accurate assessments of sex were not possible, but, based on local knowledge and previous research [Individual sharks were identified from distinct markings, scars, and fin shapes using a catalogue of known individuals provided by local researchers at Oceans Research  was used to calibrate the ReMoRA’s cameras before and after completion of the field work in order to make accurate proximity measurements from the footage. This process is described in detail by Harvey and Shortis . XilisofC. carcharias with the ReMoRA (appearance on the stereo-camera video footage) were classified at three levels of interaction. If a shark passed by (within the field-of-view of the cameras) without interacting, then it was categorized as a Type 0 interaction (Pass). If a shark touched the bait, ESDS or any other part of the rig with any part of its body (other than its mouth), then it was categorized as a Type 1 interaction (Bump) (All encounters of n (Bump) . Finallyn (Bump) . No indiC. carcharias.A total of 17 control deployments (inactive ESDS) and 17 active deployments (active ESDS) were conducted , which resulted in 395 encounters  from 44 individual C. carcharias individuals observed (appearance within the camera’s field-of-view within a distance of ≤ 3 m) when compared with the control  did not differ significantly , with no significant time difference observed between encounters with the control or active treatments , when only considering interactions (not proximity), there was no significant evidence of habituation between encounters during control  or activConversely, based on the same nine encounters, when considering only proximity (not interactions), there was some evidence of habituation, as significant differences were observed in how close individual sharks would approach during control  and actiThe electric field voltage gradient of the ESDS was greatest at close proximity to the electrodes and dissipated rapidly with distance . A maximC. carcharias during the first encounter with an active ESDS (35.1 ± 7.3 cm), which was not significantly different from the control  the active device compared with the control , it wask Shield . The actC. carcharias were prevented at a voltage gradient of 9.7–15.7 V/m [During prior testing of an alternative electric deterrent, the Shark Shield, almost all interactions by 15.7 V/m . Yet, de15.7 V/m . Based oet al. [As suggested by Kempster et al. , it is let al. . AlthougC. carcharias behaviour in very close proximity  or active (B) ESDS.Behavioural response of (DOCX)Click here for additional data file.


Pulmonary hypertension (PH) is a common complication of chronic respiratory disease. Recent studies have reported diabetes mellitus (DM) to be a poor prognostic factor in patients with chronic respiratory disease, including chronic obstructive pulmonary disease or interstitial pneumoniae. However, the association between DM and PH in chronic respiratory disease remains unclear. In this study, we aimed to investigate whether DM is a predictor of PH in patients with chronic respiratory disease.≥ 40 mmHg was defined as PH. We compared the clinical characteristics and impact of DM between chronic respiratory disease patients with and those without PH.We prospectively analyzed 386 patients in our hospital with chronic respiratory disease. An echocardiographic pressure gradient between the right atrium and the right ventricle of Of the 386 patients, 42 (10.9%) were diagnosed as having PH. The PH group had higher modified medical research council (mMRC) grade and complication rate of DM, but not hypertension and hyperlipidemia, when compared to the non-PH group. Multivariable logistic regression analysis revealed that mMRC scale  and presence of DM  were associated with PH in chronic respiratory disease patients.DM is potentially associated with PH and is an independent factor for prediction of PH in patients with chronic respiratory disease. Pulmonary hypertension (PH) due to chronic respiratory disease, such as chronic obstructive pulmonary disease (COPD) and/or interstitial pneumonia, is classified as group 3 PH by the World Health Organization and has been reported to be a common form of PH cases .Various degrees of PH occur in severe respiratory disease. The destruction, occlusion, and narrowing of the pulmonary vascular bed due to respiratory disease decrease the total cross-sectional area of the pulmonary vascular bed and increase pulmonary vascular resistance , 3. In aThe PH and right heart failure symptoms are non-specific , and it Recently, associations between metabolic disorders and PH have been reported , 7. In aIn this study, we examined the associations between DM and PH in patients with chronic respiratory disease.1)/forced vital capacity (FVC) < 70% by spirometry as Global Initiative for Chronic Obstructive Lung Disease criteria [This was a prospective study, which included 386 consecutive patients who had interstitial pneumonia or COPD diagnosed by expert pulmonologists and who underwent transthoracic echocardiography performed by expert cardiologists in our hospital between 2006 and 2016. COPD was diagnosed when patients met forced expiratory volume in 1 s  when the patients were in a relatively stable phase or during euvolumic phase. Spirometry was defined using standard indices: FEVcapacity .Transthoracic echocardiography was performed by experienced echocardiographers using standard techniques . TR-PG, All catheterizations were performed within 7 days after echocardiography in a resting supine position under fluoroscopic guidance. Pulmonary arterial pressure, pulmonary capillary wedge pressure, and cardiac output were measured using a 7F Swan-Ganz catheter . We mainly used the thermo dilution method for the measurement of cardiac output, however, for cases of advanced tricuspid regurgitation, we used the Fick method. PVR was calculated using the conventional formula.Normally distributed data are presented as mean ± SD, and categorical variables are expressed as numbers and percentages. The data were compared using the Student t-test, and the chi-square test was used for categorical variables. We performed multiple logistic regression analysis allowing for interaction between the presence of PH and the following clinical confounding factors: age, sex, body mass index, mMRC scale, hypertension, DM, dyslipidemia and smoking. These analyses were performed using a statistical software package .Patient characteristics are shown in The subjects in the PH group had higher scores on the mMRC scale than those in the non-PH group. Furthermore, the prevalence of DM in the PH group was significantly higher than that in the non-PH group . In contrast, the prevalence of hypertension and dyslipidemia did not significantly differ between the two groups. Regarding echocardiographic parameters, RV-FAC was significantly lower in the PH group than in the non-PH group . In contrast, LVEF and E/e’ did not differ between the two groups. Additionally, there were no significant differences between the pulmonary function tests results and laboratory data of the two groups.In the univariate logistic regression analysis, higher mMRC scale and presence of DM were found to be associated with PH complication . In the multivariate logistic regression analysis, DM and mMRC scale were shown to be independent predictors of PH complication . We verified that DM predicts PH in patients who underwent RHC. In our study, of the 45 patients on whom we performed RHC, 13 had PH. The number of patients with DM was significantly higher in the PH group than in the non-PH group (69.2% vs. 31.3%, P = 0.019; In the current study, DM was demonstrated to be an independent factor for predicting PH complication in patients with respiratory diseases, such as COPD and interstitial pneumonia.Pan et al. reported that elevation of right ventricular pressure due to hypoxia exposure was more pronounced in DM model mice than in their control group, and that increased production of reactive oxygen species and decreased superoxide dismutase were found in the pulmonary arterial endothelial cells of DM mice exposed to hypoxia . Moral-SSeveral studies on humans have demonstrated the association of PH with metabolic syndrome, insulin resistance, and dyslipidemia. For example, Zamanian et al. published the first clinical report of an association between insulin resistance and PH . Pugh etAlthough several studies have shown that DM affects the prognosis of both COPD and interstitial pneumoniae, the involvement of PH is still unclear. Makarevich et al. showed that PH is more severe in patients with COPD with type 2 DM, but not type 1 DM, compared to patients with only COPD . Since pIn addition, it has been reported that, of patients with COPD, 16% already had DM at the time of enrollment, and an additional 19% developed DM during the follow-up period . AbernetThis study has several limitations. First, the study involved a relatively small number of samples, all of which were from a single institution. Although we performed multiple logistic regression analyses to adjust possible confounding factors as much as possible, we could not rule out residual confounding factors from unknown or unmeasured variables. Second, we were unable to show the association between PH and sleep-disordered breathing because few patients underwent sleep examinations. Third, the PH and non-PH groups were classified on the basis of TR-PG values using echocardiography. RHC is a more desirable method of defining PH; however, we could perform RHC on only 45 patients. Although overestimation and underestimation are both possibilities with echocardiography, it still seems to be the most appropriate method for screening PH in respiratory disease.Thus, future studies involving multiple institutions and research results of right heart catheterization are needed to validate our findings in this study.We reported here the potential of DM as an independent predictor of PH in chronic respiratory disease patients. The presence of DM indicates increased risk of PH in these patients.


A growing number of dogs and cats live together, sharing both a common home and common owner. Nevertheless, how do owners of both cats and dogs living in the same household perceive their pets’ personalities? We tried to answer this question by using a questionnaire targeted at people who owned both dogs and cats. Sociability, protectiveness, reactivity, neuroticism, and fearfulness were the traits that emerged and that diversified themselves according to species. Moreover, intrinsic animal factors, such as age and gender, demographic characteristics of the owner, and environmental context seem to modulate the perceived personality traits in a species-specific way. As personality might influence pets’ welfare and adaptability to the home environment, owners of multiple pets should know and take into consideration both common and differential aspects of their pet’s personality to optimise cohabitation among dogs and cats.p < 0.001). Age similarly affected sociability (p < 0.01), and reactivity (p < 0.001) in both dogs and cats, while species-specific gender differences were found as to fearfulness (p < 0.05) and neuroticism (p < 0.001). The age of acquisition modulated several traits in dog personality, while living with conspecifics especially influenced cats. Physiological, behavioural, and evolutionary characteristics could explain species differences. Moreover, intrinsic and extrinsic factors modulated the five dimensions of dogs and cats in a diversified fashion, suggesting complex interactions between species and the environment. However, owners could have had different attitudes with their animals which could have influenced personality perception.This study aims to define the personality traits perceived by the owners of multiple pets and to evaluate how they are modulated by experiential-environmental factors. A questionnaire was administered to 1270 owners of multiple pets (dogs and cats) to collect data on the demographics, management, and personality of their pets. Data were analysed by principal component analysis, bivariate, and multivariable models. Five personality traits emerged in dogs and cats: sociability, reactivity, protectiveness, neuroticism, and fearfulness. The owners perceived differences in the personality of their pet: dogs scored higher in sociability, protectiveness, and reactivity, while lower in the neuroticism dimension compared with cats ( Personality refers to underlying behavioural tendencies that differ across individuals, that are consistent within individuals over time, and that affect the behaviour that is expressed in different contexts ,2. The tThe lack of a conventional model is attributable not only to the dispersion of animal research across disciplines and testing instruments, but also to the intricate interactions between genes and environmental factors that influence personality traits ,3,5. IndThe study of the multiple factors affecting animal personality could have significant implications for animal welfare. Personality traits influence the adaptation reactions to different environments, modulating physiological stress responses and, ultimately, changes in immunity ,16. An uTo date, the literature on pets’ personalities has been predominantly focused on dogs ,17,18, wTaking into account this growing phenomenon, and comparing how environmental and social factors intervene in the personality of dogs and cats, we chose to administer a questionnaire to owners of both species. Theoretically, people owning either a dog or a cat may have a low preference for one of these species, thereby providing a more equitable judgment on their personality. One might expect parallels in personality traits of dogs and cats living in the same household, because they share the same social and physical environment ,2. FurthThe multiple factorial approach adopted in this study aims to define the personality traits perceived by the owners of dogs and cats living in the same household, as well as to evaluate how the experiential-environmental factors, and their interaction with the species, has modulated their personality traits.A survey through a questionnaire was targeted at people who owned both dogs and cats. Data were collected over a three-month period (from May to July 2014) from 1270 residents in Italy, who voluntarily and anonymously completed the questionnaire. We could not calculate the relative response rate because the questionnaire was distributed through email and social networks, using the virtual snowball sampling technique.®”, which aims to increase the adoptability of adult shelter dogs in the Umbria region of Italy . The quSection A included five multiple-choice questions on participant demographic data: age, gender, region of residence, and number of pets owned. The respondent was also asked for his expertise on animals, then if he was a veterinarian, a dog trainer, a volunteer for animals, a dog/cat breeder, or an animal passionate.strongly disagree) to 5 (strongly agree): playful; loving; sociable; shy; aggressive; calm; independent; lazy; fearful; patient; hyperactive; noisy; territorial; protective; and jealous.Section B consisted of 25 multiple-choice questions concerning the dogs’ physical characteristics , the amount of time it had been left with the mother and the age of acquisition, management (where the dog lives and sleeps), and personality of the owned dog. To facilitate comparison between dogs and cats, breed, age, the amount of time it had been left with the mother and age of acquisition were classified in categories as showed in Section C contained the same questions as Section B, but about the cat.Apart from the participant’s demographic characteristics, the questionnaire was specifically developed to collect data on three main areas concerning dogs and cats living in the same household: (a) owner-pet management choice and relationship; (b) personality traits of the dog and the cat; and (c) dog-cat relationship. This paper analyses only the area concerning pets’ personalities, which, in turn, is divided into three sections:® were entered into an Excel spreadsheet and transferred into the statistical program SPSS Statistics version 23  for analysis. The level of statistical significance was set at <0.05.The data obtained from the questionnaires using Google FormsDistributions within categorical variables of owner and pet demographic characteristics were analysed using chi-square goodness of fit tests. We used the McNemar test and Pearson chi-square to test the independence of demographic characteristics of dogs and cats.Behavioural descriptors of dogs and cats were preliminarily analysed by principal component analysis (PCA). Components (PCs) showing eigenvalues greater than 1 were retained and rotated with the Varimax method . Only fat-tests to compare dogs and cats living in the same household. Then, we built multivariate models by the Generalized Linear Models procedure with identity link function and normal distribution. We stratified by species to show, in the easiest way, the interactions between species and environmental factors. Indeed, influence of the species was very strong, and the introduction of interaction terms into the models would have further complicated the presentation of the results. We included in these models the PCs as the dependent variable and all the factors (both related to the pet and the owner) as predictors. We used graphics tests to verify the assumptions and Bonferroni correction for pairwise comparisons. Estimated parameters (with standard error) and p-values from the Wald test were reported.Subscales of behaviours, as defined by the PCs, were analysed using paired p < 0.001) aged between 26 and 40 years . A large portion of participants were found to live in Northern (44.6%) or Central (31.5%) Italy (p < 0.001) and claimed to be an expert of both dogs and cats . Most participants owned one (56.4%) or 2–5 dogs (40.5%) and one (36.9%) or 2–5 cats . A higher number of participants owned only one dog rather than one cat, and 2–5 cats or more rather than 2–5 dogs or more (p < 0.001). The majority of participants were women . Female dogs (55.7%) were more represented than female cats . More than half of the participants (52.9%) had neutered both their cat and dog, but 36.1% had sterilised their cat but not their dog (p < 0.001). More than half of the participants owned both mixed-bred (51.6%), but purebred dogs (45.4%) were more represented than purebred cats . More cats had been left with their mother less than one month compared with dogs  and were acquired before three months of age, compared with dogs .Demographic characteristics of the cat and the dog living in the same household are detailed in The PCA of the overall dataset revealed five components with eigenvalues greater than 1, accounting for 69% of the total variance . The itet-test to check whether there were differences between dogs and cats living in the same household. Dogs scored higher in sociability (p < 0.001), protectiveness (p < 0.001), reactivity (p < 0.001), and fearfulness components compared with cats, that scored higher in neuroticism PCs (p < 0.001) compared with dogs . Cat’s sociability was higher in males (p < 0.001), in North than Central or South Italy residents (p < 0.01) and increased as the number of cats in the house increases (p < 0.001).Both in dogs and in cats, sociability  reduced p < 0.01) and age of owner (p < 0.05). It was higher in dogs living indoors or both indoors and outdoors than only outdoors (p < 0.01) and was affected by sleeping habits  and was affected by living habits  and with the age of acquisition (p < 0.05). It was also affected by age and expertise of owners in both dogs and cats . Reactivity was lower in purebred dogs (p < 0.05) and in dogs sleeping outdoors than indoors (p < 0.01). In cats, reactivity was affected by the region of residence (p < 0.01).Reactivity reduced with the age of both dog and cat  while in cats it was negatively associated with age (p < 0.01) but positively with age of owner (p < 0.01) and number of pets in the house (p < 0.001). Neuroticism was higher in male than in female cats , in mixed breed (p < 0.001), and in dogs living outdoors than indoors or both in and outdoors (p < 0.05). It was positively associated with age of acquisition  and the number of conspecifics in the house (p < 0.01). Fearfulness was lower in cats sleeping outdoors than indoors , as well as the interaction between species and environment.Factors emerging from our PCA have elements in common with other studies on humans and pets, but also have some innovative aspects. In particular, the sociability and neuroticism dimensions are personality traits also included in the five-factor model, the most widely accepted structure of human personality, and show considerable generality across species ,4,8. ConA relevant finding for the present work was the species-related differences perceived by the owner. Disparities in scores obtained for each trait between the two species could be due to physiological and ethological species-specific characteristics, to different domestication processes, as well as to various human perceptions. Dogs have a long history of domestication—and then of commensalism—with humans, while others would argue that cats were never genuinely domesticated ,26,38,39However, we also hypothesised that prejudices and stereotypical perceptions could affect judgment on pets’ personalities. For example, owners more often describe their cat as independent as opposed to their dog . RecentlMoreover, there are different human perceptions and knowledge of dog and cat personalities. First, behavioural traits of dogs are widely recognised ,17,35, wAfter considerations of species differences, we performed a multiple regression to highlight experiential-environmental factors affecting pets’ personalities . This muAs previously shown ,12,18,19Comparisons between purebred and mixed dogs showed that purebred dogs are perceived as calmer, less neurotic, and more fearful. Several authors claimed that genetically-based differences in behavioural traits between purebred dogs ,45 are pPersonality dimensions are affected by genetics, as well as physiological factors, such as circulating hormone levels, hormone receptor density, and external factors ,5. PhysiSurprisingly, the length of time spent with the mother did not affect many perceived behavioural traits of pets. Nonetheless, the role of maternal care up to the “socialisation period” of altricial species is well recognised. The mother is critical to the learning of social and adaptive behaviours, which also induces physiological and neurological changes ,49,50. UIn addition to experiences during the “socialisation period”, other environmental and social factors differently affect the perceived personality of dogs and cats, such as demographic characteristics and management choices of the owner. This finding suggests that complex interactions between environment and genotype modulate the personalities of dogs and cats, although they live in the same house and with the same owner. Furthermore, we also hypothesised that the owner’s attitudes could condition the perception of the pets’ personalities.We found that younger owners enhanced the perceived protective instinct and dynamism of their dogs while dampening the neuroticism of their cats. Perhaps young owners have more free time and spend more time with their animals . HoweverInterestingly, living with conspecifics has essential importance on pets’ perceived personalities, especially as it regards the cat. Indeed, the presence of other cats improves the fear and sociability aspects but also increases the neurotic one. These results support the idea that the social life and interaction dynamics of the cat are quite complicated to understand! Some authors claim that socialisation in cats is a result of domestication since it is solitary in the wild ,39,53 orFinally, we investigated the effects of perceived personality traits on living and sleeping habits. Keeping dogs in the home reduced their fear, but increased the protective instinct. Exclusive cohabitation with humans may serve as a secure base for the dog in exploring the environment  but coulA similar effect could be found in cats since the sociability component increased and neuroticism reduced when cats sleep on the bed. Heidenberger  found thAs regards to the limits of the present work, we can note the imbalance in the gender of participants, since nine out of ten were women, and the voluntary participation in the questionnaire ,13,32. HOur survey described differences in personalities of dogs and cats as perceived by their owners. We investigated the influences of species, intrinsic, and environmental factors, though we cannot exclude the impact of owner attitude in the perception of pet personality. Overall, five traits were extracted and labelled as ‘sociability’, ’protectiveness’, ‘reactivity’, ‘neuroticism’, and ‘fearfulness’. The sociability and neuroticism dimensions are personality traits also included in human five-factor models, while reactivity, protectiveness, and fearfulness are added ones. Inter- and intra-species differences were also investigated in these five factors.Differences between the perceived personalities of cats and dogs living in the same household are attributable to physiological and ethological species-specific characteristics as well as to different domestication processes. We also hypothesised the influence of stereotypical perceptions of owners regarding cat and dog personalities, as well as inadequate knowledge of cat communication tools. Moreover, the owner could have built different types of relationships with dogs and cats that may have led to perceptions of diversified personalities. Indeed, in agreement with common belief, we found dogs to be more sociable and protective as opposed to cats, which were more neurotic. As expected, we discovered differences in personality traits linked to demographic features of pets. Some differences were cross-species, such as those relating to age, while the effects of gender differed among the species. Demographic characteristics, such as age, the region of residence, and management habits of the owner also influence the perceived dog and cat personality.As pet personality might influence the adaptability to the home environment, both common and differential aspects identified in our work should be considered to optimise the coexistence of dogs and cats, or in the introduction of new animals in the home. Further studies could investigate the influence of owner personality and dog-cat or pet-owner relationship on personality traits, as well as any differences between single and multi-pet households.


Background: Alzheimer's disease (AD) is traditionally subdivided into early onset (EOAD) and late onset (LOAD). EOAD has an onset before age 65 years and accounts for 1–5% of all cases. Two main presentation types of AD are familial and sporadic.Case presentation: The authors present the case of a 68-year-old retired white man, with a college level educational background. At 55 years of age, the patient presented cognitive decline with short-term memory impairment and slowed, hesitant speech. At 57 years, he was unable to remember the way to work, exhibiting spatial disorientation. PET-CT: revealed hypometabolism and atrophy in the left temporal lobe and posterior region of the parietal lobes.Disease course: Evolving with difficulties in comprehension and sentence repetition over past 3 years and with global aphasia in past 6 months, beyond progressive memory impairment.Discussion: Possibly due to the young age and atypical presentation, and the diagnosis of EOAD is often delayed. To the best of our knowledge, this case can be classified as a sporadic EOAD with aphasia. Clinical variant and neuroimaging findings were crucial to the diagnosis and treatment of this atypical presentation of AD. A 68-year-old retired white man, married, and with college-level educational background presented at our inpatient service accompanied by his wife and daughter, reporting complaints of “aggressivity and intense agitation.”He showed restlessness and disorganized behavior, and failed to recognize people (agnosia). He was unable to answer any questions because he could not understand what was being said (receptive aphasia) and did not adhere to clinical orientations or follow instructions given by the team, proving unable to perform basic motor actions . Patients with receptive aphasia have impaired comprehension of their speech, thus they may have trouble answering basic orientation questions.Results of complete blood count and coagulogram, biochemistry, renal, liver, and thyroid function tests, vitamin B12 levels, serology for syphilis and anti-HIV, qualitative urine test, urine, and blood cultures (2 samples), CSF profile and chest x-ray were all within normal limits. Computed tomography of the brain was performed on January 2018 and underlying neurologic conditions were ruled out.The patient was admitted to the emergency service on January 2018. The reason reported by the family members for the current admission was agitation “he can't keep still, walking back and forth the whole time” and aggressiveness “he tried to physically harm his wife and had to be kept away from mirrors and windows because he would try and shatter them.”At 55 years of age, the patient first presented cognitive decline with predominantly short-term memory loss and slowed, hesitant speech. According to the reports of his wife and daughter he tended to forget where he had left his keys and had trouble remembering recent events such as appointments.At 57 years, he was no longer able to remember the way to work, stopped driving, and exhibited spatial disorientation. He became apathetic and had difficulties taking decisions at work and was unable to manage his finances. At this time, due to social and occupational deficits, the family decided to seek a Neurologist for clinical assessment. In October 2009 (at 59 years), he underwent a Magnetic Resonance of brain which revealed a reduced volume of hippocampi, particularly the choroidal fissures [grade II/III on Scheltens et al.  scale]. Since 2013 (past 5 years after the diagnosis), he has been followed by a neurologist for treatment of cognitive symptoms with: donepezil 10 mg and memantine 20 mg. A follow-up Computed Tomography of the brain (August 2013) depicted bilateral (posterior) parietal atrophy, and most affected in the left temporal lobe. These regions were markedly atrophied.A PET-CT scan July 2015) showed signs of diffuse symmetrical volume reduction of the parenchyma in the cerebral hemispheres. Bilateral hypodensity of the periventricular white matter was evident. Hypometabolism was observed in the left temporal lobe and posterior region of the parietal lobes, diagnosis of probable EOAD  in past 6 months. The patient has cognitive progressive decline when comparing his evaluations between January 2015: Mini-Mental State Examination (MMSE) = 13; Verbal Fluency Test (VFT) = 7; Clinical Dementia Rating (CDR) = 1; Katz—Index of Independence in Activities of Daily Living (ADL) = 4; Pfeffer—Functional Activities Questionnaire (FAQ) = 25; and January 2018: MMSE = not assessed; VFT = 0 (aphasia); CDR = 2, besides behavioral and psychological symptoms of dementia (BPSD), including: agitation, emotional lability, shifting between increased irritability or aggressiveness and apathy. The patient exhibited lack of initiative such as reduced interest in previously enjoyed activities. Inability to plan was another serious symptom. Occasionally the patient showed emotional blunting .He was taking losartan 50 mg, rosuvastatin calcium 10 mg, vitamin D, memantine 20 mg, donepezil 10 mg, venlafaxine 150 mg, and quetiapine 50 mg.delirium was rejected.During the current hospital stay, in January 2018, he had a major episode of psychomotor agitation with risk of aggression. The patient was medicated with haloperidol and midazolam and physical restraints were applied for the patient's safety. The patient was distraught but showed no change in level of conscientiousness, and The daughter assisted by providing a calm care environment, playing the patient's favorite song. Other measures taken were: promoting the patient's mobility ; increasing the level of lighting and reducing noise level in the room; and introducing protocols for sleep and fall prevention. Because the patient was in use of memantine 20 mg and donepezil 10 mg, quetiapine dose was increased from 50 to 400 mg . After no response to quetiapine, we switched to olanzapine 10 to 20 mg as alternative on the management of BPSD.His wife reported that the patient was calm and more cooperative after adjusting medication and introducing the nonpharmacologic measures. Sleep quality improved and the patient walked with assistance, and no further chemical control or physical restraints were required up until hospital discharge on February 2018. The patient was referred for out-patient unit follow-up at Geriatrics and Geriatric Psychiatry services.This study was carried out in accordance with the recommendations of the Declaration of Helsinki. Written informed consent was obtained from the patient for the publication of this case report. His anonymity has been preserved.AD has two forms, with an estimated 5–10% of patients having the “pure familial” type, while the remaining 90–95% is generally referred to as having the “sporadic form” .In the past 20 years, a number of researchers have identified three genes  that are defective in chromosomes 1, 14 and 21, respectively –5. IndivCase reports of EOAD are scarce in the literature. A search of the PubMed databases using the terms: (“Alzheimer's Disease” AND “early-onset”) AND  for the past five years, retrieved 34 published reports, only 15 of which were considered early-onset or familial AD cases. Of these reports, 10 cases were associated with genetic changes or mutations in PSEN1, 3 in PSEN2, only 1 in PPA and another in APOE. This explains the disease observed in family members over successive generations, directly associated with a pattern of autosomal dominant gene transmission . Even thde novo” mutations  was indentified as a major risk factor contributing to the pathogenesis of AD in about 20% of the cases  and atypical presentation.Behavior variant frontotemporal dementia (bvFTD) is characterized by prominent changes in personality, interpersonal relationships and conduct. Behavior changes are often the first symptoms in bvFTD, however they tend to occur later in EOAD. Besides, problems with spatial orientation, for example getting lost in familiar places, are more common in EOAD than in frontotemporal dementia (FTD).Aphasia is categorized as expressive (Broca) or receptive (Wernicke's). Many patients have a component of both types of aphasia. Degenerative brain disorders cause mainly Wernicke's aphasia. Primary progressive aphasia (PPA) is the second major form of FTD that affects language skills, such as speaking, writing and comprehension. Individuals with logopenic variant of PPA, lose the ability to understand or formulate words in a spoken sentence. In the 45 to 65 age range, both bvFTD and PPA are nearly as common as EOAD .Logopenia is described as “mixed aphasia” because language expression is not fluent and understanding is impaired. In this case we reported the occurrence of receptive (Wernicke's) aphasia with logopenic characteristics in the course of EOAD.Imaging studies investigated the overlap of the logopenic PPA and EOAD, comparing the pattern of cortical atrophy between AD variants , 14. ConCommon atrophy across variants was found in temporoparietal regions that comprise the posterior default mode network (DMN) , 16. At The differential diagnosis of the dementias (FTD vs. AD) is vital for correct drug treatment. Treatment of moderate-to-severe AD consists of medications that affect the activity of the neurotransmitters acetylcholine and glutamate. Preliminary evidence of the DOMINO-AD study shows that this combination can delay the need for nursing home replacement of patient .In addition, Howard et al.  demonstrExperts recommend quetiapine as the most appropriate agent for all BPSD , as seenBiologically, important subgroups of AD patients may respond to different treatments. In this patient, pharmacologic and nonpharmacologic measures were effective in treatment of acute and treatment-resistant BPSD. Clinical variant and neuroimaging findings were crucial to the diagnosis and treatment of this atypical presentation of AD.This case study was carried out in accordance with the recommendations of the Ethical Committee of SMS—Curitiba (CAAE number: 93786618.9.0000.0101). An informed consent form authorizing the use of his clinical data for research purposes was signed by a responsible proxy.MKB, MMB, and IA substantial contributions to the conception or design of the work. MKB, TNL, AS, and SM the acquisition, analysis or interpretation of data for the work. MKB and IA drafting the work or revising it critically for important intellectual content. MKB, TNL, MMB, AS, SM, and IA final approval of the version to be published.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.


To evaluate the effect of high-dose vitamin C on cardiac reperfusion injuryand plasma levels of creatine kinase-muscle/brain (CK-MB), troponin I, andlactate dehydrogenase (LDH) in patients undergoing coronary artery bypassgrafting (CABG).This is a double-blind randomized clinical trial study. Fifty patients (50-80years old) who had CABG surgery were selected. The intervention groupreceived 5 g of intravenous vitamin C before anesthesia induction and 5 g ofvitamin C in cardioplegic solution. The control group received the sameamount of placebo . Arterial blood samples were taken todetermine the serum levels of CK-MB, troponin I, and LDH enzymes. Leftventricular ejection fraction was measured and hemodynamic parameters wererecorded at intervals.High doses of vitamin C in the treatment group led to improvement ofventricular function (ejection fraction [EF]) and low Intensive Care Unit(ICU) stay. The cardiac enzymes level in the vitamin C group was lower thanin the control group. These changes were not significant between the groupsin different time intervals  for CK-MB, LDH, and troponin I. Hemodynamicparameters, hematocrit, potassium, urinary output, blood transfusion,arrhythmia, and inotropic support showed no significant difference betweenthe groups.Vitamin C has significantly improved the patients’ ventricular function (EF)72 h after surgery and reduced the length of ICU stay. No significantchanges in cardiac biomarkers, including CK-MB, troponin I, and LDH, wereseen over time in each group.IRCT2016053019470N33 The harmful effect of CBP can be produced by freeoxygen radicals. During ischemiaand reperfusion, the free radicals of oxygen affect the mitochondria, sarcoplasm,vascular endothelial cells, adenosine, and nitric oxide (NO), causing an undesirableeffect. This effect increases the damage to the myocardium by arrhythmia, impairedcontractions, and necrosis. Thesystemic release of free radicals during CPB disrupts the reperfusion process of theischemic heart and causes a secondary damage to the myocardium.The cardiopulmonary bypass (CPB) pump, which is used for coronary artery bypassgrafting (CABG) surgery, can cause inflammatory reactions.On the other hand, the production of free oxygen radicals leads to the use of mainantioxidants. The plasma concentration of vitamin C decreases by approximately 70%in all subjects under CPB within 24 hours after surgery, and this decrease persistsin most patients for up to two weeks. Therefore, the serious reduction of vitamin Cleads to destruction of the body’s defense against activated oxygen species producedduring cardiac surgery,6.Studies have shown that the ascorbic acid acts as a free radical scavenger to reducethe lipid peroxidation in the cell membrane and effectively protects from myocardialdamage against ischemic reperfusion, by removing the free radicals during and aftersurgery-9.Myocardial injury (MI) and myocardial infarction during the surgery are determined bymeasuring serum myocardial necrosis indices, such as creatine kinase-muscle/brain(CK-MB), troponin I, and lactate dehydrogenase (LDH). Cell membrane damage causesthese cardiac markers to spread to the bloodstreamRegarding the mentioned issues, free radicals of oxygen are considered as the maincause of myocardial reperfusion ischemic injury in patients under CPB, whichincreases the myocardial damage, by arrhythmias, impaired contractions, andnecrosis. Studies have been conducted to find and remove free radicals and protectthe myocardium, including strengthening the antioxidant defense, which may help toprotect tissues from reperfusion damage in surgical procedures under CPB. Vitamin Creduces free radicals, as an antioxidant, and may play an important role in reducingcardiac enzymes and postoperative complications. Our main objective in this studywas to evaluate the effect of high doses of vitamin C on plasma levels of CK-MB,troponin I, and LDH (after CABG) and the cardiac protective effect of vitamin C.Also, the incidence of arrhythmia and the patients’ hemodynamic symptoms have beeninvestigated.This is a double-blind randomized clinical trial study. The study was approved by theEthics Committee of the Shiraz University of Medical Sciences (No. 10263). Fiftypatients, males and females, with the age range of 50-80 years and who had CABGsurgery were selected using a simple sampling method for the study. The inclusioncriteria were: patients who referred to Shiraz hospitals for undergoing CABG and whosigned the written consent for the participation in the study. The exclusioncriteria were: history of arrhythmias, ejection fraction (EF) < 30%, severe renalor hepatic failure, permanent or temporary pacemaker, treatment with antiarrhythmicdrugs and digoxin, presence of a degree of atrioventricular block (AV-block) orbradycardia with a rate of < 50 per minute, history of recent myocardialinfarction (less than a month), high initial troponin I level, and history of redoor complex  surgery. Left ventricular ejection fraction(LVEF) was measured by transthoracic echocardiography (TTE). Sample selection wasdone using a block randomization method. A demographic information form wascompleted for the patient.Patients in group A received 5 g of intravenous vitamin C before induction ofanesthesia and 5 g of vitamin C in the cardioplegic solution. Patients in group B,as control group, were given the same amount of placebo . Arterialblood samples were taken at the following intervals to determine the serum levels ofCK-MB, troponin I, and LDH: during induction of anesthesia, at the end of CABG, sixhours after surgery, and 24 hours after surgery. In all patients, blood samples weretaken before the injection of vitamin C or placebo and considered as baseline.Hemodynamics of patients, including systolic and diastolic pressures, mean arterialpressure, and heart rate, were recorded at specified intervals.The method of anesthesia was the same in all patients. The induction of generalanesthesia was done by midazolam (0.1-0.2 mg/kg), fentanyl (5-10 µg/kg),sodium thiopental (1-3 mg/kg), and pancuronium bromide (0.1 mg/kg) and it wasmaintained with propofol (50-100 µg/kg/min), remifentanil (0.1-0.2µg/kg/min), and oxygen and nitrous oxide (50%/50%). After the sternotomy andseparation of the graft , following the administration of heparin, at a dose of 300u/kg and achieving activated clotting time (ACT) up to 400 seconds, the aortic andright atrium cannulation was performed by the surgeon and CPB pump was used. Afterthe patient's aortic clamping, a cold blood cardioplegic solution containing 5 g ofvitamin C or placebo was injected, respectively, into group A and group B patients,through a cardioplegia cannula and using antegrade techniques. The cardioplegia usedwas the same in all patients, with the combination of blood and hypothermiccrystalloid, and it was repeated every 20 minutes. At the same time, patients werecooled down to 32-34 °C. The surgical technique was the same in all patients and itwas performed by the same surgeon. In all cases, LIMA and saphenous vein were usedin CABG.Anastomosis of the distal grafts (on the heart) was performed by the surgeon inpatients in cardiac arrest. According to the surgeon opinion, the patients startedto warm up, and after aortic declamping, any arrhythmia, such as irregular rhythmand rate , the time, and the method of intervention for the treatment of arrhythmia were recorded in the checklist. The rateof reception and the number of inotropic drugs prescribed for heart rehabilitationwere also recorded. After proximal anastomosis on the aorta, the end of bypass isannounced. Separation of patients from the CPB was based on the standard protocol,including the appropriate left ventricular filling pressure and proper hemodynamicusing liquid and vasoactive drugs administration. Inotropic drugs were administeredbased on hemodynamic and underlying conditions of the patient. Epinephrine anddopamine were the first line inotropes to support the heart. At the end, after thepatient's separation from the CPB pump, for heparin reversal, protamine sulfate wasgiven to patients at a rate of 50 mg per 5000 units of heparin and ACT was checkedagain. After insertion of the chest tube and examination of the patient in terms ofhemorrhage and hemostasis, in sternum, subcutaneous tissue, and sutured skin,patients were transferred to the Intensive Care Unit (ICU) and, after stablehemodynamic conditions, isolated from the ventilator in the ICU. The level ofbiochemical markers and the hemodynamic changes in the patient, the type andtreatment of arrhythmia, and the time and number of inotropes were also recorded atsix hours after surgery and 24 hours after surgery.P<0.05.Data was analyzed using the Statistical Package for the Social Sciences (SPSS)software version 24. Qualitative variables were represented by number andpercentage. Quantitative variables with normal distribution were representedwith mean and standard deviation (mean ± SD), and quantitative variableswith abnormal distribution with median and interquartile range (median [IQR]).To test the normality, Kolmogorov-Smirnov test was used. For comparison of thevariables between the two groups according to the need, Student t-test,Mann-Whitney U test, and chi-square test and repeated measure were used. Thevalues are significant when The levels of CK-MB, LDH, and troponin I in four times  were measured andrecorded. The values of each of the three biochemical markers at all times in thecontrol group were greater than those of the treatment group. Data analysis was donein two ways: (1) comparison of changes in biochemical markers over time in eachgroup and (2) comparing biochemical markers changes between the two groups ingeneral and then at each time.P=0.0001). Incomparing the two times in each group, the first time showed a significantdifference from the three other times (P=0.0001) and it indicates asignificant increase in the enzyme during and after surgery, but the second, third,and fourth times have only significant difference from the first time, but not fromother times (P=1). The comparison of CK-MB enzymes changes betweenthe two groups reveals that the overall comparison between the two groups did notshow statistically significant differences (P=0.27). Therefore, theenzyme values were evaluated in each time in two groups and there was no significantdifference between the two groups (P>0.05).In the comparison of CK-MB enzymes over time in each group, the CK-MB levels from thefirst to the second time showed a sharp increase in both groups, there was a slowdecrease from the third to the fourth time in the treatment group, whereas in thecontrol group, after a slow decrease, the enzyme levels increased again. Thesechanges were significant over time in each group (P<0.05). In comparing two differenttimes in each group, troponin I changes were significant between the first time andthe second and third times (P=0.0001) and the fourth time(P=0.001), therefore there is a significant increase in thelevel of troponin I during and after surgery. The second, third, and fourth timesshowed a significant difference only from the first; no significant difference wasshowed from other times (P>0.05). The comparison of troponin Ichanges between the groups showed no significant difference(P=0.35). Also, the comparison of troponin I values in each of thefour study times didn’t show significant differences between the two groups(P>0.05).In the comparison of troponin I changes over time within the groups, the treatmentgroup was steadily increasing until the second time, and thereafter until the fourthtime, there is a slow increase in the amount of troponin I. But in the controlgroup, there is a rapid and steady increase in all times. These changes aresignificant in each group (P<0.05). Comparison of two times in each groupshowed that the first time had a relatively significant relationship with the secondtime (P=0.057). And with the third and fourth times, it wascompletely significant (P=0.0001). The third and fourth timesdidn’t show significant changes (P=0.87). The comparison of LDHenzyme changes between the two groups showed no significant statistical difference(P=0.09) and also the amount of LDH enzyme was notstatistically different at any time between two groups (P>0.05). Table 4P=0.002). Also, the EF changes variable, whichindicates changes in EF from preoperative time to 72 hours after surgery, wascompared in both groups. The results indicate that the EF of the treatment groupexperienced an increase of 0.8% and the control group experienced a decrease of 4.2%(P=0.009). These results show statistically significantdifferences in EF changes during 72 hours after operation between the two groups  .P=0.0001), there are nosignificant differences between the two groups (P=0.34).The urinary output of both groups of patients was measured in three times, before theonset of bypass (time 1), at the end of bypass (time 2), and 24 hours after surgery(time 3). The results show that the amount of urine output in patients was increasedat the end of the pump until 24 hours after the surgery, and these changes were thesame between the two groups. Although changes in time are significant, regardless ofbeing in the treatment or control group (P=0.89). Blood potassium levels in both groups increased byup to six hours postoperatively and decreased in 24 hours after surgery, andalthough these changes in all patients were meaningful over time(P=0.0001), there was no significant difference between the twogroups (P=0.85).Plasma levels of hemoglobin and potassium were measured at four-time intervals:anesthesia induction time, bypass termination, six hours after surgery, and 24 hoursafter surgery. The results did not show any significant difference between thetreatment and control groups. Hemoglobin levels from the first to the second time,the end of bypass, showed a sharp decline, but increased in 24 hours after surgeryin both groups. But these changes are not statistically significant between the twogroups . Also, the heart rate ofpatients in the control group was lower than of those in the treatment group, andpatients in both groups had the highest and the lowest heart rate in six and 24hours after surgery, respectively. These changes were significant over time(P=0.004), but no significant differences were observed betweentwo groups (P=0.56).Comparison of hemodynamic parameters, including systolic and diastolic bloodpressures and heart rate, in both groups in the four mentioned times showed thatuntil the third time (six hours after surgery), a decrease in blood pressure wasobserved, and thereafter a relative increase was detected. These changes aresignificant over time, but they are not statistically different between the twogroups , proteins, andlipids. Vitamin C hasthe ability of scavenging free radicals. This vitamin has cardioprotectiveproperties, which were demonstrated to reduce oxidative damage in diabetic rats andduring ischemia/reperfusion (I/R)-injury,13. In somestudies, vitamin C improved myocardial stunning and enhanced left ventricularfunction. Also,vitamin C inhibits the expression of inducible nitric oxide synthetase (iNOS) inendothelial cells and neuronal nitric oxide synthetase (nNOS), and thereby reducesthe level of NO in plasma, that is responsible for the guanylate cyclase activation,which counteracts the effects of vasoconstrictors. This might maintain the vascularresistance and baroreceptor reflex and, as a result, the mean arterial pressurecould also be maintained.During ischemia, the disruption of the cell membrane integrity leads to release ofcalcium and phospholipid A2 and formation of polyunsaturated fatty acids and fattyacid radicals study, the CK-MB level was lowerin vitamin C group than in the control group. In another study, by Dingchao etal., the levels of CK-MBand LDH were higher in the control group after surgery than in the vitamin C group.In Lee et al. study, troponinI and LDH levels were lower in the treatment group than in the control group, butsimilarly to our study, the level of CK-MB was not significantly different. On theother hand, the outcome of this study is consistent with the study by Westhuyzen etal., where thepre-operation administration of supplements of vitamins C and E did not have asignificant effect on myocardial damage and the level of CK-MB enzyme. Also, Gao etal. found out that theadministration of 1 mM of vitamin C alone did not reduce post-ischemic injury, butcoadministration with glutathione increased the protective effects of glutathione.All of these studies have different conditions, doses, and administration methods, and perhaps thereason for the different results is related to these variations.The focus of this study was to evaluate the effect of vitamin C on the plasma levelsof CK-MB, troponin I, and LDH in four-time intervals  intreatment and control groups. The results showed that the changes in the levels ofall three cardiovascular biomedical markers over time in each group were significantwithin the group. CK-MB and troponin I changes were significant only between thefirst time and the three other times, indicating a significant increase in thecardiac biomarkers during and after the surgery. Also, in the LDH enzyme levels, thedifference between the first time and the second time was relatively significant andthe difference was quietly significant between the first and the third and fourthtimes. However, in comparing between the two groups, although the level of enzymesin the control group was always greater than in the treatment group, the differencewas not significant between the groups. There was no significant difference betweenthe two groups in each of the four study times. In the Oktar et al.,16, the level ofcardiac biomarkers was clearly reduced. In our study, at all times, with anyreduction or increase process, the level of biomedical markers in the treatmentgroup was lower than in the control group and this shows the clinical effect ofvitamin C on reducing the levels of ischemic enzymes, but there was no statisticallysignificant difference between the two groups, which may be due to a low sample sizeor a significant increase in biomedical markers at all intervals, especially fromthe first to the second time, which resulted in large dispersion of data andincreased the SD, and the difference between the two groups was not significant. Itis expected that by increasing the sample size or using longer intervals, thedifference becomes statistically significant.In studies with a high dose of vitamin CIn this study, high doses of vitamin C were injected intravenously and in acardioplegic solution in patients undergoing CABG surgery. According to the results,the significant decrease of all three biomarkers after the onset of thecardiopulmonary pump is clear..The comparison between EF values showed an increase in EF in the control group within72 hours after the operation, and this difference was significant. Also, thevariable EF changes, which indicates the changes in EF before and after theoperation, well demonstrates this difference. The percentage of EF in the vitamin Cgroup showed 0.8 of increase and in the control group, it showed 0.4 of decrease.Therefore, it seems that vitamin C has been effective in improving the function ofthe left ventricle and the heart because patients receiving vitamin C have a bettercontractile power than those in the control group after 72 hours. This result isconsistent with the study by Mak and Newton, which revealed that vitamin C has alsoenhanced the response of the left ventricle to the inotropic drugs, which improvesleft ventricular contraction, in which the patients had shorterICU stay and hospital stay than the control group. Also, in Rezk et al. study, patients in the vitamin Cgroup had shorter length of ICU stay than those in the control group.The length of ICU stay in patients receiving vitamin C was shorter than in those fromthe control group, and this difference was significant. Although the hospital stayand intubation time were shorter in the vitamin C group than in the control group,there were no significant differences between these two items in the two groups.This is consistent with the result of the study by Dinqchao et al.There was no significant difference in the need for blood transfusion between the twogroups. In fact, vitamin C seems to have no effect on reducing the need for blood inpatients who have received it..Regarding the need for inotrope support 24 hours after surgery in both groups and thenumber and hours of drug intake, vitamin C seems to have no effect on the need forinotropic drugs during the postoperative period. This conclusion is consistent withthe study by Oktar et al.The urinary output rate was measured before the onset of bypass until 24 hourspostoperatively. The changes in both groups were similar over time, and the patientsreceiving vitamin C did not differ in the level of urinary output from those in thecontrol group. The comparison of plasma levels of hemoglobin and potassium in thefour periods, before the onset of the bypass until 24 hours after surgery, did notshow any significant difference between the two groups. The changes made over timebetween the treatment and control groups had the same trend and vitamin C had noeffect on this process.. Inanother study by Jouybar et al., ascorbic acid had no significant effect on hemodynamicparameters, such as systolic and diastolic blood pressures and heart rate. But inthe study by Lee et al., meanarterial blood pressure was better in the vitamin C group than in the control group,but the patients’ heart rate showed no difference between the two groups.Hemodynamic parameters, including systolic and diastolic blood pressures and heartrate, were compared in four-time intervals between patients from treatment andcontrol groups. Blood pressure changes in both groups increased and decreasedsignificantly, and no significant difference was observed. There was also a slightimprovement in heart rate in the treatment group, but there was no statisticallysignificant difference. Therefore, the vitamin C intervention did not have a cleareffect on hemodynamic conditions in patients. These results are similar to the onesfrom Mak and Neutron study. However, in the study by Rebrova et al., it was determined that vitamin Cprevents cardiac rhythm disturbances 24 hours after surgery, that the use of vitaminC with beta blockers is recommended after bypass surgery to prevent arrhythmias, andit also suggested the use of vitamin C in patients with advanced heart disease. Inthe present study, patients have no acute underlying problems, such as severecardiac arrhythmias, MI, very low EF, etc., and they were undergone surgery in arelatively stable general condition, and this may be a reason for ignoring theeffect of vitamin C in preventing cardiac arrhythmias.In this study, we monitored the incidence of arrhythmias before the onset of thebypass up to 24 hours after surgery in five intervals. Type and treatment ofarrhythmias between the two groups did not differ significantly. The highestincidence of arrhythmias was observed at the time of aortic clamp removal, which wassimilar in the treatment and control groups. Compared to the control group, nosignificant changes were observed in the incidence of cardiac arrhythmias during andafter operation. Vitamin C seems to have no effect on reducing the incidence ofcardiac rhythm disturbances in patients. The result of this study is consistent withthe ones from the study by Oktar et al.This study was performed on a limited number of patients and it is recommended toperform studies with larger sample sizes than this and in different countries,so the results could be applicable throughout the world.Vitamin C has significantly improved the ventricular function (EF) of patients 72 hafter surgery and reduced the length of ICU stay.No significant changes in cardiac biomarkers including CK-MB, troponin I, and LDHwere seen over time in each group. For future researches, longer intervals (48 and72 hours after surgery) or higher sample sizes are recommended. The combination ofvitamin C with other antioxidants or their comparison can more accurately reveal itsinfluence on prevention of coronary heart disease and reduction of cardiacbiomarkers.