The evaluation of SWB was performed using a novel approach that appraises three aspects of SWB. This approach of evaluating SWB has not been used in odor exposure studies. A proportional odds logistic regression model was used to estimate nine measures of SWB. The results showed that participants who reported that the air is very fresh or the odor is highly acceptable had higher levels of SWB. This association suggests that residents who live in areas exposed to strong industrial odors had lower levels of SWB. A subset of participants in this study took the survey four times in one year. Longitudinal analysis showed that evaluative satisfaction was slightly associated with seasonality. Both satisfaction with how life turned out and satisfaction with standards of living slightly increased during the fourth quarter of the year. The study also found that four of the nine measures can be used to represent SWB in future studies. Two of those measures were evaluative SWB, and the other two were positive hedonic SWB measures. A comparison between the five communities showed that well-being levels in North Denver and Greeley were not significantly different than those in Fort Collins or Fort Lupton. The comparison, however, showed that Pueblo had the lowest levels of well-being among all communities.Odor pollution was identified as a top priority of the community of North Denver. Previous studies that investigated the impact of air pollution in North Denver focused on adverse health effects, rather than mental well-being. This study assessed the impact of odors from industrial sources on the subjective well-being (SWB) of North Denver residents, and of four similar communities in Colorado for comparison. An online survey was sent to participants from Greeley, Fort Collins, Fort Lupton, North Denver, and Pueblo, asking questions about SWB and odors in their areas ( The residents of the northern part of the Denver metropolitan area frequently experience odors from commercial and industrial businesses, two major highways, railyards, and utilities. Globeville and Elyria Swansea are probably the most affected neighborhoods in North Denver, in which over 70% of their areas contain these types of businesses. The residents of both neighborhoods, who are predominantly Hispanic (Globeville is 68% and Elyria Swansea 84% Hispanic) have a long history of odor complaints. Since 2004, Denver City has received 1322 odor complaints [Understanding the psychological impact  of odor exposure, in particular odors from industrial sources, in the nearby residential communities is challenging ,5. AssesOdors are characterized with instrumental or odor sensory methods. The instrumental methods measure the chemical components of odors in the air, typically using gas chromatography/mass spectrometry  or photoUsing standardized questionnaires for odor exposure assessment is common and reliable. A six-point scale question about odor intensity (odor strength from 1 = very slight to 6 = extremely strong) and a nine-point scale question about hedonic tone (pleasant and unpleasant odor), in addition to odor frequency data, were used in an odor exposure assessment study . In a stBoth academic and policy circles have showed an increased interest in the impact of quality of life recently, which is a catch-all term used to describe the health, comfort, and happiness experienced by an individual. Many aspects need to be addressed when measuring quality of life . Subjective well-being (SWB) is one of the most frequent methods used to measure quality of life, which is often done using surveys. Well-being is defined most simply as the state of being comfortable, healthy, or happy.Satisfaction and happiness are widely used to measure subjective well-being ,31,32,33All studies that have been conducted in the North Denver area mainly focused on linking air pollution or industrial odor pollution to odor sources or adverse health effects, not well-being ,39. TherOther studies focused on the impact of odor exposure  on mental state indices such as depression, anger, confusion, tension, fatigue, and ability to focus. Schiffman et al.  reportedThis study investigates whether odors from industrial sources impair the subjective well-being (SWB) of residents in the often-low-income surrounding communities in Colorado. The study expands the scope and includes all north of Denver metropolitan neighborhoods . In addition, four other Colorado communities were chosen outside of Denver for comparison purposes. Three of them are demographically similar to Globeville and Elyria Swansea . These three communities are Greeley, Fort Lupton, and Pueblo. Unlike these three communities, Fort Collins was selected to be different. A 60-question online survey was designed to collect data from the five Colorado communities. The online survey covers aspects related to SWB (48 questions), odors (5 questions), and demographic information (7 questions). The SWB part of the survey is a widely-used and validated survey that was adopted from the New Economics Foundation (NEF) in the United Kingdom .This study was approved by the University of Colorado Boulder’s Institutional Review Board, Protocol #16-0065.none of the time I was recently happy to all the time I was recently happy. Similarly, recent depression was arranged from all the time I was depressed to none of the time I was depressed. In the results section, the selection of these nine measures is compared with a selection based on principal component analysis (PCA).The purpose of the online survey data collection was to quantify any relationships between SWB and the independent variables (demographics and odor-related characteristics). To measure SWB, three aspects of SWB were used: evaluative well-being (EWB), positive hedonic well-being (+HWB), and negative hedonic well-being (−HWB) ,36,38. Eair is very fresh, air is fresh, air is neutral, air has strong odor, and air has very strong odor. The second odor-related variable is odor acceptability, with response categories of low acceptability, middle acceptability, and high acceptability. Three binary demographic variables were considered as independent variables: employment , age , and gender . As explanatory (independent) variables, two odor-related variables of interest were chosen, as well as three demographic variables. The first odor-related variable is perceived odor, with response categories of Principal Component Analysis (PCA) is a widely-used data reduction procedure by which the matrix of possibly correlated variables is decomposed into eigenvectors. These eigenvectors will then be sorted based on the corresponding eigenvalues. Following the authors of , only eiThe chi-squared test was used to explore relationships between the dependent variables  and the independent variables . An ordinal logistic regression model was also applied to quantify the associations between the variables.all the time, most of the time, some of the time, and none of the time. The proportional odds regression was used in this study and it is one of the most popular and widely-used models among the ordinal regression models [An ordinal logistic regression is a model that can be used when the dependent variable is ordinal in nature, for example, the amount of time a person feels happy can be classified as n models ,58,59. Cn models .The Center of Well-being at NEF recommends using three sets of well-being questions. The first set is the Office for National Statistics (ONS) subjective well-being questions. This set of questions was added to the Integrated Household Survey (IHS) in April 2011. The IHS is a composite survey consisting of four questions that collects data from more than 200,000 people in United Kingdom , employment (seven questions), health (three questions), appreciation (five questions), and freewill (two questions). In addition to these groups from NEF, our survey includes an odor-related group (four questions) and demographics (seven questions), which were added to the survey as a part of the study design.Four different approaches were compared to determine the sample size in our study. First, a power analysis for an ordinal logistic regression was conducted to determine a sufficient sample size using an alpha of 0.05, power of 0.95, odds ratio of 1.3, and one-tail test. The analysis assumes that all dependent variables are log-normally distributed. Based on those assumptions, the desired sample size is 221. Secondly, we calculated the sample size using Whitehead’s formula, which is based on the proportional odds model. Using this formula, the maximum sample size among the nine dependent variables is 192 participants ,61,62. AThe survey contains 24 (out of 60) questions that can directly measure well-being . Principall things considered, how satisfied are you with life as a whole nowadays?, loaded on component 1 with the evaluative well-being items. This is not totally unexpected as nowadays could be thought of as an extend period of time other than recent time. The classification of the nine measures into three groups agrees with the classification from the literature.PCA was also performed on the nine selected well-being measures themselves. Above 45 years old group and the 45 or below group A total of 351 participants joined the study and submitted the online survey . This number of participants was reduced to 326 by excluding surveys from outside the five communities and repeated surveys when they were identified. The weighted sample was 25% male and all participants were at least 18 years of age . To avoid the effect of small numbers of participants in certain groups of age, the variable age was dichotomized at the median .forest plots in x-axis are the ORs obtained from the proportional odds regression model output. The increase in OR values in the forest plots indicates better SWB and confidence intervals excluding one are considered significant.The proportional odds logistic regression model was used to estimate associations between the five independent variables and measures of SWB at the conventional 5% level of significance. The results from the proportional odds model are obtained in the form of odds ratios (ORs), which are presented graphically as higher levels of lack of a well-being (WB) measure has the same meaning as lower levels of that WB measure. These results are in good agreement with the strong evidence in the literature of the negative impact of unemployment on SWB [The proportional odds model results indicate that the three measures of satisfaction and −HWB measures were associated with employment. The OR of 2.25 (95% CI = 1.43–3.56), OR of 1.76 (95% CI = 1.14–2.74), and OR of 1.79 (95% CI = 1.13–2.84) suggest that employed participants tended to have higher levels of satisfaction with how life turned out, satisfaction with standards of living, and recent satisfaction, respectively. Similarly, the OR of 1.76 (95% CI = 1.11–2.79), OR of 1.73 (95% CI = 1.09–2.76), and OR of 1.60 (95% CI = 1.03–2.54) suggest that employed participants reported higher levels of lack of recent depression, recent powerlessness, and recent sadness, respectively. It is probably worth mentioning that t on SWB ,65,66,67t on SWB ,69 also Male participants tended to have lower levels of SWB. Precisely, male participants had lower levels of general happiness , and satisfaction with how life turned out . Measures of +HWB are significantly associated with gender. The OR of 0.60 (95% CI = 0.37–0.98), OR of 0.45 (95% CI = 0.27–0.75), and OR of 0.56 (95% CI = 0.34–0.92) indicate that males had a lower level of recent satisfaction, recent enjoyment, and recent happiness, respectively. Male participants also had higher levels of recent depression  and recent sadness .According to the literature, the gender impact on SWB seems to lack consistency. A number of studies ,70 showe45 years old or below and Above 45 years old, showed significant association with only the measures of −HWB. The participants who were aged 45 or below had nearly half the odds of those who were above 45 years old. The OR of 0.47 (95% CI = 0.26–0.85), OR of 0.50 (95% CI = 0.27–0.91), and OR of 0.42 (95% CI = 0.24–0.75) indicate that participants aged 45 years old or below had higher levels of recent depression, recent powerlessness, and recent sadness, respectively. The measures of both EWB and +HWB did not show significant association with binary age. We decided to use a dichotomized age variable because the number of participants in some age groups was not sufficient [The binary variable of age, fficient . The weifficient , who foufficient ,65,75,76fficient ,65.Almost all measures of EWB and +HWB showed a strong association with perceived odor, while −HWB measures did not show significant association. The OR of 6.06 (95% CI = 1.80–20.40), OR of 5.08 (95% CI = 1.49–17.33), and OR of 6.16 (95% CI = 1.81–20.91) suggest that the participants who reported that the air was very fresh had higher levels of general happiness, recent satisfaction, and recent enjoyment, respectively. Correspondingly, the OR of 0.36  and OR of 0.39  suggest that the participants who reported that the air had strong odor (smelly) had lower levels of satisfaction with how life turned out and satisfaction with standards of living, respectively. Recent happiness is the only measure of +HWB that did not show significant association with perceived odor.Satisfaction with how life turned out and satisfaction with standards of living were associated with odor acceptability. The OR of 2.16  and OR of 2.41  suggest that the participants who reported that odor was highly acceptable had higher levels of satisfaction with how life turned out and satisfaction with standards of living, respectively.From the two previous sections, we can see that perceived odor was associated with five measures of SWB that represent EWB and +HWB. On the other hand, odor acceptability was associated with only two of measures that represent EWB. This association indicates that residents who lived in areas exposed to strong industrial odors (air has strong odor and low odor acceptability) had lower levels of EWB and +HWB. This lends support to previous findings in the literature, as summarized below.The number of studies that linked well-being to odor exposure is limited. Some of these studies used psychological stress as a measure of well-being. In a study on health effects of odors from a petroleum refinery in Oakville, Ontario, Luginaah et al.  found thOther studies focused on the impact of odor exposure  on mental state indices such as depression, anger, confusion, tension, fatigue, and ability to focus. In a study about health and quality of life of residents from North Carolina near intensive livestock operations , it was Our findings of the association between odor exposure, represented by perceived odor, with EWB, and +HWB agree with the reduction in quality of life and increase in general environmental stress caused by odor exposure found in previous studies ,40,77. TWhen interpreting our findings, it could be implied that four of our measures can be chosen to represent SWB . Satisfaction with how life turned out, satisfaction with standards of living, recent satisfaction, and recent enjoyment are associated with both employment and perceived odor. They are associated with employment, which is known to be correlated with well-being measures. They are also associated with perceived odor, which is indicative of air quality. On the other hand, negative hedonic measures of SWB  may not be good representatives of SWB in communities affected by industrial odors. While they are associated with both employment and age, they did not show a significant association with perceived odor or odor acceptability.target variables that could be potential confounders includes three binary variables and four ordinal variables. Our hypothesis is that people who live in industrial areas experience lower levels of SWB. One might argue that areas surrounding the industrial facilities are often communities of color and/or lower socioeconomic communities. In the context of this argument, residents of those communities have lower levels of well-being because of other factors, such as level of education or income. In other words, the hypothesized association might be influenced by some third confounding variable. In this section, we investigated the effect of potential confounding variables. Diener et al.  pointed A confounder variable is a variable that was not accounted for (not included in the model), which can bias the model results and lead to incorrect conclusions. In order for a variable to be a confounder, (1) it must be predictive of the dependent variable; (2) it must be correlated with the independent variable; (3) it must be unequally distributed between treatment groups; and (4) it must not be a link in the causal chain ,81.The ordinal logistic regression model showed that perceived odor was associated with happiness, satisfaction with how life turned out, satisfaction with standards of living, recent satisfaction, and recent enjoyment. It also showed that odor acceptability was associated with satisfaction with how life turned out and satisfaction with standards of living. The goal was to test whether the target variable correlated with the dependent variables (condition 1) and with the independent variables (condition 2).p-values from the chi-square test for independence between target variables and variables of interest (both independent and dependent). Except for gender, all target variables are not confounders because they do not meet condition (1). Gender seems to be associated only with perceived odor (p = 0.04). When we further test condition (2) for gender, we can see that gender is also associated with happiness (p = 0.012), satisfaction with how life turned out (p = 0.017), and recent enjoyment (p = 0.003). This indicates that gender is a potential confounder of perceived odor, because it is not equally distributed and obviously it is not on the causal chain between perceived odor and the SWB measures. Many studies found that gender is a potential confounder [nfounder ,83.One way to control for confounding effects in analysis is by using a multivariable model , which assesses the hypothesized relationship, and at the same time, adjusting for the potential confounder, age. Consequently, ORs from our model were adjusted for age. The model also has two odor-related variables of interest and two binary demographic variables in order to compare with the literature. Regardless of which of the independent variables is a confounder or an exposure (variable of interest), the model treats all variables the same way .r = 0.78, n = 326, p < 2.2 × 10−16), as well as with SWEMWBS .We combined our measures of SWB to formulate a single measure and compared it with well-known, reliable, and tested SWB measures already in the literature. From the proportional odds regression conducted in this study, we hypothesized that SWB can be well represented by four measures . We used the total score (composite score) of the four measures as a subjective well-being representative (WB-Rep). The possible answers of each of the four questions are scored on a scale ranging from 0 to 4. The total composite scores of our WB-Rep, therefore, will be 0 to 16 points . Figure r = 0.81, n = 326, p < 2.2 × 10−16) is shown in Don’t know were replaced with the value “2” [A scatter plot between the total composite scores of SWB explanatory questions and SWB measures  in order to see if WB changed from season to season. A total of 55 people took the survey at least twice during the period of time from March 2016 to June 2017. In detail, thirty-six people (65%) took the survey twice, 14 people (26%) took the survey three times, and only 5 people (9%) took the survey four times. The following analysis was conducted on 134 responses. We divided the year to four quarters. The first quarter includes January, February, and March. The second includes April, May, and June. The third includes July, August, and September. The fourth includes October, November, and December. There were 38 responses in the first quarter, 41 in the second, 37 in the third, and 18 in the last quarter.Because the sample size in this longitudinal analysis was very small, the contingency table analysis assumption was violated. That is, the number of cell values (expected frequencies) that are less than five (<5) exceeded the conditional limit of 20% see . Therefoboxplots  show tha−6). However, there was not a statistically significant difference between communities in odor acceptability levels. North Denver and Greeley clearly stand out as the most affected communities by industrial odors represented by perceived odor levels, as shown by the Tukey Post Hoc Test results in It was hypothesized that the North Denver and Greeley well-being would be different (lower) than the other communities because of the impact of industrial odors. A one-way Analysis of Variance (ANOVA) was conducted to compare the industrial odor levels in the five communities. There was a statistically significant difference between the five communities in regard to perceived odor  = 7.02, P = 2 × 10Knowing the significant difference in industrial odor exposure (based on perceived odor levels), we need to answer the following question: are the overall well-being levels in North Denver and Greeley lower than in the other communities? One of the objectives of this work is to compare the well-being levels in the five communities .satisfaction nowadays, recent powerlessness, and recent sadness. Lastly, Pueblo’s satisfaction nowadays was also lower than Fort Lupton’s. The difference in well-being levels between North Denver and the other communities was not statistically significant.An ANOVA was used to investigate the differences in the levels of the nine well-being measures between the five communities. The differences were statistically significant in four well-being measures: satisfaction with standards of living  = 2.57, P = 0.04), satisfaction nowadays  = 4.92, P = 0.0007), powerlessness  = 3.104, P = 0.016), and sadness  = 3.798, P = 0.005). Since the ANOVA does not show which specific location (community) is different from the others, a Post Hoc Test, such as the Tukey Post Hoc Test, needs to be used. The results from the Tukey Post Hoc Test are presented in satisfaction with standard of living and satisfaction nowadays with perceived odor. However, from the ANOVA and Tukey Test analysis, the high levels of industrial odors in Greeley and North Denver did not lead to lower levels in the overall well-being in the two communities. In fact, the Tukey test implied that the overall well-being in North Denver is not different than the other communities (except Pueblo). One possibility is that some of the North Denver participants in this study were from neighborhoods that were more likely to be affected by industrial odors, such as Globeville and Elyria Swansea, while other participants were from neighborhoods that were less likely to be affected by industrial odors, such as Sloan Lake and Wheat Ridge. The analysis indicated that Pueblo’s overall well-being levels were lower than all other communities. This might require an urgent, more detailed study to investigate the reasons behind this low level of well-being.The proportional odds regression model showed a strong association between, for example, Odor pollution was identified as a top priority of the community of North Denver. Previous studies that investigated the impact of air pollution in North Denver focused on air pollution sources and adverse health effects, rather than impact on mental well-being. In this study, we investigated whether odors from industrial sources impair the SWB of residents in North Denver and four communities in Colorado. To evaluate SWB in the five communities, nine measures from an online survey were used. The nine measures were grouped into three aspects: evaluative well-being, positive hedonic well-being, and negative hedonic well-being. This classification was based on recent studies and is in good agreement with the results from the PCA analysis. To the best of our knowledge, this approach of evaluating SWB has not been used in previous odor exposure studies. For every SWB measure, an ordinal logistic regression  was used to quantify the relationship between that particular SWB measure and five independent variables. The five independent variables were employment, age, gender, perceived odor, and odor acceptability. The ordinal logistic regression we used showed that participants who were employed and female participants had higher levels of SWB. Almost all previous studies showed that unemployment had a strong negative impact on SWB. Our finding about the employment and SWB relationship was in good agreement with the literature. The impact of gender on SWB in the literature lacks consistency. However, our findings showed that female participants had higher levels of SWB. We also found that participants who were aged 45 or below had higher levels of recent depression, recent powerlessness, and recent sadness. Regarding the relationship between odor exposure and SWB, which is the aim of this study, we found that the participants who reported that the air is very fresh or odor is highly acceptable had higher levels of SWB. This association indicates that residents who live in areas exposed to strong industrial odors had lower levels of SWB. This lends support to previous findings in the literature, which indicated that unpleasant odors induced annoyance and general psychological stress, and reduced quality of life. While some studies showed that odor exposure  had an impact on mood state and ability to focus, our study did not show a significant association between odor exposure and negative hedonic well-being. Using the three aspects of EWB, +HWB, and −HWB in odor exposure studies is important and should not be overlooked. Depending on the odor exposure assessment method, the association between odor exposure could be with one or two SWB aspects. While the odor exposure assessed by odor acceptability seems to be associated with evaluative well-being, the odor exposure assessed by perceived odor was associated with both evaluative and hedonic well-being.We also found that four of our nine measures can be used to represent SWB in future studies. Two of those measures were evaluative SWB (satisfaction with how life turned out and satisfaction with standards of living) and the other two were positive hedonic SWB measures (satisfaction with life recently and recent enjoyment). The composite score of these four measures (named WB-Rep by us) showed good agreement with reliable, well-known, and tested SWB measures, namely ONS and SWEMWBS. Longitudinal analysis showed that evaluative satisfaction was slightly associated with seasonality. Both satisfaction with how life turned out and satisfaction with standards of living slightly increased during the fourth quarter of the year (October to December).A comparison between the five communities showed that well-being levels in North Denver and Greeley were not significantly different than in Fort Collins or Fort Lupton. The comparison, however, showed that Pueblo had the lowest levels of well-being among all communities.


Supplemental Digital Content is available in the text The incidence of atrial fibrillation (AF) varies from 5.4% to 47.1% in patients with mitral annulus calcification (MAC). We conducted a systematic review and meta-analysis on the association between MAC and AF, as well as the relation between MAC and major cardiac adverse events (MACEs) in AF patients.We conducted comprehensive search for literature on associations between MAC and AF using the following databases: MEDLINE, PubMed, Embase, and the Web of Science. The pooled odds ratio (OR) or relative risk and the corresponding 95% confidence intervals (CIs) were calculated to assess the relationship between MAC and AF, as well as the rates of MACEs in AF patients with or without MAC.P = .000). And the pooled analysis demonstrated a statistically significant increased risk of development of MACEs in AF patients with MAC .Thirteen studies met our eligibility criteria on associations between MAC and AF, including 6232 patients with MAC and 15,199 patients without MAC. Moreover, 5 studies met our eligibility criteria on the rates of MACEs in AF patients with or without MAC. The pooled analysis demonstrated a statistically significant increased risk of development of incident AF in patients with MAC than those without MAC (random effects OR: 2.34; 95% CI: 1.91, 2.85; MAC was independently associated with AF and AF patients with MAC were at greater risk for cardiovascular and cerebrovascular events. AF, associated with its complications such as stroke and myocardial infarction, generates a substantial burden in terms of costs, morbidity, and mortality. Given that patients with paroxysmal or asymptomatic AF and elderly people over 60 with other risk factors like hypertension, coronary heart disease, and diabetes may remain undiagnosed or underdiagnosed, the morbidity and the menace of AF may be underestimated. Therefore, further study of the disease is still particularly important.Atrial fibrillation (AF) is the most common cardiac arrhythmia but non-fatal in itself. It is initially thought to be an age-related process. However, many reported studies showed that MAC is associated with a variety of conditions including ventricular and atrial enlargement, congestive heart failure, structural and functional impairment of the aortic and mitral valve, endocarditis, conduction defects, carotid artery stenosis, coronary artery disease, and ischemic strokes. MAC is a predictor of incident AF and is independently associated with all-cause mortality and with cardiovascular morbidity and mortality in patients with AF. O’Neal et al also found that MAC was a predictor of incident AF in 6641 participants free of clinical cardiovascular disease and AF at baseline. However, currently, there is scant data on the relationship between MAC and cardiovascular morbidity and mortality in AF patients. Potpara et al studied 1056 nonvalvular AF patients and found that MAC correlated with all-cause death , and cardiovascular death . By contrast, Mazzone et al showed that MAC was an independent predictor of all-cause mortality in patients with sinus rhythm , but did not predict all-cause mortality in AF patients.Mitral annulus calcification (MAC) is characterized by calcium and lipid deposition in the fibrous support structure of the mitral valve.In the present study, we conducted a systematic review and meta-analysis of observational cross-sectional, case-control, or cohort studies on MAC and AF to examine the association between MAC and AF, as well as the relation between MAC and major cardiac adverse events (MACEs) in AF patients.22.1 A comprehensive search was conducted independently by 2 reviewers (YML and XYL) for literature on associations between MAC and AF using the following databases: MEDLINE, PubMed, Embase, and the Web of Science. To identify and retrieve all potentially relevant articles regarding this topic, we used the following terms in the search: . A manual search was also performed by analyzing the reference list of retrieved original publications and review articles.This study followed the protocols specified in the preferred reporting items for systematic reviews and meta-analysis statement.2.2Articles published between March 1, 1988 and March 1, 2018 were included. The current meta-analysis included observational cross-sectional, case-control, or cohort studies that allowed for assessment of associations between MAC and AF and the rates of MACEs in AF patients with or without MAC. AF was defined as electrocardiographic (ECG) recording of AF  from standard 12-lead ECG, Holter monitoring, and/or documented diagnosis of AF by International Classification of Diseases, Ninth Revision. MAC was assessed by transesophageal echocardiography or computed tomography scan. MACEs were defined as stroke, myocardial infarction, and all-cause death. Studies were excluded if they were conducted in specific populations: patients with thyroid and parathyroid diseases, chronic kidney diseases or immune diseases, and children. If multiple articles were published from the same cohort, the latest paper was chosen.2.3Data from relevant studies were extracted independently by 2 reviewers (YML and XYL) using a standard form. Any disagreement was discussed between the 2 reviewers or all authors to reach a consensus. The following data were extracted: title of study, name of first author, country of origin, publication year, number of participants in the MAC group and the control group, demographic data of participants, number of cases of AF, mean follow-up duration, and cases of MACEs. The status of AF includes prevalent AF (cases of AF at the time of inclusion) and incident AF (cases of developed AF in the follow-up period).2.4 The quality of cross-sectional study was assessed as described by Rostom et al. Furthermore, the risk of bias of the included studies was assessed with the following criterions:Newcastle–Ottawa quality assessment scale was used to evaluate each study in 3 domains: recruitment and selection of the participants, similarity and comparability between the groups, and ascertainment of the outcome of interest among cohort studies.(1)random sequence generation,(2)allocation concealment,(3)blinding of participants and personnel,(4)blinding of outcome assessment,(5)incomplete outcome data,(6)selective reporting, and(7)other biases.2.5All results and analyses were from previous published studies; thus, no ethical approval and patient consent are required.2.6Q- and I2- statistic. For Q statistic, substantial heterogeneity was defined as P > .10. The I2 statistic ranges from 0% to 100% . For studies with substantial heterogeneity (I2 > 50%), the random-effects model was used. If substantial heterogeneity was not present, the fixed-effects model was used to calculate the combined OR values. Otherwise, the random-effects model was used. In subgroup analysis, we compared the incidence of AF in MAC and non-MAC population between studies according to the population (community patients or inpatients) and other characteristics .The pooled odds ratio (OR) or relative risk and the corresponding 95% CIs were calculated to assess the relationship between MAC and AF, as well as the rates of MACEs in AF patients with or without MAC. Heterogeneity was assessed using the Chi-square test based on P < .05. Publication biases were assessed by both Begg test and Egger test. All statistical analysis was performed by using STATA software .We performed sensitivity analysis of included articles. All results in this analysis were considered as significant only with a 2-tailed 33.1The study flowchart is shown in Figure Moreover, 5 studies met our eligibility criteria on the rates of MACEs in AF patients with or without MAC Table .3.2P = .000). In subgroup analysis, pooled analysis also demonstrated a statistically significantly increased risk of development of incident AF in patients with MAC than those without MAC among both community populations  and inpatients  , sample size , or study design   . These findings strongly suggested a strong association of MAC with AF.3.3P = .009)  in 1 study and MACEs in 1 study. Four of the 5 studies revealed an increased risk of MACEs among AF patients with MAC versus those without MAC, with 3 of the 5 achieving statistical significance. The pooled analysis demonstrated a statistically significantly increased risk of development of MACEs in AF patients with MAC . Significant heterogeneity was still present among the community and patient population . Obvious heterogeneity was also found in studies on MAC and MACEs in AF patients . Sensitivity analysis revealed that the pooled ORs were stable in association between MAC and AF, while the pooled ORs on MAC and MACEs in AF patients were unstable because of the SPAF study  , and severe MAC is associated with increased all-cause and cardiovascular mortality.,32 Hence, MAC may not only be a risk factor for AF, but may also be an important prognostic predictor.MAC is a common echocardiographic finding in 9% of women and 3% of men older than 60 years. MAC can cause mild or moderate mitral regurgitation, which will result in volume and pressure overload in the left atrium, leading to left atrial enlargement and predisposing subjects to AF. MAC may also interrupt inter-atrial and intra-atrial conduction, leading to conduction system and atrial conduction defects, thus resulting in AF. Finally, MAC may be associated with other unappreciated risk factors, such as arterial stiffness or inflammation that could predispose patients to the development of AF.Left atrial enlargement is regarded as a key medium to the association between MAC and AF in the Strong Heart Study.,36 In these reports; however, MAC is considered a risk factor for coronary atherosclerosis, leading to adverse events. In patients with AF, the relationship between MAC and cerebrovascular diseases is still controversial. Randomized controlled studies also showed increased stroke risk in patients with MAC; AF was observed in Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators  while it was not significant in the stroke prevention in atrial fibrillation trial (SPAF). In our study, MAC in AF patients was directly related to cardiovascular and cerebrovascular adverse events. It is noteworthy that MAC itself could serve as a nidus for thrombus formation.MAC is also reported to be related to more cardiovascular events. For patients with MAC, clinicians should take measures to prevent AF and to reduce the burden of adverse outcomes if AF is apparent. MAC patients prone to AF may need more reasonable rhythm control strategies, while patients already with complicated AF may need more rigorous anticoagulation regimens. Additionally, considering the prognostic value of MAC in AF ablation and TAVI, MAC is a potential preoperative and post-operative evaluative factor.These findings of our study have important clinical significance. MAC not only predicts AF development but its presence infers an increased risk of adverse cardiovascular outcomes among those who already have the arrhythmia. which may explain the instability of the results. According to sensitivity analysis on studies on MAC and MACEs in AF, the study by SPAF was the key contributor to the instability of the pooled ORs. As it met the eligibility criteria, we did not remove this study. In addition, as this study was a study-level meta-analysis, due to the lack of patient-level data, inherent clinical heterogeneity among trials should be taken into consideration in the interpretation of our findings. Moreover, due to limited data, further stratified analysis was unavailable. Therefore, the study of MAC and AF still needs further research in subgroups of different individuals and age groups, and also requires dynamic observation in single population.Meanwhile, our study has several limitations. First and foremost, we observed substantial heterogeneity in the included studies. The clinical features of the population may be the main reason for the heterogeneity. For example, community populations or patients, different ages, different races, and other factors may all contribute to heterogeneity. Only 5 studies conducted research in the community population, and the age span was also large, from 17 to 103 years. Subgroup analysis based on community populations showed that AF was highly prevalent in the MAC population and heterogeneity declined sharply. Meanwhile, through sensitivity analysis, we found that the pooled ORs were not stable because the large sample size and the high prevalence of AF (78.2%) in the study by Dittrich et al,In conclusion, the present article indicates that MAC is independent predictor of AF patients. A general consideration emerges from this analysis concerning the identification of MAC. MAC is often considered a trivial finding and is not worth reporting. Our analysis strongly suggests that this is not the case and that evidence of MAC should be highlighted, especially in patients with AF. According to the severity of MAC, it is particularly important to further explore risk stratification of AF by MAC.Conceptualization: Yimin Li.Data curation: Yimin Li, Xiangyu Li.Formal analysis: Yimin Li.Methodology: Zhiping Lu.Project administration: Zhiping Lu.Resources: Zhiping Lu.Software: Zhiping Lu, Xiangyu Li.Validation: Xiangyu Li.Visualization: Xiangyu Li.Writing – original draft: Yimin Li.Writing – review and editing: Jin Huang, Qinghua Wu.


The aim of this study was to compare the effects of supervised combined physical training and unsupervised physician-prescribed regular exercise on the functional capacity and quality of life of heart failure patients. n = 17) and nontrained group (n = 11). All patients were submitted to clinical evaluation, transthoracic echocardiography, the Cooper walk test, and a Quality of Life questionnaire before and after a 12-week study protocol. Categorical variables were expressed as proportions and compared with the chi-square test. Two-way ANOVA was performed to compare the continuous variables considering the cofactor groups and time of intervention, and Pearson correlation tests were conducted for the associations in the same group.  This is a longitudinal prospective study composed of 28 consecutive heart failure with reduced ejection fraction patients randomly divided into two age- and gender-matched groups: trained group (p < 0.05). There was time and group interaction for improvement in the quality of life in the trained group.  No significant differences between groups were found at baseline. At the end of the protocol, there were improvements in the functional capacity and ejection fraction of the trained group in relation to the nontrained group ( In patients with heart failure with reduced ejection fraction, supervised combined physical training improved exercise tolerance and quality of life compared with the unsupervised regular exercise prescribed in routine medical consultations. Left ventricular systolic function was improved with supervised physical training. Heart failure (HF) is a pathological state in which an abnormality of cardiac function is responsible for failure of the heart to pump blood at a rate commensurate with the requirements of the metabolizing tissues or to do so only from an elevated filling pressure .Despite advances in the treatment of HF, its mortality and morbidity are still alarming . In addiIt has already been established in the literature that regular physical exercise (PE) can act favorably in several aspects: higher exercise tolerance, improvement in NYHA functional class, increased oxygen consumption at peak and at anaerobic threshold, and quality of life –8. HowevBecause of the beneficial effects of exercise on several aspects of heart failure outcome, it has been routinely prescribed to patients with HF in cardiology consultations –10. HoweREF) and to correlate these findings with clinical and echocardiographic variables.The aim of this study was to compare the effects of a supervised CPT and unsupervised physician-prescribed regular exercise on the FC and QOL of patients with HF and reduced ejection fraction  statement, as reported in n = 17: all patients were submitted to 12 weeks of CPT supervised three times a week by the same physical educator. The CPT program consisted of moderate-intensity aerobic exercise (50 to 65% peak VO2), complemented by moderate-intensity resistance exercise , which included the main muscle groups: biceps, triceps, quadriceps, hamstrings, and gastrocnemius. The prescription of CPT was individualized. The frequency considered as attendance of the supervised exercise sessions was 80%.TG, n = 11: patients were prescribed only regular exercise, at least three times a week, according to American Society guidelines for HF10, and did not take part in the supervised CPT program.NTG, The patients were divided into two groups matched for age and gender: trained group (TG) and nontrained group (NTG). Random allocation of patients was performed using computer-generated random numbers. Initially, 17 patients were included in each group; however, five patients of the NTG discontinued the study and one patient of the NTG died before undergoing the last evaluations. There was no loss to follow-up in the TG.NCT02571270).This study was conducted in accordance with human research ethics standards and was approved by the Ethics Committee of São Paulo State University (UNESP) Medical School (protocol no. 19683313.5.0000.5411). The study was also registered in the ClinicalTrials.gov registry  and metabolic equivalents (METs) [Physical evaluation includes anthropometric measurements, body composition, and the Cooper walk test with measurement of relative oxygen consumption (VOs (METs) . The exaTransthoracic echocardiography evaluates systolic and diastolic function according to recent guidelines from the American Society of Echocardiography . The exaQuality of life assessment is performed using the “Medical Outcomes Study 36-Item Short-Form Health Survey” (SF-36) . The patAll patients were submitted to the following evaluations at the beginning and end of the protocol:p < 0.05.Continuous variables were expressed as means and standard deviations, or medians and interquartile ranges. Categorical variables were expressed as proportions and compared with the chi-square test. Two-way ANOVA was performed to compare the continuous variables considering the cofactor groups and time of intervention, and Pearson correlation tests were conducted for the associations in the same group. The level of significance was set at p=0.022). The groups were similar as to the prescribed drug therapy, which included angiotensin-converting enzyme (ACE) inhibitors (p=0.31), aldosterone inhibitors (p=0.61), angiotensin II receptor blockers (ARBs) (p=0.39), beta-blockers (p=0.33), digitalis (p=0.80), and diuretics (p=0.25).The study included 17 patients in the TG and 11 patients in the NTG. The exercise of the TG was supervised by a physical educator in all patients, 3 times a week. p=0.029). There was no change in diastolic function assessed by tissue Doppler imaging and left atrial volume index.2 (METS) in the TG compared with that in the NTG at the end of the protocol (p=0.002). There was no interaction between time and group (p=0.27) for this increase in VO2.p < 0.001), role-physical (p=0.017), vitality (p=0.011), and mental health (p < 0.001). There was a significant difference between groups at the end of the protocol in social functioning (p < 0.001) and role-emotional (p < 0.001). There was a difference in the time of the protocol in the TG in the dimension bodily pain (p < 0.001).The results of the QOL questionnaire are presented in 2 in METs, and the QOL questionnaire in the following dimensions: vitality , social functioning , and role-emotional .At the end of the protocol, the TG showed a significant association between FC, assessed by peak VOThere was no Pearson correlation with improvement in left ventricular systolic function and FC and QOL.REF. Although there is controversy regarding the mechanisms underlying the improvement in exercise tolerance and quality of life in these patients, our study has shown that CPT improved FC and QOL independently of any change in either left ventricular diastolic or systolic function.Regular PE is beneficial for patients with HFAt baseline, the TG and NTG were quite homogeneous, without significant differences in age, gender, ejection fraction, and optimized drug therapy.Regarding the echocardiographic variables, only the LV ejection fraction in the TG showed a significant improvement at the end of the study. The mechanisms implied in this effect were not investigated in the present study. However, it is reasonable to assume that exercise-induced vasodilation might have a role by reducing the cardiac afterload and consequently increasing cardiac output and ejection fraction , 14–26. The mechanisms involved in the improvement in FC and QOL by exercise training are not well established. The available literature suggests that peripheral mechanisms, such as improved oxygen extraction in the active skeletal muscles, vasodilation promoted by increased nitric oxide synthesis, and attenuation of inflammatory response, may be responsible for greater exercise tolerance –17.p=0.022) suggested a beneficial effect of CPT. Additionally, the social effect of the CPT probably contributed to the improvement in QOL and perception of symptoms.The significant improvement of subjective sensation of dyspnea in the TG  was more marked than in most previous studies –19 and sREF, supervised CPT plays an important role in improving exercise tolerance and quality of life compared with the unsupervised regular exercise prescribed in routine medical consultations. We also found an improvement in systolic cardiac function as assessed by transthoracic echocardiography.In patients with HF


Spirulina (Arthrospira) maxima has shown beneficial effects such as being anti-dyslipidemic, antiviral, antioxidant and antihypertensive. However, there are few and limited clinical studies. (2) Methods: a prospective, randomized, parallel pilot study of 4.5 g administration of Spirulinamaxima or placebo for 12 weeks in 16 patients with systemic arterial hypertension (SAH) undergoing treatment with angiotensin-converting enzyme (ACE) inhibitors was performed to assess the effects on endothelial damage and oxidative stress indicators. The blood levels of sICAM-1, sVCAM-1, endothelin-1, and sE-selectin were quantified; the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and concentrations of reduced glutathione, oxidized glutathione, and thiobarbituric acid reactive substances, were also quantified before and after the treatment period. (3) Results: There were statistically significant (p < 0.05) decreases in systolic blood pressure, sVCAM-1, sE-selectin and endothelin-1 levels, and increases in glutathione peroxidase activity and oxidized glutathione levels. (4) Conclusion: The effects found in the present study agree with antihypertensive and antioxidant effects previously reported for Spirulina maxima. However, this is the first report about the effects on indicators of endothelial damage. More research in this field is necessary to gain an insight into the effects of Spirulina on these indicators.(1) Background:  Systemic arterial hypertension (SAH) is a syndrome of multiple etiology characterized by the persistent elevation of blood pressure levels as a response to the increase in peripheral vascular resistance resulting in systemic vascular damage . CardiovThe vascular tone depends on equilibrium of the action of vasoconstrictor and vasodilator systems and the capacity of the vascular smooth muscle response. In normotensive subjects, the vasodilator system predominates, whereas in subjects with hypertension it is the vasoconstrictor system . High anTo prevent the progression of the disease or acute and chronic complications, maintaining an adequate quality of life and reducing mortality are treatment goals for SAH. In this way, angiotensin-converting enzyme (ACE) inhibitors have shown that they have effects on the two pathophysiological mechanisms. Enalapril, zofenopril and perindopril have demonstrated their effects decreasing the oxidative stress indicator molecules ,19, whilIn hypertension, an increase in reactive oxygen species (ROS) due to a decrease in the bioavailability of endothelial nitric oxide synthase with subsequent decoupling in the production of nitric oxide (NO) has been observed as well as its interaction with other molecules generating radical peroxynitrite, which has been implicated in endothelial damage . The lowSpirulina maxima (SM) has been recognized as GRAS  food by the Food and Drug Administration (FDA) and it has been shown to have several biological effects, which have been demonstrated in some clinical investigations. Thus, there are clinical studies carried out in HIV-1 seropositive subjects [subjects ,25, withsubjects , chronicsubjects , allergisubjects , heavy msubjects , and hypp > 0.05)  diagram is shown in  > 0.05) . There wp > 0.05).Placebo group: 7 women and one man; for SM group, 6 women and two men. BMI, Body Mass Index; HR, Heart Rate; RR, Respiratory Rate; SBP, Systolic Blood Pressure; DBP, Diastolic Blood Pressure; SAH, Systemic Arterial Hypertension; CHAL , Quality of life questionnaire in hypertension. No statistical changes were found in both groups . Regarding the diastolic blood pressure, no statistically significant changes were observed throughout the treatment.p = 0.002) was observed in the SM group when compared with that of the placebo group. With respect to the levels of sICAM-1, no significant changes were observed between groups (p > 0.05) after the 12-week follow-up period. Regarding E-selectin levels at the end of the treatment, SM group showed a significantly lower value (p = 0.007) with respect to that of the placebo group. Finally, endothelin-1 showed a significantly lower value (p < 0.0002) in the group treated with SM when compared to that of the placebo group . GR activity was lower in the placebo group after intervention (p = 0.0156), and GPx activity was increased in SM group after treatment (p = 0.0234). GSSG (Oxidized Glutathione) concentrations were higher and statistically significant in SM group compared to placebo group before intervention (p = 0.041), and after treatment period (p = 0.0002); furthermore, after intervention in the SM group, GSSG levels increased (p = 0.0156). No significant differences were found in GSH (Reduced Glutathione) and TBARS (Thiobarbituric Acid Reactive Substances) concentration (p > 0.05).p > 0.05) or at the end of the intervention period for 12 weeks. The scores for the end of treatment were 24.13 ± 4.72 for the group treated with placebo and 18.75 ± 1.71 for the group treated with SM.No statistically different changes were observed in the CHAL questionnaire before starting treatment with placebo or SM , and in the group treated with SM all patients presented at least one adverse event, accounting for a total of 16 adverse events . There were no serious adverse events or with severity/intensity greater than Grade 2 and the evaluation of causality did not determine a certain relationship in the cases presented.p > 0.05).No statistically significant changes were observed in hematology, serum chemistry, urine analysis nor electrocardiogram before and after intervention in groups that were assigned to receive placebo or SM  increase in NO concentrations mediated by the increase in endothelial nitric oxide synthase gene expression and, therefore, a decrease in vascular wall resistance with a decrease in mechanical stress to the blood vessel; and, (3) inhibition of the angiotensin-converting enzyme by the bioactive peptides, which would result in a decrease in the ligand of the AT-II (Angiotensin-II) receptor, with the consequent decrease in intracellular signaling cascades related to cell damage and, in addition, decrease in the mechanical stress induced by the angiotensin.The high and sustained figures of blood pressure result in the release of mechanisms that increase vascular remodeling and endothelial activation . The actSpirulina is administered [Spirulina.SM has been shown to have antioxidant properties in both in vivo and in vitro studies ,53,54,55nistered ,57. Likenistered . GSH/GSSSpirulina has been traditional since ancient times in some regions of the world, with many considering it a safe food. The FDA of the United States accepts it as a safe supplement/food. A review of the scientific literature and of the various clinical studies indicates the lack of information on the safety profile of SM; in 30 clinical studies conducted from the year of 1987 until 2016 there is no information on adverse events or adverse reactions to Spirulina. In the present study, adverse events did not have a causal relationship with the administration of SM.The consumption of Spirulina administration.The work was exploratory since there are no reports in the medical literature evaluating the effect of the administration of SM on indicators of activation and/or endothelial damage. The results obtained will allow the calculation of sample size, based on the different variables determined, to carry out a larger clinical study. For future investigations it will be appropriate to perform an endothelial function test by doppler ultrasound assay to quantify the endothelium response to An experimental prospective, pilot, parallel design, single blind, randomized, placebo-controlled study was conducted; the study was based on a screening evaluation, three follow-up visits and one final visit. Patients with stage 1–2 SAH, according to Official Mexican Standard, NOM-030-SSA2-1999 “For prevention, treatment, and control of arterial hypertension”, under stable treatment with ACE inhibitors  were included; medications were given by their physician at therapeutic and recommended doses. This clinical trial was carried out in accordance with the declaration of Helsinki and was approved by Centro Especializado en Diabetes, Obesidad y Prevención de Enfermedades Cardiovasculares, S.C. (CEDOPEC) Ethics Committee No. 7-08-2014, and by the Research Committee of the Faculty of Medicine, UNAM, Mexico.Inclusion criteria: patients who decided their voluntary participation, who understood the nature of the study and the procedures and the restrictions that involved the participation of the same, and patients older than 18 years.Exclusion criteria: uncontrolled, stage 3 or systolic isolated hypertension, patients without pharmacological treatment, smoking history, secondary hypertension, women under pregnancy or in lactation period or who planned to become pregnant during treatment period; presence of coronary or peripheral vascular disease, diagnosed through medical history and physical examination; transaminase levels 2–3 times higher than upper normal limit, creatinine levels up to 1.5 mg/dL in screening visit.The procedures were performed in screening, follow-up and final visits. The screening visit was carried out two weeks prior to patients’ randomization, informed consent was obtained, also demographical data, medical history, physical examination, blood pressure measurement, vital signs, electrocardiogram, and safety labs . If patients were eligible, they were randomized in visit 1.The following procedures were performed in visit 1: review for inclusion and exclusion criteria, concomitant drugs review, questionnaire for quality of life in hypertension, physical examination, vital signs, blood pressure measurement and blood sampling for baseline determination of endothelial damage indicators and oxidative stress status. Additionally, in this visit SM or placebo were dispensed according with the randomization list, in sufficient quantity for patients’ consumption at the established dose until the following visit. The follow up visits 2 and 3 were performed in weeks 4 and 8 after randomization; in these visits a review of concomitant medication, adverse events and physical examination, vital signs and blood pressure measurement was performed. The final visit was performed in week 12, and the following procedures were performed: physical examination, review for adverse events, questionnaire for quality of life in hypertension, safety labs , blood sampling for measuring endothelial damage indicators and antioxidant status, as well as an electrocardiogram. Once these procedures were completed, the clinical study was terminated for each patient who had complied with all the mentioned activities.The outcome measures were blood pressure levels, changes in endothelial damage indicators, antioxidant status and quality of life. The quality of life of patients with hypertension was assessed through the application of CHAL questionnaire, developed and modified in Spain by Roca-Cusachs . The queSafety and tolerability of SM or placebo was carried out through the presence and severity of adverse events, in accordance with the provisions of the Official Mexican Standard, NOM-220-SSA1-2016 “Installation and operation of Pharmacovigilance. Safety labs  and electrocardiogram performed in the screening visit and final visit by certified laboratory and interpreted by specialist physicians, according to their standard operating procedures.Patients were assigned to one of two treatments: SM or placebo. SM was at a dose of 4.5 g per day over a period of 12 weeks. The SM and placebo were provided by “Alimentos Esenciales para la Humanidad”  in sealed bags, labeled with the patients’ number and the amount required between each study visit. The placebo was identical to SM in its organoleptic characteristics. In addition, a follow-up diary was provided for the ambulatory administration of SM or placebo, where the adverse events during treatment were recorded and the participants registered the antihypertensive treatment indicated by their treating physician. This was done in order to verify the adherence to treatment and consumption of SM or placebo.After blood sampling in weeks 0 and 12, the samples were centrifuged at 4500 rpm to obtain the blood plasma, which was transferred to two polypropylene cryotubes duly labeled and stored at −78 °C under controlled conditions in ultrafreezer  until the moment of their analyses. The sample analyses were performed in a period of 30 days after blood sampling. All the reactive were purchased from Sigma-Aldrich Química, S. de RL. de CV . All spectrophotometric measurements were performed using a Genesys-10 uv spectrophotometer . Biochemical measurements were performed in duplicate with a coefficient of variation <0.05.The activity of CAT was performed by the method proposed by Aebi , which iTotal activity of the SOD enzyme was based on the experiments carried out by Kono . The metThe activity of GR was based on the consumption of NADPH. The results were expressed as moles of NADPH/mL plasma per minute. The disappearance of NADPH was recorded spectrophotometrically at a wavelength of 340 nm .Glutathione peroxidase activity was based on the method developed by Paglia and Valentine where the moles of oxidized NADPH per minute/mL of plasma are determined. This technique is based on the ability of peroxidase to reduce organic peroxides through the oxidation of two GSH molecules. The oxidation of NADPH was monitored at 340 nm .Measurement of GSH was based on the Ellman reaction, a plasma sample reacted with dinitrobenzene in the presence of phosphate buffer. A standard curve was made with known concentrations of glutathione, the results being expressed as mg of GSH/mL of plasma. The spectrophotometric reading was performed at 412 nm. For the case of GSSG, the samples were treated with 4-vinylpyridine, to precipitate the reduced glutathione, leaving only the oxidized glutathione as substrate for the assay.The final products of the peroxidation were evaluated as TBARS as described by Torres-Durán et al. . A standTM microplate reader .Measurements of the soluble forms of sICAM-1, sVCAM-1 and sE-selectin, as well as levels of endothelin-1, were carried out by commercial ELISA kits  following the manufacturer’s instructions. All ELISA determinations were performed using an EPOCHp < 0.05 as statistically significant.The statistical analysis was performed with SPSS software v.11; a t for unpaired groups and Mann-Whitney tests were carried out considering a Spirulina. This is the first clinical study that demonstrates the effect of cyanobacteria on indicators of endothelial damage, which makes it necessary to perform clinical studies of greater proportions to have sufficient statistical power to support the findings of this research.The results obtained demonstrate that the administration of SM has an add-on effect in the treatment of arterial hypertension; it has an effect on the decrease of indicators of endothelial activation damage ; as well as increasing antioxidant defenses  supporting previous research on the antioxidant properties of


Objective: This study investigates excessive mind wandering (MW) in adult ADHD using a new scale: the Mind Excessively Wandering Scale (MEWS). Method: Data from two studies of adult ADHD was used in assessing the psychometric properties of the MEWS. Case-control differences in MW, the association with ADHD symptoms, and the contribution to functional impairment were investigated. Results: The MEWS functioned well as a brief measure of excessive MW in adult ADHD, showing good internal consistency (α > .9), and high sensitivity (.9) and specificity (.9) for the ADHD diagnosis, comparable with that of existing ADHD symptom rating scales. Elevated levels of MW were found in adults with ADHD, which contributed to impairment independently of core ADHD symptom dimensions. Conclusion: Findings suggest excessive MW is a common co-occurring feature of adult ADHD that has specific implications for the functional impairments experienced. The MEWS has potential utility as a screening tool in clinical practice to assist diagnostic assessment. The diagnosis of ADHD is based mainly on descriptions of behaviors that reflect inattention, hyperactivity, and impulsivity. Yet older children, adolescents, and adults frequently report phenomenological descriptions of internal subjective experiences that may underlie the behavioral changes seen in ADHD. Characteristic descriptions of the mental state in ADHD include reports of ceaseless mental activity, thoughts that are constantly on the go, or a mind constantly full of thoughts. Thoughts are experienced as uncontrolled, with multiple occurring at the same time. Another common description is of short-lived thoughts that flit from one thing to another, jumping between different ideas . Here, wMW is conceptualized as periods in time when attention and the contents of thoughts shift away from external sources and/or ongoing tasks to unrelated internal thoughts or feelings . It is aExcessive spontaneous MW has been associated with functional impairment and implicated in psychopathologies such as ADHD . Mental Using an experience sampling technique to measure on- and off-task thoughts during an attention task, ADHD symptomatology has also been shown to positively correlate with both the frequency of MW and the lack of awareness of engaging in MW . A sub-cCollectively, these findings suggest that adults with ADHD are highly susceptible to excessive spontaneous MW and may have a core difficulty controlling spontaneous thoughts unrelated to the current context. Excessive MW could therefore underlie many of the symptoms and impairments that characterize the disorder. To explore the role that MW may play in the pathogenesis of ADHD, as well as its potential role in diagnosis, our research group developed the Mind Excessively Wandering Scale  participated in the MIRIAD project. There were no significant differences between groups for age or IQ  project, a longitudinal case-control study of emotional lability (EL) and neuropsychological functioning in adult men with ADHD with no co-occurring comorbidities . Forty-or IQ see . ADHD par IQ see .As the MEWS was developed after the MIRIAD project began, only a subset of the ADHD cases and controls provided MEWS data. At study entry (baseline), 25 cases and 24 controls completed the MEWS. Follow-up assessments completed approximately 9 months after baseline provided data on 18 cases and 18 controls at both time points. In addition, six cases and 18 controls provided MEWS data at follow-up assessment alone. Of the 18 ADHD cases with data at both time points, 16 were treated with methylphenidate and one with atomoxetine at follow-up, initiated by local services and not following a specific protocol. Ethical approval for this study was obtained from the Joint Research Ethics Committee of the Institute of Psychiatry and SLaM.M age = 33.52 years, SD = 10.26 years) and 30 healthy controls . Groups did not significantly differ on age, sex, or IQ (see Participants were from the OCEAN (Oils and Cognitive Effects in Adult ADHD Neurodevelopment) project, a study investigating the relationship of omega-3 dietary supplementation  to cognitive and electrophysiological measures in adults with ADHD. Participants were aged between 18 and 65 years. The sample consisted of 81 adults with ADHD , 79 cases and 29 controls provided MEWS data. Two separate follow-up assessments of the ADHD cases took place, 3 months (Time 2) and 6 months (Time 3) after baseline. At Time 2 and Time 3, 79 and 55 ADHD cases provided MEWS data, respectively. Ethical approval for the study was granted by the National Research Ethics Service (NRES) Committee London.Diagnostic and Statistical Manual of Mental Disorders  was measured using the Affective Lability Scale–Short Form ALS-SF; , which mFunctional impairment across major life domains  was measured using the Weiss Functional Impairment Rating Scale–Self-Report WFIRS-S; .MW was measured using the newly created MEWS see . This puMean values for each rating scale and subscale were used as summary measures. The raw data and square-root transformations were used in analysis, and parametric and non-parametric tests were used as appropriate.t tests and Mann–Whitney U tests to investigate case-control differences. Receiver operating characteristic (ROC) analysis was used to examine diagnostic accuracy and the optimal cut-off point of the measure.Principal components analysis (PCA) with varimax rotation was conducted to examine the factor structure of the MEWS. Cronbach’s alpha was used as a measure of reliability to assess internal consistency and Pearson’s correlation coefficient was used to analyze test–retest reliability of the scale. Construct validity was assessed with independent z value threshold for affection status corresponding to 3.4% prevalence of ADHD in adults . Factor loadings were greater than .7, with the exception of Item 14 (.51). SD = 3.3 months) for cases and 9.5 months (SD = 4.0 months) for controls between baseline and follow-up. Test–retest reliability was significant for the whole sample , and for both cases  and controls .There was a mean interval of 9.7 months (t(47) = −7.83, p < .0001, comparable with that found for the other rating scales of ADHD symptom domains: inattention, t(73.07) = −14.58, p < .0001; hyperactivity/impulsivity, t(85) = −11.40, p < .0001; emotional lability, U = 168.5, z = −6.53, p < .0001 (t(86) = −13.08, p < .0001, as well as for each domain of impairment, t range = −5.78-11.40, p < .0001, for impairment in family life, work, school, life-skills, self-concept, social problems, and risk taking. Similar results were found at follow-up .Case-control comparisons at baseline revealed significantly elevated ratings of MW in individuals with ADHD,  < .0001 . Particip < .0001) which, being close to 1, indicates excellent discriminant capacity of the MEWS. This was comparable with the AUC value of existing rating scales of ADHD symptom domains . A score of 15 or above provides the optimal balance of sensitivity (.88) and specificity (.88), suggesting a cut-off for disorder threshold .ROC analysis was used to examine the capacity of the scale to discriminate between cases and controls. Area under the curve (AUC) was .92 , hyperactivity/impulsivity , emotional lability , and impairment , as well as ADHD affection status . The strongest correlation was between MW and impairment , hyperactivity/impulsivity , emotional lability , and impairment  = 2.28, p = .04, between the baseline medication-free period  and follow-up .For the sub-sample with both baseline and follow-up data, the correlation of baseline to follow-up change scores for MW with change scores for the rating scale measures of ADHD symptoms and impairments revealed temporal covariance between the measures: positive correlations were found between change in MW and change in inattention (R2 = .824). The addition of MW as a predictor led to a significant increase in predictive power of the model (R2Δ = .024), with the variability accounted for by the model increasing to 84.9%, FΔ = 7.17, p = .01. This indicates that MW is having a small but significant effect beyond that accounted for by inattention and hyperactivity/impulsivity. Inattention carried the most importance in the model (β = .45), followed by MW (β = .31) and hyperactivity/impulsivity (β = .21). Only inattention and MW significantly contributed to the model .Data from 49 participants were used in regression analyses with the WFIRS-S total impairment score. Inattention and hyperactivity/impulsivity accounted for 82.4% of the variability in functional impairment  = 6.57, p < .02, and social problems, R2Δ = .137, FΔ = 4.50, p < .05. For the social problems domain, MW carried more importance in the model (β = .44) than inattention (β = −.42), but not hyperactivity/impulsivity (β = .50). Only MW and hyperactivity/impulsivity significantly contributed to the model . Interpretation of work and life-skills dimensions was not possible due to heteroskedasticity in the data.Within the ADHD group, MW had an independent effect on impairment in the domains of self-concept, The scree plot and eigenvalues suggested a one-factor solution with an eigenvalue of 9.44, accounting for 62.92% of the variance . All items loaded highly onto this factor . Internal consistency was high for all scales for both cases and controls , and MEWS scores showed satisfactory retest reliability across this time period .The mean interval between Time 1 and Time 3 was 6.4 months . This difference was comparable with that found for the other rating scales of ADHD symptom domains , as well as for each domain of impairment .Case-control comparisons revealed significantly elevated ratings of MW in individuals with ADHD (p < .0001). This was comparable with the AUC value of existing rating scales of ADHD symptom domains . A score of 15 on the MEWS provides the optimal balance of sensitivity (.90) and specificity .ROC curve analysis indicated that the MEWS successfully discriminated between cases and controls , hyperactivity/impulsivity , emotional lability , impairment , and ADHD affection status . The strongest correlation was between MW and impairment , hyperactivity/impulsivity , emotional lability , and impairment . MW and impairment showed the strongest relationship . The addition of MW as a predictor led to a significant increase in predictive power of the model (R2Δ = .076), with the variability accounted for by the model increasing to 78.9%, FΔ = 37.17, p < .0001. MW carried the most importance in the model (β = .49), followed by inattention (β = .29) and hyperactivity/impulsivity (β = .17). Only MW (p < .0001) and inattention (p = .002) significantly contributed to the model.Data from 108 participants were used in regression analysis with the WFIRS-S total impairment score. Inattention and hyperactivity/impulsivity accounted for 71.3% of the variability in functional impairment  = 24.79, p < .0001; self-concept, R2Δ = .10, FΔ = 9.72, p = .003; social problems, R2Δ = .10, FΔ = 9.92, p = .002; and risk taking, R2Δ = .09, FΔ = 9.37, p = .003. MW carried the most importance in the model for life-skills (β = .52), self-concept (β = .39), and social problems (β = .39), and was the only significant contributor to the model for the self-concept (p = .003) and social problems (p = .002) domains. Interpretation of the family and work domains was not possible due to heteroskedasticity in the data.Within the ADHD group, MW had an independent effect on impairment in life-skills, We report the psychometric properties and initial validation findings for a new self-report scale of excessive MW in adults with ADHD. Using two independent samples, we found that MEWS scores functioned extremely well as a measure of the mental phenomenon of MW in ADHD, with good reliability and high sensitivity and specificity for ADHD case-control differences. We found that elevated levels of MW (as indexed by the MEWS) in participants with ADHD were related to self-report measures of functional impairment. Furthermore, the contribution of MW to impairment was independent of the core ADHD symptoms of inattention and hyperactivity/impulsivity. These findings suggest that excessive MW is a characteristic feature of adult ADHD that has specific effects on impairment.Principal components analysis indicated a unidimensional structure to the scale and other psychometric properties of the MEWS were comparable with existing rating scales of ADHD core symptoms, including good internal consistency and test–retest reliability. The MEWS was able to differentiate between those with and without ADHD with high sensitivity and specificity of the scale, using a threshold score of 15. This is remarkable given that patients were selected for high ADHD symptoms and not specifically for subjective reports of internal thought processes as measured by the MEWS.In both studies, item total correlations with the full 15-item scale and factor loadings were high apart from Items 6 , 10 (I try to distract myself from my thoughts by doing something else or listening to music), and 14 . This is likely explained by the nature of these items, which refer to how individuals cope with MW or how it directly affects their functioning, as opposed to a description of the mental phenomenon. To investigate whether the scale could be shortened by dropping Items 6, 10, and 14 without reducing its sensitivity and specificity, we repeated the ROC analysis, finding the shorter 12-item scale had a sensitivity of .89 and specificity of .90 . Further analyses in larger data sets could be used to further refine the scale, but based on these data we recommend that future studies use the reduced 12-item scale.Our findings are in line with previous studies which report elevated levels of MW in ADHD compared with controls, whether measured using clinical rating scales  or experChange scores for MW also covaried with ADHD symptoms and impairments over time, indicating a close temporal relationship consistent with a potential causal role of MW in ADHD. The finding of significant pre–post treatment effects of methylphenidate in a subset of Study 1 participants raises the possibility that treatment effects on ADHD might be mediated by reductions in MW. However, we were unable to test specifically for treatment effects of methylphenidate because we did not randomize to treatment or include a placebo control arm.The link between MW and impairment was particularly strong, indicating the clinical importance of MW in adults with ADHD. Of specific interest was the finding that MW showed a main effect on impairment beyond the influence of inattention and hyperactivity/impulsivity and was overall the strongest predictor of impairment in Study 2. Investigating specific domains of impairment, MW was found to be an independent predictor of self-concept and social problems in both studies, and additionally life-skills and risk taking in Study 2. The reasons the MEWS is a particularly good predictor of impairment in ADHD are not well understood, but could be explained by both clinical and theoretical considerations. One possible explanation is that the scale items are rooted in qualitative accounts from adult ADHD patients of experiences of their mental state. When asked to describe the subjective experience of the flow of their thoughts, adults with ADHD repeatedly give descriptions of ceaseless, short-lived, and unfocused thoughts that flit from one topic to another . Such a not listen or lack awareness of social cues. MW may make it difficult to follow a single line of thought and interrupting others during conversations could be a strategy to avoid losing their train of thought. Behaviors such as these are likely to have negative effects on an individual’s social interactions.First, excessive MW may have a specific effect on functional outcomes due to the failure to deal with distraction and deficient mental processing of “task”relevant events. In social situations, an individual with excessive MW may miss verbal and non-verbal information and effectively Second, lack of attention paid to events due to one’s mind constantly being “on the go” in a non-focused way can also create difficulties with thinking through and planning activities, linked to forgetfulness and disorganization and leading to impairments in basic life-skills. Impaired self-concept may then arise as a bi-product of the effect of excessive MW on other domains of functioning, but could also be due to distress from the constant effort to focus or the experience of having a mind constantly full of unfocused distractible thoughts. Many patients report a sense of calm and relief when the flow of their thoughts becomes more focused and regulated following stimulants or other treatments for ADHD.Third, the connection between MW and risk-taking behavior is less obvious, but could be due to the impact of highly salient activities, which engage the attention of individuals, leading to a reduction of spontaneous MW and a sense of relief. For the same reasons, some patients with even severe levels of ADHD may excel at activities such as exciting/stimulating sports. Although there is as yet no direct evidence for this hypothesis, studies investigating default mode deactivation  and reacThese accounts of MW leading to impairment in ADHD remain speculative because of the lack of research on MW in ADHD. However, an increase in understanding of MW states in control participants provides a strong theoretical basis for the hypothesis that excessive MW may underlie many of the behavioral symptoms and impairments seen in ADHD. In healthy control samples, MW is associated with performance deficits that overlap with impairments seen in ADHD, including educational performance, driving accidents, and performance on cognitive tasks including errors of commission and RTV during sustained attention and inhibition tasks . Understd = .85 on ADHD symptoms compared with a treatment as usual group  was found to mediate the relationship between ADHD symptoms and detrimental forms of MW, suggesting that psychological treatments aimed at enhancing meta-awareness of MW, such as mindfulness-based interventions (MBIs), might ameliorate the negative consequences of MW in ADHD . Recent al group . Future Current screening tools for adult ADHD consist of rating scales for inattention and hyperactivity/impulsivity. Our findings suggest potential utility of the MEWS as an additional screening tool for adult ADHD in clinical practice, particularly as the MEWS is a strong predictor of impairment. Furthermore, as discussed above MW may also be measured more objectively using experience sampling methods in daily life or during experimental paradigms. Measures of MW may therefore assist in the accurate diagnosis of individuals based on their mental state rather than descriptions of behavior, which may be more subject to bias or influenced by an individual’s ability to develop compensatory behavioral strategies.However, currently we do not know the role that excessive MW, as measured by the MEWS, plays in other clinical disorders. For example, in depression depressive rumination represents another form of MW. Thus, the specificity of the MEWS across common mental health disorders needs to be explored. Therefore, we do not currently recommend the routine use of the MEWS to identify patients with ADHD until the scale has been comprehensively evaluated in other psychiatric disorders with overlapping clinical features, although high MEWS scores could be used to support the diagnosis. Investigation of the role of excessive MW in childhood and early adolescent ADHD is also recommended, including use of the scale in this population. Whether children and young adolescents would be able to conceptualize MW and reliably report on their mental state requires investigation.Some participants in Study 2 presented with co-occurring anxiety and depression, raising the possibility that MW might be linked to comorbid conditions. However, in Study 1 participants were free from co-occurring disorders , yet simIn relation to ADHD, a key question is whether MW differs conceptually from the inattentive symptoms currently used to define the disorder or whether the mental phenomenon of MW underlies the behavioral expression of inattention. As discussed above, it is feasible that measures of MW in ADHD are a more direct reflection of the neurobiology, leading to the inattentive symptoms of ADHD. Further work is required to evaluate the plausible hypothesis that aberrant regulation of DMN activity linked to excessive MW leads to ADHD symptoms and impairments. The study of MW has several potential advantages over behavioral inattention for research, because it may be measured using rating scales, as reported here, as well as experience sampling during daily life , or duriA fruitful next step in this research will be to take the MEWS into experimental paradigms. For example, an experimental trial of methylphenidate could be used to formally evaluate whether improvements in MW mediate improvements in ADHD symptoms and impairments, and to investigate the underlying neural mechanisms. Yet, currently, there are very little data that link rating scale measures of MW to experimentally derived measures in ADHD. Validation of MW in ADHD is therefore required across the various levels of measurement . We hypothesize that MW is a phenomenon that can be reliably measured, and it will be highly informative to see to what extent MEWS scores reflect TUTs measured during cognitive task performance in ADHD. It will also be advantageous to see how it relates to various cognitive measures such as omission and commission errors , and RTVThis research provides further insight into the mental phenomenon of MW in ADHD. We investigate a questionnaire-based measure of excessive MW recently developed in our research group. The MEWS was found to be a valid and reliable measure, with comparable sensitivity and specificity for case-control differences as existing rating scale measures of core ADHD symptoms currently used in clinical practice. The MEWS functioned extremely well for a brief 15-item measure and is potentially a useful measure to incorporate in future clinical and etiological research. MEWS scores were found to be a particularly good predictor of impairment, highlighting the clinical utility of the tool for diagnosis and treatment. Based on these findings, there is strong premise to view MW as a common co-occurring feature of adult ADHD with a specific effect on impairment, potentially explaining a variety of deficits not easily accounted for by the core symptom dimensions.Click here for additional data file.Supplemental material, Mindwandering_and_ADHD_SupplementaryMaterial_JAD for Validation of the Mind Excessively Wandering Scale and the Relationship of Mind Wandering to Impairment in Adult ADHD by Florence D. Mowlem, Caroline Skirrow, Peter Reid, Stefanos Maltezos, Simrit K. Nijjar, Andrew Merwood, Edward Barker, Ruth Cooper, Jonna Kuntsi and Philip Asherson in Journal of Attention Disorders


Background and objectives: Despite its wide use in thoracic procedures, to date, few studies have assessed the effectiveness of paravertebral block (PVB) in laparoscopic cholecystectomy (LC) in an adult population. In these studies, PVB was performed bilaterally using nerve stimulator guidance. To the best of our knowledge, the effectiveness of unilateral preoperative and postoperative ultrasound-guided PVB has not been evaluated in patients undergoing elective LC. The aim of this study was to evaluate the efficacy of single-dose unilateral paravertebral block (PVB) in patients undergoing laparoscopic cholecystectomy (LC) under general anesthesia. Materials and Methods: Patients undergoing LC were randomly separated into control, preoperative block, and postoperative block groups. PVB was performed unilaterally using bupivacaine under ultrasound guidance. Postoperative pain within the first 24 h, side effects, intraoperative opioid and postoperative analgesic requirements were noted. Evaluation was made of a total of 90 patients  with a mean age of 45.78 ± 14.0 years . Results: Opioid and additional analgesic needs and nausea/vomiting rates were significantly reduced in the preoperative block group compared to the other groups (p < 0.05). Visual Analog Scale (VAS) scores were significantly lower in the preoperative and postoperative block groups compared to the control group . When the VAS scores were compared between the preoperative and postoperative block groups, a significant difference in favor of the preoperative group was observed in terms of the zero minute-, 1st and 2nd h assessments . Conclusions: Ultrasound-guided PVB is a useful and safe approach for pain management during and after LC. Preoperative block can also reduce the rate of requirement for intraoperative opioid and postoperative analgesia. The mechanism of pain after laparoscopic procedures is thought to be multifactorial. The main causes of pain after laparoscopic cholecystectomy (LC) include pain arising from the incision site, pneumoperitoneum and cholecystectomy . To dateParavertebral block, which was first described in the early 20th century, is the administration of local anesthetic into the wedge-shaped space on the antero-lateral thoracic spine in order to provide abdominal analgesia . The appParavertebral block can be performed using ultrasound-guided, stimulation-guided or landmark-based approaches, and can be applied before or after surgery. To obtain an effective analgesic effect, some authors perform multiple injections ,6,7.Despite its wide use in thoracic procedures, to date, few studies have assessed the effectiveness of PVB in LC in an adult population ,8. In thThe study included 90 patients who underwent LC between January 2018 and June 2018 at Kırıkkale University Medical Faculty Hospital. The patients included were aged 18–75 years, with an American Society of Anesthesiologists Patient Classification (ASA) score of ASA I–III. Using the sealed envelope method, patients were randomly and equally assigned to three groups. A record was made of their demographic characteristics, including age, gender, height, and weight, and ASA category, operation duration, and perioperative opioid requirement. The study was approved by the Local Ethics Committee of the hospital (decision no.: 2018-15/02). Informed consent was obtained from all participants.Patients who were planned for elective cholecystectomy due to cholelithiasis were included. Patients with acute cholecystitis, acute cholangitis, jaundice, and biliary colic symptoms were excluded. Patients with local infections at the PVB site, hypersensitivity to the drugs used for the PVB, coagulopathy, spinal/paravertebral deformities, morbid obesity, and severe aortic stenosis were excluded from the study ,6,7. Then = 30). PVB was applied preoperatively to patients in Group 2 (n = 30) under sedation with 0.03–0.05 mg/kg midazolam on admission to the operating room, just before the operation, and this was followed by general anesthesia. In Group 3 (n = 30), PVB was applied postoperatively to the patients while still in the operating room and under general anesthesia immediately after surgery. The anesthesia was terminated after PVB in this group.The standard general anesthesia protocol required for LC was applied to all patients included in the study. No additional procedure except general anesthesia was applied to the patients in Group 1  was placed between two transverse processes sagittally on the paramedian surface, then the transverse processes, superior costotransverse ligament (SCL) and pleura were identified at the level of the thoracic 7 vertebra. The skin and subcutaneous tissue were infiltrated with 2% lidocaine. An 18-gauge 50 mm needle  was advanced under the US probe using the in-plane technique. After passing through the SCL and reaching the paravertebral space, an aspiration was performed to check for air and/or blood. After negative aspiration, 20 mL of 0.5% bupivacaine was injected. The pleural collapse due to the injected local anesthetic volume was observed. An example image is shown in The required opioid dose during the operation was noted and set according to the depth of the general anesthesia and increased sympathetic activity, i.e., hypertension, and/or tachycardia. The operation duration was accepted as the period between the beginning of the operation and the last skin suture.The visual analog scale (VAS) for pain, with 0 being the least and 10 being the worst pain during rest, was recorded at 0–1–2–6–12 and 24 h postoperatively.Possible complications such as hypotension due to sympathetic blockade, nausea and vomiting, and urinary retention during the first 24 h postoperatively were noted. Patients were also evaluated for local complications such as nerve root injury, infection, hematoma, vascular puncture, and pleural puncture. The subjects were treated with intra-muscular (im) 50 mg of dexketoprofen trometamol in cases where the VAS score was ≥4, and if the pain persisted, an additional 50 mg meperidine was administered intra-muscularly. All additional analgesic requirements were noted.n) and percentage (%). Numerical variables were compared using One-Way Anova or Kruskal Wallis tests after checking the normal distribution. Post hoc analyses were performed to determine from which group the difference originated. Categorical variables were compared using the Chi Square test or Fisher’s Exact test. A value of p < 0.05 was accepted as statistically significant.The SPSS  version 20.0 was used for the statistical analysis of the data. Data were stated as mean ± standard deviation (SD), median (25–75%) values or number . Intraoperative opioid requirement, extra analgesic requirement, and nausea/vomiting rates were significantly lower in the preoperative anesthesia group compared to the other groups. Extra analgesic requirement and nausea/vomiting rates were significantly lower in both the preoperative and the postoperative block groups compared to the control group. A total of 90 patients  with a mean age of 45.78 ± 14.0 years  were included in this study. The clinical and demographic features of the groups are summarized in p < 0.05 for all). The VAS scores for each evaluation were significantly lower in the preoperative and postoperative block groups compared to the control group . When the VAS scores were compared between the preoperative and postoperative block groups, there was a significant difference in terms of the 0, 1 and 2-h assessments . No significant difference was observed between the 6, 12, and 24-h assessments.Comparisons of the VAS scores of the groups just after the operation (0), then at the 1st, 2nd, 6th, 12th, and 24th h are shown in The aim of this study was to investigate the effectiveness of the ultrasound-guided one-point PVB at the thoracic 7 vertebrae level in reducing postoperative pain in patients undergoing LC and to compare the outcomes of the preoperative and postoperative timing of this procedure on pain and intraoperative opioid requirement. The main findings can be summarized as follows: the patients treated with preoperative PVB required no opioids during surgery, and the analgesic effect of preoperative PVB was superior to that of postoperative PVB in the first two hours after surgery. Patients in both the preoperative and the postoperative groups requested less additional analgesia and reported less nausea after surgery. There have been previous reports of the additional analgesic effects of PVB when combined with general anesthesia. Furthermore, the preoperative and postoperative applications of PVB in LC were also compared. To the best of our knowledge, there has been no previous study which has compared ultrasound-guided unilateral preoperative and postoperative PVB and a control group in patients undergoing LC.Paravertebral block allows for the blockage of ipsilateral, segmental, somatic, and sympathetic nerves. It can be performed using single- or multiple-level injection techniques, unilaterally or bilaterally. To date, clinicians have used different guidance for PVB injections. Initially, PVB injections were performed using a landmark-based conventional technique, but in recent years, the nerve stimulation technique and ultrasound-guided PVB techniques have been performed successfully for pain management after various thoracic and abdominal surgeries ,6,7,8,9.In a study by Cowie et al. , ultrasoIn the study by Naja et al., bilateral nerve stimulator-guided PVB with 0.3 mL/kg of a local anesthetic mixture containing lidocaine, bupivacaine, fentanyl and clonidine was applied at T5-6 level to patients undergoing LC. In the first 72 h postoperatively, improved pain relief was reported together with the use of less additional analgesia and a lower rate of complications such as nausea compared to the control group . In a prThe main causes of pain after LC are thought to be pain arising from the incision site, pneumoperitoneum, and cholecystectomy. Factors such as diaphragmatic stretching, residual gas volume, type of gas, increased pressure due to pneumoperitoneum, the temperature of the insufflated gas, the length of the operation, and the rate of carbon dioxide insufflation might contribute to the pain after LC . In the In another study by Naja et al., the authors compared the effectiveness of bilateral PVB applied preoperatively and postoperatively in 60 patients undergoing LC . The PVBVascular puncture, hypotension, epidural or intratechal spread, pleural puncture and pneumothorax have been reported as possible complications during thoracic and lumbar PVB using a landmark technique facilitated by nerve stimulation. There has been reported to be an increased risk of vascular puncture and pneumothorax in bilateral compared to unilateral PVB . LonnqviThe current study had some limitations. The number of patients included in the study was relatively low compared to previous studies. Since we did not perform bilateral PVB, we were not able to compare unilateral PVB and bilateral PVB with regards to their effectiveness and complication rates. As the study included only patients who underwent elective cholecystectomy due to cholelithiasis, we were not able to generalize our results to all those undergoing cholecystectomy for any reason. Future studies with a larger number of patients are warranted, including patients with other biliary pathologies.The present study revealed that ultrasound-guided PVB for LC is a useful and safe approach for pain management during and after LC for elective cholecystectomy due to cholelithiasis. PVB with a single unilateral injection can provide efficient analgesia. Furthermore, PVB combined with general anesthesia also reduced postoperative complications, and preoperative application of the block reduced the rate of intraoperative opioid requirement.