Is chorioamnionitis a risk factor for developing bronchopulmonary dysplasia in preterm infants?This systematic review, meta-analysis, and metaregression found that chorioamnionitis was associated with an increased risk of bronchopulmonary dysplasia in preterm infants but also found significant differences in baseline characteristics between infants with and infants without chorioamnionitis. A multivariate metaregression model combining the difference in gestational age and the odds of respiratory distress syndrome was associated with 64% of the variance in the association between chorioamnionitis and bronchopulmonary dysplasia.Exposure to chorioamnionitis is associated with a higher risk of developing bronchopulmonary dysplasia in preterm infants, but this association may be modulated by gestational age and risk of respiratory distress syndrome. Bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurity, remains one of the major and most common complications of very preterm birth. Insight into factors associated with the pathogenesis of BPD is key to improving its prevention and treatment.To perform a systematic review, meta-analysis, and metaregression of clinical studies exploring the association between chorioamnionitis (CA) and BPD in preterm infants.bronchopulmonary dysplasia, chorioamnionitis, and risk factors.PubMed and Embase were searched without language restriction . Key search terms included Included studies were peer-reviewed studies examining preterm (<37 weeks’ gestation) or very low-birth-weight (<1500 g) infants and reporting primary data that could be used to measure the association between exposure to CA and the development of BPD.The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline was followed. Data were independently extracted by 2 researchers. A random-effects model was used to calculate odds ratios (ORs) and 95% CIs. Heterogeneity in effect size across studies was studied using multivariate, random-effects metaregression analysis.The primary outcome was BPD, defined as supplemental oxygen requirement on postnatal day 28 (BPD28) or at the postmenstrual age of 36 weeks (BPD36). Covariates considered as potential confounders included differences between CA-exposed and CA-unexposed infants in gestational age, rates of respiratory distress syndrome (RDS), exposure to antenatal corticosteroids, and rates of early- and late-onset sepsis.P < .001; heterogeneity: I2 = 84%; P < .001) and BPD36 . The association between CA and BPD remained significant for both clinical and histologic CA. In addition, significant differences were found between CA-exposed and CA-unexposed infants in gestational age, birth weight, odds of being small for gestational age, exposure to antenatal corticosteroids, and early- and late-onset sepsis. Chorioamnionitis was not significantly associated with RDS , but multivariate metaregression analysis with backward elimination revealed that a model combining the difference in gestational age and the odds of RDS was associated with 64% of the variance in the association between CA and BPD36 across studies.A total of 3170 potentially relevant studies were found, of which 158 met the inclusion criteria . Meta-analysis showed that CA exposure was significantly associated with BPD28 (65 studies; OR, 2.32; 95% CI, 1.88-2.86; The results of this study confirm that among preterm infants, exposure to CA is associated with a higher risk of developing BPD, but this association may be modulated by gestational age and risk of RDS. This systematic review, meta-analysis, and metaregression of clinical studies explores the association between chorioamnionitis and bronchopulmonary dysplasia in preterm infants. This observation led to the hypothesis that CA exposure accelerated functional lung maturation but increased the vulnerability of the preterm lung to postnatal injury.16 However, the data supporting this hypothesis are inconsistent, and subsequent studies during the past 20 years have found that CA was associated with increased, decreased, or no risk of either BPD or RDS.16Besides the aforementioned detrimental effects, clinical observations support the concept that fetal exposure to infection or inflammation may also be beneficial to the very preterm lung.10 included 59 studies (15 295 preterm infants). They found in unadjusted analyses that CA was significantly associated with BPD . They found substantial statistical heterogeneity and evidence of publication bias. They also observed that infants exposed to CA had a significantly lower gestational age and birth weight than infants who were not exposed to CA. Moreover, studies adjusting for important confounders  showed more conservative measures of association between CA and BPD. They concluded that “despite a large body of evidence, CA cannot be definitely considered a risk factor for BPD.”10(pF8)The role of CA as a potential pathogenic factor for BPD has already been the subject of a systematic review and meta-analysis. Hartling et al10 many more studies assessing the association between CA and BPD have been published. Some of these studies are of high methodological quality and included a large number of infants. Therefore, in the present study, we aimed to update and expand the meta-analysis of Hartling et al.10 In addition, we investigated not only the association between CA and BPD but also the association between CA and RDS and how these 2 associations correlate. We also analyzed the role of potential confounders or intermediate factors, such as gestational age, birth weight, the presence of fetal inflammatory response , exposure to antenatal corticosteroids, sepsis, or patent ductus arteriosus, in the association between CA and BPD.After the publication of the meta-analysis by Hartling et al,17 CA and retinopathy of prematurity,18 and CA and intraventricular hemorrhage.19 The study was conducted according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline20 and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.21 A protocol was developed prospectively that detailed the specific objectives, criteria for study selection, approach to assessing study quality, clinical outcomes, and statistical methods. The study is reported according to the PRISMA checklist.We based the method for this systematic review, meta-analysis, and metaregression on earlier meta-analyses on the associations between CA and patent ductus arteriosus,chorioamnionitis, intrauterine infection, intrauterine inflammation, antenatal infection, antenatal inflammation, bronchopulmonary dysplasia, chronic lung disease, risk factors, outcome, cohort, and case-control. No language limit was applied. Narrative reviews, systematic reviews, case reports, letters, editorials, and commentaries were excluded but were read to identify potential additional studies. Additional strategies to identify studies included a manual review of reference lists from key articles that fulfilled our eligibility criteria and other systematic reviews on CA, use of the “related articles” feature in PubMed, and use of the “cited by” tool in Web of Science and Google Scholar.A comprehensive literature search was undertaken using the PubMed/MEDLINE and Embase databases from their inception to October 1, 2018. The search terms involved various combinations of the following key words: Studies were included if they examined preterm  or very low-birth-weight (<1500 g) infants and reported primary data that could be used to measure the association between exposure to CA and the development of BPD. Therefore, we selected studies assessing the outcomes of infants exposed to CA when BPD was one of the reported outcomes and studies assessing the risk factors for BPD when CA was one of the reported risk factors. To identify relevant studies, 2 of us (A.M.T.G. and E.V.) independently screened the results of the searches and applied inclusion criteria using a structured form. Discrepancies were resolved through discussion or consultation with a third reviewer (P.D.).BPD28. Bronchopulmonary dysplasia defined as oxygen requirement at the postmenstrual age (PMA) of 36 weeks  was coded as BPD36. Using these definition criteria, BPD28 was considered to include all severities of BPD, whereas BPD36 was considered to include a combination of moderate and severe BPD.2 Data on separate categories of BPD  were collected when available.Two of us (A.M.T.G. and P.D.) extracted data from relevant studies using a predetermined data extraction form, and 3 of us  checked data extraction for accuracy and completeness. Discrepancies were resolved by consulting the primary report. Data extracted from each study included citation information, language of publication, location where research was conducted, time period of the study, study objectives, study design, definitions of CA and BPD, inclusion and exclusion criteria, patient characteristics, and results . Studies that did not define CA were assumed to use a clinical definition. Bronchopulmonary dysplasia defined as supplemental oxygen requirement on postnatal day 28 was coded as 22 This scale uses a rating system  that scores 3 aspects of a study: selection (0-4 points), comparability (0-2 points), and exposure or outcome (0-3 points). Studies were evaluated as though the association between CA and BPD was the primary outcome. Two of us (E.V.-M. and E.V.) independently assessed the methodological quality of each study. Discrepancies were resolved through discussion.Methodological quality was assessed using the Newcastle-Ottawa Scale for cohort or case-control studies.23 and the calculator they provided.24Studies were combined and analyzed using Comprehensive Meta-Analysis, version 3.0 software (Biostat Inc). For dichotomous outcomes, the OR with 95% CI was calculated from the data provided in the studies. Odds ratios adjusted for potential confounders were extracted from the studies reporting these data. For continuous outcomes, the mean difference with 95% CI was calculated. When studies reported continuous variables as median and range or interquartile range, we estimated the mean and SD using the method of Wan et al25 In this model, a random-effects model is used to combine studies within each subgroup, and a fixed-effect model is used to combine subgroups and yield the overall effect. The study-to-study variance (τ2) is not assumed to be the same for all subgroups. This value is computed within subgroups and not pooled across subgroups. Statistical heterogeneity was assessed by use of the Cochran Q statistic and by use of the I2 statistic, which is derived from the Q statistic and describes the proportion of total variation that is due to heterogeneity beyond chance.26 We used the Egger regression test and funnel plots to assess publication bias.Owing to anticipated heterogeneity, summary statistics were calculated with a random-effects model. This model accounts for variability between studies as well as within studies. Subgroup analyses were conducted according to the mixed-effects model.27 The potential sources of variability defined a priori were CA type , differences in gestational age and birth weight between infants with and infants without CA, use of antenatal corticosteroids, mode of delivery, rate of small-for-gestational-age infants, rate of premature rupture of membranes, rate of preeclampsia, rate of early-onset sepsis, rate of late-onset sepsis, rate of RDS, and mortality. Covariates were selected for further modeling if they significantly (P < .05) modified the association between CA and BPD. Subsequently, preselected covariates were included in a backward multiple metaregression analysis with P = .05 as a cutoff point for removal. P < .05 (P < .10 for heterogeneity) was considered statistically significant. All tests were 2-tailed.To explore differences between studies that might be expected to influence the effect size, we performed random effects (method of moments) univariate and multivariate metaregression analyses.183 met the inclusion criteria. The PRISMA flow diagram of the search process is shown in 183 were designed from the perspective of CA; they examined the outcomes of preterm infants with or without CA, and BPD was one of these outcomes. Sixty-seven studies167 were designed from the perspective of BPD; they studied risk factors for BPD, and CA was one of these risk factors. Sixteen studies182 were designed to primarily examine the association between CA and BPD. Forty-eight included studies examined the association between CA and RDS.Of 3170 potentially relevant studies, 158 (5.0%)146 One study required infants to have both histologic and clinical CA to be considered exposed to CA.84 Nine studies defined CA using a microbiological definition.152 Finally, 16 studies170 did not define CA and, for the purposes of analysis, were considered to evaluate clinical CA.Forty-two studies defined CA clinically, and 97 studies defined CA histologically. Six studies provided BPD outcomes for infants with histologic and clinical CA separately.Most studies included infants with a gestational age less than 32 weeks or a birth weight less than 1500 g, as described in eTable 1 in the Sixty-five studies provided data on BPD28, and 108 studies provided data on BPD36. Fifteen studies provided data on the incidence of mild BPD, 7 studies provided data on the incidence of moderate BPD, and 8 studies provided data on the incidence of severe BPD.P < .001; heterogeneity: I2 = 84%; P < .001)   A. When s < .001) . We also < .001) B. This a < .001)  and clin < .001) .When further stratified by grade of BPD, meta-analysis did not find a significant association between CA and mild BPD .To examine confounding factors, we pooled studies that provided adjusted data on the association between CA and BPD. Eleven studies reported adjusted data on BPD28. Meta-analysis of these adjusted data showed a significant association between CA and BPD28  .Twenty-one studies reported adjusted data on BPD36. Meta-analysis of these adjusted data showed a significant association between CA and BPD36     or sever < .001) .k = 25), revealed that heterogeneity in effect size across studies was significantly explained by the mean difference in gestational age  and risk of RDS . We retested this model, including all studies with complete data on mean difference in gestational age and risk of RDS (k = 27) . The variance did not seem to be inflated owing to multicollinearity (variance inflation factor = 1.08). Each week that infants with CA are born earlier than control infants resulted in an increase in BPD36 log OR of 0.23 . Each point increase in the RDS log OR resulted in an increase in the BPD36 log OR of 0.31 .Relevant covariates were preselected using univariate metaregression analyses. Results of all univariate analyses are presented in eTable 2 in the (k = 27) . This fiP > .05). As shown in eFigure 14 in the P < .05), CA was significantly associated with BPD28  , a much larger number of infants (244 096 vs 15 295), and a wider range of analysis of covariates. Our study confirms the results of Hartling et al10 and adds new information on the role of funisitis and RDS, which have not been previously systematically reviewed, to our knowledge. Chorioamnionitis was a significant risk factor for BPD28  and for BPD36 (moderate and severe BPD), but a significant association with severe BPD was not demonstrated. Exposure to funisitis was not significantly associated with a higher risk of BPD compared with exposure to CA in the absence of funisitis. Meta-analysis did not demonstrate a significant association between CA and RDS. As in earlier meta-analyses of CA and morbidities,185 we found significant differences between CA-exposed and CA-unexposed infants in gestational age, birth weight, odds of being small for gestational age, exposure to antenatal corticosteroids, early- and late-onset sepsis, and patent ductus arteriosus. Multivariate metaregression analysis revealed that a model combining the difference in gestational age and the odds of RDS explained 64% of the variance in the association between CA and BPD36 across studies. In conclusion, our results confirm the positive association between CA and BPD in preterm infants, but the pathogenic effect of CA on BPD may be modulated by the effect of CA on gestational age and risk of RDS.The present study is a substantial update to the systematic review of Hartling et al,186 one important limitation inherent to any meta-analysis of BPD is the heterogeneity of the definition of the condition.189 The first clinical definition for BPD was adopted as infants requiring supplemental oxygen on postnatal day 28.187 In 1988, the definition was refined to oxygen use at 36 weeks of PMA,190 and 12 years later, a categorization of BPD as mild, moderate, or severe was proposed.2 Mild BPD included infants who received oxygen or respiratory support at the postnatal age of 28 days but who were breathing room air at 36 weeks PMA. When infants required supplemental oxygen at 36 weeks PMA, BPD was classified as moderate (need for <30% oxygen) or severe (need for ≥30% oxygen and/or positive airway pressure).2 A further refinement in the definition included a physiological challenge of supplemental oxygen withdrawal to test for oxygen need at 36 weeks PMA.191 Most of the studies included in our meta-analysis defined BPD using the 36 weeks of PMA criteria (BPD36). Therefore, they provided data on combined moderate and severe BPD. This combination fails to differentiate the infants with more severe BPD, who remain dependent on mechanical ventilation and more often have severe complications, including pulmonary hypertension, poor growth, and neurodevelopmental problems.6 Only 7 studies provided separate data on severe BPD. Meta-analysis could not demonstrate a significant association between CA and severe BPD, but the small number of studies is the main limitation of this subanalysis.As discussed elsewhere,192 Chorioamnionitis is associated with infection and/or inflammation, and we and others have previously found that infants exposed to CA differ substantially from nonexposed infants in relevant clinical characteristics and outcomes.185 We replicated these findings in the present study and found that CA-exposed infants were born earlier (1.2 weeks) and weighed less (48 g) than infants without CA. In addition, they were more frequently exposed to antenatal corticosteroids, they were less frequently small for gestational age, and they had higher rates of early- and late-onset sepsis, as well as a higher mortality rate. We performed metaregression to analyze how these differences between the CA-exposed and the nonexposed infants affected the association between CA and BPD. Univariate metaregression showed that differences in gestational age and birth weight, as well as rate of RDS, significantly modified the CA-associated risk of BPD36. As already mentioned, multivariate regression found that 64% of variance in CA-associated BPD risk was explained by the differences in gestational age and rate of RDS.Another main difficulty when assessing CA as a risk factor for neonatal adverse outcomes is the absence of a “healthy” control group. Possible causes of very preterm birth  can be divided into 2 main categories: infection and/or inflammation and dysfunctional placentation.16 To test this hypothesis, we also analyzed the association between CA and RDS in the included studies. In contrast to BPD, meta-analysis of unadjusted data could not demonstrate a significant association between CA and the development of RDS. Prematurity is the most important risk factor for RDS. The CA-exposed infants were born 1.2 weeks earlier but did not show a higher rate of RDS. This finding may suggest some degree of protection against RDS, compatible with the Waterberg hypothesis. In contrast, metaregression showed a significant positive association between the effect size of the CA-RDS association and the effect size of the CA-BPD association , which, however, did not modify the lack of association between CA and RDS.The so-called Waterberg hypothesis or early-protection, late-damage effect suggests that CA may be associated with a reduction in RDS but an increase in BPD.195 Been et al34 showed that the presence of funisitis categorized infants at risk for severe RDS who were less responsive to surfactant treatment. In contrast, infants exposed to CA without funisitis had less severe RDS than did infants without the CA exposure. Therefore, exposure to CA and/or funisitis may be more strongly associated with the severity than with the incidence of respiratory complications. Our meta-analysis did not demonstrate that the presence of funisitis significantly increased the risk of BPD or RDS compared with CA in the absence of funisitis (eFigure 7 in the 185It remains unclear whether the most severe grades of CA with a fetal inflammatory response further increase the risk for developing BPD and/or RDS. Funisitis is considered the histologic counterpart of the fetal inflammatory response syndrome.10 noted 2 problems that made the interpretation of their results difficult: significant publication bias and substantial statistical heterogeneity. Our larger study showed a similarly high degree of heterogeneity, but we did not find statistical evidence of publication bias. Egger regression can test only for data trends that may be caused by selective reporting, publication, or inclusion.196 Even highly significant data trends do not necessarily mean that the results of the primary analysis are biased.196 In addition, the Egger regression test has a high type I error rate and may generate false-positives when dealing with many studies and a high degree of heterogeneity.197Hartling et alclinical CA are highly variable, and recent recommendations propose restricting the term chorioamnionitis to pathologic diagnosis.198 In addition, the term funisitis was not included in our search strategy. Second, only a limited number of studies evaluated the association between CA and BPD as their main objective. Similarly, adjusted data were available only from a subset of all studies included in the meta-analysis. In addition, we had to rely on the adjusted analyses as presented in the published reports and the variables for which they adjusted, which were not consistent across studies. Third, metaregression uses summary data at the study level, which means that we cannot comment on data of individual infants within a study and that there is a risk of ecological bias.199 The main strengths of the present study are the large number of studies included and the use of rigorous methods, including duplicate screening, inclusion, and data extraction to reduce bias; meta-analysis of baseline and secondary characteristics; and the use of metaregression to control for potential confounders.Some additional limitations of our systematic review and meta-analysis deserve consideration. First, the published literature showed great heterogeneity in the definition of CA and in the assessment of confounders. In particular, criteria for the use of the term 5 Our data show that CA is frequently the cause of prematurity among these youngest and smallest infants. This higher degree of prematurity may alter the association between CA and BPD. In addition, CA may initiate the pathogenic sequence leading to BPD but also may alter the rate of exposure to other anti-inflammatory or proinflammatory stimuli, such as antenatal corticosteroids, RDS, patent ductus arteriosus, mechanical ventilation, oxygen, and sepsis. Nevertheless, CA, RDS, and BPD are imprecise diagnoses and have been partially changed over time, making the analysis of their associations and correlations difficult.Overall, the results of this study confirm that, among preterm infants, exposure to CA is associated with a higher risk of developing BPD, but this association may be modulated by gestational age and risk of RDS. Bronchopulmonary dysplasia remains a persistent problem in part because advances in neonatal care have improved the survival of the youngest and smallest infants, who are more prone to develop BPD.


Breast cancer is the most frequently diagnosed malignancy in women, and comorbidities like hypertension and obesity diminish their quality of life and negatively affect their response to chemotherapy. Furthermore, inulin supplementation is associated with the reduction of cardiovascular diseases (CVD) risk. To determine whether inulin supplementation prevents the elevation of blood pressure in women with breast cancer undergoing neoadjuvant therapy with cyclophosphamide and doxorubicin. This was a randomized, double-blind placebo controlled trial which included women with early-stage breast cancer undergoing neoadjuvant therapy (n=38). Patients were randomly assigned to participate in two different groups to receive either 15 g of inulin or 15 g of placebo  for 21 days. Body composition and blood pressure were evaluated before and after the supplementation period. p<0.001). However, SBP increased in the placebo supplemented group. Diastolic blood pressure (DBP) nonsignificantly decreased in the inulin group. Inulin supplementation also increased BMI (p<0.001) but reduced BFP (p=0.288). Furthermore, confounding variables, such as BMI, baseline fasting glucose, age, menopause status, vomiting, constipation, and chronic medication did not have a statistical influence over the inulin effect on SBP. Women in the inulin group showed a lower systolic blood pressure (SBP) after the supplementation (-4.21 mmHg, Inulin supplementation reduces SBP and prevents increases in DBP in women with breast cancer. This could be an innovative nutraceutical approach to prevent hypertension present in women with this type of cancer at an early stage and may improve the quality of life of the patients and their prognostic development through chemotherapy.ACTRN12616001532493. This trial is registered with  Hypertension is the comorbidity associated with breast cancer with the highest prevalence 21.8%), which is followed by chronic pulmonary obstruction (19.9%) and diabetes mellitus 16.7%) .8%, whic. The use2 , 5. In a.7% .8%, The origin of hypertension in patients with cancer is not clear; it could appear before cancer diagnosis or after that. For instance, women who used antihypertensive medications have an increased risk of breast cancer . Also, cDiet components can play a regulatory role in the development of hypertension as well. Particularly, some vegetables contain fiber and prebiotics that modulate blood pressure, preventing the appearance of hypertension . For insPrebiotics provide a variety of health benefits like the ability to increase concentrations of vitamin B and plasma glutamine, which could improve immune function . In part2/ 60mg/m2), by infusion, as part of the medical scheme established in the State Cancer Center. Patients were randomly assigned to participate in two different groups to receive 15 g of powdered agave inulin  or 15 g of maltodextrin  as a placebo. Both products were supplied in sealed packages and previously codified by trained personnel in the Molecular Biology Laboratory of the Medical Sciences Research Center (CICMED) in Toluca, State of Mexico. Once participants were assigned to one of the two groups, they were provided with 21 packages according to their respective group. After that, patients from both groups were asked to dissolve the contents of an envelope in 240 mL of drinking water, to be consumed during the breakfast. Patients initiated the ingestion of the supplement on the same day that the first cycle of chemotherapy started, and they kept taking the respective supplement for 21 days. The study was conducted in accordance with the Declaration of Helsinki and the Mexican Legislation on Scientific Research in Humans; also, the study was registered in the Australian New Zealand Clinical Trials Registry with number ACTRN12616001532493, on November 7, 2016. The protocol was approved by the Ethics Committees of the ISSEMYM State Oncology Center and the School of Medicine of the Autonomous University of the State of Mexico. Written informed consent from each participant was obtained once every patient accepted to be included in the study.A randomized, double-blind trial was conducted, involving women (n=38) diagnosed with breast cancer at early stage, beneficiaries of the State Oncology Center of the Social Security Institute of the State of Mexico and Municipalities (ISSEMYM). The inclusion criteria were women aged >18 years and planned to receive neoadjuvant chemotherapy with doxorubicin and cyclophosphamide for the first time. The participants received a standard chemotherapeutic treatment, with cyclophosphamide and doxorubicin . This analysis included body weight, body mass index (BMI), body fat percentage (BFP), lean body mass (LBM), and skeletal muscle mass (SMM), and it was conducted three hours after eating or drinking. To perform the measurement, patients were barefoot and stood on a platform at a 90° position facing ahead, holding both handles of the apparatus until the impedance scan finished and the analysis results were printed. Moreover, blood pressure was measured before and after supplementation (at the end of the 21 days). The procedure to measure blood pressure was performed according to the Official Mexican Norm for prevention, detection, diagnosis, treatment, and control of systemic arterial hypertension (NOM-030-SSA2-2009). Once systolic blood pressure (SBP), diastolic blood pressure (DBP), arterial mean pressure (MAP), and hear rate (HR) were measured, the results were compared between both study groups, before and after the supplementation period. HR was computed as the number of beats in 15 seconds by four, and it was expressed as beats per minute (bpm). The classification of patients according to blood pressure recordings was performed using the criteria established by the American College of Cardiology and the American Association of Hypertension. BMI and BFP classification was conducted according to the criteria established by World Health Organization (WHO) and to Bray G, et al. .Diet information and clinical data of renal function (urea and creatinine concentrations) were extracted from medical records in the State Oncology Center; the data corresponded to results from laboratory tests that were performed prior the beginning of the chemotherapy cycles. Furthermore, it is important to point out that, before starting chemotherapy, adequate renal and hepatic functions were verified in all participants. Regarding that, creatinine clearance was calculated with the Cockcroft-Gault equation. Dietary data were collected by the nutrition department, through an institutional questionnaire of habitual diet; the consumption was reported in equivalent measures according to the Mexican System of Equivalent Foods . In addiThe normality of SBP, DPB, MAP, HR, BMI, and BFP was assessed by the Kolmogorov-Smirnov test. Chi-square test was used to compare frequencies of blood pressure and body composition categories before and after supplementation between placebo and inulin groups. Measures of central tendency were obtained, and the effect size for each variable by group was computed as follows: (mean before supplementation - mean after supplementation)/ standard deviation. To identify significant mean differences between placebo and inulin groups a Student t-test was performed. Also, Mantel-Haenszel test was used to rule out the effect of confounders factors on blood pressure. All tests were performed in the statistical software SPSS 21, considering a significance level of 0.05.p=0.646).The original sample  included (p=0.123). There were 3 women with ductal carcinoma and DBP >90 mmHg, but there were no women with lobular carcinoma and this level of DBP. Women with ductal carcinoma (n=10) presented a higher frequency of elevated MAP (>102.2) than those with lobular carcinoma (n=3). Nonetheless, only one patient with ductal carcinoma presented with an elevated HR (>100.1 BPM). In addition, patients were classified according to their BMI; they were grouped into the following categories: underweight (n=2), overweight (n=15), and obesity (n=11) in both study groups. Most of the participants showed a high BFP . The frequency was higher in the ductal carcinoma group.Moreover, the frequencies of women under placebo and inulin supplementation with high or low blood pressure, HR, BMI, and BFP are shown in  p<0.001), DBP , MAP , and HR  increased significantly, but BMI  and BFP decreased  after supplementation. Nonetheless, in the inulin group, SBP  and HR  decreased significantly. DBP in the inulin supplemented group increased as that in the placebo group did , but the increase in MAP  was not as high as the placebo group. Cohen's d values were lower in the inulin group than the placebo group for SBP (-0.27), DBP (0.18), MAP (0.11), and HR (-0.01). Effect size was determined by Cohen's d test and it revealed that inulin supplementation generated a small effect size (d<0.5) in SBP, DBP, MAP, HR, BMI, BFP, LBM, and SMM; nonetheless, supplementation in the placebo group exerted a medium size effect (d=0.75). Furthermore, inulin supplementation produced a significant increase in BMI  with a nonsignificant loss of BFP . There was also an increase in LBM  and a minimum change in SMM  after 21 days of inulin supplementation, but they were not statistically significant.In p=0.336), BMI (p=0.910), BFP (p=0.054), menopause status (p=0.280), tobacco use (p=0.456), general use of chronic medication (p=0.520), use of antihypertensive medications (p=0.874), vomiting presence (p=0.511), and constipation (p=0.483).In addition, the Mantel-Haenszel test was applied to assess whether confounding variables could influence inulin supplementation net effect. The analysis showed that any of the following variables had a significant influence on the reduction of blood pressure by inulin supplementation: age  of the patients had a normal energy intake, 24.1% (n=7) had a low intake, and 31.0% (n=9) had a high intake; however, this is not a direct indicator of quality of the diet. Moreover, the presence of nausea and vomiting in the placebo group was 13.2% (n=5) at baseline and 23.7% (n=9) after the supplementation period. In the inulin group, the frequencies were 10.5% (n=4) and 13.2 % (n=5), respectively. Finally, the presence of constipation in the placebo group was 21.1% (n=8) at baseline and 23.7% (n=9) after supplementation and in the inulin group 26.3% (n=10) and 10.5% (n=4), respectively. Despite the fact that the presence of these events was lower in the inulin group, it was not significantly different from the placebo group.In this double-blind placebo controlled trial, we found that supplementation with inulin reduces SBP and attenuates increases in DBP and MAP in women with breast cancer under neoadjuvant therapy. Similar to our findings, some trials have shown that supplementation with dietary fiber promotes the reduction of blood pressure although there are some differences associated with the time of supplementation and the change in blood pressure. For instance, fiber intake for 8 weeks nonsignificantly reduces SBP (-1.15 mmHg) and significantly reduces DBP (-1.65 mmHg) . In contOne of the main findings in this study is that the effect of inulin supplementation on SBP is more pronounced than the one on DBP. This is consistent with experimental studies where SBP, systolic volume, and left ventricular diameter in systole were lower in rats fed with a high-fat diet and supplemented with inulin than in unsupplemented rats fed only with the high-fat diet . TherefoSupplementation with 10 and 20 g of inulin for 3 weeks has been linked to decreases in triacylglycerols and hypercholesterolemia in men , 39. In It is important to mention that there is any statistical influence from other confounding variables such as changes in BMI, glucose concentrations, age, menopause status, vomiting, constipation, and use of antihypertensive drugs. This suggests that the decrease in SBP in the group supplemented with inulin is due to the supplementation itself. Furthermore, creatinine clearance  and hepa p value was greater than 0.05 in the group supplemented with inulin, but it was lower in the placebo group. This also suggests that BMI and BFP may not exert an influence on blood pressure after inulin supplementation. Increases in BFP are usually associated with hypertension and breast cancer metastasis [Another interesting finding is the contrasting effect of inulin on BMI and BFP. At the beginning of our study, 68.4% of the patients were overweight and obese, 89.4% had a high BFP, and 34.2% had a MAP above 120 mmHg. However, the frequency of women with overweight or obesity is nonsignificantly different after 21 days of supplementation between both groups . Also, Btastasis –47, but tastasis . In our Hypertension and breast cancer are multifactorial diseases that involve complex molecular and physiological mechanisms. Besides that, there is little evidence about the effects of prebiotics on these two diseases and particularly in women with breast cancer under neoadjuvant therapy. This is the first double-blind placebo controlled clinical trial in women where the supplementation with inulin elicits a reduction in SBP and HR and prevents increases in DBP. Furthermore, inulin supplementation nonsignificantly reduces BFP and increases BMI. Therefore, this might be a novel nutraceutical approach to improve the quality of life and cardiovascular health of women who are at early stages of breast cancer and who are under this type of therapy. Consequently, supplementation with inulin might help to improve the prognosis of women with breast cancer and CVD risk. For future experimental or clinical trials, it would be interesting to consider the assessment of variables  that could further help to explain the physiological mechanisms by which inulin elicits beneficial responses as well as to increase the supplementation period and sample size.


Toxocara canis.Eye diseases, including, Uveitis, inflammation of the retina, and choroid are caused by different agents in humans and has a variety of anterior medial and posterior types. The agent of eye diseases is very different from simple bacterial to acute viral, fungal and parasitic infection. There is limited information regarding the type of eye diseases and T. canis infection.Blood samples of 359 individuals  together with their information were collected from ophthalmology hospitals in Tehran, Iran from Feb 2013 to Jan 2015. The patient's serum was evaluated for the presence of anti-Toxocara antibodies by ELISA kits and blood smears for high eosinophilia. The positive samples were confirmed by Western blot analysis for T. canis antibodies. Nineteen (5.6%) patients had anti-T. canis IgG that 14 (6.1%) were male and 5 (4.5%) were female, and all the patients had negative eosinophilia as well. The results of Western blot analysis for 19 positive patients indicated that 15 were infected by T. canis and 4 were infected by other parasitic infection. The results for control group were negative.Overall, 339 patients sera with eye diseases and control group were tested for anti-Toxocara infection in this research work were at risk. Therefore, in contrast to the previous idea, all eye inflammatory diseases in ocular patients should be considered for Toxocara antibodies in addition to Uveitis.All the patients with inflammatory eye diseases such as endophthalmitis, uveitis DCR, glaucoma and cataract were studied for  Eye disease is one of the most important problems of human and can cause irreversible harm like blindness. There are so many causes of blindness, but uveitis is one of the major cause. Uveitis is a general term used for inflammation of the uvea. Uveitis can be unilateral or bilateral, Granulomatous or non-granulomatous, Acute anterior uveitis, Intermediate uveitis, Posterior uveitis, and Uveitis-complications has included Glaucoma, Hypotonia, Cataract, Eye Toxoplasmosis, Histoplasmosis and eye toxocariasis ,2.Toxocara canis and Toxocara cati, the signs and symptoms of covert toxocariasis are coughing, fever, abdominal pain, headaches, and changes in behavior and ability to sleep. Upon medical examination, wheezing, hepatomegaly, and lymphadenitis are often noted. High parasitic loads or repeated infection can lead to visceral larva migrans. it is generally a unilateral sickness, which usually shows as retinal granuloma, with a yellowish or whitish inflaming mass, in the rear pole or surrounding retina  kit . The optical absorbance and OD of all the samples were measured at 450/620 nm and positive, negative and gray zone results were calculated via the kit's cut off. The OD of each sample changed to digits using kit's calculation formula. The numbers from 9–10 are in the range of gray area, numbers less than 10 are negative and more than 10 are positive.In this descriptive study, 339 patients with eye diseases including 229 males and 110 females with idiopathic uveitis symptoms: papilitis, vitritis, endophethalimitis and granuloma, and 20 individuals: 10 males and 10 females without eye disease as control group, were enrolled from Feb 2013 to Jan 2015 in five ophtalemic hospitals in Tehran, Iran. Blood samples were collected from all the individuals to analyze complete blood cell count (CBC), including eosinophil count, and sera for Toxocara or other ascarids. The use of a confirmatory test like Western blot is needed to approve the dependence of IgG on Toxocara infection.Increasing the IgG titer in patients' sera depends on infection with Toxocara western blot IgG kit, LDBIO, Diagnostics, LYON-FRANCE. The specificity of Western blot kit for T. canis detection was certified as 100%, and IgG positive sera by ELISA was recon-firmed by Western blot.We used commercial All information in this research is confidential and has been left to the researcher and no information has been disclosed elsewhere. Participants were free to enter the study and, after obtaining necessary information about the research, informed consent was taken from the participants.T. canis IgG, of which 14 (6.1%) were male and 5 (4.5%) were female, but the control group had a negative ELISA titier for T. canis IgG. However, no patient had eosinophilia.The results of the other two variables, sex and contact with dogs, were not statistically significant; however, infection was more frequent in children below 10 yr than other groups (Toxocara antibody was observed in different types of eye diseases and maximum frequency was seen in the Dacryocystorhinostomy (DCR) group  had a positive ELISA titer for r groups . Anyway,R) group . The Wes no band .Toxocara spp. and is less common in comparison to VLM  and more than 17 yr 37 persons). About 14% of the adults,  and 17% 7 persons persons The other study on 98 patients with uveitis showed the prevalence of ocular toxocariasis and toxoplasmosis in 2013. The patients consist of 34 anterior uveitis, 39 posterior uveitis and 25 pan uveitis. ELISA, PCR method and eosinophilia count were used for all the blood samples. Finally, Western blot test was conducted for positive samples to confirm the ELISA results.T. gondii but 23 patients, 23.5%  had a positive titer for T. canis and all the positive results were reconfirmed by Western blot test. The maximum seropositive results is related to male posterior uveitis patients 47%, which is similar to the results of the present study  were infected by nt study . The othToxoxcara and ocular vision disorders confirmed the patient's Toxocariasis (Toxocara larvae (T. cati larvae, from the eye of a child. All these reports confirmed the present study's results that Toxocariasis was seen in different age and gender, and it is the cause of some eye disease (However, some different case reports have shown the presence of ocular toxocariasis in different parts of Iran, as the reports on ocular toxocariasis from Babol City. A 40 yr old man with vision disorders and clinical symptoms in the eye were considered to have Toxocariasis by IFA test. A high IgG titer of cariasis . Anothercariasis . Anothera larvae . In addi disease .Toxocara infection in this research work were at risk. Therefore, in contrast to the previous idea, all eye inflammatory diseases in ocular patients should be considered for Toxocara antibodies in addition to Uveitis.Ocular toxocariasis is prevalent and children are more likely to be at risk of the infection than other age groups. Using ELISA + Western-blot is a reliable method for detecting toxocariasis. All the patients with inflammatory eye diseases such as endophthalmitis, uveitis DCR, glaucoma and cataract were studied for


Background and Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) mainly affects the cerebral small arteries. We aimed to analyze changes in the lenticulostriate arteries (LSAs) and the basal ganglia in patients with CADASIL using high-field magnetic resonance imaging (7.0-T MRI).Methods: We examined 46 patients with CADASIL and 46 sex- and age-matched healthy individuals using 7.0-T MRI. The number and length of the LSAs, and the proportion of discontinuous LSAs were compared between the two groups. The Mini-Mental State Examination score, the modified Rankin Scale, the Barthel Index, and the MRI lesion load of the basal ganglia were also examined in patients with CADASIL. We analyzed the association between LSA measurements and the basal ganglia lesion load, as well as the association between LSA measurements and clinical phenotypes in this patient group.Results: We observed a decrease in the number of LSA branches , and an increase in the proportion of discontinuous LSAs  in patients with CADASIL when compared with healthy controls. However, there was no significant difference in the total length of LSAs between CADASIL patients and healthy individuals . There was a positive association between the number of LSA branches and the Mini-Mental State Examination scores of CADASIL patients after adjusting for age and educational level . However, there was no association between LSA measurements and the basal ganglia lesion load among CADASIL patients.Conclusions: 7.0-T MRI provides a promising and non-invasive method for the study of small artery damage in CADASIL. The abnormalities of small arteries may be related to some clinical symptoms of CADASIL patients such as cognitive impairment. The lack of association between LSA measurements and the basal ganglia lesion load among the patients suggests that changes in the basal ganglia due to CADASIL are caused by mechanisms other than anatomic narrowing of the vessel lumen. NOTCH3 gene  is an inherited small vessel disease caused by mutations in the CH3 gene , 2. The CH3 gene . GranulaCH3 gene , 6. MagnCH3 gene , 8.in vivo. However, because of the limitations in signal-to-noise ratio, traditional 3.0-T MRA is incapable of visualizing the intracranial small arteries. Recently, several studies have confirmed the superiority of 7.0-T time-of-flight MRA (TOF-MRA) for examining the intracranial small arteries, especially the LSAs  are the major cerebral small arteries supplying blood to the basal ganglia, a region of the brain that is particularly susceptible in CADASIL , 10. Ultthe LSAs –16, provIn the present study, we aimed to examine changes of the LSAs and the basal ganglia in patients with CADASIL using 7.0-T MRI, and to analyze the association between LSA measurements and the basal ganglia lesion load, as well as the association between LSA measurements and clinical phenotypes in this patient population.NOTCH3 gene. If GOM deposits on the basement membrane of VSMCs were found in skin biopsy of the patient, the gene results were considered positive, even though the mutation was not previously reported , history of hypertension (defined as blood pressure at the time of presentation (≥140/90 mmHg) or previous diagnosis of hypertension), history of diabetes (defined by previous diagnosis), history of hyperlipidemia (defined by previous diagnosis), and history of smoking/alcohol consumption . We also recorded the clinical symptoms of the patients, such as TIA/stroke, cognitive impairment, etc. Patients with cognitive impairment were defined as those whose Mini-Mental State Examination (MMSE) scores were lower than the lower quartile of the age- and educational level-matched healthy controls . The degAll patients underwent MRI examination using a 7.0-T whole-body research MR system . The following imaging sequences were included in the scanning: T1-weighted (T1w) magnetization-prepared rapid gradient-echo for the localization and the identification of LIs, 3-dimensional (3D) high-resolution TOF-MRA for displaying the LSAs, T2-weighted (T2w) fluid-attenuated inversion recovery (FLAIR) for identifying the WMHs and LIs, and susceptibility weighted imaging (SWI) for detecting CMBs. The imaging parameters of the sequences are summarized in ®https://horosproject.org)  , 20. FirWe then counted the number of stems and branches of the LSAs derived from the first segment of the bilateral anterior cerebral arteries (ACAs) and from the first segment of the bilateral middle cerebral arteries (MCAs). Only the blood vessels pointing toward the anterior perforated substances were counted. Stems were defined as LSAs that originated directly from the ACAs or MCAs. The branches were defined as daughter vessels originating from the parent LSA stems, without any subordinate branches (single vessels) , 22. If ltissue) . The samCircular or elliptical lesions with a diameter of 3–15 mm, with a surrounding rim of high signal intensity on the FLAIR sequence, and with the same signal as the cerebrospinal fluid on both T1 and FLAIR sequence were defined as LIs; WMH was defined as a high signal intensity region with a diameter ≥5 mm on FLAIR sequence; Circular lesions with a diameter of 2–10 mm on SWI sequence were defined as CMBs . The numThe number and length of LSAs, as well as the proportion of discontinuous LSAs were examined by a clinician and a radiologist (LC and KQL), and the MRI lesions were assessed by two clinicians (LC and FXJ). The mean of the measurements was used for final statistical analyses. The intraclass correlation coefficient (ICC) for the number of LSA stems of healthy controls was 0.769 [95% confidence interval (CI): 0.618–0.865], that for the number of LSA branches of healthy controls was 0.873 (95% CI: 0.782–0.928), that for the number of LSA stems of CADASIL patients was 0.854 (95% CI: 0.750–0.916), and that for the number of LSA branches of CADASIL patients was 0.867 (95% CI: 0.773–0.924). The ICC for the length of LSAs of healthy controls was 0.992 (95% CI: 0.985–0.995), that for the length of LSAs of CADASIL patients was 0.990 (95% CI: 0.981–0.994), that for the proportion of discontinuous LSAs of healthy controls was 0.873 (95% CI: 0.782–0.928), and that for the proportion of discontinuous LSAs of CADASIL patients was 0.840 (95% CI: 0.729–0.908). Among patients with CADASIL, the ICC for ARWMC scores of the basal ganglia was 0.955 (95% CI: 0.920–0.975), that for number of LIs in the basal ganglia was 0.869 (95% CI: 0.775–0.925), and that for number of CMBs in the basal ganglia was 0.990 (95% CI: 0.982–0.994).t-tests (t), whereas non-normally distributed data were compared using Mann–Whitney U-tests (z). When grouping by history of smoking/alcohol consumption, all data were analyzed using non-parametric tests due to the small sample size, and the P-value was Bonferroni corrected (Bonferroni corrected P = P*2). Chi-square tests were used to compare the ratios.Statistical analyses were performed using SPSS version 20.0 . The normality of the data was analyzed using the Kolmogorov-Smirnov test. Normally distributed data were compared using independent two samples U-tests. Adjustments were achieved using multiple linear regression (for ARWMC scores and MMSE scores), or logistic regression (for the presence of LIs and the presence of CMBs). ARWMC scores for the basal ganglia, the presence of LIs in the basal ganglia, the presence of CMBs in the basal ganglia, and MMSE scores were used as dependent variables. Age and LSA measurements, or age and educational level were included as independent variables in the final regression model. Because of the small number of patients with hypertension, diabetes, or hyperlipidemia, we did not include these variables in the final analyses. The ICC was analyzed using a two-way random effects model. Statistical significance was defined as P < 0.05.We performed univariate analyses using Spearman rank correlation and Mann–Whitney As shown in t = 1.036, P = 0.303) between the CADASIL patients and healthy controls. The number of LSA branches was lower in patients than in controls , whereas no significant difference in the number of stems was found between the groups . An increased proportion of discontinuous LSAs was also observed in patients with CADASIL . However, there was no significant difference in the total length of LSAs between the patients and healthy individuals  (There was no significant difference in age (= 0.682) .z = −2.247, Bonferroni corrected P = 0.049) than in those without such a history, but we did not find a significant change in the number of LSA branches in patients with a history of smoking  . Moreover, there was no significant difference in the total length of LSAs between smokers/drinkers and non-smokers/non-drinkers .In addition, we observed fewer LSA branches in patients with a history of alcohol consumption (= 0.053) . There wz = −2.026; P = 0.043) and more LIs  in the basal ganglia  for the basal ganglia, the presence of LIs  in the basal ganglia, or the presence of CMBs  in the basal ganglia in CADASIL patients. Moreover, we observed no significant association between the proportion of discontinuous LSAs and ARWMC scores  for the basal ganglia, the presence of LIs  in the basal ganglia, or the presence of CMBs  in the basal ganglia in the patient group after adjusting for age. There was also no significant association between the length of LSAs and ARWMC scores  for the basal ganglia, the presence of LIs  in the basal ganglia, or the presence of CMBs  in the basal ganglia in the patient group after adjusting for age  .After adjusting for age, there was no significant association between the number of LSAs and ARWMC scores . However, no significant association was found between the number of LSA branches and the mRS/BI scores . The proportion of discontinuous LSAs and the length of the LSAs were not significantly associated with all the three clinical scores of the patients (P = 0.014). No significant difference in LSA measurements was found between patients with a history of TIA/stroke and patients without a history of TIA/stroke .Using univariate analysis, we found an association between the number of LSA branches and MMSE scores of CADASIL patients , we presume that further increase in sample size may lead to a significant decrease in the number of LSAs in patients with a history of smoking.Clinical manifestations and MRI features in our patients were consistent with those previously reported in Chinese CADASIL cohorts , 5, 28. In the present study, patients with CADASIL exhibited a decrease in the number of LSA branches and an increase in the proportion of discontinuous LSAs. Since TOF-MRA is based on the in-flow effect of cerebral blood flow, these results suggested that there was an interruption in blood flow. Some post-mortem studies have indicated that patients with CADASIL exhibit stenosis and occlusion of the cerebral small arteries , 30, whein vivo imaging (In our study, there was no association between LSA measurements and the basal ganglia lesion load, consistent with the findings of a previous 7.0-T MRI-based study on patients with CADASIL . LIs and imaging . TherefoIn addition, we found a positive association between the number of LSA branches and MMSE scores in CADASIL patients, suggesting that abnormalities of small arteries may be related to some clinical symptoms of CADASIL patients. There may be two explanations for this association. Firstly, in recent years, the importance of the basal ganglia in cognition has been reported by many studies, and it is known to participate in several cognitive pathways such as executive function, procedural memory, and attention , 39. StuThe present study possesses several limitations of note. Because CADASIL is a rare disease, our analysis is inherently limited by weaknesses in the case-control study design, including imperfect matching, inevitable recall bias, and difficulty in determining causal relationships. In addition, the method for measuring the length of LSAs was simplified because of the lack of a software for tracking and reconstructing LSAs. Although this modified method may reflect the extensive stenosis of LSAs, such measurements are easily affected by the curvature of blood vessels and may not reflect the true length of these vessels.We have shown that patients with CADASIL exhibit fewer LSA branches and a higher proportion of discontinuous LSAs than healthy individuals when examined using 7.0-T MRI. This suggests that 7.0-T MRI is a promising and non-invasive method for the study of small artery damage in CADASIL. The abnormalities of small arteries may be related to some of the clinical symptoms of CADASIL patients such as cognitive impairment. However, since we observed no association between the LSA measurements and the basal ganglia lesion load, the changes in the basal ganglia due to CADASIL are most likely caused by mechanisms other than the anatomic narrowing of the vessel lumen, such as hemodynamic abnormalities or a dysfunctional blood-brain barrier.The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.The present study was approved by the institutional review board and ethics committee at Peking University First Hospital and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Fifty patients with CADASIL and 53 age-matched healthy controls were recruited and examined after obtaining written informed consent.YY and ZZ contributed conception and design of the study. CL and XF collected and organized the database, performed the MRI analysis and the statistical analysis. CL and QK performed the MRI analysis. CL wrote the first draft of the manuscript. QK, YS, WZ, and ZW wrote sections of the manuscript. BW, YZ, and JA participated in the design and improvement of MRI scan sequences. All authors contributed to manuscript revision, read, and approved the submitted version.JA was employed by Siemens Shenzhen company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Using long-term follow-up cohort data from the Korean Genome Epidemiology Study, we assessed the dietary risk factors for incident hypertension (HTN). In total, 6792 subjects  aged 40–69 years were included in the study. Physician-diagnosed HTN self-reported by the participants was used as the outcome. Daily intake of 20 food groups was assessed while using a dish-based semi-quantitative food-frequency questionnaire. After controlling for known risk factors, the food groups that were most closely associated with HTN were identified by forward stepwise selection while using the Cox proportional hazards model. The median follow-up period was 11.5 years  and the incidence of HTN was 20 per 1000 person-years. Older age, obesity, lower education level, high alcohol intake, and having at least one parent with HTN were associated with the risk for HTN. In addition, a high intake of salted seafood and a low intake of eggs and meat were independently associated with the incidence of HTN after controlling for the known risk factors. Those in the top quartile of salted seafood intake had a 28% greater risk for incident HTN than those in the bottom quartile. The population-attributable fraction of three dietary factors accounted for 29.0% of the incidence of HTN. A high intake of salted seafood and a low intake of eggs and meat were associated with a greater risk for HTN. Hypertension (HTN) is a major concern in public health, as it is a risk factor for cardiovascular disease (CVD) with a high prevalence . The WorPrevention of HTN would be most effective in reducing the burden of both HTN and CVD. Thus, it is necessary to explore the risk factors for HTN, in terms of primary prevention. Accumulated evidence derived from a large-scale cohort study suggested several risk factors for HTN, including parental HTN ,5, smokiIdentification of dietary factors that are associated with HTN is hampered by interactions among foods and nutrients. Therefore, most studies have focused on specific food groups or nutrients. Although identifying nutrients that are related to disease aids in an understanding of the underlying biological pathways, making recommendations to the general population regarding healthy-eating habits is problematic.This study used the long-term follow-up cohort data of the Korean Genome Epidemiology Study (KoGES). We sought dietary risk factors related to incident HTN, taking into account the known risk factors. We also estimated the population-attributable fraction (PAF) of dietary factors for the incidence of HTN. n = 10,030) aged 40–69 years who resided in communities in Ansung  and Ansan  in Gyeonggi Province. All of the participants initially provided informed consent. This study was of a prospective cohort design and sought risk factors for non-communicable diseases, including HTN and diabetes, in Koreans. A follow-up survey has been conducted every two years by trained technicians/interviewers, involving questionnaires, anthropometric measurements, and serological/urine tests. Currently, data are available for all surveys up to the seventh (2013–2014). We accessed the data with approval from the National Research Institute of Health. The follow-up rate of the seventh survey (6th follow-up survey) was 62.8% [This study was conducted using community-based cohort data of the KoGES. The KoGES consists of six prospective cohort studies in two categories: population-based and gene-environment model studies . The comeventh 20–2014. Wen = 326), with a daily calorie intake <500 kcal or >5000 kcal (n = 84), and/or with a history of any type of cancer, myocardial infarction, stroke, coronary artery disease, congestive heart failure, lipidemia, or HTN in the baseline survey (n = 2828). The subjects participated in at least one follow-up survey. Thus, this study comprised 6792 persons . Those that were excluded from this study were slightly older, had a slightly lower average socioeconomic status, and were less healthy  levels, higher proportion of BMI ≥ 23.0 kg/m2, etc.) than those that were included in this study (data not shown). The study protocol was approved by the Institutional Review Board of Ewha Womans University Hospital. The following subjects were excluded from this study: those with missing dietary data (Subjects were followed from 2001–2002 to their sixth follow-up visit (2013–2014). HTN was identified when patients reported that this condition had been diagnosed by a physician. The follow-up period covered the age at entrance into the study to the age at which HTN was diagnosed or the age at the last follow-up if hypertension did not develop.At baseline, a dietary survey was conducted by a trained interviewer while using a food frequency questionnaire (FFQ) consisting of 103 food items. The validity and reliability of the FFQ are acceptable . The sem2) and reduced renal function was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m2 [Based on the evidence, we evaluated BMI , smoking 1.73 m2 . The LDL 1.73 m2  and cate 1.73 m2 ,19. Moret-test for normally distributed numerical data and the Chi-square test for categorical data. Summary statistics are presented as means with standard deviations for normally distributed numerical data and as medians with interquartile ranges (IQRs) for numerical data with a skewed distribution. We assessed the normality of the distribution of variables with the Shapiro–Wilk test with a normal quantile-quantile plot. Categorical data are presented as numbers and percentages of subjects. To compare participants’ basic characteristics in terms of the HTN incidence, we used the Student’s p < 0.1 were included in the forward stepwise selection along with the potential risk factors. As potential risk factors, the effects of BMI status, smoking status, alcohol drinking, renal function, low-density lipoprotein cholesterol, parental HTN, diabetes, education level, sex, age, and survey region on the incidence of HTN were assessed simultaneously. Furthermore, to consider the correlation between foods, those foods that correlated significantly with the selected food groups were included in the model. We then further analyzed the potential independent effects of the selected foods. The assumptions of the statistical model were examined while using the Schoenfeld residuals method and satisfied. Next, multicollinearity among risk factors was assessed based on the variance inflation factor, and had a value <5.0. The incidence rate of HTN was estimated in units of 1000 person-years. The risk factors for HTN were assessed while using the Cox proportional hazards model. The effects of risk factors on the development of HTN were expressed as hazard ratios (HRs) with 95% confidence intervals (95% CIs). In terms of dietary risk factors, we treated intake quintiles for each food group as categorical variables. We compared the effects of dietary risk factors on HTN, according to intake using the low-intake group (Q1) as the reference. Through a crude model, we assessed the incidence risk of HTN by comparing high and low intake groups (Q5 vs. Q1). The food groups that satisfied p-value < 0.05 was considered indicative of statistical significance.The PAFs of the risk factors were calculated as: ) ÷  + 1) × 100. For the calculation of PAF, we used the top quintile of food intake as a reference group when there was a negative relationship between quintile of food intake and HTN. All of the statistical analyses were conducted using SAS ver. 9.4 software  and R ver. 3.3.3 for Windows . A two-sided p < 0.06). The distribution of participants according to smoking status did not significantly differ by HTN incidence (p = 0.41). More than three quarters of subjects with HTN were obese at the baseline. The percentage of participants with one or more parent with HTN was higher in subjects with HTN than in those without HTN  . The incidence rate of HTN among Koreans aged ≥40 years was 20 per 1000 person-years (cumulative incidence = 18 per 100 persons). Of the subjects, 48.6% were males and 48.2% resided in a rural region. More than half of the subjects had a lower educational level and one-third had a lower income level. At least one of the parents of about 14.3% of the subjects had HTN. More than one quarter of the subjects were current smokers, and 66.0% were overweight or obese. Subjects with HTN were slightly older and had a slightly lower average socioeconomic status. Moreover, 14.3% of those with HTN consumed ≥25 g/day of alcohol, which was higher than the proportion of those without HTN who did so (11.9%); this association reached borderline significance ( 0.0001) .The average daily intake of the 20 food groups is shown in 2 had a 1.71-fold higher risk for HTN. Having a parent with HTN was also associated with the risk for incident HTN . A high intake of alcohol was also associated with a significant risk for HTN. When comparing the highest and lowest intake groups (Q5 vs. Q1), high salted seafood intake was associated with the development of HTN, evidenced by an HR of 1.28 , after controlling for the known risk factors with eggs and meat intake. However, high eggs and meat intake was associated with a reduced risk for incident HTN  and high alcohol consumption (3.8%). Regarding dietary factors, low meat intake (18.6%), low egg intake (5.0%), and high salted seafood intake (5.4%) contributed to incident HTN. Therefore, 42.6% and 29.0% of incident HTN was attributable to known and dietary risk factors, respectively .Using long-term follow-up data of middle-aged Koreans, our results revealed that meat, eggs, and salted seafood intake were independently associated with the incidence of HTN after controlling for known risk factors. Moreover, 29.0% of incident HTN was attributable to a low intake of meat and eggs and a high intake of salted seafood. According to a global burden of disease study, dietary factors and high systolic blood pressure were ranked second and third among factors contributing to the 2016 global burden of disease, accounting for 9.6% and 8.9% of the total disability-adjusted life years (DALY), respectively. High systolic blood pressure was also the most significant contributor to incident CVD and mortality . TherefoRegarding a healthy diet, much evidence suggests that reducing salt intake is beneficial to health, and the WHO recommends ingesting less than 2000 mg sodium per day . AlthougAs regards unfavorable effects that are associated with low levels of consumption, eggs and meat appeared significant. Although eggs have a high cholesterol content, they also contain nutrients that protect against heart disease. These include carotenoids (lutein and zeaxanthin), which have antioxidant and anti-inflammatory activities, and arginine, which improves cardiovascular health by dilating blood vessels . In paraRegarding meat consumption, a previous study using the same data reported that the risk for CVD decreases with increasing the intake of unprocessed meat, particularly poultry . The effThere is evidence that smoking causes cardiovascular damage, but our study did not shown an association. Other studies have also reported null or inverse  associatIn this study, we treated self-reported physician-diagnosed HTN as an outcome. Although questions about the validity of self-reported HTN have been raised, there is still a misclassification problem due to measurement errors when the measurements are simply applied. A recent study using KNHANES data found that the accuracy of self-reported HTN in Koreans over 50 years of age was relatively high . As a suAlthough our results are derived from a long-term cohort study, several points should be considered in their interpretation. First, the community-based cohort was not representative of the Korean population, leading to a lack of generalizability of the results. In addition, as survey instruments and food groupings were defined according to subject characteristics, they might not be comparable with populations in other countries. Second, uncertainty resulting from measurement errors and self-reported disease information might have influenced the results. Third, the misclassification bias caused by this uncertainty might have resulted in attenuated effects, but our results are supported by existing evidence. It is also necessary to consider the possibility of bias due to loss to follow-up. Residual confounding factors due to unmeasured risk or other dietary information, such as serum uric acid levels, use of statins, and eating time and duration, may have influenced the results. Changes in food intake over time can affect the association and act as a major confounder, but they were not considered. Finally, there remains the issue of multiple comparisons, which is related to the possibility of false positives. Thus, there is a need for additional studies to assess the validity of our results.Nevertheless, this study also had several strengths, being a large-scale, long-term observational study that was conducted in Asia, where there has been a lack of research thus far. Our results were obtained using the average dietary intake data extracted from a validated instrument. In view of the possibility of the use of dietary control as a therapeutic strategy, we excluded subjects with cancer, CVD, and lipidemia (including hypertension) at baseline. Accordingly, relatively healthy people remain in the analysis, and the health status effects may have been undervalued. We also identified food groups that are associated with the incidence of HTN after simultaneously controlling for dietary and other known risk factors. The PAF results imply that weight status was most closely associated with the incidence of HTN, followed by meat intake. However, in considering action plans for preventing HTN, focusing on a healthy lifestyle and diet is probably more important than any one risk factor.In conclusion, maintaining a healthy lifestyle and a balanced diet would reduce the overall disease burden. Using long-term follow-up data, we showed that a high intake of salted seafood and low intake of eggs and meat were associated with an increased incidence of HTN, even after adjusting for known risk factors. Our study focused on the foods related to incident HTN; thus, research on dietary patterns is still necessary. Furthermore, further studies are needed to confirm our results and determine the appropriate intakes of various types of foods.


M = 12.65, SD = 0.79) at the start of the study. Students were assessed twice in a 22 month-period. Descriptive analyses were conducted between major variables at both time points, and to explore the number and nature of clusters, we relied on latent profile analysis. The statistical analyses showed three different patterns: downward, stable and upward, with different outcomes and determinants. The downward pattern was associated with more negative enjoyment and a controlling style, while the upward pattern with more positive enjoyment and autonomy support. This study, which was based on a person-centered approach, provided a bigger picture of the interplay between autonomy, competence, relatedness, self-determined motivation, autonomy/control support, and physical activity enjoyment.This longitudinal study explored patterns of basic psychological needs and self-determined motivation, as well as its association with the teaching style and the physical activity enjoyment in a group of students. The sample consisted of 200 secondary education students (105 girls and 95 boys) aged 11 to 13 years ( The importance of regular exercise is indisputable in maintaining quality of life and health. Aspects related to physical exercise are particularly investigated in childhood and adolescence, since during this period a significant relationship is established between acquired behaviors and the resulting actions in adulthood . Thus, aThe factors that interfere in exercise adherence and a healthy lifestyle are related to motivational aspects. In this respect, the self-determination theory SDT; , 2000, aBasic psychological needs  and motivation are factors that have been extensively studied . Cross-sUnfortunately, these studies only provide information on the relationship between the determinant and the outcome, such as high values on autonomy correspond to high values on enjoyment. These types of studies rely on a variable-centered approach. This approach provides a small picture of the interplay among the studied variables, however, a person-centered approach allows the study of different variable configurations whilst providing a bigger picture . For insThe present study addresses this gap in the literature by examining students’ patterns of autonomy, competence, relatedness and self-determined motivation changes, and how such patterns predict enjoyment/disenjoyment, and how these patterns relate to autonomy support.The SDT, proposed by Motivation varies from the most self-determined form, called intrinsic motivation, when the choice is personal, characterizing total autonomy in terms of the activity, which generates interest, enjoyment and satisfaction inherent to the activity  to the lSatisfaction of basic psychological needs and self-determined motivation are associated with enjoyment and effort in performing activities and other positives outcomes . For insUnfortunately, these longitudinal studies relied on a variable-centered approach, and thus, it is not possible to see a big picture of the interplay among the studied variables. Nevertheless, there are cross-sectional studies that relied on a person-centered approach to increase adolescents’ motivation. Most of these studies analyzed the coexistence of motivational regulations , but litIn the educational and behavioral context, the SDT was broadened by During physical education classes, one of the contextual factors that can influence motivation is the teacher’s interpersonal style. Teachers offer support along a continuum, which ranges from extreme control to total support for autonomy . AccordiIn contrast to an interpersonal style that supports autonomy in the classroom, teachers with a controlling style ensure that activities are performed exactly according to their way of thinking, feeling and behaving. When teachers use controlling support, they make students abandon their own inner motivational resources in order to undertake activities and seek to solve problems based on the teachers’ needs .The motor and affective experiences perceived by students during class are influenced by the teachers’ interaction and how they present class content . The teaInvestigations on the SDT indicate that a teaching style aimed at supporting autonomy results in improved student motivation. A determining factor in physical education classes and physical activity in general is the feeling of joy. Studies show that self-determined motivation to engage in physical activity is influenced by perceived enjoyment and challenges that activities can generate in children and adolescents . The pleThe SDT highlights the positive effect of enjoyment and the feeling of pleasure as a crucial point for physical education self-determined motivation. Perceptions of competence, autonomy, success and good relationships with others increase pleasure during physical activity and reduce negative perceptions such as boredom . Taken tUnderstanding different patterns of self-determined motivation in physical education classes may help teachers improve the quality of interactions with students, favoring and increasing positive experiences during classes . DiffereWe hypothesize the existence of different clusters and that the students in motivational clusters with more self-determination will show more pleasure in practicing physical activity and more autonomy support from their teachers. Similarly, we expect that motivational clusters with less self-determination will show less pleasure in practicing the activity and will receive more controlled classes from their teachers.M = 12.65, SD = 0.79) at the beginning of the study. For the data analysis, the same individuals were considered for collection 1 when they were still in the sixth, seventh and eighth grades, and collection 2 were in the seventh, eighth and ninth grade, respectively.The sample consisted of 200 schoolchildren, 105 girls, and 95 boys, in the final grades of elementary schooling at four public schools located in the urban zone of three municipalities in Midwest Santa Catarina state, Brazil. The students were 11–13 years old (I completely disagree) to 7 (I completely agree). Since this instrument has not yet been adapted to the Brazilian educational setting, Hambleton’s back-translation method was used  = 9.686 (p = 0.08), RMSEA = 0.068  and CFI = 0.986.The Learning Climate Questionnaire LCQ;  was usedwas used . Items wI completely disagree) to 7 (I completely agree). The same procedure used in the previous scale was followed. Cronbach’s alpha was 0.86. All standardized loadings were between 0.270 and 0.565. Regarding the CFA, the χ2 value and fit indexes were: χ2  = 0.130 (p = 0.94), RMSEA = 0.000  and CFI = 0.999.The Controlling Teacher Questionnaire (CTQ), from I completely disagree) to 5 (I completely agree). Cronbach’s alpha was 0.73, 0.71, and 0.85, respectively.A questionnaire was applied to assess basic psychological needs in physical education (NPBEF), adapted for Portuguese by I completely disagree) to 5 (I completely agree). Internal consistency was 0.81, 0.76, 0.76, 0.69, and 0.74, respectively. To determine the total score of self-determined motivation, the index of self-determination (IAD): (2 × intrinsic motivation + identified regulation) – [ / 2 + 2 × amotivation]   was usedivation]  was usedI completely disagree) to 5 (I completely agree). Cronbach’s alpha was 0.91.We applied the Physical Activity Enjoyment Scale (PACES) , translaQuestionnaires were administered individually during class time on two time points. The first data collection took place in March 2015 and the second in December 2016. Both evaluations had the same sample of individuals, so the data represent the answers of the students at the beginning of the 2015 school year while they were in the sixth, seventh and eighth grades. At the end of 2016, these same students were in the seventh, eighth and ninth grade, respectively. It is important to consider that the Brazilian school year begins in February and ends in December. The questionnaires were applied in the classroom under the supervision of the authors of this study. Prior authorization was requested from management staff and teachers at the schools involved in the study, as well as the parents and/or guardians of the participants. The questionnaires were answered during physical education (PE) classes under the supervision of the researcher, who explained how subjects should complete the instrument and remained available to answer any questions that might arise during the process. Completion time was approximately 35 min, and anonymity was respected to ensure sincere answers. Whilst the students answered the questionnaire, only the researchers were in the classroom. The teachers were not present during the data collection. This study was carried out in accordance with the recommendations of Human Research Ethics Committee of Unoesc/Hust with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Human Research Ethics Committee of Unoesc/Hust, under protocol number 937.597 on December 19, 2014.2 – T1). Finally, to ease interpretation, we standardized these values (mean = 0 and standard deviation = 1).Descriptive analyses were conducted, including Pearson’s correlations between major variables at both time points  are displayed in Table 1 Negative Enjoyment) and 10.061 (T1 Self-determination). With regard to correlations, they ranged from 0.614 (Self-determination with Positive Enjoyment) to -0.007 (Teacher Controlling Style with Positive Enjoyment). All correlations were significant (p < 0.05).Means for variables at both time points and correlations between the standardized differences scores T2–T are dispWe compared models between one and four clusters. As can be seen in Table Figure M = -1.238) and Positive Enjoyment (M = -1.261) variation, subjects in the average cluster showed more Autonomy Support (M = 0.0881) and Positive Enjoyment (M = -0.024) than subjects in the low cluster, while subjects in the high cluster were characterized by more Positive Enjoyment (M = 0.786), but not more Autonomy Support (M = 0.493). Results are displayed in Table Subjects in the low cluster had the lowest Autonomy Support (M = -0.02 than subM = 0.773) and Negative Enjoyment variation (M = 1.351), subjects in the average cluster showed less Teacher Controlling style (M = -0.092) and Negative Enjoyment (M = 0.009) than subjects in the low cluster, while subjects in the high cluster were characterized by less Negative Enjoyment (M = -0.800), but not less Teacher Controlling style (M = -0.214).As can be seen in Table With regard to gender differences, all clusters were significantly different. The low and high cluster were characterized by more females, while more males were observed in the average cluster Table .The aim of this longitudinal study was twofold: (1) explore different clusters based on autonomy, competence, relatedness and self-determined motivation changes over a 22-months period, and (2) test how these clusters differ on enjoyment and on teacher style (autonomy/control support). The hypothesis presented seeks for the existence of patterns of change and for the association of these patterns with an outcome and a determinant.Three patterns were identified: decreases in all psychological needs and self-determination; no changes, and increases in self-determination, competence, autonomy but no changes in relatedness. The downward pattern was associated with more Negative Enjoyment and a Controlling Style, while the upward pattern, with more Positive Enjoyment and Autonomy Support. In a similar study, Importantly, those three patterns differed on the outcome (positive and negative enjoyment), and the determinant (autonomy/control support). In a cross-sectional study The group with low self-determination also showed low fulfillment of the basic psychological needs of autonomy, competence and relatedness with moderate self-determination exhibited moderate fulfillment of these needs. Changes in satisfaction related to basic psychological needs were associated with self-determined motivation, and it is important to examine competence, autonomy and the relationship with others separately, in order to obtain a more complete understanding of the role played by the teaching style, fulfillment of psychological needs and enjoyment of physical activity in adolescents.Earlier studies gathered evidence of the positive influence of teaching style on autonomy on self-determined motivation, basic psychological needs and satisfaction with physical activity , since tIt is important to underscore the relationship between enjoyment and physical activities, given that the sense of fulfillment and pleasure in performing an activity promotes adherence and regularity . EnjoyinThere is also an intergroup difference between the sexes. In this study the boys obtained moderate results, while the girls showed both extremes (low and high self-determination). Most of the studies that analyze self-determined motivation to attend physical education classes, considering the students’ sex, found that boys are more intrinsically motivated than girls . Moreno-Educational programs that stimulate the development of self-determined motivation may lead students to habitually engage in physical activities so that they are less likely to discontinue them after the school year ends. Thus, enjoyment in physical education classes results from a more self-determined behavior and fulfillment of the basic psychological needs for competence, autonomy and relationships with others, with an influence of interpersonal teaching style. The present findings support the use of educational strategies that favor autonomy and influence self-determined motivation, thereby promoting commitment to physical activity. In this respect, a number of aspects are important in improving self-determined motivation in physical education classes, such as varying activities, transmitting the feeling of responsibility, enabling student decision making, and recognizing efforts and personal improvement . As suchA study limitation was the fact that the authors used the self-determination index, as observed in earlier studies. However, recent research indicates that using a continuum as a general index may dilute the richness of the findings obtained, given that the model can be tested by considering each type of self-determined motivation or separating it into two large categories (autonomous and controlled). Nevertheless, the information collected may help future studies, where it will be important to design interventions with teachers in order to enhance experiences in physical education classes, thereby improving adherence to physical activities.In conclusion, more self-determined motivation is related to greater teacher support for autonomy, greater fulfillment of basic psychological needs and increased enjoyment with physical activity. It is important to underscore that the group characterized by high self-determination exhibited high competence values. As such, it is recommended that physical education teachers use a style that supports autonomy, applying strategies that improve student self-determined motivation as well as feelings of pleasure and satisfaction with physical education.JM-M conceptualized the study, supervised and managed the data, drafted and revised the manuscript, approved the manuscript to be published, and agreed to be accountable for all aspects of the work in this manuscript. GF and EB analyzed and managed the data, drafted and revised the manuscript, approved the manuscript to be published, and agreed to be accountable for all aspects of the work in this manuscript. JL and authors conceptualized the study, analyzed and wrote the results, approved the manuscript to be published, and agreed to be accountable for all aspects of the work in this manuscript. RNJ supervised the data, drafted and revised the manuscript, approved the manuscript to be published, and agreed to be accountable for all aspects of the work in this manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Breast cancer (BC) is the most common cause of cancer among women, with a high incidence rate occurrence every year worldwide despite advances in its management. BC is characterized by a spectrum of subtypes which respond differently to treatments due to their biological features, representing the main issue in the control of this type of malignancy. Androgen receptor (AR) is emerging as a target to investigate among hormone receptors, since it seems to play a role at various stages of development of specific BC subsets. For this reason, in recent years AR has become very important in the clinical practice, although its role remains controversial. A number of studies have proposed a correlation between microRNAs (miRNAs), a class of gene expression modulators, and AR in prostate cancer (PC), but there are still few evidences about the relationship between miRNAs and AR in BC. The purpose of this review is to present a state of the art scenario with consideration to the most recent discoveries about miRNAs involved in the AR associated pathogenesis of BC, in order to provide new insights into the role of miRNAs as key drivers in the modulation of AR, and possible actors in the development and progression of BC. Moreover, we consider findings about involvement of AR signaling in all stages of BC, highlighting its association with different subsets of breast carcinomas and with pre- and postmenopausal state of patients. Breast cancer (BC) is the most common cause of cancer among women and in 2018 in the United States 266,120 new cases and 40,920 deaths have been estimated . DespiteAndrogen receptor is a member of the family of steroid nuclear receptors which mediates the biological effects of androgens. It is well established that AR is considered an oncogenic driver at all stages of PC, but its role in BC remains controversial. In fact, expression of AR splice variants (ARVs) has been elucidated in PC, but only recently the presence of multiple known and novel ARV transcripts has been demonstrated in a panel of BC cell lines and human tissues: AR-V1, -V3, -V4, -V7, and -V9 . In partIn the last years several studies have focused on the role of AR in ER-α positive (ER+) BCs, since there would seem to be a correlation between its expression grade and some clinical advantages. In fact high levels of AR are associated to reduced lymph node involvement, better DFS, RFS, and OS, response to endocrine therapies and chemotherapy, lower tumor grade, Ki67 expression, smaller tumor size and less necrosis, suggesting for AR a possible role as a tumor-suppressor in malignant breast epithelial cells . Rangel in vitro using BC cell lines whose growth was promoted by AR expression. Robinson et al. demonstrated that in the absence of ER-α more than a half of AR binding events showed an analogous pattern to that of ER-α in ER+ cells, promoting the expression of ER target genes, and suggesting a role of AR as a ER-α mimic  subtype had a distinct transcriptional landscape independent of HER2-amplificated (HER2A) that reflected and confirmed how AR signaling can replace ER-driven tumorigenesis . In fact, it is estimated that up to 90% of primary BC and up to 75% of metastatic lesions expressed AR (in situ (DCIS)  , althougu (DCIS) , Schrijv with ET . This ne with ET . Usually with ET , and E2  with ET . Whereas with ET . Severaln levels . How horn levels .MicroRNAs are the most explored non-coding RNAs, and give rise to a large family of short (19–24 nucleotides) single-strand RNAs which take part in a variety of biological processes, such as cell proliferation, death, differentiation, and stress response . They opIQWD1 (IQ motif and WD repeats-1) and miR-363: under low androgens levels IQWD1 was downregulated by miR-363, but this negative modulation did not occurred after DHT administration  is known to promote EMT, thereby progression, invasion and metastasis, and is found abnormally overexpressed. Yang et al. identified an AR negatively induced long non-coding RNA (lncRNA) ARNILA that correlated to poor PFS, tightly connected to AR and able to sequester miR-204, in turn facilitating the expression of its target Sox4. Particularly in AR+ carcinomas, ARNILA is suppressed by the action of DHT and AR, resulting in the decreased adsorption of miR-204 thus favoring Sox4 expression inhibition. On the other hand, in AR- tumors, the action of ARNILA leads to Sox4 expression by increasing the sequestration of miR-204, leading to the induction of EMT and metastatic propagation (A number of studies have proposed a correlation between miRNAs and AR in PC , but thestration . Interesoteasome . In AR+/oteasome . Similaroteasome . Resultsoteasome . Moreovec target . Anotherc target . In TNBCpagation . All togpagation . Again ipagation  (Al-Othmpagation . In anotpagation . Again, pagation . Interespagation . This hypagation .Many studies support the idea that BC is a heterogeneous pathology and this consideration is mainly motivated by the existence of different subtypes classified on the basis of hormone receptor expression. About 70–80% of BC express considerable level of ER and are estrogen-dependent , but, asSince the findings that miRNAs play a role in carcinogenesis and are deregulated in several types of tumor, they have obtained a lot of interest about their potential use as therapeutic agents in chemotherapy. Furthermore, the supposing of the existence of a specific uptake can help the purpose to customize miRNAs as therapeutics alone or, more likely, in combination with today’s anti-cancer therapies. Surely more stress should be placed on understanding the balance between AR and ER in relation to the different subtypes, which gives rise to main questions regarding a different response to endocrine therapies in BC. For instance, the interesting positive feedback mechanism identified by Lyu et al. between AR and miR-30a could be a starting point for further studies about the role of miRNAs as a therapeutic predictive markers, besides the identification of other miRs that are able to target AR, or molecules involved in the AR pathway, can certainly help to find more answers about this interaction . Also, nEB wrote the first draft of the manuscript. FF contributed to the writing of the manuscript. FF and EB drew figures and tables. Both authors critically reviewed the manuscript and approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.