This study aims to evaluate the school careers of patients with congenital heart disease (CHD) and microcephaly.n = 2818). A total of 750 patients participated in the online survey (26.6%). This publication focuses on 91 patients (12.1%) diagnosed with CHD and microcephaly who participated in the new online survey.An exploratory online survey was conducted on patients from a previous study on somatic development in children with CHD in 2018 (p < 0.001). Microcephalic patients suffered from psychiatric comorbidity two times as often (67.0%) as non-microcephalic patients (29.8%). In particular, the percentage of patients with developmental delay, intellectual debility, social disability, learning disorder, or language disorder was significantly increased in microcephalic CHD patients (p < 0.001). A total of 85.7% of microcephalic patients and 47.6% of non-microcephalic patients received early interventions to foster their development. The school enrollment of both groups was similar at approximately six years of age. However, 89.9% of non-microcephalic but only 51.6% of microcephalic patients were enrolled in a regular elementary school. Regarding secondary school, only half as many microcephalic patients (14.3%) went to grammar school, while the proportion of pupils at special schools was eight times higher. Supportive interventions, e.g., for specific learning disabilities, were used by 52.7% of microcephalic patients and 21.6% of non-microcephalic patients.Microcephaly was significantly associated with CHD severity (Patients with CHD and microcephaly are at high risk for impaired educational development. Early identification should alert clinicians to provide targeted interventions to optimize the developmental potential. Children with congenital heart disease (CHD) are at risk of impaired somatic growth, especially those with single ventricle physiology , 2. The Most studies analyzing somatic development focus on body weight and length but less often on the head circumference , 4, 5. HTo date, the association between microcephaly and education in children with CHD has not been analyzed. Hence, this study aimed to evaluate the scholastic development of CHD patients with microcephaly.This is an exploratory cross-sectional follow-up study using an online survey to evaluate the school careers of patients with CHD. The ethics committee of the Charité—Universitätsmedizin Berlin, Germany, approved this study (no. EA2/190/19), which was conducted in 2020.Study participants received an invitation to participate in the survey by email or postal letters, and if a response was missing, they were reminded once to participate. The survey could be completed by the patient, a parent, or a third party . The corresponding addressee received a slightly different questionnaire. The survey consisted of a maximum of 74 questions, depending on the participant and the option of sequential questions. A total of 92% of the survey's questions were closed multiple-choice questions. Most questions offered the participant the option of adding their own answer if none of the possible answers adequately described their situation in a free-text box. The survey comprised questions about medical data such as further chronic diseases, psychiatric comorbidities , genetic syndromes, and subjective health conditions. The focus was on questions about the school career: enrollment age, school form (primary and secondary), (early) supportive therapy , school year repetition, absenteeism from school, and participation in physical education. Furthermore, the educational achievement and qualifications of the parents were elicited. Medical data were supplemented by the database of the National Register for Congenital Heart Defects (NRCHD). The NRCHD is Germany's national repository for medical data on CHD patients. With ~55,000 members, the NRCHD is Europe's largest register for CHD patients and can be regarded as a basis for representative studies .From 2006 to 2011, the Competence Network for Congenital Heart Defects  conducted the “PAN-study” , which analyzed the prevalence of CHD prospectively in newborns in Germany . To deteParticipation in the “PAN-study” and “PAN-KU-study”Availability of complete and up-to-date contact information at the time of the present studyComplete answering the online-surveyrd percentile.To analyze the prevalence of microcephaly in the presented study, head circumference data at the child's three-month checkup  were used. These data were converted into sex- and age-adjusted percentiles, taking into account the date of measurement, date of birth, sex, and gestational age at birth. The percentiles, according to Braegger et al., commonly used in Germany, served as the basis for the calculation . MicroceIn Germany, school attendance is compulsory until the age of 15 years and is free. Usually, children start elementary school at the age of 5–7 years, mainly, however, at the age of 6 years. If a child has special needs in their educational, developmental, and learning possibilities , they are introduced to a special school. After finishing primary education , there are several options for secondary schooling according to the student's abilities: the highest is the grammar school (“Gymnasium”), where pupils graduate after 8–9 years with a high school diploma, enabling them to study at university. Graduation from secondary school options  allows for starting an apprenticeship.The cardiac diagnoses were arranged in accordance with the classification of the International Pediatric and Congenital Cardiac Code (IPCCC) . FollowiFor the various research questions, different subgroups were defined. The influence of parental education level was analyzed using descriptive analysis due to limited data.t-test. A p-value of < 0.05 was considered statistically significant. SPSS  was used for statistical analysis.For this, the parental education level was classified as “high,” “medium,” and “low” according to the International Standard Classification of Education (ISCED) . Group dA total of 750/2818 study participants (26.6%) answered all survey questions and were included in the statistical analyses. The mean age of the overall study cohort was 12.16 years , and 50.4% were females . SubjectAt the age of 3–4 months, the mean head circumference of CHD patients from our cohort (percentile 44.1 ± 33.3) equaled the age-dependent percentile; In total, 91 out of 750 patients (12.1%) had a head circumference below the 3rd percentile and thus were classified as microcephalic , 4. ThisSyndromal diseases existed in 30.8% of the microcephalic patients . Ventricp < 0.001; A total of 29.8% of non-microcephalic patients suffered from psychiatric comorbidity, while in microcephalic patients, this proportion was more than two times as high (67.0%) . In partThe educational career and usage of support interventions of microcephalic patients compared to CHD patients without microcephaly are visualized in Staying down a year was statistically insignificant between microcephalic and non-microcephalic patients ; school Our data demonstrate that microcephaly in early childhood is a crucial risk factor for impaired scholastic development in patients with CHD. These results expand the current state of research, as the educational career of microcephalic vs. non-microcephalic CHD patients has not been evaluated. This is noteworthy as education is a particularly important and objectively measurable characteristic of neurodevelopment. In our study, microcephalic participants had a high demand for early and specific interventions. They frequently attended special schools more frequently and compared to non-microcephalic CHD patients, their likelihood of attending a grammar school was halved. Approximately two-thirds of microcephalic patients were diagnosed with psychiatric disorders such as learning, emotional, or behavioral disorders.Previous studies have shown that a small head circumference in CHD patients is related to neurodevelopmental outcomes in early childhood , 7, 18, First, mounting evidence suggests that prenatal factors play a crucial role. It has been proven that intrauterine brain growth is predominantly altered in children with complex CHD and may result in a smaller head circumference and brain volume at birth , 22. HemSecond, postnatal growth is often impaired in CHD patients. This has mainly been attributed to disrupted normal feeding behavior in the neonatal and infant period . In CHD Third, social environment in the meaning of parental education and supportive therapy may be a rationale as this is an important determinant in childhood development , 32. In Another noteworthy result of the present analysis is the prevalence of psychiatric comorbidities: nearly one-third of non-microcephalic patients suffered from psychiatric comorbidity, but in microcephalic patients, this proportion was more than two times as high. Numerous studies have observed the clinical manifestation of developmental delay, intellectual debility, social disability, learning disorder, or language disorder , 36. UndInterestingly, the subjective health status of microcephalic patients was not as good as the non-microcephalic patients' but still very good. This has been reported before . A possiIt is important for CHD patients, affected families, and treating physicians to be aware of microcephaly as a risk factor for impaired scholastic development. Routine follow-up examinations should be established to identify developmental deficits. Unfortunately, underlying variables such as prenatal hemodynamic factors or the number and point of time of CHD operations are hardly modifiable. However, supportive therapy seems to be a promising compensation mechanism. Therefore, CHD patients and their families should be given low-threshold access to supportive interventions.Due to the data privacy policy of the NRCHD, a non-responder analysis could not be performed. Our results need to be interpreted in light of a potential selection bias. Highly educated and/or healthier CHD patients might be more inclined to participate in scientific studies than patients with lower educational levels and/or more health problems. However, a proportion of 48% of microcephalic patients attending a particular school speaks against this assumption. Our analysis of parental ISCED and child education supports this assumption that in microcephalic patients, somatic (co-) morbidities have a more significant influence than the parental level of education. However, parents with higher education might be overrepresented compared to the German general population. The response rate of 26.6% is in the middle range and may still be considered valid and quite representative . The resPatients with CHD and microcephaly are at risk for impaired educational development. Head circumference measurement in infants and children with CHD should be integrated into the serial routine monitoring of somatic parameters in children with CHD. Microcephaly in early childhood should alert clinicians to provide targeted interventions to optimize the developmental potential. Further studies are necessary to evaluate the impact of these interventions and to determine the long-term follow-up of this specific patient cohort at risk.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of the Charité—Universitätsmedizin Berlin, Germany (No. EA2/190/19). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.CP, H-AK, MP, FB, UB, PH, and KS: study concept/design. CP, PH, and KS: data interpretation. CP: drafting of the original manuscript. LS and AH: data analysis. AH: acquisition of data. LS: interpretation, visualization, and drafting of the original manuscript (results). PH, H-AK, MP, and KS: critical revisions of the manuscript. H-AK and MP: acquisition of data. FB and UB: critical revisions of the manuscript. All authors approved the final version of the manuscript.This study received funding from Deutsche Herzstiftung e.V. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. CP is participant in the BIH Charité Clinician Scientist Program funded by the Charité—Universitätsmedizin Berlin and the Berlin Institute of Health. This work was supported by the Competence Network for Congenital Heart Defects  and the National Register for Congenital Heart Defects . We acknowledge financial support by Land Schleswig-Holstein within the funding program Open Access Publikationsfonds.Authors UB and PH were employed by the companies National Register for Congenital Heart Defects and Competence Network for Congenital Heart Defects.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.The reviewer JL declared a shared affiliation with the author LS to the handling editor at the time of review.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Klebsiella pneumoniae is a gram-negative rod belonging to the order Enterobacterales and having a wide distribution in the environment, including the human colon. Recently, the bacterium is one of the known problems in the healthcare setting as it has become resistant to last-resort drugs like carbapenems. The colonized person can serve as a reservoir for his/herself and others, especially in the healthcare setting leading to nosocomial and opportunistic infections. Therefore, we aimed to quantitatively estimate the rate of prevalence and incidence of colonization with carbapenem-resistant K. pneumoniae.K. pneumoniae colonization. Data were extracted onto format in Microsoft Excel and pooled estimates with a 95% confidence interval calculated using Der-Simonian-Laird random-effects model. With the use of I2 statistics and prediction intervals, the level of heterogeneity was displayed. Egger’s tests and funnel plots of standard error were used to demonstrate the publication bias.A literature search was conducted on PubMed/MEDLINE, Google Scholar, Science Direct, Cochrane Library, WHO Index Medicus, and university databases. The study includes all published and unpublished papers that addressed the prevalence or incidence of K. pneumoniae colonization varies by location and ranges from 0.13 to 22%, with a pooled prevalence of 5.43%. (3.73–7.42). Whereas the incidence of colonization ranges from 2 to 73% with a pooled incidence of 22.3% (CI 12.74–31.87), both prevalence and incidence reports are majorly from developed countries. There was a variation in the distribution of carbapenem resistance genes among colonizing isolates with KPC as a prominent gene reported from many studies and NDM being reported mainly by studies from Asian countries. A univariate meta-regression analysis indicated continent, patient type, study design, and admission ward do not affect the heterogeneity .A total of 35 studies were included in the review and 32 records with 37,661 patients for assessment of prevalence, while ten studies with 3643 patients for incidence of colonization. The prevalence of carbapenem-resistant K. pneumoniae is higher in a healthcare setting with variable distribution in different localities, and resistance genes for carbapenem drugs also have unstable distribution in different geographic areas.The review revealed that colonization with The online version contains supplementary material available at 10.1186/s13643-022-02110-3. Klebsiella pneumoniae is an omnipresent Gram-negative, non-motile bacterium belonging to the Enterobacterales order. It is a common bacterium in the colon and an opportunistic pathogen capable of causing many infections in mammals. Initial colonization is commonly from environmental sources  , Carbapenem [MeSH], carrier state [MeSH], Asymptomatic infections [MeSH] “carbapenem-resistant,” carriage, colonization, carbapenemase, “carbapenemase producer”, “carbapenem non-susceptible,” and CRE. Boolean operators , truncation, MeSH, and key terms were used appropriately for the systematic identification of records for the research question. The search was conducted from August 14 to 19, 2021, and all published and unpublished articles available online till the day of data collection were considered. Gray literature from organizations and online university repositories were accessed through Google Scholar with the help of Harzing’s publish or perish 7.0 program [Literature was searched on electronic databases and indexing services like PubMed/MEDLINE, Science Direct, and other supplementary sources like WHO Index Medicus, Google Scholar, Cochrane library, and university databases. Advanced search, on major databases, was applied to retrieve relevant findings closely related to colonization with carbapenem-resistant  program .Identified records were exported to ENDNOTE reference software version 20.0.1  with compatible formats. Records with duplication were traced, documented, and removed with ENDNOTE and manually due to variation in referencing styles across sources. Afterward, the title and abstract of the article were screened by TT, HM, and ME in triplicate with predefined inclusion criteria and full texts evaluation for eligibility.There were predefined inclusion-exclusion criteria to come up with the final included articles during the initial screening of titles and abstracts and evaluating full texts for eligibility.K. pneumoniae among patients or community memberArticle dealing with intestinal colonization of carbapenem-resistant K. pneumoniaeRetrospective and prospective studies addressing the prevalence or incidence of colonization with carbapenem-resistant Online records published in the English languageResearch article which fulfills the following criteria were included and eligible for further analysisIt is a review article regardless of the contentK. pneumoniae or characterization of isolates from infection siteDealing with infection of K. pneumoniae colonizationIf the outcome is incomplete or missing, or if it does not indicate the prevalence or incidence of carbapenem resistant The full article is not accessible after communicating with author (after requesting authors via email and/or Research Gate).Articles are excluded for the review ifFor the incidence of CRKP colonization, a patient who was admitted with a negative CRKP stool culture but later received a positive result at any point after thatFor the prevalence of CRKP colonization, a person who tests positive for stool culture at the time of admission, during admission, or in the community.We have utilized the following case definitions for prevalence and incidence of colonization:The number of carbapenem-resistant culture-positive results was the outcome of interest. Using a data abstraction format made in Microsoft Excel, significant information about study characteristics , type of drug resistance genes, etc.) was extracted by TT and HM (Sheet 1).Critical appraisal to assess the internal (systematic error) and external  validity of studies and to reduce the risk of biases was conducted by TT, HM, and ME separately according to the Joanna Briggs Institute critical appraisal tools for prevalence study, case-control study, and cohort studies , 30 and I2 statistics and predictive interval. A univariate meta-regression model was performed on study characteristics to assess the possible source of heterogeneity. Egger’s test was used to evaluate the presence of publication bias and presented with funnel plots of the standard error of proportions [p value less than 0.05 (one-tailed) was considered a cutoff point for statistical significance.Relevant data extracted onto format in Microsoft Excel and exported to STATA 16  for analyses of outcome measures. DerSimonian and Laird’s random-effects model was applied for the analyses at a 95% confidence level considering variation in true-effect sizes across the population . Heterogeneity of studies was determined using portions . A p valK. pneumoniae.The primary outcome measure is the prevalence and incidence of colonization with carbapenem-resistant We performed a systematic review following the PRISMA statement , and aftK. pneumoniae.As shown in Table With the exception of two studies from India  and CambI2 value of 97.87% . Five of the published studies are from Asia , 45, 64,The incidence of colonization was 22.3% CI 12.74–31.87)  and for incidence of colonization (p=0.017)  Fig. .Fig. 7FuK. pneumoniae. This is the first report, to the best of our knowledge, on the global frequency of human colonization with carbapenem-resistant K. pneumoniae. This report also details the occurrence of resistance genes in different geographic locations. Studies show that colonization with carbapenem-resistant K. pneumoniae is increasing from 2010 until now. This review evaluates 37,661 patients from 18 countries between 2010 and 2021.This analysis included 35 original studies addressing colonization with carbapenem-resistant K. pneumoniae is 5.43%. This finding indicates that a significant portion of the population is colonized with CRKP, which a tremendous burden as colonization could be a risk factor for infection, and one in third of people infected with CRKP will die [K. pneumoniae colonization in Europe was 1.2%, 0.3% in the Americas, and 0.07% in Africa. Only two studies have reported colonization with carbapenem-resistant K. pneumoniae in Africa, from Egypt and Morocco. This picture may not represent the practical scenario as most countries, especially Africa and America have no data on colonization with CRKP.The pooled prevalence of colonization with carbapenem-resistant will die . The stuThough higher prevalence is reported in China and India, there is still variation within those countries’ reports. In China, the prevalence report ranges from 1  to 21% , and alsI2 statistics showed a high heterogeneity even after subgroup analysis and sensitivity testing, but the prediction interval was relatively narrow (4–7%).The metaregression analysis on the type of admission ward has not shown any difference in colonization likewise with continents, sample size, and study design. The This finding indicates a significant threat posed by the pathogen as colonized peoples will be a source of infection for themselves and others, and people infected with CRKP have a higher healthcare cost and mortality , 68.The incidence of CRKP colonization was reported in 3643 admitted patients, and most of the studies included patients admitted to ICU. As people admitted to ICU are not devoid of several invasive procedures facilitating the introduction of microorganisms to other systems, a high incidence of CRKP colonization poses a higher risk of nosocomial infection with CRKP. CRKP is found commonly on contaminated medical devices and hands of medical personnel in addition to the patient gastrointestinal tract . All patEuropean countries have reported a high incidence rate (14.03%), 3.2% in Asian countries, and 0.14% in Africa. For the occurrence of CRKP colonization, only South Africa represents Africa, and Greece and Italy represent Europe. The pooled estimate of colonization incidence is 22.3%, with significant variation between continents (9.8% for Asia and 37.5% for European countries). These continent data variations could be due to data unavailability with the absence of well-organized surveillance programs in healthcare settings of other continents, unlike Europe.In general, the finding indicates that the risk of colonization is higher in institutional and healthcare settings than in communities where such pathogenic bacteria will have been derived from patients and have continual exposure to last-resort drugs. The reality on the ground could be significantly higher as the data is generated only from a limited number of studies and few countries.Controlling the spread of drug-resistant bacterial isolates involves strict adherence to the infection control program, early detection, and restricted utilization of antibiotics. Early screening and detection of colonization allow rapid control by contact precautions. Infections with CRKP has important implication due to limited treatment options and the risk of an outbreak from environmental contamination , 74. As Only blaKPC was reported from the Americas, with blaKPC-2 being the most prevalent, while the most frequent carbapenemase-producing gene, blaKPC, was recorded from all continents except Africa. Other genes like blaVIM, blaOXA-like, and blaIMP were reported from different continents. The most reported variant of blaOXA-like was blaOXA-48 in many parts, but one variant, blaOXA-181, was reported only from Kuwait. European countries have not reported blaNDM variants though these variants were common in Asian countries. This finding is in line with , 80 wherSeveral earlier studies have demonstrated the widespread occurrence of KPC gene variants, primarily blaKPC-2 and blaKPC-3, as well as NDM and OXA-48 from middle eastern nations –85. CounHeterogeneity across studies represents a critical limitation in combining observational studies for meta-analysis. We attempted to limit this heterogeneity through the use of relatively narrow inclusion criteria and assessing the quality of included studies via a JBI protocol. For the identified heterogeneity, we use meta-regression to explain potential sources of heterogeneity. Although a large number of patients are part of the studies, the small number of included studies limited the power to assess for publication bias.The strength of this review lies in its adherence to established methods for conducting systematic reviews, extensive searching, an inclusive date range, and a combined quality assessment of the included studies. Compiling all available evidence on this matter will help Healthcare settings for an informed decision for screening and segregating colonization, organizations working on human health to devise strategies in the decolonization of colonized peoples as well as design a plan to reduce colonization with this resistant pathogen.K. pneumoniae and drug resistance genes. Under-developed nations and community people are underrepresented in this study as most studies come from developed countries and medical settings. Studies have reported a variable distribution of colonization with K. pneumoniae from different areas ranging from 0.13 to 22% for prevalence in the community or at admission into setup, whereas the incidence colonization ranges from 2 to 73%, with a pooled prevalence of 5.43% and incidence of 22.3%. The incidence rate is relatively higher than the prevalence depicting that colonization is more elevated in healthcare settings than in the community. There was a significant heterogeneity in both prevalence and incidence pooled estimates with I2 statistics, yet, the predictive value for the prevalence is narrow.In conclusion, this review details the prevalence and incidence of colonization with carbapenem-resistant On the other hand, various drug resistance genes have been reported from colonizing strains, KPC and NDM being common, in Asian countries mainly. All in all, resistance genes have variable distribution across geography.K. pneumoniae which alarms devising a strategy for decolonization.As most of the reports are from healthcare settings and in developed countries, there is no clear picture of the problem in the community and the developing world. Thus, we recommend more studies from developing parts of the world and community setting. In general, this review has detailed a higher presence of colonizing Additional file 1.Additional file 2.Additional file 3.


Proteinuria, frequently observed in hypertensive crisis, is a risk factor for cardiovascular and all-cause mortality in patients with hypertension. Here we investigated the association between proteinuria and all-cause mortality in patients with a hypertensive crisis in the emergency department (ED). This retrospective study included patients admitted to the ED of a tertiary referral center between 2016 and 2019 with hypertensive crisis (systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg); 3599 patients with an assay for proteinuria were included in this study. Proteinuria was defined as a trace or more protein on a urine dipstick test. Proteinuria was present in 1964 (54.6%) of 3599 patients. At 3 years, crude all-cause mortality rates were 10.8% for patients with negative proteinuria, 21.7% for those with trace proteinuria, 29.0% for those with proteinuria (1+), 32.0% for those with proteinuria (2+), and 35.4% for those with proteinuria (≥3+). After adjusting for age, sex, blood pressure, and comorbid conditions, the hazard ratio  for dipstick proteinuria was 1.91 (1.53–2.37) for those with trace proteinuria, 2.32 (1.85–2.91) for those with proteinuria (1+), 2.40 (1.86–3.10) for those with proteinuria (2+), and 2.40 (1.78–3.24) for those with proteinuria (≥3+) compared to the reference of negative proteinuria. In patients with hypertensive crisis, dipstick proteinuria was a significant predictor of all-cause mortality, and the risk of all-cause mortality increased in a dose-dependent manner according to its degree. Moreover, even trace proteinuria was associated with an increased risk of mortality. The dipstick urine test could be used as a simple and useful method for risk assessment of all-cause mortality in patients with hypertensive crisis. Hypertensive crisis presents as an abrupt elevation of blood pressure (BP) associated with or without hypertension-mediated organ damage (HMOD) . ApproxiProteinuria, which is a marker of renal damage and a marker of HMOD, is associated with an increased risk of cardiovascular disease and all-cause and cardiovascular mortality . The diaSeveral studies have demonstrated the association between proteinuria and mortality outcomes in patients with hypertension and the general population ,8,9,12. This observational study was conducted at a single regional emergency medical center affiliated with the Academic University Hospital in Guri-si, Gyeonggi-do, Korea. Detailed information about the study design and definitions used in the study have been previously published ,13. In bUrine protein levels were measured using AUTION dipsticks  using a fully automated urine chemistry analyzer  during the index visit, which was part of the routine care for admitted patients in our hospital throughout the study period. The dipstick reader and strips are known to be reliable based on the database of the Korean Association of External Quality Assessment Service . Using aData were collected using electronic medical records by trained data collectors under the supervision of the principal investigator. The collected data included demographic and clinical characteristics, cardiovascular risk factors, BP, previous medical history, presence and types of acute HMOD, and diagnostic test findings at the index visit to the ED. In addition, events during the hospitalization and follow-up periods  were collected. In the ED, BP was measured on the brachial artery using an automated BP machine, Spot Vital Signs LXi . Cardiomegaly on chest radiography was diagnosed when the ratio between the maximal horizontal cardiac diameter and the maximal horizontal inner thoracic cage diameter was >0.5 . Left veThe included patients were followed up until death from any cause or on March 2021 (study endpoint), whichever came first. The incidence and timing of mortality were obtained from the National Health Insurance Service in South Korea.Continuous variables were presented as means , whereas categorical data were presented as numbers (percentages). One-way analysis of variance was performed to compare baseline characteristics according to the degree of proteinuria for continuous variables. The Cochran-Mantel-Haenszel test was performed to show the trend of the categorical data according to the degree of proteinuria. The Kaplan–Meier method and log-rank test were used to compare cumulative survival probability. 2), and presence of diabetes mellitus by constructing a multivariable Cox model with adjustment for the same variables. All tests were two-tailed, and the null hypothesis was rejected for a value of p < 0.05. All analyses were performed using the Statistical Analysis Software package .Using a Cox proportional hazard model and negative proteinuria as a reference, hazard ratios (HRs) and 95% confidence intervals (CIs) for 3-year all-cause mortality according to the degree of proteinuria were analyzed. A multivariable Cox proportional hazard model was performed by adjusting for other clinically relevant variables, including baseline characteristics , comorbidities , and components of subclinical HMOD . Furthermore, subgroup analyses were performed on the basis of age (<65 or ≥65 years), sex, presence of acute HMOD, estimated glomerular filtration rate (eGFR) . Other principal diagnoses included neurologic disorders , and infectious diseases (12.9%) . Follow-p <0.001). There were no differences between groups in the rate of ED revisits and rate of readmission within 1 month; however, rates of ED revisit and rates of readmission within 3 months and 1 year increased along with the degree of proteinuria  patients were admitted and 1108 (30.8%) patients were discharged: 288 (8.0%) patients were discharged against medical advice, and 4 (0.1%) patients died in the ED. The admission rate increased with the degree of proteinuria, while the discharge rate decreased with the degree of proteinuria (both teinuria .p < 0.001). In contrast, this trend was not prominent in patients with acute HMOD. However, the cumulative survival probability was significantly lower in patients with proteinuria than in those without proteinuria. During the follow-up period, 3-year all-cause mortality increased along with an increase in proteinuria in all patients A. At 3 yTo examine the independent association between proteinuria and all-cause mortality, we performed a Cox regression analysis . In the 2), and presence of diabetes mellitus. The adjusted HRs and 95% CIs for 3-year all-cause mortality of the four categories , proteinuria (2+), and proteinuria (≥3+)) were similarly higher than negative proteinuria in all subgroups, except that trace proteinuria in patients aged <65 years were not significantly associated with an increased risk of 3-year all-cause mortality , sex, presence of acute HMOD, eGFR (<60 or ≥60 mL/min/1.73 mortality .This study investigated the association between dipstick proteinuria and the risk of long-term mortality in patients with hypertensive crisis. Patients with proteinuria had a higher risk of mortality independent of other risk factors, including age, sex, BP, comorbidities, and components of subclinical HMOD. The risk of all-cause mortality increased in a dose-dependent manner according to the degree of dipstick proteinuria. Our study findings suggest that the dipstick proteinuria test may be valuable for identifying patients with a hypertensive crisis who are at high risk of mortality.Hypertension can be both a cause and a complication of chronic kidney disease. Moreover, uncontrolled BP, which can lead to rapid renal impairment and even mild reductions in kidney function, is associated with a higher risk of cardiovascular events in hypertensive patients ,18. TherProteinuria is a marker of kidney disease and is associated with cardiovascular disease and mortality in the general population. In addition, studies in hypertensive populations indicate that proteinuria is an adverse prognostic indicator of clinical cardiovascular disease and mortality ,22. MoreSeveral potential mechanisms may help explain the relationship between proteinuria and all-cause mortality in patients with hypertensive crisis. First, patients with a higher degree of proteinuria had a higher frequency of acute HMOD. Second, patients with a higher degree of proteinuria tended to have more comorbidities and cardiovascular risk factors such as hypertension, diabetes mellitus, ischemic or hemorrhagic stroke, coronary artery disease, heart failure, and chronic kidney disease. Third, patients with a higher degree of proteinuria more frequently showed abnormal laboratory findings associated with subclinical HMOD, such as cardiomegaly on chest radiography, and LVH on ECG; in addition, these patients had higher levels of creatinine, troponin-I, and BNP associated with a risk of adverse cardiovascular events ,27,28. MIn this study, we used a urine dipstick test, which is routinely used in daily practice in the ED to assess proteinuria. There are concerns over the low sensitivity and accuracy of the urine dipstick test for the detection of proteinuria . HoweverTaken together, our results suggest that the identification of proteinuria by a simple dipstick urine test may be important in the management of patients with hypertensive crisis in the ED. Early detection and treatment of kidney injury can help clinical doctors determine appropriate kidney protective agents for high-risk patients. Moreover, as a result of this study, the dose-response increase in all-cause mortality risk according to the degree of proteinuria suggests that proteinuria reduction would have a beneficial effect on the prevention of mortality. Modifications in lifestyle factors and antihypertensive therapies such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may provide an additive effect on the reduction of proteinuria ,36,37. TOur study has a few limitations. First, it was a single-center retrospective study. Given its retrospective nature, data on the study participants’ baseline characteristics were insufficient compared with those of prospective studies. Due to the limitation of the observational design without interventions, we could not conclude whether proteinuria had a causal effect on the risk of mortality or only reflected other deteriorating conditions associated with uncontrolled hypertension. We were also unable to explain the exact mechanism of the association between proteinuria and the risk of all-cause mortality. Second, urine dipstick proteinuria was assessed using a single measurement, which may have led to a measurement error. Although this value may be inaccurate, it can better reflect the actual screening test in practice. Moreover, we collected only the diagnostic test results that were performed in the ED. Third, as we used only initial BP values and did not consider BP control in the ED or after discharge, further analysis of the outcomes according to the BP control patterns was limited. In addition, we could not obtain data on the reasons for revisits or readmissions after the index ED visits. Fourth, we could not identify the cardiovascular and renal events or cardiovascular mortality because the National Health Insurance Service data did not provide information on the causes of death. However, data regarding all-cause mortality and date of death were mathematical because they were obtained from the National Health Insurance Service, which covers the entire Korean population. Fifth, the study included data from a single center, it may not be representative of the entire population. Further research is needed to determine the optimal screenings, risk stratifications, and treatment strategies related to cardiovascular events or deaths according to dipstick proteinuria results in patients with hypertensive crisis. Finally, diagnostic tests, including the dipstick urine test, were not performed in all patients, and it is possible that more tests were performed in relatively high-risk patients than in low-risk patients. Therefore, selection bias could not be excluded from this study.In conclusion, the present study demonstrated that dipstick proteinuria was an independent risk factor for long-term mortality in patients with hypertensive crisis. The risk of all-cause mortality increased proportionally with the severity of dipstick proteinuria. Moreover, even trace proteinuria was associated with an increased risk of mortality. Further, large-scale clinical studies should be conducted to investigate the exact mechanisms of proteinuria and the risk of death in patients with hypertensive crisis.


Depression and alcohol dependence (AD) are among the most prevalent psychiatric disorders that commonly co-occur. Therefore, gaining a better grasp of factors related to this comorbidity is particularly interesting for clinicians. Past research has highlighted the significant role that time perspective and family history of alcohol dependence (FH) play in the occurrence of depression and AD. However, much remains unexplored in the understanding of the association between them. This study explored how temporal profile and other sociodemographic characteristics of patients diagnosed with AD impact the severity of depression and AD in them.This study was multi-centered, including 381 patients. Cross-sectional information was collected from both inpatient and outpatient psychiatric clinics in China. Data were acquired using validated self-report scales, including Michigan Alcoholism Screening Test, Zung Self-Rating Depression Scale, and Zimbardo Time Perspective Inventory-Chinese version. Multiple linear regression analyzes were conducted to control social demographic variables and construct prediction models to inspect the influence factors of variables. Moderation models were constructed to inspect further interplay between variables using hierarchical regression and PROCESS Macro.Results showed that of all the patients in Chinese psychiatry clinics diagnosed with AD according to the International Classification of Diseases-10, 59.9% met the criteria of depression according to the questionnaire, and time perspective was correlated with the severity of depression. Furthermore, using regression analysis, we found that time perspective and depression could predict AD severity. The moderating role of a past negative time perspective and FH was confirmed between depression and AD. We found that, in our study, only in patients with FH and relatively moderate to high scores of past negative time perspective could the severity of depression predict the severity of AD. Therefore, during the treatment and care of patients with AD, their depression level, time perspective score, and FH should be considered. DSM-V , with mild, moderate, and severe classifications.The excessive and harmful use of alcohol has been associated with more than 200 diseases, unintentional injuries, and sometimes even death. Studies have found that repeated consumption of alcohol in large quantities over an extended period is detrimental to both physical and mental health. Globally, alcohol is the seventh leading risk factor for poor health, accounting for 4.2% of total disability-adjusted life years (DALY) and 5.2% of deaths in 2016  , PF (r = 0.29), and PP (r = –0.32) time perspectives among general populations in China, although PI and F showed insignificant results. Few studies have sought the relationship between time perspective and relation in the context of patients with psychiatric disorders. One study found that clinically depressed patients showed a tendency to focus more on negative past experiences (PN) and fatalism (F), whereas less on the present moment (PI)  and fatalistic present (PF) and lower levels with positive past (PP), hedonistic present (PH), and future orientation (F) . Another study from France enrolled outpatient participants (n = 139) and added all five dimensions into one regression model to predict the severity of AUD; however, no significant variable was found  The heterogeneity could also be caused by different questionnaires utilized in the study to assess depression and alcohol-related problems. More importantly, earlier studies have not focused on the moderating role of time perspective or FH, exploring when depression could predict AD severity. Thus, our study is the first to examine the moderation effect of time perspective and FH in the relationship between depression and AD.The etiology of co-morbid depression and AD has been widely studied. In addition, many studies have addressed AD, depression, and how time perspective and FH are associated with the two disorders. However, neither the time perspective nor FH's role has been explicitly studied in the relationship between depression and AD in a clinical setting. Furthermore, data from Chinese cultural backgrounds are warranted, which would make valuable contributions to the existing body of research. This study aimed to examine the cross-sectional condition of the temporal profile, depression severity, and alcohol dependence in patients with AD in Chinese addiction treatment clinics. We also investigated how scores of the five ZTPI sub-scales and sociodemographic information would relate to the severity of depression and predict the severity of AD. Accordingly, the following hypothesis was proposed:Hypothesis 1 (H1): Among patients with alcohol dependence, the Zung Self-Rating Depression Scale (SDS) score, Past Negative score (PN), Present fatalistic score (PF), Present impulsive score (PI), as well as a positive family history of alcohol dependence (FH) will positively predict Michigan Alcoholism Screening Test (MAST) score; Past positive score (PP) and Future score (F) will negatively predict MAST. SDS score is positively correlated with PN and PF and negatively correlated with PI, F, and PP.Few studies target patients with alcohol dependence, investigating the role depression plays in contributing to AD severity. In light of previous studies indicating genetic susceptibility could explain the causative effect of depression on AD : Among patients with AD, FH and time perspective  would interact with depression and have a moderate association between depression and AD.Our study is expected to expand the knowledge regarding the comorbidity of depression and alcohol dependence in patients with AD. It is of contemporary relevance as its results can help target interventions for patients experiencing or those susceptible to experiencing the disorders of alcohol use and depression as comorbidity. Moreover, it is especially relevant to the Chinese context, considering the genetic differences between Chinese and Western individuals and social differences related to alcohol consumption in Chinese context.Our research interest was in Alcohol Dependent patients, which existed in DSM-4 and ICD-10 instead of DSM-5. AD is more severe and devastating compared to alcohol abuse, and previous research reveals that genetic susceptibility could explain the causative effect of depression on AD, instead of AUD. In our study design, we decided to choose AD patients diagnosed by psychiatrists, instead of both AD and alcohol abuse patients.Questionnaires were distributed by trained healthcare workers in outpatient and inpatient departments of multiple psychiatric clinics, including psychiatric hospitals located in Wenzhou, Hangzhou, and Shaoxing, from January to December 2020. The inclusion criteria of participants were: (1) Diagnosed with AD according to the ICD-10; (2) having a stable mental condition, not accompanied by hallucinations, delusions, or other psychotic symptoms; having clear consciousness, and the ability to understand the questionnaire; (3) signing the informed consent or getting it signed by a family guardian; (4) being aged between 18 and 75 years old.The exclusion criteria, based on the structural interview by medical staff, were the following: (1) having other psychiatric disorders such as intellectual disability, dementia, schizophrenia, and affective disorders; (2) having severe and unstable major somatic diseases; (3) engaging in abuse of other psychoactive substances.R2 was from 0.10 to 0.21, and ΔR2 was from 0.001 to 0.005  , education level, monthly income, and whether they lived alone or with others. They were also asked about who mainly took care of them (which meant whether they were being visited regularly and supervised to take medications), family history of AD (parents or grandparents), for how long they had been drinking heavily (consuming more than four drinks on any day for men and more than three drinks for women), and the number of times they had been to psychiatry clinics for alcohol use problems. We added demographic variables to the regression models to see whether these potential risk factors would impact the dependent variables.Our study used a validated Chinese version of ZTPI (ZTPI-C). The author indicated that, after revision of the inventory, the “present hedonistic” dimension only reflected impulsivity. Therefore, similar to the change implemented by the authors, we also used “Present Impulsivity” instead of “Present Hedonistic,” . All the mean comparison tests were two-tailed, and n ≥ 30), the distribution of sample means will be approximately normally distributed. We, therefore, applied the normal probability model to quantify uncertainty when making inferences about a population mean based on the sample mean.According to the Central Limit Theorem, when the sample is large enough . We also calculated Cohen's d for the t-test and eta squared for ANOVA as effect size.For groups with data distributing normality, we used Mean ± SD for description, and for data without normality, we used Median ± Interquartile for description. To compare quantitative data between subgroups, we used Correlation analysis was used to examine the extent to which two quantitative variables are linearly related. For quantitative and ordinal variables, we used Pearson's correlation. These analyzes quantify the direction and strength of the relationship between two variables.For multiple linear regression, the following few assumptions needed to be tested: (i) each predictor has a linear relation with our outcome variable; (ii) the prediction errors are normally distributed in the population; (iii) the variance of the errors is constant in the population (homoscedasticity). Assumptions were checked before making conclusions.Michigan Alcoholism Screening Test was the outcome value. Besides the scores for five dimensions of time perspective , we also input age and times (times to the AUD treatment clinic) into the regression model. “Income,” “education level,” and “years of heavy drinking” were ordinal variables, and we put the directional numbers into the model. We had dummy-coded nominal variables into multiple dichotomous variables, including insurance type, marital status, family history, caretaker, gender, inpatient or outpatient treatment, and whether the participant lived alone. This step was followed by adding these variables into the regression model. We eliminated dummy-coded marital status from the regressors because the variance inflation factor went above 5 when adding this variable.p-values and the criteria in which probability-of-F-to-enter. ≤ 0.05, Probability-of-F-to-remove ≥ 0.1, was used to limit the total number of variables included in the final model. Adjusted R square indicated the proportion of variance in the dependent variable accounted for by the predicted values. Standardized coefficients β were the values for the regression equation for predicting the dependent variable from the independent variable after standardization.Stepwise linear regression analysis was used to identify possible predictors of the outcome out of the above-listed candidate variables. At each step, variables were added based on To conduct moderation analysis, we utilized hierarchical multiple regression analysis and bootstrap analysis employing the PROCESS macro  Hayes, . We firsThe composition of participants and values of quantitative variables in demographic subgroups in the study are presented in Patients being female, have a self-paid insurance type, negative family history of alcohol dependence, a longer duration of drinking, and lower income, tend to have a higher score of SDS. Medical treatment type (inpatient or outpatient) did not affect MAST or SDS. We also found that patients being visited regularly and supervised by parents tended to have higher SDS and MAST scores, and patients supervised by their spouse tended to have higher depression scores compared with having any other type of caregiver (such as friends or siblings) or no caregiver.r = 0.23, r = 0.14, respectively) and SDS . PP and F displayed a negative correlation with SDS , yet showed no significant correlation with MAST . PN had a positive correlation with MAST (r = 0.23), and no significant correlation with SDS (r = 0.04). MAST and SDS were positively correlated.R2 = 0.17, P < 0.01). Higher scores in PN , PI , and the SDS score  positively predicted the MAST score. Patients with more frequent relapse  and higher income  had more severe AD. We also found that patients who lived alone , and were supervised and visited by parents to have their condition monitored  tended to have higher MAST scores , family history still played a significant role in AD pathology.To test the hypothesis that time perspective and FH moderate the predictive relationship of depression on AD, we performed hierarchical multiple regression as well as Hayes's process. All variables had been standardized. We conducted five moderation analyzes for each dimension of time perspective , in whicβ = –0.03, p = 0.5). Therefore, PN did not interact with FH, while they both interact with SDS.In addition, since a family history of AD could lead to higher scores of PN than no history, we tested whether the interaction between PN and FH would also significantly influence the association between depression and AD. After putting SDS, PN, FH, and the interaction terms, PN*SDS, FH*SDS PN*FH into the hierarchical regression model, the interaction between PN*FH was insignificant in predicting MAST . In it, patients with a positive FH had a lower major depression disorder rate (25.4%) than patients with a negative FH (63.6%), which was consistent with our study results , and longer duration of heavy drinking were found to be associated with less depression. Consistent with previous research . Studies have shown that depressed patients showed decreased present hedonism (PH) scores . This converse finding might stem from the property of ZTPI-C's PI subscale, which, as the authors indicated, merely reflected impulsiveness, instead of hedonism , but acted as a protective factor against depression. The unexpected results related to FH and heavy drinking duration may relate to alcoholism type. Type II alcoholism, being primarily genetically driven, has an earlier age of onset. Hence, it is more closely associated with a family history of alcohol-related problems. Type I alcoholism, being less genetic in nature, has a later age of onset but is more closely related to anxiety and depression  scores, widely used to assess problematic alcohol consumption. In these studies, R2 was 14.2%  of depression in alcohol-dependent patients. We also verified the predictive effects of temporal profile in AD, hence offering a more comprehensive understanding of the time perspective profile of patients with AD. The study demonstrates that time perspective should be taken into account during the treatment and nursing care of patients with AD. Identifying patients with biased time perspectives and providing them with tailored interventions including time-related alterations could help promote change in depression and alcohol-related problems. Moreover, we clarified the moderating roles of a PN time perspective and FH of AD in the association between depression and AD, as an enhancing effect. Screening patients with a family history of AD and a negative past perspective is valuable during treatment. We suggest that specific intervention programs tailored for patients with FH and negative perceptions of the past constitute a valid therapeutic path for addressing the comorbidity of depression and AD.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Affiliated Mental Health Center & Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, China. The patients/participants provided their written informed consent to participate in this study.HW and XZ acquired the funding, composed the research proposal, and collected data. YZ and HW were responsible for data processing and composing the manuscript. All authors contributed to the article and approved the submitted version.HW and XZ were supported by Medicine and Health Science and Technology Plan Project of Zhejiang Province, China (No. 2020KY746). Open access funding provided by École Polytechnique Fédérale de Lausanne to YZ.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Subjects with tooth wear showed significantly higher free testosterone levels than those without . After controlling for confounding variables, the risk of tooth wear increased by approximately 30.0% with each year of life . In addition, the risk of tooth wear increased by 6.0% per free testosterone scale score only in boys . (4) Conclusions: Tooth wear is common in children and in adolescents, and it increases steadily with age in both sexes. The stronger increase and the higher prevalence among male adolescents can be explained by the additional effect of free testosterone.(1) Background: From a young age, boys are more often affected by tooth wear than girls. This suggests an influence of the male sex hormone (testosterone) on the aetiology of tooth wear. The aim of the present study was to investigate the incidence of tooth wear in relation to steroid hormone levels in children. (2) Methods: 1022 test persons aged between 10 and 18  from the LIFE Child study underwent medical and dental examination. Tooth wear was measured through clinical inspection. Blood samples were taken to determine hormone levels . The level of free testosterone was calculated from the ratio of testosterone to SHBG. Using multivariable methods, the incidence of tooth wear was analyzed as a function of hormone levels, while controlling for confounders such as age, sex, social status, and orthodontic treatment. (3) Results: The incidence of tooth wear increased with age in both sexes. Boys showed significantly more often attrition facets than girls (17.5% vs. 13.2%,  As caries experiences throughout young adults are considerably declining, the daily practicing dentist is becoming more focused on treating abnormal degrees of tooth wear . AttritiThe loss of tooth structure represents a clinical sign of bruxism, next to fractures of teeth or restorations, hypersensitive or painful teeth, masticatory muscle hypertrophy, and others . The losDue to past studies perceiving that bruxism is not solely teeth grinding or clenching, an international team decided on a new universal definition in 2013. There, it was added that bruxism can, as well or exclusively, describe the bracing or the thrusting of the mandible . BruxismBruxism’s importance, as with any other health condition, is determined by its impact on patients, i.e., its quality-of-life influence and how often this impact occurs and lasts. Indeed, bruxism is one of the most frequent chronic oral health conditions, lasting over substantial time periods and even spanning one’s lifetime ,12,13,21Studying the hormone–bruxism relationship in children and in adolescents offers a unique opportunity because hormone levels change substantially over one’s lifetime. Unfortunately, as pointed out above, only a limited number of studies exist, and those that do exist typically suffer from methodological problems. On the one hand, the evaluation system is not yet fully accepted as knowledge about bruxism and its aetiology is still improving. In most cases, bruxism is measured by self-report or tooth wear . On the The present study aimed to investigate the relationship between the blood levels of sex hormones and attrition facets in male and female children and in adolescents, while considering potential confounders .The LIFE Child study  is a part of the “Research Center for Civilization Diseases”, and it is a large epidemiological as well as population-based cohort study of the University of Leipzig. The dental examination was approved by the Ethics Committee of the University of Leipzig (registration number: 354-10-13122010), and it took place between May 2012 and August 2015. This study includes 1022 participants between the ages of 10 and 18 years , who were medically and dentally examined . From thBefore starting the medical and the dental examinations, parents and participants received information about the aim and the procedure, obtaining from them written approval. The test persons or guardians filled in a questionnaire with information about general health, medical history, socioeconomic status, and well-being. The survey took place in the study center from 2012 until 2015 by calibrated dentists according to standardized procedures. The oral health assessment was performed in a dental chair, with the use of a halogen light, a blunt probe, compressed air, and a mirror. The clinical data, such as orofacial pain, attrition, and orthodontic treatment, were collected with the help of a data processor. Wisdom teeth were not included in the assessment.The outcome of interest was dental attrition (tooth wear). It was assessed for all anterior teeth (incisors and canines of maxilla and mandible). First, qualification of the tooth wear took place according to the clinical appearance described by Gandara and Truelove ,4: shiny2 and antagonistic teeth showed corresponding wear facets. Tooth wear was dissected for further analyses by means of two categories: the category “tooth wear” corresponded to grade 1 to 4 (wear in enamel and/or exposed dentin and/or loss of crown height) of the TWES  /height [m]the norm . NegativSocioeconomic status (SES) was assessed using the Winkler Index  that disPubertal development was evaluated using the 5-level Tanner scale  (secondaOrthodontic treatment was determined and divided into the categories “Yes” (orthodontic appliance in past or present) or “No” (no appliance in past or present).t-test concerning continuous variables  and the chi-square test concerning categorical variables . Secondly, multivariable logistic regressions were performed to analyze the association between incisal tooth wear and the sex hormone level after controlling for the influence of confounding variables. All analyses were performed using IBM SPSS Statistics 24.0 software The incidence of dental attrition  was presented separately regarding the sexes of the test persons. Based on the absence or the presence of tooth wear, each group of female and male participants was then split in two categories. Firstly, the subjects of each sex were compared according to their category (tooth wear yes/no) regarding age, adjusted BMI, Tanner stage, socioeconomic status, orthodontic treatment, and hormone levels. Statistical tests were then performed: the n = 984) were affected by tooth wear (n = 151). Among the 10- to 13-year-old children (n = 620), a tenth  were affected by tooth wear, whereas it applied to one quarter  of the youth aged 14 and older (n = 364). A constantly higher percentage of boys with dental attrition than girls was observed. Among the male test persons (n = 491), 17.5% were affected by tooth wear (n = 86). Among the female test persons (n = 493), 13.2% were affected by tooth wear (n = 65). Additionally, the respective percentage increases at a stronger rate among the male participants [n = 33) of the 10- to 13-year-old and 31.0% (n = 53) of the 14- to 18-year- old boys. Concerning girls, the incidence of attrition facets shows a constant rise from 8.3% (n= 25) of the 10- to 13-year-olds to 20.7% (n = 40) of the 14-year-old and above group. A statistical significance of p < 0.001 is given for both sexes.In this study, 491 boys and 493 girls, between the ages of 10 and 18, were included in the analyses. In total, 15.3% of all participants (icipants . Tooth wp < 0.001). Among female subjects with tooth wear, the serum level of testosterone and free testosterone was significantly higher than without (p < 0.05). The body mass index and the socioeconomic status score did not differ between children with or without attrition facets. Additionally, a deviation between the number of children with or without tooth wear under orthodontic treatment could not be seen.Regardless of the sex, test persons with attrition facets showed significantly higher ages and higher Tanner stages . FurtherMultivariable analyses reveal a significant increase in tooth wear with age in both sexes as well as an additional effect of testosterone in males . The oddThe present study aimed to answer the question of whether the incidence of tooth wear was attributed to the higher sex hormone levels of children and/or adolescents. In the multivariable analyses, the prevalence of tooth wear as a cumulative lifetime experience increased with age in both sexes. Amongst boys, an additional effect of free testosterone on tooth wear was observed, that is, the higher the hormone level, the more frequently attrition facets were present. Because dentists are not able to influence the hormonal status of their patients, the options for dental therapy based on this knowledge are limited. However, we now have a better understanding of the aetiopathogenesis as well as another diagnostic marker for bruxism. Furthermore, it is a possible explanation for the sex differences in bruxism among juveniles. These considerations contribute positively to the dental consultation with patients and the current scientific debate on bruxism.Until now, there were no studies that considered the influence of sex hormone levels on wear facets amongst children and adolescents. There are several reasons for this. First, there are ethical difficulties in obtaining blood samples. The present study was embedded in a large project (LIFE Child study) in which, among other things, blood was obtained ,44. No bTooth wear is a cumulative lifetime experience. The observed attrition may have taken place in the past or may still be ongoing in the present.It has been associated with the hormone status of individuals. However, in an earlier publication we were able to show that sex hormone status stays constant for at least 2 years concerning the 10- to 18-year-old subjects . So, we The universal comparability of the results is partly limited due to the following reasons. First, there is a wide range of grading scales for tooth wear. In the present study, a modified scale described by Egermark-Eriksson 1982)  is emplo  is emplEven if the loss of tooth structure is a major clinical sign of bruxism, it is not itself sufficient to make a definitive diagnosis of bruxism . Tooth wThere is currently no consensus on which hormone should be studied in the context of bruxism. Recent studies have contested the long-prevailing belief in a direct association between bruxism and the stress hormone cortisol that is usually isolated from the saliva ,55. BecaMany risk factors besides hormones can trigger bruxism. In a case-control study, a consideration of additional risk factors such as caffeine, alcohol, sleep problems, stress, or anxiety  would beAs participants of higher compliance and social inclusion are more likely to take part in that kind of study , a shiftIn conclusion, the results of the current study revealed a positive association between serum levels of testosterone (index of free androgen) and tooth wear in male adolescents. Therefore, the higher level of sex hormones could be an accompanying factor for this phenomenon. The observed effect was independent of age, sex, and other possible confounding factors such as BMI or orthodontic treatment. This study contributes positively to the understanding of the aetiology of bruxism in the current scientific debate. Therefore, it represents a clinical benefit in an improved dentist–patient communication. The dentist can explain that tooth wear occurs more likely in boys and that it may be accompanied by a higher testosterone level in the affected person.


To investigate the prevalence of depression or anxiety in patient with multiple myeloma (MM) in China during maintenance treatment and its associated influencing factors.n = 160) received maintenance therapy, and control subjects  matched on age, sex, and BMI were recruited. Patients completed questionnaires, including the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder 7-item Scale (GAD-7), and the Verbal Pain Rating Scale (VPRS). Data on the Clinical characteristics, biochemical indicators of de novo MM were from the database of the Hematology Department of Beijing Chao-yang Hospital. Multiple linear regression model analysis was used to compare the differences in PHQ-9 and GAD-7 scale scores between the control group and the case group after correction for relevant variables. Multiple logistic regression models were subsequently used to analyze the correlation between the presence or absence of anxiety and depression and clinical indicators in the MM groups.Patients with MM . Analyses of multiple logistic regressions: biochemical indicators and clinical typing were not significantly associated with anxiety and depression. Compared to the pain rating 1, the risk of depressive mood was greater in the case group with the pain rating 2 (OR = 2.38) and the pain rating ≥ 3 (OR = 4.32). The risk of anxiety was greater in the case group with the pain rating ≥ 3 than the pain rating 1 (OR = 2.89).Depression symptoms was present in 33.33% and anxiety symptoms in 24.68% of first-episode MM in the maintenance phase of treatment, and depression symptoms in the index-corrected MM group was significantly different from that in the control group (Despite being in clinical remission, depressive mood problems in patients with MM remain prominent. Clinicians should enhance mood assessment and management in patients with concomitant pain. Multiple myeloma (MM), a plasma cell malignancy, has the second-highest prevalence among hematological malignancies, accounting for 1% of all cancers and 15% of hematologic neoplasms . In a stRecent research has revealed that depression and anxiety in cancer patients are strictly related to poor treatment compliance, low quality of life, and reduced survival rate . The preMM is one of the common diseases in human hematological system. Patients with hematological malignancies tumors generally have more complications than patients with solid tumors . HematolThere are two potential causes for depression and anxiety in patients with cancer. In essence, one is the biopsychosocial model, and the other is the specific neuropsychiatric effects of certain cancers and its associated treatments . Levels de novo MM during the maintenance period. To our knowledge, no previous studies have analyzed the prevalence of anxiety and depression symptoms among Chinese MM patients with maintenance therapy. The current study tries to fill a gap in the literature to help doctors identify the signs of anxiety and depression to prevent its progression using the interventional treatment. In this study, 160 patients with MM were selected as big data samples to explore the risk factors of depression and anxiety during maintenance therapy. It is not only helpful to identify and diagnose them, but also has value for their clinical treatment. The major aims of this study, therefore, is to investigate the relationship between biological indicators of MM and depression or anxiety, and to explore whether depression or anxiety are disease-specific changes in MM.Given the adverse effects of depression and anxiety in patients with malignant tumors, it is crucial to identify them clinically. Previous studies have examined the relationship between anxiety, depression and myeloma. Five years after the diagnosis of myeloma patients, about 27.4% of patients reported signs of anxiety and 25.2% reported signs of depression . HoweverFrom May 2017 to April 2019, outpatients with MM who received maintenance therapy in Beijing Chao Yang Hospital were included in this case-control study. Patients were included, if they: (1) were diagnosed according to the International Myeloma Working Group (IMWG) 2006 diagnosis criteria , in the The ethics of the study was approved by the Institutional Review Board of Beijing Chaoyang Hospital, Beijing, China (No. 2019-7-24-1). Qualified physicians reviewed electronic medical record systems and approached patients who met inclusion and exclusion criteria. The investigator explained the purpose of the study to the patient who came to the hematology clinic and conducted a face-to-face inquiry after the patient agreed to sign the informed consent form.2), which is a person’s weight (in kilograms) divided by the square of height (in meters), were also collected. Patients were also investigated whether they had a medical history such as cardiocerebrovascular disease or diabetes mellitus. All participants completed the questionnaire.The demographic characteristics of the participants were collected using an initial questionnaire that included age, gender, race, education level , and income. In addition, drinking status , smoking status , and body mass index  : As a siGeneralized Anxiety Disorder 7-item scale (GAD-7) : The GADVerbal Pain Rating Scale (VPRS) : There ade novo MM patients were extracted from the database of the hematology department of Beijing Chaoyang Hospital. The baseline clinical parameters comprised: hemoglobin, Hb (g/L); lactate dehydrogenase, LDH (U/l); creatinine, Cr (mol/l); osteolytic lesion; Durie and Salmon (DS) staging system; International Staging System (ISS); Revised International Staging System (R-ISS). Treatment included conventional chemotherapy and novel agent containing therapy. The response was evaluated by the IMWG 2006. Based on the reaction, the MM patients were classified as at least excellent partial response (VGPR) and less than VGPR . For the comparison of two groups, independent t-test was used to compare depression and anxiety between the groups. The dependent variables of this study are depression and anxiety in patients with MM. In order to avoid omitting the possible related factors, the factors with p-value less than 0.15 were included in multiple logistic regression, and the effects of each clinical indexes on depression and anxiety in patients with MM were analyzed. SAS software version 9.4 was used for data analysis, and two-sided p-values of 0.05 were considered statistically significant.According to the statistical analysis of the case group, the outcome was defined as whether depression or anxiety. The classified data was described by frequency and proportion, and the continuous data was described by mean ± standard deviations. The related factors of depression and anxiety were analyzed, respectively. Chi-square test or Z = 2.3476, P = 0.0189). After adjusting for smoking, drinking, and medical history in rank-based multiple linear regression, there was still a statistical difference in PHQ-9  between the two groups but was with no significant difference in GAD-7 at the 0.05 test level .183 patients with MM met the criteria, of which 10 refused, and 13 did not adequately complete the survey. From 298 controls in community health centers case-control matched according to sex, age, and BMI (in the ratio of 1:1), 160 patients and 160 controls were involved in the result analysis. P < 0.5. Then, these four variables were included in multiple logistic regression analysis. As shown in According to the results of PHQ-9 scores, patients with MM were divided into two groups: no-depression (PHQ < 5) and depression (PHQ ≥ 5). P < 0.5. Then, these three variables were included in multiple logistic regression analysis. The multiple logistic regression showed that there was a correlation between anxiety and pain rating. Patients with a pain level greater than or equal to 3 were at greater risk of anxiety than those with a pain level of 1 (OR = 2.89)  and anxiety (GAD-7 ≥ 5).  = 2.89) .To date, only a few studies have assessed the depressive and anxious states of MM patients in the early survivorship period . PractitPrevious studies have shown that MM is prone to depression  and anxiety  in the early treatment of the disease, which may be due to the lack of certainty of the disease. This increases the psychological burden of patients and predisposing them to acute stress reactions . With thPain is the most important factor affecting quality of life in cancer patients . AccordiFor patients with cancer pain, clinicians often rely on traditional analgesics to control pain. However, with the prolongation of the action time of analgesics, the risk of drug resistance increases . The resThe advantage of this study is the observation of a homogeneous patient group in the clear-cut stage of treatment. The case-control association study obtained a broad understanding of the prevalence of depression and anxiety symptoms with MM patients in China. To the best of our knowledge, this is the first experimental study to analyze clinical characteristics associated with depression and anxiety symptoms in MM. The anxiety and depression of patients during maintenance treatment are not closely related to the objective index of the baseline, but are closely related to pain rating.On the other hand, there are several methodological limitations in our study. First, due to the limitation of sample size, this study was not involved more factors such as economic conditions, personality, course of disease, and so on . Second,The results showed that excluding acute stress response at the initial stage of the disease, MM patients still had a certain proportion of anxiety and depression when they were in the “functional cure” stage. The anxiety and depression of patients during maintenance are not closely related to objective indicators of the baseline, but to pain. Depression and anxiety symptoms are strongly associated with subjective pain levels at the remission phase but not with objective indicators of disease prognosis. Under the multi-disciplinary management mode of diagnosis and treatment, it is important to focus on emotional problems in patients with MM during maintenance stage of treatment. Physicians should regularly evaluate MM patients’ state of depression and anxiety, especially paying attention to the patients who have complained of pain at the time of onset. Because of these investigations, it is proved that a psycho-biological integrated intervention model is essential to guide patients’ treatment comprehensively, systematically and scientifically.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical approval was obtained from the Ethics Committee of the Medical Faculty of Beijing Chao-Yang Hospital, Capital Medical University . The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.HS: conceptualization, formal analysis, methodology, writing—original draft and review and editing, and supervision. HR: methodology, original draft—review and editing, and data curation. YT: conceptualization, methodology, and data curation. ZC: data curation, methodology, and project administration. CX, LL, XM, and XL: original draft, methodology, and data curation. WC: conceptualization and supervision. TG: supervision and methodology. CF and WG: conceptualization, supervision, methodology, and original draft—review and editing. All authors contributed to the article and approved the submitted version.


Candida albicans is the most common pathogen causing clinical Candida infections. Neutrophils are a key member of the host innate immunity that plays an essential role in clearing invading C. albicans. In addition to the well-known defensive approaches such as phagocytosis, degranulation, and reactive oxygen species production, the formation of neutrophil extracellular traps (NETs) has also become an important way for neutrophils to defend against various pathogens. C. albicans has been reported to be capable of activating neutrophils to release NETs that subsequently kill fungi. The induction of NETs is affected by both the morphology and virulence factors of C. albicans, which also develops specific strategies to respond to the attack by NETs. Our review specifically focuses on the mechanisms by which C. albicans triggers NET formation and their subsequent interactions, which might provide meaningful insight into the innate immunity against C. albicans infection. Candida spp. frequently cause local infection by invading the host mucosa and tissues and, occasionally, lead to life-threatening invasive candidosis. Recently, the widespread use of broad-spectrum antibiotics, glucocorticoids, and immunosuppressants, and the continuous development of medical treatments such as tumor chemotherapy and organ transplantation, has increased the yearly incidence of invasive candidosis. Furthermore, Candida albicans is the pathogen that accounts for the highest proportion of infections , or hyphae , and the formation of neutrophil extracellular traps (NETs)  . The yeachanisms . In contchanisms .NETs, large extracellular networks consisting of DNA fibers 15–17 nm in diameter and spherical proteins approximately 25 nm in diameter, are mainly released by neutrophils to defend against the invasion of various pathogens , 12. TheStaphylococcus aureus.Originally, NETs were thought to be released through a cell death process that was later named “NETosis” . First, Both nuclear DNA and granular proteins are expelled in a vesicle-wrapped form, and eventually assembled into NETs in the extracellular space. This rapid release of NETs, which is not accompanied by cell death or ROS-dependent, is considered an antimicrobial behavior of neutrophils in the early stage of infection. Studies suggests that ROS-independent NET formation could be initiated by protein-arginine deiminase 4 (PAD4)-mediated histone citrullination . YousefiC. albicans also triggered the formation of NETs. Subsequently, studies were conducted to explore the correlation between C. albicans infection and NET formation, including those indicating that the morphology of C. albicans affected its stimulation of the release of NETs by neutrophils.Multiple stimuli activate neutrophils to release NETs –22, whicC. albicans hyphae  and surface proteins were observed to induce NET release  are the major receptors on the surface of neutrophils that recognize mannans –28. Thisβ-glucans were the first substances discovered to induce NET formation, but the signaling pathways involved have not been clearly elucidated. Previous work demonstrated that β-glucans triggered NET formation in a concentration-dependent manner, primarily through an ROS-dependent pathway , 31. HowSaccharomyces cerevisiae and its β-glucan-containing capsular constituent zymosan, Bruggen et al.  and VLA5 (or α5β1) that regulate homotypic aggregation and NET formation respectively  mechanism  were released with the help of DNase disrupting the framework of NETs, and then recovered. Nevertheless, the following two points should be considered. 1) If the co-incubation time is extended, would the trapped pathogens still survive, and 2) since C. albicans spores and S. aureus can be phagocytosed by neutrophils, would the selection of filamentous fungi as alternative microbes in the experiment produce the same result?Although the antifungal activity of NETs has been shown in numerous studies, Menegazzi et al.  argued tC. albicans develops several defensive strategies to deal with NETs killing  whether CR3 on the surface of neutrophils always participates in NET formation triggered by various stimuli, 3) the signaling pathways and regulatory factors, and 4) the mechanisms underlying the actions of antifungal proteins in NETs. Therefore, more in-depth researches are urgently needed. Nevertheless, we hope that this review provides meaningful insight into the study of the innate immunity driving the clearance of C. albicans infection, which might eventually contribute to the developing treatment strategies in clinical practice.Several fundamental scientific questions remain to be answered, such as: 1) whether YH: Conceptualization , Writing—original draft preparation (lead); JL: Investigation , Visualization ; YC: Investigation , Visualization ; LY: Funding acquisition (lead), Writing—review and editing ; JW: Conceptualization , Writing—review and editing . All authors contributed to the article and approved the submitted version.This work was supported by National Natural Science Foundation of China (82173867), Shanghai Science and Technology Innovation Action Plan, International Science and Technology Cooperation Project (21430713000), Shanghai Science and Technology Support Project in the Field of Biomedicine Project (19431901300), Shanghai Pujiang Program (21PJD0081).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


There were no differences in the Doppler MCA and DV before or after ECV. All patients were discharged after the procedure. ECV is associated with changes in the UA Doppler indices that might reflect interference in placental perfusion. These changes are probably short-term and have no detrimental effects on the outcomes of uncomplicated pregnancies. ECV is safe; yet it is a stimulus or stress that can affect placental circulation. Therefore, careful case selection for ECV is important.External cephalic version (ECV) is a cost-effective and safe treatment option for breech presentation at term. Following ECV, fetal well-being is assessed via a non-stress test (NST). An alternative option to identify signs of fetal compromise is via the Doppler indices of the umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV). Inclusion criteria were an uncomplicated pregnancy with breech presentation at term. Doppler velocimetry of the UA, MCA and DV were performed up to 1 h before and up to 2 h after ECV. The study included 56 patients who underwent elective ECV with a success rate of 75%. After ECV, the UA S/D ratio, UA pulsatility index (PI) and UA resistance index (RI) were increased compared to before the ECV ( Breech presentation is the most common non-vertex presentation and one of the main indications for Cesarian section (CS), as vaginal delivery in this presentation is correlated with higher fetal morbidity and mortality . HoweverECV is performed by manipulating the abdomen in a circular motion, rotating the fetal head to vertex. The procedure is successful in 58% of attempts, reduces the risk for CS by two-thirds, and enables 80% of these patients to eventually deliver vaginally . In a 20Several prognostic parameters are associated with the success of ECV, including a higher parity , amniotiAfter ECV is performed, fetal wellbeing is assessed via prolonged fetal heart rate monitoring (NST) and an ultrasound biophysical profile. Transient abnormal cardiotocography has been described after ECV; however, it does not accurately predict fetal mortality and seldom leads to the need for cesarean section ,9,10. OtDoppler ultrasound is another important tool for evaluating fetal well-being. Doppler ultrasound technology is based on sound waves detecting blood flow in vessels   and is oIts main applications are in high-risk pregnancies, to detect fetal anemia and manage fetuses with intrauterine growth restriction (IUGR) . It alsoIn pregnancies with early IUGR, the waveforms and the angle-independent indices become abnormal, and the changes allow the physician to track the physiological compensatory fetal state and decide how to best manage the pregnancy ,17. ThesUsing a Doppler examination as a screening test for fetal wellbeing is still controversial due to the possibility that integrating this examination may lead to unnecessary interventions and adverse obstetrical outcomes .It has been demonstrated that in acute hypoxia, the proportion of placental blood passing through the DV increases, which reduces the placental fraction of the cardiac output  and promInformation regarding Doppler indices following ECV is scarce. Lau et al.  used DopThis prospective observational study included 56 women who underwent ECV, in a tertiary university teaching hospital, over a 6-month period. The cohort consisted of women who were referred for ECV after being diagnosed with a fetus in a non-vertex position; inclusion criteria were gestational age of at least 36 completed weeks, an uncomplicated pregnancy, normal fetal cardiotocography prior to the ECV, and normal amniotic fluid index on ultrasound examination. Exclusion criteria included patients who did not wish to be included or asked to stop their participation without completing the post-ECV examination, or any contraindication for ECV .The procedure took place in a designated room in the labor and delivery complex, only in the morning and early afternoon hours, by an assigned team. After admission, reassessment of the normal biophysical profile and verification of the non-vertex position were performed clinically and via ultrasound. Data regarding socioeconomic and clinical characteristics, gestational and previous delivery course, Doppler sonographic measurements of the fetal UA, MCA, and DV circulation were recorded. Fetal cardiotocography were placed for at least 20 min; if fetal well-being was not established after 20 min, monitoring was extended until satisfactory. A senior obstetrician attempted the ECV procedure. During the process, the fetal cardiotocography was disconnected but not removed and was replaced after the attempt was completed.In cases where the first attempt failed and the clinical impression of the performing physician was that tocolysis might assist the procedure, 0.025 mg ventolin was given subcutaneously to relax the uterine smooth muscle, and the procedure was defined as complicated. The procedure was attempted again 20 min later. After successful ECV, a second NST was performed for at least 1 h to establish fetal well-being and no significant uterine activity. If both conditions were met, the patient was discharged. Otherwise, the fetal examination was extended, or the patient was hospitalized for longer surveillance and repeated monitoring. In the rare cases where severe fetal distress was established, an emergency CS was performed.The ultrasound examination, including the Doppler studies, were performed up to 1 h before and up to 2 h after the ECV. All ultrasound studies were performed by physicians who were certified sonographers. A GE Voluson P6 ultrasonography machine with a 4C convex transabdominal probe, with 2–5.5 MHz band width was used for all examinations. All Doppler studies were performed in the absence of gross fetal body or breathing movements. A pulsed Doppler gate was optimized according to the diameter of the vessel examined until a regular circulation wave pattern appeared . After the examiner verified the quality and accuracy of the waves, they were measured automatically by the machine. All measurements were printed for documentation. Delivery and neonatal characteristics were documented postpartum.The maternal, ECV, and delivery characteristics are depicted in p-value of <0.05 was considered significant.All patients who met the inclusion criteria were included in the statistical analysis. The nonparametric paired Wilcoxon signed-rank test was used to compare the pre- and post-ECV Doppler results. This test was used to accurately compare the median values of continuous non-normally distributed data generated via Doppler examination and considering the cohort size, since it does not require any assumptions of normality or equal variances. A The study included 56 patients who underwent elective ECV. The overall success rate was 75%. There were no significant differences in the socioeconomic variables and pregnancy complications between women who experienced successful or failed ECV. In the group who underwent successful ECV but ultimately delivered via CS were two patients who presented with recurrent non-vertex presentation in the presence of latent or active phase labor, and eight with nonreassuring fetal heart rates requiring urgent delivery. No patient had an indication for urgent CS immediately after ECV.n = 56).All Doppler sonographic measurements of the circulation of the fetal UA, MCA, and DV were documented. The measurements are detailed in Doppler studies of the MCA, UA, and DV were classified according to the level of difficulty of the procedure, either as routine, complicated, or failed .p = 0.03) and RI (p = 0.3) of the MCA after a complicated ECV , UA PI (p = 0.042), and UA resistance index (RI) (p = 0.022)  . When anThere was no significant difference between the pre- and post-ECV Doppler results in the studies of the DV, regardless of whether the comparison was in the entire group or stratified for parity, outcome of ECV, or its level of difficulty .p = 0.006), number of attempts , number of physicians involved , and CS delivery (0.007). There was also a significant correlation between the need for manual lysis of the placenta at birth (p = 0.04).As expected, there was a significant association between the level of difficulty of the procedure and the duration of the ECV , maternal height (p = 0.49), BMI at presentation (p = 0.7), weight gained during the pregnancy (p = 0.73), gestational age (p = 0.73), amniotic fluid index (p = 0.56), estimated fetal weight (p = 0.99), neonatal blood pH at birth , delivery weight (p = 0.69), 5-min Apgar score (p = 0.27), meconium stained amniotic fluid (p = 0.62), placental abruption (p = 1), post-partum hemorrhage (p = 1), true umbilical cord knot (p = 0.28), or nuchal cord at birth (p = 0.31).There was no significant difference between the level of difficulty and the pregnancy and delivery characteristics of the maternal age . There was no fetal mortality or morbidity attributable to the ECV.This study describes the effect of ECV on fetal circulation in the MCA, UA, and DV, measured via Doppler ultrasound.Our findings revealed significant decreases in the RI, PI, and S/D ratio in the UA following ECV. These changes represent the placental resistance and suggest that the ECV mainly affected the placental arterial vessels . We specNevertheless, several previous studies demonstrated that ECV is a safe procedure ,5,23. ThFurthermore, the venous system, represented in this study by the Doppler studies in the DV, was not affected by the ECV, regardless of whether the comparison was in the entire group or stratified according to the difficulty of the procedure.To the best of our knowledge, this is the first report to assess venous fetal circulation during ECV. The waveform in the DV has two peaks representing chronological hemodynamic changes in pressure gradients between the umbilical vein and the right atrium . The effHowever, in normal pregnancies, there is no conclusive evidence that routine Doppler ultrasound exams affect neonatal outcomes. There is some evidence that UA Doppler velocimetry may reduce the risk of potentially preventable perinatal deaths, but these findings are based on a few trials and subgroup analyses . Also thThe literature discussing the effect of acute stress on the fetoplacental circulation is sparse. Nevertheless, two prevalent risk factors have been investigated. Maternal smoking was correlated with acute circulatory changes, manifested by changes in the UA flow and diameter, and chronic or acute fetal anemia, which is seen as changes in the flow velocity and diameter of MCA ,37. The p = 0.03). These vascular changes in cerebral arterial blood flow were unlikely to be related to the direct effects of the ventolin used for uterine relaxation before the ECV, since it has been shown that there is no effect on the systolic/diastolic ratios of the uterine arcuate, umbilical, or middle cerebral arteries during the first 2 h after administration [Cases defined as difficult ECVs were correlated with significant reductions in the resistance measurements of RI and PI in the MCA (both stration ,39. Thisstration ,41,42. Lstration . Brain sstration . The brastration , and depstration . In latestration .Low MCA PI correlates with fetal outcomes, not only in early severe cases accompanied by an abnormal UA PI, but also in late and term IUGR in which the UA PI might be normal .When examining the effect of acute stress on the cerebral circulation, such as during uterine contractions, the MCA PI was found to decease significantly due to the vasodilatation involved in the brain-sparing effect, but was more prominent in OCT-positive cases . This vaThis study had several advantages. It was prospective, all Doppler studies were performed in one of two designated beds and with cardiotocogram monitors, using the same ultrasound machine, and by only three physicians, who are certified sonographers. The ECV was performed by a small team of certified obstetricians with at least 5 years’ experience in performing ECV.The present study also had some limitations, including the relatively short interval between the ECV and the doppler examination, which did not allow us to determine how long the effect of the ECV on fetal circulation persisted. Another limitation was the relatively small cohort.ECV is associated with changes in UA Doppler indices that might reflect interference in placental perfusion. The changes in the MCA Doppler might reflect an adaptive reaction to counter fetal stress and acute hypoxia. Both changes are probably short-term and have no detrimental effect on the outcomes of healthy pregnancies.ECV is a safe procedure, yet it affects the placental circulation. Hence, careful case selection for ECV is very important.