Coronavirus disease 2019 (COVID-19) is an infection with possible serious consequences. The plasma of recovered patients might serve as treatment, which we aim to assess in the form of a prospective meta-analysis focusing on mortality, multi-organ failure, duration of intensive care unit stay, and adverse events.A systematic search was conducted to find relevant registered randomized controlled trials in five trial registries.A comprehensive search will be done continuously on a monthly basis in MEDLINE (via PubMed), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science to find the results of previously registered randomized controlled trials. The selection will be done by two independent authors. Data extraction will be carried out by two other independent reviewers. Disagreements will be resolved by a third investigator.An update of the search of the registries and the first search of the databases will be done on the 21st of July.P less than 0.05 will be considered statistically significant. In the case of ICU stay, weighted mean difference with a 95% confidence interval will be calculated. Heterogeneity will be tested with I2, and χ2 tests. Meta-analysis will be performed if at least 3 studies report on the same outcome and population.Data synthesis will be performed following the recommendations of the Cochrane Collaboration. In the case of dichotomous outcomes , we will calculate pooled risk ratios with a 95% confidence interval (CI) from two-by-two tables . Data from models with multivariate adjustment  will be preferred for the analysis. Convalescent plasma therapy is a considerable alternative in COVID-19, which we aim to investigate in a prospective meta-analysis. Recently, two papers have been published reporting on efficient and safe vaccines, [There is currently an outbreak of respiratory disease caused by a novel coronavirus. The virus has been named “SARS-CoV-2,” and the disease it causes has been named “coronavirus disease 2019” (COVID-19). The outbreak has affected almost every country of the world, and as of 5 July 2020, a total of 11,046,917 confirmed cases and 526,465 deaths had been reported . As the question requires sufficient statistical power, PMA also proves to be beneficial. Furthermore, as the hypotheses, selection criteria, and intended analyses are stated before the availability of the results of the actual randomized trials, it overcomes the limitations of traditional, retrospective meta-analyses .We aim to assess the efficacy of convalescent plasma treatment of COVID-19 patients for the outcomes of mortality, multi-organ failure, and duration of intensive care unit (ICU) stay in a prospective meta-analysis.The protocol is based on the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement . Throughhttps://www.crd.york.ac.uk/prospero/).This protocol has been registered at PROSPERO International prospective register of systematic reviews in advance under the number of CRD42020197442. registry, Australia and New Zealand Clinical Trial Registry (ANZCTR), and NIPH Clinical Trials Search registry to find eligible, registered randomized controlled trials. Two independent review authors performed the selection first based on the title, then based on the full protocol individually. In the case of disagreements, a third investigator was involved. A trial protocol proved to be eligible by title if it contained the term “plasma” in the context of intervention. A protocol was included in the level of full-text selection if it was a two-arm, randomized trial reporting on at least one of the populations and outcomes in question. All included patients should be PCR-confirmed COVID-19 cases, which will be divided into four subpopulations: P1: respiratory involvement ; P2: patients admitted to the intensive care unit or are critically ill; P3: hospitalized patients without restriction on the severity, including mild, moderate, severe, and critically ill patients; P4: severe condition, defined as following the most recent World Health Organization (WHO) classification; intervention (I): convalescent plasma; control (C): placebo or any other active control; outcomes (O): mortality at any points of time after baseline, intensive care unit stay, multi-organ failure, adverse events. To quantify the level of agreement, Cohen’s kappa of both stages of the selection was calculated. The selection process and Cohen’s kappa results are presented in Fig. A systematic search will be performed on 21 July 2020 in four scientific databases, MEDLINE (via PubMed), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science, for randomized controlled trials (RCT). The following query will be used in all databases without any filters or restrictions: ((COVID 19 OR “SARS-CoV2” OR “2019-nCoV”) AND (plasma OR serotherapy OR “passive immun*”)). Reference lists of eligible articles and citing articles (via Google Scholar search engine) will also be screened to capture all relevant studies.After the automatic and manual removal of duplicates using a reference management software , two review authors will independently screen titles, abstracts, and full-texts against predefined eligibility criteria. A third review author will resolve any disagreements at each level of the selection process.Inclusion criteria specified any RCTs that are reporting on the population and outcomes  in question, as stated above. We will exclude non-randomized clinical trials and trials not reporting on the population and outcomes in question. In the case of overlapping study populations and updates, we will include the study with a higher patient number.Regarding the trial registries and scientific databases, we intend to extract all records every month with the same methodology. The first systematic search and update on the trial registries will be on 21 July 2020.A standardized data extraction form will be developed a priori and will be piloted by the authors performing the data extraction. Two independent reviewers will extract data from all included studies. The following data will be extracted: first author, year of publication, study location, study design, study population, the type and details of interventions received, mean age, sex, number of patients in each group, inclusion criteria, and outcomes. Outcomes will include mortality, multi-organ failure, and intensive care unit stay. Discrepancies will be resolved by consensus and the involvement of a third author. All data will be compiled in an Excel spreadsheet  for analysis.P less than 0.05 will be considered statistically significant. Statistical analysis will be performed using random effects model. In the case of ICU stay, weighted mean difference with a 95% confidence interval will be calculated. Heterogeneity will be tested with I2, and χ2 tests, p less than 0.1, will indicate significant heterogeneity.Data synthesis will be performed using the methods recommended by the working group of the Cochrane Collaboration . Data frMeta-analysis will be performed using STATA v.16 , Comprehensive Meta-Analysis v.3 , and R v.4.0.0  software if at least three studies of same outcomes, assessed at the same point of time after the baseline are available.Z curve, a p value less than 0.05 will be considered significant.A Trial Sequential Analysis (TSA 0.9.5.10.) will also be performed to quantify the statistical reliability and to estimate the optimal information size (OIS), if it is possible. We plan to perform the TSA for every included outcome. In the case of the The presence of publication bias will be assessed visually by examining a funnel plot, as well as statistically by using Egger’s regression method if at least 8 studies are available. We will also use the trim and fill method to address this question .If possible, subgroups of treatment modalities (dose and administration of plasma), age , gender, and comorbidities will be presented. In the case of missing data, the corresponding authors will be contacted, or if individual patient data is available the missing variables will be calculated.The quality of all the included studies will be independently assessed by two reviewers using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) . Bias wiThe quality of evidence will be assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The certainty of evidence will be classified into four levels: high, moderate, low, or very low. Evidence is downgraded by concerns about the risk of bias, imprecision, inconsistency, indirectness, or publication bias. Two independent reviewers will decide the overall quality of the evidence. A third review author will resolve disagreements.No patients were or will be involved in the design, conduction, or interpretation of our review.Convalescent plasma therapy might be a good alternative to prevent the negative effects of COVID-19, but the clear benefits remain unclear. A prospective meta-analysis from randomized controlled trials can fill this void in terms of mortality, need and duration of intensive care unit stay, and organ failure. Furthermore, this protocol might serve as a basis for the not widely used methodology of prospective meta-analysis. Although prospective meta-analyses might include individual patient data, we do not intend to do so, corresponding authors will be only contacted in the case of missing data.


N = 2,347) of the German population. We utilized factor analysis methods to identify the optimal short scale of the measure, finding excellent model fit and reliability for a two-factor model (FKB-6) for both real and ideal body image. Both versions of the FKB-6 can be considered invariant across sex and age groups. Good reliability indices were shown for both versions of the FKB-6. The reliability indices were similar to those mentioned in previous studies. Our study also revealed, that large discrepancies between the real and an ideal body image are correlated with somatic and body dysmorphic symptoms. Finally, we provided norm values for comparisons of individual scores with the general population. The FKB-6 is a valid and a reliable measure that economizes assessments by clinicians and researchers.The Body Image Questionnaire-20 (FKB-20) is one of the most applied self-report measures in the context of body image assessment in German-speaking regions. A version of the FKB-20 capturing an ideal concept of body image is also available. A special property of the scale is its high sensitivity for individuals suffering from anorexia nervosa. The present research provided a short version of this scale (for both variants) and examined its validity in a representative sample ( The diagnosis of body image perturbances in eating , and in other psychiatric disorders or illnesses involving physical changes and disturbances associated with body dissatisfaction  is part of the everyday clinical practice . In thisinvestment. Body image experiences vary across life span and situational contexts  and Vital Body Dynamics . This measure has been applied in numerous studies and clinical settings, showing satisfactory psychometric properties and especially a high sensitivity to change and detect eating disorders, e.g., anorexia nervosa (The FKB-20 is considered to be one of the most applied self-report measures (in German-speaking areas) in its field. It was developed to diagnose body image disorders in clinical practice and measure body image-related aspects . A pecul nervosa . It was  nervosa  and meas nervosa , cancer  nervosa , a heart nervosa  and obes nervosa . Besides nervosa . Anotherreal) and the ideal body image  and their relation to: physical and subjective well-being, quality of life, somatoform and body dysmorphic symptoms.Considering the growing demand for scientifically sound measures in the field of body image assessment in German-speaking regions and the value of such in clinical and in research settings, a short version appears convenient. Especially for patients with a background of mental illness, older participants, or for large-scale health surveys, an economical measure seems desirable. Therefore, the main aim of the present study is to develop a short scale for each version of the FKB-20 and evaluate their psychometric properties. A further aim is to provide insight of how body image perception affects relevant psychological variables. For this purpose, we explored discrepancies between the real , EURO-HIS-QOL-8 , The World Health Organization-Five Well-Being Index (WHO-5), Screening for Somatoform Disorders (SOMS) and Body dysmorphic symptoms inventory (BDSI). Physical well-being (FEW), quality of life (HIS-QOL-8) and subjective well-being (WHO-5) are expected to be positively associated to VBD, but weakly or negatively related to RBI . The final sample consists a total of N = 2,429 participants between 14 and 99 years of age , with 52.9% of the subjects being female. The methods of data collection were in accordance with the Helsinki Declaration of 1975 (as revised in 1983). Further details on the sociodemographic composition of the sample are described in 2 ≤ 4.00, p ≥ 0.550, V ≤ 0.063. However, - at least descriptively—we acknowledge a underrepresentation of individuals of age 70 or older.The data in the present study were collected on behalf of the local university, supported by a demographic research institute  as part of a population-based representative survey using a multistage sampling. The participants were selected by a random-route method and visited at home by trained and experienced interviewers from the research institute USUMA, Berlin. From all the household members the target participant at home was also randomly selected (Kish-Selection-Grid). Inclusion criteria required subjects to be at least 14 years of age in addition to sufficient command of the German language. As part of the interviews, participants filled in self-report questionnaires (participation was voluntarily). Each respondent received a signed privacy policy form. Parents or legal guardians signed a consent form approving the participating of underaged subjects. The response rate of the survey was 62.3%. Drop outs were due to dismissal of participation by the household (14%) or by the target subject (9.4%), failed attempts to contact the selected household (9%) and the target subject (3.6%). Additionally, some interviews were invalid  and Vital Body Dynamics  with 10 items each, ranging from 1 = it does not apply to 5 = it applies. The subscale scores are calculated by summing up the item values. Satisfactory psychometric values have been demonstrated in previous studies  were satisfactory .This scale measures cognitive, affective, and evaluative variables of an individual’s concept of body image and reflects relatively time-stable physical aspects, rather than current physical conditions. The questionnaire comprises two subscales: es e.g., . For thees e.g., , the oriEURO-HIS-QOL-8  based on the past 2 weeks. The total score is achieved by summing up the item scores. Extensive surveys with the questionnaire provide evidence of good psychometric properties . Norm values are available  by means of four dimensions: resilience, vitality, enjoyment, and inner peace. Each scale has four exclusive positively formulated items rated from 0 = vailable .I don’t think about it to 4 = over 8 h/day or more), as well as the extent of ritualized, appearance-related actions . Furthermore, it reflects the strain and impairment caused in daily tasks due to preoccupation with body concerns. The scale is a self-report instrument comprising 18 items. Questions two and three serve as auxiliary items to detect eating disorders and are not included in the total score. The score of the BDSI ranges from 0 to 64. Additionally, four items capture the criteria of a body dysmorphic disorder based on the DSM-IV , which is computed by summing up the item scores. The psychometric properties of the scale have shown satisfactory values in previous studies  into an exploratory  and a confirmatory one . This will allow for independent testing in the confirmatory sample of the model generated in the exploratory sample. To determine the number of substantial factors, we then conducted parallel analysis , the Tucker-Lewis-Index (TLI), the Root Mean Square Error of Approximation (RMSEA), and the Standardized Root Mean Square Residual (SRMR). CFI and TLI should be larger than 0.950, and RMSEA and SRMR should be smaller than 0.06 to evince good fit , and Items 13 and 19 had moderate discrimination . All other items had high or very high discrimination. For the Vital Body Dynamic scale, only Item 20 had a discrimination parameter which was not at least high (a20 = 1.12).The results of the EFA and the item descriptive analyses are reported in  package : Similarstuart. Among the possible 1,200 combinations, the algorithm selected those items marked in 2(24) = 51.850, p < 0.001, CFI = 0.992, TLI = 0.989, RMSEA (90% CI) = 0.044 , SRMR = 0.033. The item inter-correlations exceed 0.300 for all scales, and are, thus, satisfactory  = 20.488, p = 0.009, CFI = 0.995, TLI = 0.991, RMSEA (90% CI) = 0.040 , SRMR = 0.021. As fixed rules of thumb for model fit evaluation have been criticized again and again .We then tested this configuration in the confirmatory subsample, and were able to affirm the very good fit, χgain cf. , we utilzCutoffs  to deter2(8) = 18.438, p = 0.018, CFI = 0.994, TLI = 0.989, RMSEA (90% CI) = 0.041 , SRMR = 0.021. Here four of the five fit measures where acceptable according to the simulated cut-offs, χ2 = 21.799, CFI = 0.992, TLI = 0.984, RMSEA = 0.038, and SRMR = 0.025. Standardized factor loadings were greater than or equal to λ = 0.645 for all six indicators and the latent variables correlated at r = −0.570. Reliability for both subscales was good, ωVBD = 0.853 and ωRBI = 0.756.A confirmatory analysis was also computed for the short form of the ideal version of the FKB-20. Results show a very good fit, χreal, ideal—see Next, we tested for measurement invariance in both questionnaire variants  are positively associated with somatoform  and body dysmorphic symptoms  and negatively with physical and subjective well-being as well as with quality of life. As seen in resilience subscale of the FEW , while the weakest was with somatic symptoms . As further hypothesized, somatoform and body dysmorphic symptoms were positive correlated with RBI, but negatively or low with VBD. The highest positive correlation in terms of RBI was with specific symptoms of the BDSI scale , while the lowest was with health-related quality of life .We correlated the scales of the real and the ideal version of the FKB-6 with other related measures to test convergent validity see . CorrelaWe tested for differences in the subscales of the real and ideal body image scale with regard to sociodemographic variables see . Almost In terms of vital body dynamics sex  had barely an effect in explaining differences. However, in the real version sex exhibited a slightly larger effect size, as well as education (both versions) and family status . The largest effect was attributed to age and employment (both versions) which explained more than 10% of the variance.In sum, compared to other variables family status had the largest effect in explaining differences concerning rejecting body image . With reference to vital body dynamics age and employment were the most influential variables (both versions).In The main aim of the present study was to provide a short version of the FKB-20  and demonstrate its validity by means of associated constructs. Such a measure would economize clinical assessments and research endeavors. A further aim, was to illustrate the effects related to discrepancies between a real and an ideal body image, in the matter of somatic and body dysmorphic symptoms, quality of life, psychological and physical well-being.The psychometric analyses evinced satisfactory results for both versions of the scale. The reliability indices were similar to those mentioned in previous studies . The oveStrict measurement invariance across age and sex was found for the ideal version. This was also true for the real version when considering age, but not for sex. However, partial invariance was established in this case. This is a relevant and novel finding regarding the measurement of body image, since this reveals that the measurement model is identical for these groups. If these prerequisites were not fulfilled, comparisons of latent and observed means and variances between groups would be questionable . SpecifiThe largest intercept deviation was exhibited for Item 8 (“Unhappy with one’s figure”).This makes sense since compared to men, women are generally more unhappy with their body, even across age . Even thScalar invariance was then only obtained after relaxing the equality constraint for one item (Item 8), This means that—even given the same factor score—one will still find differences in the observed means between groups. As pointed out by ideal values of the participants.Evidence of validity was exhibited by means of correlations of the FKB-6 (both versions) with other related constructs. As expected, convergent validity was indicated by means of strong correlations between vital body dynamics and physical well-being, quality of life, and subjective well-being. This shows that VBD is well reflected in these qualities. The strongest correlation was shown between VBD and physical well-being properly emphasizing the physical component in this dimension. Previous studies demonstrated similar results, underlining the relevance of these findings ,b, 2009.Comparisons between sociodemographic variables revealed that in both versions age and employment were the most influential variables in terms of explaining differences in vital body dynamics. On the other hand, family status had the largest effect regarding rejecting body image . This goes in line with literature on body image, showing changes in body image perception relevant to age, employment and family status .The present study utilized primarily a statistical approach grounded in classical test theory (CTT). A growing body of research has discussed differences between CTT and an alternative approach: Item response theory IRT; . In mostIn the face of growing body image disturbances and its pervasive effects on physical and mental health, there is a crucial demand in the field of body image assessment to provide proper measures, especially given the need of such in German-speaking populations. The FKB-6 aims to meet these demands providing an economic and a validated tool that is best of use in in research settings and economic clinical assessments. The short versions of the FKB-20 are valid and reliable instruments that measure body image issues by means of affective and cognitive variables. They facilitate and economize diagnosis and aids treatment in clinical contexts. Its brevity provides advantages for large scientific surveys.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation, to any qualified researcher.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study. The methods of data collection were in accordance with the Helsinki Declaration of 1975 (as revised in 1983).IS contributed to the writing of the draft of the manuscript and managing information of new editions and corrections. CA was responsible for data collection and conception data management. EB contributed to the design of the study idea. BS contributed to the data analysis and discussion. KP and HB contributed to the writing and editing of the manuscript and literature review. MZ contributed to the writing and editing of the manuscript. All authors have contributed to the preparation of the manuscript and report of results, and approve the submitted manuscript for publication.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.


Kidney pathologies often result in change in renal size. Knowledge of normal kidney sizes is important for screening, diagnosis, prognosis and follow-up management of paediatric renal diseases.The aim of this study was to establish the age-, height- and weight-matched kidney dimensions in apparently healthy Nigerian children.A descriptive, cross-sectional study of right and left kidney parameters  of 1315 school-aged Nigerian children was conducted over 8 months. Ages ranged from 5 to 17 years. Parameters were obtained using a General Electric (GE) LOGIC 400CL ultrasound machine. Kidney dimensions were correlated with age, sex and anthropometric measurements.p < 0.01). Length of the left kidneys in females was noted to be more than those of the males in the age- and weight-matched categories (p < 0.05). The width of both kidneys was higher in the males in all the categories (p < 0.05). Males showed higher values of thickness and volume in the height category. All the renal parameters significantly correlated with body size indicators, except for body mass index.Normative values for all the kidney parameters for each age, height and weight groups and also gender were established for the study population. The left kidneys were noted to be longer and thicker, and of more volume than the right kidneys. The right kidneys were seen to be wider (This study has established gender-, age-, weight- and height-specific range of values of the kidney parameters of apparently healthy children together with regression models. It also provides a quick and accurate assessment of other visceral organ dimensions.3 Reports have demonstrated that renal length differs from race to race.6 The size and weight of an organ have also been shown to be influenced by environmental variations, ethnicity, hereditary components, routine diet, water intake8 and high altitudes, where atmospheric pressure is reduced, with the partial pressure of oxygen altering the physiology of the kidneys.9Anomalies of renal sizes are associated with and are manifestations of diseases involving the kidneys.10 multicystic and polycystic kidneys, acute malaria because of plasmodium falciparum,11 auto-immune diseases such as Kawasaki disease,12 recurrent urinary tract infection, neoplasms, urolithiasis, trauma, drugs, ingestion of native concoctions, diabetes, hypertension, renal artery stenosis and so on. Knowledge of renal size helps in differentiating acute from chronic kidney diseases (CKD).13 Chronic diseases include diseases that reduce the size of the kidneys such as chronic glomerulonephritis, nephrosclerosis and diabetic nephropathy, and those that increase its sizes such as multi- or polycystic kidney diseases and so on. In addition, renal length and volume are very important parameters for numerous purposes such as the assessment of candidates for/with kidney transplant, decision in obtaining renal biopsies and follow-up of patients with end-stage liver disease in which nephromegaly and increased echogenicity of renal cortex can be associated with pathological findings . Kidney size is an important parameter used for the clinical evaluation of renal abnormalities, such as atrophy, hypoplasia and hypertrophy in children. Sonography is used to monitor the kidneys of children before and after liver transplants with sizes compared with published normative values.14 Renal involvement can be a part of a syndrome such as Beckwith–Wiedemann syndrome (BWS). This syndrome is reported to have a high risk of development of embryonic tumours such as Wilm’s tumour.15 Screening protocols with ultrasonography have been implemented in some countries for the early detection of these tumours16 because a criterion for its diagnosis is evidence of renal enlargement.The kidneys can be affected by congenital or acquired diseases, either localised or systemic. Examples are solitary kidney, renal hypoplasia,17 demonstrated that renal volume, which correlates better with renal mass, is a more sensitive means of diagnosing kidney abnormality than any single linear measurement. Also at autopsy, renal volume has been reported to correlate well but indirectly with the number of functioning nephrons,18 hence its inclusion in this study.A study by Jones et al.19 showed that acute renal disease accounted for up to 82.9% of admissions. It is invaluable to have a more comprehensive, standardised, sonographic measurement for use in the course of the renal assessment of a child, hence this study.A Nigerian study on paediatric hospital admissions by Esezobar et al.This was a descriptive, cross-sectional study of the kidney parameters of apparently healthy, school-aged, Nigerian children without any known renal disease. Whilst informed consent was received from the parents of the children, child assent was also obtained from each child involved in this study. Detailed medical history of each child was acquired from the parents including pre-existing diseases that could affect the kidneys, past urologic surgeries and known history of chronic diseases. After clinical examination of each child by one of the authors who is a clinician, only apparently healthy children were recruited for the study.Clinical exclusion criteria were fever, periorbital or pedal edema, macular or maculopapular rashes and sickle cell anaemia. Imaging exclusion criteria were altered echogenicity, presence of renal cysts, urolithiasis, unilateral kidney, hydronephrosis, ureterocele, renal ectopia, horseshoe kidneys and other developmental anomalies, and neoplasm.A total of 1315 children (633 boys and 682 girls) between the ages of 5 and 17 years were selected for this study using a random selection method. Age, sex and anthropometric measurement of the body size indicators such as weight (WT), height (HT), body surface area (BSA) and body mass index (BMI) were obtained for each subject. Using the vertical scale of a portable stadiometer, each participant was placed, without shoes, in an upright position with the head held in the Frankfort plane and the height measured to the nearest 0.5 cm. With each participant lightly clothed, weight was measured with a weighing scale to the nearest 0.1 kg.20 and in quiet respiration. The bipolar length of each kidney was measured from the highest to its lowest point. The width and thickness were obtained in the transverse plane in an orthogonal direction, near the renal hilum but free of the pelvis. The renal thickness or anterioposterior (AP) diameter, was measured in the same transverse plane with a line perpendicular to the width , as shown in Kidney parameters were obtained using a GE LOGIC 400CL ultrasound machine made by GE medical systems with a 3.5 MHz curvilinear probe. Renal sizes by ultrasound were obtained by one of the authors who is a radiologist. To achieve greater accuracy, two sequential measurements were taken and the mean calculated. Kidney measurements were obtained with subjects in a prone position1/2 (Mosteller formula).BSA = (weight (kg) × height (m)/3600)2 (m).BMI = weight (kg)/heightRenal volume = length (cm) × width (cm) × thickness (cm) × 0.523.Ethical approval to conduct the study was obtained from the College of Medicine Research Ethics Committee, University of Nigeria Enugu Campus (Reference no. 070/06/2019).The mean values of the left and right renal dimensions of the various age groups of the studied population have been presented in p < 0.01), the reverse was noted for the right renal width. Significant sexual dimorphism was observed in the kidney dimensions (p < 0.05). The left kidney was significantly longer in females (p < 0.05) in the age and weight categories, whilst the males showed significantly wider kidneys in all the categories . Females were also noted to have thicker kidneys in most of the categories (age and weight) and larger volume in all the categories than males, though without statistical significance (p > 0.05).Significant asymmetry was noted in all the measured renal parameters. Whilst the left renal length, thickness and volume were greater than those of the right in all the age-, weight- and height-matched categories  with all the renal dimensions with the exception of BMI which is in agreement with reports by Younus et al.28 that BMI may not be a good predictor of renal measurement. However, this is contrary to another report where BMI was demonstrated to significantly relate to renal length.42Previous Nigerian-based results on renal parameters of adults22 in a similar study carried out in infants.The prevalence of congenital anomaly as revealed in this study was 0.46% which is slightly lower than the 0.89% recorded by Scott et al.We have established age-, weight- and height-specific normal values of the kidneys in apparently healthy Nigerian children and developed regression equations for adequate evaluation and follow-up of renal diseases in clinical radiology and general medicine. We also noted significant sexual dimorphism and bilateral asymmetries in the kidney parameters of the studied population.Urinalysis, serum electrolyte, urea and creatinine or glomerular filtration rate tests were not carried out for the study population, which may have further eliminated possibilities of including children with renal diseases. These investigations are more specific for kidney function than they are for renal morphology, which is the focus of this work.


One of the characteristics of the cerebral aging process is the presence of chronic inflammation through glial cells, which is particularly significant in neurodegeneration. On the other hand, it has been demonstrated that the aryl hydrocarbon receptor (AHR) participates in the inflammatory response. Currently, evidence in animal models shows that the hallmarks of aging are associated with changes in the AHR levels. However, there is no information concerning the behavior and participation of AHR in the human aging brain or in Alzheimer’s disease (AD). We evaluated the expression of AHR in human hippocampal post-mortem tissue and its association with reactive astrocytes by immunohistochemistry. Besides this, we analyzed through ELISA the AHR levels in blood serum from young and elder participants, and from AD patients. The levels of AHR and glial fibrillar acid protein were higher in elder than in young post-mortem brain samples. AHR was localized mainly in the cytosol of astrocytes and displayed a pattern that resembles extracellular vesicles; this latter feature was more conspicuous in AD subjects. We found higher serum levels of AHR in AD patients than in the other participants. These results suggest that AHR participates in the aging process, and probably in the development of neurodegenerative diseases like AD. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor widely known for its role in mediating the detoxification of xenobiotics. In the absence of its ligands, AHR remains inactive and forms a complex with the chaperone heat shock protein 90, p23, and AHR-associated protein, whose primary function is to retain AHR in the cytoplasm. When AHR interacts with its ligands, it undergoes conformational changes that expose its nuclear localization sequence, thus promoting AHR translocation to the nucleus, where it heterodimerizes with the AHR nuclear translocator (ARNT). The complex formed by the AHR–ligand–ARNT binds to specific DNA regions called xenobiotics response elements or dioxin response elements located in the promoter regions of their target genes, to regulate their expression . In addiAging is a time-related decline in biological functions, which ultimately results in organismal death . It is mAt present, evidence in different cell lines  and animt = 2.537, df = 11, p = 0.0276, We confirmed the hippocampus integrity through hematoxylin–eosin staining A. We fout = 2.616, df = 11, p = 0.024, The antibody against AHR was previously tested in C57BL/6 mouse liver tissue to evaluate its effectiveness in immunohistochemistry . We fount = 1.006, df = 28, p = 0.3232, t = 2.621, df = 43, p = 0.0121, t = 2.151, df = 27, p = 0.04,  = 0.4772, p = 0.6291; As AHR was almost undetectable in blood serum and considering the possibility that AHR could be present in extracellular vesicles, we treated the serum samples with 4% Tween 20, a reported way to break circulating exosomes . In thesIn this study, we show evidence that supports, to our knowledge for the first time, the AHR association in the aging process of the human brain and, probably, in the development of AD through the response of glial cells to a pro-inflammatory environment in the central nervous system. We found an increase in the AHR expression in the brain of elder individuals and AD patients, with the most visible changes in astrocytes. Additionally, the AHR serum level was higher in AD patients compared with elderly participants. Taking into account that AHR-knockout mice are more susceptible to inflammation stimulus  and thatRegarding the cell-type location, the AHR protein was located in astrocytes. This finding can be explained by the fact that astrocytes are among the principal cells that participate in the modulation of inflammation during aging. We observed the AHR protein mainly in the cytosol and not in the cell nuclei, which suggests that during human aging and in AD, AHR has an impediment to act as a transcription factor. Also, in AD post-mortem brain tissue, we observed AHR with a morphology that resembles extracellular microvesicles . Our findings using post-mortem tissue are consistent with our evidence about serum AHR, since AHR could only be detected in the detergent-treated blood serum, which suggests that AHR is circulating through the bloodstream in microvesicles derived from the brain or other tissues. The microvesicles, such as exosomes, participate in cellular communication mechanisms, with the ability to cross the blood–brain barrier allowing the circulation through the bloodstream. The molecular mechanisms involved in cell–to–cell communication through exosomes that transport proteins associated with neuropathologies can not only be used as a molecular marker of diseases, but can also provide a molecular pathway to identify and study the fundamental pathological changes of diseases like AD, from a different approach . The preThe AHR and the astrocytes are critical elements as mediators of diverse biological processes, such as the regulation of the immune system homeostasis in response to environmental toxicants  or in reIn conclusion, the AHR participates in the aging process and probably in the development of AD through the response of astrocytes, which can release AHR into microvesicles. Our findings open a gap in the knowledge about the AHR regulation in the human neurodegenerative pathology, its association with glia, and the possibility that the AHR detected in the serum of patients with AD comes from the brain and is released into extracellular microvesicles . This is a case-control study, in Mexican participants, that was performed in two phases. For the first one, we studied post-mortem hippocampus tissue from young  and elder  subjects of either sex, without infectious, inflammatory, or neoplastic systemic disease and macroscopic abnormalities in the brain. These samples were obtained from the Hospital General de México “Eduardo Liceaga”. We also studied post-mortem hippocampus tissues from AD patients of either sex (n = 3) that were obtained from the Brain Bank-LaNSE CINVESTAV-IPN, Mexico. In the second phase of this study, we recruited young  and elder  healthy participants of either sex without cognitive impairment. We also recruited AD patients of either sex  with the diagnosis of probable AD dementia determined according to the National Institute of Aging-Alzheimer’s Association (NIA-AA) criteria  from the2O2 for immunohistochemistry or with 7% Sudan Black in 70% ethanol for immunofluorescence. After washing, the tissue was blocked with 5% ASB with 0.2% triton by one h and incubated overnight with primary antibodies against AHR  or glial fibrillary acidic protein . After washing the primary antibody, sections were incubated with a secondary antibody, Goat anti-Mouse  or Anti-Rabbit  for immunohistochemistry, and Alexa 488 and Alexa 568 for immunofluorescence, washed and mounted using Entellan for immunohistochemistry or Vectashield with DAPI for immunofluorescence. Slides were examined with a Nikon Eclipse 801 . Samples obtained from Hospital General de México were post-fixed in 4% formaldehyde, embedded in paraffin, and sectioned to obtain slices of 5 µm. Then, we analyzed the morphology trough the hematoxylin–eosin staining. We received the samples from the Brain Bank-LaNSE as slices of 30 µm. These slices were from hippocampal tissue fixed with 4% paraformaldehyde and cut in freezing conditions. Sections were washed with PBS and incubated with citrate buffer pH = 6 for antigenic retrieval, then they were washed and incubated with 0.3% H2. To discriminate between neuron and non-neuron cells, we manually counted the stained nuclei, taking into account size and morphology using decision-making algorithms and descriptions previously reported [We quantified the data through the Image J software  using three sections of each hippocampus sample from young (n = 7) and elder (n = 6) donors. From each section, we took five micrographs of adjacent regions in the CA1 and CA3 hippocampal regions in a total area of 17 mmreported . We quanBlood samples were collected and processed to obtain blood serum according to the NIA-AA guidelines for the standardization of preanalytical variables in the study of blood-based biomarkers in AD . Particiv/v)-treated serum samples [Serum protein levels were determined using the Lowry assay. Tween .


Of the GISTs, 53 (75.71%) were in the stomach, 3 (4.29%) in the small intestine, and 14 (20.0%) in the large intestine. The mean age of the malignant GIST group was significantly higher than that of the benign GIST group (p = 0.032), their tumor long axes were significantly greater (p = 0.073), their tumor volumes were significantly larger (p = 0.001), and the frequency of tumor necrosis was higher (p = 0.001). In multivariate analysis, malignant GIST was associated with location in organs other than the stomach , longer axis , larger volume , and necrosis . The mean age of the recurrent GIST group was higher than that of the non-recurrent group (p = 0.045), their tumor long axes were significantly longer (p = 0.005), and their volumes were greater, but this last difference was not significant (p = 0.072). Conclusions: Tumor volume can be considered an additional risk factor in assessing the malignant potential of GISTs and tends to increase in recurrent GISTs.Background and purpose: Gastrointestinal stromal tumors (GISTs) are rare diseases of the gastrointestinal tract but they are the most common gastrointestinal tumors of mesenchymal origin. Since most GISTs have malignant potential, their probability of malignant progression must be evaluated. This study was conducted to examine the correlation between three-dimensional GIST volume measured by CT and malignant potential. Materials and methods: A retrospective study was performed on 70 patients diagnosed with GIST after surgical resection in Hanyang University Seoul Hospital from 2012 to 2017. Linear regression analysis was used to establish which between the length of the long axis of GISTs, originally considered a predictor of malignancy, and their volume was a more accurate predictor of malignancy. Tumor dimensions were measured by CT. Results: Data were analyzed using the chi-square test or Student’s  Gastrointestinal stromal tumors (GISTs) are rare diseases of the gastrointestinal tract but they are the most common digestive tract tumors of mesenchymal origin, accounting for 50% of submucosal tumors . AccordiRecent technical advances have suggested that it is helpful to evaluate three-dimensional tumor burden by PET and MRI . Since GAlthough it has been suggested that tumor volume can be used as a method for GIST evaluation, this issue has not been much studied. It is difficult to use previous data to test this hypothesis because of limitations such as that only patients with metastasis were examined, tumor diameters were not evaluated by experts, and follow-up periods were short. The aim of this study was to determine whether tumor three-dimensional volume is helpful in predicting the malignant potential of GISTs.This study was performed on adult patients over 18 years of ages who underwent surgical or endoscopic resection and were diagnosed with GIST in Hanyang University Medical Center from 2012 to 2017. The study was approved by the Hanyang University Review Committee. (HYUH 2017-07-045-005) and is a retrospective study of electronic records in the Hanyang University Medical Center from 1 January 2012 to 31 December 2017.The longest axis, traditionally used as a malignancy predictor, and three-dimensional volume, the potential predictor examined in this study, were measured by CT performed by a specialist in radiology. Through the cooperation of the radiology department, the patient’s CT was reconstructed into 3D, and the radiology specialist evaluated the 3D volume through the reconstructed CT.Baseline characteristics such as patients’ sex, age, and location of GIST based on endoscopic images and descriptive results were investigated. Patients who underwent EUS (Endoscopic ultrasonography) were evaluated for pattern, density, induced layers, subtype, and mitotic counts (per 50 HPF (High power field)) examined by histology.Primary outcome was defined as malignant change, and secondary outcome was defined as recurrence. Malignant changes at the time of diagnosis, duration of follow-up, and recurrence during follow-up were evaluated. Previous studies have defined tumor necrosis as the presence of microscopic coagulation necrosis without inflammation or fibrosis, regardless of the proportion of tumor necrosis to tumor cells. Tumor necrosis was defined by referring to previous studies.t-test. To examine factors associated with GIST malignancy potential, we used logistic regression and analyzed Hosmer–Lemeshow chi-square values. Odds ratio and 95% confidence intervals were calculated for each variable. All reported p values were 2-tailed, and the significance level was set at 0.05.We used Microsoft Office Excel 2010  and IBM SPSS Statistics version 25.0  for data processing. Data are expressed as median values, and differences in variables between the pairs of groups were analyzed using the chi-square test or Student’s p = 0.032), and the malignancies were more frequent in non-stomach organs than in the stomach (p = 0.011). The long axes of tumors were significantly greater in the patients with malignancies , tumor volumes were also larger , and the frequency of necrosis was higher . There was no significant difference in gender or mitotic count (<5 versus ≥5)  were malignant at the time of diagnosis. Patients with malignancy at the time of diagnosis were significantly older than those without malignancy  .p = 0.045), and recurrence was more common in non-stomach organs than in the stomach (p < 0.001). In the group with recurrence, the long axes of the original tumors were longer than in the group without recurrence , and their volumes were larger, though this difference was not significant . Gender and mitotic count were not significantly different  suffered recurrence. Mean follow-up was 3.79 years, and there was no statistically significant difference in the follow-up period between the patients who suffered recurrence and those who did not. Patients in the former group were older than those in the non-recurrent group  and had longer axes . Their volumes were also larger . When the tumors were divided into two groups, one comprising those with long axes ≥5 cm and the other those with long axes <5 cm, it was found that the frequency of malignancy was significantly higher in the former . The incidence of necrosis was higher in malignant tumors .In a multivariate analysis , malignaThe tumor long axis and tumor volume were compared for their potential as malignancy predictors, and ROC curves were drawn to measure area-under-the-curve (AUC) values. The tumor long axis was found to have an AUC of 0.876 (95% CI 0.771–0.982), and the tumor volume was found to have an AUC of 0.89 (95% CI 0.796–0.984). These values were not significantly different, but the positive predictive value of the tumor volume was slightly higher than that of the tumor long axis .In this study, it was shown that tumor volume can be used as a risk factor for GIST malignancy and tends to increase in recurrent GISTs.About 50% of submucosal tumors are GISTs. Since the need for additional treatments, such as the administration of imatinib and simple resection, is dependent on the risk of malignancy or recurrence, it is important to assess this risk at the time of tumor diagnosis . CT, MRIp = 0.023), tumors composed of non-spindle cells (p = 0.027), tumors with mitotic count ≥5 (p = 0.000), and tumors with myxoid change (p = 0.002); recurrence was associated with myxoid change (p = 0.045) [Several studies have been conducted on risk factors for GIST malignancy and recurrence. In 2002, a method of classification  was proposed, based on tumor size and mitotic count, and has been used up to the present . Accordi= 0.045) . In thisRecently, studies evaluating risk have been carried out using tumor volumes calculated from 3D images. A study of 56 patients with liver metastasis suggested that 3D volume was a better method to evaluate the risk of liver metastasis after imatinib treatment than the tumor long axis . In addiA previous study evaluating the degree of predictability of tumor volume was limited by the small number of patients and by the fact that diameter evaluation was not carried out by experts. Our study shows that tumor volume is an effective measure of the risk of malignancy in patients with GIST. Three-dimensional reconstruction and volume measurement are possible in standard centers. Therefore, GIST volume measurement can be a practically useful method to establish treatment strategies.However, this study has several limitations. It was performed in a single institution, so the number of patients was quite small; although the usefulness of tumor volume measurements was established, the accuracy of the appropriate cut-off value was limited, as was the accuracy of the measurement of risk factors associated with recurrence. Further studies with a large number of patients are needed to fully evaluate risk factors associated with recurrence.In conclusion, measuring tumor volume at the time of diagnosis in GIST patients may be helpful to predict malignancy and recurrence.


Weight loss interventions using mobile phone apps have recently shown promising results.This study aimed to analyze the short-term weight loss effect of a mobile coaching intervention when it is integrated with a local public health care center and a regional hospital’s antiobesity clinic as a multidisciplinary model.t tests and multiple linear regression analysis were used to identify the intervention factors related to weight change.A total of 150 overweight or obese adults signed up to complete an 8-week antiobesity intervention program with human coaching through a mobile platform. Paired P=.06), △MET , number of articles read , and frequency of weight records  were identified as significant factors of weight change. Moreover, age , sex , △MET , and number of articles read  were identified as significant variables of fat mass change.Among the 150 participants enrolled in this study, 112 completed the 8-week weight loss intervention. Weight , body mass index, waist circumference, fat mass , and fat percentage all showed a statistically significant decrease, and metabolic equivalent of task (MET) showed a statistically significant increase after intervention. In multiple linear regression analysis, age  care app by health care providers, was effective for short-term weight loss. Additional studies are needed to evaluate the efficacy of mHealth care apps in obesity treatment. Obesity is one of the most prominent problems in the global public health domain. Worldwide, in 2016, more than 1.9 billion adults were overweight, and 650 million were obese [Dietary restriction and increased physical activity are known treatments for obesity. Self-weighing is also known to be associated with weight loss . To deliAs South Korea has a well-organized health care access, high-quality medical infrastructure, and high mobile phone penetration rate , it is aThe purpose of this study was to analyze the short-term weight-loss effect of mobile coaching intervention when it is integrated with a local public health care center and a regional hospital’s antiobesity clinic as a multidisciplinary model. For mobile coaching intervention, we used a commercially available mobile app to target a broader population.This was a single-arm study that assessed the impact of a mobile short-term weight loss intervention combined with a conventional offline intervention based on the local health care infrastructure. Participants were recruited by a local public health care center and sent to Myongji Hospital, a local hospital, for the initial offline intervention led by a physician. An 8-week mobile intervention using the Noom Coach (Noom Inc) was provided to the participants with the offline intervention after each participant underwent an orientation of the antiobesity program . Various2 or waist circumference greater than or equal to 90 cm for men and greater than or equal to 80 cm for women per the World Health Organization criteria for Asian population [Participants were recruited by Ilsan Dong-gu Public Health Center, a local public health center run by the government. A total of 150 participants were recruited from March 2017 to September 2017. We included participants who were overweight or obese, defined as a body mass index (BMI) greater than or equal to 23 kg/mpulation . ParticiAll participants visited the hospital’s antiobesity clinic once a month during the 8-week study period. The offline weight loss intervention consisted of an evaluation of the participants’ initial obesity status followed by consultation for lifestyle modification with an obesity specialist. All the participants were recommended by physicians and dietitians to reduce 500 kcal from their daily dietary intake . The parNoom Coach is a commercialized mobile app launched in 2012 that provides various lifestyle-related logs and is available in Android and Apple app markets. The mobile intervention consisted of (1) food logging, (2) exercise logging, (3) weight logging, (4) in-app group activities, (5) in-app articles, and (6) messages from the coaches. Total counts using mobile app is the sum of diet records, exercise records, weight records, all in-app group records, number of messages, and number of articles read. The participants were encouraged to log their food intake and exercises on a daily basis and record their weight on a weekly basis. The participants were assigned to an in-app group where they can communicate with other participants, sharing their healthy behaviors. In-app articles were also provided for the participants to gain knowledge about healthy dietary intake and physical activities. In-app articles were written by physicians, nutritionists, and clinical psychologists. Individual coaches offered feedback to the participants based on their entries with praise, emotional support, encouragement, and validation. A Web-based dashboard was used to monitor the participants’ data and provide individualized feedback . The coaThe coaches received education from physicians, clinical nutritionists, and clinical psychologists before starting coaching services regarding the medical, nutritional, and behavioral components of obesity and weight loss. Among the 93 techniques of the Behavior Change Technique Taxonomy , 10 were2). Waist circumference was measured at the midpoint between the lower border of the rib cage and the iliac crest. Body composition, including whole-body muscle mass, fat mass, and fat percentage, was estimated using a bioelectrical impedance analysis device . Blood pressure was measured in the right arm after the participant was seated and allowed to rest for 15 min; two measurements were recorded. Metabolic equivalent of task (MET) was measured to track the exercise levels of the participants. MET was calculated using the MET formula using the exercise intensity and duration and physical activity data collected during the survey [All measurements were taken according to a standard protocol at baseline and week 8. Adiposity indices, such as BMI, waist circumference, and body composition, were measured by registered nurses at both public health centers and the Myongji Hospital. Anthropometric measurements were performed with the subjects wearing light clothing without shoes. BMI was calculated by dividing weight by height squared  components in the regression model. We presented an effect estimate for the interquartile increase in each variable on weight, which was calculated by multiplying the regression coefficient by the interquartile range (75th–25th percentile) of each variable. The equation was applied for effective comparison of the effect estimates across various variables with different units and easy interpretation of weight change corresponding to a realistic increment of each risk factor [P values <.05 were considered significant.The mean values and standard deviations of all variables before and after the weight reduction were calculated. The mean difference and 95% CI of all variables were also calculated. A paired k factor . We analAmong the 150 participants, 112 completed the 8-week intervention (completion rate 74.7%). The mean age of the participants was 47.8 years (SD 10.2), and the proportion of females was 72.3% (82/112). The values of the variables before and after the 8-week intervention are presented in P=.04), △MET , and total counts using a mobile app  significantly predicted short-term weight loss. Moreover, specific components of total counts using a mobile app were analyzed with multiple linear regression. Age , △MET , number of articles read , and frequency of weight records  were identified as significant factors of weight change (P=.07), sex , △MET , and total counts using a mobile app  significantly related to fat mass change. In the analysis of specific components of the total counts using a mobile app, age , sex , △MET , and number of articles read  were identified as significant variables. The results indicated that for every 1-year increase in age, there was a corresponding 0.07 kg increase in weight and 0.06 kg increase in fat mass. For every unit increase in MET, there was a 0.0009 kg decrease in weight and 0.00009 kg decrease in fat mass. Furthermore, for every one-time increase in the number of articles read, there was a 0.01 kg decrease in weight and a 0.02 kg decrease in fat mass, and for every one-time increase in weight record, there was a 0.05 kg decrease in weight in our study. In another explanation, the weight change per the interquartile range increase in age, △MET, and total counts using a mobile app were 0.75, −0.75, and −2.24 kg, respectively, and fat mass change per the interquartile range increase in age, △MET, and total counts using a mobile app were 0.63, −0.75, and −2.24 kg, respectively, in model 1. The fat mass change per the interquartile range increase in age, △MET, number of articles read, and frequency of weight record were 0.88, −0.75, −1.57, and −0.55 kg, respectively, and the fat mass change per the interquartile range increase in age, △MET, and total use frequency were 0.75, −0.75, and −3.14 kg, respectively, in model 2.The variables associated with weight changes in the multiple linear regression analysis are displayed in t change . MoreoveThis study examined the effectiveness of the obesity management program on the basis of the hospital setting with the mobile coaching program and revealed that younger age, increased number of articles read, and the amount of exercise were significant variables for short-term weight loss.On the basis of the analysis, younger age showed a positive correlation with weight loss effect. The accessibility of the mobile platform might have been affected by age, which was reported in other studies on mobile platforms -19. The A significant association between self-monitoring and weight loss was reported in multiple studies -27, and One of the key factors in the mobile intervention in this study was the use of human lifestyle coaches. Although a smartphone app is an effective method for recording and self-monitoring, the general retention rate is relatively low over time for many reasons . A mobile phone app designed for accessibility and personalized features is most important . The appThe major strategy of our intervention was using a multidisciplinary approach to weight loss . OverallSecond, the combination of hospitals and mobile coaching provided continuous care within the participants’ lifestyle on a daily basis. Mobile coaching supported the participants by providing them with specific daily tasks to meet the weight loss goals suggested by the hospital clinicians. The hospital clinic visits and mobile intervention supplemented their respective weaknesses. Offline encounters with and feedback from health care providers at the hospital clinic supplemented the low compliance and motivation problems of the mHealth care platform. The daily penetration of mobile coaching and easy logging supplemented the fragmented care in offline intervention.Third, public health centers and mobile intervention showed a synergistic effect on the engagement of the users. The local public health centers promoted local resident leaderships to participate in in-app groups to better activate the mobile groups. As the group was always accessible through the mobile app, the dynamics between the participants were different from that among the participants of the offline group sessions at the local public health centers in terms of continuity.Our study has several limitations. First, this was a single-arm study designed to analyze effective intervention factors related to weight change. Therefore, a randomized control trial is required to analyze the effectiveness of the intervention compared with the control group. Second, the sample size was relatively small, and the intervention duration was short, so we could not measure the sustainability and long-term effect of our intervention. Third, our study has a potential reporting bias because the mobile data collected through the mobile app were self-reported data. Under- or overreporting was possible on the basis of the characteristics of each participant. This might be from some limitation of the calibration of the frequency and types of intervention.The major outcome of this study shows that the multidisciplinary approach combining the public health sector and hospitals by health care providers with a mHealth care app had shown a short-term weight loss outcome. Further large, long-term studies are needed to evaluate the effectiveness and efficiency of the mobile health care app in an antiobesity program and to examine the possibility of a synergistic effect between mobile health care and the face-to-face approach for managing obesity.


To identify the possible cause of IVF failure, 555 patients were enrolled in the present study to determine their relevant clinical characteristics and vaginal microbiota. Our results indicated that the age and endometrium thickness significantly affected the pregnancy success rate of pregnant patients (P group) and non-pregnant patients (NP group) receiving IVF, and high values of luteinizing hormone, estrogen and progesterone were observed from P group. Furthermore, the Partial Least Squares Discriminant Analysis (PLS-DA) indicated a different microbial composition in P group and NP group, and a higher microbial abundance had been identified in non-pregnant patients compared with pregnant patients. At phylum level, a higher abundance of Firmicutes and Proteobacteria, and a lower abundance of Actinobacteria, Fusobacteria, and Bacteroidetes were obtained in pregnant patients compared with non-pregnant patients. At genus level, a lower abundance of the probiotic Lactobacillus, and higher abundance of pathogens Gardnerella and Prevotella were identified from non-pregnant patients. Therefore, the disordered microbiota, characterizing by the reduction of probiotics and overgrowth of pathogens in non-pregnant patients, may be used as a potential indicator for a higher IVF failure rate.Infertility is one of the most common reproductive system diseases, and no effective method is available for its treatment. Although  Infertility belongs to one of the reproductive system diseases, which is defined as having not reached at a clinical pregnancy for 12 months or more of unprotected sexual intercourse by the World Health Organization (WHO)  is the most common assisted reproductive technology. Up to now, five million babies have been born through IVF technology and increases at an annual rate of 200,000  and non-pathogenic  organisms  agreed to receive IVF treatment and signed informed consent for IVF. Patients coincided with the following features were excluded: interruption or discontinuation of treatment for any reason, abnormal ovarian function, abnormal cervical cytology, abnormal semen examination of partner, or other diseases combined with infectious diseases, malignant tumors, severe diabetes, severe liver, and kidney disease. The enrolled patients were mainly tubal infertility , because it is the main cause of female infertility. However, ovarian dysfunction will cause abnormal basic hormone levels in patients, and it cannot be ruled out that the imbalance of hormone levels leads to the failure of IVF. In addition, infertility caused by male factors  is essentially not directly related to female infertility. Therefore, we excluded infertility caused by ovarian dysfunction and male factors from the enrolled criteria. In addition, in order to ensure the homogeneity of the experimental data, the IVF treatment of the infertility patients enrolled in this experiment are all used in frozen embryo transfer.Before collecting vaginal secretion samples, it is required to ensure that no cervical treatment and no vaginal irrigation within seven days, no sexual activity within 2 days and all patients did not use any antibiotic within 15 days, so as not to affect the results of the study. Vaginal secretion samples were collected before the preparation of the endometrium, using vaginal speculum to expose the cervix, the clinician used a sterile suction tube to obtain a vaginal secretion sample from the posterior iliac crest, added 20% glycerol, and immediately frozen at −80°C until further use. Reproductive outcomes were recorded on the basis of the definition of biochemical and clinical pregnancy. According to the pregnancy outcome of IVF, the samples were divided into two groups, the pregnancy successful group (P) and the pregnancy failure group (NP). All patients were allowed to obtain medical records to obtain their reproductive history and reproductive outcomes.Fifteen days after the embryo transfer, the pregnancy result was detected by the detection of β-Human Chorionic Gonadotropin (β-HCG) in serum, and the clinical diagnosis of pregnancy was determined by detecting the pregnancy sac, embryonic bud and embryonic heartbeat using transvaginal sonography after the 6th week of pregnancy . EctopicAccording to the pregnancy outcome of IVF, patients were divided into P group (pregnancy group) and NP group (none pregnancy group) , and theThirty-seven vaginal secretions in P group and twenty-one vaginal secretions in NP group were used to compare vaginal microbial diversity using high-throughput sequencing. The steps for this technique are as follows:PRJNA554010) sequencer in Personal Biotechnology Co., Ltd., Shanghai, China.DNA extraction and amplification: the genomic DNA kits  and the bead beating method were used  to extrahttp://qiime.org/, (http://www.drive5.com/usearch/). Sequence analysis was subsequently performed using UCLUST software package (http://qiime.org/) software package (version 1.8.0) before the cluster analysis. P < 0.05 showed the statistical significance. Finally, PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) was used to predict the metabolic function of bacteria in KEGG functional spectrum database.Sequencing and analysis: the TruSeq Nano DNA LT Library Preparation Kit (Illumina company) was used to prepare sequencing libraries and then use the Agilent High Sensitivity DNA Kit to check the quality of the library before the sequencing begins. Finally, the sequencing results were analyzed as follows: he paired-end reads were checked and removed using QIIME  and USE package , and seqhttps://www.graphpad.com/) and SPSS 23.0 software . Statistical significance was determined using a Student's test, one-way or two-way ANOVA and were annotated using the international convention related to the statistical representation. For continuous variables that satisfy a normal distribution, such as age, the data will be reported as mean ± SD. Otherwise, it is expressed in quartiles.Data handling, analyses and graphical representations were processed by Microsoft Excel, GraphPad Prism 8 (The patient enrollment process is described in p = 0.00) and endometrium thickness (p = 0.02) had a strong connection with the pregnancy outcomes. Although no significant difference were observed between IVF successes with luteinizing hormone (p = 0.52), estrogen (p = 0.52), progesterone (p = 0.34), taking days (p = 0.28) and embryo number (p = 0.38), high values of luteinizing hormone (8.93 vs. 7.82), estrogen (402.84 vs. 380.07), and progesterone (0.49 vs. 0.42) were obtained from P group.As shown in N = 37) and NP group (N = 21) based on their pregnancy situations.To further explore the potential factors on IVF successes, vaginal sections of 58 patients were randomly sampled from the enrolled 475 infertile patients, and these samples were divided into P group  and 3,413 OTUs were obtained from all the samples (data not shown). As shown in Firmicutes, Actinobacteria, Proteobacteria, Fusobacteria, and Bacteroidetes constituted the most common dominant phyla in P group  and NP group , which accounted for 99.91 and 99.83% of the total sequencing number in these two groups. Compared with the NP group, a higher abundance of Firmicutes (80.77 vs. 72.61%) and Proteobacteria (9.18 vs. 8.01%), and a lower abundance of Actinobacteria , Fusobacteria , and Bacteroidetes  were observed in P group (The top 10 microorganism populations at the phylum level were shown in  P group .Lactobacillus (74.61 vs. 63.09%), and the lower abundance of pathogens Gardnerella , Atopobium , Sneathia , and Prevotella   .P = 0.10), replication and repair , lipid metabolism , and enzyme families  compared with NP group, and the microbial difference in these two group had little effect on cell motility and carbohydrate metabolism  is used to compare the effect of altered microbial changes on host functions. As shown in tabolism .The human uterus cavity is traditionally considered to be sterile, while the vaginal microbiota plays an important role in fending against pathogens . Emerginlactobacillus bacteria in the vagina, such as Gardnerella, Atopbium, Prevotella and so on, was related to the negative effects of reproductive function.In the present study, 555 patients who received IVF were enrolled and our results indicated that the age and endometrium thickness significantly affected the outcome of the IVF, and higher values of luteinizing hormone, estrogen and progesterone were obtained from P groups although these hormones had been adjusted to normal levels before the IVF for patients with abnormal hormones. Similarly, studies conducted by Grondahl ML et al. confirmed that woman's age did pose significant influence on early embryo morphological development . To bettInfertility has become a social issue. Considering the ineffective of traditional medicines and surgery, IVF technology brings hope to infertile patients. However, the low success rate and high abortion rate for IVF bring tremendous pressure and pain to countless families. Although related factors including age, endocrine, immune, and infection have been recognized , little Lactobacillus is the most common probiotics in the vagina, the lactic acid and fatty acids produced by Lactobacillus acidify the environment to pH ≦ 4.5 in the vagina and inhibit the growth of other pathogenic or dysbiotic bacteria in the vagina, maintaining a healthy vaginal environment  .Previous studies have found that chlamydia trachomatis detected in the vagina of women receiving IVF correlates with adverse pregnancy outcome . The maiginalis) , 39. It bacteria . TherefoLactobacillus and the overgrowth of Gardnerella, Atopbium and Prevotella possessed strong connection with the success of IVF. Interestingly, these correlations were even more significant following the overgrowth of the Gardnerella, Atopbium and Prevotella genus, as patients with high incidence of Gardnerella, Atopbium and Prevotella either failed to be pregnant after embryo transfer or experienced abortion. Therefore, it seems worthwhile to discuss the role of vaginal microbiome in IVF, and prove their potential as biomarker to predict the outcomes of IVF.Currently, the IVF treatment for infertility is quite expensive for most of patients, and once the treatment is failed, it will cause physical and mental harm to patients. So, there is an urgent need to predict biomarkers for pregnancy outcomes in women receiving IVF. In our study, we found that the reduction of However, some limitations should be taken note. One limitation of this study is the various time points for vaginal secretion collection and the no comparison of the vaginal microbiota among different ages. In previous studies, the female age has been considered to be one of the main limiting factors for fertility and reproductive outcomes , and theLactobacillus, and the overgrowth of Gardnerella, Atopbium, and Prevotella possessed strong connection with the success of IVF, and the bacterial intervention via restoring vaginal microbial diversity to “health” status may be a good choice to enhance positive reproductive outcomes of IVF.In the present study, high-throughput sequencing method was firstly used to explore the microbial diversity among different outcomes of IVF female. Our group found that the age, endometrial thickness, reduction of PRJNA554010.The datasets generated for this study can be found in the GenBank, accession number The studies involving human participants were reviewed and approved by The Second Affiliated Hospital of Nanchang University and Jiujiang Maternal and Child Health Care Hospital and this project was registered at Chinese Clinical Trial Registry (NO. ChiCTR1900022537). The patients/participants provided their written informed consent to participate in this study.TC, ZL, and XD designed the study. YK, XL, QS, YG, and CZ carried out the experiments. TC, ZL, YK, QS, YG, CZ, and XD analyzed the references and wrote the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Wheat in the diet promoted the presence of Lactobacillaceae, Bifidobacteriaceae and Bacteroides xylanisolvens, which can degrade complex carbohydrates. Maize positively affected the abundance of Bacteroides vulgatus. The addition of CP promoted the family Rikenellaceae, while sodium butyrate as feed supplement was positively related to the family Lachnospiraceae. Functional predictions showed an effect of the cereal type and a statistical significance across all supplementations and their corresponding interactions. The composition of diets affected the overall structure of broilers’ intestinal microbiota. The source of NSP as a substrate for bacterial fermentation had a stronger stimulus on bacterial communities than CP content or supplementation of butyrate.The intestinal microbiome can influence the efficiency and the health status of its host’s digestive system. Indigestible non-starch polysaccharides (NSP) serve as substrates for bacterial fermentation, resulting in short-chain fatty acids like butyrate. In broiler’s nutrition, dietary crude protein (CP) and butyrate’s presence is of particular interest for its impact on intestinal health and growth performance. In this study, we evaluated the effect on the microbial ecology of the ceca of dietary supplementations, varying the cereal type (maize and wheat), adequate levels of CP and supplementation of sodium butyrate on broiler chickens with 21 days. The overall structure of bacterial communities was statistically affected by cereal type, CP, and sodium butyrate ( Diet composition has a significant impact on poultry due to its influence on digestibility, gut wall morphology, and microbial structure, which might affect the health status, carcass composition and meat quality . Maize-bGrowth parameters in broiler chicks are also influenced by the dietary concentration of crude protein (CP), which might affect carcass yield and breast meat yield and causes a decrease in pancreas weight . MoreoveThe addition of butyrate in the form of sodium butyrate is seen as an alternative to promote broiler chickens’ development. This compound is solid, stable and is associated with the improvement of body weight, feed conversion ratio and the development of gut wall tissues by increasing villus height and crypt depth ratio of duodenum and jejunum . FurtherRuminococcus, Streptococcus, Faecalibacterium, Lactobacillus, and Clostridium cluster IV, XIVa and XIVb .n = 30 per group). Specific details for experimental design have been previously published  and randomly allocated to eight dietary groups  following the manufacturer’s instructions. The quality and concentration of DNA were assessed through NanoDrop 2000 Spectrophotometer , and DNA was stored until use at −20°C. The V1-2 region of the 16S rRNA gene was amplified to produce Illumina sequencing library. The protocol followed the same methodology as Kaewtapee et al. . BrieflyRaw reads were quality filtered, assembled, and aligned using Mothur pipeline . Sequencp as 0.05 and a correlation threshold as 0.3 at the genus taxonomical level. Nodes indicated the genus and were colored based on their abundance for each treatment, while edges represented the correlations’ strength.Correlation network analysis was done based on the SparCC algorithm , making p ≤ 0.05. The community similarity structure was depicted through Principal Coordinates Analysis (PCoA). Similarity percentage (SIMPER) analysis was used to identify the OTUs responsible for the differences between the groups (p < 0.05. Diversity indices (Shannon diversity and Pielou’s evenness) were calculated based on abundance data with PRIMER software.Datasets were analyzed with the multivariate software PRIMER  was used to test for individual effects on each output . Calculations were based on ANOVA and multiple comparisons based on the least-squares mean estimates and followed the model:Notwithstanding that the present trial was not designed to study the animals’ growth performance, it should be addressed that the growth of the broilers matched the standards of the Ross 308 breed. Body weight and average daily body weight gain data are presented in [p = 0.001; p ≤ 0.05; A significant interaction between the type of cereal, the normal or decreased content of crude protein, and the presence or absence of sodium butyrate CeXCPxSo) was found in the caecal microbial communities , and in lower abundance in LP WB But , and no sodium butyrate supplementation  was more abundant in case of diets LP WB But and LP MB Ctr , whereas it was found with 4% abundance in diets NP MB Ctr, NP WB But, and LP WB Ctr (p = 0.0008): maize as cereal type, low CP, and no sodium butyrate supplementation  and positive correlations to other OTUs , and a tendency was detected for the cereal type and CP  while it was detected in lower abundance in NP WB Ctr (in av. 3%). OTU4 was affected by the interaction of the three supplementations (p = 0.011). L. vaginalis (OTU11) was more abundant when wheat was used as a cereal with highest abundance in diet LP WB But (4%). This result was supported by the significant effect found with the cereal type  was 2% abundant in the LP MB Ctr diet, while the other registered percentages were lower than one. The interaction of cereal type and CP content was significant (p = 0.02) for this OTU. In diets with maize and wheat supplementation and normal CP (NP MB Ctr and NP WB Ctr), an uncultured Parasutterella (OTU6) was found in higher abundance (4%) when compared to other diets. This OTU was significantly affected by crude protein (p = 0.003) and sodium butyrate supplementation  and galactose metabolism (Carbohydrate metabolism), where normal levels induced a higher abundance of genes .Cereal type, CP levels, and presence/absence of sodium butyrate have a decisive impact on the gut microbial structure. Diet is one of the main contributors that influence both the host and its microbes . TherefoBacteroides vulgatus is a common colonizer of the chicken cecum  can be found at: The animal study was reviewed and approved by Government Office of Pest County, Food Chain Safety, Plant Protection and Soil Conservation Directorate, Budapest, Hungary.GM, ZN, KH, JS, and AC-S: conceptualization. DB-M, MM: methodology. DB-M, GM, and MM: performed the experiment. DB-M, JS, and AC-S: formal analysis. DB-M, GM, MM, ZN, KH, JS, and AC-S: writing—review and editing. ZN and AC-S: funding acquisition. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The moderator analysis by duration of exposure showed a positive association between duration of exposure and primary DNA damage. Conclusions: This systematic review clearly shows a significant association between occupational exposure to ANDs and the extent of primary DNA damage in health professionals. Considering these results, health professionals should be warned against this potential occupational risk.Background: Antineoplastic drugs (ANDs) are a broad group of chemicals showing, at the same time, carcinogenic effects. The potential, albeit true, risk of side effects cannot be accepted, especially if resulting from occupational exposure. The aim of this study was to evaluate the association between occupational exposure to ANDs and the extent of primary DNA damage in health professionals. Methods: A systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/Medline, Web of Science, and Scopus were used to perform the literature search. The databases were examined in July 2019. Sub-group, moderator, and cumulative analyses were conducted. The trim and fill method was used in the case of potential publication bias. Results: Twenty studies were included in the qualitative analysis, and 19 in quantitative evaluation. The pooled effect size was 1.27 [ = 0.66–1.88),  Antineoplastic drugs (ANDs) are a broad group of chemicals, mainly used in chemotherapy; their anti-proliferative effect was accidentally discovered during the First and Second World Wars, when bone marrow and lymph nodes depletion was registered in soldiers exposed to sulfur mustard ,2. Howev10 Daltons  and 3 in the Americas [United States (n = 1) and Brazil (n = 2)]. The remaining studies were conducted in Asia, particularly China (n = 2), Turkey (n = 2), Japan (n = 2), and India (n = 1). The majority of the studies performed the comet assay using lymphocyte cells, while two studies incorporated the results of the comet assay of buccal cells  based on 180 subjects . No publication bias was found by the visual assessment of the funnel plot, and confirmed by Egger’s linear regression test  , subjects a. Low st= 0.378) b.p-value = 0.006] based on 1127 subjects . No potential publication bias was found by visual assessment of the funnel plot, and confirmed by Egger’s linear regression test  , subjects a. A high= 0.300) b.p-value < 0.001] based on 849 subjects . The sub-group analysis considering only males included five studies and the pooled ES was 2.50  based on 95 subjects . Potential publication bias was found by visual assessment of the funnel plot, and confirmed by Egger’s linear regression test . However, after applying the trim and fill method, the estimated ES did not change.In order to increase the robustness of the results, a sub-group analysis by gender was performed. The sub-group analysis considering only females included 10 datasets, and the pooled ES was 1.95  based on 361 subjects . No publication bias was found by visual assessment of the funnel plot, which was confirmed by Egger’s linear regression test . The sub-group analysis considering a high level of protection , included six studies, and the pooled ES was 2.13  based on 429 subjects . Potential publication bias was found by visual assessment of the funnel plot, and confirmed by Egger’s linear regression test . However, after the trim and fill method was applied, the estimated ES did not change.The sub-group analysis including studies with a low level of protection  counted six datasets. The pooled ES was 2.19  based on 924 subjects . No publication bias was found by visual assessment of the funnel plot and confirmed by Egger’s linear regression test .In the sub-group analysis by work task, we included only studies that considered, as controls, health professionals not exposed to ANDs different from nurses. In this analysis, 13 datasets were included for females and the pooled ES was 1.24  based on 890 subjects . The number of datasets of studies conducted in Asia was seven and the pooled ES was 1.85  based on 494 subjects . The number of datasets of studies conducted in Americas was three and the pooled ES was 1.15  based on 185 subjects . Potential publication bias was found by visual assessment of the funnel plot and confirmed by Egger’s linear regression test . However, after applying the trim and fill method, the estimated ES did not change.In the sub-group analysis by continent, the number of datasets of studies conducted in Europe was 11 and the pooled ES was 0.92 .The current systematic review with meta-analysis—which included 20 studies in the qualitative evaluation and 19 studies in the quantitative analysis—provided data on the association between occupational exposure to ANDs and the extent of primary DNA damage, as evaluated by the comet assay. As some studies separately reported data for gender, work task, and protective equipment, and a total of 21 datasets were considered. The pooled ES based on 1569 subjects indicated a significantly higher extent of primary DNA damage in health professionals exposed to ANDs compared with controls, with an ES of 1.27 [(95% CI = 0.66–1.88), 2 remained around 95%. Only in one case was the heterogeneity below 40%, when datasets performing the comet assay on buccal cells were considered. However, only four datasets provided this data, resulting in a small sample size (n = 180 subjects), wide 95% CI, and loss of statistical significance. The high value of heterogeneity found could be explained considering the methodological variation of the comet assay used in the considered primary studies. Indeed, primary papers expressed the results of the comet assay using different types of unit of measures. Moreover, an I2 value higher than 90% means that heterogeneity is directly the result of heterogeneity among studies, rather than sampling errors [2. Another potential explanation of heterogeneity could be the different type of ANDs used or the type of exposure . Moreover, even if the primary studies tried to match exposed and control subjects for several confounders, only a few studies perfectly matched for the most important elements, such as smoking, alcohol, and nutritional intake. Nevertheless, there are several strengths in this study: first, this is an extensive systematic review conducted according the PRISMA guidelines, which allowed retrieving a large number of studies; second, the pooled ES was based on 1569 subjects; and third, several sub-group analyses as well as sensitivity and moderator analyses were conducted. Particularly, the ES was estimated in both women and men, considering the work task and the protective equipment used. Moreover, in the meta-regression, the duration of exposure was considered as moderator. Furthermore, whenever we found potential publication bias, a trim and fill method was applied. Even if high heterogeneity was found, a random effect model was considered. Lastly, the pooled ES was estimated both in lymphocytes and buccal cells.In order to deeply understand the strength of the association between occupational exposure and primary DNA damage, a sub-group analysis by protective equipment was conducted. When studies that assessed the damage among health professionals who did not use any protective equipment or only masks and gloves were considered, the pooled ES was higher compared with the studies where health professionals used a combination of personal and environmental protective equipment . The importance of protective equipment could explain the differences obtained in the sub-group analysis by continent. Particularly, studies conducted in Asia showed the highest pooled ES compared with studies conducted in the Americas and even more in Europe. As suggested by Hon et al., different standard procedures, protocols, level of education, and legislations across the globe might influence the level of occupational risk, and consequently the conclusions drawn from one country might not be fully applicable to another . Furtherg errors . Even ifTo conclude, the results of this systematic review with meta-analysis clearly show a statistically significant association between occupational exposure to ANDs and the extent of primary DNA damage. The comet assay method is able to identify reversible DNA damage; in this perspective, the identified damage is still potentially repairable. However, a prolonged exposure, a concomitant action of other risk factors, and the senescence of DNA repair systems might induce a risk of neoplasms or other side effects . Having said that, health professionals should be made aware of this potential occupational risk.