title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
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Outcome analysis | SECONDARY | Continuous variables with normality are presented as mean (standard deviation, SD) and variables without normality are presented as median (interquartile range, IQR). The binary variables are presented as numbers (percentages).For the primary outcome, the correlation between left–right SctOFor the secondary analysis, t... | PMC9906862 | |
Results | PMC9906862 | |||
Correlation of baseline left and right SctO | Baseline left and right SctOCorrelation of left–right SctO | PMC9906862 | ||
Secondary outcomes | PMC9906862 | |||
Correlations between left–right SctO | Correlations between the left and right SctO | PMC9906862 | ||
The trend of SctO | The trend of left and right SctOComparison of left and right SctO | PMC9906862 | ||
Correlation between left and right SctO | The correlation of left–right SctOSamples of correlation between left and right SctO | PMC9906862 | ||
Discussion | REGRESSION, SECONDARY | The present study found that OLV increased the discrepancy in left–right SctOAlthough there are data to support the poor correlation of bilateral SctOOne strength of our study is that we employed a linear regression model to adjust for confounders that might affect SctOBecause the correlation at a single time point cou... | PMC9906862 | |
Conclusions | In the present study, we found that the correlation between left and right SctO | PMC9906862 | ||
Acknowledgements | Not applicable. | PMC9906862 | ||
Authors’ contributions | HQ J, DL M helped in concept and design, and data interpretation. CJ Zh, JH M, F J, XH L helped in data acquisition, data analysis. CJ Zh wrote the manuscript. DL M revised the manuscript. All authors are aware of and responsible for the research data. All authors read and approved the manuscript in its final version. | PMC9906862 | ||
Funding | This study was supported by the National Key R&D Program of China (2018YFC2001800). The sponsors had no role in designing or conducting the study; collecting, managing, analysing, or interpreting the data; or preparing and approving the manuscript. | PMC9906862 | ||
Availability of data and materials | The datasets generated and analysed during the current study are not publicly available due to institutional restrictions, but are available from the corresponding author upon reasonable request. | PMC9906862 | ||
Declarations | PMC9906862 | |||
Ethics approval and consent to participate | SECONDARY | This study was a secondary analysis of a cohort study approved by the Clinical Research Review Board of Peking University First Hospital (#2017–1378). Written informed consent was obtained from all subjects and/or their legal guardians. This study was registered in the Chinese Clinical Trial Registry on 10/09/2017 ( | PMC9906862 | |
Consent for publication | Not applicable. | PMC9906862 | ||
Competing interests | The authors declare no competing interests. | PMC9906862 | ||
References | PMC9906862 | |||
1. Introduction | overactive bladder, Overactive Bladder | OVERACTIVE BLADDER, INCONTINENCE, OVERACTIVE BLADDER, URINARY INCONTINENCE, OVERACTIVE BLADDER | Postmenopausal women are at risk of developing an overactive bladder (OAB). Conventional vaginal estrogen has shown promise for symptom relief. Isoflavones have proven effective as an alternative to estrogen treatment against menopause-related symptoms. However, its effect on OAB symptoms has not been studied. This stu... | PMC10574253 |
2. Materials and Methods | PMC10574253 | |||
2.1. Study Design | incontinence | SECONDARY, INCONTINENCE, OVERACTIVE BLADDER, INCONTINENCE | This study focusing on OAB symptoms was part of a three-month randomized, double-blinded, placebo-controlled trial (ClinicalTrials.gov NCT05013593) investigating RCE as a treatment for postmenopausal women with bladder symptoms. The primary outcome of the trial was changes in the urinary and vaginal microbiota composit... | PMC10574253 |
Randomization and Double Blinding | The women were randomized to either RCE or placebo with a 1:1 allocation ratio between groups using the data management program Research Electronic Data Capture (REDCap) [ | PMC10574253 | ||
2.2. Study Population | PMC10574253 | |||
2.2.1. Sample Size | We aimed for the inclusion of 50 women in each randomization arm. This was based on a previous study on RCE in the treatment of osteopenic postmenopausal women, where treatment effects were observed in a similar group of women [ | PMC10574253 | ||
2.2.2. Participants | endometrial cancer, infections, cancer of the digestive, hematuria, dysuria, cystitis, tenderness/pain | RECURRENT URINARY TRACT INFECTION, ENDOMETRIAL CANCER, RECURRENT URINARY TRACT INFECTION, CNS INFECTIONS, INFECTIONS, HEMATURIA, CYSTITIS | Participants were recruited through advertisements (posters, social media, and personal electronic mail from the public sector) from the community in Northern Denmark, at the North Denmark Regional Hospital, and Aalborg University Hospital. The first woman was enrolled in September 2019, and the last was enrolled in Oc... | PMC10574253 |
2.3. Questionnaires and Data Acquisition | PMC10574253 | |||
2.3.1. Demographic and Clinical Data | At the baseline visit, health-demographic information (such as age, body mass index (BMI), smoking status, treatment, self-reported past medical/disease history, etc.) was collected using a structured questionnaire survey. | PMC10574253 | ||
2.3.2. ICIQ-OAB Questionnaire | OAB symptoms were assessed using a modified Danish translation of the ICIQ-OAB [ | PMC10574253 | ||
2.3.3. ICIQ-UI-SF Questionnaire | INCONTINENCE, URINARY INCONTINENCE | Overall severity and bother of urinary incontinence, together with the type of incontinence, were evaluated using the Danish version of the ICIQ-UI-SF questionnaire [ | PMC10574253 | |
2.3.4. Fluid Intake and Voiding Diary | incontinence | INCONTINENCE, INCONTINENCE | To objectively evaluate the frequency of urination, bladder volume, and incontinence episodes, the women were asked to complete a three-day fluid intake and voiding diary, following the considerations of the International Consultation on Incontinence [ | PMC10574253 |
2.3.5. Diet Intake Registration | The women were also asked to complete a three-day food diary to monitor habitual diets, including the consumption of isoflavone-rich food. Food items were either weighed individually or given in portions. Each food diary was typed into an online diet and nutrition calculation program (VITAKOST ApS, Kolding, Denmark) by... | PMC10574253 | ||
2.4. Standard Urine Culture | STERILE, RECURRENT URINARY TRACT INFECTION | At the baseline and follow-up visits, a urine sample was collected using sterile intermittent catheterization to assess if a current urinary tract infection was present. Ten mL of urine was collected in a Urine Monovette with boric acid (Saarstedt, Germany) and analyzed by standard urine culturing. | PMC10574253 | |
2.5. Red Clover Extract and Placebo Formulations | COLD | The RCE and placebo formulations were produced by Herrens Mark ApS (Odense, Denmark). A heterogeneous culture (proprietary) of bacteria was used to facilitate the cold fermentation of pressed red clover to improve the bioavailability of the isoflavones. The isoflavone content in the RCE was determined as previously des... | PMC10574253 | |
2.6. Compliance and Adverse Events | ADVERSE EVENT | Compliance was calculated based on self-reported diaries. The women were instructed to register in the diary every time they consumed the treatment, by which the percentage of missing intakes could be calculated. This was subtracted from 100% to calculate compliance. Adverse events were monitored every month during the... | PMC10574253 | |
2.7. Statistical Analysis | Data were analyzed using R Statistical Software (v4.1.3; R Core Team 2022, | PMC10574253 | ||
2.8. Ethics | The trial was conducted according to the principles expressed in the Declaration of Helsinki and was executed at the North Denmark Regional Hospital. The study was approved by The North Denmark Region Committee on Health Research Ethics (N-20190028). The categories of personal data collected in the project were registe... | PMC10574253 | ||
3. Results | PMC10574253 | |||
3.1. Study Participants | A total of 48 women were enrolled in the study ( | PMC10574253 | ||
3.3. ICIQ-OAB Score | A tendency was seen towards a decrease in the ICIQ-OAB score in the RCE group from baseline to follow-up (with a median score of 6.5 (5.0−8.25) at baseline versus 6.0 (3.75−8.25) at follow-up ( | PMC10574253 | ||
3.4. Individual ICIQ-OAB Items | nocturia | NOCTURIA | When looking at individual items in the ICIQ-OAB questionnaire, we found no differences in urinary frequency (question 3a) or nocturia (question 4a) for either the RCE or placebo group ( | PMC10574253 |
3.5. Patient-Reported Symptom Bother (NRS Values) for Urinary Frequency, Nocturia, Urgency, and Urge Urinary Incontinence from the ICIQ-OAB Questionnaire | NRS | In the RCE group, a reduction was detected in the bother of urinary urgency on an NRS (0–10) from baseline to follow-up ( | PMC10574253 | |
3.6. The ICIQ-UI Score | No significant difference in the ICIQ-UI score was found between baseline and follow-up in either the RCE group or placebo group ( | PMC10574253 | ||
3.8. Compliance and Adverse Events | stomach pain | The median duration of the treatment in the trial was 99.5 (91–107) days, and the median compliance was 96% (90.9–98.5%). The treatments were generally well tolerated. Four women taking RCE had difficulties with the taste, and two women, one in each treatment group, experienced stomach pain after intake; these women al... | PMC10574253 | |
4. Discussion | OAB symptoms, urinary incontinence | STRESS URINARY INCONTINENCE, SYNDROME, URINARY INCONTINENCE, PATHOPHYSIOLOGY | The present study showed no clear improvements in the majority of OAB symptom parameters in postmenopausal women suffering from OAB following treatment with fermented RCE compared to a placebo. OAB is a complex syndrome, and its pathophysiology is not fully understood [By evaluating the ICIQ-OAB questionnaire, we saw t... | PMC10574253 |
Strengths and Limitations | Some limitations should be considered. OAB symptom complexity can be influenced by many factors, such as the type of fluid intake. However, we did not have information about the participants’ consumption of different types of fluids, e.g., caffeine-containing drinks, which are known to affect voiding habits. The sample... | PMC10574253 | ||
5. Conclusions | OAB symptoms | BLADDER DISORDERS | The present study has not been able to demonstrate the effect of systemic treatment with isoflavones on the relief of OAB symptoms in postmenopausal women. Larger studies are needed to unravel the possible role of isoflavones in female bladder disorders. In addition, better in-depth knowledge of the mechanisms that iso... | PMC10574253 |
Supplementary Materials | The following supporting information can be downloaded at: Click here for additional data file. | PMC10574253 | ||
Author Contributions | Conceptualization, A.B.V., P.B.J., S.S. and L.T.S.A.; methodology, A.B.V., P.B.J., S.S. and L.T.S.A.; validation, P.H.; formal analysis, A.B.V., J.N.H.-J., B.K.P., C.B.-N. and J.B.K.; investigation, A.B.V., J.N.H.-J. and B.K.P.; resources, J.B.K., K.G. and L.P.C.; data curation, A.B.V.; writing—original draft preparati... | PMC10574253 | ||
Institutional Review Board Statement | The study was conducted in accordance with the Declaration of Helsinki and approved by The North Denmark Region Committee on Health Research Ethics (N-20190028). | PMC10574253 | ||
Informed Consent Statement | Informed consent was obtained from all subjects involved in the study. | PMC10574253 | ||
Data Availability Statement | All data generated or analyzed in the study are included in this published article and its | PMC10574253 | ||
Conflicts of Interest | Herrens Mark ApS (Odense, Denmark) produced and delivered the RCE and placebo. They had no role in the design of the study, in the collection, analysis, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results. | PMC10574253 | ||
References | incontinence, mellitus, Overactive Bladder, NRS | INCONTINENCE, OVERACTIVE BLADDER, INCONTINENCE, UTI, URINARY INCONTINENCE, URINARY TRACT INFECTION | A schematic representation of the study design. Screening was scheduled approximately two weeks before the baseline visit, at which time, if the women decided to participate, they were asked to answer the ICIQ questionnaires to ensure eligibility. Before baseline and follow-up visits, the women were asked to fill out d... | PMC10574253 |
1. Introduction | stunting, diarrhea, malnutrition | MALNOURISHED, WASTED, MALNUTRITION | These authors contributed equally to this work.Deceased.The profile of the intestinal microbiota is known to be altered in malnourished young children in low- and middle-income countries. However, there are limited studies longitudinally evaluating the intestinal microbiota in malnourished young children in resource-li... | PMC10005232 |
2. Materials and Methods | PMC10005232 | |||
2.1. Study Design and Participants | This was a planned prospective pilot sub-study nested within a cluster-randomized trial of two micronutrient powder formulations with or without zinc, in children between the ages of 6 and 18 months in two representative populations to assess impact on growth and morbidity. The parent trial and characteristics of the p... | PMC10005232 | ||
2.2. Fecal Sample Collection, DNA Extraction, Amplicon Generation, and 16S rRNA Sequencing | diarrhea | COLD, INFECTIOUS DISEASE | Fecal samples were routinely collected at baseline (3 months) as well as at 6, 9, 12, 18, and 24 months for enteric pathogens, ensuring the absence of diarrhea in the preceding 72 h. Once the subject was identified by the field teams in their weekly visits, a stool kit (comprising of diaper, spoon, container, and glove... | PMC10005232 |
2.3. Computational and Bioinformatics Analyses | Computational analyses were performed using the open-source software platform QIIME Version 1.5 ( | PMC10005232 | ||
2.4. Statistical Analysis | diarrheal | Statistical analyses were performed in R (Beta diversity, defined as partitioning of diversity among communities, which is characterized using the number of species shared between communities, was determined by principal coordinates analysis (PCoA) of weighted UniFrac distances in QIIME based on age, residential locati... | PMC10005232 | |
3. Results | PMC10005232 | |||
3.2. Gut Microbiota | diarrheal, well-nourished | MALNOURISHED, WASTED | Beta Diversity: We first assessed the beta diversity of the gut microbial community composition from all the children at each time point, in both locations (urban and rural) and within each intervention arm using PCoA of weighted UniFrac distances. The UniFrac algorithm measures similarity among microbial communities b... | PMC10005232 |
4. Discussion | diarrheal, well-nourished | MALNOURISHED, ZINC DEFICIENCY, WASTED | In this pilot study, we investigated the nutritional status and composition, relative abundance, and diversity of the gut microbiota of children in urban and rural areas of Pakistan from 3 to 24 months of age. The most significant findings were age-related changes with a decrease in HAZ score, increase in alpha and bet... | PMC10005232 |
Supplementary Materials | The following supporting information can be downloaded at Click here for additional data file. | PMC10005232 | ||
Author Contributions | Conceptualization, E.N.N., C.A.W., H.D.W. and Z.A.B.; Methodology, E.N.N., C.A.W., H.D.W. and Z.A.B.; Validation, Formal analysis, V.B., D.M.D., I.A. and A.R.; Investigation, V.B., D.M.D., A.V.K., S.S. and J.D.; Resources, A.V.K., H.D.W. and Z.A.B.; Data Curation, V.B., D.M.D., I.A., J.M., A.R. and S.B.; Writing-Origin... | PMC10005232 | ||
Institutional Review Board Statement | The study was duly approved by the Ethics Review Committee at the Aga Khan University and the Institutional Review Board at Tufts University, as well as the National Bioethics committee of the Government of Pakistan. | PMC10005232 | ||
Informed Consent Statement | All subjects provided written informed consent for the main study inclusive of the microbiome collection and analysis. | PMC10005232 | ||
Data Availability Statement | The de-identified data for the main study is available through the Ki initiative at the Bill & Melinda Gates Foundation. Additional microbiota data can be requested from the corresponding authors. | PMC10005232 | ||
Conflicts of Interest | The authors declare no conflict of interest. | PMC10005232 | ||
Subject terms | depressive disorder, depression, MDD, dysregulation of mood | TSD | JNJ-54175446 is a selective purine P2X7 receptor (P2X7R) antagonist that attenuates microglial IL-1β/IL-18 release. In healthy volunteers, JNJ-54175446 suppressed peripheral interleukin (IL)-1β release, and attenuated dexamphetamine-induced improvements of mood and (visuo)motor performance in a human dexamphetamine-cha... | PMC10363543 |
Introduction | neuroinflammation, unipolar and bipolar mood disorders, mood disorders, ’s mood, MDD, depression | TSD, PATHOLOGY, PATHOPHYSIOLOGY | The purine P2X7 receptor (P2X7R) is one of seven identified subtypes of adenosine triphosphate (ATP)-gated P2X ion channels present on various human cell types. The P2X7R is predominantly expressed in central nervous system (CNS) in microglial cells and peripherally in monocytes [Several lines of evidence implicate neu... | PMC10363543 |
Material and methods | PMC10363543 | |||
Population | Male and female patients aged 18–64 years with a body mass index (BMI) between 18 and 32 kg/m | PMC10363543 | ||
Dose selection | In an earlier single ascending dose study with JNJ-54175446 in healthy male volunteers, full antagonism of peripheral ex-vivo IL-1β stimulation was demonstrated following single doses of ≥50 mg JNJ-54175446 [ | PMC10363543 | ||
Safety evaluations | Suicidal ideation | ADVERSE EVENTS | During the study, safety and tolerability evaluations were performed by monitoring adverse events, clinical laboratory tests (hematology, serum chemistry urinalysis and serum pregnancy test at screening and urine pregnancy tests during the treatment phase). 12-lead electrocardiograms (ECG), vital signs, and physical an... | PMC10363543 |
Pharmacokinetics (PK) | PK blood samples were collected predose, at 1, 2, 4, 8, and 10 h post dose on day 1 and day 10 and at 24 h and 48 h after the last dose of JNJ-54175446. The maximum plasma concentration (Cmax), minimum observed plasma concentration (Cmin) and the area under the plasma concentration-time curve (AUCτ) was measured during... | PMC10363543 | ||
Exploratory proof-of-concept related assessments | PMC10363543 | |||
Procedure for acute total sleep deprivation (TSD) | TSD | TSD | The TSD procedure consisted of restructuring the individual’s diurnal rhythm and providing activities that prevented sleep and promoted wakefulness. As shown in Table | PMC10363543 |
Hamilton depression rating scale, 17 items (HDRS17) | MDD, HDRS17 | The HDRS17 is a clinician-administered rating scale designed to assess the severity of symptoms in MDD patients. Each of the 17 items was rated by the clinician on either a 3- or a 5-point scale; higher scores indicated a worse outcome. | PMC10363543 | |
Inventory of depressive symptoms, clinician rated 30-items (IDS-C30) | The IDS-C30 [ | PMC10363543 | ||
The self-rated quick inventory of depressive symptoms-10/16 (QIDS-SR10/16) | depressive symptoms | TSD | The QIDS-SR10/16 is a subjective measure to assess the severity of depressive symptoms over a 1-week recall period (QIDS-SR16), or within a 2 h recall period (QIDS-SR10). The QIDS-SR16 was administered at screening, baseline, day 3, day 10 and at follow up and the QIDS-SR10 was administered in the morning and evening d... | PMC10363543 |
Profile of mood states brief form (POMS) | The POMS [ | PMC10363543 | ||
Snaith-Hamilton pleasure scale (SHAPS) | The SHAPS [ | PMC10363543 | ||
The probabilistic instrumental learning task (PILT) | The PILT [ | PMC10363543 | ||
Interleukin-1-beta (IL-1β) | peripheral white blood cells | TSD | IL-1β in peripheral blood was analyzed on day 1 (predose, 2 h and 8 h post dose), on day 2 (24 h after the initial dose of JNJ-54175446), and on day 4 during TSD (predose, 2 h and 8 h post dose). Venous blood samples were taken (TruCulture) to obtain peripheral white blood cells (WBCs) for ex-vivo stimulation using LPS... | PMC10363543 |
Analysis | PMC10363543 | |||
Sample size calculation | TSD | This safety and tolerability study involved TSD as an exploratory proof-of-concept intervention to induce acute mood improvement and was preceded and/or followed by JNJ-54175446 and/or placebo. Hence, it was impossible to make any plausible assumptions of the effect sizes and/or the interactions between sleep deprivati... | PMC10363543 | |
Statistics | SE, TSD | TSD | Since the study was not primarily powered to assess the pharmacodynamic effects of JNJ-54175446, descriptive statistics were performed for HDRS17, QIDS-SR POMS, PILT and SHAPS, with mean ± SD values and changes from baseline being summarized by treatment group at the respective scheduled time points per instrument. Dat... | PMC10363543 |
Results | Sixty-nine patients received at least one dose of JNJ-54175446, and a total of 64 patients completed the study. The study disposition schedule is shown in Fig. | PMC10363543 | ||
Disposition schedule. | This schedule describes how many patients were assigned to each group and completed the study. | PMC10363543 | ||
Adverse events | nausea, abdominal pain, vomiting, influenza-like illness, headache, dysgeusia, deaths, chills | ADVERSE EVENTS, INFLUENZA-LIKE ILLNESS | JNJ-54175446 was well-tolerated and all adverse events were mild to moderate. There were no deaths, serious AEs, or persistent AEs reported in this study. In group A (JNJ-54175446 early start) two TEAEs, headache and abdominal pain lead to study discontinuation. Both were classified as severe and considered by the inve... | PMC10363543 |
Exploratory proof-of-concept related assessments | Table | PMC10363543 | ||
Mood symptoms | PMC10363543 | |||
Hamilton depression rating scale (HDRS) | TSD | At baseline (day-1), the HDRS17 total score (mean [SD] was 20.0 [4.03] for group A (JNJ-54175446 early start); 18.1 [4.38] for group B (JNJ-54175446 late start); and 18.9 [4.04] for group C (placebo), respectively.Effects of TSD per average HDRS17 total score [SD], measured as change from baseline (day -1) on day 4, we... | PMC10363543 | |
The self-rated quick inventory of depressive symptoms (QIDS-SR) | TSD, Depressive | TSD | The average Quick Inventory of Depressive Symptoms (QIDS-SR) total score (mean [SD]) at baseline (day -1) was 13.0 [3.98] for group A (JNJ-54175446 early start); 12.2 [4.63] for group B (placebo pre TSD and JNJ-54175446 late start) and 10.8 [3.52] for group C (placebo) (supplemental Fig. TSD decreased the average QIDS-... | PMC10363543 |
Profile of mood scales (POMS) | tension/anxiety, anger/hostility | TSD | The Profile of Mood Scales (POMS) total score (mean [SD]) at baseline (day -1) was 38.9 [16.2] for group A (JNJ-54175446 early start); 34.4 [15.9] for group B (JNJ-54175446 late start) and 32.4 [15.7] for group C (placebo).The average POMS total score (SD) decreased following TSD and recovery sleep from day 4 to day 5 ... | PMC10363543 |
Snaith-Hamilton pleasure scale (SHAPS) | TSD | The Snaith-Hamilton Pleasure Scale (SHAPS) total score (mean [SD]) at baseline (day -1) was 8.6 [2.26] for group A (JNJ-54175446 starting before TSD); 8.15 [3.50] for group B (placebo pre-TSD and JNJ-54175446 starting with loading dose on recovery night) and 8.2 [2.68] for group C (all-placebo) (Fig. | PMC10363543 | |
Snaith-Hamilton Pleasure Scale (SHAPS). | This figure displays the Snaith-Hamilton Pleasure Scale (SHAPS) Total Score Mean [SD] over time for group A (green square), group B (blue triangle) and group C (red circle).The TSD-induced decrease of total SHAPS score, measured as the change from day 3 to day 5, was significantly attenuated in group A (JNJ-54175446 ea... | PMC10363543 | ||
The probabilistic instrumental learning task (PILT) | The results of the PILT are shown in Table | PMC10363543 | ||
Probabilistic Instrumental Learning Task (PILT). | This figure displays the Mean [SD] over time for group A (green square), group B (blue triangle) and group C (red circle) for the Probabilistic Instrumental Learning Task (PILT) for total points loss ( | PMC10363543 | ||
Interleukin-1-beta (IL-1β) | TSD | Compared to placebo, no differences were observed in either treatment group for plasma IL-1β at the various assessed time points. TSD however increased levels of ex-vivo stimulated IL-1β release on day 4. These elevations were markedly attenuated compared to baseline (day -1) in the early start JNJ-54175446 (pre-TSD) t... | PMC10363543 |
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