Low-risk Population Research Articles

Characterization of neuroendocrine regulation- and metabolism-associated molecular features and prognostic indicators with aid to clinical chemotherapy and immunotherapy of patients with pancreatic cancer.

The worldwide prevalence of pancreatic cancer has been rising in recent decades, and its prognosis has not improved much. The imbalance of substance and energy metabolism in tumour cells is among the primary causes of tumour formation and occurrence, which is often controlled by the neuroendocrine system. We applied Cox and LASSO regression analysis to develop a neuroendocrine regulation- and metabolism-related prognostic risk score model with three genes (GSK3B, IL18 and VEGFA) for pancreatic cancer. TCGA dataset served as the training and internal validation sets, and GSE28735, GSE62452 and GSE57495 were designated as external validation sets. Patients classified as the low-risk population (category, group) exhibited considerably improved survival duration in contrast with those classified as the high-risk population, as determined by the Kaplan-Meier curve. Then, we combined all the samples, and divided them into three clusters using unsupervised clustering analysis. Unsupervised clustering, t-distributed stochastic neighbor embedding (t-SNE), and principal component analysis (PCA) were further utilized to demonstrate the reliability of the prognostic model. Moreover, the risk score was shown to independently function as a predictor of pancreatic cancer in both univariate and multivariate Cox regression analyses. The results of gene set enrichment analysis (GSEA) illustrated that the low-risk population was predominantly enriched in immune-associated pathways. "ESTIMATE" algorithm, single-sample GSEA (ssGSEA) and the Tumor Immune Estimation Resource (TIMER) database showed immune infiltration ratings were enhanced in the low-risk category in contrast with the high-risk group. Tumour immune dysfunction and exclusion (TIDE) database predicted that immunotherapy for pancreatic cancer may be more successful in the high-risk than in the low-risk population. Mutation analysis illustrated a positive link between the tumour mutation burden and risk score. Drug sensitivity analysis identified 44 sensitive drugs in the high- and low-risk population. GSK3B expression was negatively correlated with Oxaliplatin, and IL18 expression was negatively correlated with Paclitaxel. Lastly, we analyzed and verified gene expression at RNA and protein levels based on GENPIA platform, HPA database and quantitative real-time PCR. In short, we developed a neuroendocrine regulation- and metabolism-associated prognostic model for pancreatic cancer that takes into account the immunological microenvironment and drug sensitivity.

Copy number variations in SPAST and ATL1 are rare among Brazilians.

Copy number variations (CNV) may represent a significant proportion of SPG4 and SPG3A diagnosis, the most frequent autosomal dominant subtypes of hereditary spastic paraplegias (HSP). We aimed to assess the frequency of CNVs in SPAST and ATL1 and to update the molecular epidemiology of HSP families in southern Brazil. A cohort study that included 95 Brazilian index cases with clinical suspicion of HSP was conducted between April 2011 and September 2022. Multiplex Ligation Dependent Probe Amplification (MLPA) was performed in 41 cases without defined diagnosis by different massive parallel sequencing techniques (MPS). Diagnosis was obtained in 57/95 (60%) index cases, 15/57 (26.3%) being SPG4. Most frequent autosomal recessive HSP subtypes were SPG7 followed by SPG11, SPG76 and cerebrotendinous xanthomatosis. No CNVs in SPAST and ATL1 were found. Copy number variations are rare among SPG4 and SPG3A families in Brazil. Considering the possibility of CNVs detection by specific algorithms with MPS data, we consider that this is likely the most cost-effective approach to investigate CNVs in these genes in low-risk populations, with MLPA being reserved as an orthogonal confirmatory test.

Safety of endoscopist-guided sedation in a low-risk collective.

Worldwide, gastrointestinal endoscopies are predominantly performed under sedation. National and international guidelines and recommendations contain very different specifications for the use of sedation in gastrointestinal endoscopy. These differences come from specific requirements for staffing during endoscopy. The aim of the study is to evaluate whether endoscopist-guided sedation without additional sedation assistance is not inferior to endoscopist-guided sedation with additional sedation assistance with respect to the rate of sedation-associated complications in a defined low-risk population (low-risk procedure and low-risk patient). Prospective, multicenter, randomized study. 27 German study centers participated in the study. A total of 30 569 endoscopies were recorded during the study period from 1.8.2015 to 10.3.2020. The final data analysis included 28 673 examinations (64.1 % esophagosgastroduodenoscopies and 35.9 % colonoscopies). In 307 (1.1 %) examinations, 322 sedation-associated complications occurred. Of these, 321 (1.1 %) were minor complications and one (0.003 %) was a major complication. There was no statistically significant difference in the frequency of sedation-associated complications between endoscopist-guided sedation with versus without additional sedation assistance. Within the legal framework, a "shadow" sedation assistant was present in the study group without sedation assistance. This assistant intervened because of sedation-associated complications in 101 (0.7 %) of the endoscopies. The study documents the safety of propofol-based endoscopist-guided sedation in a low-risk population. In 98.9 % of all endoscopies, no sedation-associated complication occurred or it was so minimal that no intervention (e. g., increase of oxygen supply) was necessary. The study cannot answer to what extent a serious complication was avoided by the active intervention of the "shadow" sedation assistance in the group without sedation assistance.The study proves in a randomized, prospective design that sedation in low-risk endoscopy (low-risk patient, low-risk procedure) can be performed as endoscopist-guided sedation without additional sedation assistance, without demonstrably accepting a reduction in safety.

Pathways to prevention: insights on stemming HIV outbreaks in Larkana, Pakistan

In the past two decades, Pakistan has faced multiple human immunodeficiency virus outbreaks, with Larkana appearing to be the hub of such outbreaks. While the previous Larkana outbreaks happened in high-risk populations, the alarming outbreak in 2019 occurred in a low-risk paediatric population, raising several concerning questions. Human immunodeficiency virus infections spilling into the general population is indicative of a steady increase in the number of cases, and the failure of control strategies to stem the concentrated epidemic from evolving. Although several causative factors have been identified from previous outbreaks, the one that occurred in 2019 may have been influenced by an additional, hitherto unexplored factor; child sexual abuse. The current narrative review was planned to summarise human immunodeficiency virus risk factors and causes identified in previous Larkana epidemics, to explore potential reasons for the outbreaks in children, ---Continue

VIDAS3® TB-IGRA assay: evaluation of performance characteristics in a predominantly low risk, low incidence population

ObjectivesTo evaluate the analytical performance of the TB-IGRA® assay on the VIDAS3 platform (bioMérieux) when testing a predominantly low risk population in a low incidence area. ResultsEighty-eight percent of the results were concordant between QuantiFERON®-TB Gold-Plus (QFT®-Plus, QIAGEN) and TB-IGRA®. All 12 of 99 (12.1%) discordant results were determined positive only with the TB-IGRA® assay. In 11 of 12 of these discordant cases, no explanation could be found in the medical record. Five of these discrepant results were probably caused by the use of contaminated stimulation reagents. The remaining 6 discrepant samples were also part of the reproducibility experiment and only 2 results were reproducible positive. Overall, in the reproducibility experiment 5 of 25 (20.0 %) results were not repeatable. Conclusionsthe TB-IGRA® assay seems prone to contamination. Besides, we documented a reproducibility of only 80.0% with the TB-IGRA® assay.

Whole-cycle analysis of echocardiographic tissue Doppler velocities as a marker of biological age.

Tissue Doppler imaging (TDI) is a sensitive marker of impaired cardiac function and different phases of the TDI curve carry different prognostic information. It is not known how continuous TDI curves change with age in normal subjects, and whether these changes differ from changes seen in individuals at risk of future cardiac events. A total of 1,763 individuals from the general population were examined with color TDI at the septal and lateral mitral sites. A low-risk group was defined as without cardiac risk factors (hypertension, diabetes or ischemic heart disease) at baseline and without any cardiac events (cardiovascular death or admission due to either heart failure or acute myocardial infarction) during 10-years follow-up. All TDI curves were corrected for heart rate, and whole-cycle analysis of age-related changes to TDI velocities was performed in both low-risk (n = 881) and high-risk individuals (n = 882). In the low-risk population, four phases where myocardial velocity differed most (p < 10-10) according to age were identified [in a standardized cardiac cycle of 1 second (s)]: Systolic peak (0.09-0.13 s), systolic plateau (0.18-0.27 s), early diastole (0.43-0.54 s) and late diastole (0.88-0.95 s). With increasing age, systolic velocities decreased, early diastolic velocities decreased and had delayed peak, and late diastolic velocities increased until age 70 and then stopped increasing. In the high-risk population, comparison to corresponding age groups of the low-risk population showed: Lower early diastolic velocities in 20-40-year-olds; higher late diastolic velocities and lower peak systolic velocities in 40-60-year-olds; further decreased systolic velocities including the systolic plateau and decreased late diastolic velocities in 60-year-olds. The time segments around the systolic peak (p = 0.002) and early diastole (p < 0.001) differed significantly between the high-risk and low-risk population, thus making it possible to use the individual age gap between a TDI-derived biological age and the real chronological age as a tool to discriminate high-risk individuals from low-risk individuals. We found that individuals with cardiac risk factors display findings compatible with an accelerated aging of the heart and thus propose TDI-derived biological age as a tool to identify high-risk patients.

Prevalence and predictive factors of depressive symptoms among primiparae in antenatal care: A cross-sectional study in the new families programme.

To estimate the prevalence and assess the strength of associations between antenatal depressive symptoms and selected possible predictive factors among women attending antenatal care for the first time at the Child Health Centre. Evidence suggests that antenatal depression is a health problem as prevalent as postpartum depression. Antenatal depressive symptoms may persist into the postpartum period and potentially disturb the attachment between mother and family. Cross-sectional. A sample of 228 women who participated in the New Families research programme answering a questionnaire at Week 28 of pregnancy were included. The Edinburgh Postnatal Depression Scale was used as outcome measure. Prevalence was estimated, and backward stepwise logistic regression analysis was performed to examine associations with somatic, psychiatric and social factors. STROBE checklist was followed. Prevalence of depressive symptoms in this sample was 17.9%. Women reporting not sleeping enough had significantly higher odds of having depressive symptoms. Pregnant women with high relationship satisfaction were less likely to have depressive symptoms. Neither maternal age, education, previous depression, coming from a non-Nordic country nor having complications during pregnancy were statistically significantly associated with depressive symptoms. High prevalence of depressive symptoms may also be present in low-risk populations. Sleep and relationship satisfaction are topics that need to be addressed during pregnancy. The prevalence of depressive symptoms in this sample of low-risk pregnant women indicates that health personnel needs to be aware of depressive symptoms among women with no risk indicators. Identifying predictive factors associated with depressive symptoms may help midwives, public health nurses and general practitioners support parents. Our results indicate a potential need for screening for depressive symptoms in pregnancy and underscore the importance of involving partners in antenatal care. Parents and health personnel participated in designing the New Family research programme.

Population attributable fraction estimates of cardiovascular diseases in different blood pressure levels in a large-scale cross-sectional study: a focus on prevention strategies and treatment coverage.

Hypertension is one of the major modifiable risk factors in developing cardiovascular diseases (CVD). Hence, we aimed to ascertain age- and sex-specific population attributable fraction (PAF) for CVD in different blood pressure levels to implement efficient preventive strategies at the population level. Participants' data were obtained from the Iranian stepwise approach for surveillance of noncommunicable disease risk factors (STEPs) survey to calculate PAF in four subsequent phases. In phase 0, PAF was measured, irrespective of the diagnosis status. In phase 1, the theoretical minimum range of 115 ≤SBP less than 130 mmHg was considered as the low-risk and measurements equal to or higher than 130 mmHg as the high-risk group. Across phase 2, patients were divided into normal and hypertensive groups based on the American College of Cardiology/American Heart Association guideline. In phase 3, patients were divided into two categories based on treatment coverage. A total number of 27 165 participants aged ≥25 years had valid blood pressure measurements and were enrolled. Phase 0: PAF generally had an upward trend with age advancing. Phase 1: participants with BP ≥130 mmHg comprised the largest PAF, extending from 0.31 (0.25-0.37) in older male individuals to 0.85 (0.79-0.91) in younger females. Phase 2: higher values were found in younger ages for hypertension. Phase 3 represented that attributable fractions among hypertensive patients who received treatment were much lower than drug-naïve hypertensive participants. Our study enlightens the necessity for implementing effective screening strategies for the younger generation and providing adequate access to antihypertensive medications for the low-risk population.

Comprehensive Characterization of RNA-Binding Proteins in Colon Adenocarcinoma Identifies a Novel Prognostic Signature for Predicting Clinical Outcomes and Immunotherapy Responses Based on Machine Learning.

RNA-binding proteins (RBPs) are crucial factors that function in the posttranscriptional modification process and are significant in cancer. This research aimed for a multigene signature to predict the prognosis and immunotherapy response of patients with colon adenocarcinoma (COAD) based on the expression profile of RNA-binding proteins (RBPs). COAD samples retrieved from the TCGA and GEO datasets were utilized for a training dataset and a validation dataset. Totally, 14 shared RBP genes with prognostic significance were identified. Non-negative matrix factorization clusters defined by these RBPs could stratify COAD patients into two molecular subtypes. Cox regression analysis and identification of 8-gene signature categorized COAD patients into high- and low-risk populations with significantly different prognosis and immunotherapy responses. Our prediction signature was superior to another five well-established prediction models. A nomogram was generated to quantificationally predict the overall survival (OS) rate, validated by calibration curves. Our findings also indicated that high-risk populations possessed an enhanced immune evasion capacity and low-risk populations might benefit immunotherapy, especially for the joint combination of PD-1 and CTLA4 immunosuppressants. DHX15 and LARS2 were detected with significantly different expressions in both datasets, which were further confirmed by qRTPCR and immunohistochemical staining. Our observations supported an eight-RBP-related signature that could be applied for survival prediction and immunotherapy response of patients with COAD.

Identifying new onset postpartum hypertension in a low risk population using remote blood pressure monitoring

Identifying new onset postpartum hypertension in a low risk population using remote blood pressure monitoring

Racial and ethnic differences in 39-week induction of labor and cesarean delivery in low-risk populations

Racial and ethnic differences in 39-week induction of labor and cesarean delivery in low-risk populations

Integrated strategies for chemotherapy cycles in nasopharyngeal carcinoma patients: Real-world data from two epidemic centers guiding decision-making.

Two cycles of induction chemotherapy (IC) followed by 2 cycles of platinum-based concurrent chemoradiotherapy (CCRT) (2IC+2CCRT) for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is widely adopted but not evidence-confirmed. This study aimed to determine the clinical value of 2IC+2CCRT regarding efficacy, toxicity and cost-effectiveness. This real-world study from two epidemic centers used propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses. The enrolled patients were divided into three groups based on treatment modality: Group A (2IC+2CCRT), Group B (3IC+2CCRT or 2IC+3CCRT) and Group C (3IC+3CCRT). Long-term survival, acute toxicities and cost-effectiveness were compared among the groups. We developed a prognostic model dividing the population into high- and low-risk cohorts, and survivals including overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) were compared among the three groups according to certain risk stratifications. Of 4,042 patients, 1,175 were enrolled, with 660, 419, and 96 included in Groups A, B and C, respectively. Five-year survivals were similar among the three groups after PSM and confirmed by IPTW. Grade 3-4 neutropenia and leukocytopenia were significantly higher in Groups C and B than in Group A (52.1% vs. 41.5% vs. 25.2%; 41.7% vs. 32.7% vs. 25.0%) as were grade 3-4 nausea/vomiting and oral mucositis (29.2% vs. 15.0% vs. 6.1%; 32.3% vs. 25.3% vs. 18.0%). Cost-effective analysis suggested that 2IC+2CCRT was the least expensive, while the health benefits were similar to those of the other groups. Further exploration showed that 2IC+2CCRT tended to be associated with a shorter PFS in high-risk patients, while 3IC+3CCRT potentially contributed to poor PFS in low-risk individuals, mainly reflected by LRRFS. In LA-NPC patients, 2IC+2CCRT was the optimal choice regarding efficacy, toxicity and cost-effectiveness; however, 2IC+2CCRT and 3IC+3CCRT probably shortened LRRFS in high- and low-risk populations, respectively.

First trimester uterine artery Doppler indices in prediction of small gestational age pregnancy and intrauterine growth restriction in low-risk population

First trimester uterine artery Doppler indices in prediction of small gestational age pregnancy and intrauterine growth restriction in low-risk population

Impact of choosing wisely on imaging in men with newly diagnosed prostate cancer.

Encouraging the appropriate use of staging imaging in patients with newly diagnosed prostate cancer remains a challenge. Assessing the effects of national efforts may help guide future initiatives in curtailing low-value care. The purpose of this study was to determine the impact of the Choosing Wisely campaign on imaging utilization among men with prostate cancer. Surveillance, Epidemiology, and End Results - Medicare data were used to complete a longitudinal population-based study of men diagnosed with prostate cancer from 2007 to 2015. An interrupted time series analysis evaluated the impact of the Choosing Wisely campaign on trends of imaging utilization. From 2007 to 2015 imaging utilization in low-risk patients decreased, with computed tomography (CT) usage declining from 45.0% to 34.4% (P<0.001) and nuclear medicine bone scan (NMBS) from 27.8% to 11.7% (P<0.001). Choosing Wisely likely contributed to an absolute reduction of 2.9% (P=0.03) in utilization of NMBS in the low-risk population. Imaging usage for all modalities increased in the high-risk population, but with 32.8% continuing to not receive guideline-supported imaging. In 2012, the Choosing Wisely campaign sought to decrease inappropriate staging imaging for men with low-risk prostate cancer and encourage stewardship of medical resources. Overall decreases in staging imaging trends suggest a move towards higher value care. However, this study found that the Choosing Wisely recommendations had a modest impact on utilization of NMBS, but not CT or PET scans. These results may help inform future efforts to promote guideline concordant imaging.

PTGIS May Be a Predictive Marker for Ovarian Cancer by Regulating Fatty Acid Metabolism.

Ovarian cancer tends to metastasize to the omentum, which is an organ mainly composed of adipose tissue. Many studies have found that fatty acid metabolism is related to the occurrence and metastasis of cancers. Therefore, it is possible that fatty acid metabolism-related genes (FAMRG) affect the prognosis of ovarian cancer patients. First, profiles of ovarian cancer and normal ovarian tissue transcriptomes were acquired from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. A LASSO regression predictive model was developed via the "glmnet" R package. The nomogram was created via the "regplot." Gene Set Variation Analysis (GSVA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) analyses were conducted to determine the FAMRGs' roles. The percentage of immunocyte infiltration was calculated via CIBERSORT. Using "pRRophetic," the sensitivity of eight regularly used medications and immunotherapy was anticipated. 125 genes were determined as different expression genes (DEGs). Based on RXRA, ECI2, PTGIS, and ACACB, a prognostic model is created and the risk score is calculated. Analyses of univariate and multivariate regressions revealed that the risk score was a distinct prognostic factor (univariate: HR: 2.855, 95% CI: 1.756-4.739, P < 0.001; multivariate: HR: 2.943, 95% CI: 1.800-4.812, P < 0.001). The nomogram demonstrated that it properly predicted the 1-year survival rate. The expression of memory B molecular units, follicular helper T molecular units, regulatory T molecular units, and M1 macrophages differed remarkably between the groups at high and low risk (P < 0.05). Adipocytokine signaling pathways, cancer pathways, and degradation of valine, leucine, and isoleucine vary between high- and low-risk populations. The findings of the GO enrichment revealed that the extracellular matrix and cellular structure were the two most enriched pathways. PTGIS, which is an important gene in fatty acid metabolism, was identified as the hub gene. This result was verified in ovarian cancer and ovarian tissues. The connection between the gene and survival was statistically remarkable (P = 0.015). The pRRophetic algorithm revealed that the low-risk group was more adaptable to cisplatin, doxorubicin, 5-fluorouracil, and etoposide (P < 0.001). PTGIS may be an indicator of prognosis and a possible therapeutic target for the therapy of ovarian cancer patients. The fatty acid metabolism of immune cells may be controlled, which has an indirect effect on cancer cell growth.

Testosterone is positively associated with coronary artery calcium in a low cardiovascular disease risk population.

In industrialized populations, low male testosterone is associated with higher rates of cardiovascular mortality. However, coronary risk factors like obesity impact both testosterone and cardiovascular outcomes. Here, we assess the role of endogenous testosterone on coronary artery calcium in an active subsistence population with relatively low testosterone levels, low cardiovascular risk and low coronary artery calcium scores. In this cross-sectional community-based study, 719 Tsimane forager-horticulturalists in the Bolivian Amazon aged 40+ years underwent computed tomography (49.8% male, mean age 57.6 years). Coronary artery calcium levels were low; 84.5% had no coronary artery calcium. Zero-inflated negative binomial models found testosterone was positively associated with coronary artery calcium for the full sample (Incidence Rate Ratio [IRR] = 1.477, 95% Confidence Interval [CI] 1.001-2.170, P = 0.031), and in a male-only subset (IRR = 1.532, 95% CI 0.993-2.360, P = 0.053). Testosterone was also positively associated with clinically relevant coronary atherosclerosis (calcium >100 Agatston units) in the full sample (Odds Ratio [OR] = 1.984, 95% CI 1.202-3.275, P = 0.007) and when limited to male-only sample (OR = 2.032, 95% CI 1.118-4.816, P = 0.024). Individuals with coronary artery calcium >100 had 20% higher levels of testosterone than those with calcium <100 (t = -3.201, P = 0.007). Among Tsimane, testosterone is positively associated with coronary artery calcium despite generally low normal testosterone levels, minimal atherosclerosis and rare cardiovascular disease (CVD) events. Associations between low testosterone and CVD events in industrialized populations are likely confounded by obesity and other lifestyle factors.

Is BMI responsible for variation in hsCRP with aspirin exposure?

To determine if high sensitivity C-reactive protein (hsCRP) serum concentrations changed significantly between the first and third trimesters in subpopulations exposed to different doses of aspirin (LDA) prophylaxis stratified by BMI. This is a secondary analysis from an open-label randomized control study of 81 vs 162 mg LDA prophylaxis with patients enrolled based on USPSTF major criteria (pooled cohort of all aspirin-exposed defined as the high-risk group). A third convenience, low-risk control population was also simultaneously recruited. Serum samples were obtained prior to aspirin initiation and at 28-32 weeks’ gestation. Analysis included groupings based on LDA exposure to any dose vs controls; and also based on specific dose, 0 vs 81 mg vs 162 mg. hsCRP levels were analyzed using an enzyme immunoassay test kit (BioCheck, Inc, Foster City, CA; Cat # BC-1119) utilizing quantitative sandwich enzyme immunoassay technique (ELISA). Statistical analysis included oneway ANOVA and pooled T-test. 171 subjects were grouped based on LDA exposure: 81mg (n= 69), 162mg (n= 75), and no LDA / control (“low risk”, n= 65). Serial first and third hsCRP results were available for 129 patients (76%). Groups were similar with regard to age and race; see Table 1. Women in the high-risk group were more likely to be obese (p=0.0003). Women who received 162mg LDA were more likely to report tobacco use (p=0.0037). At baseline a significant difference in hsCRP was not identified between 3 subgroups stratified by aspirin exposure (p=0.09); however, in the third trimester, this biomarker did differ significantly between these groups (p=0.048). No difference in hsCRP concentrations in the third trimester or change in hsCRP from baseline to third trimester was evident in subgroups stratified by BMI; see Table 2. Although variation in hsCRP was evident in third trimester between high-risk aspirin exposed subgroups and low-risk patients, BMI was not clearly associated as an explanatory variable for this difference suggesting a potential mechanism for LDA on inflammation.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Comorbidity score for the prediction of severe maternal morbidity in a high-risk population

Comorbidity scores predict severe maternal morbidity (SMM) and are used to identify and develop interventions for patients at risk of SMM. Most comorbidity scores are developed from claims databases and are representative of low-risk populations (risk of SMM of 1.2% and < 5% prevalence of obesity, diabetes, substance use and chronic hypertension [CHTN]). We sought to assess the predictive ability of a previously developed comorbidity score for SMM in a high-risk population.

Biomimetic polymeric transcatheter heart valve leaflets with low calcification and good regenerative ability.

Transcatheter aortic valve replacement (TAVR) technology is quickly advancing in clinic, however, as it expands to low-risk populations and younger patients (age <65 years), device durability is becoming a major challenge. Tissue-engineered heart valves (TEHVs) are a potential alternative. In this study, a bionic tri-layer tissue-engineered heart valve was constructed using poly (L-lactate-co-ε-caprolactone) (PLCL), gelatin (GEL), hyaluronic acid (HA) and silk fibroin (SF), to simulate the fibrosa, spongiosa and ventricular layer of natural heart valves. To obtain a scaffold with sufficient strength and regenerative capacity, we optimized the ratio of components of each layer. The physical and mechanical properties were tested, and the cytocompatibility, calcification deposition and regeneration potential were tested in a rat model of subcutaneous implantation. Finally, the hydrodynamic function of the new TAVR device was verified. The results demonstrated that the strength of the tri-layer valve could reach up to 10 MPa, significantly higher than that of the PLCL and mono-layer groups. Most importantly, calcification related gene expression was down-regulated in the TEHV groups compared to valvular interstitial cells (VICs) treated with calcification induced medium, and calcification levels of TEHVs in in vivo assay were below 0.5 μg mg-1. Besides, we found HA in the middle layer was very conducive to rapid cell infiltration and good angiogenesis, which ultimately promoted host tissue regeneration at 8 weeks after implantation. Collectively, we provide a bionic tri-layer electrospun leaflet with appropriate mechanical strength, low calcification and good regenerative capacity, which has great potential as a TEHV leaflet.

Möglichkeiten des Frühgeburtsscreenings

Every birth prior to 37 weeks of pregnancy is a premature birth. Premature births prior to 34 weeks of pregnancy are associated with significantly increased perinatal morbidity and mortality. A screening to improve prevention and treatment of premature birth is therefore useful. A fundamental component for the determination of risk factors is the patient history. A rapid second pregnancy within 12 months and a preterm birth in a previous pregnancy are considered to be the most important risk factors in the patient history. Examination of the neck of the cervix and particularly sonography provide additional information. They are particularly recommended for high-risk pregnant women or for pregnancies with existing symptoms, such as premature contractions, but are not recommended as a standard screening in the low-risk population. The same applies for the determination of biomarkers from vaginal secretions, which, in the case of symptoms, enables a better assessment of the overall situation. Laboratory diagnostics play a subordinate role in the diagnostics of premature birth.