INTRODUCTION: The objective of this study was to assess the relationship between longitudinal changes in the uterine Doppler velocimetry and the maternal profile of angiogenic factors in the third trimester and to assess their ability to predict term preeclampsia (PE). METHODS: A cohort of low-risk pregnant women was scheduled for a uterine Doppler evaluation and measurement of the circulating levels of angiogenic factors at ∼30 and ∼36 weeks. The performance of both parameters and their change over time in predicting term PE was evaluated. RESULTS: A total of 1,191 women were analyzed, of which 28 (2.4%) women developed term PE. At ∼30 weeks, a model including the sFlt-1/PlGF (fms-like tyrosine kinase-1/placental growth factor) ratio and the uterine Doppler explained 16.2% of the uncertainty of developing term PE, while at ∼36 weeks, the same variables explained 25.2% [p < 0.001]. The longitudinal changes of both predictors had an R2 of 26.8%, which was not different from that of the ∼36 weeks evaluation [p = 0.45]. The area under the curve (AUC) of the ∼36 weeks ratio was significantly higher than at ∼30 weeks (0.86 [0.77-0.94] vs. 0.81 [0.73-0.9]; p = 0.043). The AUC of the longitudinal change of the ratio (0.85 [0.77-0.94]) did not differ from that of at ∼36 weeks (p = 0.82). At ∼36 weeks, for a 10% of false positives, the ratio had a detection rate of 71.4%. CONCLUSION: A cross-sectional measurement of the sFlt-1/PlGF ratio outperforms uterine Doppler in predicting term PE. The combination of both markers does not improve such prediction, nor the evaluation of the longitudinal changes between weeks.
- MeSH
- Adult MeSH
- Humans MeSH
- Placental Circulation physiology MeSH
- Placenta Growth Factor * blood MeSH
- Area Under Curve MeSH
- Predictive Value of Tests MeSH
- Pre-Eclampsia * blood diagnostic imaging MeSH
- Vascular Endothelial Growth Factor Receptor-1 * blood MeSH
- Rheology * methods statistics & numerical data MeSH
- Reproducibility of Results MeSH
- Blood Flow Velocity physiology MeSH
- Pregnancy MeSH
- Pregnancy Trimester, Third * blood physiology MeSH
- Ultrasonography, Doppler methods statistics & numerical data MeSH
- Ultrasonography, Prenatal * methods statistics & numerical data MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
Úvod a cíl studie: Uterinní NK (uNK) buňky jsou specializovanou subpopulací NK (natural killer) lymfocytů nacházejících se v endometriu. Hrají klíčovou roli v regulaci imunitní odpovědi a v procesu implantace embrya. Cílem této studie je retrospektivní analýza výsledků léčby metodou in vitro fertilizace (IVF) v souboru žen, které podstoupily imunofenotypizaci uNK buněk a na základě výsledků tohoto vyšetření byly, nebo nebyly léčeny imunomodulační terapií. Metody: Studie zahrnovala 122 pacientek, které podstoupily imunofenotypizaci uNK buněk v období od dubna do prosince 2023. Imunofenotypizace byla provedena metodou průtokové cytometrie. Pacientky byly roztříděny do čtyř skupin dle fenotypu uNK buněk: normální nálezy, nízké absolutní a relativní počty uNK (LOW-IMMUNE profil), nízké počty uNK v kombinaci s nežádoucím posunem směrem k cytotoxickému uNKdim imunofenotypu (MIXED-IMMUNE profil) a normální počty uNK, ale nežádoucí posun v poměru cytotoxických a regulačních uNK s cytotoxickým fenotypem (OVER-IMMUNE profil). Byly hodnoceny výsledky embryotransferu a výskyt potratů do ukončeného 12. týdne těhotenství v jednotlivých skupinách. Výsledky: Nejvyšší míra dosažení klinické gravidity byla nalezena v léčené skupině OVER- -IMMUNE (70 %), následované skupinou MIXED-IMMUNE (60 %). Skupina LOW-IMMUNE se od neléčené NORMAL skupiny signifikantně nelišila (p = 0,205). Nedostatečná imunitní aktivace (LOW-IMMUNE profil) byla signifikantně nejčastěji sdružena s prvotrimestrální těhotenskou ztrátou (p < 0,0001). Závěr: Tato studie přináší nové poznatky o potenciálu imunofenotypizace uNK buněk a následné imunomodulační terapie v léčbě poruch plodnosti. Ačkoli výsledky naznačují možné klinické přínosy, je zapotřebí dalšího výzkumu k potvrzení těchto zjištění a k objasnění mechanizmů, které vedou ke zlepšení výsledků léčby technikami asistované reprodukce.
Introduction and objective: Uterine NK (uNK) cells, a specialized subpopulation of natural killer (NK) lymphocytes located in the endometrium, play a crucial role in regulating the immune response and in the process of embryo implantation. This study aims to retrospectively analyze the outcomes of in vitro fertilization (IVF) treatment in a cohort of women who underwent uNK cell immunophenotyping with subsequent immunomodulatory therapy applied based on the results. Methods: The study included 122 patients who underwent uNK cell immunophenotyping between April and December 2023. Immunophenotyping was performed using flow cytometry. Patients were categorized into four groups according to their uNK cell phenotypes: normal findings, low absolute and relative numbers of uNK cells (LOW-IMMUNE profile), low numbers of uNK cells combined with the shift towards the cytotoxic uNKc dim immunophenotype (MIXED-IMMUNE profile), and normal numbers of uNK cells, but an undesirable shift in the ratio of cytotoxic to regulatory uNK cells towards the cytotoxic uNK dim phenotype (OVER-IMMUNE profile). Embryo transfer outcomes and the occurrence of miscarriages up to the 12th week of pregnancy were evaluated in each group. Results: The highest clinical pregnancy rate was observed in the treated OVER-IMMUNE group (70%), fol lowed by the MIXED-IMMUNE group (60%). The LOW-IMMUNE group did not differ significantly from the untreated NORMAL group (P = 0.205). Insufficient immune activation (LOW-IMMUNE profile) was significantly associated with first-trimester pregnancy loss (P < 0.0001). Conclusion: This study provides new insights into the potential benefits of uNK cell immunophenotyping and subsequent immunomodulatory therapy in treating fertility disorders. While the results indicate possible clinical advantages, further research is necessary to confirm these findings and elucidate the mechanisms leading to improved outcomes in assisted reproductive techniques.
- Keywords
- uterinní NK buňky, imunofenotypizace lymfocytů, opakované selhání implantace,
- MeSH
- Killer Cells, Natural MeSH
- Endometrium cytology MeSH
- Fertilization in Vitro * MeSH
- Abortion, Habitual MeSH
- Immunophenotyping MeSH
- Immunomodulation MeSH
- Humans MeSH
- Flow Cytometry methods MeSH
- Retrospective Studies MeSH
- Infertility, Female * MeSH
- Check Tag
- Humans MeSH
- Female MeSH
OBJECTIVES: Risk-based stratification approaches using measurable residual disease (MRD) successfully help to identify T-acute lymphoblastic leukemia (T-ALL) patients at risk of relapse, whose treatment outcomes are very poor. Because of T-ALL heterogeneity and rarity, a reliable and standardized approach for flow cytometry (FC)-based MRD measurement and analysis is often missing. METHODS: Within the international AIEOP-BFM-ALL-FLOW study group we made a consensus on markers and a standard operating procedure for common 8- and 12-color T-ALL MRD panels. Custom manufactured tubes with dried backbone antibodies were tested in parallel to local FC standards. RESULTS: Altogether, 66 diagnostic and 67 day 15 samples were analyzed. We designed two guided MRD gating strategies to identify blast cells in parallel to expert-based evaluation. We proved that the optimized tubes allowed the correct identification of blast cells in all diagnostic samples. Both, expert and guided analysis of day 15 samples correlated to local standard (Spearman R=0.98 and R=0.94, respectively). Only in 2 (3 %) and 4 (6 %) patients expert gating and guided analysis results were substantially discordant from local standard, respectively. The cases that require an individualized approach may be partially identified at diagnosis through a rare immunophenotype or mixed phenotype acute leukemia status. CONCLUSIONS: Our work shows that standardized operating procedures together with guided analysis are applicable in a great majority of T-ALL cases. Further improvement of MRD detection is needed, as in some cases an individualized analytical approach is still required due to the challenging nature of the T-ALL phenotype.
- MeSH
- Child MeSH
- Infant MeSH
- Consensus MeSH
- Humans MeSH
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma * diagnosis pathology MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Flow Cytometry * standards methods MeSH
- Neoplasm, Residual * diagnosis MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
OBJECTIVES: This cross-sectional analysis from the CZecking Heart Failure in patients with advanced Chronic Kidney Disease trial (ISRCTN18275480) examined pulmonary hypertension and right ventricular-pulmonary arterial coupling in patients on chronic hemodialysis. The aims of this analysis were: 1. To analyze relations between pulmonary hypertension and right ventricular-pulmonary arterial coupling with dialysis access flow and current hydration; 2. To analyze structural heart changes associated with right ventricular-pulmonary arterial uncoupling; 3. To reveal the prevalence, etiology and severity of pulmonary hypertension in the Czech hemodialysis population. METHODS: We performed expert echocardiography, vascular access flow measurements, bioimpedance analysis, and laboratory testing in 336 hemodialysis patients. RESULTS: Pulmonary hypertension was present in 34% (114/336) patients and right ventricular-pulmonary arterial uncoupling was present in 25% of patients with pulmonary hypertension. Only weak associations between the flow of the dialysis arteriovenous access and estimated pulmonary arterial systolic pressure and right ventricular-pulmonary arterial coupling was proved. There was a strong association between hydration status assessed by estimated central venous pressure with pulmonary arterial systolic pressure (Rho 0.6, p < 0.0001) and right ventricular-pulmonary arterial coupling (Rho -0.52, p < 0.0001) and association between overhydration to extracellular water ratio with pulmonary arterial systolic pressure (Rho 0.31, p = 0.0001) and right ventricular-pulmonary arterial coupling (Rho -0.29, p = 0.002). The prevalence of heart failure was significantly higher in patients with right ventricular-pulmonary arterial uncoupling (88% vs. 52%, p = 0.0003). CONCLUSION: These findings suggest that optimizing volume status and treating heart failure should be prioritized in hemodialysis patients to prevent pulmonary hypertension progression and right ventricular-pulmonary arterial uncoupling.
- MeSH
- Pulmonary Artery * physiopathology MeSH
- Kidney Failure, Chronic * therapy complications physiopathology MeSH
- Renal Dialysis * adverse effects MeSH
- Echocardiography MeSH
- Middle Aged MeSH
- Humans MeSH
- Hypertension, Pulmonary * etiology physiopathology MeSH
- Cross-Sectional Studies MeSH
- Aged MeSH
- Heart Ventricles physiopathology diagnostic imaging MeSH
- Heart Failure physiopathology complications etiology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Cíl: Observační studie pacientů diagnostikovaných s těžkou komunitní pneumonií (sCAP) sledovala hladiny interleukinu-17A a počtu T helper 17 (Th17) lymfocytů v periferní cirkulaci a tekutině z bronchoalveolární laváže (BAL) v časném průběhu komunitní pneumonie různé etiologie a porovnala je s charakteristikami pacientů a klinickým výsledkem. Materiál a metody: Kohorta 74 pacientů s těžkou komunitní pneumonií byla analyzována s identifikací jednotlivých původců pneumonie. Podle etiologie byli pacienti rozděleni do tří skupin: bakteriální, virové a smíšené etiologie. Počet Th17 lymfocytů a koncentrace IL-17A byly měřeny s využitím průtokové cytometrie a metody ELISA v periferní krvi a tekutině z BAL. Data byla porovnána podle etiologie sCAP a statistickou analýzou stanovena jejich korelace s 30a 90denní mortalitou. Výsledky: Statistická korelace mezi počtem Th17 lymfocytů a koncentrací IL-17A v krvi ani v tekutině z BAL s 30a 90denní mortalitou nebyla prokázána. Nicméně, zvýšený počet Th17 lymfocytů v periferní cirkulaci, nikoli však v tekutině z BAL, v časném průběhu sCAP koreloval se zvýšeným relativním rizikem úmrtí. Dalšími faktory zvyšujícími relativní riziko smrti byl věk a mužské pohlaví. Závěr: Hladiny Th17 a IL-17A v systémové cirkulaci v časném průběhu sCAP (v prvních 7 dnech od diagnózy) mohou korelovat s tíží a mortalitou sCAP.
Objective: Observational study of patients diagnosed with severe community acquired pneumonia (sCAP) carried out to evaluate levels of interleukin 17A (IL-17A) and T helper 17 (Th17) lymphocyte count in peripheral circulation and bronchoalveolar lavage fluid (BALF) in the early course of sCAP of different etiology and to compare them with patient’s characteristics and outcome. Material and methods: Cohort of 74 patients with sCAP was analyzed and respective microbial etiology established. According to pathogens, 3 subgroups of patients were created: bacterial, viral and mixed etiology. Th17 count and IL-17A levels were measured using flow cytometry and ELISA in peripheral blood and BALF. Data were compared with respect to etiology and their correlation with 30and 90-day mortality was statistically analyzed. Results: There was no statistically significant correlation in Th17 count and IL-17A levels in blood and BALF between etiological subgroups of CAP and no correlation was found with respect to measured parameters and 30and 90-day mortality. Nevertheless, increased Th17 cell count and IL-17A levels in peripheral blood, but not in BALF, in the early course of sCAP are correlated with increased relative risk of death from sCAP. Other factors increasing relative risk of death in patients with sCAP found in our cohort were male sex and advanced age. Conclusions: Systemic Th17 count and IL-17A levels in the early course (up to 7 days from admission) of sCAP may be correlated with severity and outcome of sCAP.
- MeSH
- Th17 Cells * immunology MeSH
- Immunologic Tests methods MeSH
- Community-Acquired Infections diagnosis immunology mortality MeSH
- Interleukin-17 * analysis immunology MeSH
- Humans MeSH
- Microbiological Techniques methods MeSH
- Pneumonia * etiology immunology mortality MeSH
- Observational Studies as Topic methods MeSH
- Prognosis MeSH
- Risk Factors MeSH
- Severity of Illness Index MeSH
- Check Tag
- Humans MeSH
BACKGROUND: The presence of ACPA significantly increases the risk of developing RA. Dysregulation of lymphocyte subpopulations was previously described in RA. Our objective was to propose the predictive model for progression to clinical arthritis based on peripheral lymphocyte subsets and ACPA in individuals who are at risk of RA. METHODS: Our study included 207 at-risk individuals defined by the presence of arthralgias and either additional ACPA positivity or meeting the EULAR definition for clinically suspect arthralgia. For the construction of predictive models, 153 individuals with symptom duration ≥12 months who have not yet progressed to arthritis were included. The lymphocyte subsets were evaluated using flow cytometry and anti-CCP using ELISA. RESULTS: Out of all individuals with arthralgia, 41 progressed to arthritis. A logistic regression model with baseline peripheral blood lymphocyte subpopulations and ACPA as predictors was constructed. The resulting predictive model showed that high anti-CCP IgG, higher percentage of CD4+ T cells, and lower percentage of T and NK cells increased the probability of arthritis development. Moreover, the proposed classification decision tree showed that individuals having both high anti-CCP IgG and low NK cells have the highest risk of developing arthritis. CONCLUSIONS: We propose a predictive model based on baseline levels of lymphocyte subpopulations and ACPA to identify individuals with arthralgia with the highest risk of progression to clinical arthritis. The final model includes T cells and NK cells, which are involved in the pathogenesis of RA. This preliminary model requires further validation in larger at-risk cohorts.
- MeSH
- Arthralgia * immunology MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymphocyte Subsets * immunology MeSH
- Predictive Value of Tests MeSH
- Disease Progression * MeSH
- Anti-Citrullinated Protein Antibodies * blood immunology MeSH
- Arthritis, Rheumatoid * immunology blood MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Presence of minimal residual disease (MRD), detected by flow cytometry, is an important prognostic biomarker in the management of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, data-analysis remains mainly expert-dependent. In this study, we designed and validated an Automated Gating & Identification (AGI) tool for MRD analysis in BCP-ALL patients using the two tubes of the EuroFlow 8-color MRD panel. The accuracy, repeatability, and reproducibility of the AGI tool was validated in a multicenter study using bone marrow follow-up samples from 174 BCP-ALL patients, stained with the EuroFlow BCP-ALL MRD panel. In these patients, MRD was assessed both by manual analysis and by AGI tool supported analysis. Comparison of MRD levels obtained between both approaches showed a concordance rate of 83%, with comparable concordances between MRD tubes (tube 1, 2 or both), treatment received (chemotherapy versus targeted therapy) and flow cytometers (FACSCanto versus FACSLyric). After review of discordant cases by additional experts, the concordance increased to 97%. Furthermore, the AGI tool showed excellent intra-expert concordance (100%) and good inter-expert concordance (90%). In addition to MRD levels, also percentages of normal cell populations showed excellent concordance between manual and AGI tool analysis. We conclude that the AGI tool may facilitate MRD analysis using the EuroFlow BCP-ALL MRD protocol and will contribute to a more standardized and objective MRD assessment. However, appropriate training is required for the correct analysis of MRD data.
- MeSH
- Child MeSH
- Adult MeSH
- Immunophenotyping methods MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma * pathology diagnosis MeSH
- Child, Preschool MeSH
- Flow Cytometry * methods MeSH
- Reproducibility of Results MeSH
- Neoplasm, Residual * pathology diagnosis MeSH
- Aged MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
OBJECTIVES: Minimal residual disease (MRD) status in multiple myeloma (MM) is an important prognostic biomarker. Personalized blood-based targeted mass spectrometry detecting M-proteins (MS-MRD) was shown to provide a sensitive and minimally invasive alternative to MRD-assessment in bone marrow. However, MS-MRD still comprises of manual steps that hamper upscaling of MS-MRD testing. Here, we introduce a proof-of-concept for a novel workflow using data independent acquisition-parallel accumulation and serial fragmentation (dia-PASEF) and automated data processing. METHODS: Using automated data processing of dia-PASEF measurements, we developed a workflow that identified unique targets from MM patient sera and personalized protein sequence databases. We generated patient-specific libraries linked to dia-PASEF methods and subsequently quantitated and reported M-protein concentrations in MM patient follow-up samples. Assay performance of parallel reaction monitoring (prm)-PASEF and dia-PASEF workflows were compared and we tested mixing patient intake sera for multiplexed target selection. RESULTS: No significant differences were observed in lowest detectable concentration, linearity, and slope coefficient when comparing prm-PASEF and dia-PASEF measurements of serial dilutions of patient sera. To improve assay development times, we tested multiplexing patient intake sera for target selection which resulted in the selection of identical clonotypic peptides for both simplex and multiplex dia-PASEF. Furthermore, assay development times improved up to 25× when measuring multiplexed samples for peptide selection compared to simplex. CONCLUSIONS: Dia-PASEF technology combined with automated data processing and multiplexed target selection facilitated the development of a faster MS-MRD workflow which benefits upscaling and is an important step towards the clinical implementation of MS-MRD.
- MeSH
- Automation MeSH
- Precision Medicine methods MeSH
- Humans MeSH
- Multiple Myeloma * diagnosis blood MeSH
- Workflow * MeSH
- Neoplasm, Residual * diagnosis MeSH
- High-Throughput Screening Assays methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Natural killer cells (NK) and innate lymphoid cells with their subsets (ILC) are part of the innate immune system. OBJECTIVE: The aim is to evaluate how NK cells and ILC cells interact in atopic dermatitis (AD) patients (with and without dupilumab therapy) compared to control group. MATERIALS AND METHODS: Complete dermatological examination was performed in all patients included in the study (19 AD patients with dupilumab, 17 AD patients without dupilumab). Surface molecules expressed on NK cells and ILC cells were analyzed by flow cytometry. The association between NK cells and total ILC cells, ILC-1, ILC-2, ILC-3, NCR+ILC3, NCR-ILC3 were compared in AD patients and in the control group. The non-parametric Spearman's rank correlation coefficient was used for this statistical analysis. We evaluated the association of parameters with AD severity at the time of treatment.Non-parametric Mann-Whitney, Kolmogorov-Smirnov tests were used. RESULTS: We confirmed the higher association between NK cells and total ILC cells in AD patients without dupilumab therapy (in 30.3 %) and in healthy controls (in 27.2 %); this association is low in AD patients with dupilumab therapy (in 0.1 %). The higher association was confirmed between NK cells and ILCs subsets only in AD patients without dupilumab therapy; in these patients the highest association was confirmed between NK cells and ILC-2 cells (in 38.6 %). No statistically significant difference in the count of NK cells and ILC cells was found between mild and moderate form of AD patients treated with dupilumab. CONCLUSION: Targeting these cell types or the cytokines they produce could represent potential therapeutic strategies for controlling inflammation and alleviating symptoms in AD patients.
- MeSH
- Dermatitis, Atopic * drug therapy immunology MeSH
- Killer Cells, Natural * immunology drug effects MeSH
- Adult MeSH
- Antibodies, Monoclonal, Humanized * therapeutic use pharmacology MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymphocytes immunology drug effects MeSH
- Cell Communication MeSH
- Young Adult MeSH
- Lymphocyte Subsets immunology drug effects MeSH
- Immunity, Innate drug effects MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
OBJECTIVE: Provide a synthesis of the current literature about the effects of detraining on cognitive functions in older adults. METHODS: The PICOS acronym strategy was performed in PubMed/MEDLINE, Web of Science, Cochrane Library and PsycINFO database. The Preferred Reporting Items for Systematic Review and Meta-Analyses statement had been followed in the present study, in which the search was conducted on October 2023. The study selection consisted in original articles including older adults, detraining after training exercise period, use of tests or scales to measure cognitive function. The Downs and Black checklist had been used to assess the studies quality. Sample characteristics, type of previous training, detraining period, cognitive functions measurements and main results were extracted by 2 investigators. RESULTS: From 1927 studies, 12 studies were included, being 11 studies identified via systematic research, and 1 study by citation search. Older adults, ranged from 60 to 87 years old, were assessed after detraining. The cognitive functions most evaluated were global cognition and executive functions. One study evaluated both cognitive outcome and cerebral blood flow. Most of the studies demonstrated a decline in the cognitive function after detraining. CONCLUSION: Exercise detraining period, ranging from 10 days to 16 weeks, can effect negatively the cognitive function in older adults.
- MeSH
- Exercise * psychology physiology MeSH
- Executive Function physiology MeSH
- Cognition * physiology MeSH
- Cognitive Dysfunction MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Systematic Review MeSH