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Mesenchymal stromal cells for the prophylaxis of graft-versus-host disease after hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials

Expert Rev Hematol. 2025 Jul 23. doi: 10.1080/17474086.2025.2535422. Online ahead of print.

ABSTRACT

BACKGROUND: Mesenchymal stromal cells (MSCs) have emergedas a potential alternative therapeutic strategy for the prophylaxisof graft-versus-host disease (GVHD) in patients undergoinghematopoietic stem cell transplantation (HSCT).

RESEARCH DESIGN AND METHODS: This meta-analysis included eight randomizedcontrolled trials (RCTs) involving 570 patients. The primary outcomesassessed were overall survival (OS), the development of acute GVHD(aGVHD), and chronic GVHD (cGVHD). Secondary outcomes includedprimary disease relapse and adverse events. The statistical analysiswas performed using Review Manager (RevMan 5.4) with a random-effectsmodel.

RESULTS: The meta-analysis showed a significantimprovement in overall survival in the MSC group compared to thecontrol group (RR 1.12; 95% CI: 1.02-1.23), with no evidence ofheterogeneity (I² = 0%). MSC prophylaxis was associated with asignificant reduction in the incidence of aGVHD (RR 0.67; 95% CI:0.40-0.83, I² = 33%) and cGVHD (RR 0.65; 95% CI: 0.49-0.87, I² = 0%).However, no significant difference was found between the MSC andcontrol groups regarding primary disease relapse (RR 1.00; 95% CI:0.73-1.38, I² = 0%) or the incidence of infections (RR 0.80; 95% CI:0.57-1.11, I² = 0%). In terms of patients with at least one adverseevent, no statistically significant difference was observed betweenthe two groups (RR 1.10; 95% CI: 0.74-1.63, I² = 34%).

CONCLUSIONS: MSC prophylaxis significantly improves overallsurvival and reduces the incidence of both aGVHD and cGVHD in HSCTpatients, without increasing the risk of relapse, infections, oradverse events, indicating its potential as a safe and effectiveintervention for GVHD management. Further large-scale, multicenterRCTs are needed to validate or refute the current findings.

REGISTRATION: This review has been registered with theInternational Prospective Register of Systematic Reviews (PROSPERO)(CRD42024569358).

PMID:40699555 | DOI:10.1080/17474086.2025.2535422

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Sensory impairment and dementia risk among older adults in rural South Africa

Alzheimers Dement. 2025 Jul;21(7):e70513. doi: 10.1002/alz.70513.

ABSTRACT

INTRODUCTION: South Africa faces growing dementia challenges, worsened by limited medical resources and low education. Modifiable risk factors like hearing and vision impairments remain understudied despite their high prevalence.

METHODS: We analyzed data from 567 participants in a rural South African cohort to examine the associations between vision and hearing impairment, and dementia outcomes. Multinomial logistic regression assessed associations between sensory impairments (distance vision, near vision, hearing) and mild cognitive impairment (MCI) or dementia. Linear regression examined sensory impairment and predicted dementia probability score 2 years later.

RESULTS: Half of the participants were over 70, with no formal education. Sensory impairments were common, especially in dementia cases. Distance vision impairment was linked to both MCI and dementia, while near vision and hearing impairments were associated with dementia. Hearing impairment also predicted higher dementia probability after 2 years.

DISCUSSION: Addressing sensory impairments is key to dementia prevention in rural South Africa.

HIGHLIGHTS: Among rural older South Africans, 65% had near vision impairment and 47% had hearing impairment. Distance or near vision and hearing impairments are linked to an increased risk of dementia. Distance vision impairment is also associated with a higher risk of mild cognitive impairment (MCI). Dementia risk was seven times higher with distance vision, near vision and hearing impairment. Hearing impairment increased the probability of dementia 2 years later in initially non-demented individuals.

PMID:40693440 | DOI:10.1002/alz.70513

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Response Surface Methodology-Based Extraction of Fumaric Acid From Fumaria officinalis L. and Quantification by RP-HPLC

Biomed Chromatogr. 2025 Sep;39(9):e70173. doi: 10.1002/bmc.70173.

ABSTRACT

In the present study, it was aimed to optimize the extraction of fumaric acid from Fumaria officinalis L. by response surface methodology and its quantification by a newly developed and validated reverse phase high performance liquid chromatography method. Chromatographic separations were performed at 40°C with a C18 column. Aqueous o-phosphoric acid solution and methanol were used as the mobile phase by gradient elution. The flow rate was set at 1.0 mL/min, and the injection volume was 20 μL. Fumaric acid was detected at 215 nm with a UV detector. The method was linear in the range of 10.00-200.00 μg/mL. The limits of detection and quantification were 3.02 μg/mL and 9.15 μg/mL, respectively. The relative mean errors were ≤ 3.77%, whereas the relative standard deviation values were calculated as ≤ 0.48%. The conditions to obtain an extract with high fumaric acid content were optimized by central composite design, a type of response surface methodology. The independent variables were extraction time, solvent volume, and temperature for the maceration procedure, where fumaric acid concentration was the response. The experimental model was evaluated statistically and found to fit well, considering the lack-of-fit p value of 0.211 and coefficient of determination 0.9862 at a confidence level of 95%.

PMID:40693429 | DOI:10.1002/bmc.70173

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Recurrence of thrombosis in patients with primary antiphospholipid syndrome: emphasis on arterial events

Clin Exp Rheumatol. 2025 Jul 21. doi: 10.55563/clinexprheumatol/t0xgtk. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess risk factors for rethrombosis, the intensity and maintenance of anticoagulation in primary antiphospholipid syndrome (APS).

METHODS: We retrospectively included 81 patients with thrombotic APS under VKAs with ≥4 INR determinations per year in at least 1 year. We defined an index period as the time between the first available INR value and the next thrombotic event, or the time between the first and last available INR if rethrombosis-free. We recorded demographic and clinical/serologic variables, mean INR, mean INR-AUC, and anticoagulation intensity (INR<2.5, INR 2.5-3.5, and INR>3.5). For the statistical analysis we used Cox survival analysis, hazard function (H(t)) curves and AUC.

RESULTS: The median follow-up time was 6.4 years. 64 patients had no rethrombosis, whereas 17 did (15 arterial, 2 venous). The risk factors for rethrombosis were number of previous rethrombosis (RR 7.3 95% CI 2.3-322.7, p=0.007) and INR intensity (RR 0.03, 95% CI 0.002-0.367, p=0.001). Results were similar when only arterial events were analysed. At the H(t) curves, the cumulative risk was higher in patients with an INR <2.5 than those in an INR of 2.5-3.5. A mean INR of 2.2 identified patients at risk of rethrombosis (SE=0.82, SP=0.20, AUC=0.42).

CONCLUSIONS: The number of previous thrombotic events and the intensity of anticoagulation are rethrombosis risk factors. An INR ranging 2.5-3.5 protects against re-thrombosis, including arterial events.

PMID:40693427 | DOI:10.55563/clinexprheumatol/t0xgtk

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Emerging frontiers in visual ecology

J Exp Biol. 2025 Aug 1;228(15):jeb250537. doi: 10.1242/jeb.250537. Epub 2025 Jul 22.

ABSTRACT

Visual ecology, the study of how animals acquire and respond to visual information in nature, has grown rapidly over the past few decades. Research in this field has transformed our understanding of fundamental processes, such as the neurobiological basis of behavior and the diversification of species through sensory drive. The recent growth in the field has been accompanied by leaps in our understanding of the diversity of visual systems and in the development of novel technologies and techniques (for example, those allowing us to measure scenes and signals). With such growth, however, it is more important than ever to integrate wide perspectives and expertise to move the field forward in the most productive way. To that end, in summer 2024, 30 visual ecologists from around the world – spanning all career stages – met to discuss the state of the field. From that meeting, we identified two broad emerging themes in the study of visual ecology. (1) Can we further ‘step inside’ the perceptual experience of a non-human animal? (2) Can foundational ‘rules’ of vision and visual stimuli be identified? Although large questions such as these can feel unanswerable, this is where some of the most exciting discoveries in visual ecology remain to be made. Here, we outline eight relevant areas of research and identify ways in which researchers can bring us closer to answering these complex questions.

PMID:40693401 | DOI:10.1242/jeb.250537

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Effects of hypomethylation on immune system of Galleria mellonella L. (Lepidoptera: Pyralidae)

Insect Sci. 2025 Jul 22. doi: 10.1111/1744-7917.70123. Online ahead of print.

ABSTRACT

Galleria mellonella is becoming increasingly used as a model organism for studying human pathogen infection disease. Therefore, all factors affecting the level of immune response of G. mellonella should be evaluated. One of these factors is DNA methylation, among the most important epigenetic modifications. Firstly, we investigated the presence of CpG dinucleotides and their methylation status of eggs, last instars, pupae, and adults using HpaII, MspI, and ScrFI methylation-sensitive restriction endonucleases. The gel analysis of the restriction pattern of HpaII, MspI, ScrFI, and MspI+ScrFI on G. mellonella genomic DNA showed that all enzymes produced a wide range of smears. The digestion of DNA samples of egg, pupa, and adult resulted in a smear at higher molecular weight for MspI+ScrFI, and these differences were statistically significant. These results confirm the presence of CpG dinucleotides and methylation at the internal and outer cytosines in different developmental stages of G. mellonella. Presence of global DNA methylation, which was by 3%-5% was investigated in various developmental stages of G. mellonella. Then, different levels of DNA methylation in the last instars of G. mellonella were created with the hypomethylation agent, zebularine (0.25-32 mg/mL), and immunity responses were examined. The most effective doses of zebularine, to create a global hypomethylation status in G. mellonella larvae, were 0.25 and 1 mg/mL. The humoral/cellular immune response of G. mellonella larvae became weak at high hypomethylation. These results present the level of DNA methylation during all developmental stages of G. mellonella and how zebularine treatment affects physiological processes.

PMID:40693385 | DOI:10.1111/1744-7917.70123

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Quantitative assessment of mucosal fibrosis and its correlation with disease severity and outcome in cats with chronic enteropathy

J Feline Med Surg. 2025 Jul;27(7):1098612X251338174. doi: 10.1177/1098612X251338174. Epub 2025 Jul 22.

ABSTRACT

ObjectivesThis study aimed to develop a quantitative scoring method for the evaluation of mucosal fibrosis (MF) and assess its correlation with World Small Animal Veterinary Association scores, clinical abnormalities, disease severity, diagnosis and outcome in cats with lymphoplasmacytic enteritis (LPE) or low-grade intestinal T-cell lymphoma (LGITL).MethodsFormalin-fixed, paraffin-embedded small intestinal biopsy specimens from 13 cats with LPE and 14 cats with LGITL were included. MF was quantitatively measured in three separate areas (villi, apical crypts [ACs] and basal crypts) using an image processing program. The fractional fibrotic area (%FFA) was calculated based on the mean fibrosis scores in five representative fields. MF was also scored by a single board-certified pathologist on sequential slides stained with either hematoxylin and eosin (H&E) or Masson’s trichrome (MT) on a four-point scale in the areas described above. Statistical analysis was performed to assess the correlation between clinical and pathological variables, diagnosis and outcome.ResultsThe %FFA scores correlated well with fibrosis scores on MT stains (r = 0.52, P = 0.01) but did not correlate with H&E stains (r = 0.29, P = 0.14). The %FFA in the villi and AC area was negatively correlated with a modified Feline Chronic Enteropathy Activity Index in cats with LGITL (r = -0.57, P = 0.04). A histopathologic diagnosis of LPE showed a weak correlation with MF in the AC area (r = 0.38, P = 0.05). The survival time of cats with chronic enteropathy (CE) was weakly negatively correlated with MF (r = -0.38, P = 0.05).Conclusions and relevanceMF is more effectively assessed using MT staining compared with H&E staining alone. Increased MF in the AC region may indicate a diagnosis of LPE. Although increased MF did not correlate with increased disease activity, it appears to be a negative prognostic factor for survival in cats with CE.

PMID:40693384 | DOI:10.1177/1098612X251338174

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Global, regional and national burden of blindness and vision loss attributable to diabetic retinopathy, 1990-2021: A systematic analysis for the Global Burden of Disease Study 2021

Diabetes Obes Metab. 2025 Jul 22. doi: 10.1111/dom.16588. Online ahead of print.

ABSTRACT

AIMS: Diabetes is increasingly reported as a cause of blindness and vision loss. However, the trends in the burden of blindness and vision loss attributed to diabetic retinopathy (DR) have yet to be fully elucidated.

MATERIALS AND METHODS: Utilizing the latest data from the Global Burden of Disease Study 2021, we extracted prevalence and years lived with disability (YLD) data for these conditions, including their respective age-standardized rate (ASR) indicators. The data were categorized by time, location, age and sociodemographic index (SDI). This study conducted comprehensive analyses over a span of 32 years (1990-2021) to identify trends in blindness and vision loss attributed to DR, employing advanced statistical methods such as estimated annual percentage change (EAPC), health inequity analysis (slope index and concentration index), decomposition analysis, frontier analysis, and predictive modelling using the Bayesian age-period-cohort method.

RESULTS: From 1990 to 2021, the global burden of blindness and vision loss attributed to DR (measured by prevalence and YLD) increased rapidly, and this trend was projected to remain stable until 2046. The age-standardized prevalence rates (ASPR) and age-standardized YLD rates (ADYR) in all five SDI regions exhibited an upward trend. Notably, the high and high-middle SDI regions surpassed global levels, with their EAPC and 95% CI values all greater than 0. In 2021, the prevalence cases, YLD cases, prevalence rates and YLD rates for females across all age groups were generally higher than those for males, and were approximately 1.4 times those of males. Health inequality analysis indicates that over the past 32 years, there have been significant disparities in the distribution of prevalence rates and YLD rates associated with the SDI across 204 countries and regions. Decomposition analysis on a global and cross-SDI regional scale indicated that ageing, population growth and epidemiological changes had all increased the burden of prevalence and YLD. The frontier analysis showed that high SDI regions had greater potential for improvement. In 2021, compared with the relatively stable trend of type 1 diabetes, the prevalence and YLD rates of blindness and vision loss attributable to type 2 diabetes rapidly increased with age.

CONCLUSIONS: Blindness and vision loss attributed to DR pose significant global health and economic challenges. It is imperative for health system managers to formulate strong strategies to address these growing issues effectively.

PMID:40693378 | DOI:10.1111/dom.16588

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The effectiveness of 12.5 and 25 micrograms 17β-estradiol vaginal gel for postmenopausal vaginal atrophy: A randomized non-inferiority trial

Int J Gynaecol Obstet. 2025 Jul 22. doi: 10.1002/ijgo.70403. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the effectiveness of two dosages (12.5 and 25 μg) of 17β-estradiol vaginal gel for treating postmenopausal vaginal atrophy.

METHODS: A randomized non-inferiority trial was conducted in the Gynecologic Endocrinology and Menopause Clinic of a university hospital from June 2022 to February 2023. A total of 80 postmenopausal women were randomly assigned to receive a 12.5 μg (half-dose) or 25 μg (full-dose) 17β-estradiol vaginal gel daily for 14 days, followed by twice-weekly for 10 weeks. Efficacy outcomes were vaginal maturation value (VMV), vaginal health index (VHI), vaginal pH, most bothersome symptoms (MBSs), and female sexual function index (FSFI). Safety outcomes were endometrial thickness, serum estradiol level, and adverse events. All study outcomes were evaluated at three time points: baseline, week 4, and week 12.

RESULTS: At week 12, both the half-dose and full-dose groups displayed a significant improvement in the VMV, with median (25th-75th percentile) of 67.3 (59.1-72.9) and 71.8 (60.3-79.5), respectively. While the full-dose group exhibited slightly greater improvement in VMV, the difference was not statistically significant. The upper bound of the 95% confidence interval (CI) for the median difference in VMV was below the predefined non-inferiority margin of 15 (4.5, 95% CI: -0.5, 10.0; P = 0.082). Additionally, both groups demonstrated significant improvements from baseline in all efficacy outcomes without any safety concerns.

CONCLUSION: Both 12.5 and 25 μg doses of 17β-estradiol vaginal gel are safe and effectively improve vaginal atrophy in postmenopausal women. The non-inferiority of the half-dose to the full-dose suggests its potential as a cost-effective treatment option with comparable benefits.

PMID:40693355 | DOI:10.1002/ijgo.70403

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Prescription Medication Expenditures for Patients With Diabetes in the United States: 2012-2021

J Diabetes. 2025 Jul;17(7):e70106. doi: 10.1111/1753-0407.70106.

ABSTRACT

Glucose-lowering medication expenditures per user by different payers among patients with diabetes.

PMID:40693336 | DOI:10.1111/1753-0407.70106