Tag: pubmed

Front Cell Dev Biol. 2024 Dec 9;12:1446363. doi: 10.3389/fcell.2024.1446363. eCollection 2024.

ABSTRACT

INTRODUCTION: T-cadherin, a non-canonical member of the cadherin superfamily, was initially identified for its involvement in homophilic recognition within the nervous and vascular systems. Apart from its adhesive function, T-cadherin acts as a receptor for two ligands: LDL, contributing to atherogenic processes, and HMW adiponectin, a hormone with well-known cardiovascular protective properties. However, the precise role of T-cadherin in adipose tissue remains elusive. Previously, we generated Cdh13^∆Exon3 mice lacking exon 3 in the Cdh13 gene, which encodes the T-cadherin protein, and characterized their phenotype.

METHODS: Using wild-type (WT) and T-cadherin-deficient mice (Cdh13ΔExon3), we isolated and cultured mesenchymal stem cells to explore the role of T-cadherin in adipogenic differentiation. The experimental approaches employed include culturing cells under standard or adipogenic conditions, performing Oil Red O and Nile Red staining followed by quantitative analysis, conducting rescue experiments to reintroduce T-cadherin using lentiviral constructs in T-cadherin-deficient cells combined with automated adipocyte differentiation quantification via a neural network. Additionally, Western blotting, ELISA assays, and statistical analysis were utilized to verify the results.

RESULTS: In this study, we demonstrate for the first time that T-cadherin influences the adipogenic differentiation of MSCs. The presence of T-cadherin dictates distinct morphological characteristics in MSCs. Lack of T-cadherin leads to spontaneous differentiation into adipocytes with the formation of large lipid droplets. T-cadherin-deficient cells (T-/- MSCs) exhibit an enhanced adipogenic potential upon induction with differentiating factors. Western Blot, ELISA assays, and rescue experiments collectively corroborate the conclusion that T-/- MSCs are predisposed toward adipogenic differentiation. We carried out an original comparative analysis to explore the effects of T-cadherin ligands on lipid droplet accumulation. LDL stimulate adipogenic differentiation, while T-cadherin expression mitigates the impact of LDL on lipid droplet accumulation. We also examined the effects of both low molecular weight (LMW) and high molecular weight (HMW) adiponectin on lipid droplet accumulation relative to T-cadherin. LMW adiponectin suppressed lipid droplet accumulation independently of T-cadherin, while the absence of T-cadherin enhanced susceptibility to the suppressive effects of HMW adiponectin on adipogenesis.

DISCUSSION: These findings shed light on the role of T-cadherin in adipogenic differentiation and suggest an interplay with other receptors, such as LDLR and AdipoRs, wherein downstream signaling may be modulated through lateral interactions with T-cadherin.

PMID:39717846 | PMC:PMC11663858 | DOI:10.3389/fcell.2024.1446363

Arthroplast Today. 2024 Dec 7;30:101574. doi: 10.1016/j.artd.2024.101574. eCollection 2024 Dec.

ABSTRACT

BACKGROUND: Aseptic loosening is the most common aseptic failure modality following total knee arthroplasty. Recent literature suggests that the implant-cement interface is the “weak-link” in fixation and lipid contamination may drive this debonding pattern. Therefore, the purpose of this study was to determine if the “double-butter” technique would significantly decrease lipid contamination of the tibial tray.

METHODS: Transparent acrylic models of 7 different tibial baseplates were created to allow for direct visualization of fluid contamination of the implant-cement interface during experimental cementation. Three cementation techniques were then employed in triplicate for each implant: coating only the tibia (“single butter”) and coating of the tibia and baseplate (with and without keel included; “double-butter”). A dye was added centrally to simulate lipid contamination. After each trial, the degree of implant-cement contamination was calculated. Standard statistical analyses were conducted.

RESULTS: With the double-butter technique, there was a significant reduction in contamination for all studied implant designs (range: 0%-7%; P < .05) and contamination was eliminated when the entire implant was coated prior to implantation. The single-butter technique resulted in contamination of 16%-43% of the tibial undersurface. There were significant differences in percent contamination between component designs (P < .05).

CONCLUSIONS: Cementation technique and implant design each influenced baseplate lipid contamination. While significant differences were noted between keel geometries, we found that the double-butter technique effectively eliminated baseplate contamination, even in the most susceptible designs in this study. We therefore advocate for the incorporation of the double-butter technique to limit lipid contamination and potentially reduce aseptic tibial loosening.

PMID:39717839 | PMC:PMC11665463 | DOI:10.1016/j.artd.2024.101574

Front Glob Womens Health. 2024 Dec 9;5:1423639. doi: 10.3389/fgwh.2024.1423639. eCollection 2024.

ABSTRACT

INTRODUCTION: Globally, maternal mortality is a major public health problem mainly due to a lack of access to skilled care during childbirth. Maternity waiting homes (MWHs) play a critical role in accessing emergency obstetric care for pregnant women during childbirth. However, available studies show inconsistent findings about women’s utilization of maternity waiting homes. Therefore, the aim of this review was to identify the pooled prevalence of women’s utilization of maternity waiting homes and its associated factors in Ethiopia.

METHOD: We used the PRISMA guidelines to report the review. We searched for potentially eligible studies in Google Scholar, PubMed, Cochrane Library, and Google using Medical Subject Heading terms and keywords. The retrieved articles were screened and assessed for quality. The heterogeneity across studies was checked using Cochran’s Q test and I ² statistics. The pooled levels of women’s utilization and associated factors were analyzed using meta-analysis. The publication bias was measured using the funnel plot and Egger’s test. The subgroup analysis and sensitivity analysis were carried out to identify the studies with high effects.

RESULTS: A total of 11 eligible studies with 11,784 study participants were included. The utilization of MWHs was in the range of 7%-42.5%. The pooled estimate of women’s utilization of maternity waiting homes was 22.49%. Factors associated with utilization included women’s decision-making power, access to transport, walking distance to the nearest facility, and having a companion.

CONCLUSION AND RECOMMENDATION: The overall prevalence of maternity waiting home utilization in Ethiopia is low, with significant variation across regions. Health sector program administrators should focus on both the consumer and healthcare system.

SYSTEMATIC REVIEW REGISTRATION: The review protocol was registered in PROSPERO (number CRD42021243526).

PMID:39717798 | PMC:PMC11663854 | DOI:10.3389/fgwh.2024.1423639

Front Vet Sci. 2024 Dec 9;11:1468906. doi: 10.3389/fvets.2024.1468906. eCollection 2024.

ABSTRACT

The African swine fever (ASF) epidemic has severely challenged the Philippines’ swine industry since 2019. The National African Swine Fever Prevention and Control Program (NASFPCP), launched in 2021, aims to provide guidance for managing ASF through surveillance, monitoring, and swine repopulation. This study evaluates the effectiveness of post-outbreak disinfection protocols and government-mandated measures for repopulation standard. Surveillance data from three repopulation phases-(I) depopulation, cleaning, and disinfection; (II) downtime (20 days); and (III) sentinel animals (40 days)-were collected from February 2020 to December 2021 in the province of Batangas. Time-to-detection of positive events were analyzed for different farm types, seasons, or location using survival analysis modeling. Probability of detecting infected farms at different sampling times was estimated in terms of sensitivity of the sampling time. Data from 145 swine farms, including 99 backyard and 46 commercial farms, revealed positive rates of 10.1 and 8.7%, respectively. The failure rate during repopulation surveillance was 9.66%, whereas 90.34% farms remained ASF negative. Sensitivity estimate increased from 18-21 to 89% by day 27, with sentinel animals on that day exhibiting the highest estimated sensitivity. This highlights the importance of sentinel pigs in the NASFPCP for effective ASF control in the Philippines. Survival analysis showed no statistically significant differences in the results between either farm type, season, or municipality level. Geographic mapping of surveyed farms and those with positive detections identified high-risk locations including San Juan and Lipa City as key areas of concern. Enhancing targeted surveillance is critical for improving an early ASF detection and national response in the Philippines.

PMID:39717795 | PMC:PMC11663853 | DOI:10.3389/fvets.2024.1468906

Front Immunol. 2024 Dec 9;15:1455334. doi: 10.3389/fimmu.2024.1455334. eCollection 2024.

ABSTRACT

Age-associated differences in the effect of repetitive vaccination, particularly on memory T-cell and B-cell responses, remain unclear. While older adults (aged ≥65 years) exhibited enhanced IgG responses following COVID-19 mRNA booster vaccination, they produced fewer spike-specific circulating follicular helper T cells-1 than younger adults. Similarly, the cytotoxic CD8⁺ T-cell response remained diminished with reduced PD-1 expression even after booster vaccination compared with that in younger adults, suggesting impaired memory T-cell activation in older adults. In contrast, although B-cell responses in older adults were weaker than those in younger adults in the primary response, the responses were significantly enhanced upon booster vaccination, reaching levels comparable with that observed in younger adults. Therefore, while booster vaccination ameliorates impaired humoral immunity in older adults by efficiently stimulating memory B-cell responses, it may less effectively enhance T-cell-mediated cellular immunity. Our study provides insights for the development of effective therapeutic and vaccine strategies for the most vulnerable older population.

PMID:39717779 | PMC:PMC11663736 | DOI:10.3389/fimmu.2024.1455334

Front Immunol. 2024 Dec 9;15:1453703. doi: 10.3389/fimmu.2024.1453703. eCollection 2024.

ABSTRACT

BACKGROUND: Autoimmune diseases pose significant health challenges worldwide and affect millions. In recent years, there has been growing interest in exploring preventive strategies through nutritional interventions using vitamins, antioxidants, and micronutrients to reduce the risk of developing autoimmune diseases. However, excessive supplementation has also been associated with toxicity.

OBJECTIVE: We aim to assess how the intake of vitamins, antioxidants and micronutrients affect the risk of developing autoimmune diseases.

METHODS: This PRISMA-adherent systematic review involved a systematic search of PubMed, Embase and Cochrane for controlled studies that evaluated the risk of incident autoimmune diseases after supplementation. Random effects meta-analyses were used for primary analysis.

RESULTS: 18 studies were included. Overall meta-analyses observed that vitamin D did not influence the risk of autoimmune diseases (RR=0.99, 95%CI: 0.81-1.20). However, among the different vitamin D dosages, subgroup analysis demonstrated that those who were supplemented with 600-800IU/day may have a statistically significant reduction in risk (RR=0.55, 95%CI: 0.38; 0.82). Systematic review suggested that consumption of most vitamins, micronutrients and antioxidants may not have any effect on the risk of autoimmune diseases. Smoking, age, physical or outdoor activity and diet were significant confounding factors that affected the efficacy of such interventions.

CONCLUSION: We studied the effect of various vitamins, micronutrients and antioxidants on the risk of developing autoimmune diseases. Our study contributes to the evolving landscape of nutritional immunology, providing a foundation for future research to unravel more definite relationships with supplementation and the development of incident autoimmune diseases.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42024504796.

PMID:39717776 | PMC:PMC11663920 | DOI:10.3389/fimmu.2024.1453703

Front Oncol. 2024 Dec 9;14:1465334. doi: 10.3389/fonc.2024.1465334. eCollection 2024.

ABSTRACT

INTRODUCTION: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) constitute myeloid malignancies, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered as a potentially optimal approach for achieving a long term cure. However, post-allo-HSCT relapse remains a leading cause of mortality and therapeutic failure.

METHODS: To evaluate the efficacy and safety of combining hypomethylating agents (HMAs) with Bcl-2 inhibitors in the treatment of AML/MDS relapse following allo-HSCT, we retrospectively collected data from 42 patients who experienced relapse between April 2012 and March 2022 at Peking University First Hospital. Among these patients, 21 underwent intensive chemotherapy (IC) alone, while the other 21 received treatment with HMAs after IC treatment, either alone or in combination with the Bcl-2 inhibitor venetoclax (VEN).

RESULTS: The median overall survival (OS) was 9 ± 2.153 months, and the one-year OS rate was 41.5%. The overall response rate (ORR) in the chemotherapy group and the IC+HMAs ± VEN group was 52.38% (11/21) and 76.19% (16/21), respectively, with no significant difference found (P=0.107). Kaplan-Meier analysis revealed a significant difference in OS between the chemotherapy group and the IC+HMAs ± VEN group in our retrospective cohort study (P=0.041, χ2= 4.016). Additionally, a significant difference in overall survival (OS) rates was observed between the two groups for patients categorized as intermediate/high risk (P=0.008). The secondary relapse rate was 45.45% (5/11) in the IC cohort and 25% (4/16) in the IC+HMAs ± VEN group, respectively, with no significant difference identified between the two cohorts (P=0.268). Furthermore, upon assessing the risk of graft-versus-host disease (GvHD), infection, and agranulocytosis, no notable differences were observed with the use of HMAs, suggesting that HMAs did not increase the risk. In the IC+HMAs ± VEN group, 7 patients received VEN in addition to HMAs, and no significant statistical difference was found in OS when comparing patients who received HMAs alone and those who received HMA+VEN (P=0.183), also, a statistically significant difference in OS was noted between the two groups whenaccounting for competing risks (P=0.028).

CONCLUSIONS: This retrospective study highlights the efficacy of IC+HMAs ± VEN in treating AML/MDS patients experiencing relapse post allo-HSCT, improving survival rates, especially for those classified as intermediate/high risk, with favorable tolerability.

PMID:39717745 | PMC:PMC11663890 | DOI:10.3389/fonc.2024.1465334

Ther Adv Musculoskelet Dis. 2024 Dec 22;16:1759720X241295920. doi: 10.1177/1759720X241295920. eCollection 2024.

ABSTRACT

BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory condition that can affect individuals of all ages. Patients may experience a range of physical and psychological issues.

OBJECTIVE: To examine the impact of PsA on an individual’s quality of life (QoL) and physical function.

DESIGN: A systematic review of the literature.

DATA SOURCES AND METHODS: A comprehensive search was conducted across seven electronic databases (Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, AMED, EMBASE, Global Health, MEDLINE and PsycINFO) to retrieve articles related to QoL and lifestyle in adults with PsA. The inclusion criteria were studies published between 2010 and 2021 that used outcomes validated in patients with PsA. The methodological quality was assessed using Joanna Briggs Institute Critical Appraisal Tools. Our primary outcomes were patient-reported outcomes (PROs) measuring QoL and the impact of disease on physical function. The secondary outcomes were assessments of fatigue, anxiety, depression, sleep, work productivity and employment.

RESULTS: The study included 37 comprehensive studies that examined the impact of PsA on QoL and physical function. The findings revealed that the impact of PsA extends to various aspects of life, including activities of daily living, physical, and emotional aspects, such as fatigue, sleep disturbance, anxiety and depression. Notably, people with PsA experience reduced health-related quality of life (HRQoL), particularly in emotional, social and mental health aspects. The severity of pain and/or fatigue is directly linked to decreased HRQoL. Importantly, those who fail to achieve minimal disease activity face challenges in work productivity and employment status.

CONCLUSION: To conclude, our review underscores the significant impact of PsA on patients’ HRQoL beyond joint disease. The emotional, social, and mental aspects of PsA require compassionate and holistic management.

TRIAL REGISTRATION: The PROSPERO international prospective register of systematic reviews – CRD42021257395.

PMID:39717741 | PMC:PMC11664531 | DOI:10.1177/1759720X241295920

Front Plant Sci. 2024 Dec 9;15:1486564. doi: 10.3389/fpls.2024.1486564. eCollection 2024.

ABSTRACT

BACKGROUND: Alfalfa, scientifically identified as Medicago sativa, is repeatedly referred to as the “king of forages”. Because of its tight relationship to winter hardiness, the alfalfa’s root crown plays a significant role as a storage organ over the winter. At present, it is still unknown what molecular process makes the alfalfa root crown resistant to cold. This study was aimed to study these knowledge gaps. Using RNA sequencing (RNA-Seq) technology, significant genes associated with cold hardiness were found.

METHODS: According to the random block design, Longmu 806 alfalfa and Sardi alfalfa were planted in regional experiments. Under the condition of low-temperature treatment in winter, the differentially expressed genes (DEGs), winter survival rate (WSR), and physiological characteristics were, in turn, calculated by RNA-Seq, chemical analysis, and field investigation.

RESULTS: The WSR of the Longmu 806 alfalfa was 3.68-fold greater than that of the Sardi alfalfa. The jasmonic acid (JA), soluble sugar (SS), proline (Pro), and glutathione (GSH) concentration in the roots of Longmu 806 alfalfa was more than the same amount in Sardi alfalfa in other words P is less than 0.05. An entire set of 878 DEGs related to winter hardiness was found by statistical analysis. Among them, 463 DEGs showed an increase in expression, whereas 415 DEGs showed a decrease in expression. The metabolic pathways’ examination presented that the DEGs (MsERF1, MsCHIB, MsJAZ, MsAOC, MsGST, MsINV, MsTPS, and MsOAT) were linked to the pathways of “plant hormone signaling transduction”, “Amino sugar and nucleotide sugar metabolism”, and “glutathione metabolism”. Furthermore, the physiological changes in JA, SS, Pro content, and GSH were influenced by the dynamic transcription profile of LT (low- temperature) resistance-related genes.

PMID:39717732 | PMC:PMC11663680 | DOI:10.3389/fpls.2024.1486564

Virus Evol. 2024 Nov 22;10(1):veae100. doi: 10.1093/ve/veae100. eCollection 2024.

ABSTRACT

Interest in phage therapy-the use of bacterial viruses to treat infections-has increased recently because of the rise of infections with antibiotic-resistant bacteria and the failure to develop new antibiotics to treat those infections. Phages have shown therapeutic promise in recent work, and successful treatment minimally requires giving the patient a phage that will grow on their infecting bacterium. Although nature offers a bountiful and diverse supply of phages, there have been a surprising number of patient infections that could not be treated with phages because no suitable phage was found to kill the patient’s bacterium. Here, we develop computational models to analyze an alternative approach to obtaining phages with new host ranges-directed evolution via laboratory propagation of phages to select mutants that can grow on a new host. The models separately explore alternative directed evolution protocols for phage variants that overcome three types of bacterial blocks to phage growth: a block in adsorption, temperate phage immunity to superinfection, and abortive infection. Protocols assume serial transfer to amplify pre-existing, small-effect mutants that are initially rare. Best protocols are sensitive to the nature of the block, and the models provide several insights for enhancing success specific to each case. A common result is that low dilution rates between transfers are beneficial in reducing the mutant growth rate needed to ascend. Selection to overcome an adsorption block is insensitive to many protocol variations but benefits from long selection times between transfers. A temperate phage selected to grow on its lysogens can evolve in any of three phenotypes, but a common protocol favors the desired changes in all three. Abortive infection appears to be the least amenable to evolving phage growth because it is prone to select phages that avoid infection.

PMID:39717707 | PMC:PMC11665826 | DOI:10.1093/ve/veae100