Tacrolimus intra-patient variability measures and its associations with allograft clinical outcomes in kidney transplantation.

AIMS: Tacrolimus (Tac) is commonly prescribed in solid organ transplantation to prevent immune-mediated damage to the graft. However, its pharmacokinetics show substantial variability between and within patients. Intra-patient variability of tacrolimus (Tac-IPV) has emerged as a novel marker to predict transplant outcomes. Numerous studies report varying associations between Tac-IPV and clinical outcomes, with Tac-IPV measures showing wide discrepancies among these studies. This inconsistency could be a significant factor that influences the various outcomes reported in different studies. Our review comprehensively assesses the relationship between various Tac-IPV measures and their associations with clinical outcomes in transplant patients. METHODS: A comprehensive literature search was conducted using the PubMed and Embase databases, covering the period from 2004 to March 31, 2023. The search focused on studies that examined the relationship between Tac-IPV and clinical outcomes in kidney transplantation (KT). The inclusion criteria were specific to studies addressing Tac-IPV, including measures such as standard deviation (SD), coefficient of variation (CV), time-weighted coefficient of variability (CV), mean absolute deviation (MAD), and Tac variability score (TVS). Clinical outcomes included the development of de novo donor-specific antibodies (dnDSA), rejection episodes, graft loss, and graft failure. RESULTS: Among the 33 studies that met the inclusion criteria, a notable proportion presented conflicting findings in their assessment of various Tac-IPV measures regarding dnDSA, rejection episodes, graft loss, and graft failure. CONCLUSIONS: Most studies have identified a correlation between high Tac-IPV and poor clinical outcomes; however, this relationship is multifactorial. Influencing factors include the metabolic status of KT patients, the timing of Tac-IPV calculations, and the criteria for defining high and low Tac-IPV thresholds, including the size and selection method. CV, MAD, and TWCV are the metrics that are most frequently used to determine Tac-IPV. Additionally, most of the methods for establishing Tac-IPV thresholds typically employ receiver operating characteristic (ROC) curves and median values. It is also notable that studies examining the clinical significance of Tac-IPV often include tacrolimus levels measured six months after kidney transplantation.

Analysis of the clinical and epidemiologic characteristics of 644 children with dental trauma / 中国学校卫生

Objective@#The clinical data involving pediatric dental trauma and the features of dental trauma in children were summarized to provide a reference for the treatment and prevention of dental trauma.@*Methods@#A retrospective analysis was performed on 644 children with dental trauma who were admitted to the Department of Children s Stomatology, Stomatology Hospital of Xiamen Medical College from January to December 2022. Descriptive methods were used to analyze the general demographic characteristics of the children and clinical features of dental trauma.@*Results@#The characteristics of the children with dental trauma were as follows: male-to-female ratio, 2.16∶1; mean age, (6.73±3.42) years; most frequently affected age groups, 2-4 and 7-9 years (26.09%, 33.85%); most frequent season for dental trauma, spring (27.61%) and autumn (28.55%); least common season for dental trauma, summer(18.88%); most frequent time of day for dental trauma, evening (51.47%); least common time of day for dental trauma, morning (2.68%); >24 h elapsed from dental trauma-to-treatment (42.08%); most common type of injuries; simple tooth hard tissue and pulp injury in permanent teeth(65.25%) and simple periodontal tissue injury of primary teeth( 53.35 %); most likely teeth involved, maxillary central incisors (80.10%); and number of affected teeth, 1-2.@*Conclusions@#The incidence of dental trauma in children has common features, but most children do not see a dentist timely after dental trauma occurs. Educating parents of children with dental trauma should be encouraged to reduce the incidence of dental injury.

RGD-directed 24 nm micellar docetaxel enables elevated tumor-liver ratio, deep tumor penetration and potent suppression of solid tumors.

Nanomedicines while showing a great potential in improving the performance of chemotherapeutics like docetaxel (DTX) are distressed by a high liver deposition and poor tumor penetration, which might not only cause liver toxicity but also moderate therapeutic effect. Herein, we report that cRGD-directed 24 nm disulfide-crosslinked micellar docetaxel (cRGD-MDTX) presents low liver accumulation, high tumor uptake, and deep tumor penetration, leading to the potent suppression of different solid tumors. cRGD-MDTX was optimized with a cRGD density of 4% and DTX loading of 10 wt%. Interestingly, cRGD-MDTX enabled an extraordinary tumor-liver ratio of 2.8/1 with a DTX uptake of 8.3 %ID/g in αvß3 over-expressing PC3 prostate tumor. The therapeutic studies demonstrated striking antitumor effects of cRGD-MDTX toward PC3 prostate tumor, prostate cancer patient-derived xenografts (PDX), orthotopic A549-Luc lung cancer and orthotopic SKOV3-Luc ovarian tumor models, in which tumor growth was effectually inhibited and 6-8 times better improvement of median survival time over free DTX was observed. This small disulfide-crosslinked micellar drug capable of relegating liver deposition opens a new avenue to nanomedicines for targeted therapy.

Artificial intelligence-based diagnosis of Alzheimer's disease with brain MRI images.

Alzheimer's disease, a primary neurodegenerative condition, predominantly impacts the elderly and pre-elderly population. This progressive neurological disorder is characterized by an array of symptoms including memory loss, cognitive decline, and various physiological and psychological disturbances, significantly compromising the quality of life of patients and their caregivers. Recent advancements in Magnetic Resonance Imaging (MRI) technology have catalyzed research in AI-enhanced diagnostics for Alzheimer's disease, fostering optimism for early detection and timely interventions. This progress has paved the way for the development of sophisticated algorithms and models adept at analyzing complex brain imaging data, thereby augmenting diagnostic accuracy and efficiency. This advancement fuels optimism regarding the transformative potential of AI-driven diagnostics in revolutionizing Alzheimer's disease management, with the prospect of facilitating more effective treatment strategies and improved patient outcomes. The objective of this review is to provide a comprehensive overview of recent developments in deep learning methodologies applied to brain MRI images for the classification of various stages of Alzheimer's disease, with a particular emphasis on early diagnosis. Furthermore, this review underscores the limitations of current research, discussing potential challenges and future research directions in this dynamic field.

LPCGF and EDTA conditioning of the root surface promotes the adhesion, growth, migration and differentiation of periodontal ligament cells.

BACKGROUND: Liquid-phase concentrated growth factor (LPCGF), a new-generation platelet concentrate, may potently stimulate human periodontal ligament (PDL) cells. This study assessed the effectiveness of ethylenediaminetetraacetic acid (EDTA) and/or LPCGF on periodontally diseased root surfaces through their effects on PDL cells. METHODS: Dentin blocks prepared from periodontal teeth were divided into four groups and treated as follows: group I, scaling and root planning (SRP); group II, SRP + EDTA; group III, SRP + LPCGF; and group IV, SRP+EDTA + LPCGF. PDL cells were cultured on dentin blocks, and LPCGF-induced biological effects were evaluated by migration and cell adhesion/proliferation assays. Furthermore, PDL cell differentiation was assessed by real-time polymerase chain reaction (PCR). RESULTS: Significantly more adherent cells were observed in the EDTA, LPCGF and combination treatment groups than in the control group. Root conditioning with EDTA and/or LPCGF enhanced cell proliferation and migration more than SRP did. Compared with the control group, the combined treatment group exhibited significant upregulation of cell differentiation-related genes. Electron microscopy of the tooth surface revealed removal of the smear layer and exposed dentin holes in the EDTA-treated group but not in the control group. CONCLUSION: EDTA and LPCGF application to periodontitis-affected root surfaces forms a surface suitable for cell attachment, growth, migration and differentiation. Thus, LPCGF is promising in clinical periodontics applications. Further studies to support these results are necessary.