Decreased levels of brain-derived neurotrophic factor (BDNF) are assumed to play a crucial role in the pathophysiology of mild neurocognitive disorders (MNCDs). In this study, we compared plasma BDNF levels (at baseline and after two months of treatment with escitalopram) in patients with the main types of MNCDs and normal controls. 21 patients met the DSM-5 diagnostic criteria for possible MNCD due to Alzheimer's disease (MNCD-AD); 22 patients fulfilled the diagnostic criteria for subcortical vascular MNCD (ScVMNCD) according to Frisoni et al. (2002) and neuroimaging-supported probable diagnosis of vascular MNCD according to DSM-5; 16 subjects entered control group. At baseline, we detected lower BDNF levels in both MNCD groups, which was significant only in subjects with MNCD-AD. Moreover, plasma BDNF level of 21160 pg/mL showed high sensitivity (94%) to discriminate patients with MNCD-AD. Decreased plasma BDNF highly correlated with the severity of memory impairment and total MMSE score in MNCD-AD group. Escitalopram treatment in patients with MNCD-AD or ScVMNCD led to an increase of plasma BDNF concentrations and as a result to a decrease of cognitive, depressive, and anxiety symptom severity. In conclusion, plasma BDNF might be a reliable biomarker for the validation of MNCD-AD diagnosis and treatment efficacy.
Background. Identification of patients at risk for kidney allograft (KAG) failure beyond the first posttransplant year is an unmet need. We aimed to determine whether serum beta-2-microglobulin (β2MG) in the late posttransplant period could predict a decline in KAG function. Methods. We assessed a value of single measurement of serum β2MG at one to seventeen years after transplantation in predicting the estimated glomerular filtration rate (eGFR) and the decline in eGFR over a period of two years in 79 recipients of KAG. Results. At baseline serum β2MG concentration was higher (P = 0.011) in patients with allograft dysfunction: 8.67 ± 2.48 µg/mL versus those with satisfactory graft function: 6.67 ± 2.13 µg/mL. Higher β2MG independently predicted the lower eGFR, the drop in eGFR by ≥25% after one and two years, and the value of negative eGFR slope. When combined with proteinuria and acute rejection, serum β2MG had excellent power in predicting certain drop in eGFR after one year (AUC = 0.910). In conjunction with posttransplant time serum β2MG had good accuracy in predicting certain eGFR drop after two years (AUC = 0.821). Conclusions. Elevated serum β2MG in the late posttransplant period is useful in identifying patients at risk for rapid loss of graft function.
Background Hepatocellular carcinoma (HCC) is a fatal disease characterized by early genetic alterations in telomerase reverse transcriptase promoter (TERTp) and β-catenin (CTNNB1) genes and immune cell activation in the tumor microenvironment. As a novel approach, we wanted to assess patient survival influenced by combined presence of mutations and densities of CD8+ cytotoxic T cells. Methods Tissue samples were obtained from 67 HCC patients who had undergone resection. We analysed CD8+ T cells density, TERTp mutations, rs2853669 polymorphism, and CTNNB1 mutations. These variables were evaluated for time to recurrence (TTR) and disease free survival (DFS). Results TERTp mutations were found in 75.8% and CTNNB1 mutations in 35.6% of the patients. TERTp mutations were not associated with survival but polymorphism rs2853669 in TERTp was associated with improved TTR and DFS. CTNNB1 mutations were associated with improving TTR. High density of CD8+ T-lymphocytes in tumor center and invasive margin correlated with longer TTR and DFS. Combined genetic and immune factors further improved survival showing higher predictive values. E.g., combining CTNNB1 mutations and high density of CD8+ T-lymphocytes in tumor center yielded HRs of 0.12 (0.03–0.52), p = 0.005 for TTR and 0.25 (0.09–0.74), p = 0.01 for DFS. Conclusion The results outline a novel integrative approach for prognostication through combining independent predictive factors from genetic and immune cell profiles. However, larger studies are needed to explore multiple cell types in the tumor microenvironment.
Only a fraction of specimens under study are usually selected for quantification in histology. Multilevel sampling or tissue probes, slides and fields of view (FOVs) in the regions of interest (ROIs) are required. In general, all parts of the organs under study should be given the same probability to be taken into account; that is, the sampling should be unbiased on all levels. The objective of our study was to provide an overview of the use of virtual microscopy in the context of developing sampling strategies of FOVs for stereological quantification. We elaborated this idea on 18 examples from
Colorectal cancer (CRC) is the third most common cancer worldwide, and metastatic CRC is a fatal disease. The CRC-affected tissues show several molecular markers that could be used as a fresh strategy to create newer methods of treating the condition. The liver and the peritoneum are where metastasis occurs most frequently. Once the tumor has metastasized to the liver, peritoneal carcinomatosis is frequently regarded as the disease’s final stage. However, nearly 50% of CRC patients with peritoneal carcinomatosis do not have liver metastases. New diagnostic and therapeutic approaches must be developed due to the disease’s poor response to present treatment choices in advanced stages and the necessity of an accurate diagnosis in the early stages. Many unique and amazing nanomaterials with promise for both diagnosis and treatment may be found in nanotechnology. Numerous nanomaterials and nanoformulations, including carbon nanotubes, dendrimers, liposomes, silica nanoparticles, gold nanoparticles, metal-organic frameworks, core-shell polymeric nano-formulations, and nano-emulsion systems, among others, can be used for targeted anticancer drug delivery and diagnostic purposes in CRC. Theranostic approaches combined with nanomedicine have been proposed as a revolutionary approach to improve CRC detection and treatment. This review highlights recent studies, potential, and challenges for the development of nanoplatforms for the detection and treatment of CRC.
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