Particularities of Electrophysiological and Psychoneurological Assessment of Mild Traumatic Brain Injury

Neuropsychological functioning after mTBI is individualized and dynamic, with no currently known predictors and usually having a trajectory of gradual improvement. It is still a challenge to identify specific cognitive profiles associated with mTBI. One of the causes is the transient character of TBI symptoms as they are not appearing immediately after the injury. Another explanation resides in the individual and group variability of cognitive impairements following mTBI, which also affects the standardisation of the neuropsychological tests to use in mTBI assessment batteries (Iverson et al., 2013; Prince & Bruhns, 2017; Tulsky et al., 2017). Presently concussion has no accepted definition or diagnostic criteria. Also, there is no standard (or gold standard) for screening or properly identifying and diagnosing all population with concussion. (Borg et al., 2004). Patients with mTBI could evolve in a bunch of physical, cognitive, and emotional symptoms (Permenter et al., 2021) that are usually known as post-concussion syndrome (PCS). In terms of symptoms, we target neuropsychological evaluation of four key domains (“higher-order attention”, “executive function”, “episodic memory”, and “speed of information processing”) implicated in chronic impairment after mTBI. Alternatively, studies on the EEG frequency domain shed new light on the possibility to have a diagnostic marker based on QEEG patterns identified in the mTBI population and some prognostic factors for the PCS syndrome.(Rapp et al., 2015; Thornton & Carmody, 2009). Given the particularities of neuropsychological functioning after mTBI we emphasize the need of a mixed methodology, using both electrophysiological and psychoneurological tools, to provide the best sensitivity and specificity in assessing cognitive and functional deficits and in predicting further PCS.

CpG Island Methylator Phenotype—A Hope for the Future or a Road to Nowhere?

The CpG island methylator phenotype (CIMP) can be regarded as the most notable emanation of epigenetic instability in cancer. Since its discovery in the late 1990s, CIMP has been extensively studied, mainly in colorectal cancers (CRC) and gliomas. Consequently, knowledge on molecular and pathological characteristics of CIMP in CRC and other tumour types has rapidly expanded. Concordant and widespread hypermethylation of multiple CpG islands observed in CIMP in multiple cancers raised hopes for future epigenetically based diagnostics and treatments of solid tumours. However, studies on CIMP in solid tumours were hampered by a lack of generalisability and reproducibility of epigenetic markers. Moreover, CIMP was not a satisfactory marker in predicting clinical outcomes. The idea of targeting epigenetic abnormalities such as CIMP for cancer therapy has not been implemented for solid tumours, either. Twenty-one years after its discovery, we aim to cover both the fundamental and new aspects of CIMP and its future application as a diagnostic marker and target in anticancer therapies.

Serum exosomal miR-451a acts as a candidate marker for pancreatic cancer

Objectives The aim of this study was to explore the diagnostic efficiency of serum exosomal miR-451a as a novel biomarker for pancreatic cancer. Methods Serum samples were collected prior to treatment. First, we analyzed microRNA (miRNA) profiles in serum exosomes from eight pancreatic cancer patients and eight healthy volunteers. We then validated the usefulness of the selected exosomal miRNAs as biomarkers in another 191 pancreatic cancer patients, 95 pancreatic benign disease (PB) patients, and 90 healthy controls. Results The expression of miR-451a in serum-derived exosomes from pancreatic cancer patients was significantly upregulated compared with those from PB patients and healthy individuals. Serum exosomal miR-451a showed excellent diagnostic power in identifying pancreatic cancer patients. In addition, exosomal miR-451a showed a significant association with clinical stage and distant metastasis in pancreatic cancer, and the expression level of serum exosomal miR-451a was sensitive to therapy and relapse. Conclusions Serum exosomal miR-451a might serve as a novel diagnostic marker for pancreatic cancer.

lncRNA PCAT14 Is a Diagnostic Marker for Prostate Cancer and Is Associated with Immune Cell Infiltration

Objective. To investigate the relationship between the long noncoding RNA (lncRNA) Prostate cancer-associated transcription factors 14 (PCAT14) and the clinical characteristics of prostate cancer and immune cell infiltration. Methods. The relationship between PCAT14 expression and the clinicopathological characteristics of prostate cancer was analyzed based on The Cancer Genome Atlas (TCGA) database. Receiver operating characteristic (ROC) curves were used to evaluate the value of PCAT14 as a diagnostic marker for prostate cancer. The relationship between PCAT14 and immune cell infiltration was analyzed to explore the effect of PCAT14 on the immune-related functions of prostate cancer. Results. The ROC curve showed that PCAT14 had a significant diagnostic ability ( area under curve = 0.818 ) for prostate cancer. A reduced expression of PCAT14 in prostate cancer was related to T stage, N stage, primary therapy outcome, residual tumor, Gleason score, and age. The expression of PCAT14 was independently associated with the progression-free interval in prostate cancer patients. The infiltration of immune cells in prostate cancer showed a significant negative correlation between the expression of PCAT14 and plasmacytoid dendritic cells, activated dendritic cells, regulatory T cells, and neutrophils. Conclusions. PCAT14 is highly expressed in prostate cancer and is expected to be a diagnostic marker. PCAT14 might promote the development of prostate cancer through chemokines, antimicrobials, and cytokines that affect the infiltration of immune cells.

SATB2 and MDM2 Immunoexpression and Diagnostic Role in Primary Osteosarcomas of the Jaw

Primary osteosarcomas of the jaw (OSJ) are rare, accounting for 6% of all osteosarcomas. This study aims to determine the value of SATB2 and MDM2 immunohistochemistry (IHC) in differentiating OSJ from other jawbone mimickers, such as benign fibro-osseous lesions (BFOLs) of the jaw or Ewing sarcoma of the jaw. Certain subsets of osteosarcoma harbor a supernumerary ring and/or giant marker chromosomes with amplification of the 12q13–15 region, including the murine double-minute type 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) genes. Special AT-rich sequence-binding protein 2 (SATB2) is an immunophenotypic marker for osteoblastic differentiation. Cases of OSJ, BFOLs (ossifying fibroma and fibrous dysplasia) of the jaw, and Ewing sarcoma of the jaw were retrieved from the Departments of Oral Pathology and Oral Medicine, Faculty of Dentistry, Obafemi Awolowo University and Lagos State University College of Medicine, Nigeria. All OSJ retrieved showed histologic features of high-grade osteosarcoma. IHC for SATB2 (clone EP281) and MDM2 (clone IF2), as well as fluorescence in situ hybridization (FISH) for MDM2 amplification, were performed on all cases. SATB2 was expressed in a strong intensity and diffuse staining pattern in all cases (11 OSJ, including a small-cell variant, 7 ossifying fibromas, and 5 fibrous dysplasias) except in Ewing sarcoma, where it was negative in neoplastic cells. MDM2 was expressed in a weak to moderate intensity and scattered focal to limited diffuse staining pattern in 27% (3/11) of cases of OSJ and negative in all BFOLs and the Ewing sarcoma. MDM2 amplification was negative by FISH in interpretable cases. In conclusion, the three cases of high-grade OSJs that expressed MDM2 may have undergone transformation from a low-grade osteosarcoma (LGOS). SATB2 is not a dependable diagnostic marker to differentiate OSJ from BFOLs of the jaw; however, it could serve as a valuable diagnostic marker in differentiating the small-cell variant of OSJ from Ewing sarcoma of the jaw, while MDM2 may be a useful diagnostic marker in differentiating OSJ from BFOLs of the jaw, especially in the case of an LGOS or high-grade transformed osteosarcoma.

Circulating miR-147b as a diagnostic marker for patients with bacterial sepsis and septic shock

Background Early diagnosis, precise antimicrobial treatment and subsequent patient stratification can improve sepsis outcomes. Circulating biomarkers such as plasma microRNAs (miRNAs) have proven to be surrogates for diagnosis, severity and case management of infections. The expression of four selected miRNAs (miR-146-3p, miR-147b, miR-155 and miR-223) was validated for their prognostic and diagnostic potential in a clinically defined cohort of patients with sepsis and septic shock. Methods The expression of plasma miRNAs was quantified by quantitative PCR (qPCR) in patients with bacterial sepsis (n = 78), in patients with septic shock (n = 52) and in patients with dengue haemorrhagic fever (DHF; n = 69) and in healthy controls (n = 82). Results The expression of studied miRNA was significantly increased in patients with bacterial sepsis and septic shock. The plasma miR-147b was able to differentiate bacterial sepsis from non-sepsis and septic shock (AUC = 0.77 and 0.8, respectively, p≤ 0.05), while the combination of plasma miR-147b and procalcitonin (PCT) predicted septic shock (AUC = 0.86, p≤ 0.05). Conclusions The plasma miR-147b may be an useful biomarker independently or in combination with PCT to support clinical diagnosis of sepsis and equally prognosis of patients with septic shock.