Glycomics-based serum markers as reliable tool for assessment of viral response after treatment with direct-acting antiviral drugs in hepatitis C virus infection.

OBJECTIVES: Patients with chronic hepatitis C virus (HCV) infection have a genuine risk of developing liver fibrosis and cirrhosis, potentially resulting in hepatocellular carcinoma (HCC), a risk that remains even after sustained viral response (SVR). Glycomics-based biomarkers are an attractive tool to closely monitor these patients during and after antiviral treatment, as alterations in the abundance of N-glycans reflect an altered state of the liver. This study assessed serum glycomics for the evaluation of inflammation-related fibrosis regression during and after treatment of HCV with DAAs. METHODS: The GlycoFibroTest and GlycoCirrhoTest were analyzed in the sera 36 HCV-infected patients with advanced fibrosis (F3) or established cirrhosis (F4), before (week 0), during (week 12) and after (week 24) a twelve-week oral administration of DAAs therapy - using an optimized glycomic technology on a DNA sequencer. RESULTS: All patients achieved SVR after treatment and two of them developed HCC in the subsequent five years. A significant decrease of the GlycoFibroTest (p < 0.0001) was seen after 12 weeks, consistent with other measured biomarkers (APRI, FIB-4, FibroTest). Statistical analysis was performed in IBM SPSS Statistics version 28.0, using the non-parametric Friedman's test with a statistical significance α level of 0.05. CONCLUSION: This study suggests that the GlycoFibroTest is a serum biomarker for viral response in HCV patients. The rapid decrease of the glycomics-based biomarker probably reflects the amelioration of liver inflammation as underlying process, rather than the improvement of liver fibrosis itself.

Neural correlates of pantomiming familiar and unfamiliar tools: action semantics versus mechanical problem solving?

This study aims to reveal the neural correlates of planning and executing tool use pantomimes and explores the brain's response to pantomiming the use of unfamiliar tools. Sixteen right-handed volunteers planned and executed pantomimes of equally graspable familiar and unfamiliar tools while undergoing fMRI. During the planning of these pantomimes, we found bilateral temporo-occipital and predominantly left hemispheric frontal and parietal activation. The execution of the pantomimes produced additional activation in frontal and sensorimotor regions. In the left posterior parietal region both familiar and unfamiliar tool pantomimes elicit peak activity in the anterior portion of the lateral bank of the intraparietal sulcus--A region associated with the representation of action goals. The cerebral activation during these pantomimes is remarkably similar for familiar and unfamiliar tools, and direct comparisons revealed only few differences. First, the left cuneus is significantly active during the planning of pantomimes of unfamiliar tools, reflecting increased visual processing of the novel objects. Second, executing (but not planning) familiar tool pantomimes showed significant activation on the convex portion of the inferior parietal lobule, a region believed to serve as a repository for skilled object-related gestures. Given the striking similarity in brain activation while pantomiming familiar and unfamiliar tools, we argue that normal subjects use both action semantics and function from structure inferences simultaneously and interactively to give rise to flexible object-to-goal directed behavior.

Intrapancreatic accessory spleen mimicking pancreatic NET: can unnecessary surgery be avoided?

Pancreatic nodules are frequently found incidentally and often pose a diagnostic and therapeutic challenge when surgery is considered. We present the case of a 66-year-old cirrhotic patient with a pancreatic nodule with signal intensity and contrast enhancement pattern suggestive for a non-functional neuroendocrine lesion. A 68Gallium-DOTATOC PET-CT scan revealed a correspondent focal tracer uptake in the pancreatic tail. After distal pancreatectomy, the specimen surprisingly revealed intrapancreatic splenic tissue. Nuclear imaging has previously been reported to produce a false-positive result for the presence of a neuroendocrine tumor when an intrapancreatic accessory spleen is present. This case reminds us of the diagnostic pitfalls in pancreatic nodules, to consider a broad differential diagnosis and to remain critical before referring the patient for surgery.

Human left ventral premotor cortex mediates matching of hand posture to object use.

Visuomotor transformations for grasping have been associated with a fronto-parietal network in the monkey brain. The human homologue of the parietal monkey region (AIP) has been identified as the anterior part of the intraparietal sulcus (aIPS), whereas the putative human equivalent of the monkey frontal region (F5) is located in the ventral part of the premotor cortex (vPMC). Results from animal studies suggest that monkey F5 is involved in the selection of appropriate hand postures relative to the constraints of the task. In humans, the functional roles of aIPS and vPMC appear to be more complex and the relative contribution of each region to grasp selection remains uncertain. The present study aimed to identify modulation in brain areas sensitive to the difficulty level of tool object - hand posture matching. Seventeen healthy right handed participants underwent fMRI while observing pictures of familiar tool objects followed by pictures of hand postures. The task was to decide whether the hand posture matched the functional use of the previously shown object. Conditions were manipulated for level of difficulty. Compared to a picture matching control task, the tool object - hand posture matching conditions conjointly showed increased modulation in several left hemispheric regions of the superior and inferior parietal lobules (including aIPS), the middle occipital gyrus, and the inferior temporal gyrus. Comparison of hard versus easy conditions selectively modulated the left inferior frontal gyrus with peak activity located in its opercular part (Brodmann area (BA) 44). We suggest that in the human brain, vPMC/BA44 is involved in the matching of hand posture configurations in accordance with visual and functional demands.