Evaluating LINE-1 methylation in cleft lip tissues and its association with early pregnancy exposures

Aim: To pilot investigation of methylation of long interspersed nucleotide element-1 in lip tissues from infants with nonsyndromic cleft lip, and its association with maternal periconceptional exposures. Methods: The lateral and medial sides of the cleft lips of 23 affected infants were analyzed for long interspersed nucleotide element-1 methylation by bisulfite conversion and pyrosequencing. Results: The medial side showed 1.8% higher methylation compared with the lateral side; p = 0.031, particularly in male infants (2.7% difference; p = 0.011) or when the mothers did not take folic acid during periconceptional period (2.4% difference; p = 0.011). These results were not statistically significant when Bonferroni adjustment was used. Conclusion: The observed differences in DNA methylation, although nonsignificant after correction for multiple comparisons, suggest that differential regulation of the two sides may impact lip fusion and warrant larger-scale replication

2023 ESC Guidelines for the management of acute coronary syndromes.

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Deregulation of manganese superoxide dismutase (SOD2) expression and lymph node metastasis in tongue squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Lymph node metastasis is a critical event in the progression of tongue squamous cell carcinoma (TSCC). The identification of biomarkers associated with the metastatic process would provide critical prognostic information to facilitate clinical decision making. Previous studies showed that deregulation of manganese superoxide dismutase (SOD2) expression is a frequent event in TSCC and may be associated with enhanced cell invasion. The purpose of this study is to further evaluate whether the expression level of SOD2 is correlated with the metastatic status in TSCC patients.</p> <p>Methods</p> <p>We first examined the SOD2 expression at mRNA level on 53 TSCC and 22 normal control samples based on pooled-analysis of existing microarray datasets. To confirm our observations, we examined the expression of SOD2 at protein level on an additional TSCC patient cohort (n = 100), as well as 31 premalignant dysplasias, 15 normal tongue mucosa, and 32 lymph node metastatic diseases by immunohistochemistry (IHC).</p> <p>Results</p> <p>The SOD2 mRNA level in primary TSCC tissue is reversely correlated with lymph node metastasis in the first TSCC patient cohort. The SOD2 protein level in primary TSCC tissue is also reversely correlated with lymph node metastasis in the second TSCC patient cohort. Deregulation of SOD2 expression is a common event in TSCC and appears to be associated with disease progression. Statistical analysis revealed that the reduced SOD2 expression in primary tumor tissue is associated with lymph node metastasis in both TSCC patient cohorts examined.</p> <p>Conclusions</p> <p>Our study suggested that the deregulation of SOD2 in TSCC has potential predictive values for lymph node metastasis, and may serve as a therapeutic target for patients at risk of metastasis.</p

Intention Understanding in Autism

When we observe a motor act (e.g. grasping a cup) done by another individual, we extract, according to how the motor act is performed and its context, two types of information: the goal (grasping) and the intention underlying it (e.g. grasping for drinking). Here we examined whether children with autistic spectrum disorder (ASD) are able to understand these two aspects of motor acts. Two experiments were carried out. In the first, one group of high-functioning children with ASD and one of typically developing (TD) children were presented with pictures showing hand-object interactions and asked what the individual was doing and why. In half of the “why” trials the observed grip was congruent with the function of the object (“why-use” trials), in the other half it corresponded to the grip typically used to move that object (“why-place” trials). The results showed that children with ASD have no difficulties in reporting the goals of individual motor acts. In contrast they made several errors in the why task with all errors occurring in the “why-place” trials. In the second experiment the same two groups of children saw pictures showing a hand-grip congruent with the object use, but within a context suggesting either the use of the object or its placement into a container. Here children with ASD performed as TD children, correctly indicating the agent's intention. In conclusion, our data show that understanding others' intentions can occur in two ways: by relying on motor information derived from the hand-object interaction, and by using functional information derived from the object's standard use. Children with ASD have no deficit in the second type of understanding, while they have difficulties in understanding others' intentions when they have to rely exclusively on motor cues

Suppression in Pb-Pb Collisions at the LHC.

The production of the ψ(2S) charmonium state was measured with ALICE in Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV, in the dimuon decay channel. A significant signal was observed for the first time at LHC energies down to zero transverse momentum, at forward rapidity (2.5<y<4). The measurement of the ratio of the inclusive production cross sections of the ψ(2S) and J/ψ resonances is reported as a function of the centrality of the collisions and of transverse momentum, in the region p_{T}<12  GeV/c. The results are compared with the corresponding measurements in pp collisions, by forming the double ratio [σ^{ψ(2S)}/σ^{J/ψ}]_{Pb-Pb}/[σ^{ψ(2S)}/σ^{J/ψ}]_{pp}. It is found that in Pb-Pb collisions the ψ(2S) is suppressed by a factor of ∼2 with respect to the J/ψ. The ψ(2S) nuclear modification factor R_{AA} was also obtained as a function of both centrality and p_{T}. The results show that the ψ(2S) resonance yield is strongly suppressed in Pb-Pb collisions, by a factor of up to ∼3 with respect to pp. Comparisons of cross section ratios with previous Super Proton Synchrotron findings by the NA50 experiment and of R_{AA} with higher-p_{T} results at LHC energy are also reported. These results and the corresponding comparisons with calculations of transport and statistical models address questions on the presence and properties of charmonium states in the quark-gluon plasma formed in nuclear collisions at the LHC

C-Kit expression, angiogenesis, and grading in canine mast cell tumour: a unique model to study C-Kit driven human malignancies

Canine cutaneous mast cell tumour (CMCT) is a c-Kit driven tumour sharing similar c-Kit aberrations found in human gastrointestinal stromal tumour. CMCT is classified into three forms: well-(G1), intermediately (G2) (more benign diseases), and poorly (G3) differentiated (malignant) forms. We assess a correlation between c-Kit status, grading, and angiogenesis in CMCTs to explore their potential significance in humans. C-Kit receptor (c-KitR) expression, microvascular density (MVD), and mast cell granulated and degranulated status density (MCGD and MCDD, resp.) were analyzed in 97 CMCTs, by means of histochemistry, immunohistochemistry double staining, and image analysis system. Data showed that predominantly diffuse cytoplasmic-and predominantly focal paranuclear-(Golgi-like) c-Kit protein (PDC-c-Kit and PFP-c-Kit, resp.) expression correlate with high MVD, G3 histopathological grade, and MCDD. Moreover, predominant cellmembrane-c-KitR (PCM-c-KitR) expression status correlates with low MVD, G1-G2 histopathological grade, and MCGD. These findings underline the key role of c-Kit in the biopathology of canine MCTs, indicating a link between aberrant c-Kit expression, increased angiogenesis, and higher histopathological grade. CMCT seems to be a model to study contributions of c-Kit activated MCs in tumour angiogenesis and to evaluate the inhibition of MCs activation by means of c-Kit tyrosine kinase inhibitors, currently translated in humans