Genetic determinants in a critical domain of ns5a correlate with hepatocellular carcinoma in cirrhotic patients infected with hcv genotype 1b

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain‐1 interacts with cellular proteins inducing pro‐oncogenic pathways. Thus, we explore genetic variations in NS5A domain‐1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype‐1b infected DAA‐naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p < 0.001), M133I (20.6% vs. 3.9%, p < 0.001), and Q181E (11.8% vs. 0.6%, p < 0.001). By multivariable analysis, the presence of >1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7–82.3); p < 0.001). Focusing on HCC‐group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4–6.2) log IU/mL vs. 5.3 (4.4–5.6) log IU/mL, p = 0.02) and lower ALT (35 (30–71) vs. 83 (48–108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell‐cycle regulation (p53, p85‐PIK3, and β‐ catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV‐mediated oncogenesis. The role of these NS5A domain‐1 mutations in triggering pro‐oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation

52 Genetic Loci Influencing Myocardial Mass.

BACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. OBJECTIVES: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. METHODS: We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. RESULTS: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. CONCLUSIONS: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets

The neural progenitor-restricted isoform of the MARK4 gene in 19q13.2 is upregulated in human gliomas and overexpressed in a subset of glioblastoma cell lines

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Cephalometric assessment of vertical control in the treatment of class II malocclusion with a combined maxillary splint

Vertical control is one of the primary objectives sought by orthodontists when treating malocclusions in hyperdivergent individuals. This investigation aimed at assessing vertical control, by cephalometric measurements, during the treatment of Angle Class II Division 1 malocclusion. Thirty cases, selected from the files of the São Leopoldo Mandic Dental Research Center, Brazil, of subjects with Angle Class II Division 1 malocclusion and facial hyperdivergence, were used in this study. The patients were treated using a combined extraoral appliance during a mean treatment time of 1.1 years. Pre- and posttreatment cephalometric measurements were compared to assess vertical control. The results were submitted to ANOVA (p = 5%). The ANOVA test revealed no statistically significant difference between the pretreatment and posttreatment values of OP (Occlusal plane angle) and SN.MP. While there was a decrease in Y-axis, FMA, and PP.MP, there was an increase in SN.PP, Co-Go, AFH, PFH, and FHI. It was concluded that the divergence in the facial lower third of the patients did not increase, suggesting that the combined extraoral appliance with the line of force application directed to the resistance center of the maxilla was effective in treating Angle Class II malocclusion in hyperdivergent subjects

Nasolabial angle in finger sucking patients

The purpose of this study is to analise the nasolabial angle and other cephalometric measurements that express the anteroposterior relationship of maxilla and mandibule in individuals with finger sucking habit. Thirty lateral cephalograms were selected from the patient files of the scientific documentation service, Orthodontic Graduation Course of the Piracicaba College of Dentistry, FOP/UNICAMP. The selection criteria was white Brazilian female subjects, 7 to 10 years old, in the phase of mixed dentition, and presenting finger sucking habit. The observed cephalometric measurements were: nasolabial angle, SNA, SNB, ANB, 1.NA, 1-NA and Nperp-A. The results were compared using Student's 't' test and, significance level of 5% (á = 0,05). The analysis showed no differences in the nasolabial angle in subjects presenting finger sucking habit; the maxilla and mandibule was well positioned, relative to the cranial base, and the upper incisors were well positioned

Nasolabial angle in finger sucking patients

pose of this study is to analise the nasolabial angle and other cephalometric measurements that express the anteroposterior relationship of maxilla and mandibule in individuals with finger sucking habit. Thirty lateral cephalograms were selected from the patient files of the scientific documentation service, Orthodontic Graduation Course of the Piracicaba College of Dentistry, FOP/UNICAMP. The selection criteria was white Brazilian female subjects, 7 to 10 years old, in the phase of mixed dentition, and presenting finger sucking habit. The observed cephalometric measurements were: nasolabial angle, SNA, SNB, ANB, 1.NA, 1-NA and Nperp-A. The results were compared using Students t test and, significance level of 5% (á = 0,05). The analysis showed no differences in the nasolabial angle in subjects presenting finger sucking habit; the maxilla and mandibule was well positioned, relative to the cranial base, and the upper incisors were well positioned

Craniofacial analysis of the Tweed Foundation in Angle Class II, division 1 malocclusion

This study has defined the cephalometric values of the Craniofacial Analysis of the Tweed Foundation for a sample of Brazilian subjects. The sample consisted of 211 cephalometric radiographs from subjects aged 12-15, which were divided into two groups: Class II group, with 168 lateral teleradiographs (cephalograms) of white Brazilian subjects, with Angle Class II, division 1 malocclusion, of both genders (82 males and 86 females); and the Control Group, with 43 lateral teleradiographs (cephalograms) of subjects whose occlusion was clinically excellent, and also of both genders (21 males and 22 females). The teleradiographs were selected from the files of the Department of Orthodontics, School of Dentistry of Piracicaba, State University of Campinas, previously to the orthodontic treatment. The results demonstrated no sexual dimorphism for each group, as attested by the Student's t-test. The exploratory analysis (± 0.5 standard deviation) enabled the tolerance limits to be determined and a Craniofacial Analysis Table to be constructed using the respective cephalometric intervals. In addition, the difference between the two groups was not statistically significant according to the maxilla position. The maxilla was in a good position in relation to the cranial base. On the other hand, the mandible was retruded in relation to the cranial base in the Class II cases. The skeletal pattern was not defined because only the Facial Height Index (FHI) showed a vertical pattern in Class II subjects, while the Y Axis, SN.PlO, SN.GoMe and FMA values did not show any statistically significant difference between the groups. The Class II division 1 subjects showed lower incisors more labially tipped and a convex facial profile