Genetic aberration analysis in thai colorectal adenoma and early-stage adenocarcinoma patients by whole-exome sequencing

Colorectal adenomas are precursor lesions of colorectal adenocarcinoma. The transition from adenoma to carcinoma in patients with colorectal cancer (CRC) has been associated with an accumulation of genetic aberrations. However, criteria that can screen adenoma progression to adenocarcinoma are still lacking. This present study is the first attempt to identify genetic aberrations, such as the somatic mutations, copy number variations (CNVs), and high-frequency mutated genes, found in Thai patients. In this study, we identified the genomic abnormality of two sample groups. In the first group, five cases matched normal-colorectal adenoma-colorectal adenocarcinoma. In the second group, six cases matched normal-colorectal adenomas. For both groups, whole-exome sequencing was performed. We compared the genetic aberration of the two sample groups. In both normal tissues compared with colorectal adenoma and colorectal adenocarcinoma analyses, somatic mutations were observed in the tumor suppressor gene APC (Adenomatous polyposis coli) in eight out of ten patients. In the group of normal tissue comparison with colorectal adenoma tissue, somatic mutations were also detected in Catenin Beta 1 (CTNNB1), Family With Sequence Similarity 123B (FAM123B), F-Box And WD Repeat Domain Containing 7 (FBXW7), Sex-Determining Region Y-Box 9 (SOX9), Low-Density Lipoprotein Receptor-Related Protein 5 (LRP5), Frizzled Class Receptor 10 (FZD10), and AT-Rich Interaction Domain 1A (ARID1A) genes, which are involved in the Wingless-related integration site (Wnt) signaling pathway. In the normal tissue comparison with colorectal adenocarcinoma tissue, Kirsten retrovirus-associated DNA sequences (KRAS), Tumor Protein 53 (TP53), and Ataxia-Telangiectasia Mutated (ATM) genes are found in the receptor tyrosine kinase-RAS (RTK–RAS) signaling pathway and p53 signaling pathway, respectively. These results suggest that APC and TP53 may act as a potential screening marker for colorectal adenoma and early-stage CRC. This preliminary study may help identify patients with adenoma and early-stage CRC and may aid in establishing prevention and surveillance strategies to reduce the incidence of CRC

Observational study investigating the relationship between maxillomandibular characteristics and temporomandibular disc conditions in female patients with a skeletal class III pattern

OBJECTIVES: The objective of this study was to analyze the relationship between maxillomandibular characteristics and the severity of temporomandibular disc displacement in female patients with a skeletal class III (SKIII) pattern. METHODS: Fifty-seven samples were included in the study. The evaluation of articular disc conditions was conducted using magnetic resonance imaging, while 25 cephalometric variables from lateral and postero-anterior (P-A) cephalograms were measured to determine their maxillomandibular characteristics. The samples were categorized into three groups based on the articular disc conditions: (1) normal disc position (NDP), (2) disc displacement with reduction (DDwR), and (3) disc displacement without reduction (DDwoR). The relationship between the maxillomandibular characteristics and disc conditions was examined through both basic statistical analysis and multivariate analysis using principal component analysis (PCA). RESULTS: The Kruskal–Wallis and Dunn–Bonferroni tests revealed a significant difference between the groups in terms of the deviation of mandibular characteristics observed on the P-A cephalogram. The DDwoR group exhibited significantly larger menton deviation, ramal height asymmetry index, and total mandibular length asymmetry index compared to the NDP and DDwR groups. Moreover, the PCA successfully extracted all cephalometric variables into eight principal components. Among them, only the principal component related to mandibular asymmetry was able to differentiate the SKIII samples with DDwoR from the other groups. CONCLUSIONS: The findings of this study highlight a significant relationship between mandibular asymmetry and the severity of disc displacement, particularly DDwoR, in female patients with a SKIII pattern

Duration of Hepatitis B Vaccine-Induced Protection among Medical Students and Healthcare Workers following Primary Vaccination in Infancy and Rate of Immunity Decline

Since the introduction of hepatitis B virus (HBV) vaccines, the numbers of HBV infections and complications have significantly decreased. However, the evidence on whether primary vaccination of infants confers lifelong immunity varies. We aimed to assess long-term immunity among healthcare workers and medical students, and the rate of decline of HBV surface antigen antibodies (anti-HBs). Hepatitis B status among participants born after 1 January 1992 was reviewed at Chulabhorn Royal Academy, Thailand. Participants were stratified by intervals since primary vaccination. HBV immunity was determined and analyzed as anti-HBs decline rate in participants with multiple follow-ups. A total of 464 participants were analyzed, with a median age of 23. Protective immunity against HBV (anti-HBs ≥ 10 mIU/mL) at 16–20, 21–25 and 26–28 years post-primary vaccination was 28%, 51.7% and 60%, respectively. The overall declining rate of anti-HBs was −42.39 mIU/mL per year. Participants with anti-HBs levels of >100–1000 mIU/mL at baseline had a faster decline rate than those with anti-HBs levels of 10–100 mIU/mL. Primary vaccination may not provide lifelong protection since HBV immunity deteriorates over time. Individuals with higher initial HBV immunity levels may experience a faster decline rate

Association of MTHFR Polymorphisms and Chromosomal Abnormalities in Leukemia

Genetic variation in MTHFR gene might explain the interindividual differences in the reduction of DNA repaired and the increase of chromosome breakage and damage. Nowadays, chromosomal rearrangement is recognized as a major cause of lymphoid malignancies. In addition, the association of MTHFR polymorphisms with aneuploidy was found in several studies, making the MTHFR gene as a good candidate for leukemia etiology. Therefore, in this study, we investigated the common sequence variation, 677C>T and 1298A>C in the MTHFR gene of 350 fixed cell specimens archived after chromosome analysis. The distribution of the MTHFR polymorphisms frequency was compared in leukemic patients with structural chromosome abnormality and chromosome aneuploidy, as well as in those with no evidence of chromosome abnormalities. We observed a significant decrease in the distribution of T allele in 677C>T polymorphisms among patients with chromosomal abnormalities including both structural aberration and aneuploidy. The same significance result also found in patients with structural aberration when compare with the normal karyotype patients. Suggesting that polymorphism in the MTHFR gene was involved in chromosome abnormalities of leukemia. However, further investigation on the correlation with the specific types of chromosomal aberrations is needed

Immunogenicity and reactogenicity after heterologous prime-boost vaccination with CoronaVac and ChAdox1 nCov-19 (AZD1222) vaccines

Mass vaccination with a safe and effective vaccine may be the best way to control the COVID-19 pandemic. Heterologous prime-boost vaccination with the CoronaVac and AZD1222 vaccines may increase the immunogenicity elicited by either vaccine alone. This study sought to compare the immunogenicity of a heterologous CoronaVac and AZD1222 prime-boost with a homologous CoronaVac prime-boost. From July 13 to September 2, 2021, 88 participants were enrolled in the study. Half (n = 44) of the participants were assigned to the AZD1222/CoronaVac cohort and half were assigned to the CoronaVac/AZD1222 cohort. Both cohorts had a prime-boost interval of 4 weeks. A control group of 136 health care personnel who received the homologous CoronaVac/CoronaVac prime-boost was matched by age and sex to the experimental cohorts. The primary endpoint was the geometric mean ratio (GMR) of the anti-receptor binding domain (RBD) antibody concentration 4 weeks after the booster dose was administered. The CoronaVac/CoronaVac cohort served as the reference group. Baseline age and sex were similar, and the median age was 42.5 years. The GMR was 2.58 (95% confidence interval [CI] 1.80–3.71) and 8.69 (95% CI 6.05–12.47) in the AZD1222/CoronaVac and CoronaVac/AZD1222 cohorts, respectively. Reactogenicity was similar following prime and booster doses with the same vaccine. Findings indicated that the heterologous CoronaVac and AZD1222 prime-boost combination elicited a more robust immune response than the homologous CoronaVac prime-boost. While both heterologous prime-boost combinations showed similar reactogenicity, the immunogenicity of the CoronaVac/AZD1222 cohort was higher, indicating that the order of prime-boost vaccine administration was important

Effect of Corticosteroid on Immunogenicity of SARS-CoV-2 Vaccines in Patients With Solid Cancer

PURPOSECorticosteroids are known to diminish immune response ability, which is generally used in routine premedication for chemotherapy. The intersecting of timeframe between the corticosteroid's duration of action and peak COVID-19 vaccine efficacy could impair vaccine immunogenicity. Thus, inquiring about corticosteroids affecting the efficacy of vaccines to promote effective immunity in this population is needed.METHODSThis was a prospective longitudinal observational cohort study that enrolled patients with solid cancer classified into dexamethasone- and nondexamethasone-receiving groups. All participants were immunized with two doses of ChAdOx1 nCoV-19 or CoronaVac vaccines. This study's purpose was to compare corticosteroid's effect on immunogenicity responses to the SARS-CoV-2 S protein in patients with cancer after two doses of COVID-19 vaccine in the dexamethasone and nondexamethasone group. Secondary outcomes included the postimmunization anti–spike (S) immunoglobin G (IgG) seroconversion rate, the association of corticosteroid dosage, time duration, and immunogenicity level.RESULTSAmong the 161 enrolled patients with solid cancer, 71 and 90 were in the dexamethasone and nondexamethasone groups, respectively. The median anti–S IgG titer after COVID-19 vaccination in the dexamethasone group was lower than that in the nondexamethasone group with a statistically significant difference (47.22 v 141.09 U/mL, P = .035). The anti–S IgG seroconversion rate was also significantly lower in the dexamethasone group than in the nondexamethasone group (93.83% v 80.95%, P = .023). The lowest median anti–SARS-CoV-2 IgG titer level at 7.89 AU/mL was observed in patients with the highest dose of steroid group (≥37 mg of dexamethasone cumulative dose throughout the course of chemotherapy [per course]) and patients who were injected with COVID-19 vaccines on the same day of receiving dexamethasone, 25.41 AU/mL.CONCLUSIONPatients with solid cancer vaccinated against COVID-19 disease while receiving dexamethasone had lower immunogenicity responses than those who got vaccines without dexamethasone. The direct association between the immunogenicity level and steroid dosage, as well as length of duration from vaccination to dexamethasone, was observed

Safety after BBIBP-CorV (Sinopharm) COVID-19 Vaccine in Adolescents Aged 10–17 Years in Thailand

Coronavirus disease 2019 affected child health and impacted learning because of the resulting onsite school closures. This prospective cohort study included children aged 10–17 who received two 4 µg doses of BBIBP-CorV administered intramuscularly 21–28 days apart. To assess vaccine safety, 36,808 participants were then followed with paper- and web-based online questionnaire surveys that captured local and systemic reactogenicities following vaccine administration on days 1, 7, and 30. Among participants, 76% (27,880) reported reactogenicity within the first 24 h and 7 days following the first dose. Half (51.41%) of participants experienced pain at the injection site; the majority of cases were mild in severity. Injection site tenderness (37.93%) was another common local reaction. Fatigue (37.89%), myalgia (33.56%), and headache (26.76%) were the most common systemic reactions. On days 2–7 after the first dose, 25.85% of participants experienced adverse reactions. Following the second dose, reactogenicity was 7.6% and 1.09% within 24 h and between days 2–7. The majority of reactions were of mild to moderate severity. We report that two doses of the BBIBP-CorV caused mild to moderate side effects in adolescents in Thailand. The findings confirm the vaccine’s safety profile in this age group