Fifteen new nucleotide substitutions in variants of human papillomavirus 18 in Korea

High-risk human papillomavirus (HPV) infection is an essential factor for the development of cervical cancer. HPV18 is the second most common carcinogenic HPV type following HPV16, but the lineages of HPV18 have been less well studied than those of HPV 16. The purpose of this study was to analyze the nucleotide variants in the E6, E7, and L1 genes of HPV18, to assess the prevalence of HPV18 variants in Korea and to explore the relationship between HPV18 genetic variants and the risk for cervical cancer. A total of 170 DNA samples from HPV18-positive cervical specimens were collected from women admitted to a secondary referral hospital located in Seoul. Among them, the lineages of the 97 samples could be successfully determined by historical nomenclature. All the studied HPV 18 variants were lineage A. Sublineages A1 and A4 comprised 91.7% (89/97) and 1.0% (1/97), respectively. Sublineages other than A1 or A4 comprised 7.2% (7/97). We identified 15 new nucleotide substitutions among 44 nucleotide substitutions: C158T, T317G, T443G, A560G, A5467G, A5560C, A5678C, A6155G, G6462A, T6650G, G6701A, T6809C, A6823G, T6941C and T6953C. Among them, 6 substitutions at positions 317, 443, 5467, 5560, 6462, and 6823 resulted in amino acid changes (E6: F71L and N113K; L1: H13R, H44P, A345T, and N465S, respectively). The pathologic results were classified as normal in 25.8% (25/97) of the women, atypical squamous cells of undermined significance (ASCUS) in 7.2% (7/97), cervical intraepithelial neoplasia (CIN) 1 in 36.1% (35/97), CIN2/3 in 19.6% (18/97), and carcinoma in 12.4% (12/97). There was no significant association between the HPV18 sublineages and the severity of pathologic lesion or the disease progression. This study is the first to analyze the distribution of HPV18 variants in Korean and to associate the results with pathologic findings. Although the HPV18 variants had no significant effect on the degree and progression of the disease, the newly discovered nonsynonymous mutation in L1 might serve as a database to determine vaccine efficacy in Korean women

The Skin Antiseptic agents at Vaginal dElivery (SAVE) trial: study protocol for a randomized controlled trial

Background Cleansing of the vulva and perineum is recommended during preparation for vaginal delivery, and special attention is paid to cleansing before episiotomy because episiotomy is known to increase the risk of perineal wound infection and/or dehiscence. However, the optimal method of perineal cleansing has not been established, including the choice of antiseptic agent. To address this issue, we designed a randomized controlled trial to examine whether skin preparation with chlorhexidine-alcohol is superior to povidone-iodine for the prevention of perineal wound infection after vaginal delivery. Methods In this multicenter randomized controlled trial, term pregnant women who plan to deliver vaginally after episiotomy will be enrolled. The participants will be randomly assigned to use antiseptic agents for perineal cleansing (povidone-iodine or chlorhexidine-alcohol). The primary outcome is superficial or deep perineal wound infection within 30 days after vaginal delivery. The secondary outcomes are the length of hospital stay, physician office visits, or hospital readmission for infection-related complications, endometritis, skin irritations, and allergic reactions. Discussion This study will be the first randomized controlled trial aiming to determine the optimal antiseptic agent for the prevention of perineal wound infections after vaginal delivery. Trial registration ClinicalTrials.gov NCT05122169. First submitted date on 8 November 2021. First posted date on 16 November 202

Expression of nicotinamide N-methyltransferase in hepatocellular carcinoma is associated with poor prognosis

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is the most common tumor in the adult liver, with high relapse and mortality rates despite diverse treatment modalities. In this study, nicotinamide N-methyltransferase (NNMT), a key enzyme in drug metabolism, was investigated as a potential prognostic factor.</p> <p>Methods</p> <p>Frozen tumors and non-cancerous surrounding tissues from 120 patients with primary HCC were studied. Expressions of NNMT and internal control genes were measured by real-time reverse-transcription PCR (RT-PCR). The relationship of NNMT mRNA level with clinicopathologic parameters and clinical outcome was evaluated.</p> <p>Results</p> <p>NNMT mRNA level is markedly reduced in HCCs compared to non-cancerous surrounding tissues (P < 0.0001), and NNMT expression in tumors was significantly correlated with tumor stage (P = 0.010). Moreover, stratification of patients based on tumor NNMT mRNA levels revealed that the patients who expressed higher NNMT mRNA levels tended to have a shorter overall survival (OS) time (P = 0.053) and a significantly shorter disease-free survival (DFS) time (P = 0.016). Both NNMT expression (P = 0.0096) and tumor stage (P = 0.0017) were found to be significant prognostic factors for DFS in a multivariate analysis.</p> <p>Conclusion</p> <p>The results of this study indicated that NNMT gene expression is associated with tumor stage and DFS time in HCC cases. Because of the broad substrate specificity of NNMT, which could alter the efficacy and adverse effects of chemotherapy, NNMT merits further investigation regarding its role as a prognostic factor with a larger cohort of HCC patients.</p

Does radiation therapy increase gadolinium accumulation in the brain?: Quantitative analysis of T1 shortening using R1 relaxometry in glioblastoma multiforme patients

Objective This study evaluated the possibility of accelerated gadolinium accumulation in irradiated brain parenchyma where the blood-brain barrier was weakened. Methods From January 2010 to June 2015, 44 patients with supratentorial glioblastoma were retrospectively identified who underwent pre- and post-radiation brain MR imaging, including R1 mapping. The mean dose of administered gadobutrol (Gadovist, Bayer, Germany) was 5.1 vials. Regions of interest (ROIs) were drawn around tumors that were located within 50- 100% iso-dose lines of maximum radiation dose. ROIs were also drawn at globus pallidus, thalamus, and cerebral white matter. Averages of R1 values (unit: s-1) before and after radiation and those of R1 ratio (post-radiation R1 / pre-radiation R1) were compared by t-test or rank sum test as appropriate. Multiple linear regression analysis was performed to evaluate independent association factors for R1 value increase at irradiated parenchyma. Results The mean R1 values in peri-tumoral areas were significantly increased after radiotherapy (0.7901-0.0977 [mean-SD] vs. 0.8146-0.1064; P <.01). The mean R1 ratio of high radiation dose areas was significantly higher than that of low dose areas (1.0055±0.0654 vs. 0.9882 ±0.0642; P <.01). The mean R1 ratio was lower in those who underwent hypofractionated radiotherapy (mean dose, 45.0 Gy) than those who underwent routine radiotherapy (mean dose, 61.1 Gy) (0.9913±0.0740 vs. 1.0463±0.0633; P = .08). Multiple linear regression analysis revealed that only radiotherapy type was significantly associated with increased R1 (P = .02) around tumors. Conclusions Radiotherapy can induce R1 value increase in the brain parenchyma, which might suggest accelerated gadolinium accumulation due to damage to the blood-brain barrier. © 2018 Lim et al. This is an open ccess article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and eproduction in any medium, provided the original author and source are credite

Allergic rhinitis and rhinosinusitis synergistically compromise the mental health and health-related quality of life of Korean adults: A nationwide population-based survey.

Allergic rhinitis (AR) and rhinosinusitis (RS) negatively impact psychological well-being and health-related quality of life (HRQoL). However, few population-based studies have investigated the effects of these conditions on mental health and HRQoL.To explore independent associations of AR and/or RS with mental health and HRQoL using data from the 2013-2015 Korea National Health and Nutrition Examination Survey (KNHANES).The KNHANES is a nationwide cross-sectional survey of the non-institutionalized population of Korea. A total of 15,441 adults completed the clinical examination and the health questionnaire. We divided all participants into four groups: AR-/RS-, AR-/RS+, AR+/RS-, and AR+/RS+. Logistic regression analyses were performed after adjustment for sociodemographic characteristics, general health behaviors, and other comorbidities.The AR+/RS+ group contained the highest proportion of subjects with perceived stress and depressed mood. Subjects with AR+/RS+ also had more frequent problems in terms of pain/discomfort and anxiety/depression. After adjusting for all confounders, the odds ratios (ORs) were 2.96 (p = 0.009) for depressed mood and 3.17 (p = 0.013) for suicidal ideation in the AR+/RS+ group compared with in the AR-/RS- group. The AR+/RS- group reported more perceived stress (OR, 1.56, p = 0.003) and depression (OR, 1.72, p = 0.024) compared with the AR-/RS- group. In terms of the ORs for HRQoL, the AR+/RS+ group reported more problems in terms of self-care (OR, 3.73, p = 0.038) and more pain/discomfort (OR 2.19, p = 0.006) compared with the AR-/RS- group.In the Korean population, AR and RS exerted a synergistic negative impact on mental health and HRQoL, especially suicidal ideation. Most patients seek help from clinicians for impaired HRQoL. Therefore, clinicians should consider the underlying mental health and HRQoL of patients with AR and/or RS, as these may be impaired by their conditions

Does radiation therapy increase gadolinium accumulation in the brain?: Quantitative analysis of T1 shortening using R1 relaxometry in glioblastoma multiforme patients

<div><p>Objective</p><p>This study evaluated the possibility of accelerated gadolinium accumulation in irradiated brain parenchyma where the blood-brain barrier was weakened.</p><p>Methods</p><p>From January 2010 to June 2015, 44 patients with supratentorial glioblastoma were retrospectively identified who underwent pre- and post-radiation brain MR imaging, including R1 mapping. The mean dose of administered gadobutrol (Gadovist, Bayer, Germany) was 5.1 vials. Regions of interest (ROIs) were drawn around tumors that were located within 50–100% iso-dose lines of maximum radiation dose. ROIs were also drawn at globus pallidus, thalamus, and cerebral white matter. Averages of R1 values (unit: s^-1) before and after radiation and those of R1 ratio (post-radiation R1 / pre-radiation R1) were compared by t-test or rank sum test as appropriate. Multiple linear regression analysis was performed to evaluate independent association factors for R1 value increase at irradiated parenchyma.</p><p>Results</p><p>The mean R1 values in peri-tumoral areas were significantly increased after radiotherapy (0.7901±0.0977 [mean±SD] vs. 0.8146±0.1064; P <.01). The mean R1 ratio of high radiation dose areas was significantly higher than that of low dose areas (1.0055±0.0654 vs. 0.9882±0.0642; P <.01). The mean R1 ratio was lower in those who underwent hypofractionated radiotherapy (mean dose, 45.0 Gy) than those who underwent routine radiotherapy (mean dose, 61.1 Gy) (0.9913±0.0740 vs. 1.0463±0.0633; P = .08). Multiple linear regression analysis revealed that only radiotherapy type was significantly associated with increased R1 (P = .02) around tumors.</p><p>Conclusions</p><p>Radiotherapy can induce R1 value increase in the brain parenchyma, which might suggest accelerated gadolinium accumulation due to damage to the blood-brain barrier.</p></div