Accurately understanding prognosis is associated with fewer preferences for life-sustaining treatments and is correlated with both patient and institutional characteristics. Interventions should be developed to improve accurate prognostic understanding, thus facilitating informed EOL-care decisions that may limit the use of aggressive interventions.

Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsy-associated ion channel genes and their mutations are systematically reviewed. In this paper, we analyzed the genotypes, functional alterations (funotypes), and phenotypes of these mutations. Eleven genes featured loss-of-function mutations and six had gain-of-function mutations. Nine genes displayed diversified funotypes, among which a distinct funotype-phenotype correlation was found in SCN1A. These data suggest that the funotype is an essential consideration in evaluating the pathogenicity of mutations and a distinct funotype or funotype-phenotype correlation helps to define the pathogenic potential of a gene.

Epileptic encephalopathies comprise a group of catastrophic epilepsies with heterogeneous genetic etiology. Although next-generation sequencing techniques can reveal a number of de novo variants in epileptic encephalopathies, evaluating the pathogenicity of these variants can be challenging. Determining the pathogenic potential of genes in epileptic encephalopathies is critical before evaluating the pathogenicity of variants identified in an individual. We reviewed de novo variants in epileptic encephalopathies, including their genotypes and functional consequences. We then evaluated the pathogenic potential of genes, with the following additional considerations: (1) recurrence of variants in unrelated cases, (2) information of previously defined phenotypes, and (3) data from genetic experimental studies. Genes related to epileptic encephalopathy revealed pathogenicity with distinct functional alterations, i.e., either a gain of function or loss of function in the majority; however, several genes warranted further study to confirm their pathogenic potential. Whether a gene was associated with distinct phenotype, the genotype (or functional alteration)--phenotype correlation, and quantitative correlation between genetic impairment and phenotype severity were suggested to be specific evidence in determining the pathogenic role of genes. Data from epileptic encephalopathy-related genes would be helpful in outlining guidelines for evaluating the pathogenic potential of genes in other genetic disorders.

To explore factors affecting human papillomavirus (HPV) prevalence in all grades of cervical neoplasia among Chinese women, 1,264 women with abnormal cervical cytology attending the gynaecologic clinics of 11 major medical centres in Taiwan. Patients were interviewed and underwent complete gynaecologic examination including colposcopy. Cervical scrapings were collected for HPV DNA detection by both Hybrid Capture-2 (high-risk probe) and L1 consensus PCR-reverse line blot. The prevalences of HPV in the four different diagnosis groups: (i) suspicious (n = 316), (ii) low-grade intraepithelial lesion (n = 474), (iii) high-grade intraepithelial lesion (n = 450), and (iv) cancer (n = 16), were 36.1%, 74.7%, 83.6%, and 100%, respectively. In the latter two groups, Patients less than 30 or 40 years old, respectively, tended to be infected more frequently with HPV than the older patients were. The main correlates of HPV prevalence were lifetime number of sex partners (odds ratio (OR) for two or more partners: 2.44; 95% CI, 1.44-4.15), vaginal douching after intercourse (OR for douching frequently: 1.44; 95% CI, 1.01-2.04), vitamin supplementation (OR for regular vitamin supplement: 0.71, 95% CI, 0.55-0.92), and performance of Pap smear tests (OR for never having a Pap smear performed: 2.22; 95% CI, 1.19-4.17). The risk for vaginal douching was augmented by the promiscuity of sex partners (OR of 3.19 (1.91-5.34)) and smoking (OR of 1.90 (1.15-3.13)), whereas vitamin supplementation reduced the odds ratio to 1.35 (0.85-2.15). The results of this study provide further evidence of the role of HPV in cervical carcinogenesis. The data also indicate the main areas of risk for the prevalence of HPV in cervical neoplasia in Chinese women living in Taiwan.