Oral cancer prediction by noninvasive genetic screening

Oral squamous cell carcinomas (OSCCs) develop in genetically altered epithelium in the mucosal lining, also coined as fields, which are mostly not visible but occasionally present as white oral leukoplakia (OL) lesions. We developed a noninvasive genetic assay using next-generation sequencing (NGS) on brushed cells to detect the presence of genetically altered fields, including those that are not macroscopically visible. The assay demonstrated high accuracy in OL patients when brush samples were compared with biopsies as gold standard. In a cohort of Fanconi anemia patients, detection of mutations in prospectively collected oral brushes predicted oral cancer also when visible abnormalities were absent. We further provide insight in the molecular landscape of OL with frequent changes of TP53, FAT1 and NOTCH1. NGS analysis of noninvasively collected samples offers a highly accurate method to detect genetically altered fields in the oral cavity, and predicts development of OSCC in high-risk individuals. Noninvasive genetic screening can be employed to screen high-risk populations for cancer and precancer, map the extension of OL lesions beyond what is visible, map the oral cavity for precancerous changes even when visible abnormalities are absent, test accuracy of promising imaging modalities, monitor interventions and determine genetic progression as well as the natural history of the disease in the human patient.     

Whole Exome Sequencing Reveals Uncommon Mutations in the Recently Identified Fanconi Anemia Gene SLX4/FANCP

Fanconi anemia (FA) is a rare genetic disorder characterized by congenital malformations, progressive bone marrow failure (BMF), and susceptibility to malignancies. FA is caused by biallelic or hemizygous mutations in one of 15 known FA genes, whose products are involved in the FA/BRCA DNA damage response pathway. Here, we report on a patient with previously unknown mutations of the most recently identified FA gene, SLX4/FANCP. Whole exome sequencing (WES) revealed a nonsense mutation and an unusual splice site mutation resulting in the partial replacement of exonic with intronic bases, thereby removing a nuclear localization signal. Immunoblotting detected no residual SLX4 protein, which was consistent with abrogated interactions with XPF/ERCC1 and MUS81/EME1. This cellular finding did not result in a more severe clinical phenotype than that of previously reported FA‐P patients. Our study additionally exemplifies the versatility of WES for the detection of mutations in heterogenic disorders such as FA.     

Über Ulcus simplex des Dickdarms

Ohne Zusammenfassung     

Trauma und Carcinom

Ohne Zusammenfassung     

The influence of social rank on the susceptibility of rats toMycoplasma arthritidis

Social ranks (A, O, rest) of adult male inbred rats housed in groups of four per cage were determined by repeated observations of their ejaculatory patterns under competitive conditions. Once ranked, they were intravenously infected. Fifteen clinical, hematological, and serological characters were continously observed during 110 days. Body weight reduction, arthritis score, and specific IgG antibody titers were chosen as guideline characteristics and compared between different genotypes and social rank classes. Genotypic differences account for 60–80% of the individual differences and social rank differences account for 0–40% of the individual differences within isogenic animals. Social rank affects the individual genotypes in an opposite way. Rank A males are less susceptible in genotype DA but showed increased susceptibility in genotypes AS. In genotype LEW, influence of social rank on susceptibility to Mycoplasma arthritidiscould not be verified. Specific IgG antibody titers are lower in ranks showing a higher degree of susceptibility.     

Child access to health services during the economic crisis: An Indonesian experience of the safety net program

Child health has been a serious problem in Indonesia for several decades. The prolonged Indonesian economic crisis in 1997 had a tremendous impact on poor children who suffered due to malnutrition. In 1998, the Indonesian government launched a broad social safety net program to protect the poor from becoming poorer. In the health sector this took the form of Jaring Pengaman Sosial Bidang Kesehatan (JPS-BK) or the Social Safety Net in Health Sector program. Adopting the model of health services utilization of Andersen and Newman, I examine the extent to which JPS-BK contributed to better health services for poor children in four provinces, by using a simplified version of Andersen and Newman's model of health services utilization which emphasizes the importance of contextual determinants. Variables used in the study included child outpatient visits, health card possession, household income, and poverty status. Using data sets from the JPS-BK longitudinal study, I compared utilization of health services between baseline data collection at Rounds One and Three, which was taken a year afterward. In addition, I used the Village Potentials data set from the Indonesian Bureau of Statistics and employed factor analysis to raise one variable representing the village/neighborhood developmental level. Basic statistics were used to examine possible changes between study rounds and logistic regression was used to examine the effect of health card possession on child health services utilization. Two significant improvements occurred during the first year of the program: (i) more sick children visited outpatient facilities and (ii) more children lived in households possessing health cards. The JPS-BK increased the "potential access" that was demonstrated by the significant increase in health card possession regardless of the visit, and "realized access" that was demonstrated by the significant increase in child outpatient visits regardless of health card possession. Further research needs to be undertaken to explore the dynamics of outpatient visits and the actual use of health cards.     

Changes of lactate dehydrogenase in corneal edema after cataract surgery treated with trans-corneal oxygenation therapy

AIM: To investigate the changes in levels of the lactate dehydrogenase (LDH) enzyme in corneal edema after cataract surgery with trans-corneal oxygenation therapy. METHODS: This pre-post design study design conducted on 15 patients with corneal edema after cataract surgery and receiving trans-corneal oxygenation therapy. Tear sample (using Schirmer paper, from the inferior fornix of the conjunctiva) was carried out prior to trans-corneal oxygenation therapy, on the day 2 (D2) and day 5 (D5) postoperatively before and after trans-corneal oxygenation therapy. Visual acuity [VA (LogMAR)], corneal endothelial density, central corneal thickness (CCT), and coefficient of variation corneal endothelial (CoV) were recorded. The value of LDH was measured using ELISA. The difference in mean LDH value before and after trans-corneal oxygenation therapy, between two groups were analyzed using Wilcoxon signed rank test. RESULTS: There was a decrease in LDH tear concentration at D2 (pre vs post: 1127.54±497.09 vs 696.91±489.49; P=0.002) and D5 (pre vs post: 1064.17±677.77 vs 780.28±428.95; P=0.027) after trans-corneal oxygenation therapy as well as decrease in LDH concentration on the D2 compared to D5 (P=0.041). The mean CCT was decreased significantly after the administration of trans-corneal oxygenation (pre vs post: 632.10±25.66 vs 563.90±51.54; P=0.005). The mean VA and CoV increased significantly after the administration of trans-corneal oxygenation (P=0.001 and P=0.028, respectively). However, there was no difference in mean of corneal endothelial density (P=0.814). CONCLUSION: Trans-corneal oxygenation therapy is associated with significant decrease of tears LDH levels in post cataract surgery with corneal edema. It is accompanied by clinical improvement such as significant reduction of CCT.