Identification and in silico analysis of noval alteration Arg420Gly in KIT proto oncogene among acute myeloid leukemia patients.

A number of studies have reported frequent incidence of c-kit gene mutations in association with core binding factor acute myeloid leukemia (CBF-AML). These genetic changes have become important prognostic predictors in patients with abnormal karyotype. Aim of this study was the detection of nucleotide alterations in newly diagnosed acute myeloid leukemia patients for three exons of c-kit gene, including cytogenetically normal patients. Thirty-one de novo AML patients were screened for any possible variations in exon 8, 11 and 17 sequences of c-kit proto-oncogene leading to amino acid substitutions or frame shift. Sanger sequencing method was employed followed by sequence analysis. Mutation data was then correlated with clinical and hematological parameters of patients and prognostic significance of genetic changes was assessed as well. The computational tools were then used to further understand the extent of damage caused by these mutations to c-kit protein. Fifteen (48.4%) mutant patients were observed with single, double or multiple mutations in one, two or all three exons studied. The analysis revealed eight new alterations which were not reported previously. Significant variation among mutant and non-mutant group of patients was observed with respect to FAB subtypes (x2 = 12.524, p = 0.029), Spleen size (x2 = 4.288, p = 0.038) and Red blood cell count (x2 = 8.447, p = 0.007). The survival analysis indicates poor overall and event free survival outcomes in mutant individuals. Furthermore, the in silico analysis suggests that changes in nucleotide sequences can possibly damage the protein structure and effect it's function. This study emphasizes the need to consider screening of c-kit gene alterations not only in CBF-AML but in cytogenetically normal AML patients as well. In current investigation the effect of mutation Arg420Gly on structure and function of c-kit protein was investigated, as this was the most observed substitution in present cohort. Various bioinformatics tools and techniques were employed, which determined that Arg420Gly is possibly non-pathogenic mutation.

Forms of Health System Fragmentation During Conflict: The Case of Yemen.

The continuous and protracted conflict in Yemen has evolved into the worst humanitarian situation in modern history. All public structures in the country, including the health system and its basic functions, have been under tremendous pressures. One of the key obstacles to improve the health outcomes in Yemen is fragmentation of the health system. This study aims at exploring and documenting the forms of health system fragmentation in humanitarian and conflict-affected contexts by studying Yemen as a case study. We collected national qualitative data from key informants through in-depth interviews. A pool of respondents was identified from the Ministry of Public Health and Population, donors, and non-governmental organizations. Data were collected between May and June 2019. We interviewed eight key informants and reviewed national health policy documents, and references provided by key informants. Interviews were recorded, transcribed, and analyzed using qualitative content analysis. We further conducted a literature review to augment and triangulate the findings. Six themes emerged from our datasets and analyses, representing various forms of fragmentation: political, structural, inter-sectoral, financial, governance, and health agenda-related forms. Health system fragmentation in Yemen existed before the conflict eruption and has aggravated as the conflict evolves. The humanitarian situation and the collapsing health system enabled the influx of various national and international health actors. In conclusion, the protracted conflict and fragile situation in Yemen have accentuated the fragmentation of the health system. Addressing these fragmentations' forms by all health actors and building consensus on health system agenda are recommended. Health system analysis and in-depth study of fragmentation drivers in Yemen can be beneficial to build common ground and priorities to reduce health system fragmentation. Furthermore, capacity building of a health system is fundamental for the humanitarian development nexus, health system integration, and recovery efforts in the future.