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Background: Ketogenic compounds derived from medium chain triglyceride (MCT) oils have been claimed to have beneficial health effects in the Alzheimer's disease (AD] mainly attributed to its medium chain triglycerides. AD is known to have been characterized by early and region specific decline in cerebral glucose metabolism. It is hypothesized that Alzheimer brain tends to preferentially utilize ketones generated from medium chain triglycerides in light of decreased glucose metabolism to improve cognition. Extra virgin coconut oil with predominance of MCT content was used in subjects with moderate to severe AD to examine its efficacy in improving cognitive performance. Methods: Daily oral administration of extra virgin coconut oil (20 gm) was evaluated in 31 subjects with predominantly moderate to severe AD diagnosed as per DSM IV TR criteria for AD in a 6 week trial using quasi experimental non randomized pre-post intervention design. Subjects were on a normal diet and continued taking approved AD medications. Primary cognitive end points were mean change from baseline in the AD Assessment Scale-Cognitive subscale [ADAS-Cog], and Clinicians Interview based Impression of Change Plus Caregivers input [CIBIC-Plus]. Active oil administration continued for 4 weeks from baseline with successive ratings on measures of cognitive change at 2, 4 and 6 weeks respectively. Results: There was a significant difference between the ADAS-Cog scores from baseline over repeated ratings at 2, 4 and 6 weeks (Mauchly's Chi Square Χ2 = 61.1, ε=0.4, F =14, p=0.00, η2=0.31). Post hoc comparisons of ADAS-Cog scores from baseline at 4 and 6 weeks were similar [At 4 weeks, Mean difference=4.1, P=0.00, C.I= (1.4-6.7); at 6 weeks, Mean difference=4.1, p=0.00, C.I= (1.0-7.2). The response rate of CIBIC-Plus defined as improved or no change was significantly improved over successive ratings from 2 weeks to 6 weeks (Cochran's Q=22.5, df=2, P=.00). No statistically significant difference could be noted for the total cholesterol, Triglycerides and LDL fractions over the study trial except for the HDL fraction over repeated measures at 4 and 6 weeks over baseline (Mauchly's Chi Square Χ2 (df=2)=6.5, ε=0.8, F (df 1.6, 49.9)=6.4, p=0.005, η2=0.17). Conclusions: Addition of adjunctive coconut oil is likely to have beneficial effects in cognitive performance for those suffering from moderate to severe AD and the effects were sustained for at least 2 weeks after the oil administration stopped. No deleterious effects on the overall lipid profile could be elicited.

Background: Non-small cell lung carcinoma (NSCLC) incidence and progression is increasing because of genetic and epigenetic changes. The mutations in the Kirsten rat sarcoma (KRAS) are the most frequently oncogene aberrations in lung carcinoma patients. A candidate tumor suppressor gene (TSG) Ras Association Domain Family 1 Isoform A (RASSF1A), is silenced by promoter hypermethylation in several human malignancies including nonsmall cell lung carcinoma (NSCLC). We hypothesized that RASSF1A methylation and KRAS mutations may play an important role in NSCLC. Methods: Non-small cell lung carcinoma patients (n ¼ 100) and equal number of healthy controls were assessed for activating KRAS (exon 2) mutations using allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) and promoter hypermethylation of RASSF1A using methylation specific PCR. Results: The frequency of mutations in Kirsten rat sarcoma (KRAS) were found in 31% of NSCLC patients in the Kashmiri population and occur most commonly, but not exclusively, in adenocarcinoma histology and life-long smokers. The NSCLC patients in advanced stage reported the higher frequency of mutation in KRAS (exon 2). A significant higher frequency of this mutation was reported in patients with NSCLC (29.16%) who are positive for metastasis (P < 0.03). The frequencies of promoter hypermethylation at Ras Association Domain Family 1 Isoform A (RASSF1A) were 41% in cases and 3% in control samples. The frequency of KRAS mutation and RASSF1A promoter methylation were significantly different between adenocarcinomas (ADC) and squamous cell carcinomas (SCC) patients with NSCLC (P < 0.03). In addition, we reported that NSCLC patients having RASSF1A promoter methylation was significantly associated with smoking (P ¼ 0.01). It was identified that NSCLC patients with RASSF1A promoter region hypermethylation had poorer survival and faster disease progression compared with those without hypermethylation of RASSF1A promoter region (P ¼ 0.0001). The Median survivals among with cases containing promoter region hypermethylation of RASSF1A were 17.20 and 42.13 months for patients without promoter region hypermethylation of RASSF1A and the patients with KRAS mutation with or without hypermethylation of the promoter region of RASSF1A a tumor suppressor gene had poorer survival compared with those patients with wild type KRAS gene, with or without hypermethylation of RASSF1A promoter region. These differences were statistically significant based on Log-rank (Mantel-cox) test (P ¼ 0.0001). The median survivals among patients with mutation in KRAS protooncogene were 16 months and 42 months for NSCLC patients with wild type KRAS gene. Conclusions: The aberrant RASSF1A gene promoter methylation with the subsequent mutation in KRAS gene (exon 2) plays a significant role in the pathogenesis and disease progression of non-small cell lung carcinoma (NSCLC).

Background: The gene associated with the CAD disease was found out to be the HFE (High Iron Fe) gene and the disease is described with the two, missense mutations of the gene-C282Y and H63D. The focus of this study was to assess the C282Y mutation in CAD patients that results from transition of guanine to adenine (G-A) at the nucleotide position 845, which in turn changes cysteine to tyrosine at the 282 nd position.

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