Ketogenic Diet and Inflammation: Implications for Mood and Anxiety Disorders.

The ketogenic diet, known as a low-carbohydrate, high-protein, and high-fat diet, drastically restrains the major source of energy for the body, forcing it to burn all excess fat through a process called ketosis-the breaking down of fat into ketone bodies. First suggested as a medical treatment for children suffering from epilepsy, this diet has gained increased popularity as a rapid weight loss strategy. Over the past few years, there have been numerous studies suggesting that the ketogenic diet may provide therapeutic effects for several psychiatric conditions such as mood- and anxiety-related disorders. However, despite significant progress in research, the mechanisms underlying its therapeutic effects remain largely unexplored and are yet to be fully elucidated. This chapter provides an in-depth overview of preclinical and clinical evidence supporting the use of a ketogenic diet in the management of mood and anxiety disorders and discusses its relationship with inflammatory processes and potential mechanisms of actions for its therapeutic effects.

Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer.

CONTEXT: The accurate identification and interpretation of germline mutations in mismatch repair genes in colorectal cancer cases is critical for clinical management. Current data suggest that mismatch repair mutations are highly heterogeneous and that many mutations are not detected when conventional DNA sequencing alone is used. OBJECTIVE: To evaluate the potential of conversion analysis compared with DNA sequencing alone to detect heterogeneous germline mutations in MLH1, MSH2, and MSH6 in colorectal cancer patients. DESIGN, SETTING, AND PARTICIPANTS: Multicenter study with patients who participate in the Colon Cancer Family Registry. Mutation analyses were performed in participant samples determined to have a high probability of carrying mismatch repair germline mutations. Samples from a total of 64 hereditary nonpolyposis colorectal cancer cases, 8 hereditary nonpolyposis colorectal cancer-like cases, and 17 cases diagnosed prior to age 50 years were analyzed from June 2002 to June 2003. MAIN OUTCOME MEASURES: Classification of family members as carriers or noncarriers of germline mutations in MLH1, MSH2, or MSH6; mutation data from conversion analysis compared with genomic DNA sequencing. RESULTS: Genomic DNA sequencing identified 28 likely deleterious exon mutations, 4 in-frame deletion mutations, 16 missense changes, and 22 putative splice site mutations. Conversion analysis identified all mutations detected by genomic DNA sequencing--plus an additional exon mutation, 12 large genomic deletions, and 1 exon duplication mutation--yielding an increase of 33% (14/42) in diagnostic yield of deleterious mutations. Conversion analysis also showed that 4 of 16 missense changes resulted in exon skipping in transcripts and that 17 of 22 putative splice site mutations affected splicing or mRNA transcript stability. Conversion analysis provided an increase of 56% (35/63) in the diagnostic yield of genetic testing compared with genomic DNA sequencing alone. CONCLUSIONS: The data confirm the heterogeneity of mismatch repair mutations and reveal that many mutations in colorectal cancer cases would be missed using conventional genomic DNA sequencing alone. Conversion analysis substantially increases the diagnostic yield of genetic testing for mismatch repair mutations in patients diagnosed as having colorectal cancer.

Quark and lepton masses from Gaussian landscapes.

The flavor structure of the standard model (SM) might arise from random selection on a landscape. We propose a class of simple models, "Gaussian landscapes," where Yukawa couplings derive from overlap integrals of Gaussian wave functions on extra-dimensions. Statistics of vacua are generated by scanning the peak positions of these zero-modes, giving probability distributions for all flavor observables. Gaussian landscapes can account for all observed flavor patterns with few free parameters. Although they give broad probability distributions, the predictions are correlated and accounting for measured parameters sharpens the distributions of future neutrino measurements.