How to make stone soup: Is the "Paleo diet" a missed opportunity for anthropologists?

For the past few years, people everywhere have been "going Paleo." Websites and social media touting the benefits of eating a "Paleo diet" and following a "Paleolithic life style" serve as calls to arms for health-conscious individuals seeking information about the latest health and fitness trends. Many of these people participate in programs such as Crossfit, which involve major social and life-style modification components and therefore facilitate the dissemination of dietary fads.1 The PALEOf(x)TM conference, which bills itself as "the world's premier holistic wellness event," has attracted sellout crowds of thousands of attendees for the last four years.2 Consumers can wear Paleo clothing, download Paleo shopping and exercise apps to their smartphones, order prepackaged Paleo food, prepare it using Paleo cooking implements, or expediently buy Paleo convenience foods from Paleodiet™ vending machines3 and "Cultured Caveman" food trucks.4 The Paleo diet is touted by movie stars, reality TV personalities, and professional athletes, including LeBron James and the entire Miami Dolphins NFL team.5,6 Books with titles such as The Primal Blueprint,7 Cavewomen Don't Get Fat,8 and Paleo Perfected9 (the latter by the stodgy America's Test Kitchen) are legion, and many are bestsellers.

Accuracy and radiation dose reduction of a limited abdominopelvic CT in the diagnosis of acute appendicitis.

PURPOSE: To determine the accuracy and radiation dose reduction of a limited abdominopelvic CT from the bottom of T10 to the top of the pubic symphysis in patients with suspected acute appendicitis. METHODS: We performed a HIPAA compliant and IRB-approved retrospective study of adult patients who underwent CT abdomen/pelvis for suspected appendicitis. The Z-axis length and whole body effective doses of the original full scan and theoretical limited scan from the bottom of T10 to the top of the pubic symphysis were recorded. Images were reviewed to determine if the appendix or entire cecum would be visualized and if any cases of appendicitis or alternative diagnoses would be missed with the limited scan. RESULTS: 235 patients (89 male, mean age 44.6 years) were included. The limited scan resulted in a mean Z-axis length reduction of 5.1 cm superiorly, 6.1 cm inferiorly, and a total reduction of 11.2 cm (24%). The mean whole body effective dose was 11.8 and 9.1 mSv for the original and limited scans, respectively (23% reduction). The entire appendix or cecum was visualized in all cases. Appendicitis was present in 24 cases and an alternative diagnosis was made in 75. No cases of appendicitis or alternative diagnoses were missed using the limited scan. CONCLUSIONS: A limited range CT from the bottom of T10 to the top of the pubic symphysis is as accurate as full abdominopelvic CT in evaluating patients with suspected acute appendicitis and results in approximately 23% dose reduction.

Variation in genes related to cochlear biology is strongly associated with adult-onset deafness in border collies.

Domestic dogs can suffer from hearing losses that can have profound impacts on working ability and quality of life. We have identified a type of adult-onset hearing loss in Border Collies that appears to have a genetic cause, with an earlier age of onset (3-5 years) than typically expected for aging dogs (8-10 years). Studying this complex trait within pure breeds of dog may greatly increase our ability to identify genomic regions associated with risk of hearing impairment in dogs and in humans. We performed a genome-wide association study (GWAS) to detect loci underlying adult-onset deafness in a sample of 20 affected and 28 control Border Collies. We identified a region on canine chromosome 6 that demonstrates extended support for association surrounding SNP Chr6.25819273 (p-value = 1.09 × 10(-13)). To further localize disease-associated variants, targeted next-generation sequencing (NGS) of one affected and two unaffected dogs was performed. Through additional validation based on targeted genotyping of additional cases (n = 23 total) and controls (n = 101 total) and an independent replication cohort of 16 cases and 265 controls, we identified variants in USP31 that were strongly associated with adult-onset deafness in Border Collies, suggesting the involvement of the NF-κB pathway. We found additional support for involvement of RBBP6, which is critical for cochlear development. These findings highlight the utility of GWAS-guided fine-mapping of genetic loci using targeted NGS to study hereditary disorders of the domestic dog that may be analogous to human disorders.

Unrecognized Potent Activities of Colistin Against Clinically Important mcr+ Enterobacteriaceae Revealed in Synergy with Host Immunity.

Colistin (COL) is a cationic cyclic peptide that disrupts negatively-charged bacterial cell membranes and frequently serves as an antibiotic of last resort to combat multidrug-resistant Gram-negative bacterial infections. Emergence of the horizontally transferable plasmid-borne mobilized colistin resistance (mcr) determinant and its spread to Gram-negative strains harboring extended-spectrum ß-lactamase and carbapenemase resistance genes threatens futility of our chemotherapeutic arsenal. COL is widely regarded to have zero activity against mcr+ patients based on standard antimicrobial susceptibility testing (AST) performed in enriched bacteriological growth media; consequently, the drug is withheld from patients with mcr+ infections. However, these standard testing media poorly mimic in vivo physiology and omit host immune factors. Here we report previously unrecognized bactericidal activities of COL against mcr-1+ isolates of Escherichia coli (EC), Klebsiella pneumoniae (KP), and Salmonella enterica (SE) in standard tissue culture media containing the physiological buffer bicarbonate. Moreover, COL promoted serum complement deposition on the mcr-1+ Gram-negative bacterial surface and synergized potently with active human serum in pathogen killing. At COL concentrations readily achievable with standard dosing, the peptide antibiotic killed mcr-1+ EC, KP, and SE in freshly isolated human blood proved effective as monotherapy in a murine model of mcr-1+ EC bacteremia. Our results suggest that COL, currently ignored as a treatment option based on traditional AST, may in fact benefit patients with mcr-1+ Gram negative infections based on evaluations performed in a more physiologic context. These concepts warrant careful consideration in the clinical microbiology laboratory and for future clinical investigation of their merits in high risk patients with limited therapeutic options.

The story of life: critical insights from evolutionary biology.

The notion that humans, in all their complexity, are merely an evolutionary accident, an insignificant speck in a boundless cosmos, is deeply unsatisfying for most nonscientists and fails to resonate with their life experience. What, then, can evolutionary biology ultimately tell us about the meaning of our lives? In conversation with Steve Paulson, executive producer and host of To the Best of Our Knowledge, paleoanthropologists Melanie Lee Chang and Ian Tattersall, and paleontologist Simon Conway Morris share their insights on these competing concepts and explain how meaning and purpose can be gleaned from the remarkable story of life itself.

Large-scale SNP genotyping with canine buccal swab DNA.

The dog is an attractive model for genetic studies of complex disease. With drafts of the canine genome complete, a large number of single-nucleotide polymorphisms (SNPs) that are potentially useful for gene-mapping studies and empirical estimations of canine diversity and linkage disequilibrium (LD) are now available. Unfortunately, most canine SNPs remain uncharacterized, and the amount and quality of DNA available from population-based samples are limited. We assessed how these real-world challenges influence automated SNP genotyping methods such as Illumina's GoldenGate assay. We examined 384 SNPs on canine chromosome 9 and successfully genotyped a minimum of 217 and a maximum of 275 SNPs using buccal swab samples for 181 dogs (86 beagles, 76 border collies, and 15 Australian shepherds). Call rates per SNP and sample averaged 97%, with reproducibility within and between analyses averaging 98%. The majority of these SNPs were polymorphic across all 3 breeds. We observed extensive LD, albeit less than reported for surveys using fewer dogs, consistent between breeds. Analyses of population substructure indicated that beagles are distinct from border collies and Australian shepherds. These results demonstrate the suitability of amplified canine buccal samples for high-throughput multiplex genotyping and confirm extensive LD in the dog.