Molecular diversity at 18 loci in 321 wild and 92 domesticate lines reveal no reduction of nucleotide diversity during Triticum monococcum (Einkorn) domestication: implications for the origin of agriculture.

The diploid wheat Triticum monococcum L. (einkorn) was among the first crops domesticated by humans in the Fertile Crescent 10,000 years ago. During the last 5,000 years, it was replaced by tetraploid and hexaploid wheats and largely forgotten by modern breeders. Einkorn germplasm is thus devoid of breeding bottlenecks and has therefore preserved in unfiltered form the full spectrum of genetic variation that was present during its domestication. We investigated haplotype variation among >12 million nucleotides sequenced at 18 loci across 321 wild and 92 domesticate T. monococcum lines. In contrast to previous studies of cereal domestication, we sampled hundreds of wild lines, rather than a few dozen. Unexpectedly, our broad sample of wild lines reveals that wild einkorn underwent a process of natural genetic differentiation, most likely an incipient speciation, prior to domestication. That natural differentiation was previously overlooked within wild einkorn, but it bears heavily upon inferences concerning the domestication process because it brought forth 3 genetically, and to some extent morphologically, distinct wild einkorn races that we designate here as alpha, beta, and gamma. Only one of those natural races, beta, was exploited by humans for domestication. Nucleotide diversity and haplotype diversity in domesticate einkorn is higher than in its wild sister group, the einkorn beta race, indicating that einkorn underwent no reduction of diversity during domestication. This is in contrast to findings from previous studies of domestication history among more intensely bred crop species. Taken together with archaeological findings from the Fertile Crescent, the data indicate that a specific wild einkorn race that arose without human intervention was subjected to multiple independent domestication events.

Suprameatal approach: new surgical approach for cochlear implantation.

The conventional technique for cochlear implantation is via a mastoidectomy and posterior tympanotomy. An alternative approach for cochlear implantation is hereto described. The middle ear is entered through a suprameatal approach (SMA) bypassing the mastoid cavity. This surgical approach shortens the duration of the procedure to approximately one hour. The introduction of the cochlear implant electrode array involves drilling in the suprameatal region and the osseous portion of the external auditory canal at a safe distance from the anatomical position of the facial nerve. This prevents possible injury by direct trauma or drill overheating of the chorda tympani or facial nerves. We report 15 consecutive patients who were operated on using the SMA technique. No complications were encountered as a result of this surgical technique but further experience may be necessary.

Phenotype-genotype correlation in familial Mediterranean fever: evidence for an association between Met694Val and amyloidosis.

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent attacks of inflammation of serosal membranes. Amyloidosis is the most severe complication of the disease. The aim of this study was to investigate the genotype-phenotype correlation and specifically the association between amyloidosis and the four common mutations in exon 10 of the gene causing FMF (MEFV) in a total of 83 FMF families from three ethnic groups: North African Jews, Armenians and Turks. A significant association was found between amyloidosis and the specific mutation at the MEFV gene: Met694Val (RR = 1.41, P = 0.02). Amyloidosis was present in 18 out of 87 homozygous FMF patients (20.7%) and in only two out of the 41 compound heterozygous FMF patients (4.9%). No patients carrying other mutations had amyloidosis. There was no significant association between the various mutations and the type or severity of the FMF symptoms. This finding underscores the importance of performing molecular studies on all suspect FMF patients. In addition to providing accurate diagnosis, these tests allow identification of presymptomatic genetically affected individuals, detection of carriers and assessment of the risk for amyloidosis in later life.

Clinical relevance of therapeutic drug monitoring of digoxin and gentamicin in the saliva of children.

Digoxin and gentamicin are widely used in pediatric medicine, and therapeutic monitoring is mandatory because of their narrow margin of safety and wide interpatient and intrapatient pharmacokinetic variabilities. Saliva sampling may be of potential interest, especially in children, in whom blood sampling is often difficult. In 11 children treated with digoxin for various cardiac conditions, and in 24 children treated with gentamicin (14 patients were administered gentamicin three times a day, and 10 once-daily), drugs levels were measured in plasma and saliva. There was no correlation between plasma total or free digoxin concentrations and saliva levels, precluding the clinical use of the saliva test for digoxin. No correlation was found between plasma gentamicin concentrations and saliva levels when the drug was administered three times a day; however, good correlation was found when the drug was administered once-daily (r2 = 0.89, p < 0.0001). Saliva may be used as a noninvasive method of measuring gentamicin serum concentrations to guide dosage adjustments in patients administered the drug once-daily.

Doppler diastolic transmitral flow patterns in severe heart failure: response to controlled changes in filling pressure using intravenous isosorbide dinitrate.

Serial Doppler diastolic transmitral flow patterns were compared with simultaneous hemodynamic measurements in a homogeneous group of patients with severe (New York Heart Association class 4) heart failure who were receiving high dose (508 +/- 271 micrograms/min) intravenous isosorbide dinitrate. The Doppler tracing uniformly showed a severe restrictive pattern, with tall peak early diastolic filling (E) wave (84 +/- 12 cm/s), small late filling (A) wave (28 +/- 8 cm/s) and very high E/A ratio (3.2 +/- 0.8). Isosorbide dinitrate decreased wedge pressure and systemic vascular resistance by a third and increased cardiac index by more than 40%. Transmitral Doppler E/A ratio changed directly in relation to the changes in pulmonary capillary wedge (r = 0.85, p = 0.03) and right atrial pressure (r = 0.84, p = 0.03), indicating preload dependence of transmitral flow velocity, even in severe heart failure.

Persistent painless ST-segment depression after exercise testing and the effect of age.

The relation between the duration of ischemic ST-segment depression (1 mm or more 60 ms after the J point) and the clinical awareness of chest pain was studied in 31 patients (aged 39-73 years) undergoing symptom-limited, graded treadmill exercise testing. The response of these patients to nitrate therapy (spray or sublingual tablet) given immediately on cessation of exercise was also studied. During exercise, angina pectoris appeared at an estimated workload of 4.6 +/- 2.2 metabolic equivalents (METS) (mean +/- SD), and pathological ST-segment depression at 4.9 +/- 1.9 METS (p = NS.) On cessation of exercise, angina disappeared after 3.0 +/- 1.9 min, but ST-segment depression persisted for more than twice as long (6.6 +/- 4.1 min) (p less than 0.0001). The ratio of time to ST-segment recovery/time to relief of pain (a quantitative measure of silent ischemia during recovery) increased with age (r = 0.49, p = 0.002), and in 16 patients over 60 years of age was higher than in 15 younger patients (3.6 +/- 2.5 vs. 2.1 +/- 1.4) (p less than 0.04). The silent ischemia ratio after exercise tended to decrease, although not significantly so (p = 0.2), in patients who received oral nitrates; there was no difference in the response to spray or tablet in this regard. We conclude that ST-segment depression frequently persists after relief of exercise-induced angina pectoris and more so in elderly patients.