A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies—a whole-genome assembly and a regional chromosome assembly—were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional ∼12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

This pilot study investigating the genetics of the bitter taste receptor T2R38 in the context of primary sinonasal surgery demonstrates supertaster patients are less likely to need surgical intervention for chronic rhinosinusitis. Additional study is necessary to ascertain postsurgical outcomes.

Objective Patients with diabetes mellitus (DM) are known to be liable to infection. However, the association between diabetes and chronic rhinosinusitis (CRS) has not been well studied. We sought to determine the effects of DM on CRS culture results and quality of life (QOL) after functional endoscopic sinus surgery (FESS). Methods We conducted a retrospective cohort study. Adult CRS patients undergoing FESS were recruited from 10/1/2007 to 12/31/2011. Patient demographics, comorbidities, medication use, Lund-Mackay CT scores were collected prior to FESS. Intraoperative culture was obtained. Preoperative and 1-, 3- and 6-month postoperative QOL was measured by the 22 item Sinonasal Outcome Test (SNOT-22) scores. A mixed effects model was performed for analysis. Results Among the 376 CRS patients included, 19 patients (5.05%) had DM. Compared to non-DM patients, DM patients were significantly more likely to have Pseudomonas aeruginosa (26.32% versus 7.56%, p=0.004) and gram negative rods (26.32% vs. 8.96%, p= 0.013), but there were no significant difference in the prevalence of Staphylococcus aureus; DM patients were also significantly more likely to have nasal polyps and gastroesophageal reflux disease. Additionally, DM patients had significantly less improvement of postoperative SNOT-22 scores from baseline to 6-month follow-up than non-DM patients (adjusted mean=11.14, 95% CI (0.14, 22.15), p=0.047) after adjusting for all the other risk factors for CRS. Conclusion DM patients may be prone to gram negative bacterial sinus infections, and have significantly worse short-term postoperative QOL. Special postoperative care may need to be considered in CRS patients with DM

SUMMARY Hypothyroid ism has been known to be associated, at times, with diastolic hypertension. We have found in 40 thyrotoxic patients that the induction of hypothyroid ism by radioiodine therapy significantly increased diastolic blood pressure, raising it above 90 mm Hg in 16 (40%) of the patients. Restoration of euthyroidism with thyroxine administration significantly reduced the systolic and diastolic blood pressures in these patients, with a fall in diastolic pressure below 90 mm Hg in nine of 16 patients. The prevalence of hypothyroid ism was determined by measurements of serum thyroxine and thyrotropin concentrations in 688 consecutive hypertensive patients, referred for evaluation and therapy of their hypertension. Hypothyroidism was found in 25 (3.6%) of the patients. Restoration of normal serum thyroxine and thyrotropin levels with thyroid hormone replacement therapy lowered diastolic blood pressure to levels below 90 mm Hg in 32% of these patients who could be followed up after withdrawal of all antihypertensive drug therapy when euthyroidism had been restored (i.e., 1.2% of the 688 patients). It is concluded that diastolic hypertension resulting from hypothyroidism is a relatively common disorder, present in 1.2% of our referred hypertensive patients, that should be sought and treated. (Hypertension 11: 78-83, 1988) KEY WORDS • hypothyroid hypertension • endocrine hypertension • thyroid in hypertension H YPERTHYROIDISM is usually associated with peripheral vasodilatation and reduction of the diastolic blood pressure (BP) and sometimes with systolic hypertension, while hypothyroidism may be accompanied by diastolic hypertension, as many clinicians are aware. Elevation of the diastolic BP was found to be common in patients with hypothyroidism 1 and has been reported in small groups of patients with hypothyroidism and myxedema by several investigators, 2 " 6 who have all found a fall in diastolic BP when the hypothyroidism was corrected with thyroid replacement therapy. The latter observations were preceded by a report that desiccated thyroid administration lowered the BP to normal levels in 14% of 334 patients with essential hypertension, at a time (in 1950) when virtually no effective forms of antihypertensive therapy were available. Received February 11, 1987; accepted August 13, 1987. were reported by Fuller et al. 2 However, in a comparison of BP measurements in 80 hypothyroid patients and 73 euthyroid subjects, Endo et al. 8 found no evidence that hypothyroidism predisposed to hypertension. Apart from this negative study, there have been no recent attempts to determine the frequency with which hypertension may be associated with and caused by hypothyroidism, the treatment of which will restore the BP to normal. We have sought to obtain this information 1) by studying the BP responses of a series of patients with thyrotoxicosis to therapy with radioiodine as they became euthyroid and, frequently, hypothyroid and during correction of the iatrogenic hypothyroidism with thyroxine therapy and 2) ...

Background Despite their widespread use, antibiotics have not been shown to improve chronic rhinosinusitis (CRS) outcomes. We aimed to determine whether culture-inappropriate postoperative antibiotic therapy was associated with less quality of life (QOL) improvement following functional endoscopic sinus surgery (FESS). Methods This retrospective cohort study recruited 376 adult CRS patients undergoing FESS between 10/1/2007 to 12/31/2011. Patient demographics, comorbidities and medications were collected at baseline. Trimethoprim-sulfamethoxazole and clindamycin were administered for 2 weeks postoperatively. The antibiotic appropriateness was determined based on bacterial resistance profile of organisms identified during intraoperative culture. The QOL outcome was defined as change of 22 item Sinonasal Outcome Test scores from preoperative visit to 1-, 3- and 6-month post-FESS. Clinically significant difference was defined as at least ½ SD of baseline QOL score in the reference group. Mixed-effects regression models were performed. Results Seven percent of patients (n=27) had culture-inappropriate antibiotic therapy, and additional 5% (n=19) had culture-specific antibiotic adjustment. Compared to patients with culture-appropriate antibiotics, patients with culture-inappropriate antibiotics had significantly less improvement of QOL from baseline to postoperative 1-month and 3-month follow-up where the difference became clinically significant; patients with antibiotic adjustment had more QOL improvement from baseline to 1-month follow-up, but their QOL worsened at 3-month follow-up, and these changes were not clinically significant. However, all effects washed out at 6-month follow-up with no significant differences. Conclusions Culture-inappropriate postoperative antibiotic therapy decreased short-term QOL improvement to a clinically meaningful level after FESS. Culture guided selection of antibiotics may improve short-term FESS outcome.