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- StatPearls: Klebsiella Pneumonia [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- In 1882, Carl Friedlander first described Klebsiella pneumoniae as an encapsulated bacillus after isolating the bacterium from the lungs of those who had died from pneumonia. Originally named Friedla…
In 1882, Carl Friedlander first described Klebsiella pneumoniae as an encapsulated bacillus after isolating the bacterium from the lungs of those who had died from pneumonia. Originally named Friedlander's bacillus, it was not until 1886 when the bacterium garnered the name Klebsiella. Klebsiella pneumoniae is a gram-negative, encapsulated, non-motile bacterium that is found in the environment and has been associated with pneumonia in the alcoholic and diabetic patient population. The bacterium typically colonizes human mucosal surfaces of the oropharynx and gastrointestinal (GI) tract. Once the bacterium enters the body, it can display high degrees of virulence and antibiotic resistance. Today, K. pneumoniae pneumonia is considered the most common cause of hospital-acquired pneumonia in the United States and the organism accounts for 3% to 8% of all nosocomial bacterial infections.
- Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis. [Meta-Analysis]
- PMPLoS Med 2017; 14(9):e1002383
- CONCLUSIONS: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.
- Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. [Journal Article]
- JAMAJAMA 2017 06 20; 317(23):2402-2416
- CONCLUSIONS: These findings provide estimates of cancer risk based on BRCA1 and BRCA2 mutation carrier status using prospective data collection and demonstrate the potential importance of family history and mutation location in risk assessment.
- Communicating BRCA research results to patients enrolled in international clinical trials: lessons learnt from the AGO-OVAR 16 study. [Randomized Controlled Trial]
- BMBMC Med Ethics 2016 10 21; 17(1):63
- CONCLUSIONS: This study illustrates the importance of increasing the clarity and scope of informed consent and the need for patient engagement to ensure clinical trial participants can indicate their preference regarding receipt of potentially important individual pharmacogenetic results.
- Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers. [Journal Article]
- PlosPLoS One 2015; 10(4):e0120020
- While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer …
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04-1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03-1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.
- Genetic studies of body mass index yield new insights for obesity biology. [Meta-Analysis]
- NatNature 2015 Feb 12; 518(7538):197-206
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass ind…
Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
- Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. [Journal Article]
- CECancer Epidemiol Biomarkers Prev 2015; 24(1):308-16
- CONCLUSIONS: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers.Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.
- Defining the role of common variation in the genomic and biological architecture of adult human height. [Meta-Analysis]
- NGenNat Genet 2014; 46(11):1173-86
- Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different nu…
Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
- Incorporation of pazopanib in maintenance therapy of ovarian cancer. [Randomized Controlled Trial]
- JCJ Clin Oncol 2014 Oct 20; 32(30):3374-82
- CONCLUSIONS: Pazopanib maintenance therapy provided a median improvement of 5.6 months (HR, 0.77) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy. Overall survival data to this point did not suggest any benefit. Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity (NCT00866697).
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- Synthesis of spirocyclic carbazole- and acridine-lactams. [Journal Article]
- OBOrg Biomol Chem 2010 Apr 21; 8(8):1894-8
- Spirocyclic carbazole- and acridine-lactams were prepared by Fischer-indole or Friedländer-quinoline synthesis starting from spirocyclic ketones with a lactam ring. All annulation products were obtai…
Spirocyclic carbazole- and acridine-lactams were prepared by Fischer-indole or Friedländer-quinoline synthesis starting from spirocyclic ketones with a lactam ring. All annulation products were obtained as mixtures of separable regioisomers, which differ only in the position of one methyl group. The starting materials were prepared from 2-pyrrolidone and 2-piperidone by a sequence of protection (by N-allylation), alpha-acylation, iron-catalyzed Michael reaction followed by Robinson-annulation, palladium-catalyzed N-deprotection and catalytic hydrogenation. The overall yields of this six-step sequence are 13 and 17%, respectively, and the racemic ketones are obtained as single diastereoisomers.