Design, synthesis and biological activity of acyl substituted 3-amino-5-methyl-1,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones as potential hypnotic drugs

Among the known non-benzodiazepinic hypnotic drugs acting on the alpha1 subunit of the GABA-A receptor, Zolpidem, Zaleplon and Indiplon have showed high affinity and selectivity. Following a design methodology including pharmacophoric requirements and ADME-predicted properties, we have synthesized a library of 3-amino-4,5-dihydro-1H-pyrazolo[3,4-b]pyridin-6(7H)-ones and their N1-alkyl derivatives as new scaffolds for designing non-benzodiazepine BZ receptor ligands.     

Treatment of males with post-prostatectomy stress urinary incontinence by a mesh anchored to the ischio-pubic bones

We presented the results of an alternative in the treatment of the stress urinary incontinence of male radical postprostatectomy. Is a technique of renewed interest in the last years, cradle in the procedure of Stamey, consisting of placing an on guard suburetral polypropylene mesh, anchored by means of screws to the isquiopubian branches. We have applied the procedure in 4 patients and with stress urinary incontinence of long evolution. After an average pursuit of 12.5 months, two patients present total continence, one has improved significantly and in the other the incontinence persists. There have been no postoperating complications nor rejection of the mesh. From these preliminary results and the reviewed bibliography, we thought that this technique can constitute an alternative to the artificial urinary sphincter, dices its clinical results, its facility of execution, the good tolerance and his low cost.     

The ABO blood group genotype and factor VIII levels as independent risk factors for venous thromboembolism

Factor VIII (FVIII), von Willebrand factor (vWF) and the ABO blood groups have been associated with thrombosis. The ABO locus has functional effects on vWF and FVIII levels and is genetically correlated with FVIII, vWF and thrombosis. We carried out a case-control study to assess the role of FVIII, vWF and ABO types on thrombotic risk. We analyzed 250 patients with venous thrombosis and 250 unrelated controls. FVIII, vWF and other factors related to thrombophilia were measured, ABO groups were analyzed by genotyping. FVIII and vWF were higher in non-O individuals. Group O was more frequent in the controls (44.3% v 23.3%; difference 21.1%; 95% CI: 13.0-29.3%) and Group A in patients (59.2% v. 41.5%; difference 17.7%, 95% CI: 9.1-26.4%). Individuals carrying the A1 allele had a higher risk of thrombosis (OR 2.6; 95% CI, 1.8-3.8). The risk attributed to vWF disappeared after adjusting for the ABO group. Patients with FVIII above the 90th percentile had a high thrombotic risk (adjusted OR 3.7; 95% CI, 2.1-6.5), and a high risk of recurrence (OR 2.3; 95% CI: 1.3-4.1). In conclusion, high FVIII levels and non-O blood groups, likely those with the A1 allele, are independent risk factors for venous thromboembolism and should be considered in evaluating of thrombophilia.     

Perception of general and oral health in White and African American adults: assessing the effect of neighborhood socioeconomic conditions

OBJECTIVES: This study investigates the independent and joint effects of family income and neighborhood socioeconomic status (SES) on general health and oral health before and after controlling for traditional risk factors in a representative sample of adults aged 18+ years residing in the Detroit tri-county area, Michigan. METHODS: Individuals data were obtained through interviews, while neighborhood data came from the 1990 US Census. SUDAAN was used to accommodate the complex sampling design and correlation of outcomes within the same neighborhoods. RESULTS: Whites in disadvantaged neighborhoods were four times more likely to rate their oral health as fair or poor [odds ratio (OR): 4.0; 95% confidence intervals (CI): 1.6-10.3] than their counterparts in advantaged neighborhoods. When evaluating the joint effects of family income and neighborhood SES, low-income Whites in disadvantaged neighborhoods were six times more likely to rate their oral health as fair or poor (OR: 6.4; 95% CI: 1.6-26.5) than their high-income counterparts in advantaged neighborhoods. The odds of rating general health as fair or poor was six times greater in low-income African Americans in disadvantaged neighborhoods (OR: 6.1; 95% CI: 1.6-23.8) than high-income African Americans in advantaged neighborhoods. Similarly, low-income African Americans in disadvantaged neighborhoods were almost three times (OR: 2.8; 95% CI: 1.0-8.1) more likely to rate their oral health as fair/poor than high-income African Americans in advantaged neighborhoods. CONCLUSIONS: SES conditions at the neighborhood-level, independently or jointly with individual-level income, appear to be important in evaluating racial/ethnic differences in self-rated oral health. Neighborhood conditions could tap into constructs not captured by individual-level variables on self-rated oral health.     

Do patients and their families expect what we really offer them?

Frequently we evaluate user satisfaction for the treatment procedures provided (quality perceived), but we do not study the prior expectations (quality desired). Our objective is to discover what these patient and their family expectations are about treatment procedures and nurses' role so that we can make improvements and contribute to maximizing the quality of treatment provided. The aspects which cause greatest concern so that a patient's hospital stay is comfortable are the interpersonal relationships with family members, room mate, and professionals. Furthermore, the authors evaluate the treatment with nurses as a primary aspect in quality treatment.     

The geography of the highest mortality areas in Spain: a striking cluster in the southwestern region of the country

Methods: Age adjusted relative risk of death by gender was estimated in each of 2218 small areas of the country using a non-parametric empirical Bayes method. To determine areas with "significantly increased risk" a Poisson based score test was used.

Results: Mapping of the highest risk areas showed a striking geographical clustering in the southwestern region of the country. This region, comprising 8% of the Spanish population, accounts for about one third (2884 deaths) of the total excess mortality.

     

Association after linkage analysis indicates that homozygosity for the 46C-->T polymorphism in the F12 gene is a genetic risk factor for venous thrombosis

In a family-based study called GAIT (Genetic Analysis of Idiopathic Thrombophilia) that included a genome-wide scan we demonstrated that a polymorphism (46C-->T) in the F12 locus jointly influences variability of plasma (Factor XII) FXII levels and susceptibility to thrombotic disease. It then became germane to determine the prevalence of the 46C-->T polymorphism and its relative risk of thrombotic disease. We followed up evidence for genetic linkage with a case-control study, including 250 unrelated consecutive Spanish patients suffering from venous thrombotic disease and 250 Spanish subjects matched for sex and age as a controls. We measured FXII levels and genotyped the 46C-->T polymorphism, as well as a number of classical risk factors for thrombotic disease.We confirmed that individuals with different genotypes for this polymorphism showed significant differences in their FXII levels. Most importantly, the mutated T allele in the homozygous state (genotype T/T) was associated with an increased risk of thrombosis (adjusted OR of 4.82; 95% CI 1.5-15.6), suggesting that the polymorphism itself is an independent risk factor for venous thromboembolism. This study confirms that the 46C-->T polymorphism is a genetic risk factor for venous thrombosis in the Spanish population. In addition, our results confirm that a genome-wide scan coupled with a classical case-control association study is an extremely valuable approach to identify DNA variants that affect complex diseases.