Synthesis,Molecular Docking and Biological Evaluation of Diaryl Pyrimidine Derivatives as Urease Inhibitors

Pharmaceutical Chemistry Journal - Urease is a dinickel enzyme that is responsible for the hydrolysis of urea to ammonia and carbon dioxide. A series of bacteria like Helicobacter pylori produce...     

Severity of erectile dysfunction could predict left ventricular diastolic dysfunction in patients without overt cardiac complaint

IntroductionIt has been repeatedly demonstrated that presence of erectile dysfunction (ED) may predate the occurrence of overt event of coronary artery disease. However, the association between severity of ED and left ventricular diastolic dysfunction (LVDD) was rarely reported.AimThe aim of this study was to assess the association between severity of ED and LVDD in patients without overt cardiac complaint.Main Outcome MeasuresThe International Index of Erectile Function (IIEF) was used to assess erectile function. Diastolic Doppler parameters measurements and tissue Doppler imaging were used to assess left ventricular diastolic function.MethodsA total of 230 male ED patients without overt cardiac complaint were enrolled in this study. Erectile function was assessed using the IIEF. Patients were also screened for socio demographic data and medical comorbidities that included age, smoking, diabetes, hypertension, and dyslipidemia. All patients were referred to cardiologist for cardiac assessment. Left ventricular diastolic function that included diastolic Doppler parameters measurements and tissue Doppler imaging were also assessed.ResultsMean age ± standard deviation was 57.5 ± 5.6 (range of 42–81). There were significant associations between the following risk factors: age, obesity, smoking, hypertension, dyslipidemia, and increased severity of ED (P < 0.05 for each). Of the patients, 77.4%, 74.8%, 80%, and 66.1% had abnormal transmitral E/A (E/A) ratio, deceleration time (DT), isovolumic relaxation time (IVRT), mitral E velocity/tissue Doppler imaging E velocity (E/Em) ratio, respectively. Only the means of IVRT and (E/Em) ratio had significant associations with increased severity of ED (P < 0.001 for each). There were significant associations between increased severity of ED and the following categorical echo parameters: grades 1 and 2 of E/A ratio, DT, IVRT, and grades 1, 2, and 3 of (E/Em) ratio (P < 0.05 for each).Conclusions. The current study clearly demonstrated that LVDD is prevalent among patients with ED‐associated medical comorbidities without overt cardiac complaint. There were significant associations between increased severity of ED and presence of LVDD in those patients. El‐Sakka AI, Morsy AM, and Fagih BI. Severity of erectile dysfunction could predict left ventricular diastolic dysfunction in patients without overt cardiac complaint. J Sex Med 2011;8:2590–2597.     

A comparison between patient recall and concurrent measurement of preoperative quality of life outcome in total hip arthroplasty

The objective is to evaluate the reliability of patients' recall of preoperative pain and function during the immediate postoperation period after total hip arthroplasty. A prospective cohort of 104 patients completed a survey about their quality of life before operation, and recalled preoperative status at 3 days, 6 weeks, and 12 weeks after operation. Quality of life was measured by the Western Ontario and McMaster University Osteoarthritis Index, the Oxford-12 hip score, and the 12-item Short-Form score. The intraclass correlation coefficient and Spearman correlation coefficient were used to compare preoperative quality of life scores to the scores recalled. The reliability of recall remained high up to 3 months postoperation. Patients are able to accurately recall their preoperative function for up to 3 months after total hip arthroplasty.     

Missense MED12 variants in 22 males with intellectual disability: From nonspecific symptoms to complete syndromes

We describe the phenotype of 22 male patients (20 probands) carrying a hemizygous missense variant in MED12. The phenotypic spectrum is very broad ranging from nonspecific intellectual disability (ID) to the three well-known syndromes: Opitz–Kaveggia syndrome, Lujan–Fryns syndrome, or Ohdo syndrome. The identified variants were randomly distributed throughout the gene (p = 0.993, χ² test), but mostly outside the functional domains (p = 0.004; χ² test). Statistical analyses did not show a correlation between the MED12-related phenotypes and the locations of the variants (p = 0.295; Pearson correlation), nor the protein domain involved (p = 0.422; Pearson correlation). In conclusion, establishing a genotype–phenotype correlation in MED12-related diseases remains challenging. Therefore, we think that patients with a causative MED12 variant are currently underdiagnosed due to the broad patients' clinical presentations.     

Comparative Evaluation of Microleakage of Flowable Composite Resin Using Etch and Rinse,Self-Etch Adhesive Systems,and Self-Adhesive Flowable Composite Resin in Class V Cavities: Confocal Laser Microscopic Study

The essential factor in determining the preservation of restoration is the marginal seal. Restoring cervical lesions with a resin composite has always been a challenge. Composite resins with various viscosities and different bonding systems are being researched to reduce the microleakage. Confocal laser scanning microscopy (CLSM) is the latest non-destructive technique for visualizing the microleakage. Objectives: To evaluate and compare the microleakage of Universal Flo composite resin (G-aenial) using etch and rinse adhesive system ER-2 steps (Adper Single Bond 2), self-etch adhesive system SE-1 step (G-Bond), and self-adhesive flowable composite resin (Constic) in Class V cavities using a confocal laser scanning microscope. Materials and Method: Class V cavities were prepared on 27 caries-free human extracted premolar teeth on the buccal and lingual surfaces with standardized dimensions of 2 mm height, width 4 mm, and a depth of 2 mm. After the cavity preparation, all teeth were randomly divided into three groups, namely Group-I: G-aenial Universal Flo with Single Bond 2 (n = 9 teeth); Group-II: G- aenial Universal Flo with G-Bond (n = 9 teeth), and Group-III: Constic (n = 9 teeth). The prepared and restored specimens were then subjected to thermocycling for 500 cycles in a water bath at 5 °C and 55 °C with a dwelling time of 30 s. The specimens were placed in 0.6% aqueous rhodamine dye for 48 h. Sectioning was carried out bucco-lingually and specimens were evaluated for microleakage under a confocal laser scanning microscope. Results: There was a significant difference (p = 0.009) in microleakage when comparing total etch and rinse, specifically between Adper Single Bond 2 ER-2 steps (fifth generation) and self-adhesive flowable composite resin, which is Constic. There was more microleakage in the self-etch bonding agent, particularly G-Bond, SE-1 step (seventh generation), when compared to ER-2 steps (fifth generation bonding agent); however, the results were not statistically significant (p = 0.468). The self-adhesive flowable composite resin showed more microleakage than SE-1 step and ER-2 steps. Conclusions: None of the adhesive systems tested were free from microleakage. However, less microleakage was observed in the total etch and rinse, especially Adper Single Bond 2 (ER-2 steps), than the self-etch adhesive system SE-1 step and self-adhesive flowable composite resin. Clinical significance: Constant research and technological advancements are taking place in dentin adhesives to improve the marginal seal. This has led to the evolution of total acid-etching dentin bonding agents termed as etch and rinse (ER)-2 steps (fifth generation dentin bonding agents) and self-etching (SE) 2 steps, and SE-1 step dentin bonding agents termed as the sixth and seventh generation bonding agents, respectively.     

Clinical and pathologic description of stroke patients (1990-1994)

Data relating to stroke patients at a department of internal medicine (50 beds) in a county teaching hospital were studied in period 1990-1994. In this five-year period, 1184 patients were admitted because of some forms of stroke. The mortality due to the stroke was 16.8% (199 patients, deceased group). Autopsy was performed on 159 of these 199 patients (autopsy rate: 79.8%). Age- and sex-matched controls were selected from the survivors (n = 159). The main risk factors of stroke were analyzed in both groups: hypertension, cardiac events (decompensation, atrial fibrillation, and old myocardial infarction), previously verified diabetes, and recurrent stroke in the history. The mean hospital nursing time for the survivors was 12.3 +/- 6.3 days, while that in the deceased 7.2 +/- 7.6 days. RESULTS: 1. Hypertension was present to similar extents in both groups (survivors: 82.1%, deceased group: 77.8%) 2. Decompensation occurred in 5% vs 18.2% fibrillation in 11.3% vs 13.8%, and old myocardial infarction in 5.6% vs 18.2% 3. Diabetes was observed in 21.3% vs 36.4% and 4. Recurrent stroke in 22.6% vs 39.6%. These risk factors strongly predicted the outcome of the stroke. Other recently observed factors (haemorrhagic form, conscious state, time of hospital admission, seasonal variation, higher erythrocyte sedimentation rate, hyperglycaemia, proteinuria, early deep vein trombosis) revealed also significant differences between survivors and deceased patients. Since pulmonary thromboembolism was twice as frequent in the deceased patients as in the survivors, early heparin prevention is necessary immediately after computer tomography which excluded the haemorrhagic type of cerebrovascular diseases.     

Performance of the pegfilgrastim on-body injector as studied with placebo buffer in healthy volunteers

Objective: The pegfilgrastim on-body injector (OBI) is a single-use, disposable, battery-powered injector that is designed to automatically deliver a single subcutaneous dose of pegfilgrastim beginning approximately 27?hours after activation and continuing over approximately 45?minutes. In this open-label study, we assessed performance of the OBI delivering placebo buffer in healthy volunteers.

Research design and methods: Healthy men and women aged 18–55 years, with a body mass index of 18–35?kg/m², were enrolled. OBIs were activated by filling them with placebo buffer, and two injectors were applied concurrently to each subject: one to the abdomen and one to the back of the upper arm. Subjects were monitored for substantial leakage during and after administration.

Main outcome measures: The primary endpoint of the study was successful delivery of placebo buffer based on a composite of the following: no substantial leakage during or after administration, green status light indicator on the injector during and after administration, and fill indicator bar at the empty position after administration. The secondary endpoint was the incidence of treatment-emergent adverse events (AEs).

Results: Of the 150 subjects enrolled, 149 (99.3%) completed the study. Study subjects were 48.0% men, and 52.0% women; 47.3% were white, 35.3% black or African American, 12.7% Asian, and 4.7% other. Mean (SD) age was 35.9 (10.8) years. Of the 297 total deliveries, 292 (98.3%) were considered successful: 147/149 (98.7%; 95% confidence interval [CI]: 95.2%–99.6%) to the abdomen and 145/148 (98.0%; 95% CI: 94.2%–99.3%) to the back of the upper arm. Five deliveries were considered unsuccessful: two due to hazard alarms, and three due to substantial leakage. The most common treatment-emergent AEs (in >2% of subjects overall) by preferred term were medical device site reaction (20.7%), catheter-site hemorrhage (8.7%), and headache (3.3%). No serious AEs were reported.

Conclusions: The pegfilgrastim OBI was well tolerated, and deliveries of placebo buffer were successful 98.3% of the time. The generalizability of these results may be limited by the conduct of this study in healthy subjects in a controlled environment.