The role of COX-2 in angiogenesis and rheumatoid arthritis

Recent evidence suggests that cyclooxygenase (COX)-2 is a mediator of angiogenesis, and COX-2 activity is known to be upregulated in the rheumatoid arthritis (RA) synovium. We examined whether mediation of angiogenesis by COX-2 was occuring in cells of the RA synovium and in microvascular endothelial cells (ECs) that are similar to those found in the RA synovium. We demonstrate that rofecoxib, a selective COX-2 inhibitor, acts directly on human dermal microvascular ECs (HMVECs) to inhibit their chemotactic and tube forming ability. Likewise, pretreatment of HMVECs with rofecoxib significantly inhibited their ability to form tubes induced by conditioned media (CM) of activated RA synovial fibroblasts. When RA synovial fibroblasts were pretreated with rofecoxib for 16 h and then stimulated with interleukin (IL)-1beta, their CM induced significantly less HMVEC tube formation when compared with CM from vehicle-treated RA synovial fibroblasts. ELISAs performed on activated RA fibroblast CM for known proangiogenic factors demonstrated a significant reduction in bFGF, in addition to the expected decrease in PGE(2). Our studies suggest that COX-2-induced angiogenic activity is an active mechanism within diseased synovium and may provide an additional rationale for the use of COX-2 inhibitors in RA.     

Synthesis and characterization of acrylate-terminated unsaturated copolyesters

The reaction of the potassium salt of acrylic acid with the potassium salt of a dicarboxylic acid and 1,4-dibromobutane was applied to the synthesis of three series of acrylate-terminated copolyesters: poly(tetramethylene maleate-co-tetramethylene phthalate) (BMPA), poly(tetramethylene fumarate-co-tetramethylenephthalate) (BFPA) and poly(tetramethylene phthalate-co-tetramethylene succinate) (BPSA). The monofunctional monomer, the potassium salt of acrylic acid, was used for the introduction of double bonds at the end of the chains and for the regulation of the molecular weight of the polyesters. The telechelic copolyesters were characterized by ¹H and ¹³C NMR spectroscopy, in almost all cases providing an acrylate functionality of two.     

The First Genome-Wide Association Study for Type 2 Diabetes in Youth: The Progress in Diabetes Genetics in Youth (ProDiGY) Consortium

The prevalence of type 2 diabetes in youth has increased substantially, yet the genetic underpinnings remain largely unexplored. To identify genetic variants predisposing to youth-onset type 2 diabetes, we formed ProDiGY, a multiethnic collaboration of three studies (TODAY, SEARCH, and T2D-GENES) with 3,006 youth case subjects with type 2 diabetes (mean age 15.1 ± 2.9 years) and 6,061 diabetes-free adult control subjects (mean age 54.2 ± 12.4 years). After stratifying by principal component–clustered ethnicity, we performed association analyses on ∼10 million imputed variants using a generalized linear mixed model incorporating a genetic relationship matrix to account for population structure and adjusting for sex. We identified seven genome-wide significant loci, including the novel locus rs10992863 in PHF2 (P = 3.2 × 10⁻⁸; odds ratio [OR] = 1.23). Known loci identified in our analysis include rs7903146 in TCF7L2 (P = 8.0 × 10⁻²⁰; OR 1.58), rs72982988 near MC4R (P = 4.4 × 10⁻¹⁴; OR 1.53), rs200893788 in CDC123 (P = 1.1 × 10⁻¹²; OR 1.32), rs2237892 in KCNQ1 (P = 4.8 × 10⁻¹¹; OR 1.59), rs937589119 in IGF2BP2 (P = 3.1 × 10⁻⁹; OR 1.34), and rs113748381 in SLC16A11 (P = 4.1 × 10⁻⁸; OR 1.04). Secondary analysis with 856 diabetes-free youth control subjects uncovered an additional locus in CPEB2 (P = 3.2 × 10⁻⁸; OR 2.1) and consistent direction of effect for diabetes risk. In conclusion, we identified both known and novel loci in the first genome-wide association study of youth-onset type 2 diabetes.     

The Influence of Obesity on Hospital Admission After Outpatient Foot and Ankle Surgery

We examined the association of body mass index (BMI) with sociodemographic data, medical comorbidities and hospital admission following ambulatory foot and ankle surgery. We conducted an analysis utilizing data from the American College of Surgeons National Surgical Quality Improvement Program database from 2007 to 2016. Adult patients who underwent ankle surgery defined as ankle arthrodesis, ankle open reduction and internal fixation, and Achilles tendon repair in the outpatient setting. We examined 6 BMI ranges: <20 kg/m² underweight, ≥20 to <25 kg/m² normal weight, ≥25 to <30 kg/m² overweight, ≥30 to <40 kg/m² obese, ≥40 kg/m²to <50 kg/m² severely obese, and ≥50 kg/m² extremely obese. The primary outcome was hospital admission. We performed multivariable logistic regression and reported odds ratios (OR) and their associated 95% confidence interval (CI) and considered a p value of <.05 as statistically significant. Data extraction yielded 13,454 adult patients who underwent ambulatory ankle surgery. We then performed listwise deletion to exclude cases with missing observations. After excluding 5.4% of the data, the final study population included 12,729 patients. The overall rate of hospital admission was in the population was 18.6% (2,377/12,729). The overall rate of postoperative complications was 0.03% (4/12,729). We found no significant association of BMI with hospital admission following multivariable logistic regression. We recommend that BMI alone should not be solely used to exclude patients from having ankle surgery performed in an outpatient setting, especially since this patient group makes up a significant proportion of orthopedic surgery.     

Gay Community Involvement and Condomless Anal Sex Among Sexual Minority Men in the USA

Archives of Sexual Behavior - Sexual minority men (SMM) remain disproportionately burdened by sexually transmitted infections. Although gay community involvement has been theorized to be protective...     

Influence of surgery on renal amyloidosis

It is well known that renal amyloidosis (RA) leads to ESRD in a few years. This evolution may be accelerated by several factors such as steroids, renal vein thrombosis, infections or surgery. We report 22 patients (14M,8F) mean age = 41.6 years (13-72) with RA in whom surgery revealed or aggravated renal disease. The group I includes 15 patients with no previous history of renal disease and who developed oedema few days after surgery with acute renal failure in 5 of them. Proteinuria was present in all the cases with a nephrotic syndrome in 10. Percutaneous kidney biopsy (KB) showed renal amyloidosis in all patients (AA+ = 8 cases, AA- = 3 cases). Only 9 patients were followed-up (mean period = 40 months): 2 patients are stationary; 1 is on complete remission 2 are on HD and 4 died. The group II includes 7 patients with a previous history of nephropathy (Histologically proven amyloidosis: 3 CRF = 1, Oedema: 3). All these patients developed oedema few days after surgery with acute RF in 4 patients. KB performed in all of them showed RA (AA+ = 33, AA- = 1). 6 patients were followed up for a mean period of 11 months: 5 died, 1 patient is on HD. The influence of surgery on renal amyloidosis is often unforeseeable. It may have no effect on renal disease, but very often it reveals RA and sometimes dramatically aggravates the course of the disease with occurrence of irreversible CRF. The pathogenic role of surgery on RA is discussed.     

Primitive intracranial ependymomas. Salah-Aza?z institute experience]

PURPOSE: - To assess the outcome and prognostic factors of patients with primitive intracranial ependymomas treated at the department of radiotherapy of Salah-Aza?z Institute. METHODS AND MATERIAL: - Between 1972 and 1997, 31 patients aged one to 53 years received postoperative radiotherapy. There were 16 males and 15 females. Location of tumor was infratentorial in 24 cases and supratentoriel in seven cases. Surgical treatment consisted of complete resection in 14, incomplete resection in 13 and unknown type in four patients. All patients were treated with radiotherapy to the craniospinal axis in 26 cases, whole brain in five cases. RESULTS: - Five years survival rate was 63%. For infratentorial tumors, two patients failed locally, two patients failed locally and at distance and four patients failed only at distance, while one patient with supratentorial tumor relapsed locally. Age, performances status, tumor site, gender and extent of surgery had no impact on survival. The treatment field extent was the only variable predictive of outcome. Patients treated with craniospinal irradiation had a survival rate of 86% compared with 37,5% for patients treated with whole brain irradiation. CONCLUSION:- Infratentorial ependymomas seem to have a worse prognosis than supratentorial ones. Irradiation field extent should be correlated to prognostic factors.