Background: Statins are the most commonly prescribed agents for hypercholesterolemia because of their efficacy and tolerability. As the number of patients in need of statin therapy continues to increase, information regarding the relative efficacy and safety of statins is required for decisionmaking. Objective: This study will use systematic review to compare the efficacy and safety profiles of different statins at different doses and determine the therapeutically equivalent doses of statins to achieve a specific level of low-density lipoprotein cholesterol (LDL-C) lowering effect. Methods: Publications of head-to-head randomized controlled trials (RCTs) of statins were retrieved from the Oregon state database The publications were evaluated with predetermined criteria by a reviewer before they were included in the review. The mean change in cholesterol level of each statin was calculated and weighted by number of subjects involved in each RCT. Where possible, meta-analysis was performed to generate pooled estimates of the cholesterol lowering effect of statins and the difference between statins.

The zona pellucida (ZP) domain is a bipartite protein structural element comprised of ZP-N and ZP-C regions. Most notable for its ability to mediate protein polymerization, many ZP proteins polymerize and assemble into long fibrils that form specialized extracellular matrices. Other ZP proteins (namely, betaglycan and endoglin) do not polymerize but serve as important membrane coreceptors for ligands in the transforming growth factor-β (TGF-β) superfamily. Here, we present the 2.0-Å resolution crystal structure of the betaglycan ZP-C region in combination with a downstream region known as the external hydrophobic patch (EHP). Similar to the ZP-N region, the ZP-C region also adopts an immunoglobulin-like fold, despite sharing no sequence homology and possessing different disulfide linkages. The EHP region, which was previously thought to be external to the ZP region, is integral to the ZP-C domain and corresponds to the ZP-C G strand. Our structure also indicates that the critical maturation cleavage of ZP proteins, a process that activates nascent ZP proteins for polymerization, occurs within the immunoglobulin domain at the FG loop. Nonpolymerizing ZP proteins such as betaglycan and endoglin do not contain this cleavage site. Finally, our structure suggests that the AB loop and the convex surface pocket are regions important for TGF-β ligand binding.reproductive biology | signaling | inhibin T he zona pellucida (ZP) domain is a structural element found in the extracellular region of many eukaryotic proteins (1, 2). This structural element is characterized by a set of eight highly conserved cysteines and predicted to exist as a bipartite structure corresponding to ZP-N and ZP-C regions tethered by a linker (3, 4). The crystal structure of the ZP-N region has been solved and shown to adopt an immunoglobulin-like fold (5), suggesting that the ZP-C region is likely also a distinct domain by itself and that the so-called ZP domain, the collective structural element comprised of distinct ZP-N and ZP-C domains, may be more aptly referred to as the ZP region.The ZP region is important for protein polymerization and protein-protein interactions (6, 7). Many ZP proteins polymerize to become long fibrils that form specialized extracellular matrices. The best-known example is the pericellular matrix known as zona pellucida or vitelline envelope that surrounds mammalian and nonmammalian oocytes, respectively, to ensure speciesspecific fertilization and prevent polyspermy. This matrix is composed from homologues of ZP1, ZP2, ZP3, and in some species, ZP4 proteins, all of which contain a single ZP region in the ectodomain (1). In Drosophila melanogaster, two ZP proteins, Piopio and Dumpy, contribute to the apical extracellular matrix and play crucial roles in tracheal development and tubulogenesis (8). In mammals, other well-characterized polymerizing ZP proteins include uromodulin (also known as Tamm-Horsfall protein) that likely forms the water-impermeable layer around the thick ascending loop of Henle in the kidney (9) and...

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A pharmacoepidemiology study was conducted using the health insurance database in Taiwan to assess compliance with osteoporosis drug regimens and the impact of compliance on the risk for secondary fractures. Patients >50 years of age with vertebral/hip fracture who had been started on alendronate therapy for the first time only after the fracture were included. Compliance was measured using the medication possession ratio (MPR) and was included as a time-dependent covariate in the Cox model to compare the difference between compliant (MPR ≥ 80%) and noncompliant patients (MPR <80%) with respect to risk for subsequent hip fractures. Only 38% of the study population remained compliant during the first year of treatment. Over the 4-year follow-up period, the risk of hip fracture among the compliant patients was 70% lower than that among the noncompliant ones (adjusted hazard ratio (HR) 0.30). Among patients with osteoporosis in Taiwan who had experienced a fracture and had started alendronate therapy, compliance with the dosage regimen was suboptimal. It was also found that compliance significantly reduced the risk of secondary hip fracture up to 4 years.