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Independent bookstores (often called “indies” or “independents”) sustained threats to their basic business model because of the growth of national bookstore chains and the proliferation of book sales online, in price clubs, supermarkets, convenience stores, mass merchants, and specialty stores, the emergence of digital e-books and eReaders, and the U.S. recession of 2007–2009. These events triggered the closing of hundreds of independent bookstores. In spite of stiff online and brick-and-mortar competition and the recession, many independents were able to grow in size and importance. This article outlines the competitive advantages utilized by many independent bookstores between 2009 and 2018, resulting in an increase in the number of independent bookstores between 2009 (1651) and 2018 (2470).

Articular cartilage lesions, which can progress to osteoarthritis, are a particular challenge for regenerative medicine strategies, as cartilage function stems from its complex depth-dependent microstructural organization, mechanical properties, and biochemical composition. Fibrous scaffolds offer a template for cartilage extracellular matrix production; however, the success of homogeneous scaffolds is limited by their inability to mimic the cartilage's zone-specific organization and properties. We fabricated trilaminar scaffolds by sequential electrospinning and varying fiber size and orientation in a continuous construct, to create scaffolds that mimicked the structural organization and mechanical properties of cartilage's collagen fibrillar network. Trilaminar composite scaffolds were then compared to homogeneous aligned or randomly oriented fiber scaffolds to assess in vitro cartilage formation. Bovine chondrocytes proliferated and produced a type II collagen and a sulfated glycosaminoglycan-rich extracellular matrix on all scaffolds. Furthermore, all scaffolds promoted significant upregulation of aggrecan and type II collagen gene expression while downregulating that of type I collagen. Compressive testing at physiological strain levels further demonstrated that the mechanical properties of trilaminar composite scaffolds approached those of native cartilage. Our results demonstrate that trilaminar composite scaffolds mimic key organizational characteristics of native cartilage, support in vitro cartilage formation, and have superior mechanical properties to homogenous scaffolds. We propose that these scaffolds offer promise in regenerative medicine strategies to repair articular cartilage lesions.

Articular cartilage provides a low-friction, wear-resistant surface for diarthrodial joints. Due to overloading and overuse, articular cartilage is known to undergo significant wear and degeneration potentially resulting in osteoarthritis (OA). Regenerative medicine strategies offer a promising solution for the treatment of articular cartilage defects and potentially localized early OA. Such strategies rely on the development of materials to restore some aspects of cartilage. In this study, microfibrous poly(ɛ-caprolactone) scaffolds of varying fiber orientations (random and aligned) were cultured with bovine chondrocytes for 4 weeks in vitro, and the mechanical and frictional properties were evaluated. Mechanical properties were quantified using unconfined compression and tensile testing techniques. Frictional properties were investigated at physiological compressive strains occurring in native articular cartilage. Scaffolds were sheared along the fiber direction, perpendicular to the fiber direction and in random orientation. The evolution of damage as a result of shear was evaluated via white light interferometry and scanning electron microscopy. As expected, the fiber orientation strongly affected the tensile properties as well as the compressive modulus of the scaffolds. Fiber orientation did not significantly affect the equilibrium frictional coefficient, but it was, however, a key factor in dictating the evolution of surface damage on the surface. Scaffolds shear tested perpendicular to the fiber orientation displayed the highest surface damage. Our results suggest that the fiber orientation of the scaffold implanted in the joint could strongly affect its resistance to damage due to shear. Scaffold fiber orientation should thus be carefully considered when using microfibrous scaffolds.

Current antiretroviral therapy (ART) regimens efficiently limit HIV replication, thereby improving the life expectancy of people living with HIV; however, they also cause metabolic side effects. The ongoing obesity epidemic has resulted in more people with metabolic comorbidities at the time of HIV infection, yet the effect of preexisting metabolic dysregulation on infection sequelae and response to ART is unclear. Here, to investigate the impact of preexisting obesity and insulin resistance on acute infection and subsequent long-term ART, we infected a cohort of lean and obese adult male macaques with SIV and administered ART. The responses of lean and obese macaques to SIV and ART were similar with respect to plasma and cell-associated viral loads, ART drug levels in plasma and tissues, SIV-specific immune responses, adipose tissue and islet morphology, and colon inflammation, with baseline differences between lean and obese groups largely maintained. Both groups exhibited a striking depletion of CD4+ T cells from adipose tissue that did not recover with ART. However, differential responses to SIV and ART were observed for body weight, omental adipocyte size, and the adiponectin/leptin ratio, a marker of cardiometabolic risk. Thus, obesity and insulin resistance had limited effects on multiple responses to acute SIV infection and ART, while several factors that underlie long-term metabolic comorbidities were influenced by prior obesity and insulin resistance. These studies provide the foundation for future investigations into the efficacy of adjunct therapies such as metformin and glucagon-like peptide-1 receptor agonists in the prevention of metabolic comorbidities in people living with HIV.