Magnetic Shielding Analysis of Bonding in [1.1.1]Propellane.

The bonding in [1.1.1]propellane, bicyclo[1.1.0]butane, bicyclo[1.1.1]pentane, tetrahedrane, and cyclopropane is investigated by analyzing changes in the off-nucleus isotropic magnetic shielding within the space surrounding each of these molecules and, for [1.1.1]propellane, by examining also the diamagnetic and paramagnetic contributions to this shielding. Any shielding arising from the two "exo" sp3-like hybrid atomic orbitals on the bridgehead carbon atoms that have been used to support the idea of an inverted bond between these two atoms is found to be almost entirely contained within the [1.1.1]propellane cage and to contribute to a strongly shielded central region. This strongly shielded region suggests the establishment of a mainly covalent bonding interaction involving all carbon atoms that cannot be straightforwardly decomposed into contributions from individual carbon-carbon bonds. The emergence of the strongly shielding central region is traced by comparing the shielding variations in and around molecules with one three-membered carbon ring (cyclopropane), two fused three-membered carbon rings (bicyclo[1.1.0]butane), and three fused three-membered carbon rings ([1.1.1]propellane).

Implications of humeral short-stem diametral sizing on implant stability.

Background: Shoulder arthroplasty humeral stem design has evolved to include various shapes, coatings, lengths, sizes, and fixation methods. While necessary to accommodate patient anatomy characteristics, this creates a surgical paradox of choice. The relationship between the surgeon's selection of short-stem implant size and construct stiffness, resistance to subsidence and micromotion has not been assessed. Methods: Eight paired cadaveric humeri were reconstructed with surgeon-selected (SS) and 2-mm diametrically larger (SS+2) short-stemmed press-fit implants. Each reconstruction was subjected to 2000 cycles of 90° forward flexion loading, and stem subsidence and micromotion were measured using optical tracking. Compressive stiffness of the stem-bone reconstruction was then assessed by applying a load in-line with the stem axis that resulted in 5 mm of stem subsidence. Results: Increasing stem size by 2 mm resulted in the construct stiffness more than doubling compared to SS stems (-741 ± 243 N/mm vs. -334 ± 120 N/mm; P = .003; power = 0.971). These larger stems also subsided significantly less than their SS counterparts (SS: 1.2 ± 0.6 mm; SS+2: 0.5 ± 0.5 mm; P = .029; power = 0.66), though there were no significant changes in micromotion (SS: 169 ± 59 µm; SS+2: 187 ± 52 µm; P = .506; power = 0.094). Conclusions: The results of this study highlight the importance of proper short-stem sizing, as a relatively small 2 mm increase in diametral size was observed to significantly impact construct stiffness, which could increase the risk of stress shielding and implant loosening. Future work should focus on developing tools that objectively quantify bone quality and aid surgeons in selecting the appropriate size short-stem humeral implants for a particular patient.

Effects of long-term ethanol administration in a rat total enteral nutrition model of alcoholic liver disease.

Male Sprague-Dawley rats were chronically fed a high-unsaturated-fat diet for 130 days by using total enteral nutrition (TEN), or the same diet in which ethanol (EtOH) isocalorically replaced carbohydrate calories. Additional groups were supplemented with the antioxidant N-acetylcysteine (NAC) at 1.7 g·kg(-1)·day(-1). Relative to an ad libitum chow-fed group, the high-fat-fed controls had three- to fourfold greater expression of fatty acid transporter CD36 mRNA and developed mild steatosis but little other hepatic pathology. NAC treatment resulted in increased somatic growth relative to controls (4.0 ± 0.1 vs. 3.1 ± 0.1 g/day) and increased hepatic steatosis score (3.5 ± 0.6 vs. 2.7 ± 1.2), associated with suppression of the triglyceride hydrolyzing protein adiponutrin, but produced no elevation in serum alanine aminotransferase (ALT). Chronic EtOH treatment increased expression of fatty acid transport protein FATP-2 mRNA twofold, resulting in marked hepatic steatosis, oxidative stress, and a twofold elevation in serum ALT. However, no changes in tumor necrosis factor-α or transforming growth factor-ß expression were observed. Fibrosis, as measured by Masson's trichrome and picrosirius red staining, and a twofold increase in expression of type I and type III collagen mRNA, was only observed after EtOH treatment. Long-term EtOH treatment increased hepatocyte proliferation but did not modify the hepatic mRNAs for hedgehog pathway ligands or target genes or genes regulating epithelial-to-mesenchymal transition. Although the effects of NAC on EtOH-induced fibrosis could not be fully evaluated, NAC had additive effects on hepatocyte proliferation and prevented EtOH-induced oxidative stress and necrosis, despite a failure to reverse hepatic steatosis.

Primary Care 2030: Creating an Enabling Ecosystem for Disruptive Primary Care Models to Achieve Universal Health Coverage in Low- and Middle-Income Countries.

Background: Forty years after Alma Ata, there is renewed commitment to strengthen primary health care as a foundation for achieving universal health coverage, but there is limited consensus on how to build strong primary health care systems to achieve these goals. Methods: We convened a diverse group of global stakeholders for a high-level dialogue on how to create an enabling ecosystem for disruptive primary care innovation. We focused our discussion on four themes: workforce innovation and strengthening; impactful use of data and technology; private sector engagement; and innovative financing mechanisms. Findings: Here, we present a summary of our convening's proceedings, with specific recommendations for strengthening primary health care systems within each of these four domains. Conclusions: In the wake of the Astana Declaration, there is global consensus that high-quality primary health care must be the foundation for universal health coverage. Significant disruptive innovation will be required to realize this goal. We offer our recommendations to the global community to catalyze further discourse and inform policy-making and program development on the path to Health for All by 2030.