A Comparative Study of Additive and Subtractive Manufacturing Techniques for a Zirconia Dental Product: An Analysis of the Manufacturing Accuracy and the Bond Strength of Porcelain to Zirconia

This study was aimed at preparing zirconia samples via additive manufacturing (AM) and subtractive manufacturing (SM) and testing the following aspects: (1) the manufacturing accuracy of the zirconia samples and (2) the bond strength of porcelain to zirconia to evaluate the applicability of the zirconia fabricated by AM in dental clinics. We used three milling machines for SM (AR, K5, and UP) and a 3D printer for AM (AO). The manufacturing accuracy of the zirconia specimen in the internal and marginal areas was evaluated by superimposing techniques to calculate the root mean square (RMS) values. The bond strengths of porcelain to zirconia prepared via SM and AM were measured using a universal testing machine. The internal and marginal RMS values of the zirconia prepared by AM (AO) were within the range of those of the zirconia prepared by SM (AR, K5, and UP). Moreover, the bond strength value of the zirconia prepared by AM (35.12 ± 4.09 MPa) was significantly higher than that of the zirconia prepared by SM (30.26 ± 5.20 MPa). Therefore, AM technology has significant potential for applications in dentistry.     

From Powders to Dense Metal Parts: Characterization of a Commercial AlSiMg Alloy Processed through Direct Metal Laser Sintering

In this paper, a characterization of an AlSiMg alloy processed by direct metal laser sintering (DMLS) is presented, from the analysis of the starting powders, in terms of size, morphology and chemical composition, through to the evaluation of mechanical and microstructural properties of specimens built along different orientations parallel and perpendicular to the powder deposition plane. With respect to a similar aluminum alloy as-fabricated, a higher yield strength of about 40% due to the very fine microstructure, closely related to the mechanisms involved in this additive process is observed.     

Novel system for storage of buffy-coat-derived platelet concentrates in a glucose-based platelet additive solution: parameters and metabolism during storage and comparison to plasma

Background  In Europe, buffy-coat processing allows for the use of platelet additive solutions (PAS). These solutions, however, have long been questioned for their lack of glucose, a potentially essential nutrient for platelet storage. Using a novel, practical, two-part system for incorporation of glucose into an additive solution (PAS-G), this study compares platelet storage in plasma to storage in PAS-G.
Study Design and Methods  A paired study design of platelet concentrates (PC) were prepared from leucoreduced pools of eight buffy coats (BCP) split into two equal pools, with suspension in autologous plasma, or PAS-G. On days 2, 5, 7 and 9 of storage, samples were tested using standard in vitro platelet parameters. Data were analysed by paired Student's t -tests.
Results  During storage, PCs in PAS-G maintain a quality profile that is strikingly similar to PCs stored in plasma in terms of platelet activation (CD62) morphology score, swirl, glucose metabolism and pH. However, PCs in PAS-G perform lower ( P  < 0·05) in the %ESC and %HSR assays.
Conclusion  PAS-G's novel presentation allows incorporation of glucose into the additive solution so that it is roughly equivalent to plasma for the maintenance of buffy-coat PCs.     

Evaluation of the 3D Printing Accuracy of a Dental Model According to Its Internal Structure and Cross-Arch Plate Design: An In Vitro Study

The amount of photopolymer material consumed during the three-dimensional (3D) printing of a dental model varies with the volume and internal structure of the modeling data. This study analyzed how the internal structure and the presence of a cross-arch plate influence the accuracy of a 3D printed dental model. The model was designed with a U-shaped arch and the palate removed (Group U) or a cross-arch plate attached to the palate area (Group P), and the internal structure was divided into five types. The trueness and precision were analyzed for accuracy comparisons of the 3D printed models. Two-way ANOVA of the trueness revealed that the accuracy was 135.2 ± 26.3 µm (mean ± SD) in Group U and 85.6 ± 13.1 µm in Group P. Regarding the internal structure, the accuracy was 143.1 ± 46.8 µm in the 1.5 mm-thick shell group, which improved to 111.1 ± 31.9 µm and 106.7 ± 26.3 µm in the roughly filled and fully filled models, respectively. The precision was 70.3 ± 19.1 µm in Group U and 65.0 ± 8.8 µm in Group P. The results of this study suggest that a cross-arch plate is necessary for the accurate production of a model using 3D printing regardless of its internal structure. In Group U, the error during the printing process was higher for the hollowed models.     

From the Cover: In-cell thermodynamics and a new role for protein surfaces

There is abundant, physiologically relevant knowledge about protein cores; they are hydrophobic, exquisitely well packed, and nearly all hydrogen bonds are satisfied. An equivalent understanding of protein surfaces has remained elusive because proteins are almost exclusively studied in vitro in simple aqueous solutions. Here, we establish the essential physiological roles played by protein surfaces by measuring the equilibrium thermodynamics and kinetics of protein folding in the complex environment of living Escherichia coli cells, and under physiologically relevant in vitro conditions. Fluorine NMR data on the 7-kDa globular N-terminal SH3 domain of Drosophila signal transduction protein drk (SH3) show that charge–charge interactions are fundamental to protein stability and folding kinetics in cells. Our results contradict predictions from accepted theories of macromolecular crowding and show that cosolutes commonly used to mimic the cellular interior do not yield physiologically relevant information. As such, we provide the foundation for a complete picture of protein chemistry in cells.Classic theories about the effects of complex environments consider only hard-core repulsions (volume exclusion) and so predict entropy-driven protein stabilization (1–3). Here, we use the 7-kDa globular N-terminal SH3 domain of Drosophila signal transduction protein drk (SH3) as a model to test this idea in living cells. SH3 exists in a dynamic equilibrium between the folded state and the unfolded ensemble (4). This two-state behavior (5) is ideal for NMR-based studies of folding. Fluorine labeling (6) of its sole tryptophan leads to only two ¹⁹F resonances (7): one from the folded state, the other from the unfolded ensemble (Fig. 1A). The area under each resonance is proportional to its population, ρ_f and ρ_u, respectively. These populations are used to quantify protein stability via the modified standard state free energy of unfolding,ΔGU,T°′=−RTlnρUρF,[1]where R is the gas constant and T is the absolute temperature. Furthermore, the width at half height of each resonance is proportional to the transverse relaxation rate, which is an approximate measure of intermolecular interactions (8–10). Thus, this simple system yields both quantitative thermodynamic knowledge and information about interactions involving the folded state and the unfolded ensemble.Open in a separate windowFig. 1.Fluorine spectra acquired at 298 K, in buffer (A) and cells (B). The blue trace is from the postexperiment supernatant and shows that the red spectrum arises from protein inside cells. Stability curves (C) in buffer (black), in cells (red and green), and in 100 g/L urea (magenta). In-cell metabolite correction and analysis of uncertainties are discussed in Results and Discussion and Materials and Methods, respectively. Shaded regions are 95% confidence intervals. Error bars for buffer are smaller than the labels and represent the SD of three trials. Error bars for the in-cell data at 273, 298, and 313 K represent the SD of three trials. Stability in buffer (black) and solutions of 100 g/L BSA (blue) and lysozyme (red) at different pH values (D–F). The curve for buffer from C is reproduced in D. The net charges on SH3, BSA, and lysozyme (based on sequence) are shown. Error bars (298 K) represent the SD from three trials. Appearance of new resonances in the pH 3 BSA sample prevented extraction of thermodynamic parameters.To assess the enthalpic (ΔHU°′) and entropic (ΔSU°′) components, we measured the temperature dependence of ΔGU°′. These data were fitted to the integrated Gibbs–Helmholtz equation (11), assuming a constant heat capacity of unfolding, ΔCp,U°:ΔGU,T°′=ΔHU,Tref°′−TΔSU,Tref°′+ΔCp,U°′[T−Tref−T⁡lnTTref],[2]where T_ref is either the melting temperature, T_m (where ρ_f = ρ_u), or the temperature of maximum stability, T_s (where ΔSU°′ = 0) (11).     

From the Cover: Feature Article: Adaptation to a new environment allows cooperators to purge cheaters stochastically

Cooperation via production of common goods is found in diverse life forms ranging from viruses to social animals. However, natural selection predicts a “tragedy of the commons”: Cheaters, benefiting from without producing costly common goods, are more fit than cooperators and should destroy cooperation. In an attempt to discover novel mechanisms of cheater control, we eliminated known ones using a yeast cooperator–cheater system engineered to supply or exploit essential nutrients. Surprisingly, although less fit than cheaters, cooperators quickly dominated a fraction of cocultures. Cooperators isolated from these cocultures were superior to the cheater isolates they had been cocultured with, even though these cheaters were superior to ancestral cooperators. Resequencing and phenotypic analyses revealed that evolved cooperators and cheaters all harbored mutations adaptive to the nutrient-limited cooperative environment, allowing growth at a much lower concentration of nutrient than their ancestors. Even after the initial round of adaptation, evolved cooperators still stochastically dominated cheaters derived from them. We propose the “adaptive race” model: If during adaptation to an environment, the fitness gain of cooperators exceeds that of cheaters by at least the fitness cost of cooperation, the tragedy of the commons can be averted. Although cooperators and cheaters sample from the same pool of adaptive mutations, this symmetry is soon broken: The best cooperators purge cheaters and continue to grow, whereas the best cheaters cause rapid self-extinction. We speculate that adaptation to changing environments may contribute to the persistence of cooperative systems before the appearance of more sophisticated mechanisms of cheater control.     

From the bench to the bedside: emerging new treatments in multiple myeloma

Within the last decade, several novel classes of anti-myeloma therapeutics have become available. The clinical successes achieved by thalidomide, lenalidomide, and the proteasome inhibitor bortezomib, and in particular the ability of these agents to lead to major clinical responses in patients resistant to conventional or high-dose chemotherapy, have highlighted the importance of expanding further the spectrum of classes of agents utilized for the treatment of myeloma. Herein, we review the current status for the development of novel anti-myeloma agents, with emphasis on classes of therapeutics which have already translated into clinical trials or those in advanced stages of preclinical development. These include second-generation proteasome inhibitors (NPI-0052 and PR-171), heat shock protein 90 (hsp90) inhibitors, 2-methoxyestradiol, histone deacetylase (HDAC) inhibitors (e.g. SAHA and LBH589), fibroblast growth factor receptor 3 (FGF-R3) inhibitors, insulin-like growth factor 1 receptor (IGF-1R) inhibitors, mTOR inhibitors, monoclonal antibodies, and agents specifically targeting the tumor microenvironment, such as defibrotide.     

Reliability of progressive and additive MRI scoring systems for evaluation of haemophilic arthropathy in children: Expert MRI Working Group of the International Prophylaxis Study Group

Effective treatment of haemophilic arthropathy requires a detailed evaluation of joint integrity. Methodological assessment of magnetic resonance imaging (MRI) scores are needed to assure reproducibility of measurements when comparing results of clinical trials conducted in different centres. We compared the reliability of two MRI scoring systems for assessment of haemophilic arthropathy: one progressive system that displays the most severe change and one additive system that depicts osteochondral and soft tissue-related changes. A total of 47 1.5 T MRI examinations of knees (n = 21) and ankles (n = 26) of 42 haemophilic boys, age range, 22 months to 18 years, performed at different centres (Toronto, n = 20, Europe, n = 12 and Denver, n = 15) were independently reviewed by four radiologists at two occasions. Twenty-two examinations were from children <9 years and 25 from children >/=9. Sagittal and coronal gradient-echo (MPGR, 3D FLASH with fat saturation, GRASS) images were obtained. The MRI examinations of the ankle and knee studies presented with osteochondral abnormalities in 38.5% and 23.8% of the cases respectively. The two scoring systems demonstrated an excellent inter-reader [progressive, 0.88; additive (A, e, s and h components), 0.86] and intra-reader [progressive, 0.92; additive (A, e, s and h components), 0.93] reliability using intraclass correlation coefficients (ICCs). Although ICCs were slightly higher for knees when compared with ankles, and for older children when compared with younger children, all values fell within excellent inter- and intra-reader reliability categories. The two MRI scoring systems demonstrated a comparable reliability. This result constitutes the basis for further development of a combined MRI scoring system for assessment of haemophilic arthropathy, which incorporates progressive and additive components.     

From blood transfusion to patient blood management: a new paradigm for patient care and cost assessment of blood transfusion practice

The ageing population in developed countries, including Australia, is putting increasing demands on blood transfusion services. With a falling donor pool there is likely to be a shortage of blood and blood products in the next 20 to 30 years unless there are significant changes in medical practice. The National Health and Medical Research Council/Australasian Society of Blood Transfusion Clinical Practice Guidelines on the Use of Blood Components from 2001 are being redeveloped by the National Health and Medical Research Council/Australian and New Zealand Society of Blood Transfusion as evidence-based patient-focused Patient Blood Management guidelines with the aim of improving patient outcomes by reducing inappropriate blood and blood product use and targeting therapies for improving the management of anaemia and coagulopathies.     

From the Cover: A new feather type in a nonavian theropod and the early evolution of feathers

All described feathers in nonavian theropods are composite structures formed by multiple filaments. They closely resemble relatively advanced stages predicted by developmental models of the origin of feathers, but not the earliest stage. Here, we report a feather type in two specimens of the basal therizinosaur Beipiaosaurus, in which each individual feather is represented by a single broad filament. This morphotype is congruent with the stage I morphology predicted by developmental models, and all major predicted morphotypes have now been documented in the fossil record. This congruence between the full range of paleontological and developmental data strongly supports the hypothesis that feathers evolved and initially diversified in nonavian theropods before the origin of birds and the evolution of flight.     

From here to eternity: a unified kinetic model for the pathophysiology of atherosclerotic events

Two operative pathophysiological models underlie the clinical management of ischemic heart disease: a physical model founded on the magnitude of vascular stenosis and a biochemical model founded on the inflammatory processes within the atherosclerotic plaque. Despite their complementary natures, these 2 models are implicitly competitive—the stenotic model supporting the primacy of aggressive interventional procedures and the inflammatory model supporting the primacy of conservative medical management. We unified these alternative perspectives through a kinetic model that characterizes the pathophysiology of cardiovascular events as a network of exponential transitions between the inflammatory and stenotic states. According to this model, the prevalence of the normative (nonstenotic and noninflammatory) state falls exponentially, while the prevalences of the inflammatory and stenotic states rise to a peak and then fall off exponentially. According to this model, event rate increases as a complex function of both myocardial ischemia and vascular inflammation. Although the model has yet to be prospectively validated, it provides a theoretical foundation for predicting the degree to which atherosclerotic events are due to inflammation versus stenosis and the degree to which they can thereby be prevented by treatment strategies directed at plaque stabilization or relief of ischemia.     

From the Cover: Identification of reptilian genes encoding hair keratin-like proteins suggests a new scenario for the evolutionary origin of hair

The appearance of hair is one of the main evolutionary innovations in the amniote lineage leading to mammals. The main components of mammalian hair are cysteine-rich type I and type II keratins, also known as hard α-keratins or “hair keratins.” To determine the evolutionary history of these important structural proteins, we compared the genomic loci of the human hair keratin genes with the homologous loci of the chicken and of the green anole lizard Anolis carolinenis. The genome of the chicken contained one type II hair keratin-like gene, and the lizard genome contained two type I and four type II hair keratin-like genes. Orthology of the latter genes and mammalian hair keratins was supported by gene locus synteny, conserved exon–intron organization, and amino acid sequence similarity of the encoded proteins. The lizard hair keratin-like genes were expressed most strongly in the digits, indicating a role in claw formation. In addition, we identified a novel group of reptilian cysteine-rich type I keratins that lack homologues in mammals. Our data show that cysteine-rich α-keratins are not restricted to mammals and suggest that the evolution of mammalian hair involved the co-option of pre-existing structural proteins.     

Persistent mobility deficit in the absence of deficits in activities of daily living: a risk factor for mortality

OBJECTIVES: To investigate the extent to which self-reported mobility deficit in the absence of impairment in activities of daily living (ADL) is associated with elevated mortality risk. DESIGN: Prospective cohort study, with annual assessments of mobility and ADL status and ongoing monitoring of vital status. SETTING: Population-based cohort drawn from Medicare enrollees in New York City. PARTICIPANTS: One thousand two hundred ninety-eight older adults reporting functional status at baseline (1992-1994) and 2 years later. MEASUREMENTS: Subjects reported mobility (e.g., walking, climbing stairs, and rising from a chair) and ADL (e.g., bathing, toilet use, dressing, grooming, and feeding) limitations. Two-year functional status trajectories were noted. We used two additional follow-up periods, at 2 and 4 years, to examine the likelihood that older people with mobility deficit may face an increased risk of death without first passing through a state of enduring ADL disability. RESULTS: At 2 years, 12.7% had incident mobility deficit without ADL disability, and 21.3% were persistently disabled in mobility without ADL disability. Relative to subjects free of disability at baseline and follow-up, risk of mortality in the incident mobility deficit group was elevated at 2 and 4 years but did not achieve statistical significance. By contrast, for subjects with persistent mobility impairment who did not report ADL impairment, the mortality risk was significantly elevated both at 2 years (relative risk (RR) = 2.5; 95% confidence interval (CI) = 1.1-5.7)) and 4 years (RR = 2.9; 95% CI = 1.7-4.9)) of follow-up. Mortality was significantly elevated in this group in analyses restricted to respondents with no or only one comorbid condition. CONCLUSION: Continuing, self-reported mobility impairment in the absence of ADL deficit is a risk factor for mortality. Older people with self-reported mobility deficit face an increased risk of mortality without first passing through enduring states of ADL disability.     

与时俱进，迎接老年保健医学的挑战

本文首先对成功老化、现代老年保健医学服务理念进行了阐述,强调现代老年医学已由关注"病"转变到关注"人",老年医学的目标除了防治疾病外,更加强调对老年生理、认知功能的维持和心理康复治疗,达到"成功老化".实现现代老年医学的核心技术之一是老年综合评估.本文对老年综合评估技术、老年不合理用药、老年共病现象、常见老年疾病防治的研究进展和面临的挑战进行了深入探讨.