The wear and tear on health: What is the role of occupation?

Health is well known to show a clear gradient by occupation. Although it may appear evident that occupation can affect health, there are multiple possible sources of selection that can generate a strong association, other than simply a causal effect of occupation on health. We link job characteristics to German panel data spanning 29 years to characterize occupations by their physical and psychosocial burden. Employing a dynamic model to control for factors that simultaneously affect health and selection into occupation, we find that selection into occupation accounts for at least 60% of the association. The effects of occupational characteristics such as physical strain and low job control are negative and increase with age: late‐career exposure to 1 year of high physical strain and low job control is comparable to the average health decline from ageing 16 and 6 months, respectively.     

Effect of reverse total shoulder arthroplasty humeral inclination on glenohumeral range of motion,deltoid force,and glenoid strain: a biomechanical study

BackgroundReverse total shoulder arthroplasty (RSA) primarily varies between 2 implant design options: a 135 humeral stem inclination that closely resembles anatomic orientation, versus the Grammont-style 155 humeral stem inclination that further medializes and distalizes the center of rotation (COR). The purpose of this study was to compare deltoid force, glenoid strain, and simulated glenohumeral range of motion (ROM) between RSA 135 and RSA 155 designs, with a series of standardized permutations of glenosphere offset and rotator cuff pathology.MethodsTwelve fresh-frozen cadaveric shoulder specimens were studied using a shoulder simulator. Native shoulder motion profiles for reproducible abduction range of motion were established using a customized testing device. Optical 3-dimensional tracking and pressure sensors were used to accurately record glenohumeral range of motion (ROM), deltoid force, and glenoid strain for RSA 135 and RSA 155 designs. For each cohort, all combinations of glenosphere offsets and rotator cuff tendon involvement were evaluated.ResultsThere was no significant difference in the overall abduction ROM between the 155 and the 135 humeral stem implants (P = .75). Resting abduction angle and maximum abduction angle were significantly greater with a 155 + STD (standard offset) construct than with a 135 + STD construct (P < .001 and P = .01, respectively). Both stem inclinations decreased combined deltoid force requirements as compared the native shoulder with a massive cuff tear. Effective glenoid strain did not vary significantly between 135 + STD and 155 + STD constructs (P = .66).ConclusionOverall, range of motion between the 135 and the 155 humeral stem inclinations was not significantly different. The cumulative deltoid force was lower in RSA shoulders when compared to native shoulders with massive rotator cuff tears, highlighting the utility of both implant designs. The Grammont-style 155 stem coupled with a 2.5 mm inferior offset glenosphere required less deltoid force to reach maximum abduction than did the more anatomic, lateralized 135 stem coupled with a 4 mm lateral offset glenosphere.Level of EvidenceBasic Science, Biomechanics Controlled Laboratory Study     

Higher order aberrations,refractive error development and myopia control: a review

Evidence from animal and human studies suggests that ocular growth is influenced by visual experience. Reduced retinal image quality and imposed optical defocus result in predictable changes in axial eye growth. Higher order aberrations are optical imperfections of the eye that alter retinal image quality despite optimal correction of spherical defocus and astigmatism. Since higher order aberrations reduce retinal image quality and produce variations in optical vergence across the entrance pupil of the eye, they may provide optical signals that contribute to the regulation and modulation of eye growth and refractive error development. The magnitude and type of higher order aberrations vary with age, refractive error, and during near work and accommodation. Furthermore, distinctive changes in higher order aberrations occur with various myopia control treatments, including atropine, near addition spectacle lenses, orthokeratology and soft multifocal and dual-focus contact lenses. Several plausible mechanisms have been proposed by which higher order aberrations may influence axial eye growth, the development of refractive error, and the treatment effect of myopia control interventions. Future studies of higher order aberrations, particularly during childhood, accommodation, and treatment with myopia control interventions are required to further our understanding of their potential role in refractive error development and eye growth.     

Comparison of Hemodynamics in the Ascending Aorta Between Pulsatile and Continuous Flow Left Ventricular Assist Devices Using Computational Fluid Dynamics Based on Computed Tomography Images

This study aims to investigate differences in hemodynamic conditions in the thoracic aorta for pulsatile and continuous‐flow left ventricular assist devices (LVADs) using computational fluid dynamics (CFD). Patient‐specific models were reconstructed from three patients with continuous‐flow LVAD (HeartMate II, Thoratec Corporation) and three patients with biventricular assist devices (Excor, Berlin Heart) where only the aortic part was included in the simulations. CFD simulations were performed with constant inflow for the continuous‐flow LVADs and time‐varying inflow for the pulsatile devices. Differences in flow patterns, wall shear stress (WSS), and dynamic pressure in the ascending aorta were compared for both cases. Retrograde flow patterns were observed in all cases proximal to the location of the outflow cannula anastomosis site. On average, dynamic pressures derived from the retrograde flow velocities were higher in the continuous‐flow group with large variations dependent on the angle of the cannula anastomosis relative to the ascending aorta (continuous group: 0.14 ± 0.2 mm Hg, pulsatile group: 0.013 ± 0.008 mm Hg). Elevated WSS contralaterally to the anastomosis site was observed in three of the six models with higher values for the continuous cases. Lower WSS and reduced pressure in the ascending aorta, both favorable hemodynamic conditions, were found in pulsatile versus continuous‐flow LVADs by means of CFD. These findings indicate, along with clinical observations reported by others, the superior performance of pulsatile LVADs.     

The HIV 5′ Gag Region Displays a Specific Nucleotide Bias Regulating Viral Splicing and Infectivity

Alternative splicing and the expression of intron-containing mRNAs is one hallmark of HIV gene expression. To facilitate the otherwise hampered nuclear export of non-fully processed mRNAs, HIV encodes the Rev protein, which recognizes its intronic response element and fuels the HIV RNAs into the CRM-1-dependent nuclear protein export pathway. Both alternative splicing and Rev-dependency are regulated by the primary HIV RNA sequence. Here, we show that these processes are extremely sensitive to sequence alterations in the 5’coding region of the HIV genomic RNA. Increasing the GC content by insertion of either GFP or silent mutations activates a cryptic splice donor site in gag, entirely deregulates the viral splicing pattern, and lowers infectivity. Interestingly, an adaptation of the inserted GFP sequence toward an HIV-like nucleotide bias reversed these phenotypes completely. Of note, the adaptation yielded completely different primary sequences although encoding the same amino acids. Thus, the phenotypes solely depend on the nucleotide composition of the two GFP versions. This is a strong indication of an HIV-specific mRNP code in the 5′ gag region wherein the primary RNA sequence bias creates motifs for RNA-binding proteins and controls the fate of the HIV-RNA in terms of viral gene expression and infectivity.     

Plasma levels of plasminogen activator inhibitor type 1, beta- thromboglobulin, and fibrinopeptide A before, during, and after treatment of acute myocardial infarction with alteplase

Plasma levels of plasminogen activator inhibitor type-1 (PAI-1), beta- thromboglobulin (beta TG), and fibrinopeptide A (FPA) were followed over 24 hours in 30 patients treated with alteplase for acute myocardial infarction. Samples were taken at baseline (T Oh), after 90 minutes (under alteplase, no heparin, T 1.5h), after 120 minutes (under alteplase and heparin, T 2h), 30 minutes after thrombolytic therapy (T 3.5h), as well as 12 hours (T 12h) and 24 hours (T 24h) after baseline. PAI-1 antigen levels (55 +/- 9 ng/mL at T Oh, mean +/- SEM) decreased to 35 +/- 5 (T 1.5h) and 40 +/- 6 (T 2h) ng/mL under alteplase, before increasing to 84 +/- 22 (T 3.5h), 130 +/- 30 (T 12h), and 64 +/- 7 (T 24h) ng/mL after therapy, P less than .001. A high baseline PAI-1 activity (18 +/- 3 ng/mL) decreased to 2.0 +/- 0.4 (T 1.5h) and 1.7 +/- 0.2 (T 2h) under alteplase and increased to 32 +/- 5 (T 12h) and 19 +/- 3 (T 24h) ng/mL after therapy (P less than .0001). beta TG levels (339 +/- 105 ng/mL at T Oh) decreased to 203 +/- 48 (T 2h), 154 +/- 51 (T 3.5h), 187 +/- 40 (T 12h), and 142 +/- 32 (T 24h) ng/mL under heparin (P less than .01). FPA levels (34 +/- 9 ng/mL at T Oh) increased to 85 +/- 15 ng/mL under alteplase alone (T 1.5h) and normalized under heparin (11 +/- 4, 6 +/- 2, 4 +/- 2, and 3 +/- 1 ng/mL at T 2h, T 3.5h, T 12h, and T 24h, respectively). A high level of FPA at T 3.5h correlated with reocclusion (33 +/- 12 ng/mL, n = 4 v 2.9 +/- 0.5 ng/mL, n = 21, P less than .005). We conclude that plasma levels of PAI- 1 antigen as well as activity markedly increase after alteplase therapy of acute myocardial infarction. The high activity of PAI-1 and decreasing beta TG levels suggest that platelets do not contribute significantly to this phenomenon. The marked increase of FPA levels under recombinant tissue-type plasminogen activator alone and its normalization under heparin emphasize the important role of concomitant anticoagulation in controlling further intravasal fibrin generation under alteplase.     

The growth factor requirements of STRO-1-positive human bone marrow stromal precursors under serum-deprived conditions in vitro

Factors that regulate the growth and development of primitive bone marrow stromal cell precursors are not well defined. We have examined 25 purified recombinant growth factors for their ability to initiate and support clonogenic growth of fibroblast colony-forming cells (CFU- F) from adult human bone marrow. Assays were performed using bone marrow mononuclear cells (BMMNC) enriched in CFU-F by magnetic- activated cell sorting (MACS) using the monoclonal antibody (MoAb) STRO- 1. A serum-deprived assay was developed to avoid components of fetal calf serum (FCS) that may mask or otherwise modify the response of CFU- F to exogenously added factors. L-ascorbate and the glucocorticoid dexamethasone were found to be essential for CFU-F colony development under serum-deprived conditions. Importantly, clonogenic growth of CFU- F in this culture system was absolutely dependent on an exogenous source of growth factor. Platelet-derived growth factor-BB (PDGF) and epidermal growth factor (EGF) demonstrated the greatest ability to support colony growth. Colony formation was dose-dependent, with half- maximal colony numbers at approximately 0.2 ng/mL for either factor and plateau numbers at concentrations in excess of 1.0 ng/mL. Simultaneous addition of PDGF and EGF had no effect on the number of colonies initiated but resulted in dose-dependent increases in mean colony diameter that were significant (P < or = .05) when compared with the effect of either factor alone or with the size of colonies elicited in control cultures by 20% FCS. Fluorescence-activated cell sorting (FACS) of BMMNC using MoAbs to the alpha chain of the PDGF receptor and to the EGF receptor in combination with the Moab STRO-1 demonstrated constitutive expression of both receptors by greater than 90% on CFU-F. Receptors for insulin-like growth factor-1 (IGF-1) and nerve growth factor (NGF) were also detected on STRO-1+ CFU-F, but in vitro both IGF- 1 and NGF did not support colony growth. This report demonstrates the development of a simple, reproducible, and stringent culture system for the growth and assay of stromal precursors under serum-deprived conditions and represents an important prerequisite for future studies of the role of growth factors in the regulation of stromal cell proliferation, differentiation, and development.