Interventions to Promote More Effective Balance-Recovery Reactions in Industrial Settings: New Perspectives on Footwear and Handrails

“Change-in-support” balance-recovery reactions that involve rapid stepping or reaching movements play a critical role in preventing falls. Recent geriatrics studies have led to new interventions to improve ability to execute these reactions effectively. Some of these interventions have the potential to reduce fall risk for younger persons working in industrial settings. In this paper, we review research pertaining to two such interventions: 1) balance-enhancing footwear insoles designed to improve stepping reactions, and 2) proximity-triggered handrail cueing systems designed to improve reach-to-grasp reactions. The insole has a raised ridge around the perimeter that is intended to improve balance control by providing increased stimulation of sensory receptors on the footsole in situations where loss of balance may be imminent. The cueing system uses flashing lights and/or verbal prompts to attract attention to the handrail and ensure that the brain registers its location, thereby facilitating more rapid and accurate grasping of the rail if and when sudden loss of balance occurs. Results to date support the efficacy of both interventions in geriatric populations. There is also some evidence that these interventions may improve balance control in younger persons; however, further research is needed to confirm their efficacy in preventing falls in industrial settings

Iterative Estimation of Variance Components in the 2-Way Crossed Classification, Mixed Model, with Interaction, Using Unbalanced Data

24 pages, 1 article*Iterative Estimation of Variance Components in the 2-Way Crossed Classification, Mixed Model, with Interaction, Using Unbalanced Data* (Corbeil, R. R.; Searle, S. R.) 24 page

Translation Invariant Maximum Likelihood Estimators of Variance Components in the Mixed Model

19 pages, 1 article*Translation Invariant Maximum Likelihood Estimators of Variance Components in the Mixed Model* (Corbeil, R. R.; Searle, S. R.) 19 page

Uterine Mast Cells and Immunoglobulin-E Antibody Responses During Clearance of \u3ci\u3eTritrichomonas foetus\u3c/i\u3e

We showed earlier that Tritrichomonas foetus–specific bovine immunoglobulin (Ig)G1 and IgA antibodies in uterine and vaginal secretions are correlated with clearance of this sexually transmitted infection. Eosinophils have been noted in previous studies of bovine trichomoniasis but the role of mast cells and IgE responses have not been reported. The hypothesis that IgE and mast cell degranulation play a role in clearance was tested in 25 virgin heifers inseminated experimentally and infected intravaginally with T. foetus strain D1 at estrus and cultured weekly. Groups were euthanatized at 3, 6, 9, or 12 weeks, when tissues were fixed and secretions were collected for culture and antibody analysis. Immunohistochemistry using a monoclonal antibody to a soluble lipophosphoglycan (LPG)–containing surface antigen (TF1.17) demonstrated antigen uptake by uterine epithelial cells. Lymphoid nodules were detected below antigen-positive epithelium. Little IgG2 antibody was detected but IgG1, IgA, IgM, and IgE T. foetus–specific antibodies increased in uterine secretions at weeks 6 and 9 after infection. This was inversely proportional to subepithelial mast cells numbers and most animals cleared the infection by the sampling time after the lowest mast cell count. Furthermore, soluble antigen was found in uterine epithelium above inductive sites (lymphoid nodules). Cross-linking of IgE on mast cells by antigen and perhaps LPG triggering appears to have resulted in degranulation. Released cytokines may account for production of predominantly Th2 (IgG1 and IgE) and IgA antibody responses, which are related to clearance of the infection

Effect of micromechanical stimulations on osteoblasts: development of a device simulating the mechanical situation at the bone-implant interface

Many experimental models have been developed to investigate the effects of mechanical stimulation of cells, but none of the existing devices can simulate micromotions at the cellular-mechanical interface with varying amplitudes and loads. Osteoblasts are sensitive to mechanical stimuli, so to study the bone-implant interface it would be important to quantify their reaction in a situation mimicking the mechanical situation arising at that interface. In this study, we present the development of a new device allowing the application of micromotions and load on cells in vitro. The new device allowed the cells to be stimulated with sinusoidal motions of amplitudes comprised between +/- 5 and +/- 50 microm, frequencies between 0.5 and 2 Hz, and loads between 50 and 1000 Pa. The device, with a total length of 20 cm, was designed to work in an incubator at 37 degrees C and 100% humidity. Expression of various bone important genes was monitored by real-time RT-PCR. Micromotions and load were shown to affect the behavior of osteoblasts by down-regulating the expression of genes necessary for the creation of organic extracellular matrix (collagen type I) as well as for genes involved in the mineralization process (osteocalcin, osteonectin). The developed device could then be used to simulate different mechanical situations at the bone-implant interface

Solvated interaction energy: from small-molecule to antibody drug design

Scoring functions are ubiquitous in structure-based drug design as an aid to predicting binding modes and estimating binding affinities. Ideally, a scoring function should be broadly applicable, obviating the need to recalibrate and refit its parameters for every new target and class of ligands. Traditionally, drugs have been small molecules, but in recent years biologics, particularly antibodies, have become an increasingly important if not dominant class of therapeutics. This makes the goal of having a transferable scoring function, i.e., one that spans the range of small-molecule to protein ligands, even more challenging. One such broadly applicable scoring function is the Solvated Interaction Energy (SIE), which has been developed and applied in our lab for the last 15 years, leading to several important applications. This physics-based method arose from efforts to understand the physics governing binding events, with particular care given to the role played by solvation. SIE has been used by us and many independent labs worldwide for virtual screening and discovery of novel small-molecule binders or optimization of known drugs. Moreover, without any retraining, it is found to be transferrable to predictions of antibody-antigen relative binding affinities and as accurate as functions trained on protein-protein binding affinities. SIE has been incorporated in conjunction with other scoring functions into ADAPT (Assisted Design of Antibody and Protein Therapeutics), our platform for affinity modulation of antibodies. Application of ADAPT resulted in the optimization of several antibodies with 10-to-100-fold improvements in binding affinity. Further applications included broadening the specificity of a single-domain antibody to be cross-reactive with virus variants of both SARS-CoV-1 and SARS-CoV-2, and the design of safer antibodies by engineering of a pH switch to make them more selective towards acidic tumors while sparing normal tissues at physiological pH

Human α2β1HI CD133+VE epithelial prostate stem cells express low levels of active androgen receptor

Stem cells are thought to be the cell of origin in malignant transformation in many tissues, but their role in human prostate carcinogenesis continues to be debated. One of the conflicts with this model is that cancer stem cells have been described to lack androgen receptor (AR) expression, which is of established importance in prostate cancer initiation and progression. We re-examined the expression patterns of AR within adult prostate epithelial differentiation using an optimised sensitive and specific approach examining transcript, protein and AR regulated gene expression. Highly enriched populations were isolated consisting of stem (α(2)β(1)(HI) CD133(+VE)), transiently amplifying (α(2)β(1)(HI) CD133(-VE)) and terminally differentiated (α(2)β(1)(LOW) CD133(-VE)) cells. AR transcript and protein expression was confirmed in α(2)β(1)(HI) CD133(+VE) and CD133(-VE) progenitor cells. Flow cytometry confirmed that median (±SD) fraction of cells expressing AR were 77% (±6%) in α(2)β(1)(HI) CD133(+VE) stem cells and 68% (±12%) in α(2)β(1)(HI) CD133(-VE) transiently amplifying cells. However, 3-fold lower levels of total AR protein expression (peak and median immunofluorescence) were present in α(2)β(1)(HI) CD133(+VE) stem cells compared with differentiated cells. This finding was confirmed with dual immunostaining of prostate sections for AR and CD133, which again demonstrated low levels of AR within basal CD133(+VE) cells. Activity of the AR was confirmed in prostate progenitor cells by the expression of low levels of the AR regulated genes PSA, KLK2 and TMPRSS2. The confirmation of AR expression in prostate progenitor cells allows integration of the cancer stem cell theory with the established models of prostate cancer initiation based on a functional AR. Further study of specific AR functions in prostate stem and differentiated cells may highlight novel mechanisms of prostate homeostasis and insights into tumourigenesis

Lectinhistochemical study in penis and prepuce of bulls experimantally infected with tritrichomonas foetus

En trabajos anteriores hemos demostrado, mediante lectinhistoquímica, que el patrón de carbohidratos del epitelio de los órganos genitales de las hembras bovinas se modifica en la tritricomonosis y en la campilobacteriosis. Para el caso de la tritricomonosis estas modificaciones pudieron repetirse en un modelo experimental murino. El toro actúa como transmisor de estas enfermedades venéreas, que producen severos trastornos en las hembras, incluyendo muerte embrionaria y aborto, pero que en el macho generan solo en ocasiones una inflamación local leve.Facultad de Ciencias Veterinaria

Expression of the "stem cell marker" CD133 in pancreas and pancreatic ductal adenocarcinomas

<p>Abstract</p> <p>Background</p> <p>It has been suggested that a small population of cells with unique self-renewal properties and malignant potential exists in solid tumors. Such "cancer stem cells" have been isolated by flow cytometry, followed by xenograft studies of their tumor-initiating properties. A frequently used sorting marker in these experiments is the cell surface protein CD133 (prominin-1). The aim of this work was to examine the distribution of CD133 in pancreatic exocrine cancer.</p> <p>Methods</p> <p>Fifty-one cases of pancreatic ductal adenocarcinomas were clinically and histopathologically evaluated, and immunohistochemically investigated for expression of CD133, cytokeratin 19 and chromogranin A. The results were interpreted on the background of CD133 expression in normal pancreas and other normal and malignant human tissues.</p> <p>Results</p> <p>CD133 positivity could not be related to a specific embryonic layer of organ origin and was seen mainly at the apical/endoluminal surface of non-squamous, glandular epithelia and of malignant cells in ductal arrangement. Cytoplasmic CD133 staining was observed in some non-epithelial malignancies. In the pancreas, we found CD133 expressed on the apical membrane of ductal cells. In a small subset of ductal cells and in cells in centroacinar position, we also observed expression in the cytoplasm. Pancreatic ductal adenocarcinomas showed a varying degree of apical cell surface CD133 expression, and cytoplasmic staining in a few tumor cells was noted. There was no correlation between the level of CD133 expression and patient survival.</p> <p>Conclusion</p> <p>Neither in the pancreas nor in the other investigated organs can CD133 membrane expression alone be a criterion for "stemness". However, there was an interesting difference in subcellular localization with a minor cell population in normal and malignant pancreatic tissue showing cytoplasmic expression. Moreover, since CD133 was expressed in shed ductal cells of pancreatic tumors and was found on the surface of tumor cells in vessels, this molecule may have a potential as clinical marker in patients suffering from pancreatic cancer.</p