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Sample records for age current repair

  1. Current Trends in Laparoscopic Ventral Hernia Repair

    PubMed Central

    Patapis, Paul; Zavras, Nick; Tzanetis, Panagiotis; Machairas, Anastasios

    2015-01-01

    Background and Objectives: The purpose of this study was to analyze the surgical technique, postoperative complications, and possible recurrence after laparoscopic ventral hernia repair (LVHR) in comparison with open ventral hernia repair (OVHR), based on the international literature. Database: A Medline search of the current English literature was performed using the terms laparoscopic ventral hernia repair and incisional hernia repair. Conclusions: LVHR is a safe alternative to the open method, with the main advantages being minimal postoperative pain, shorter recovery, and decreased wound and mesh infections. Incidental enterotomy can be avoided by using a meticulous technique and sharp dissection to avoid thermal injury. PMID:26273186

  2. DNA Damage, DNA Repair, Aging, and Neurodegeneration.

    PubMed

    Maynard, Scott; Fang, Evandro Fei; Scheibye-Knudsen, Morten; Croteau, Deborah L; Bohr, Vilhelm A

    2015-09-18

    Aging in mammals is accompanied by a progressive atrophy of tissues and organs, and stochastic damage accumulation to the macromolecules DNA, RNA, proteins, and lipids. The sequence of the human genome represents our genetic blueprint, and accumulating evidence suggests that loss of genomic maintenance may causally contribute to aging. Distinct evidence for a role of imperfect DNA repair in aging is that several premature aging syndromes have underlying genetic DNA repair defects. Accumulation of DNA damage may be particularly prevalent in the central nervous system owing to the low DNA repair capacity in postmitotic brain tissue. It is generally believed that the cumulative effects of the deleterious changes that occur in aging, mostly after the reproductive phase, contribute to species-specific rates of aging. In addition to nuclear DNA damage contributions to aging, there is also abundant evidence for a causative link between mitochondrial DNA damage and the major phenotypes associated with aging. Understanding the mechanistic basis for the association of DNA damage and DNA repair with aging and age-related diseases, such as neurodegeneration, would give insight into contravening age-related diseases and promoting a healthy life span.

  3. Chromatin Remodeling, DNA Damage Repair and Aging

    PubMed Central

    Liu, Baohua; Yip, Raymond KH; Zhou, Zhongjun

    2012-01-01

    Cells are constantly exposed to a variety of environmental and endogenous conditions causing DNA damage, which is detected and repaired by conserved DNA repair pathways to maintain genomic integrity. Chromatin remodeling is critical in this process, as the organization of eukaryotic DNA into compact chromatin presents a natural barrier to all DNA-related events. Studies on human premature aging syndromes together with normal aging have suggested that accumulated damages might lead to exhaustion of resources that are required for physiological functions and thus accelerate aging. In this manuscript, combining the present understandings and latest findings, we focus mainly on discussing the role of chromatin remodeling in the repair of DNA double-strand breaks (DSBs) and regulation of aging. PMID:23633913

  4. BRCA Mutations, DNA Repair Deficiency, and Ovarian Aging1

    PubMed Central

    Oktay, Kutluk; Turan, Volkan; Titus, Shiny; Stobezki, Robert; Liu, Lin

    2015-01-01

    Oocyte aging has a significant impact on reproductive outcomes both quantitatively and qualitatively. However, the molecular mechanisms underlying the age-related decline in reproductive success have not been fully addressed. BRCA is known to be involved in homologous DNA recombination and plays an essential role in double-strand DNA break repair. Given the growing body of laboratory and clinical evidence, we performed a systematic review on the current understanding of the role of DNA repair in human reproduction. We find that BRCA mutations negatively affect ovarian reserve based on convincing evidence from in vitro and in vivo results and prospective studies. Because decline in the function of the intact gene occurs at an earlier age, women with BRCA1 mutations exhibit accelerated ovarian aging, unlike those with BRCA2 mutations. However, because of the still robust function of the intact allele in younger women and because of the masking of most severe cases by prophylactic oophorectomy or cancer, it is less likely one would see an effect of BRCA mutations on fertility until later in reproductive age. The impact of BRCA2 mutations on reproductive function may be less visible because of the delayed decline in the function of normal BRCA2 allele. BRCA1 function and ataxia-telangiectasia-mutated (ATM)-mediated DNA repair may also be important in the pathogenesis of age-induced increase in aneuploidy. BRCA1 is required for meiotic spindle assembly, and cohesion function between sister chromatids is also regulated by ATM family member proteins. Taken together, these findings strongly suggest the implication of BRCA and DNA repair malfunction in ovarian aging. PMID:26224004

  5. Premature aging and cancer in nucleotide excision repair-disorders

    PubMed Central

    Diderich, K.; Alanazi, M.; Hoeijmakers, J.H.J.

    2014-01-01

    During past decades the major impact of DNA damage on cancer as ‘disease of the genes’ has become abundantly apparent. In addition to cancer recent years have also uncovered a very strong association of DNA damage with many features of (premature) aging. The notion that DNA repair systems not only protect against cancer but equally against too fast aging has become evident from a systematic, integral analysis of a variety of mouse mutants carrying defects in e.g. transcription-coupled repair with or without an additional impairment of global genome nucleotide excision repair and the corresponding segmental premature aging syndromes in man. A striking correlation between the degree of the DNA repair deficiency and the acceleration of specific progeroid symptoms has been discovered for those repair systems that primarily protect from the cytotoxic and cytostatic effects of DNA damage. These observations are explained from the perspective of nucleotide excision repair mouse mutant and human syndromes. However, similar principles likely apply to other DNA repair pathways including interstrand crosslink repair and double strand break repair and genome maintenance systems in general, supporting the notion that DNA damage constitutes an important intermediate in the process of aging. PMID:21680258

  6. Current trends in laparoscopic groin hernia repair: A review.

    PubMed

    Pahwa, Harvinder Singh; Kumar, Awanish; Agarwal, Prerit; Agarwal, Akshay Anand

    2015-09-16

    Hernia is a common problem of the modern world with its incidence more in developing countries. Inguinal hernia is the most common groin hernia repaired worldwide. With advancement in technology operative techniques of repair have also evolved. A PubMed and COCHRANE database search was accomplished in this regard to establish the current status of laparoscopic inguinal hernia repair in view of recent published literature. Published literature support that laparoscopic hernia repair is best suited for recurrent and bilateral inguinal hernia although it may be offered for primary inguinal hernia if expertise is available.

  7. Endovascular Aneurysm Repair: Current and Future Status

    SciTech Connect

    Hinchliffe, R. J. Ivancev, K.

    2008-05-15

    Endovascular aneurysm repair has rapidly expanded since its introduction in the early 1990s. Early experiences were associated with high rates of complications including conversion to open repair. Perioperative morbidity and mortality results have improved but these concerns have been replaced by questions about long-term durability. Gradually, too, these problems have been addressed. Challenges of today include the ability to roll out the endovascular technique to patients with adverse aneurysm morphology. Fenestrated and branch stent-graft technology is in its infancy. Only now are we beginning to fully understand the advantages, limitations, and complications of such technology. This paper outlines some of the concepts and discusses the controversies and challenges facing clinicians involved in endovascular aneurysm surgery today and in the future.

  8. New Technologies for Repairing Aging Cables in Nuclear Power Plants

    SciTech Connect

    Simmons, Kevin L.; Fifield, Leonard S.; Westman, Matthew P.

    2013-09-11

    The goal of this project is to demonstrate a proof-of-concept for a technique to repair aging cables that have been subjected to degradation associated with long-term thermal and radiation exposure in nuclear power plants. The physical degradation of the aging cables manifests itself primarily as cracking and increased brittleness of the polymeric electrical insulation. Therefore, the proposed cable-repair concept comprises development of techniques to impart a softening agent within the deteriorated polymer insulation jacket so as to regain the ability of the insulation to stretch without failing and possibly to heal existing cracks in the insulation. Our approach is to use commercially available ethylene-propylene rubber (EPR) as the relevant test material, demonstrate the adsorption of chemical treatments in the EPR and quantify changes in resulting physical and mechanical properties. EPR cable samples have been thermally treated in air to produce specimens corresponding to the full range of cable age-performance points from new (>350% elongation at break) to end-of-life (<50% elongation at break). The current focus is on two chemical treatments selected as candidates for restoring age-related cable elasticity loss: a rubber plasticizer and a reactive silane molecule. EPR specimens of 200, 150, 100, and 50% elongation at break have been soaked in the candidate chemical treatments and the kinetics of chemical uptake, measured by change in mass of the samples, has been determined. Mechanical properties as a function of aging and chemical treatment have been measured including ultimate tensile strength, tensile modulus at 50% strain, elongation at break, and storage modulus. Dimensional changes with treatment and changes in glass transition temperature were also investigated. These ongoing experiments are expected to provide insight into the physical-chemical nature of the effect of thermal degradation on EPR rejuvenation limits and to advance novel methods for

  9. Effect of aging and dietary restriction on DNA repair

    SciTech Connect

    Weraarchakul, N.; Strong, R.; Wood, W.G.; Richardson, A.

    1989-03-01

    DNA repair was studied as a function of age in cells isolated from both the liver and the kidney of male Fischer F344 rats. DNA repair was measured by quantifying unscheduled DNA synthesis induced by UV irradiation. Unscheduled DNA synthesis decreased approximately 50% between the ages of 5 and 30 months in both hepatocytes and kidney cells. The age-related decline in unscheduled DNA synthesis in cells isolated from the liver and kidney was compared in rats fed ad libitum and rats fed a calorie-restricted diet; calorie restriction has been shown to increase the survival of rodents. The level of unscheduled DNA synthesis was significantly higher in hepatocytes and kidney cells isolated from the rats fed the restricted diet. Thus, calorie restriction appears to retard the age-related decline in DNA repair.

  10. Mitochondrial DNA repair and association with aging - an update

    PubMed Central

    Gredilla, Ricardo; Bohr, Vilhelm A.; Stevnsner, Tinna

    2010-01-01

    Mitochondrial DNA is constantly exposed to oxidative injury. Due to its location close to the main site of reactive oxygen species, the inner mitochondrial membrane, mtDNA is more susceptible than nuclear DNA to oxidative damage. The accumulation of DNA damage is thought to play a critical role in the aging process and to be particularly deleterious in post-mitotic cells. Thus, DNA repair is an important mechanism for maintenance of genomic integrity. Despite the importance of mitochondria in the aging process, it was thought for many years that mitochondria lacked an enzymatic DNA repair system comparable to that in the nuclear compartment. However, it is now well established that DNA repair actively takes place in mitochondria. Oxidative DNA damage processing, base excision repair mechanisms were the first to be described in these organelles, and consequently the best understood. However, new proteins and novel DNA repair pathways, thought to be exclusively present in the nucleus, have recently been described also to be present in mitochondria. Here we review the main mitochondrial DNA repair pathways and their association with the aging process. PMID:20096766

  11. Metabolism, genomics, and DNA repair in the mouse aging liver.

    PubMed

    Lebel, Michel; de Souza-Pinto, Nadja C; Bohr, Vilhelm A

    2011-01-01

    The liver plays a pivotal role in the metabolism of nutrients, drugs, hormones, and metabolic waste products, thereby maintaining body homeostasis. The liver undergoes substantial changes in structure and function within old age. Such changes are associated with significant impairment of many hepatic metabolic and detoxification activities, with implications for systemic aging and age-related disease. It has become clear, using rodent models as biological tools, that genetic instability in the form of gross DNA rearrangements or point mutations accumulate in the liver with age. DNA lesions, such as oxidized bases or persistent breaks, increase with age and correlate well with the presence of senescent hepatocytes. The level of DNA damage and/or mutation can be affected by changes in carcinogen activation, decreased ability to repair DNA, or a combination of these factors. This paper covers some of the DNA repair pathways affecting liver homeostasis with age using rodents as model systems.

  12. DNA damage and repair in telomeres: relation to aging.

    PubMed Central

    Kruk, P A; Rampino, N J; Bohr, V A

    1995-01-01

    We have established a method for the detection of DNA damage and its repair in human telomeres, the natural ends of chromosomes which are necessary for replication and critical for chromosomal stability. We find that ultraviolet light-induced pyrimidine dimers in telomeric DNA are repaired less efficiently than endogenous genes but more efficiently than inactive, noncoding regions. We have also measured telomeric length, telomeric DNA damage, and its repair in relation to the progression of aging. Telomeres are shorter in fibroblasts from an old donor compared to fibroblasts from a young donor, shortest in cells from a patient with the progeroid disorder Werner syndrome, and relatively long in fibroblasts from a patient with Alzheimer disease. Telomeric DNA repair efficiency is lower in cells from an old donor than in cells from a young donor, normal in Alzheimer cells, and slightly lower in Werner cells. It is possible that this decline in telomeric repair with aging is of functional significance to an age-related decline in genomic stability. Images Fig. 1 Fig. 2 PMID:7816828

  13. Ageing airplane repair assessment program for Airbus A300

    NASA Technical Reports Server (NTRS)

    Gaillardon, J. M.; Schmidt, HANS-J.; Brandecker, B.

    1992-01-01

    This paper describes the current status of the repair categorization activities and includes all details about the methodologies developed for determination of the inspection program for the skin on pressurized fuselages. For inspection threshold determination two methods are defined based on fatigue life approach, a simplified and detailed method. The detailed method considers 15 different parameters to assess the influences of material, geometry, size location, aircraft usage, and workmanship on the fatigue life of the repair and the original structure. For definition of the inspection intervals a general method is developed which applies to all concerned repairs. For this the initial flaw concept is used by considering 6 parameters and the detectable flaw sizes depending on proposed nondestructive inspection methods. An alternative method is provided for small repairs allowing visual inspection with shorter intervals.

  14. Aging and photo-aging DNA repair phenotype of skin cells-evidence toward an effect of chronic sun-exposure.

    PubMed

    Prunier, Chloé; Masson-Genteuil, Gwénaëlle; Ugolin, Nicolas; Sarrazy, Fanny; Sauvaigo, Sylvie

    2012-08-01

    Several studies have demonstrated the deleterious effect of aging on the capacity of cells to repair their DNA. However, current existing assays aimed at measuring DNA repair address only a specific repair step dedicated to the correction of a specific DNA lesion type. Consequently they provide no information regarding the repair pathways that handle other types of lesions. In addition to aging, consequences of photo-exposure on these repair processes remain elusive. In this study we evaluated the consequence of aging and of chronic and/or acute photo-exposure on DNA repair in human skin fibroblasts using a multiplexed approach, which provided detailed information on several repair pathways at the same time. The resulting data were analyzed with adapted statistics/bioinformatics tools. We showed that, irrespective of the repair pathway considered, excision/synthesis was less efficient in non-exposed cells from elderly compared to cells from young adults and that photo-exposure disrupted this very clear pattern. Moreover, it was evidenced that chronic sun-exposure induced changes in DNA repair properties. Finally, the identification of a specific signature at the level of the NER pathway in cells repeatedly exposed to sun revealed a cumulative effect of UVB exposure and chronic sun irradiation. The uses of bioinformatics tools in this study was essential to fully take advantage of the large sum of data obtained with our multiplexed DNA repair assay and unravel the effects of environmental exposure on DNA repair pathways.

  15. Beyond Repair: Literacy, Technology, and a Curriculum of Aging

    ERIC Educational Resources Information Center

    Bowen, Lauren Marshall

    2012-01-01

    The magazine of the American Association of Retired Persons (AARP) often relies on problematic rhetorics that privilege youth-centered ideals and create limited representations of older adults' literacy in digital times. These rhetorics rest on a metaphor of repair, which labels aging adults as primarily bodies in need of fixing or protection. In…

  16. Color stability of repaired composite submitted to accelerated artificial aging.

    PubMed

    Souza, Ana Beatriz Silva; Silame, Francisca Daniele Jardilino; Alandia-Roman, Carla Cecilia; Cruvinel, Diogo Rodrigues; Garcia, Lucas da Fonseca Roberti; Pires-de-Souza, Fernanda de Carvalho Panzeri

    2012-01-01

    The aim of this study was to evaluate the color stability (ΔE) of nanoparticulate composite, with consideration for the type of surface treatment performed before repair. A Teflon matrix was used to fabricate 50 test specimens from composite. After initial color readout, the specimens were submitted to 100 hours of accelerated artificial aging (AAA). The samples were divided into five groups (n = 10), according to the surface treatment performed: sandblasting with aluminum oxide powder, phosphoric acid, and an adhesive system (Group 1); sandblasting with aluminum oxide powder, phosphoric acid, and a flowable composite (Group 2); abrasion with a diamond bur, phosphoric acid, and an adhesive system (Group 3); abrasion with a diamond bur, phosphoric acid, and a nanoparticulate composite (Group 4); and a control group (Group 5). After repair, a new color readout was taken, the test specimens were submitted to a new AAA cycle (300 hours), and the final color readout was taken. Comparison of the ΔE means (one-way ANOVA and Tukey tests, p < 0.05) demonstrated no statistically significant differences among the groups (p > 0.05) after 100 hours of AAA. After repair, Group 1 (4.61 ± 2.03) presented the highest color alteration with a statistically significant difference compared with the other groups (p < 0.05). After 300 hours, Group 4 specimens (13.84 ± 0.71) presented the lowest color alteration in comparison with the other groups, with a statistically significant difference (p < 0.05). It was concluded that the repair performed in Group 4 provided greater esthetic recovery, made possible by the regression in the ΔE values of the restorations after repair, and less color alteration of the restorations over the course of time. PMID:23032241

  17. [The correlations between aging of the human body, oxidative stress and reduced efficiency of repair systems].

    PubMed

    Michalak, Aleksandra; Krzeszowiak, Jakub; Markiewicz-Górka, Iwona

    2014-12-15

    The article presents an current knowledge overview about the importance of oxidative stress and reduced efficiency of repair processes during the aging process of the human body. Oxidative damage to cellular macromolecules (proteins, lipids, nucleic acids), are formed under the influence of reactive oxygen species (ROS). They are the part of important mechanism which is responsible for the process of aging and the development of many diseases. The most important effects result from DNA damage, due to the mutations formation, which can lead to the development of tumors. However, a well-functioning repair systems (i.a. homologous recombination) remove the damage and prevent harmful changes in the cells. Lipid peroxidation products also cause oxidative modification of nucleic acids (and proteins). Proteins and fats also have repair systems, but much simpler than those responsible for the repair of nucleic acids. Unfortunately, with increasing age, they are more weakened, which contributes to increase numbers of cell damage, and consequently development of diseases specific to old age: cancer, neurodegenerative diseases or atherosclerosis.

  18. Neutrophil depletion delays wound repair in aged mice

    PubMed Central

    Nishio, Naomi; Okawa, Yayoi; Sakurai, Hidetoshi

    2008-01-01

    One of the most important clinical problems in caring for elderly patients is treatment of pressure ulcers. One component of normal wound healing is the generation of an inflammatory reaction, which is characterized by the sequential infiltration of neutrophils, macrophages and lymphocytes. Neutrophils migrate early in the wound healing process. In aged C57BL/6 mice, wound healing is relatively inefficient. We examined the effects of neutrophil numbers on wound healing in both young and aged mice. We found that the depletion of neutrophils by anti-Gr-1 antibody dramatically delayed wound healing in aged mice. The depletion of neutrophils in young mice had less effect on the kinetics of wound healing. Intravenous G-CSF injection increased the migration of neutrophils to the wound site. While the rate of wound repair did not change significantly in young mice following G-CSF injection, it increased significantly in old mice. PMID:19424869

  19. Current Ethical Issues in Aging.

    ERIC Educational Resources Information Center

    Dubler, Nancy Neveloff, Ed.; And Others

    1994-01-01

    Articles in this special issue look at ethical issues in aging in geriatric care, improving care of the dying, the value of autonomy and respect, the role of religion in health-related decisions, protection of nursing facility residents, physician-assisted dying, conflict resolution in nursing homes, and dealing with patients' demands for…

  20. A potential impact of DNA repair on ageing and lifespan in the ageing model organism Podospora anserina: decrease in mitochondrial DNA repair activity during ageing.

    PubMed

    Soerensen, Mette; Gredilla, Ricardo; Müller-Ohldach, Mathis; Werner, Alexandra; Bohr, Vilhelm A; Osiewacz, Heinz D; Stevnsner, Tinna

    2009-08-01

    The free radical theory of ageing states that ROS play a key role in age-related decrease in mitochondrial function via the damage of mitochondrial DNA (mtDNA), proteins and lipids. In the sexually reproducing ascomycete Podospora anserina ageing is, as in other eukaryotes, associated with mtDNA instability and mitochondrial dysfunction. Part of the mtDNA instabilities may arise due to accumulation of ROS induced mtDNA lesions, which, as previously suggested for mammals, may be caused by an age-related decrease in base excision repair (BER). Alignments of known BER protein sequences with the P. anserina genome revealed high homology. We report for the first time the presence of BER activities in P. anserina mitochondrial extracts. DNA glycosylase activities decrease with age, suggesting that the increased mtDNA instability with age may be caused by decreased ability to repair mtDNA damage and hence contribute to ageing and lifespan control in this ageing model. Additionally, we find low DNA glycosylase activities in the long-lived mutants grisea and DeltaPaCox17::ble, which are characterized by low mitochondrial ROS generation. Overall, our data identify a potential role of mtDNA repair in controlling ageing and life span in P. anserina, a mechanism possibly regulated in response to ROS levels.

  1. DNA repair, insulin signaling and sirtuins: at the crossroads between cancer and aging.

    PubMed

    Mostoslavsky, Raul

    2008-01-01

    For many years organismal aging and cancer were viewed as separate entities. Recent studies however have suggested that these two seemingly disparate biological processes may in fact share common biochemical pathways. One area of emerging convergence involves the intersection of pathways known to mediate DNA repair with pathways previously implicated in insulin signaling. Recent evidence suggests that the sirtuin family of proteins act as central mediators of this molecular crosstalk. The coordination of DNA repair with overall energy balance may be essential for reducing the risk of developing cancer as well as for determining the rate at which we age. This review will summarize our current knowledge on how the maintenance of genomic integrity and insulin signaling intersect, the potential regulation of sirtuins in this crosstalk, and how this coordinated regulation may have important implication for both tumor-free and overall survival. PMID:18508709

  2. Differential age-related changes in mitochondrial DNA repair activities in mouse brain regions

    PubMed Central

    Gredilla, Ricardo; Garm, Christian; Holm, Rikke; Bohr, Vilhelm A.; Stevnsner, Tinna

    2008-01-01

    Aging in the brain is characterized by increased susceptibility to neuronal loss and functional decline, and mitochondrial DNA (mtDNA) mutations are thought to play an important role in these processes. Due to the proximity of mtDNA to the main sites of mitochondrial free radical generation, oxidative stress is a major source of DNA mutations in mitochondria. The base excision repair (BER) pathway removes oxidative lesions from mtDNA, thereby constituting an important mechanism to avoid accumulation of mtDNA mutations. The complexity of the brain implies that exposure and defence against oxidative stress varies among brain regions and hence some regions may be particularly prone to accumulation of mtDNA damages. In the current study we investigated the efficiency of the BER pathway throughout the murine lifespan in mitochondria from cortex and hippocampus, regions that are central in mammalian cognition, and which are severely affected during aging and in neurodegenerative diseases. A regional specific regulation of mitochondrial DNA repair activities was observed with aging. In cortical mitochondria, DNA glycosylase activities peaked at middle-age followed by a significant drop at old age. However, only minor changes were observed in hippocampal mitochondria during the whole lifespan of the animals. Furthermore, DNA glycosylase activities were lower in hippocampal than in cortical mitochondria. Mitochondrial AP endonuclease activity increased in old animals in both brain regions. Our data suggest an important regional specific regulation of mitochondrial BER during aging. PMID:18701195

  3. Weld repair of aged Cr-Mo steel piping -- A review of literature

    SciTech Connect

    Viswanathan, R.; Gandy, D.

    2000-02-01

    Power plant piping operating at elevated temperatures is subject to several types of service aging-related degradation, such as softening, spheroidization, embrittlement, and creep. When cracks are found in these components, weld repair is often employed to ensure continued operation. The efficacy of the weld repairs in terms of extending the life of the aged components has, however, not been documented quantitatively. The Electric Power Research institute (EPRI) has recently undertaken a comprehensive study to evaluate weld repairs performed to aged piping. In connection with this study, results from other worldwide activities have been reviewed, leading to significant conclusions regarding weld repair. this review of results from several worldwide studies has confirmed that aged high-temperature piping can be successfully weld repaired to gain additional lives in excess of several decades. The key aspects of successful weld repair include excavation and removal of all prior creep cavitation damage, elimination of external bending stresses, and implementation of good welding practice. From merely a creep rupture point of view, postweld heat treatment (PWHT) has been concluded to be superfluous by several authors. Temperbead repairs appear to offer a promising alternative to PWHT repairs from a creep, tensile, and toughness standpoint. Choice of the repair process ultimately is dictated by many considerations such as toughness, notch sensitivity, residual stresses and hydrogen embrittlement susceptibility. Several reports suggest that gas tungsten arc welding (GTAW) repairs may outperform shielded metal arc welding (SMAW) repairs with or without PWHT.

  4. Current perspectives in stem cell research for knee cartilage repair

    PubMed Central

    Orth, Patrick; Rey-Rico, Ana; Venkatesan, Jagadeesh K; Madry, Henning; Cucchiarini, Magali

    2014-01-01

    Protocols based on the delivery of stem cells are currently applied in patients, showing encouraging results for the treatment of articular cartilage lesions (focal defects, osteoarthritis). Yet, restoration of a fully functional cartilage surface (native structural organization and mechanical functions) especially in the knee joint has not been reported to date, showing the need for improved designs of clinical trials. Various sources of progenitor cells are now available, originating from adult tissues but also from embryonic or reprogrammed tissues, most of which have already been evaluated for their chondrogenic potential in culture and for their reparative properties in vivo upon implantation in relevant animal models of cartilage lesions. Nevertheless, particular attention will be needed regarding their safe clinical use and their potential to form a cartilaginous repair tissue of proper quality and functionality in the patient. Possible improvements may reside in the use of biological supplements in accordance with regulations, while some challenges remain in establishing standardized, effective procedures in the clinics. PMID:24520197

  5. [DNA repair--a fundamental factor in ageing and development of cancer].

    PubMed

    Rasmussen, Lene Juel; Stevnsner, Tinna; Bohr, Vilhelm A

    2006-06-12

    Advanced age and increased incidence of many illnesses such as cancer are closely linked. The reasons for such a link are numerous but one important factor is DNA repair. DNA repair pathways in both nuclei and mitochondria ensure that genomic instability is minimised, thus preventing transformation and premature cellular decay. However, overall cellular DNA repair capacity decreases with age; moreover, some individuals are born with defects in repair systems. The resulting lower capacity for repair of DNA damage increases mutation load and changes normal cellular functions such as transcription, thereby contributing to the ageing process as well to the onset of various cancers. DNA repair capacity is an important cellular marker that should be considered as a standard clinical test.

  6. The current state of eukaryotic DNA base damage and repair

    PubMed Central

    Bauer, Nicholas C.; Corbett, Anita H.; Doetsch, Paul W.

    2015-01-01

    DNA damage is a natural hazard of life. The most common DNA lesions are base, sugar, and single-strand break damage resulting from oxidation, alkylation, deamination, and spontaneous hydrolysis. If left unrepaired, such lesions can become fixed in the genome as permanent mutations. Thus, evolution has led to the creation of several highly conserved, partially redundant pathways to repair or mitigate the effects of DNA base damage. The biochemical mechanisms of these pathways have been well characterized and the impact of this work was recently highlighted by the selection of Tomas Lindahl, Aziz Sancar and Paul Modrich as the recipients of the 2015 Nobel Prize in Chemistry for their seminal work in defining DNA repair pathways. However, how these repair pathways are regulated and interconnected is still being elucidated. This review focuses on the classical base excision repair and strand incision pathways in eukaryotes, considering both Saccharomyces cerevisiae and humans, and extends to some important questions and challenges facing the field of DNA base damage repair. PMID:26519467

  7. Current Space Station Experiments Investigating Component Level Electronics Repair

    NASA Technical Reports Server (NTRS)

    Easton, John W.; Struk, Peter M.

    2010-01-01

    The Soldering in a Reduced Gravity Experiment (SoRGE) and Component Repair Experiment (CRE)-1 are tests performed on the International Space Station to determine the techniques, tools, and training necessary to allow future crews to perform manual electronics repairs at the component level. SoRGE provides information on the formation and internal structure of through-hole solder joints, illustrating the challenges and implications of soldering in reduced gravity. SoRGE showed a significant increase in internal void defects for joints formed in low gravity compared to normal gravity. Methods for mitigating these void defects were evaluated using a modified soldering process. CRE-1 demonstrated the removal, cleaning, and replacement of electronics components by manual means on functional circuit boards. The majority of components successful passed a post-repair functional test demonstrating the feasibility of component-level repair within the confines of a spacecraft. Together, these tasks provide information to recommend material and tool improvements, training improvements, and future work to help enable electronics repairs in future space missions.

  8. The impact of base excision DNA repair in age-related neurodegenerative diseases.

    PubMed

    Leandro, Giovana S; Sykora, Peter; Bohr, Vilhelm A

    2015-06-01

    The aging process and several age-related neurodegenerative disorders have been linked to elevated levels of DNA damage induced by ROS and deficiency in DNA repair mechanisms. DNA damage induced by ROS is a byproduct of cellular respiration and accumulation of damage over time, is a fundamental aspect of a main theory of aging. Mitochondria have a pivotal role in generating cellular oxidative stress, and mitochondrial dysfunction has been associated with several diseases. DNA base excision repair is considered the major pathway for repair of oxidized bases in DNA both in the nuclei and in mitochondria, and in neurons this mechanism is particularly important because non-diving cells have limited back-up DNA repair mechanisms. An association between elevated oxidative stress and a decrease in BER is strongly related to the aging process and has special relevance in age-related neurodegenerative diseases. Here, we review the role of DNA repair in aging, focusing on the implications of the DNA base excision repair pathways and how alterations in expression of these DNA repair proteins are related to the aging process and to age-related neurodegenerative diseases.

  9. DNA repair: Dynamic defenders against cancer and aging

    SciTech Connect

    Fuss, Jill O.; Cooper, Priscilla K.

    2006-04-01

    You probably weren't thinking about your body's cellular DNA repair systems the last time you sat on the beach in the bright sunshine. Fortunately, however, while you were subjecting your DNA to the harmful effects of ultraviolet light, your cells were busy repairing the damage. The idea that our genetic material could be damaged by the sun was not appreciated in the early days of molecular biology. When Watson and Crick discovered the structure of DNA in 1953 [1], it was assumed that DNA is fundamentally stable since it carries the blueprint of life. However, over 50 years of research have revealed that our DNA is under constant assault by sunlight, oxygen, radiation, various chemicals, and even our own cellular processes. Cleverly, evolution has provided our cells with a diverse set of tools to repair the damage that Mother Nature causes. DNA repair processes restore the normal nucleotide sequence and DNA structure of the genome after damage [2]. These responses are highly varied and exquisitely regulated. DNA repair mechanisms are traditionally characterized by the type of damage repaired. A large variety of chemical modifications can alter normal DNA bases and either lead to mutations or block transcription if not repaired, and three distinct pathways exist to remove base damage. Base excision repair (BER) corrects DNA base alterations that do not distort the overall structure of the DNA helix such as bases damaged by oxidation resulting from normal cellular metabolism. While BER removes single damaged bases, nucleotide excision repair (NER) removes short segments of nucleotides (called oligonucleotides) containing damaged bases. NER responds to any alteration that distorts the DNA helix and is the mechanism responsible for repairing bulky base damage caused by carcinogenic chemicals such as benzo [a]pyrene (found in cigarette smoke and automobile exhaust) as well as covalent linkages between adjacent pyrimidine bases resulting from the ultraviolet (UV

  10. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.

    PubMed

    Sepe, Sara; Milanese, Chiara; Gabriels, Sylvia; Derks, Kasper W J; Payan-Gomez, Cesar; van IJcken, Wilfred F J; Rijksen, Yvonne M A; Nigg, Alex L; Moreno, Sandra; Cerri, Silvia; Blandini, Fabio; Hoeijmakers, Jan H J; Mastroberardino, Pier G

    2016-05-31

    The underlying relation between Parkinson's disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD. PMID:27210754

  11. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.

    PubMed

    Sepe, Sara; Milanese, Chiara; Gabriels, Sylvia; Derks, Kasper W J; Payan-Gomez, Cesar; van IJcken, Wilfred F J; Rijksen, Yvonne M A; Nigg, Alex L; Moreno, Sandra; Cerri, Silvia; Blandini, Fabio; Hoeijmakers, Jan H J; Mastroberardino, Pier G

    2016-05-31

    The underlying relation between Parkinson's disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD.

  12. Age-related macular degeneration: current treatments

    PubMed Central

    Hubschman, Jean Pierre; Reddy, Shantan; Schwartz, Steven D

    2009-01-01

    Purpose: Although important progress has been made in understanding age-related macular degeneration (AMD), management of the disease continues to be a challenge. AMD research has led to a widening of available treatment options and improved prognostic perspectives. This essay reviews these treatment options. Design: Interpretative essay. Methods: Literature review and interpretation. Results: Current treatments to preserve vision in patients with non-exudative AMD include antioxidant vitamins and mineral supplementations. Exudative AMD is currently most often treated monthly with anti-VEGF intravitreal injections. However, investigators are beginning to experiment with combination therapy and surgical approaches in an attempt to limit the number of treatment and reduce the financial burden on the health care system. Conclusion: By better understanding the basis and pathogenesis of AMD, newer therapies will continue to be developed that target specific pathways in patients with AMD, with the hoped for outcome of better management of the disease and improved visual acuity. PMID:19668560

  13. Age of the mother as a risk factor and timing of hypospadias repair according to severity

    PubMed Central

    Jorge, Juan Carlos; Pérez-Brayfield, Marcos Raymond; Torres, Camille M.; Piñeyro-Ruiz, Coriness; Torres, Naillil

    2016-01-01

    Background & Objectives Hypospadias is characterized by a displacement of the urethral opening in males that can change from the typical position within the glans penis to a subcoronal position (Type I), to anywhere along the ventral shaft (Type II), to penoscrotal, scrotal, or perineal positions (Type III). We and others have previously reported that age of the mother (≥ 40 years old) is a risk factor for having a child with hypospadias, but there is a scarcity of reports on whether such risk is higher for having a child with the mild (Type I) or the more severe forms (Types II and III). In addition, we aimed to assess the timing of hypospadias repair according to severity. Methods Parents of children with hypospadias were interviewed by using a series of questionnaires (n = 128 cases). Severity was confirmed in the clinic and age of the mother was self-reported. Number of surgeries, age of child by the first and the last intervention was also assessed. Ordered logistic regression and the Brant test were employed to calculate risk between mild (Type I) and severe cases (Types II and III), and the assumption of proportional odds, respectively. The Mann-Whitney U Test was used to compare number of surgeries and age by the last repair between mild and severe cases. One-way ANOVA was employed to compare age of the child at the time of first surgery across severities (Types I - III). Results Women ≥ 40 years of age are 3.89 times [95% CI: 1.20-12.64] at a higher risk for having a child with the more severe forms of the condition than younger women. Repair of Type I was accomplished with 1 intervention whereas more severe cases required 1 – 4 (2 ± 0.5) surgical interventions. The timing for hypospadias repair of Type I cases occurred at an average age of 16.2 ± 4.88 months, of Type II cases occurred at an average age of 20.3 ± 8.15 months whereas the average age of the first hypospadias repair among Type III cases was 12.68 ± 2.52 months. Number of surgeries

  14. The Convergence of Fracture Repair and Stem Cells: Interplay of Genes, Aging, Environmental Factors and Disease

    PubMed Central

    Hadjiargyrou, Michael; O’Keefe, Regis J

    2015-01-01

    The complexity of fracture repair makes it an ideal process for studying the interplay between the molecular, cellular, tissue, and organ level events involved in tissue regeneration. Additionally, as fracture repair recapitulates many of the processes that occur during embryonic development, investigations of fracture repair provide insights regarding skeletal embryogenesis. Specifically, inflammation, signaling, gene expression, cellular proliferation and differentiation, osteogenesis, chondrogenesis, angiogenesis, and remodeling represent the complex array of interdependent biological events that occur during fracture repair. Here we review studies of bone regeneration in genetically modified mouse models, during aging, following environmental exposure, and in the setting of disease that provide insights regarding the role of multipotent cells and their regulation during fracture repair. Complementary animal models and ongoing scientific discoveries define an increasing number of molecular and cellular targets to reduce the morbidity and complications associated with fracture repair. Last, some new and exciting areas of stem cell research such as the contribution of mitochondria function, limb regeneration signaling, and microRNA (miRNA) posttranscriptional regulation are all likely to further contribute to our understanding of fracture repair as an active branch of regenerative medicine. PMID:25264148

  15. Current Stem Cell Delivery Methods for Myocardial Repair

    PubMed Central

    Sheng, Calvin C.; Zhou, Li; Hao, Jijun

    2013-01-01

    Heart failure commonly results from an irreparable damage due to cardiovascular diseases (CVDs), the leading cause of morbidity and mortality in the United States. In recent years, the rapid advancements in stem cell research have garnered much praise for paving the way to novel therapies in reversing myocardial injuries. Cell types currently investigated for cellular delivery include embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cell lineages such as skeletal myoblasts, bone-marrow-derived stem cells (BMSCs), mesenchymal stem cells (MSCs), and cardiac stem cells (CSCs). To engraft these cells into patients' damaged myocardium, a variety of approaches (intramyocardial, transendocardial, transcoronary, venous, intravenous, intracoronary artery and retrograde venous administrations and bioengineered tissue transplantation) have been developed and explored. In this paper, we will discuss the pros and cons of these delivery modalities, the current state of their therapeutic potentials, and a multifaceted evaluation of their reported clinical feasibility, safety, and efficacy. While the issues of optimal delivery approach, the best progenitor stem cell type, the most effective dose, and timing of administration remain to be addressed, we are highly optimistic that stem cell therapy will provide a clinically viable option for myocardial regeneration. PMID:23509740

  16. Current stem cell delivery methods for myocardial repair.

    PubMed

    Sheng, Calvin C; Zhou, Li; Hao, Jijun

    2013-01-01

    Heart failure commonly results from an irreparable damage due to cardiovascular diseases (CVDs), the leading cause of morbidity and mortality in the United States. In recent years, the rapid advancements in stem cell research have garnered much praise for paving the way to novel therapies in reversing myocardial injuries. Cell types currently investigated for cellular delivery include embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cell lineages such as skeletal myoblasts, bone-marrow-derived stem cells (BMSCs), mesenchymal stem cells (MSCs), and cardiac stem cells (CSCs). To engraft these cells into patients' damaged myocardium, a variety of approaches (intramyocardial, transendocardial, transcoronary, venous, intravenous, intracoronary artery and retrograde venous administrations and bioengineered tissue transplantation) have been developed and explored. In this paper, we will discuss the pros and cons of these delivery modalities, the current state of their therapeutic potentials, and a multifaceted evaluation of their reported clinical feasibility, safety, and efficacy. While the issues of optimal delivery approach, the best progenitor stem cell type, the most effective dose, and timing of administration remain to be addressed, we are highly optimistic that stem cell therapy will provide a clinically viable option for myocardial regeneration.

  17. Repair of nonunions by electrically pulsed current stimulation.

    PubMed

    Zichner, L

    1981-01-01

    Five congenital and 52 acquired nonunions of bone were stimulated using an invasive device. The unit delivered a constant but pulsed right-angled current of positive polarity measuring 20 to 25 muAmps (voltage of 750 mV) and a frequency of 20 Hz. The power pack encapsulated in epoxy resin was implanted at the time of operative fragment stabilization. THe cathode was inserted at the site of the nonunion gap. After two to 12 months, all but two of the acquired nonunions and one of the congenital pseudarthroses healed. In the unsuccessful cases, the bone ends were often totally necrotic. Four cases required reimplantation because of broken wires or expiration of the battery, and two cases failed owing to purulent infection. Electrostimulation is an adjuvant treatment to fragment stabilization in hyporeactive and hypovascular or congenital pseudarthroses. Electrical stimuli may be assumed to simulate conditions which are essential for bone healing.

  18. Rehabilitation following rotator cuff repair: a survey of current UK practice

    PubMed Central

    Bateman, Marcus

    2015-01-01

    Background Rotator cuff disorders, including rotator cuff tears, are common and can be treated conservatively or surgically. Data suggest that the incidence of surgery to repair the rotator cuff is rising. Despite this rise, the most effective approach to postoperative rehabilitation, a critical component of the recovery process, is not well developed. The present study aimed to describe current practice in the UK in relation to rehabilitation following rotator cuff repair. Methods An electronic survey was developed and disseminated to UK based physiotherapists and surgeons involved with rotator cuff repair. Results One hundred valid responses were received. Although there is a degree of variation, current practice for the majority of respondents consists of sling immobilization for 4 weeks to 6 weeks. During this time, passive movement would be commenced before active movement is introduced towards the end of this phase. Resisted exercise begins 7 weeks to 12 weeks postoperatively, alongside return to light work. A progressive resumption of function, including manual work and sport, is advised from approximately 13 weeks. Conclusions In the context of the current literature, it might be suggested that the current approach to rehabilitation following rotator cuff repair for the majority of respondents is somewhat cautious and has not progressed for over a decade. PMID:27582979

  19. The Role of Current Techniques and Concepts in Peripheral Nerve Repair.

    PubMed

    Houschyar, K S; Momeni, A; Pyles, M N; Cha, J Y; Maan, Z N; Duscher, D; Jew, O S; Siemers, F; van Schoonhoven, J

    2016-01-01

    Patients with peripheral nerve injuries, especially severe injury, often face poor nerve regeneration and incomplete functional recovery, even after surgical nerve repair. This review summarizes treatment options of peripheral nerve injuries with current techniques and concepts and reviews developments in research and clinical application of these therapies. PMID:26904282

  20. The Role of Current Techniques and Concepts in Peripheral Nerve Repair

    PubMed Central

    Houschyar, K. S.; Momeni, A.; Pyles, M. N.; Cha, J. Y.; Maan, Z. N.; Duscher, D.; Jew, O. S.; Siemers, F.; van Schoonhoven, J.

    2016-01-01

    Patients with peripheral nerve injuries, especially severe injury, often face poor nerve regeneration and incomplete functional recovery, even after surgical nerve repair. This review summarizes treatment options of peripheral nerve injuries with current techniques and concepts and reviews developments in research and clinical application of these therapies. PMID:26904282

  1. Stem cells in stroke repair: current success and future prospects.

    PubMed

    Gopurappilly, Renjitha; Pal, Rajarshi; Mamidi, Murali Krishna; Dey, Sovan; Bhonde, Ramesh; Das, Anjan Kumar

    2011-09-01

    Stroke causes a devastating insult to the brain resulting in severe neurological deficits because of a massive loss of different neurons and glia. In the United States, stroke is the third leading cause of death. Stroke remains a significant clinical unmet condition, with only 3% of the ischemic patient population benefiting from current treatment modalities, such as the use of thrombolytic agents, which are often limited by a narrow therapeutic time window. However, regeneration of the brain after ischemic damage is still active days and even weeks after stroke occurs, which might provide a second window for treatment. Neurorestorative processes like neurogenesis, angiogenesis and synaptic plasticity lead to functional improvement after stroke. Stem cells derived from various tissues have the potential to perform all of the aforementioned processes, thus facilitating functional recovery. Indeed, transplantation of stem cells or their derivatives in animal models of cerebral ischemia can improve function by replacing the lost neurons and glial cells and by mediating remyelination, and modulation of inflammation as confirmed by various studies worldwide. While initially stem cells seemed to work by a 'cell replacement' mechanism, recent research suggests that cell therapy works mostly by providing trophic support to the injured tissue and brain, fostering both neurogenesis and angiogenesis. Moreover, ongoing human trials have encouraged hopes for this new method of restorative therapy after stroke. This review describes up-to-date progress in cell-based therapy for the treatment of stroke. Further, as we discuss here, significant hurdles remain to be addressed before these findings can be responsibly translated to novel therapies. In particular, we need a better understanding of the mechanisms of action of stem cells after transplantation, the therapeutic time window for cell transplantation, the optimal route of cell delivery to the ischemic brain, the most

  2. Effect of age on survival between open repair and surveillance for small abdominal aortic aneurysms.

    PubMed

    Filardo, Giovanni; Lederle, Frank A; Ballard, David J; Hamilton, Cody; da Graca, Briget; Herrin, Jeph; Sass, Danielle M; Johnson, Gary R; Powell, Janet T

    2014-10-15

    Randomized controlled trials have shown no significant difference in survival between immediate open repair and surveillance with selective repair for asymptomatic abdominal aortic aneurysms of 4.0 to 5.5 cm in diameter. This lack of difference has been shown to hold true for all diameters in this range, in men and women, but the question of whether patients of different ages might obtain different benefits has remained unanswered. Using the pooled patient-level data for the 2,226 patients randomized to immediate open repair or surveillance in the United Kingdom Small Aneurysm Trial (UKSAT; September 1, 1991, to July 31, 1998; follow-up 2.6 to 6.9 years) or the Aneurysm Detection and Management (ADAM) trial (August 1, 1992, to July 31, 2000; follow-up 3.5 to 8.0 years), the adjusted effect of age on survival in the 2 treatment groups was estimated using a generalized propensity approach, accounting for a comprehensive array of clinical and nonclinical risk factors. No significant difference in survival between immediate open repair and surveillance was observed for patients of any age, overall (p = 0.606) or in men (p = 0.371) or women separately (p = 0.167). In conclusion, survival did not differ significantly between immediate open repair and surveillance for patients of any age, overall or in men or women. Combined with the previous evidence regarding diameter, and the lack of benefit of immediate endovascular in trials comparing it with surveillance repair for small abdominal aortic aneurysms, these results suggest that surveillance should be the first-line management strategy of choice for asymptomatic abdominal aortic aneurysms of 4.0 to 5.5 cm.

  3. Role of metabolic rate and DNA-repair in Drosophila aging Implications for the mitochondrial mutation theory of aging

    NASA Technical Reports Server (NTRS)

    Miquel, J.; Binnard, R.; Fleming, J. E.

    1983-01-01

    The notion that injury to mitochondrial DNA is a cause of intrinsic aging was tested by correlating the different respiration rates of several wild strains of Drosophila melanogaster with the life-spans. Respiration rate and aging in a mutant of D. melanogaster deficient in postreplication repair were also investigated. In agreement with the rate of living theory, there was an inverse relation between oxygen consumption and median life-span in flies having normal DNA repair. The mutant showed an abnormally low life-span as compared to the controls and also exhibited significant deficiency in mating fitness and a depressed metabolic rate. Therefore, the short life-span of the mutant may be due to the congenital condition rather than to accelerated aging.

  4. REHABILITATION AFTER ARTHROSCOPIC ROTATOR CUFF REPAIR: CURRENT CONCEPTS REVIEW AND EVIDENCE-BASED GUIDELINES

    PubMed Central

    Westgard, Paul; Chandler, Zachary; Gaskill, Trevor R.; Kokmeyer, Dirk; Millett, Peter J.

    2012-01-01

    Purpose: To provide an overview of the characteristics and timing of rotator cuff healing and provide an update on treatments used in rehabilitation of rotator cuff repairs. The authors' protocol of choice, used within a large sports medicine rehabilitation center, is presented and the rationale behind its implementation is discussed. Background: If initial nonsurgical treatment of a rotator cuff tear fails, surgical repair is often the next line of treatment. It is evident that a successful outcome after surgical rotator cuff repair is as much dependent on surgical technique as it is on rehabilitation. To this end, rehabilitation protocols have proven challenging to both the orthopaedic surgeon and the involved physical therapist. Instead of being based on scientific rationale, traditionally most rehabilitation protocols are solely based on clinical experience and expert opinion. Methods: A review of currently available literature on rehabilitation after arthroscopic rotator cuff tear repair on PUBMED / MEDLINE and EMBASE databases was performed to illustrate the available evidence behind various postoperative treatment modalities. Results: There is little high-level scientific evidence available to support or contest current postoperative rotator cuff rehabilitation protocols. Most existing protocols are based on clinical experience with modest incorporation of scientific data. Conclusion: Little scientific evidence is available to guide the timing of postsurgical rotator cuff rehabilitation. To this end, expert opinion and clinical experience remains a large facet of rehabilitation protocols. This review describes a rotator cuff rehabilitation protocol that incorporates currently available scientific literature guiding rehabilitation. PMID:22530194

  5. Current clinical therapies for cartilage repair, their limitation and the role of stem cells.

    PubMed

    Dhinsa, Baljinder S; Adesida, Adetola B

    2012-03-01

    The management of osteochondral defects of articular cartilage, whether from trauma or degenerative disease, continues to be a significant challenge for Orthopaedic surgeons. Current treatment options such as abrasion arthroplasty procedures, osteochondral transplantation and autologous chondrocyte implantation fail to produce repair tissue exhibiting the same mechanical and functional properties of native articular cartilage. This results in repair tissue that inevitably fails as it is unable to deal with the mechanical demands of articular cartilage, and does not prevent further degeneration of the native cartilage. Mesenchymal stem cells have been proposed as a potential source of cells for cell-based cartilage repair due to their ability to self-renew and undergo multi-lineage differentiation. This proposed procedure has the advantage of not requiring harvesting of cells from the joint surface, and its associated donor site morbidity, as well as having multiple possible adult donor tissues such as bone marrow, adipose tissue and synovium. Mesenchymal stem cells have multi-lineage potential, but can be stimulated to undergo chondrogenesis in the appropriate culture medium. As the majority of work with mesenchymal stem cell-derived articular cartilage repair has been carried out in vitro and in animal studies, more work still has to be done before this technique can be used for clinical purposes. This includes realizing the ideal method of harvesting mesenchymal stem cells, the culture medium to stimulate proliferation and differentiation, appropriate choice of scaffold incorporating growth factors directly or with gene therapy and integration of repair tissue with native tissue.

  6. Diminished Schwann cell repair responses underlie age-associated impaired axonal regeneration.

    PubMed

    Painter, Michio W; Brosius Lutz, Amanda; Cheng, Yung-Chih; Latremoliere, Alban; Duong, Kelly; Miller, Christine M; Posada, Sean; Cobos, Enrique J; Zhang, Alice X; Wagers, Amy J; Havton, Leif A; Barres, Ben; Omura, Takao; Woolf, Clifford J

    2014-07-16

    The regenerative capacity of the peripheral nervous system declines with age. Why this occurs, however, is unknown. We demonstrate that 24-month-old mice exhibit an impairment of functional recovery after nerve injury compared to 2-month-old animals. We find no difference in the intrinsic growth capacity between aged and young sensory neurons in vitro or in their ability to activate growth-associated transcriptional programs after injury. Instead, using age-mismatched nerve transplants in vivo, we show that the extent of functional recovery depends on the age of the nerve graft, and not the age of the host. Molecular interrogation of the sciatic nerve reveals that aged Schwann cells (SCs) fail to rapidly activate a transcriptional repair program after injury. Functionally, aged SCs exhibit impaired dedifferentiation, myelin clearance, and macrophage recruitment. These results suggest that the age-associated decline in axonal regeneration results from diminished Schwann cell plasticity, leading to slower myelin clearance.

  7. Base excision repair in the mammalian brain: implication for age related neurodegeneration.

    PubMed

    Sykora, Peter; Wilson, David M; Bohr, Vilhelm A

    2013-10-01

    The repair of damaged DNA is essential to maintain longevity of an organism. The brain is a matrix of different neural cell types including proliferative astrocytes and post-mitotic neurons. Post-mitotic DNA repair is a version of proliferative DNA repair, with a reduced number of available pathways and most of these attenuated. Base excision repair (BER) is one pathway that remains robust in neurons; it is this pathway that resolves the damage due to oxidative stress. This oxidative damage is an unavoidable byproduct of respiration, and considering the high metabolic activity of neurons this type of damage is particularly pertinent in the brain. The accumulation of oxidative DNA damage over time is a central aspect of the theory of aging and repair of such chronic damage is of the highest importance. We review research conducted in BER mouse models to clarify the role of this pathway in the neural system. The requirement for BER in proliferating cells also correlates with high levels of many of the BER enzymes in neurogenesis after DNA damage. However, the pathway is also necessary for normal neural maintenance as larger infarct volumes after ischemic stroke are seen in some glycosylase deficient animals. Further, the requirement for DNA polymerase β in post-mitotic BER is potentially more important than in proliferating cells due to reduced levels of replicative polymerases. The BER response may have particular relevance for the onset and progression of many neurodegenerative diseases associated with an increase in oxidative stress including Alzheimer's.

  8. DNA repair diseases: What do they tell us about cancer and aging?

    PubMed Central

    Menck, Carlos FM; Munford, Veridiana

    2014-01-01

    The discovery of DNA repair defects in human syndromes, initially in xeroderma pigmentosum (XP) but later in many others, led to striking observations on the association of molecular defects and patients’ clinical phenotypes. For example, patients with syndromes resulting from defective nucleotide excision repair (NER) or translesion synthesis (TLS) present high levels of skin cancer in areas exposed to sunlight. However, some defects in NER also lead to more severe symptoms, such as developmental and neurological impairment and signs of premature aging. Skin cancer in XP patients is clearly associated with increased mutagenesis and genomic instability, reflecting the defective repair of DNA lesions. By analogy, more severe symptoms observed in NER-defective patients have also been associated with defective repair, likely involving cell death after transcription blockage of damaged templates. Endogenously induced DNA lesions, particularly through oxidative stress, have been identified as responsible for these severe pathologies. However, this association is not that clear and alternative explanations have been proposed. Despite high levels of exposure to intense sunlight, patients from tropical countries receive little attention or care, which likely also reflects the lack of understanding of how DNA damage causes cancer and premature aging. PMID:24764756

  9. The effect of aging on the DNA damage and repair capacity in 2BS cells undergoing oxidative stress.

    PubMed

    Wang, Jin-Ling; Wang, Pei-Chang

    2012-01-01

    Aging is associated with a reduction in the DNA repair capacity under oxidative stress. However, whether the DNA damage and repair capacity can be a biomarker of aging remains controversial. In this study, we demonstrated two cause-and-effect relationships, the one is between the DNA damage and repair capacity and the cellular age, another is between DNA damage and repair capacity and the level of oxidative stress in human embryonic lung fibroblasts (2BS) exposed to different doses of hydrogen peroxide (H2O2). To clarify the mechanisms of the age-related reduction in DNA damage and repair capacity, we preliminarily evaluated the expressions of six kinds of pivotal enzymes involved in the two classical DNA repair pathways. The DNA repair capacity was observed in human fibroblasts cells using the comet assay; the age-related DNA repair enzymes were selected by RT-PCR and then verified by Western blot in vitro. Results showed that the DNA repair capacity was negatively and linearly correlated with (i) cumulative population doubling (PD) levels only in the group of low concentration of hydrogen peroxide treatment, (ii) with the level of oxidative stress only in the group of young PD cells. The mRNA expression of DNA polymerase δ1 decreased substantially in senescent cells and showed negative linear-correlation with PD levels; the protein expression level was well consistent with the mRNA level. Taken together, DNA damage and repair capacity can be a biomarker of aging. Reduced expression of DNA polymerase δ1 may be responsible for the decrease of DNA repair capacity in senescent cells.

  10. Nuclear and Mitochondrial DNA Repair in Selected Eukaryotic Aging Model Systems

    PubMed Central

    Gredilla, Ricardo; Garm, Christian; Stevnsner, Tinna

    2012-01-01

    Knowledge about the different mechanisms underlying the aging process has increased exponentially in the last decades. The fact that the basic mechanisms involved in the aging process are believed to be universal allows the use of different model systems, from the simplest eukaryotic cells such as fungi to the most complex organisms such as mice or human. As our knowledge on the aging mechanisms in those model systems increases, our understanding of human aging and the potential interventions that we could approach rise significantly. Among the different mechanisms that have been implicated in the aging process, DNA repair is one of the processes which have been suggested to play an important role. Here, we review the latest investigations supporting the role of these mechanisms in the aging process, stressing how beneficial the use of different model systems is. We discuss how human genetic studies as well as several investigations on mammalian models and simpler eukaryotic organisms have contributed to a better understanding of the involvement of DNA repair mechanisms in aging. PMID:23050036

  11. Nucleotide Excision DNA Repair is Associated with Age-Related Vascular Dysfunction

    PubMed Central

    Durik, Matej; Kavousi, Maryam; van der Pluijm, Ingrid; Isaacs, Aaron; Cheng, Caroline; Verdonk, Koen; Loot, Annemarieke E.; Oeseburg, Hisko; Musterd-Bhaggoe, Usha; Leijten, Frank; van Veghel, Richard; de Vries, Rene; Rudez, Goran; Brandt, Renata; Ridwan, Yanto R.; van Deel, Elza D.; de Boer, Martine; Tempel, Dennie; Fleming, Ingrid; Mitchell, Gary F.; Verwoert, Germaine C.; Tarasov, Kirill V.; Uitterlinden, Andre G.; Hofman, Albert; Duckers, Henricus J.; van Duijn, Cornelia M.; Oostra, Ben A.; Witteman, Jacqueline C.M.; Duncker, Dirk J.; Danser, A.H. Jan; Hoeijmakers, Jan H.; Roks, Anton J.M.

    2012-01-01

    Background Vascular dysfunction in atherosclerosis and diabetes, as observed in the aging population of developed societies, is associated with vascular DNA damage and cell senescence. We hypothesized that cumulative DNA damage during aging contributes to vascular dysfunction. Methods and Results In mice with genomic instability due to the defective nucleotide excision repair genes ERCC1 and XPD (Ercc1d/− and XpdTTD mice), we explored age-dependent vascular function as compared to wild-type mice. Ercc1d/− mice showed increased vascular cell senescence, accelerated development of vasodilator dysfunction, increased vascular stiffness and elevated blood pressure at very young age. The vasodilator dysfunction was due to decreased endothelial eNOS levels as well as impaired smooth muscle cell function, which involved phosphodiesterase (PDE) activity. Similar to Ercc1d/− mice, age-related endothelium-dependent vasodilator dysfunction in XpdTTD animals was increased. To investigate the implications for human vascular disease, we explored associations between single nucleotide polymorphisms (SNPs) of selected nucleotide excision repair genes and arterial stiffness within the AortaGen Consortium, and found a significant association of a SNP (rs2029298) in the putative promoter region of DDB2 gene with carotid-femoral pulse wave velocity. Conclusions Mice with genomic instability recapitulate age-dependent vascular dysfunction as observed in animal models and in humans, but with an accelerated progression, as compared to wild type mice. In addition, we found associations between variations in human DNA repair genes and markers for vascular stiffness which is associated with aging. Our study supports the concept that genomic instability contributes importantly to the development of cardiovascular disease. PMID:22705887

  12. The role of age and comorbidities in postoperative outcome of mitral valve repair

    PubMed Central

    Bonnet, Vincent; Boisselier, Clément; Saplacan, Vladimir; Belin, Annette; Gérard, Jean-Louis; Fellahi, Jean-Luc; Hanouz, Jean-Luc; Fischer, Marc-Olivier

    2016-01-01

    Abstract The average age of patients undergoing mitral valve repair is increasing each year. This retrospective study aimed to compare postoperative complications of mitral valve repair (known to be especially high-risk) between 2 age groups: under and over the age of 80. Patients who underwent mitral valve repair were divided into 2 groups: group 1 (<80 years old) and group 2 (≥80 years old). Baseline characteristics, pre- and postoperative hemodynamic data, surgical characteristics, and postoperative follow-up data until hospital discharge were collected. A total of 308 patients were included: 264 in group 1 (age 63 ± 13 years) and 44 in group 2 (age 83 ± 2 years). Older patients had more comorbidities (atrial fibrillation, history of cardiac decompensation, systemic hypertension, pulmonary hypertension, and chronic kidney disease) and they presented more postoperative complications (50.0% vs 33.7%; P = 0.043), with a longer hospital stay (8.9 ± 6.9 vs 6.6 ± 4.6 days; P = 0.005). To assess the burden of age, a propensity score was awarded to postoperative complications. Active smoking, chronic pulmonary disease, chronic kidney disease, associated ischemic heart disease, obesity, and cardio pulmonary by-pass duration were described as independent risk factors. When matched on this propensity score, there was no difference in morbidity or mortality between group 1 and group 2. Older patients suffered more postoperative complications, which were related to their comorbidities and not only to their age. PMID:27336886

  13. Involvement of oxidatively damaged DNA and repair in cancer development and aging

    PubMed Central

    Tudek, Barbara; Winczura, Alicja; Janik, Justyna; Siomek, Agnieszka; Foksinski, Marek; Oliński, Ryszard

    2010-01-01

    DNA damage and DNA repair may mediate several cellular processes, like replication and transcription, mutagenesis and apoptosis and thus may be important factors in the development and pathology of an organism, including cancer. DNA is constantly damaged by reactive oxygen species (ROS) and reactive nitrogen species (RNS) directly and also by products of lipid peroxidation (LPO), which form exocyclic adducts to DNA bases. A wide variety of oxidatively-generated DNA lesions are present in living cells. 8-oxoguanine (8-oxoGua) is one of the best known DNA lesions due to its mutagenic properties. Among LPO-derived DNA base modifications the most intensively studied are ethenoadenine and ethenocytosine, highly miscoding DNA lesions considered as markers of oxidative stress and promutagenic DNA damage. Although at present it is impossible to directly answer the question concerning involvement of oxidatively damaged DNA in cancer etiology, it is likely that oxidatively modified DNA bases may serve as a source of mutations that initiate carcinogenesis and are involved in aging (i.e. they may be causal factors responsible for these processes). To counteract the deleterious effect of oxidatively damaged DNA, all organisms have developed several DNA repair mechanisms. The efficiency of oxidatively damaged DNA repair was frequently found to be decreased in cancer patients. The present work reviews the basis for the biological significance of DNA damage, particularly effects of 8-oxoGua and ethenoadduct occurrence in DNA in the aspect of cancer development, drawing attention to the multiplicity of proteins with repair activities. PMID:20589166

  14. Cyclin A2 promotes DNA repair in the brain during both development and aging

    PubMed Central

    Gygli, Patrick E.; Chang, Joshua C.; Gokozan, Hamza N.; Catacutan, Fay P.; Schmidt, Theresa A.; Kaya, Behiye; Goksel, Mustafa; Baig, Faisal S.; Chen, Shannon; Griveau, Amelie; Michowski, Wojciech; Wong, Michael; Palanichamy, Kamalakannan; Sicinski, Piotr; Nelson, Randy J.; Czeisler, Catherine; Otero, José J.

    2016-01-01

    Various stem cell niches of the brain have differential requirements for Cyclin A2. Cyclin A2 loss results in marked cerebellar dysmorphia, whereas forebrain growth is retarded during early embryonic development yet achieves normal size at birth. To understand the differential requirements of distinct brain regions for Cyclin A2, we utilized neuroanatomical, transgenic mouse, and mathematical modeling techniques to generate testable hypotheses that provide insight into how Cyclin A2 loss results in compensatory forebrain growth during late embryonic development. Using unbiased measurements of the forebrain stem cell niche, we parameterized a mathematical model whereby logistic growth instructs progenitor cells as to the cell-types of their progeny. Our data was consistent with prior findings that progenitors proliferate along an auto-inhibitory growth curve. The growth retardation in CCNA2-null brains corresponded to cell cycle lengthening, imposing a developmental delay. We hypothesized that Cyclin A2 regulates DNA repair and that CCNA2-null progenitors thus experienced lengthened cell cycle. We demonstrate that CCNA2-null progenitors suffer abnormal DNA repair, and implicate Cyclin A2 in double-strand break repair. Cyclin A2's DNA repair functions are conserved among cell lines, neural progenitors, and hippocampal neurons. We further demonstrate that neuronal CCNA2 ablation results in learning and memory deficits in aged mice. PMID:27425845

  15. DNA repair and aging: the impact of the p53 family

    PubMed Central

    Nicolai, Sara; Rossi, Antonello; Di Daniele, Nicola; Melino, Gerry; Annicchiarico-Petruzzelli, Margherita; Raschellà, Giuseppe

    2015-01-01

    Cells are constantly exposed to endogenous and exogenous factors that threaten the integrity of their DNA. The maintenance of genome stability is of paramount importance in the prevention of both cancer and aging processes. To deal with DNA damage, cells put into operation a sophisticated and coordinated mechanism, collectively known as DNA damage response (DDR). The DDR orchestrates different cellular processes, such as DNA repair, senescence and apoptosis. Among the key factors of the DDR, the related proteins p53, p63 and p73, all belonging to the same family of transcription factors, play multiple relevant roles. Indeed, the members of this family are directly involved in the induction of cell cycle arrest that is necessary to allow the cells to repair. Alternatively, they can promote cell death in case of prolonged or irreparable DNA damage. They also take part in a more direct task by modulating the expression of core factors involved in the process of DNA repair or by directly interacting with them. In this review we will analyze the fundamental roles of the p53 family in the aging process through their multifaceted function in DDR. PMID:26668111

  16. DNA repair and aging: the impact of the p53 family.

    PubMed

    Nicolai, Sara; Rossi, Antonello; Di Daniele, Nicola; Melino, Gerry; Annicchiarico-Petruzzelli, Margherita; Raschellà, Giuseppe

    2015-12-01

    Cells are constantly exposed to endogenous and exogenous factors that threaten the integrity of their DNA. The maintenance of genome stability is of paramount importance in the prevention of both cancer and aging processes. To deal with DNA damage, cells put into operation a sophisticated and coordinated mechanism, collectively known as DNA damage response (DDR). The DDR orchestrates different cellular processes, such as DNA repair, senescence and apoptosis. Among the key factors of the DDR, the related proteins p53, p63 and p73, all belonging to the same family of transcription factors, play multiple relevant roles. Indeed, the members of this family are directly involved in the induction of cell cycle arrest that is necessary to allow the cells to repair. Alternatively, they can promote cell death in case of prolonged or irreparable DNA damage. They also take part in a more direct task by modulating the expression of core factors involved in the process of DNA repair or by directly interacting with them. In this review we will analyze the fundamental roles of the p53 family in the aging process through their multifaceted function in DDR.

  17. The role of aging and DNA repair in chronic disease. Final progress report, December 1, 1985--September 29, 1993

    SciTech Connect

    Grossman, L.

    1993-11-01

    We carried out a molecular epidemiological study of the DNA repair of photochemical damage as a risk factor in basal cell carcinoma (BCC). In that clinic-based control study of 88 cases and 135 cancer-free control it was found that DNA repair in the controls declined linearly at a rate of 0.61% per year over a 30-60 year age group. However, repair in younger BCC cases, significantly less than their age-matched controls, did not decline at the same rate so that the repair differences between the cases and the controls disappeared as the cases grew older. Besides this age effect, the odds are high (5:1) that an individual with low repair overexposed to sunlight will have basal cell carcinoma. That these odds increase to 10:1 for females compared to male subjects led to the observation that repair may be sensitive to hormonal control. Because of the ease of BCC diagnosis it is possible to demonstrate significantly that the level of DNA repair directly influences the multiplicity of tumors. Further, both those cases and controls with a family history of BCC invariably have reduced levels of DNA repair (p<0-05).

  18. The zebrafish as a gerontology model in nervous system aging, disease, and repair.

    PubMed

    Van Houcke, Jessie; De Groef, Lies; Dekeyster, Eline; Moons, Lieve

    2015-11-01

    Considering the increasing number of elderly in the world's population today, developing effective treatments for age-related pathologies is one of the biggest challenges in modern medical research. Age-related neurodegeneration, in particular, significantly impacts important sensory, motor, and cognitive functions, seriously constraining life quality of many patients. Although our understanding of the causal mechanisms of aging has greatly improved in recent years, animal model systems still have much to tell us about this complex process. Zebrafish (Danio rerio) have gained enormous popularity for this research topic over the past decade, since their life span is relatively short but, like humans, they are still subject to gradual aging. In addition, the extensive characterization of its well-conserved molecular and cellular physiology makes the zebrafish an excellent model to unravel the underlying mechanisms of aging, disease, and repair. This review provides a comprehensive overview of the progress made in zebrafish gerontology, with special emphasis on nervous system aging. We review the evidence that classic hallmarks of aging can also be recognized within this small vertebrate, both at the molecular and cellular level. Moreover, we illustrate the high level of similarity with age-associated human pathologies through a survey of the functional deficits that arise as zebrafish age. PMID:26538520

  19. Rejuvenation of the inflammatory system stimulates fracture repair in aged mice

    PubMed Central

    Xing, Zhiqing; Lu, Chuanyong; Hu, Diane; Miclau, Theodore; Marcucio, Ralph S.

    2010-01-01

    Age significantly reduces the regenerative capacity of the skeleton, but the underlying causes are unknown. Here, we tested whether the functional status of inflammatory cells contributes to delayed healing in aged animals. We created chimeric mice by bone marrow transplantation after lethal irradiation. In this model chondrocytes and osteoblasts in the regenerate are derived exclusively from host cells while inflammatory cells are derived from the donor. Using this model, the inflammatory system of middle-aged mice (12-month-old) was replaced by transplanted bone marrow from juvenile mice (4-week-old), or age-matched controls. We found that the middle-aged mice receiving juvenile bone marrow had larger calluses and more bone formation during early stages and faster callus remodeling at late stages of fracture healing, indicating that inflammatory cells derived from the juvenile bone marrow accelerated bone repair in the middle-aged animals. In contrast, transplanting bone marrow from middle-age mice to juvenile mice did not alter the process of fracture healing in juvenile mice. Thus, the roles of inflammatory cells in fracture healing may be age-related, suggesting the possibility of enhancing fracture healing in aged animals by manipulating the inflammatory system. PMID:20108320

  20. New areas of focus at workshop on human diseases involving DNA repair deficiency and premature aging.

    PubMed

    Kraemer, Kenneth H; Sander, Miriam; Bohr, Vilhelm A

    2007-02-01

    Researchers and clinicians interested in human diseases of DNA repair deficiency and premature aging gathered at the National Conference Center in Lansdowne, Virginia on 5-8 September 2006 to attend a workshop co-organized by Vilhelm Bohr (National Institute of Aging) and Kenneth Kraemer (National Cancer Institute). An important feature of this workshop was the participation of representatives from xeroderma pigmentosum (XP), Cockayne Syndrome (CS) and trichothiodystrophy (TTD) family support groups. Studies presented at the workshop described important new insights into the phenotypic complexity of XP, CS and TTD, renewed focus on the neurological manifestations of each of these diseases, as well as keen interest in the role of oxidative stress and mitochondrial dysfunction in neurodegenerative processes and normal and/or premature aging. This workshop report summarizes some of the presentations and outcomes of the workshop.

  1. DNA Mismatch Repair System: Repercussions in Cellular Homeostasis and Relationship with Aging

    PubMed Central

    Conde-Pérezprina, Juan Cristóbal; León-Galván, Miguel Ángel; Konigsberg, Mina

    2012-01-01

    The mechanisms that concern DNA repair have been studied in the last years due to their consequences in cellular homeostasis. The diverse and damaging stimuli that affect DNA integrity, such as changes in the genetic sequence and modifications in gene expression, can disrupt the steady state of the cell and have serious repercussions to pathways that regulate apoptosis, senescence, and cancer. These altered pathways not only modify cellular and organism longevity, but quality of life (“health-span”). The DNA mismatch repair system (MMR) is highly conserved between species; its role is paramount in the preservation of DNA integrity, placing it as a necessary focal point in the study of pathways that prolong lifespan, aging, and disease. Here, we review different insights concerning the malfunction or absence of the DNA-MMR and its impact on cellular homeostasis. In particular, we will focus on DNA-MMR mechanisms regulated by known repair proteins MSH2, MSH6, PMS2, and MHL1, among others. PMID:23213348

  2. Quiescent hematopoietic stem cells accumulate DNA damage during aging that is repaired upon entry into cell cycle

    PubMed Central

    Inlay, Matthew A; Weissman, Irving L.; Rossi, Derrick J.

    2014-01-01

    Summary Hematopoietic stem cells (HSCs) maintain homeostasis and regenerate the blood system throughout life. It has been postulated that HSCs may be uniquely capable of preserving their genomic integrity to ensure lifelong function. To directly test this, we quantified DNA damage in HSCs and downstream progenitors from young and old mice revealing that strand breaks significantly accrue in HSCs during aging. DNA damage accumulation in HSCs was associated with broad attenuation of DNA repair and response pathways that was dependent upon HSC quiescence. Accordingly, cycling fetal HSCs and adult HSCs driven into cycle up-regulated these pathways leading to repair of strand breaks. Our results demonstrate that HSCs are not comprehensively geno-protected during aging. Rather, HSC quiescence and concomitant attenuation of DNA repair and response pathways underlies DNA damage accumulation in HSCs during aging. These results provide a potential mechanism through which pre-malignant mutations accrue in HSCs. PMID:24813857

  3. Changes in the expression of DNA double strand break repair genes in primordial follicles from immature and aged rats.

    PubMed

    Govindaraj, Vijayakumar; Keralapura Basavaraju, Rajani; Rao, Addicam Jagannadha

    2015-03-01

    Oocytes present at birth undergo a progressive process of apoptosis in humans and other mammals as they age. Accepted opinion is that no fresh oocytes are produced other than those present at the time of birth. Studies have shown that DNA repair genes in oocytes of mice and women decline with age, and lack of these genes show higher DNA breaks and increased oocyte death rates. In contrast to the ethical problems associated with monitoring the changes in DNA double-strand breaks in oocytes from young and old humans, it is relatively easy to carry out such a study using a rodent model. In this study, the mRNA levels of DNA repair genes are compared with protein products of some of the genes in the primordial follicles isolated from immature (18-20 days) and aged (400-450 days) female rats. Results revealed a significant decline in mRNA levels of BRAC1 (P < 0.01), RAD51 (P < 0.05), ERCC2 (P < 0.05), and H2AX (P < 0.01) of DNA repair genes and phospho-protein levels of BRAC1 (P < 0.01) and H2AX (P < 0.05) in primordial follicles of aged rats. Impaired DNA repair is confirmed as a mechanism of oocyte ageing.

  4. The knee meniscus: structure-function, pathophysiology, current repair techniques, and prospects for regeneration

    PubMed Central

    Makris, Eleftherios A.; Hadidi, Pasha; Athanasiou, Kyriacos A.

    2011-01-01

    Extensive scientific investigations in recent decades have established the anatomical, biomechanical, and functional importance that the meniscus holds within the knee joint. As a vital part of the joint, it acts to prevent the deterioration and degeneration of articular cartilage, and the onset and development of osteoarthritis. For this reason, research into meniscus repair has been the recipient of particular interest from the orthopedic and bioengineering communities. Current repair techniques are only effective in treating lesions located in the peripheral vascularized region of the meniscus. Healing lesions found in the inner avascular region, which functions under a highly demanding mechanical environment, is considered to be a significant challenge. An adequate treatment approach has yet to be established, though many attempts have been undertaken. The current primary method for treatment is partial meniscectomy, which commonly results in the progressive development of osteoarthritis. This drawback has shifted research interest towards the fields of biomaterials and bioengineering, where it is hoped that meniscal deterioration can be tackled with the help of tissue engineering. So far, different approaches and strategies have contributed to the in vitro generation of meniscus constructs, which are capable of restoring meniscal lesions to some extent, both functionally as well as anatomically. The selection of the appropriate cell source (autologous, allogeneic, or xenogeneic cells, or stem cells) is undoubtedly regarded as key to successful meniscal tissue engineering. Furthermore, a large variation of scaffolds for tissue engineering have been proposed and produced in experimental and clinical studies, although a few problems with these (e.g., byproducts of degradation, stress shielding) have shifted research interest towards new strategies (e.g., scaffoldless approaches, self-assembly). A large number of different chemical (e.g., TGF-β1, C-ABC) and

  5. Low-fidelity compensatory backup alternative DNA repair pathways may unify current carcinogenesis theories.

    PubMed

    Wu, Jiaxi; Starr, Shane

    2014-05-01

    The somatic mutation carcinogenesis theory has dominated for decades. The alternative theory, tissue organization field theory, argues that the development of cancer is determined by the surrounding microenvironment. However, neither theory can explain all features of cancer. As cancers share the features of uncontrolled proliferation and genomic instability, they are likely to have the same pathogenesis. It has been found that various DNA repair pathways within a cell crosstalk with one another, forming a DNA repair network. When one DNA repair pathways is defective, the others may work as compensatory backups. The latter pathways are explored for synthetic lethal anticancer therapy. In this article, we extend the concept of compensatory alternative DNA repair to unify the theories. We propose that the microenvironmental stress can activate low-fidelity compensatory alternative DNA repair, causing mutations. If the mutation occurs to a DNA repair gene, this secondarily mutated gene can lead to even more mutated genes, including those related to other DNA repair pathways, eventually destabilizing the genome. Therefore, the low-fidelity compensatory alternative DNA repair may mediate microenvironment-dependent carcinogenesis. The proposal seems consistent with the view of evolution: the environmental stress causes mutations to adapt to the changing environment.

  6. A Review of Current Concepts in Flexor Tendon Repair: Physiology, Biomechanics, Surgical Technique and Rehabilitation

    PubMed Central

    Rymer, Ben; Theobald, Peter; Thomas, Peter B.M.

    2015-01-01

    Historically, the surgical treatment of flexor tendon injuries has always been associated with controversy. It was not until 1967, when the paper entitled Primary repair of flexor tendons in no man’s land was presented at the American Society of Hand Surgery, which reported excellent results and catalyzed the implementation of this technique into worldwide practice. We present an up to date literature review using PubMed and Google Scholar where the terms flexor tendon, repair and rehabilitation were used. Topics covered included functional anatomy, nutrition, biome-chanics, suture repair, repair site gapping, and rehabilitation. This article aims to provide a comprehensive and complete overview of flexor tendon repairs. PMID:26793293

  7. A Two-tiered compensatory response to loss of DNA repair modulates aging and stress response pathways

    PubMed Central

    Fensgård, Øyvind; Kassahun, Henok; Bombik, Izabela; Rognes, Torbjørn; Lindvall, Jessica Margareta; Nilsen, Hilde

    2010-01-01

    Activation of oxidative stress-responses and downregulation of insulin-like signaling (ILS) is seen in Nucleotide Excision Repair (NER) deficient segmental progeroid mice. Evidence suggests that this is a survival response to persistent transcription-blocking DNA damage, although the relevant lesions have not been identified. Here we show that loss of NTH-1, the only Base Excision Repair (BER) enzyme known to initiate repair of oxidative DNA damage inC. elegans, restores normal lifespan of the short-lived NER deficient xpa-1 mutant. Loss of NTH-1 leads to oxidative stress and global expression profile changes that involve upregulation of genes responding to endogenous stress and downregulation of ILS. A similar, but more extensive, transcriptomic shift is observed in the xpa-1 mutant whereas loss of both NTH-1 and XPA-1 elicits a different profile with downregulation of Aurora-B and Polo-like kinase 1 signaling networks as well as DNA repair and DNA damage response genes. The restoration of normal lifespan and absence oxidative stress responses in nth-1;xpa-1 indicate that BER contributes to generate transcription blocking lesions from oxidative DNA damage. Hence, our data strongly suggests that the DNA lesions relevant for aging are repair intermediates resulting from aberrant or attempted processing by BER of lesions normally repaired by NER. PMID:20382984

  8. Bone marrow cells for cardiac regeneration and repair: current status and issues.

    PubMed

    Haider, Husnain Kh

    2006-07-01

    Extensive studies in experimental animal heart models and patients have shown the promise of bone marrow cell (BMC) transplantation as an alternative strategy to the conventional treatment modalities for cardiac repair. 'Stemness' of BMC to adopt cardiac phenotype, their potential as carriers of exogenous therapeutic genes and an inherent ability to express growth factors and cytokines to exert paracrine effects have been especially focused until recently. These findings suggest that locally delivered BMCs are capable of regenerating de novo myocardium. Others have shown that extensive neovascularization due to paracrine effects of the engrafted cells resulted in improved regional blood flow and reduced infarct size. Despite initial success, there are multiple fundamental issues that remain contentious. Indeed, resolving these issues will optimize future heart cell therapy protocols to achieve better prognosis in the clinical settings. This review is a concise, in-depth and critical appreciation of the role of BMCs in heart cell therapy and builds a conceptual framework to elaborate their significance as a possible source of donor cells. Moreover, it discusses the current status of BMC transplantation as a clinical modality and the relevant issues confronting this approach in light of the published data with clinical relevance.

  9. Oxytocin and socioemotional aging: Current knowledge and future trends

    PubMed Central

    Ebner, Natalie C.; Maura, Gabriela M.; MacDonald, Kai; Westberg, Lars; Fischer, Håkan

    2013-01-01

    The oxytocin (OT) system is involved in various aspects of social cognition and prosocial behavior. Specifically, OT has been examined in the context of social memory, emotion recognition, cooperation, trust, empathy, and bonding, and—though evidence is somewhat mixed-intranasal OT appears to benefit aspects of socioemotional functioning. However, most of the extant data on aging and OT is from animal research and human OT research has focused largely on young adults. As such, though we know that various socioemotional capacities change with age, we know little about whether age-related changes in the OT system may underlie age-related differences in socioemotional functioning. In this review, we take a genetic-neuro-behavioral approach and evaluate current evidence on age-related changes in the OT system as well as the putative effects of these alterations on age-related socioemotional functioning. Looking forward, we identify informational gaps and propose an Age-Related Genetic, Neurobiological, Sociobehavioral Model of Oxytocin (AGeNeS-OT model) which may structure and inform investigations into aging-related genetic, neural, and sociocognitive processes related to OT. As an exemplar of the use of the model, we report exploratory data suggesting differences in socioemotional processing associated with genetic variation in the oxytocin receptor gene (OXTR) in samples of young and older adults. Information gained from this arena has translational potential in depression, social stress, and anxiety-all of which have high relevance in aging—and may contribute to reducing social isolation and improving well-being of individuals across the lifespan. PMID:24009568

  10. Chronic Wound Repair and Healing in Older Adults: Current Status and Future Research

    PubMed Central

    Gould, Lisa; Abadir, Peter; Brem, Harold; Carter, Marissa; Conner-Kerr, Teresa; Davidson, Jeff; DiPietro, Luisa; Falanga, Vincent; Fife, Caroline; Gardner, Sue; Grice, Elizabeth; Harmon, John; Hazzard, William R.; High, Kevin P.; Houghton, Pamela; Jacobson, Nasreen; Kirsner, Robert S.; Kovacs, Elizabeth J.; Margolis, David; Horne, Frances McFarland; Reed, May J.; Sullivan, Dennis H.; Thom, Stephen; Tomic-Canic, Marjana; Walston, Jeremy; Whitney, Jo Anne; Williams, John; Zieman, Susan; Schmader, Kenneth

    2015-01-01

    Older adults are more likely to have chronic wounds than younger people, and the effect of chronic wounds on quality of life is particularly profound in this population. Wound healing slows with age, but the basic biology underlying chronic wounds and the influence of age-associated changes on wound healing are poorly understood. Most studies have used in vitro approaches and various animal models, but observed changes translate poorly to human healing conditions. The effect of age and accompanying multimorbidity on the effectiveness of existing and emerging treatment approaches for chronic wounds is also unknown, and older adults tend to be excluded from randomized clinical trials. Poorly defined outcomes and variables; lack of standardization in data collection; and variations in the definition, measurement, and treatment of wounds also hamper clinical studies. The Association of Specialty Professors, in conjunction with the National Institute on Aging and the Wound Healing Society, held a workshop, summarized in this article, to explore the current state of knowledge and research challenges, engage investigators across disciplines, and identify research questions to guide future study of age-associated changes in chronic wound healing. PMID:25753048

  11. Chronic Wound Repair and Healing in Older Adults: Current Status and Future Research

    PubMed Central

    Gould, Lisa; Abadir, Peter; Brem, Harold; Carter, Marissa; Conner-Kerr, Teresa; Davidson, Jeff; DiPietro, Luisa; Falanga, Vincent; Fife, Caroline; Gardner, Sue; Grice, Elizabeth; Harmon, John; Hazzard, William R.; High, Kevin P.; Houghton, Pamela; Jacobson, Nasreen; Kirsner, Robert S.; Kovacs, Elizabeth J.; Margolish, David; McFarland Horne, Frances; Reed, May J.; Sullivan, Dennis H.; Thom, Stephen; Tomic-Canic, Marjana; Walston, Jeremy; Whitney, JoAnne; Williams, John; Zieman, Susan; Schmader, Kenneth

    2014-01-01

    The incidence of chronic wounds is increased among older adults, and the impact of chronic wounds on quality of life is particularly profound in this population. It is well established that wound healing slows with age. However, the basic biology underlying chronic wounds and the influence of age-associated changes on wound healing are poorly understood. Most studies have used in vitro approaches and various animal models, but observed changes translate poorly to human healing conditions. The impact of age and accompanying multi-morbidity on the effectiveness of existing and emerging treatment approaches for chronic wounds is also unknown, and older adults tend to be excluded from randomized clinical trials. Poorly defined outcomes and variables, lack of standardization in data collection, and variations in the definition, measurement, and treatment of wounds also hamper clinical studies. The Association of Specialty Professors, in conjunction with the National Institute on Aging and the Wound Healing Society, held a workshop, summarized in this paper, to explore the current state of knowledge and research challenges, engage investigators across disciplines, and identify key research questions to guide future study of age-associated changes in chronic wound healing. PMID:25486905

  12. Repairing and Renovating Aging School Facilities. ERIC Digest Series Number EA28.

    ERIC Educational Resources Information Center

    Klauke, Amy

    Recent influxes of baby boomers coupled with state reforms reducing student-teacher ratios are stretching the limits on available school facilities across the country. Several aspects of the school facilities issue are covered in question-and-answer format; (1) What is the current status of aging school buildings? (2) What are the financial…

  13. Photons bring light into DNA repair: the comet assay and laser microbeams for studying photogenotoxicity of drugs and ageing.

    PubMed

    Greulich, Karl Otto

    2011-03-01

    This contribution reviews recent applications of micromanipulation, by UV photons, in DNA repair and ageing research as well as in the evaluation of the phototoxicity of drugs. In some cases, micromanipulation is combined with the comet assay, a technique, which allows a direct view on DNA damages. It is shown that, in humans, the sensitivity of DNA to UV induced damage and its subsequent repair is surprisingly stable up to high age and that drugs which are usually non-toxic induce DNA damage when irradiated in parallel by UV irradiation. Using the immune fluorescent comet assay, IFCA, a variant of the comet assay, direct comparison of the effects of ionizing (137) Cs radiation with those of localized UV radiation is possible. When a laser microbeam is used to damage DNA in a cell nucleus with high temporal and spatial resolution, it can be observed directly how repair molecules accumulate (are recruited) at the site of damage. Comparison of the recruitment speed allows establishing an order of DNA repair events.

  14. Impact of age-associated cyclopurine lesions on DNA repair helicases.

    PubMed

    Khan, Irfan; Suhasini, Avvaru N; Banerjee, Taraswi; Sommers, Joshua A; Kaplan, Daniel L; Kuper, Jochen; Kisker, Caroline; Brosh, Robert M

    2014-01-01

    8,5' cyclopurine deoxynucleosides (cPu) are locally distorting DNA base lesions corrected by nucleotide excision repair (NER) and proposed to play a role in neurodegeneration prevalent in genetically defined Xeroderma pigmentosum (XP) patients. In the current study, purified recombinant helicases from different classifications based on sequence homology were examined for their ability to unwind partial duplex DNA substrates harboring a single site-specific cPu adduct. Superfamily (SF) 2 RecQ helicases (RECQ1, BLM, WRN, RecQ) were inhibited by cPu in the helicase translocating strand, whereas helicases from SF1 (UvrD) and SF4 (DnaB) tolerated cPu in either strand. SF2 Fe-S helicases (FANCJ, DDX11 (ChlR1), DinG, XPD) displayed marked differences in their ability to unwind the cPu DNA substrates. Archaeal Thermoplasma acidophilum XPD (taXPD), homologue to the human XPD helicase involved in NER DNA damage verification, was impeded by cPu in the non-translocating strand, while FANCJ was uniquely inhibited by the cPu in the translocating strand. Sequestration experiments demonstrated that FANCJ became trapped by the translocating strand cPu whereas RECQ1 was not, suggesting the two SF2 helicases interact with the cPu lesion by distinct mechanisms despite strand-specific inhibition for both. Using a protein trap to simulate single-turnover conditions, the rate of FANCJ or RECQ1 helicase activity was reduced 10-fold and 4.5-fold, respectively, by cPu in the translocating strand. In contrast, single-turnover rates of DNA unwinding by DDX11 and UvrD helicases were only modestly affected by the cPu lesion in the translocating strand. The marked difference in effect of the translocating strand cPu on rate of DNA unwinding between DDX11 and FANCJ helicase suggests the two Fe-S cluster helicases unwind damaged DNA by distinct mechanisms. The apparent complexity of helicase encounters with an unusual form of oxidative damage is likely to have important consequences in the

  15. The role of age and comorbidities in postoperative outcome of mitral valve repair: A propensity-matched study.

    PubMed

    Bonnet, Vincent; Boisselier, Clément; Saplacan, Vladimir; Belin, Annette; Gérard, Jean-Louis; Fellahi, Jean-Luc; Hanouz, Jean-Luc; Fischer, Marc-Olivier

    2016-06-01

    The average age of patients undergoing mitral valve repair is increasing each year. This retrospective study aimed to compare postoperative complications of mitral valve repair (known to be especially high-risk) between 2 age groups: under and over the age of 80.Patients who underwent mitral valve repair were divided into 2 groups: group 1 (<80 years old) and group 2 (≥80 years old). Baseline characteristics, pre- and postoperative hemodynamic data, surgical characteristics, and postoperative follow-up data until hospital discharge were collected.A total of 308 patients were included: 264 in group 1 (age 63 ± 13 years) and 44 in group 2 (age 83 ± 2 years). Older patients had more comorbidities (atrial fibrillation, history of cardiac decompensation, systemic hypertension, pulmonary hypertension, and chronic kidney disease) and they presented more postoperative complications (50.0% vs 33.7%; P = 0.043), with a longer hospital stay (8.9 ± 6.9 vs 6.6 ± 4.6 days; P = 0.005). To assess the burden of age, a propensity score was awarded to postoperative complications. Active smoking, chronic pulmonary disease, chronic kidney disease, associated ischemic heart disease, obesity, and cardio pulmonary by-pass duration were described as independent risk factors. When matched on this propensity score, there was no difference in morbidity or mortality between group 1 and group 2.Older patients suffered more postoperative complications, which were related to their comorbidities and not only to their age. PMID:27336886

  16. Mitochondrial base excision repair in mouse synaptosomes during normal aging and in a model of Alzheimer's disease.

    PubMed

    Gredilla, Ricardo; Weissman, Lior; Yang, Jenq-Lin; Bohr, Vilhelm A; Stevnsner, Tinna

    2012-04-01

    Brain aging is associated with synaptic decline and synaptic function is highly dependent on mitochondria. Increased levels of oxidative DNA base damage and accumulation of mitochondrial DNA (mtDNA) mutations or deletions lead to mitochondrial dysfunction, playing an important role in the aging process and the pathogenesis of several neurodegenerative diseases. Here we have investigated the repair of oxidative base damage, in synaptosomes of mouse brain during normal aging and in an AD model. During normal aging, a reduction in the base excision repair (BER) capacity was observed in the synaptosomal fraction, which was associated with a decrease in the level of BER proteins. However, we did not observe changes between the synaptosomal BER activities of presymptomatic and symptomatic AD mice harboring mutated amyolid precursor protein (APP), Tau, and presinilin-1 (PS1) (3xTgAD). Our findings suggest that the age-related reduction in BER capacity in the synaptosomal fraction might contribute to mitochondrial and synaptic dysfunction during aging. The development of AD-like pathology in the 3xTgAD mouse model was, however, not associated with deficiencies of the BER mechanisms in the synaptosomal fraction when the whole brain was analyzed.

  17. Epigenomic maintenance through dietary intervention can facilitate DNA repair process to slow down the progress of premature aging.

    PubMed

    Ghosh, Shampa; Sinha, Jitendra Kumar; Raghunath, Manchala

    2016-09-01

    DNA damage caused by various sources remains one of the most researched topics in the area of aging and neurodegeneration. Increased DNA damage causes premature aging. Aging is plastic and is characterised by the decline in the ability of a cell/organism to maintain genomic stability. Lifespan can be modulated by various interventions like calorie restriction, a balanced diet of macro and micronutrients or supplementation with nutrients/nutrient formulations such as Amalaki rasayana, docosahexaenoic acid, resveratrol, curcumin, etc. Increased levels of DNA damage in the form of double stranded and single stranded breaks are associated with decreased longevity in animal models like WNIN/Ob obese rats. Erroneous DNA repair can result in accumulation of DNA damage products, which in turn result in premature aging disorders such as Hutchinson-Gilford progeria syndrome. Epigenomic studies of the aging process have opened a completely new arena for research and development of drugs and therapeutic agents. We propose here that agents or interventions that can maintain epigenomic stability and facilitate the DNA repair process can slow down the progress of premature aging, if not completely prevent it. © 2016 IUBMB Life, 68(9):717-721, 2016. PMID:27364681

  18. When ageing meets the blues: Are current antidepressants effective in depressed aged patients?

    PubMed

    Felice, Daniela; O'Leary, Olivia F; Cryan, John F; Dinan, Timothy G; Gardier, Alain M; Sánchez, Connie; David, Denis J

    2015-08-01

    "I had to wait 110 years to become famous. I wanted to enjoy it as long as possible.", Jeanne Louise Calment (1875-1997). This review summarizes current knowledge of the effects of antidepressant drugs in elderly patients (double-blind placebo (n=27) or active comparator-controlled clinical trials (n=21) indexed in Pubmed in depressed patients aged ≥60) and in aged mice (≥9 months) and middle-aged rats (≥14 months) on depression-related symptoms and cognitive performances. Finally, other potential therapeutic targets for treating depression-related disorders in elderly patients are also addressed (neurogenesis, GABAB receptor, 5-HT4 receptor, mTOR signaling). Overall, the very few published preclinical studies (n=12 in total) in middle-aged and aged rodents seem to suggest that selective serotonin reuptake inhibitors (SSRIs) may be less effective than tricyclic antidepressant drugs (TCAs) in ameliorating depression-like behavior and cognitive functions. On the other hand, results from clinical trials suggest that there is not a marked difference in efficacy and safety profiles of current marketed classes of antidepressant drugs.

  19. Current Arthroscopic Concepts in Repairing Posterior Cruciate Ligament Tibial-Sided Avulsions.

    PubMed

    Malempati, Chaitu; Felder, Jerrod; Elliott, Michael; Brunkhorst, Joseph; Miller, Mark; Johnson, Darren L

    2015-09-01

    Posterior cruciate ligament (PCL) injuries are extremely rare and most commonly occur in the trauma setting. They can lead to instability, pain, diminished function, and eventual arthrosis. Several techniques of arthroscopic PCL repair for tibial-sided bony avulsions have been described in the literature; however, no single technique has emerged as the gold standard to predictably restore posterior knee stability, PCL function, and knee biomechanics. The authors believe that the best results will come from procedures that re-create the normal human anatomy and knee kinematics. In this article, 3 arthroscopic methods of PCL avulsion repairs performed at 2 academic institutions are analyzed. The techniques described here provide good options for the treatment of these injuries.

  20. Current Progress in Bioactive Ceramic Scaffolds for Bone Repair and Regeneration

    PubMed Central

    Gao, Chengde; Deng, Youwen; Feng, Pei; Mao, Zhongzheng; Li, Pengjian; Yang, Bo; Deng, Junjie; Cao, Yiyuan; Shuai, Cijun; Peng, Shuping

    2014-01-01

    Bioactive ceramics have received great attention in the past decades owing to their success in stimulating cell proliferation, differentiation and bone tissue regeneration. They can react and form chemical bonds with cells and tissues in human body. This paper provides a comprehensive review of the application of bioactive ceramics for bone repair and regeneration. The review systematically summarizes the types and characters of bioactive ceramics, the fabrication methods for nanostructure and hierarchically porous structure, typical toughness methods for ceramic scaffold and corresponding mechanisms such as fiber toughness, whisker toughness and particle toughness. Moreover, greater insights into the mechanisms of interaction between ceramics and cells are provided, as well as the development of ceramic-based composite materials. The development and challenges of bioactive ceramics are also discussed from the perspective of bone repair and regeneration. PMID:24646912

  1. Current advances in tissue repair and regeneration: the future is bright.

    PubMed

    Ninov, Nikolay; Yun, Maximina H

    2015-04-01

    The fifth EMBO conference on 'The Molecular and Cellular Basis of Regeneration and Repair' took place in the peaceful coastal town of Sant Feliu de Guixols (Spain) on September 2014. The meeting was organised by Emili Saló (U. Barcelona, Spain), Kimberly Mace (U. Manchester, UK), Patrizia Ferretti (University College London, UK) and Michael Brand (Centre for Regenerative Therapies Dresden, Germany) and received the generous support of Society for Developmental Biology, The Company of Biologists, Centre for Regenerative Therapies Dresden, Garland Science and the journals Regeneration and Cell Signalling. The natural surroundings provided an inspiring setting for 185 researchers from all over the world to share their latest findings and views on the field. The conference showcased the great diversity of model organisms used for studying regeneration and tissue repair, including invertebrate and vertebrate species (Fig. 1). Importantly, this diversity in animal models allowed for a global overview of the mechanisms that promote regeneration. In addition, it highlighted some of the unique aspects that confer differences in regenerative capacities among different species. These differences might lie in each of the different steps involved in performing regeneration, including triggering the regenerative response, controlling cellular plasticity, re-stablishing the correct tissue patterns, as well as determining the roles of extrinsic factors, such as the role of inflammation in regeneration. A deeper understanding of these processes in the naturally regenerating species is a prerequisite for advancing the field of regenerative medicine and tissue repair in humans. PMID:27499870

  2. Analysis of gene expression dynamics revealed delayed and abnormal epidermal repair process in aged compared to young skin.

    PubMed

    Sextius, Peggy; Marionnet, Claire; Tacheau, Charlotte; Bon, François-Xavier; Bastien, Philippe; Mauviel, Alain; Bernard, Bruno A; Bernerd, Françoise; Dubertret, Louis

    2015-05-01

    With aging, epidermal homeostasis and barrier function are disrupted. In a previous study, we analyzed the transcriptomic response of young skin epidermis after stratum corneum removal, and obtained a global kinetic view of the molecular processes involved in barrier function recovery. In the present study, the same analysis was performed in aged skin in order to better understand the defects which occur with aging. Thirty healthy male volunteers (67 ± 4 years old) were involved. Tape-strippings were carried out on the inner face of one forearm, the other unstripped forearm serving as control. At 2, 6, 18, 30 and 72 h after stripping, TEWL measurements were taken, and epidermis samples were collected. Total RNA was extracted and analyzed using DermArray(®) cDNA microarrays. The results highlighted that barrier function recovery and overall kinetics of gene expression were delayed following stripping in aged skin. Indeed, the TEWL measurements showed that barrier recovery in the young group appeared to be dramatically significant during the overall kinetics, while there were no significant evolution in the aged group until 30 h. Moreover, gene expression analysis revealed that the number of modulated genes following tape stripping increased as a function of time and reached a peak at 6 h after tape stripping in young skin, while it was at 30 h in aged skin, showing that cellular activity linked to the repair process may be engaged earlier in young epidermis than in aged epidermis. A total of 370 genes were modulated in the young group. In the aged group, 382 genes were modulated, whose 184 were also modulated in the young group. Only eight genes that were modulated in both groups were significantly differently modulated. The characterization of these genes into 15 functional families helped to draw a scenario for the aging process affecting epidermal repair capacity. PMID:25740152

  3. Current therapeutic developments in atrophic age-related macular degeneration.

    PubMed

    Hanus, Jakub; Zhao, Fangkun; Wang, Shusheng

    2016-01-01

    Age-related macular degeneration (AMD), a degenerative disorder of the central retina, is the leading cause of irreversible blindness in the elderly. The underlying mechanism of the advanced form of dry AMD, also named geographic atrophy (GA) or atrophic AMD, remains unclear. Consequently, no cure is available for dry AMD or GA. The only prevention option currently available is the Age-Related Eye Disease Study (AREDS) formulation, which has been demonstrated to slow down the progression of dry AMD. This review summarises recent advances in therapy for dry AMD and GA. Building on the new understanding of the disease and recent technological breakthroughs, numerous ongoing clinical trials have the goal of meeting the need to cure AMD. Therapeutic agents are being developed to target the key features of the disease, including inhibiting the complement pathway and other inflammatory pathways, reducing oxidative stress and protecting retinal pigment epithelial (RPE) cells, inhibiting lipofuscin and visual cycle, regenerating RPE cells from stem cells and restoring choroidal blood flow. Some of these therapeutic options, especially the stem cell-based therapy, hold great promise, which brings great hope for this devastating blinding disease. PMID:26553922

  4. Current Therapeutic Development for Atrophic Age-related Macular Degeneration

    PubMed Central

    Hanus, Jakub; Zhao, Fangkun; Wang, Shusheng

    2016-01-01

    Age-related macular degeneration (AMD), a degenerative disorder of the central retina, is the leading cause of irreversible blindness in the elderly. The underlying mechanism of the advanced form of dry AMD, also named geographic atrophy (GA) or atrophic AMD, remains unclear. Consequently, no cure is available for dry AMD or GA. The only prevention option currently available is the Age Related Eye Disease Study (AREDS) formulation which has been demonstrated to slow down the progression of dry AMD. This review summarizes recent advances in therapy for dry AMD and GA. Building on the new understanding of the disease and recent technological breakthroughs, numerous ongoing clinical trials have the goal of meeting the need to cure AMD. Therapeutic agents are being developed to target the key features of the disease, including inhibiting the complement pathway and other inflammatory pathways, reducing oxidative stress and protecting retinal pigment epithelial (RPE) cells, inhibiting lipofuscin and visual cycle, regenerating RPE cells from stem cells and restoring choroidal blood flow. Some of these therapeutic options, especially the stem-cell based therapy, hold great promise, which brings great hope for this devastating blinding disease. PMID:26553922

  5. Hospital mortality of patients aged 80 and older after surgical repair for type A acute aortic dissection in Japan

    PubMed Central

    Ohnuma, Tetsu; Shinjo, Daisuke; Fushimi, Kiyohide

    2016-01-01

    Abstract To evaluate whether patients aged 80 and older have higher risk of hospital mortality after repair of type A acute aortic dissection (TAAAD). Emergency surgery for TAAAD in patients aged 80 and older remains a controversial issue because of its high surgical risk. Data from patients who underwent surgical repair of TAAAD between April 2011 and March 2013 were retrospectively extracted from the Japanese Diagnosis Procedure Combination database. The effect of age on hospital mortality was evaluated using multivariate logistic regression analysis. A total of 5175 patients were enrolled. The mean age of patients was 67.1 ± 13.0 years, and the male:female ratio was 51:49. Patients aged 80 and older more frequently received tracheostomy than their younger counterparts (9.5% vs 5.4%, P <0.001). Intensive care unit and hospital stays were significantly longer in the elderly cohort versus the younger cohort (7.6 vs 6.7 days, P <0.001, and 42.2 vs 35.8 days, P <0.001, respectively). Logistic regression analysis showed that age ≥80 years was significantly associated with a higher risk of hospital mortality (adjusted odds ratio, 1.62; 95% confidence interval, 1.28–2.06; P <0.001). In linear regression analysis, age ≥80 years was also significantly associated with longer hospital stay (P = 0.007). In a large, nationwide, Japanese database, patients aged 80 and older were at increased risk of hospital mortality and length of hospital stay. PMID:27495057

  6. Hospital mortality of patients aged 80 and older after surgical repair for type A acute aortic dissection in Japan.

    PubMed

    Ohnuma, Tetsu; Shinjo, Daisuke; Fushimi, Kiyohide

    2016-08-01

    To evaluate whether patients aged 80 and older have higher risk of hospital mortality after repair of type A acute aortic dissection (TAAAD).Emergency surgery for TAAAD in patients aged 80 and older remains a controversial issue because of its high surgical risk.Data from patients who underwent surgical repair of TAAAD between April 2011 and March 2013 were retrospectively extracted from the Japanese Diagnosis Procedure Combination database. The effect of age on hospital mortality was evaluated using multivariate logistic regression analysis.A total of 5175 patients were enrolled. The mean age of patients was 67.1 ± 13.0 years, and the male:female ratio was 51:49. Patients aged 80 and older more frequently received tracheostomy than their younger counterparts (9.5% vs 5.4%, P <0.001). Intensive care unit and hospital stays were significantly longer in the elderly cohort versus the younger cohort (7.6 vs 6.7 days, P <0.001, and 42.2 vs 35.8 days, P <0.001, respectively). Logistic regression analysis showed that age ≥80 years was significantly associated with a higher risk of hospital mortality (adjusted odds ratio, 1.62; 95% confidence interval, 1.28-2.06; P <0.001). In linear regression analysis, age ≥80 years was also significantly associated with longer hospital stay (P = 0.007).In a large, nationwide, Japanese database, patients aged 80 and older were at increased risk of hospital mortality and length of hospital stay. PMID:27495057

  7. Retinal pigment epithelial cell multinucleation in the aging eye - a mechanism to repair damage and maintain homoeostasis.

    PubMed

    Chen, Mei; Rajapakse, Dinusha; Fraczek, Monika; Luo, Chang; Forrester, John V; Xu, Heping

    2016-06-01

    Retinal pigment epithelial (RPE) cells are central to retinal health and homoeostasis. Dysfunction or death of RPE cells underlies many age-related retinal degenerative disorders particularly age-related macular degeneration. During aging RPE cells decline in number, suggesting an age-dependent cell loss. RPE cells are considered to be postmitotic, and how they repair damage during aging remains poorly defined. We show that RPE cells increase in size and become multinucleate during aging in C57BL/6J mice. Multinucleation appeared not to be due to cell fusion, but to incomplete cell division, that is failure of cytokinesis. Interestingly, the phagocytic activity of multinucleate RPE cells was not different from that of mononuclear RPE cells. Furthermore, exposure of RPE cells in vitro to photoreceptor outer segment (POS), particularly oxidized POS, dose-dependently promoted multinucleation and suppressed cell proliferation. Both failure of cytokinesis and suppression of proliferation required contact with POS. Exposure to POS also induced reactive oxygen species and DNA oxidation in RPE cells. We propose that RPE cells have the potential to proliferate in vivo and to repair defects in the monolayer. We further propose that the conventionally accepted 'postmitotic' status of RPE cells is due to a modified form of contact inhibition mediated by POS and that RPE cells are released from this state when contact with POS is lost. This is seen in long-standing rhegmatogenous retinal detachment as overtly proliferating RPE cells (proliferative vitreoretinopathy) and more subtly as multinucleation during normal aging. Age-related oxidative stress may promote failure of cytokinesis and multinucleation in RPE cells.

  8. Current advances in tissue repair and regeneration: the future is bright

    PubMed Central

    2015-01-01

    Abstract The fifth EMBO conference on ‘The Molecular and Cellular Basis of Regeneration and Repair’ took place in the peaceful coastal town of Sant Feliu de Guixols (Spain) on September 2014. The meeting was organised by Emili Saló (U. Barcelona, Spain), Kimberly Mace (U. Manchester, UK), Patrizia Ferretti (University College London, UK) and Michael Brand (Centre for Regenerative Therapies Dresden, Germany) and received the generous support of Society for Developmental Biology, The Company of Biologists, Centre for Regenerative Therapies Dresden, Garland Science and the journals Regeneration and Cell Signalling. The natural surroundings provided an inspiring setting for 185 researchers from all over the world to share their latest findings and views on the field. The conference showcased the great diversity of model organisms used for studying regeneration and tissue repair, including invertebrate and vertebrate species (Fig. 1). Importantly, this diversity in animal models allowed for a global overview of the mechanisms that promote regeneration. In addition, it highlighted some of the unique aspects that confer differences in regenerative capacities among different species. These differences might lie in each of the different steps involved in performing regeneration, including triggering the regenerative response, controlling cellular plasticity, re‐stablishing the correct tissue patterns, as well as determining the roles of extrinsic factors, such as the role of inflammation in regeneration. A deeper understanding of these processes in the naturally regenerating species is a prerequisite for advancing the field of regenerative medicine and tissue repair in humans. PMID:27499870

  9. Characterization of recovery, repair, and inflammatory processes following contusion spinal cord injury in old female rats: is age a limitation?

    PubMed Central

    2014-01-01

    Background Although the incidence of spinal cord injury (SCI) is steadily rising in the elderly human population, few studies have investigated the effect of age in rodent models. Here, we investigated the effect of age in female rats on spontaneous recovery and repair after SCI. Young (3 months) and aged (18 months) female rats received a moderate contusion SCI at T9. Behavioral recovery was assessed, and immunohistocemical and stereological analyses performed. Results Aged rats demonstrated greater locomotor deficits compared to young, beginning at 7 days post-injury (dpi) and lasting through at least 28 dpi. Unbiased stereological analyses revealed a selective increase in percent lesion area and early (2 dpi) apoptotic cell death caudal to the injury epicenter in aged versus young rats. One potential mechanism for these differences in lesion pathogenesis is the inflammatory response; we therefore assessed humoral and cellular innate immune responses. No differences in either acute or chronic serum complement activity, or acute neutrophil infiltration, were observed between age groups. However, the number of microglia/macrophages present at the injury epicenter was increased by 50% in aged animals versus young. Conclusions These data suggest that age affects recovery of locomotor function, lesion pathology, and microglia/macrophage response following SCI. PMID:25512759

  10. Caloric restriction promotes genomic stability by induction of base excision repair and reversal of its age-related decline.

    PubMed

    Cabelof, Diane C; Yanamadala, Sunitha; Raffoul, Julian J; Guo, ZhongMao; Soofi, Abdulsalam; Heydari, Ahmad R

    2003-03-01

    Caloric restriction is a potent experimental manipulation that extends mean and maximum life span and delays the onset and progression of tumors in laboratory rodents. While caloric restriction (CR) clearly protects the genome from deleterious damage, the mechanism by which genomic stability is achieved remains unclear. We provide evidence that CR promotes genomic stability by increasing DNA repair capacity, specifically base excision repair (BER). CR completely reverses the age-related decline in BER capacity (P<0.01) in all tissues tested (brain, liver, spleen and testes) providing aged, CR animals with the BER phenotype of young, ad libitum-fed animals. This CR-induced reversal of the aged BER phenotype is accompanied by a reversal in the age-related decline in DNA polymerase beta (beta-pol), a rate-limiting enzyme in the BER pathway. CR significantly reversed the age-related loss of beta-pol protein levels (P<0.01), mRNA levels (P<0.01) and enzyme activity (P<0.01) in all tissues tested. Additionally, in young (4-6-month-old) CR animals a significant up-regulation in BER capacity, beta-pol protein and beta-pol mRNA is observed (P<0.01), demonstrating an early effect of CR that may provide insight in distinguishing the anti-tumor from the anti-aging effects of CR. This up-regulation in BER by caloric restriction in young animals corresponds to increased protection from carcinogen exposure, as mutation frequency is significantly reduced in CR animals exposed to either DMS or 2-nitropropane (2-NP) (P<0.01). Overall the data suggest an important biological consequence of moderate BER up-regulation and provides support for the hormesis theory of caloric restriction.

  11. New Technologies for Repairing Aging Cables in Nuclear Power Plants: M3LW-14OR0404015 Cable Rejuvenation Report

    SciTech Connect

    Simmons, Kevin L.; Fifield, Leonard S.; Westman, Matthew P.; Roberts, John A.

    2014-09-08

    The goal of this project is to conceptually demonstrate techniques to repair cables that have degraded through subjection to long-term thermal and radiation exposure in nuclear power plants. In fiscal year 2014 (FY14) we focused on commercially available ethylene-propylene rubber (EPR) as the relevant test material, isolated a high surface area form of the EPR material to facilitate chemical treatment screening and charaterization, and measured chemical changes in the material due to aging and treatment using Fourier Transfrom Infrared (FTIR) spectroscopy.

  12. Enabling stem cell therapies for tissue repair: current and future challenges

    PubMed Central

    Wong, Victor W.; Sorkin, Michael; Gurtner, Geoffrey C.

    2012-01-01

    Stem cells embody the tremendous potential of the human body to develop, grow, and repair throughout life. Understanding the biologic mechanisms that underlie stem cell-mediated tissue regeneration is key to harnessing this potential. Recent advances in molecular biology, genetic engineering, and material science have broadened our understanding of stem cells and helped bring them closer to widespread clinical application. Specifically, innovative approaches to optimize how stem cells are identified, isolated, grown, and utilized will help translate these advances into effective clinical therapies. Although there is growing interest in stem cells worldwide, this enthusiasm must be tempered by the fact that these treatments remain for the most part clinically unproven. Future challenges include refining the therapeutic manipulation of stem cells, validating these technologies in randomized clinical trials, and regulating the global expansion of regenerative stem cell therapies. PMID:23178704

  13. Mesenchymal Stem Cells Ageing: Targeting the "Purinome" to Promote Osteogenic Differentiation and Bone Repair.

    PubMed

    Noronha-Matos, J B; Correia-de-Sá, P

    2016-09-01

    Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into bone forming cells. Such ability is compromised in elderly individuals resulting in bone disorders such as osteoporosis, also limiting their clinical usage for cell transplantation and bone tissue engineering strategies. In bone marrow niches, adenine and uracil nucleotides are important local regulators of osteogenic differentiation of MSCs. Nucleotides can be released to the extracellular milieu under both physiological and pathological conditions via (1) membrane cell damage, (2) vesicle exocytosis, (3) ATP-binding cassette transporters, and/or (4) facilitated diffusion through maxi-anion channels, hemichannels or ligand-gated receptor pores. Nucleotides and their derivatives act via adenosine P1 (A1 , A2A , A2B , and A3 ) and nucleotide-sensitive P2 purinoceptors comprising ionotropic P2X and G-protein-coupled P2Y receptors. Purinoceptors activation is terminated by membrane-bound ecto-nucleotidases and other ecto-phosphatases, which rapidly hydrolyse extracellular nucleotides to their respective nucleoside 5'-di- and mono-phosphates, nucleosides and free phosphates, or pyrophosphates. Current knowledge suggests that different players of the "purinome" cascade, namely nucleotide release sites, ecto-nucleotidases and purinoceptors, orchestrate to fine-tuning regulate the activity of MSCs in the bone microenvironment. Increasing studies, using osteoprogenitor cell lines, animal models and, more recently, non-modified MSCs from postmenopausal women, raised the possibility to target chief components of the purinergic signaling pathway to regenerate the ability of aged MSCs to differentiate into functional osteoblasts. This review summarizes the main findings of those studies, prompting for novel therapeutic strategies to control ageing disorders where bone destruction exceeds bone formation, like osteoporosis, rheumatoid arthritis, and fracture mal-union. J. Cell. Physiol. 231: 1852

  14. Meta-analyses identify 13 novel loci associated with age at menopause and highlights DNA repair and immune pathways

    PubMed Central

    Stolk, Lisette; Perry, John RB; Chasman, Daniel I; He, Chunyan; Mangino, Massimo; Sulem, Patrick; Barbalic, Maja; Broer, Linda; Byrne, Enda M; Ernst, Florian; Esko, Tõnu; Franceschini, Nora; Gudbjartsson, Daniel F; Hottenga, Jouke-Jan; Kraft, Peter; McArdle, Patick F; Porcu, Eleonora; Shin, So-Youn; Smith, Albert V; van Wingerden, Sophie; Zhai, Guangju; Zhuang, Wei V; Albrecht, Eva; Alizadeh, Behrooz Z; Aspelund, Thor; Bandinelli, Stefania; Lauc, Lovorka Barac; Beckmann, Jacques S; Boban, Mladen; Boerwinkle, Eric; Broekmans, Frank J; Burri, Andrea; Campbell, Harry; Chanock, Stephen J; Chen, Constance; Cornelis, Marilyn C; Corre, Tanguy; Coviello, Andrea D; d’Adamo, Pio; Davies, Gail; de Faire, Ulf; de Geus, Eco JC; Deary, Ian J; Dedoussis, George VZ; Deloukas, Panagiotis; Ebrahim, Shah; Eiriksdottir, Gudny; Emilsson, Valur; Eriksson, Johan G; Fauser, Bart CJM; Ferreli, Liana; Ferrucci, Luigi; Fischer, Krista; Folsom, Aaron R; Garcia, Melissa E; Gasparini, Paolo; Gieger, Christian; Glazer, Nicole; Grobbee, Diederick E; Hall, Per; Haller, Toomas; Hankinson, Susan E; Hass, Merli; Hayward, Caroline; Heath, Andrew C; Hofman, Albert; Ingelsson, Erik; Janssens, A Cecile JW; Johnson, Andrew D; Karasik, David; Kardia, Sharon LR; Keyzer, Jules; Kiel, Douglas P; Kolcic, Ivana; Kutalik, Zoltán; Lahti, Jari; Lai, Sandra; Laisk, Triin; Laven, Joop SE; Lawlor, Debbie A; Liu, Jianjun; Lopez, Lorna M; Louwers, Yvonne V; Magnusson, Patrik KE; Marongiu, Mara; Martin, Nicholas G; Klaric, Irena Martinovic; Masciullo, Corrado; McKnight, Barbara; Medland, Sarah E; Melzer, David; Mooser, Vincent; Navarro, Pau; Newman, Anne B; Nyholt, Dale R; Onland-Moret, N. Charlotte; Palotie, Aarno; Paré, Guillaume; Parker, Alex N; Pedersen, Nancy L; Peeters, Petra HM; Pistis, Giorgio; Plump, Andrew S; Polasek, Ozren; Pop, Victor JM; Psaty, Bruce M; Räikkönen, Katri; Rehnberg, Emil; Rotter, Jerome I; Rudan, Igor; Sala, Cinzia; Salumets, Andres; Scuteri, Angelo; Singleton, Andrew; Smith, Jennifer A; Snieder, Harold; Soranzo, Nicole; Stacey, Simon N; Starr, John M; Stathopoulou, Maria G; Stirrups, Kathleen; Stolk, Ronald P; Styrkarsdottir, Unnur; Sun, Yan V; Tenesa, Albert; Thorand, Barbara; Toniolo, Daniela; Tryggvadottir, Laufey; Tsui, Kim; Ulivi, Sheila; van Dam, Rob M; van der Schouw, Yvonne T; van Gils, Carla H; van Nierop, Peter; Vink, Jacqueline M; Visscher, Peter M; Voorhuis, Marlies; Waeber, Gérard; Wallaschofski, Henri; Wichmann, H Erich; Widen, Elisabeth; Gent, Colette JM Wijnands-van; Willemsen, Gonneke; Wilson, James F; Wolffenbuttel, Bruce HR; Wright, Alan F; Yerges-Armstrong, Laura M; Zemunik, Tatijana; Zgaga, Lina; Zillikens, M. Carola; Zygmunt, Marek; Arnold, Alice M; Boomsma, Dorret I; Buring, Julie E.; Crisponi, Laura; Demerath, Ellen W; Gudnason, Vilmundur; Harris, Tamara B; Hu, Frank B; Hunter, David J; Launer, Lenore J; Metspalu, Andres; Montgomery, Grant W; Oostra, Ben A; Ridker, Paul M; Sanna, Serena; Schlessinger, David; Spector, Tim D; Stefansson, Kari; Streeten, Elizabeth A; Thorsteinsdottir, Unnur; Uda, Manuela; Uitterlinden, André G; van Duijn, Cornelia M; Völzke, Henry; Murray, Anna; Murabito, Joanne M; Visser, Jenny A; Lunetta, Kathryn L

    2011-01-01

    To identify novel loci for age at natural menopause, we performed a meta-analysis of 22 genome-wide association studies in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 new age at natural menopause loci (P < 5 × 10−8). The new loci included genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG, PRIM1) and immune function (IL11, NLRP11, BAT2). Gene-set enrichment pathway analyses using the full GWAS dataset identified exodeoxyribonuclease, NFκB signalling and mitochondrial dysfunction as biological processes related to timing of menopause. PMID:22267201

  15. Adult stem cells in neural repair: Current options, limitations and perspectives.

    PubMed

    Mariano, Eric Domingos; Teixeira, Manoel Jacobsen; Marie, Suely Kazue Nagahashi; Lepski, Guilherme

    2015-03-26

    Stem cells represent a promising step for the future of regenerative medicine. As they are able to differentiate into any cell type, tissue or organ, these cells are great candidates for treatments against the worst diseases that defy doctors and researchers around the world. Stem cells can be divided into three main groups: (1) embryonic stem cells; (2) fetal stem cells; and (3) adult stem cells. In terms of their capacity for proliferation, stem cells are also classified as totipotent, pluripotent or multipotent. Adult stem cells, also known as somatic cells, are found in various regions of the adult organism, such as bone marrow, skin, eyes, viscera and brain. They can differentiate into unipotent cells of the residing tissue, generally for the purpose of repair. These cells represent an excellent choice in regenerative medicine, every patient can be a donor of adult stem cells to provide a more customized and efficient therapy against various diseases, in other words, they allow the opportunity of autologous transplantation. But in order to start clinical trials and achieve great results, we need to understand how these cells interact with the host tissue, how they can manipulate or be manipulated by the microenvironment where they will be transplanted and for how long they can maintain their multipotent state to provide a full regeneration.

  16. Nanobiomotors of archaeal DNA repair machineries: current research status and application potential

    PubMed Central

    2014-01-01

    Nanobiomotors perform various important functions in the cell, and they also emerge as potential vehicle for drug delivery. These proteins employ conserved ATPase domains to convert chemical energy to mechanical work and motion. Several archaeal nucleic acid nanobiomotors, such as DNA helicases that unwind double-stranded DNA molecules during DNA damage repair, have been characterized in details. XPB, XPD and Hjm are SF2 family helicases, each of which employs two ATPase domains for ATP binding and hydrolysis to drive DNA unwinding. They also carry additional specific domains for substrate binding and regulation. Another helicase, HerA, forms a hexameric ring that may act as a DNA-pumping enzyme at the end processing of double-stranded DNA breaks. Common for all these nanobiomotors is that they contain ATPase domain that adopts RecA fold structure. This structure is characteristic for RecA/RadA family proteins and has been studied in great details. Here we review the structural analyses of these archaeal nucleic acid biomotors and the molecular mechanisms of how ATP binding and hydrolysis promote the conformation change that drives mechanical motion. The application potential of archaeal nanobiomotors in drug delivery has been discussed. PMID:24995126

  17. REHABILITATION OF A SURGICALLY REPAIRED RUPTURE OF THE DISTAL BICEPS TENDON IN AN ACTIVE MIDDLE AGED MALE: A CASE REPORT

    PubMed Central

    Sayers, Stephen P.; LaFontaine, Tom; Scheussler, Scott

    2012-01-01

    Background: Complete rupture of the distal tendon of the biceps brachii is relatively rare and there is little information to guide therapists in rehabilitation after this injury. The purposes of this case report are to review the rehabilitation concepts used for treating such an injury, and discuss how to modify exercises during rehabilitation based on patient progression while adhering to physician recommended guidelines and standard treatment protocols. Case Presentation: The patient was an active 38‐year old male experienced in weight‐training. He presented with a surgically repaired right distal biceps tendon following an accident on a trampoline adapted with a bungee suspension harness. The intervention focused on restoring range of motion and strengthening of the supporting muscles of the upper extremity without placing undue stress on the biceps brachii. Outcomes: The patient was able to progress from a moderate restriction in ROM to full AROM two weeks ahead of the physician's post‐operative orders and initiate a re‐strengthening protocol by the eighth week of rehabilitation. At the eighth post‐operative week the patient reported no deficits in functional abilities throughout his normal daily activities with his affected upper extremity. Discussion: The results of this case report strengthen current knowledge regarding physical therapy treatment for a distal biceps tendon repair while at the same time providing new insights for future protocol considerations in active individuals. Most current protocols do not advocate aggressive stretching, AROM, or strengthening of a surgically repaired biceps tendon early in the rehabilitation process due to the fear of a re‐rupture. In the opinion of the authors, if full AROM can be achieved before the 6th week of rehabilitation, initiating a slow transition into light strengthening of the biceps brachii may be possible. Level of evidence: 4‐Single Case report PMID:23316429

  18. Cell cycle age dependence for radiation-induced G/sub 2/ arrest: evidence for time-dependent repair

    SciTech Connect

    Rowley, R.

    1985-09-01

    Exponentially growing eucaryotic cells, irradiated in interphase, are delayed in progression to mitosis chiefly by arrest in G/sub 2/. The sensitivity of Chinese hamster ovary cells to G/sub 2/ arrest induction by X rays increases through the cell cycle, up to the X-ray transition point (TP) in G/sub 2/. This age response can be explained by cell cycle age-dependent changes in susceptibility of the target(s) for G/sub 2/ arrest and/or by changes in capability for postirradiation recovery from G/sub 2/ arrest damage. Discrimination between sensitivity changes and repair phenomena is possible only if the level of G/sub 2/ arrest-causing damage sustained by a cell at the time of irradiation and the level ultimately expressed as arrest can be determined. The ability of caffeine to ameliorate radiation-induced G/sub 2/ arrest, while inhibiting repair of G/sub 2/ arrest-causing damage makes such an analysis possible. In the presence of caffeine, progression of irradiated cells was relatively unperturbed, but on caffeine removal, G/sub 2/ arrest was expressed. The duration of G/sub 2/ arrest was independent of the length of the prior caffeine exposure. This finding indicates that the target for G/sub 2/ arrest induction is present throughout the cell cycle and that the level of G/sub 2/ arrest damage incurred is initially constant for all cell cycle phases. The data are consistent with the existence of a time-dependent recovery mechanism to explain the age dependence for radiation induction of G/sub 2/ arrest.

  19. Protein repair L-isoaspartyl methyltransferase in plants. Phylogenetic distribution and the accumulation of substrate proteins in aged barley seeds.

    PubMed Central

    Mudgett, M B; Lowenson, J D; Clarke, S

    1997-01-01

    Protein L-isoaspartate (D-aspartate) O-methyltransferases (MTs; EC 2.1.1.77) can initiate the conversion of detrimental L-isoaspartyl residues in spontaneously damaged proteins to normal L-aspartyl residues. We detected this enzyme in 45 species from 23 families representing most of the divisions of the plant kingdom. MT activity is often localized in seeds, suggesting that it has a role in their maturation, quiescence, and germination. The relationship among MT activity, the accumulation of abnormal protein L-isoaspartyl residues, and seed viability was explored in barley (Hordeum vulgare cultivar Himalaya) seeds, which contain high levels of MT. Natural aging of barley seeds for 17 years resulted in a significant reduction in MT activity and in seed viability, coupled with increased levels of "unrepaired" L-isoaspartyl residues. In seeds heated to accelerate aging, we found no reduction of MT activity, but we did observe decreased seed viability and the accumulation of isoaspartyl residues. Among populations of accelerated aged seed, those possessing the highest levels of L-isoaspartyl-containing proteins had the lowest germination percentages. These results suggest that the MT present in seeds cannot efficiently repair all spontaneously damaged proteins containing altered aspartyl residues, and their accumulation during aging may contribute to the loss of seed viability. PMID:9414558

  20. Ovarian aging and menopause: current theories, hypotheses, and research models.

    PubMed

    Wu, Julie M; Zelinski, Mary B; Ingram, Donald K; Ottinger, Mary Ann

    2005-12-01

    Aging of the reproductive system has been studied in numerous vertebrate species. Although there are wide variations in reproductive strategies and hormone cycle components, many of the fundamental changes that occur during aging are similar. Evolutionary hypotheses attempt to explain why menopause occurs, whereas cellular hypotheses attempt to explain how it occurs. It is commonly believed that a disruption in the hypothalamic-pituitary-gonadal axis is responsible for the onset of menopause. Data exist to demonstrate that the first signs of menopause occur at the level of the brain or the ovary. Thus, finding an appropriate and representative animal model is especially important for the advancement of menopause research. In primates, there is a gradual decline in the function of the hypothalamic-pituitary-gonadal (HPG) axis ultimately resulting in irregularities in menstrual cycles and increasingly sporadic incidence of ovulation. Rodents also exhibit a progressive deterioration in HPG axis function; however, they also experience a period of constant estrus accompanied by intermittent ovulations, reduced progesterone levels, and elevated circulating estradiol levels. It is remarkable to observe that females of other classes also demonstrate deterioration in HPG axis function and ovarian failure. Comparisons of aging in various taxa provide insight into fundamental biological mechanisms of aging that could underlie reproductive decline.

  1. Delirium in the elderly: current problems with increasing geriatric age

    PubMed Central

    Kukreja, Deepti; Günther, Ulf; Popp, Julius

    2015-01-01

    Delirium is an acute disorder of attention and cognition seen relatively commonly in people aged 65 yr or older. The prevalence is estimated to be between 11 and 42 per cent for elderly patients on medical wards. The prevalence is also high in nursing homes and long term care (LTC) facilities. The consequences of delirium could be significant such as an increase in mortality in the hospital, long-term cognitive decline, loss of autonomy and increased risk to be institutionalized. Despite being a common condition, it remains under-recognised, poorly understood and not adequately managed. Advanced age and dementia are the most important risk factors. Pain, dehydration, infections, stroke and metabolic disturbances, and surgery are the most common triggering factors. Delirium is preventable in a large proportion of cases and therefore, it is also important from a public health perspective for interventions to reduce further complications and the substantial costs associated with these. Since the aetiology is, in most cases, multfactorial, it is important to consider a multi-component approach to management, both pharmacological and non-pharmacological. Detection and treatment of triggering causes must have high priority in case of delirium. The aim of this review is to highlight the importance of delirium in the elderly population, given the increasing numbers of ageing people as well as increasing geriatric age. PMID:26831414

  2. Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease.

    PubMed

    Moskalev, Alexey; Chernyagina, Elizaveta; de Magalhães, João Pedro; Barardo, Diogo; Thoppil, Harikrishnan; Shaposhnikov, Mikhail; Budovsky, Arie; Fraifeld, Vadim E; Garazha, Andrew; Tsvetkov, Vasily; Bronovitsky, Evgeny; Bogomolov, Vladislav; Scerbacov, Alexei; Kuryan, Oleg; Gurinovich, Roman; Jellen, Leslie C; Kennedy, Brian; Mamoshina, Polina; Dobrovolskaya, Evgeniya; Aliper, Alex; Kaminsky, Dmitry; Zhavoronkov, Alex

    2015-09-01

    As the level of interest in aging research increases, there is a growing number of geroprotectors, or therapeutic interventions that aim to extend the healthy lifespan and repair or reduce aging-related damage in model organisms and, eventually, in humans. There is a clear need for a manually-curated database of geroprotectors to compile and index their effects on aging and age-related diseases and link these effects to relevant studies and multiple biochemical and drug databases. Here, we introduce the first such resource, Geroprotectors (http://geroprotectors.org). Geroprotectors is a public, rapidly explorable database that catalogs over 250 experiments involving over 200 known or candidate geroprotectors that extend lifespan in model organisms. Each compound has a comprehensive profile complete with biochemistry, mechanisms, and lifespan effects in various model organisms, along with information ranging from chemical structure, side effects, and toxicity to FDA drug status. These are presented in a visually intuitive, efficient framework fit for casual browsing or in-depth research alike. Data are linked to the source studies or databases, providing quick and convenient access to original data. The Geroprotectors database facilitates cross-study, cross-organism, and cross-discipline analysis and saves countless hours of inefficient literature and web searching. Geroprotectors is a one-stop, knowledge-sharing, time-saving resource for researchers seeking healthy aging solutions. PMID:26342919

  3. Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease.

    PubMed

    Moskalev, Alexey; Chernyagina, Elizaveta; de Magalhães, João Pedro; Barardo, Diogo; Thoppil, Harikrishnan; Shaposhnikov, Mikhail; Budovsky, Arie; Fraifeld, Vadim E; Garazha, Andrew; Tsvetkov, Vasily; Bronovitsky, Evgeny; Bogomolov, Vladislav; Scerbacov, Alexei; Kuryan, Oleg; Gurinovich, Roman; Jellen, Leslie C; Kennedy, Brian; Mamoshina, Polina; Dobrovolskaya, Evgeniya; Aliper, Alex; Kaminsky, Dmitry; Zhavoronkov, Alex

    2015-09-01

    As the level of interest in aging research increases, there is a growing number of geroprotectors, or therapeutic interventions that aim to extend the healthy lifespan and repair or reduce aging-related damage in model organisms and, eventually, in humans. There is a clear need for a manually-curated database of geroprotectors to compile and index their effects on aging and age-related diseases and link these effects to relevant studies and multiple biochemical and drug databases. Here, we introduce the first such resource, Geroprotectors (http://geroprotectors.org). Geroprotectors is a public, rapidly explorable database that catalogs over 250 experiments involving over 200 known or candidate geroprotectors that extend lifespan in model organisms. Each compound has a comprehensive profile complete with biochemistry, mechanisms, and lifespan effects in various model organisms, along with information ranging from chemical structure, side effects, and toxicity to FDA drug status. These are presented in a visually intuitive, efficient framework fit for casual browsing or in-depth research alike. Data are linked to the source studies or databases, providing quick and convenient access to original data. The Geroprotectors database facilitates cross-study, cross-organism, and cross-discipline analysis and saves countless hours of inefficient literature and web searching. Geroprotectors is a one-stop, knowledge-sharing, time-saving resource for researchers seeking healthy aging solutions.

  4. Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease

    PubMed Central

    Moskalev, Alexey; Chernyagina, Elizaveta; de Magalhães, João Pedro; Barardo, Diogo; Thoppil, Harikrishnan; Shaposhnikov, Mikhail; Budovsky, Arie; Fraifeld, Vadim E.; Garazha, Andrew; Tsvetkov, Vasily; Bronovitsky, Evgeny; Bogomolov, Vladislav; Scerbacov, Alexei; Kuryan, Oleg; Gurinovich, Roman; Jellen, Leslie C.; Kennedy, Brian; Mamoshina, Polina; Dobrovolskaya, Evgeniya; Aliper, Alex; Kaminsky, Dmitry; Zhavoronkov, Alex

    2015-01-01

    As the level of interest in aging research increases, there is a growing number of geroprotectors, or therapeutic interventions that aim to extend the healthy lifespan and repair or reduce aging-related damage in model organisms and, eventually, in humans. There is a clear need for a manually-curated database of geroprotectors to compile and index their effects on aging and age-related diseases and link these effects to relevant studies and multiple biochemical and drug databases. Here, we introduce the first such resource, Geroprotectors (http://geroprotectors.org). Geroprotectors is a public, rapidly explorable database that catalogs over 250 experiments involving over 200 known or candidate geroprotectors that extend lifespan in model organisms. Each compound has a comprehensive profile complete with biochemistry, mechanisms, and lifespan effects in various model organisms, along with information ranging from chemical structure, side effects, and toxicity to FDA drug status. These are presented in a visually intuitive, efficient framework fit for casual browsing or in-depth research alike. Data are linked to the source studies or databases, providing quick and convenient access to original data. The Geroprotectors database facilitates cross-study, cross-organism, and cross-discipline analysis and saves countless hours of inefficient literature and web searching. Geroprotectors is a one-stop, knowledge-sharing, time-saving resource for researchers seeking healthy aging solutions. PMID:26342919

  5. Eddy current array probe for corrosion mapping on ageing aircraft

    NASA Astrophysics Data System (ADS)

    Leclerc, Rémi; Samson, Rock

    2000-05-01

    The life of an airplane in the civil and military fleet is expanding by many years. The corrosion on aircraft is becoming a serious problem. The corrosion can also lead to the development of "multi-site damage" (MSD) and catastrophic failure. The need for a fast and reliable nondestructive technique for the detection of corrosion is a prime concern. A simple eddy current or ultrasonic probe can be very time consuming in the inspection because of the small area covered by the probe. The use of an eddy current array probe can cut the time use for an inspection or increase the surface scanned. Because it is an eddy current technology, the surface preparation is minimal compared to other techniques like ultrasound. It is also possible to detect defects beyond the first layer in a multiple layer panel. A flexible probe was employed to demonstrate the capacities of an eddy current array probe. This flexible probe can also match the profile of the structure to inspect limiting the lift-off. The C-scan technique is used in the display to see all the data on the same screen. The interpretation is also simplified.

  6. Scaffold devices for rotator cuff repair.

    PubMed

    Ricchetti, Eric T; Aurora, Amit; Iannotti, Joseph P; Derwin, Kathleen A

    2012-02-01

    Rotator cuff tears affect 40% or more of those aged older than 60 years, and repair failure rates of 20% to 70% remain a significant clinical challenge. Hence, there is a need for repair strategies that can augment the repair by mechanically reinforcing it, while at the same time biologically enhancing the intrinsic healing potential of the tendon. Tissue engineering strategies to improve rotator cuff repair healing include the use of scaffolds, growth factors, and cell seeding, or a combination of these approaches. Currently, scaffolds derived from mammalian extracellular matrix, synthetic polymers, and a combination thereof, have been cleared by the U.S. Food and Drug Administration and are marketed as medical devices for rotator cuff repair in humans. Despite the growing clinical use of scaffold devices for rotator cuff repair, there are numerous questions related to their indication, surgical application, safety, mechanism of action, and efficacy that remain to be clarified or addressed. This article reviews the current basic science and clinical understanding of commercially available synthetic and extracellular matrix scaffolds for rotator cuff repair. Our review will emphasize the host response and scaffold remodeling, mechanical and suture-retention properties, and preclinical and clinical studies on the use of these scaffolds for rotator cuff repair. We will discuss the implications of these data on the future directions for use of these scaffolds in tendon repair procedures.

  7. The androgen-deficient aging male: current treatment options.

    PubMed

    Tenover, J Lisa

    2003-01-01

    All delivery forms of testosterone should be equally efficacious in treating the androgen-deficient aging male if adequate serum testosterone levels are obtained. The testosterone preparations available in North America include the oral undecanoate, injectable testosterone esters, the scrotal patch, the nonscrotal transdermal patch, and the transdermal gels. Selection of a specific testosterone preparation for replacement therapy depends on many factors, including the magnitude and pattern of serum testosterone levels produced, side effects of the particular formulation, reversibility if an adverse event should occur, convenience of use, cosmetic issues related to the preparation, and cost. In addition, potential adverse effects of testosterone therapy applicable to all forms of testosterone delivery, such as fluid retention, gynecomastia, polycythemia, worsening of sleep apnea, change in cardiovascular-disease risk, or alterations in prostate health, need to be considered both prior to therapy and during treatment monitoring. PMID:16985939

  8. Current issues on ageing in Japan: a comparison with Australia.

    PubMed

    Someya, Yoshiko; Wells, Yvonne

    2008-03-01

    Japan's demography has changed dramatically, and with it, Japanese society and the circumstances of older people. These changes include shifts in family roles and functions, employment and social relations. Traditionally, families provided financial, physical and psychological support to their parents in the same household. While the proportion of older Japanese who live with adult children is still high in comparison to the rate in Western developed countries, patterns of care in Japan are gradually shifting towards the Western model. Public pensions supply financial support and the Long-Term Care Insurance System (LCIS) provides substantial physical care for frail older people. This paper focuses on current issues for older people in Japan, and provides a brief comparison with the situation in Australia. Japan's LCIS provides a simpler and more consistent basis for funding long-term care than Australia's system. On the other hand, Australia's pension system is comparatively robust. PMID:18713209

  9. Testosterone for the aging male; current evidence and recommended practice

    PubMed Central

    Stanworth, Roger D; Jones, T Hugh

    2008-01-01

    An international consensus document was recently published and provides guidance on the diagnosis, treatment and monitoring of late-onset hypogonadism (LOH) in men. The diagnosis of LOH requires biochemical and clinical components. Controversy in defining the clinical syndrome continues due to the high prevalence of hypogonadal symptoms in the aging male population and the non-specific nature of these symptoms. Further controversy surrounds setting a lower limit of normal testosterone, the limitations of the commonly available total testosterone result in assessing some patients and the unavailability of reliable measures of bioavailable or free testosterone for general clinical use. As with any clinical intervention testosterone treatment should be judged on a balance of risk versus benefit. The traditional benefits of testosterone on sexual function, mood, strength and quality of life remain the primary goals of treatment but possible beneficial effects on other parameters such as bone density, obesity, insulin resistance and angina are emerging and will be reviewed. Potential concerns regarding the effects of testosterone on prostate disease, aggression and polycythaemia will also be addressed. The options available for treatment have increased in recent years with the availability of a number of testosterone preparations which can reliably produce physiological serum concentrations. PMID:18488876

  10. Polymorphisms in the DNA repair gene XPD: correlations with risk and age at onset of basal cell carcinoma.

    PubMed

    Dybdahl, M; Vogel, U; Frentz, G; Wallin, H; Nexø, B A

    1999-01-01

    The XPD protein has a dual function, both in nucleotide excision repair and in basal transcription. We have studied the role of two nucleotide substitutions in the XPD gene, one in exon 23 leading to an amino acid substitution (Lys751Gln) and one silent in exon 6 in relation to basal cell carcinoma (BCC). Both are two-allele polymorphisms, with the nucleobases A and C at the given positions. We genotyped psoriasis patients with and without BCC and nonpsoriatic persons with and without BCC (4 x 20 persons). The choice to study psoriasis patients was motivated by their high genotoxic exposure via treatment and their high relative rate of early BCC. Subjects carrying two A alleles (AA genotype) in exon 23 were at 4.3-fold higher risk of BCC than subjects with two C alleles (95% CI, 0.79-23.57). In addition, the mean age at first skin tumor for BCC cases with the AA genotype was significantly lower than the mean age for BCC cases with the AC or CC genotype (P = 0.012). Thus, the variant C-allele of exon 23 may be protective. The exon 6 genotype was associated with the risk of BCC among the psoriasis patients; psoriatics carrying two A alleles in exon 6 were at 5.3-fold higher risk of BCC than psoriatics with two C alleles (95% CI, 0.78-36.31). For the psoriatics, the mean age at onset of BCC for cases with the AA genotype was marginally lower than the mean age for cases with genotype AC or CC (P = 0.060). Our results raise the possibility that the polymorphisms in the XPD gene may be contributing factors in the risk of BCC development. They are, therefore, important candidates for future studies in susceptibility to cancer.

  11. The l-Isoaspartyl Protein Repair Methyltransferase Enhances Survival of Aging Escherichia coli Subjected to Secondary Environmental Stresses

    PubMed Central

    Visick, Jonathan E.; Cai, Hui; Clarke, Steven

    1998-01-01

    Like its homologs throughout the biological world, the l-isoaspartyl protein repair methyltransferase of Escherichia coli, encoded by the pcm gene, can convert abnormal l-isoaspartyl residues in proteins (which form spontaneously from asparaginyl or aspartyl residues) to normal aspartyl residues. Mutations in pcm were reported to greatly reduce survival in stationary phase and when cells were subjected to heat or osmotic stresses (C. Li and S. Clarke, Proc. Natl. Acad. Sci. USA 89:9885–9889, 1992). However, we subsequently demonstrated that those strains had a secondary mutation in rpoS, which encodes a stationary-phase-specific sigma factor (J. E. Visick and S. Clarke, J. Bacteriol. 179:4158–4163, 1997). We now show that the rpoS mutation, resulting in a 90% decrease in HPII catalase activity, can account for the previously observed phenotypes. We further demonstrate that a new pcm mutant lacks these phenotypes. Interestingly, the newly constructed pcm mutant, when maintained in stationary phase for extended periods, is susceptible to environmental stresses, including exposure to methanol, oxygen radical generation by paraquat, high salt concentrations, and repeated heating to 42°C. The pcm mutation also results in a competitive disadvantage in stationary-phase cells. All of these phenotypes can be complemented by a functional pcm gene integrated elsewhere in the chromosome. These data suggest that protein denaturation and isoaspartyl formation may act synergistically to the detriment of aging E. coli and that the repair methyltransferase can play a role in limiting the accumulation of the potentially disruptive isoaspartyl residues in vivo. PMID:9573145

  12. EVALUATION OF THE RESULTS FROM ARTHROSCOPIC REPAIR ON ROTATOR CUFF INJURIES AMONG PATIENTS UNDER 50 YEARS OF AGE

    PubMed Central

    Miyazaki, Alberto Naoki; Fregoneze, Marcelo; Santos, Pedro Doneux; da Silva, Luciana Andrade; do Val Sella, Guilherme; Santos, Ruy Mesquita Maranhão; de Souza, Adriano; Checchia, Sérgio Luiz

    2015-01-01

    Objective: To assess the results from arthroscopic surgical treatment of rotator cuff injuries among patients under 50 years of age. Methods: Sixty-three patients with rotator cuff injuries who underwent arthroscopic surgical treatment performed by the Shoulder and Elbow Group of the Department of Orthopedics and Traumatology, in the Fernandinho Simonsen wing of Santa Casa Medical School, São Paulo, between August 1998 and December 2007, were reassessed. The study included all patients with rotator cuff injuries who were under 50 years of age and had been followed up postoperatively for at least 24 months. Results: According to the UCLA evaluation criteria, 59 patients (92%) showed excellent and good results; five (8%) showed fair results; and none showed poor results. The postoperative evaluation showed that the mean range of motion was 145° for elevation, 47° for lateral rotation and T10 for medial rotation. Unsatisfactory results were associated with prolonged duration of the injury, with a statistically significant relationship. Conclusion: Arthroscopic repair of rotator cuff injuries in young patients produces excellent or good results for most patients. PMID:27047819

  13. Mitochondrial and nuclear DNA-repair capacity of various brain regions in mouse is altered in an age-dependent manner.

    PubMed

    Imam, Syed Z; Karahalil, Bensu; Hogue, Barbara A; Souza-Pinto, Nadja C; Bohr, Vilhelm A

    2006-08-01

    Aging is associated with increased susceptibility to neuronal loss and disruption of cerebral function either as a component of senescence, or as a consequence of neurodegenerative disease or stroke. Here we report differential changes in the repair of oxidative DNA damage in various brain regions during aging. We evaluated mitochondrial and nuclear incision activities of oxoguanine DNA glycosylase (OGG1), uracil DNA glycosylase (UDG) and the endonuclease III homologue (NTH1) in the caudate nucleus (CN), frontal cortex (FC), hippocampus (Hip), cerebellum (CE) and brain stem (BS) of 6- and 18-month-old male C57Bl/6 mice. We observed a significant age-dependent decrease in incision activities of all three glycosylases in the mitochondria of all brain regions, whereas variable patterns of changes were seen in nuclei. No age- or region-specific changes were observed in the mitochondrial repair synthesis incorporation of uracil-initiated base-excision repair (BER). We did not observe any age or region dependent differences in levels of BER proteins among the five brain regions. In summary, our data suggest that a decreased efficiency of mitochondrial BER-glycosylases and increased oxidative damage to mitochondrial DNA might contribute to the normal aging process. These data provide a novel characterization of oxidative DNA damage processing in different brain regions implicated in various neurodegenerative disorders, and suggest that this process is regulated in an age-dependent manner. Manipulation of DNA repair mechanisms may provide a strategy to prevent neuronal loss during age-dependent neurodegenerative disorders. PMID:16005114

  14. Anhydrobiosis vs. aging: comparative genomics of protein repair L-isoaspartyl methyltransferases in the sleeping chironomid. .

    NASA Astrophysics Data System (ADS)

    Gusev, Oleg; Kikawada, Takahiro; Shagimardanova, Elena; Suetsugu, Yoshitaka; Ayupov, Rustam

    Origin of anhydrobiosis in the larvae of the sleeping chironomid Polypedilum vanderplanki represents unique example of set of evolutionary events in a single species, resulted in acquiring new ability allowing survival in extremely changeable environment. Complex comparative analysis of the genome of P. vanderplanki resulted in discovery of a set of features, including existence of the set of unique clusters of genes contributing in desiccation resistance. Surprisingly, in several cases, the genes mainly contributing to the formation of the molecular shield in the larvae are sleeping chironomid-specific and have no homology with genes from other insects, including P. nubifer - a chironomid from the same genus. Protein L-isoaspartyl methyltransferase (PIMT) acts on proteins that have been non-enzymatically damaged due to age, and partially restores aspartic residues, extending life of the polypeptides. PIMT a highly conserved enzyme present in nearly all eukaryotes, and microorganisms mostly in a single copy (or in a few isoforms in certain plants and some bacteria). While conducting a comparative analysis of the genomes of two chironomid midge species different in their ability to stand complete water loss, we have noticed that structure and number of PIMT-coding genes in the desiccation resistant (anhydrobiotic) midge (Polypedilum vanderplanki, Pv) is different from those of the common desiccation-sensitive midge (Polypedilum nubifer, Pn) and the rest of insects. Both species have a clear orthologous PIMT shared by all insects. At the same time, in contrast to Pn which has only one PIMT gene (PnPimt-1), the Pv genome contains 12 additional genes paralogous to Pimt1 (PvPimt-2-12) presumably coding functional PIMT proteins, which are arranged in a single cluster. Remarkably, PvPimt-1 location in the Pv is different from the rest of Pimt-like genes. PvPimt-1 gene is ubiquitously expressed during the life cycle, but expression of the PvPimt2-12 is limited to the eggs

  15. The role of DNA repair in brain related disease pathology.

    PubMed

    Canugovi, Chandrika; Misiak, Magdalena; Ferrarelli, Leslie K; Croteau, Deborah L; Bohr, Vilhelm A

    2013-08-01

    Oxidative DNA damage is implicated in brain aging, neurodegeneration and neurological diseases. Damage can be created by normal cellular metabolism, which accumulates with age, or by acute cellular stress conditions which create bursts of oxidative damage. Brain cells have a particularly high basal level of metabolic activity and use distinct oxidative damage repair mechanisms to remove oxidative damage from DNA and dNTP pools. Accumulation of this damage in the background of a functional DNA repair response is associated with normal aging, but defective repair in brain cells can contribute to neurological dysfunction. Emerging research strongly associates three common neurodegenerative conditions, Alzheimer's, Parkinson's and stroke, with defects in the ability to repair chronic or acute oxidative damage in neurons. This review explores the current knowledge of the role of oxidative damage repair in preserving brain function and highlights the emerging models and methods being used to advance our knowledge of the pathology of neurodegenerative disease.

  16. Comparative analysis of low-level laser therapy (660 nm) on inflammatory biomarker expression during the skin wound-repair process in young and aged rats.

    PubMed

    de Melo Rambo, Caroline Sobral; Silva, Jose Antônio; Serra, Andrey Jorge; Ligeiro, Ana Paula; Vieira, Rodolfo de Paula; Albertini, Regiane; Leal-Junior, Ernesto Cesar Pinto; de Tarso Camillo de Carvalho, Paulo

    2014-09-01

    The wound-healing process plays an essential role in the protective response to epidermal injury by tissue regeneration. In the elderly, skin functions deteriorate as a consequence of morphological and structural changes. This study aimed to evaluate and compare the effect of low-level laser therapy (LLLT) in cutaneous wound healing in young and aged rats. A total of 60 male rats comprising 30 young (± 30 days) and 30 aged (± 500 days) was used. The animals were divided into four experimental groups and underwent skin wound and/or treatment with LLLT (660 nm, 30 mW, 1.07 W/cm(2), 0.028 cm(2), 72 J/cm(2), and 2 J). Analyses were conducted to verify the effects of LLLT in the tissue repair process, in the gene expression, and protein expression of TNF-α, IL-1β, and IL-10, obtained in skin wound model. Results showed that there were significant differences between the young control group and the aged control group and their respective treated groups (LLLT young and LLLT aged). We conclude that LLLT has shown to be effective in the treatment of skin wounds in young and aged animals at different stages of the tissue repair process, which suggests that different LLLT dosimetry should be considered in treatment of subjects of different ages. Further clinical trials are needed to confirm these findings in clinical settings.

  17. Neuroinflammation and ageing: current theories and an overview of the data.

    PubMed

    Pizza, Vincenzo; Agresta, Anella; D'Acunto, Cosimo W; Festa, Michela; Capasso, Anna

    2011-09-01

    The increase in the average lifespan and the consequent proportional growth of the elderly segment of society has furthered the interest in studying ageing processes. Ageing may be considered a multifactorial process derived from the interaction between genetic and environmental factors including lifestyle. There is ample evidence in many species that the maximum age attainable (maximum lifespan potential, MLSP) is genetically determined and several mitochondrial DNA polymorphisms are associated with longevity. This review will address the current understanding of the relationship between ageing and several factors both genetics and life style related. Firstly we focused on the most reliable and commonly shared theories which attempt to explain the phenomenon of ageing as the genetic, cellular, neuroendocrine, immunological and free-radicals related theories. Many studies have shown that most of the phenotypic characteristics observed in the aging process are the result of the occurrence, with age, of a low grade chronic pro-inflammatory status called "inflammaging", partially under genetic control. The term indicate that aging is accompanied by a low degree of chronic inflammatory, an up-regulation of inflammatory response and that inflammatory changes are common to many age-related diseases. In this review special attention was dedicated to diseases related to age as atherosclerosis, cancer and Alzheimer disease. Despite the fact that in recent years many theories about ageing have been developed, we are still far from a full understanding of the mechanisms underlying the ageing process.

  18. Industrial motor repair in the United States

    SciTech Connect

    Schueler, V.; Leistner, P.; Douglass, J.

    1994-09-01

    This report characterizes the motor repair industry in the United States; summarizes current motor repair and testing practice; and identifies barriers to energy motor repair practice and recommends strategies for overcoming those barriers.

  19. High field dc conduction current and spectroscopy of aged transformer oil

    SciTech Connect

    El-Sulaiman, A.A.; Ahmed, O.; Hassan, M.M.; Quresh, M.

    1982-11-01

    This paper studies the experimental results of the quasi-state high field dc conduction current, and changes occuring in the molecular structure of aged transformer oil, sampled from EHV transformer operating for the last five years. Aged oil was compared with fresh transformer oil and liquid paraffin. It was found that aged oil exhibits higher conduction than both of the other oils through 600 seconds of field application. However, no molecular changes were detected using different techniques of spectroscopy such as GC; UV; IR and NMR. Metallic impurities were found to be of the same order but the acidity increased manifolds to that of fresh oil.

  20. Wound repair and regeneration: Mechanisms, signaling, and translation

    PubMed Central

    Eming, Sabine A.; Martin, Paul; Tomic-Canic, Marjana

    2015-01-01

    The cellular and molecular mechanisms underpinning tissue repair and its failure to heal are still poorly understood, and current therapies are limited. Poor wound healing after trauma, surgery, acute illness, or chronic disease conditions affects millions of people worldwide each year and is the consequence of poorly regulated elements of the healthy tissue repair response, including inflammation, angiogenesis, matrix deposition, and cell recruitment. Failure of one or several of these cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes, or aging, which are all frequently associated with healing pathologies. The search for clinical strategies that might improve the body’s natural repair mechanisms will need to be based on a thorough understanding of the basic biology of repair and regeneration. In this review, we highlight emerging concepts in tissue regeneration and repair, and provide some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies. PMID:25473038

  1. Group Therapy for School-Aged Children Who Stutter: A Survey of Current Practices

    ERIC Educational Resources Information Center

    Liddle, Hilary; James, Sarah; Hardman, Margaret

    2011-01-01

    Although group therapy is recommended for school-aged children who stutter (CWS), it is not widely researched. This study aimed to explore this provision, using a postal survey which investigated the current practices of Speech & Language Therapists (SLTs) in the UK. Seventy percent of SLT services provided some group therapy, but the level of…

  2. Effects of Age of English Exposure, Current Input/Output, and Grade on Bilingual Language Performance

    ERIC Educational Resources Information Center

    Bedore, Lisa M.; Pena, Elizabeth D.; Griffin, Zenzi M.; Hixon, J. Gregory

    2016-01-01

    This study evaluates the effects of Age of Exposure to English (AoEE) and Current Input/Output on language performance in a cross-sectional sample of Spanish-English bilingual children. First- (N = 586) and third-graders (N = 298) who spanned a wide range of bilingual language experience participated. Parents and teachers provided information…

  3. Late Na+ current and protracted electrical recovery are critical determinants of the aging myopathy

    PubMed Central

    Signore, Sergio; Sorrentino, Andrea; Borghetti, Giulia; Cannata, Antonio; Meo, Marianna; Zhou, Yu; Kannappan, Ramaswamy; Pasqualini, Francesco; O'Malley, Heather; Sundman, Mark; Tsigkas, Nikolaos; Zhang, Eric; Arranto, Christian; Mangiaracina, Chiara; Isobe, Kazuya; Sena, Brena F.; Kim, Junghyun; Goichberg, Polina; Nahrendorf, Matthias; Isom, Lori L.; Leri, Annarosa; Anversa, Piero; Rota, Marcello

    2015-01-01

    The aging myopathy manifests itself with diastolic dysfunction and preserved ejection fraction. We raised the possibility that, in a mouse model of physiological aging, defects in electromechanical properties of cardiomyocytes are important determinants of the diastolic characteristics of the myocardium, independently from changes in structural composition of the muscle and collagen framework. Here we show that an increase in the late Na+ current (INaL) in aging cardiomyocytes prolongs the action potential (AP) and influences temporal kinetics of Ca2+ cycling and contractility. These alterations increase force development and passive tension. Inhibition of INaL shortens the AP and corrects dynamics of Ca2+ transient, cell contraction and relaxation. Similarly, repolarization and diastolic tension of the senescent myocardium are partly restored. Thus, INaL offers inotropic support, but negatively interferes with cellular and ventricular compliance, providing a new perspective of the biology of myocardial aging and the aetiology of the defective cardiac performance in the elderly. PMID:26541940

  4. Thermally stimulated currents and space charge studies on field-aged extruded cable material

    SciTech Connect

    Amyot, N.; Pelissou, S.; Toureille, A.

    1996-12-31

    In the perspective of gaining more knowledge on extruded cable field aging diagnosis, complementary techniques were investigated: thermally stimulated currents (TSC) and space charge measurements, the latter being performed by the thermal step (TS) method. Measurements were taken on 28 kV extruded cable samples of cross-linked polyethylene (XLPE). Samples were peeled-off from three cables; one unaged and two field-aged. Both techniques show differences between field-aged and unaged cable material. Results obtained by TS show that aged material can store more space charges that lead to greater intensity of the electrical field in some sites in the polymer matrix and eventually initiate electrical trees leading to breakdown. Comparison with TSC results show that the origin of space charge formation cannot be attributed uniquely to traps formed by carbonyl groups from polymer oxidation.

  5. Wolf (Canis lupus) Generation Time and Proportion of Current Breeding Females by Age

    PubMed Central

    2016-01-01

    Information is sparse about aspects of female wolf (Canis lupus) breeding in the wild, including age of first reproduction, mean age of primiparity, generation time, and proportion of each age that breeds in any given year. We studied these subjects in 86 wolves (113 captures) in the Superior National Forest (SNF), Minnesota (MN), during 1972–2013 where wolves were legally protected for most of the period, and in 159 harvested wolves from throughout MN wolf range during 2012–2014. Breeding status of SNF wolves were assessed via nipple measurements, and wolves from throughout MN wolf range, by placental scars. In the SNF, proportions of currently breeding females (those breeding in the year sampled) ranged from 19% at age 2 to 80% at age 5, and from throughout wolf range, from 33% at age 2 to 100% at age 7. Excluding pups and yearlings, only 33% to 36% of SNF females and 58% of females from throughout MN wolf range bred in any given year. Generation time for SNF wolves was 4.3 years and for MN wolf range, 4.7 years. These findings will be useful in modeling wolf population dynamics and in wolf genetic and dog-domestication studies. PMID:27258193

  6. Wolf (Canis lupus) Generation Time and Proportion of Current Breeding Females by Age.

    PubMed

    Mech, L David; Barber-Meyer, Shannon M; Erb, John

    2016-01-01

    Information is sparse about aspects of female wolf (Canis lupus) breeding in the wild, including age of first reproduction, mean age of primiparity, generation time, and proportion of each age that breeds in any given year. We studied these subjects in 86 wolves (113 captures) in the Superior National Forest (SNF), Minnesota (MN), during 1972-2013 where wolves were legally protected for most of the period, and in 159 harvested wolves from throughout MN wolf range during 2012-2014. Breeding status of SNF wolves were assessed via nipple measurements, and wolves from throughout MN wolf range, by placental scars. In the SNF, proportions of currently breeding females (those breeding in the year sampled) ranged from 19% at age 2 to 80% at age 5, and from throughout wolf range, from 33% at age 2 to 100% at age 7. Excluding pups and yearlings, only 33% to 36% of SNF females and 58% of females from throughout MN wolf range bred in any given year. Generation time for SNF wolves was 4.3 years and for MN wolf range, 4.7 years. These findings will be useful in modeling wolf population dynamics and in wolf genetic and dog-domestication studies. PMID:27258193

  7. Wolf (Canis lupus) Generation Time and Proportion of Current Breeding Females by Age.

    PubMed

    Mech, L David; Barber-Meyer, Shannon M; Erb, John

    2016-01-01

    Information is sparse about aspects of female wolf (Canis lupus) breeding in the wild, including age of first reproduction, mean age of primiparity, generation time, and proportion of each age that breeds in any given year. We studied these subjects in 86 wolves (113 captures) in the Superior National Forest (SNF), Minnesota (MN), during 1972-2013 where wolves were legally protected for most of the period, and in 159 harvested wolves from throughout MN wolf range during 2012-2014. Breeding status of SNF wolves were assessed via nipple measurements, and wolves from throughout MN wolf range, by placental scars. In the SNF, proportions of currently breeding females (those breeding in the year sampled) ranged from 19% at age 2 to 80% at age 5, and from throughout wolf range, from 33% at age 2 to 100% at age 7. Excluding pups and yearlings, only 33% to 36% of SNF females and 58% of females from throughout MN wolf range bred in any given year. Generation time for SNF wolves was 4.3 years and for MN wolf range, 4.7 years. These findings will be useful in modeling wolf population dynamics and in wolf genetic and dog-domestication studies.

  8. Wolf (Canis lupus) generation time and proportion of current breeding females by age

    USGS Publications Warehouse

    Mech, L. David; Barber-Meyer, Shannon M.; Erb, John

    2016-01-01

    Information is sparse about aspects of female wolf (Canis lupus) breeding in the wild, including age of first reproduction, mean age of primiparity, generation time, and proportion of each age that breeds in any given year. We studied these subjects in 86 wolves (113 captures) in the Superior National Forest (SNF), Minnesota (MN), during 1972–2013 where wolves were legally protected for most of the period, and in 159 harvested wolves from throughout MN wolf range during 2012–2014. Breeding status of SNF wolves were assessed via nipple measurements, and wolves from throughout MN wolf range, by placental scars. In the SNF, proportions of currently breeding females (those breeding in the year sampled) ranged from 19% at age 2 to 80% at age 5, and from throughout wolf range, from 33% at age 2 to 100% at age 7. Excluding pups and yearlings, only 33% to 36% of SNF females and 58% of females from throughout MN wolf range bred in any given year. Generation time for SNF wolves was 4.3 years and for MN wolf range, 4.7 years. These findings will be useful in modeling wolf population dynamics and in wolf genetic and dog-domestication studies.

  9. Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

    PubMed Central

    Brennan, Lisa A.; Kantorow, Marc

    2009-01-01

    -destructive cycle. Consequently, the mitochondria have evolved a number of antioxidant and key repair systems to limit the damaging potential of free oxygen radicals and to repair damaged proteins (Figure 1.0). The aging eye appears to be at considerable risk from oxidative stress. This review will outline the potential role of mitochondrial function and redox balance in age-related eye diseases, and detail how the methionine sulfoxide reductase (Msr) protein repair system and other redox systems play key roles in the function and maintenance of the aging eye. PMID:18588875

  10. Optimality in DNA repair.

    PubMed

    Richard, Morgiane; Fryett, Matthew; Miller, Samantha; Booth, Ian; Grebogi, Celso; Moura, Alessandro

    2012-01-01

    DNA within cells is subject to damage from various sources. Organisms have evolved a number of mechanisms to repair DNA damage. The activity of repair enzymes carries its own risk, however, because the repair of two nearby lesions may lead to the breakup of DNA and result in cell death. We propose a mathematical theory of the damage and repair process in the important scenario where lesions are caused in bursts. We use this model to show that there is an optimum level of repair enzymes within cells which optimises the cell's response to damage. This optimal level is explained as the best trade-off between fast repair and a low probability of causing double-stranded breaks. We derive our results analytically and test them using stochastic simulations, and compare our predictions with current biological knowledge. PMID:21945337

  11. Sn-Ag-Cu to Cu joint current aging test and evolution of resistance and microstructure

    NASA Astrophysics Data System (ADS)

    Xu, Di Erick; Chow, Jasper; Mayer, Michael; Jung, Jae Pil; Yoon, Jong Hyun

    2015-11-01

    SAC 305 solder bump with 800 μm diameter were produced and soldered to a custom substrate with Cu lines as leads that allow for resistance measurement during current aging. The measured joint resistance values (leads plus solder bump) before aging are 7.7 ± 1.8 mΩ and 11.8 ± 2.8 mΩ at room temperature and 160°C, respectively. In general, the resistance of the solder joint increases instantly by about 1 mΩ, when subjected to a 2.2 A aging current at 160°C. The increase is gradual in the following hours of aging and more drastic as it approaches the final failure. Four stages are identified in the resistance signal curve and compared with observations from cross sections. The stages are IMC growth, crack formation and propagation, intermittent crack healing-forming, and final failure resulting in an open connection at the cathode. Recently a periodical drop and rise behavior was reported for the resistance signal. This behavior is reproduced and attributed to the intermittent crack healing-forming stage. The healing events observed are faster than the sampling time. Possibly, as current is concentrated when bypassing interfacial cracks, local melting occurs partially filling cracks before resolidifying. [Figure not available: see fulltext.

  12. Estimated maximal and current brain volume predict cognitive ability in old age.

    PubMed

    Royle, Natalie A; Booth, Tom; Valdés Hernández, Maria C; Penke, Lars; Murray, Catherine; Gow, Alan J; Maniega, Susana Muñoz; Starr, John; Bastin, Mark E; Deary, Ian J; Wardlaw, Joanna M

    2013-12-01

    Brain tissue deterioration is a significant contributor to lower cognitive ability in later life; however, few studies have appropriate data to establish how much influence prior brain volume and prior cognitive performance have on this association. We investigated the associations between structural brain imaging biomarkers, including an estimate of maximal brain volume, and detailed measures of cognitive ability at age 73 years in a large (N = 620), generally healthy, community-dwelling population. Cognitive ability data were available from age 11 years. We found positive associations (r) between general cognitive ability and estimated brain volume in youth (male, 0.28; females, 0.12), and in measured brain volume in later life (males, 0.27; females, 0.26). Our findings show that cognitive ability in youth is a strong predictor of estimated prior and measured current brain volume in old age but that these effects were the same for both white and gray matter. As 1 of the largest studies of associations between brain volume and cognitive ability with normal aging, this work contributes to the wider understanding of how some early-life factors influence cognitive aging.

  13. Effects of Age of English Exposure, Current Input/Output, and grade on bilingual language performance.

    PubMed

    Bedore, Lisa M; Peña, Elizabeth D; Griffin, Zenzi M; Hixon, J Gregory

    2016-05-01

    This study evaluates the effects of Age of Exposure to English (AoEE) and Current Input/Output on language performance in a cross-sectional sample of Spanish-English bilingual children. First- (N = 586) and third-graders (N = 298) who spanned a wide range of bilingual language experience participated. Parents and teachers provided information about English and Spanish language use. Short tests of semantic and morphosyntactic development in Spanish and English were used to quantify children's knowledge of each language. There were significant interactions between AoEE and Current Input/Output for children at third grade in English and in both grades for Spanish. In English, the relationship between AoEE and language scores were linear for first- and third-graders. In Spanish a nonlinear relationship was observed. We discuss how much of the variance was accounted for by AoEE and Current Input/Output.

  14. Absence of age-related dopamine transporter loss in current cocaine abusers

    SciTech Connect

    Wang, G.J.; Volkow, N.D.; Fischman, M.

    1997-05-01

    The brain dopamine (DA) system appears to play a crucial role in the reinforcing properties of cocaine. Using PET we had previously shown significant decreases in DA D2 receptors but no changes in DA transporters (DAT) in detoxified cocaine abusers (>1 month after last cocaine use). This study evaluates DAT availability in current cocaine abusers (15 male and 5 female; age = 36.2{+-}5.3 years old) using PET and [C-11]cocaine, as a DAT ligand, and compares it to that in 18 male and 2 female age matched normal controls. Cocaine abusers had a history of abusing 4.2{+-}2.8 gm /week of cocaine for an average of 11.0{+-}4.9 years and their last use of cocaine was 5.4{+-}8 days prior to PET study. DAT availability was obtained using the ratio of the distribution volume in the region of interest (caudate, pulamen) to that in cerebellum which is a function of Bmax./Kd.+1. DAT availability in cocaine abusers did not differ to that in normals (N) (C= 1.78{+-}0.14, N= 1.77{+-}0.13). In addition, there were no differences between the groups in the distribution volume or the Kl (plasma to brain transfer constant) measures for [C-11]cocaine. However, in the normals but not in the abusers striatal DAT availability decreased with age (C: r = -0.07, p = 0.76; N: r = -0.55, p < 0.01). Though this study fails to show group differences in DAT availability between normals and current cocaine abusers it indicates a blunting of the age-related decline in DAT availability in the cocaine abusers. Future studies in older cocaine abusers at different time after detoxification arc required in order to assess if cocaine slows the loss of DAT with age or whether these changes reflect compensation to increased DAT blockade and recover with detoxification.

  15. [Congenital heart disease in adults: residua, sequelae, and complications of cardiac defects repaired at an early age].

    PubMed

    Oliver Ruiz, José María

    2003-01-01

    Nowadays, it is estimated that 85% of the infants born with congenital heart disease (CHD) will survive to adulthood, thanks mainly to surgical or therapeutic procedures performed during infancy or childhood. The clinical profile and disease pattern of adults with CHD is changing. The prevalence of certain adult CHDs, such as tetralogy of Fallot, transposition of the great arteries or univentricular heart, is rising, but these conditions have practically become new diseases as a result of therapy. Most surviving patients present residua, sequelae, or complications, which can progress during adult life. These disorders can present electrophysiological disturbances, valvular disease, persistent shunts, myocardial dysfunction, pulmonary or systemic vascular disease, problems caused by prosthetic materials, infectious complications, thromboembolic events, or extravascular disorders involving multiple organs or systems. In tetralogy of Fallot, the most striking problems that affect long-term prognosis are pulmonary valve regurgitation, right ventricle dysfunction, and atrial or ventricular arrhythmias. The main problems appearing after physiological atrial repair of transposition of the great arteries are related to right ventricular function, since it is structurally unprepared for systemic circulation, and atrial arrhythmias. Surgical repair of univentricular heart using Fontan techniques should be considered a palliative procedure that does not modify the underlying structural disorder and exposes the postoperative patient to severe complications and problems. The increase in the number of patients with CHD who will reach adulthood in the coming decades makes it necessary to carefully consider the new healthcare demands that are being generated, who should be responsible for them, and how and where solutions can be found.

  16. Clubfoot repair

    MedlinePlus

    ... release; Talipes equinovarus - repair; Tibialis anterior tendon transfer Images Clubfoot repair - series References Kelly DM. Congenital Anomalies ... provided herein should not be used during any medical emergency or for the diagnosis or treatment of ...

  17. Tendon repair

    MedlinePlus

    Repair of tendon ... Tendon repair can be performed using: Local anesthesia (the immediate area of the surgery is pain-free) ... a cut on the skin over the injured tendon. The damaged or torn ends of the tendon ...

  18. Current technology for the treatment of infection following abdominal aortic aneurysm (AAA) fixation by endovascular repair (EVAR).

    PubMed

    Capoccia, L; Mestres, G; Riambau, V

    2014-06-01

    In recent years, in parallel with the increase of endovascular aortic repair (EVAR) procedures performances, a rise of late open surgical removal of EVAR implants has been observed, due to non-endovascularly correctable graft complications. Among them endograft infection is a rare but devastating occurrence, accounting for an incidence ranging from 0.2% to 0.7% in major series, and almost 1% of all causes of endograft explantations. However, a real estimation of the incidence of the problem respect to the number of EVAR implantations is difficult to obtain. Time to infection is usually defined as the period between EVAR and presentation of symptoms that leads to the infection diagnosis. It can be extremely variable, depending on bacterial virulence and host conditions. The diagnosis of an endograft infection is usually based on a combination of clinical symptoms, imaging studies and microbial cultures whenever possible. If computed tomography (CT) scan is employed in almost 100% of infection diagnosis, a combination of fluorodeoxyglucose-positron emission tomography (FDG-PET) and CT scan is nowadays used with increasing frequency in order to rise the likelihood of detecting a graft infection, since even cultures of blood or samples collected from the infected field can sometimes be negative. Complete graft excision seems the best approach whenever a surgical reconstruction could be attempted. In situ reconstruction can be performed by the interposition of an autologous vein, a cryopreserved allograft or a rifampin-soaked Dacron graft. The so-called conventional treatment contemplates the re-establishment of vascularization through extranatomical routes, thus preserving the new graft material from possible contamination by the surgical field just cleaned. When severe comorbid conditions did not allow graft excision, a conservative treatment should be taken into account. It is mainly based on broad-spectrum or culture-specific antibiotic therapy combined, whenever

  19. Tumor Mismatch Repair Immunohistochemistry and DNA MLH1 Methylation Testing of Patients With Endometrial Cancer Diagnosed at Age Younger Than 60 Years Optimizes Triage for Population-Level Germline Mismatch Repair Gene Mutation Testing

    PubMed Central

    Buchanan, Daniel D.; Tan, Yen Y.; Walsh, Michael D.; Clendenning, Mark; Metcalf, Alexander M.; Ferguson, Kaltin; Arnold, Sven T.; Thompson, Bryony A.; Lose, Felicity A.; Parsons, Michael T.; Walters, Rhiannon J.; Pearson, Sally-Ann; Cummings, Margaret; Oehler, Martin K.; Blomfield, Penelope B.; Quinn, Michael A.; Kirk, Judy A.; Stewart, Colin J.; Obermair, Andreas; Young, Joanne P.; Webb, Penelope M.; Spurdle, Amanda B.

    2014-01-01

    Purpose Clinicopathologic data from a population-based endometrial cancer cohort, unselected for age or family history, were analyzed to determine the optimal scheme for identification of patients with germline mismatch repair (MMR) gene mutations. Patients and Methods Endometrial cancers from 702 patients recruited into the Australian National Endometrial Cancer Study (ANECS) were tested for MMR protein expression using immunohistochemistry (IHC) and for MLH1 gene promoter methylation in MLH1-deficient cases. MMR mutation testing was performed on germline DNA of patients with MMR-protein deficient tumors. Prediction of germline mutation status was compared for combinations of tumor characteristics, age at diagnosis, and various clinical criteria (Amsterdam, Bethesda, Society of Gynecologic Oncology, ANECS). Results Tumor MMR-protein deficiency was detected in 170 (24%) of 702 cases. Germline testing of 158 MMR-deficient cases identified 22 truncating mutations (3% of all cases) and four unclassified variants. Tumor MLH1 methylation was detected in 99 (89%) of 111 cases demonstrating MLH1/PMS2 IHC loss; all were germline MLH1 mutation negative. A combination of MMR IHC plus MLH1 methylation testing in women younger than 60 years of age at diagnosis provided the highest positive predictive value for the identification of mutation carriers at 46% versus ≤ 41% for any other criteria considered. Conclusion Population-level identification of patients with MMR mutation-positive endometrial cancer is optimized by stepwise testing for tumor MMR IHC loss in patients younger than 60 years, tumor MLH1 methylation in individuals with MLH1 IHC loss, and germline mutations in patients exhibiting loss of MSH6, MSH2, or PMS2 or loss of MLH1/PMS2 with absence of MLH1 methylation. PMID:24323032

  20. Current contraceptive status among women aged 15-44: United States, 2011-2013.

    PubMed

    Daniels, Kimberly; Daugherty, Jill; Jones, Jo

    2014-12-01

    Nearly all women use contraception at some point in their lifetimes, although at any given time they may not be using contraception for reasons such as seeking pregnancy, being pregnant, or not being sexually active. Using data from the 2011-2013 National Survey of Family Growth (NSFG) on contraceptive use in the month of the interview, this report provides a snapshot of current contraceptive status among women aged 15-44 in the United States. In addition to describing use of any method by age, Hispanic origin and race, and educational attainment, patterns of use are described for the four most commonly used contraceptive methods: the oral contraceptive pill, female sterilization, the male condom, and long-acting reversible contraceptives, which include contraceptive implants and intrauterine devices.

  1. Stereotactic radiotherapy for wet age-related macular degeneration: current perspectives.

    PubMed

    Neffendorf, James E; Jackson, Timothy L

    2015-01-01

    Neovascular age-related macular degeneration is a leading cause of blindness in the developed world. Currently, the treatment of choice is intravitreal injections of anti-VEGF medications. These require frequent dosing, up to monthly, and impose a substantial burden on patients and the health economy. Ionizing radiation was proposed as a possible treatment for age-related macular degeneration due to its anti-inflammatory and anti-fibrotic properties. Stereotactic radiotherapy is an outpatient-based radiotherapy platform that provides stereotactic application of low energy X-ray to the retina in three highly collimated beams that cross the inferior sclera to overlap at the macula. A randomized, double-masked, sham-controlled trial of 230 patients (INTREPID) showed that a single dose of stereotactic radiotherapy significantly reduces the number of intravitreal anti-VEGF injections needed over 2 years. A larger randomized controlled trial (STAR) is underway. PMID:26491243

  2. Aging effects of U.S. space nuclear systems, currently in orbit

    NASA Astrophysics Data System (ADS)

    Bartram, Bart W.; Tammara, Seshagiri R.

    1992-01-01

    There are currently nine U.S. space nuclear systems in orbit, include eight with plutonium-238 fueled radioisotope thermoelectric generators and one fission-reactor system. Due to the inventories of radioactive materials onboard these spacecraft, the potential exists for radioactive releases during or following reentry. Projected orbital lifetimes, aging of containment materials, and radioactive decay will determine the degree of potential hazard associated with spacecraft reentry. These factors also affect consideration of possibly retrieving these spacecraft prior to reentry in order to minimize such hazards. This paper reviews the present U.S. space nuclear systems in orbit and summarizes the results of studies related to the aging effects of containment materials; describes changes in radionuclide inventory and external radiation field due to radioactive decay; and estimates the potential radioactive releases during or following reentry.

  3. An automated repair method of water pipe infrastructure using carbon fiber bundles

    NASA Astrophysics Data System (ADS)

    Wisotzkey, Sean; Carr, Heath; Fyfe, Ed

    2011-04-01

    The United States water pipe infrastructure is made up of over 2 million miles of pipe. Due to age and deterioration, a large portion of this pipe is in need of repair to prevent catastrophic failures. Current repair methods generally involve intrusive techniques that can be time consuming and costly, but also can cause major societal impacts. A new automated repair method incorporating innovative carbon fiber technology is in development. This automated method would eliminate the need for trenching and would vastly cut time and labor costs, providing a much more economical pipe repair solution.

  4. [Comparative characteristic of the formation of stereotype of aging in participants of current war conflicts and World War II].

    PubMed

    Iakymets', V M

    2006-01-01

    The study was carried out to examine participants of current war conflicts and World War II in order to compare the development of the formation of stereotype of old age. It was established that participants of World War II have higher level of the formation of pessimistic stereotype of old age than participants of current war conflicts have.

  5. Angiotensin II receptor blockade promotes repair of skeletal muscle through down-regulation of aging-promoting C1q expression

    PubMed Central

    Yabumoto, Chizuru; Akazawa, Hiroshi; Yamamoto, Rie; Yano, Masamichi; Kudo-Sakamoto, Yoko; Sumida, Tomokazu; Kamo, Takehiro; Yagi, Hiroki; Shimizu, Yu; Saga-Kamo, Akiko; Naito, Atsuhiko T.; Oka, Toru; Lee, Jong-Kook; Suzuki, Jun-ichi; Sakata, Yasushi; Uejima, Etsuko; Komuro, Issei

    2015-01-01

    Disruption of angiotensin II type 1 (AT1) receptor prolonged life span in mice. Since aging-related decline in skeletal muscle function was retarded in Atgr1a−/− mice, we examined the role of AT1 receptor in muscle regeneration after injury. Administration of AT1 receptor blocker irbesartan increased the size of regenerating myofibers, decreased fibrosis, and enhanced functional muscle recovery after cryoinjury. We recently reported that complement C1q, secreted by macrophages, activated Wnt/β-catenin signaling and promoted aging-related decline in regenerative capacity of skeletal muscle. Notably, irbesartan induced M2 polarization of macrophages, but reduced C1q expression in cryoinjured muscles and in cultured macrophage cells. Irbesartan inhibited up-regulation of Axin2, a downstream gene of Wnt/β-catenin pathway, in cryoinjured muscles. In addition, topical administration of C1q reversed beneficial effects of irbesartan on skeletal muscle regeneration after injury. These results suggest that AT1 receptor blockade improves muscle repair and regeneration through down-regulation of the aging-promoting C1q-Wnt/β-catenin signaling pathway. PMID:26571361

  6. Base Excision Repair and Cancer

    PubMed Central

    Wallace, Susan S.; Murphy, Drew L.; Sweasy, Joann B.

    2012-01-01

    Base excision repair is the system used from bacteria to man to remove the tens of thousands of endogenous DNA damages produced daily in each human cell. Base excision repair is required for normal mammalian development and defects have been associated with neurological disorders and cancer. In this paper we provide an overview of short patch base excision repair in humans and summarize current knowledge of defects in base excision repair in mouse models and functional studies on short patch base excision repair germ line polymorphisms and their relationship to cancer. The biallelic germ line mutations that result in MUTYH-associated colon cancer are also discussed. PMID:22252118

  7. Current Understanding of the Pathways Involved in Adult Stem and Progenitor Cell Migration for Tissue Homeostasis and Repair.

    PubMed

    Goichberg, Polina

    2016-08-01

    With the advancements in the field of adult stem and progenitor cells grows the recognition that the motility of primitive cells is a pivotal aspect of their functionality. There is accumulating evidence that the recruitment of tissue-resident and circulating cells is critical for organ homeostasis and effective injury responses, whereas the pathobiology of degenerative diseases, neoplasm and aging, might be rooted in the altered ability of immature cells to migrate. Furthermore, understanding the biological machinery determining the translocation patterns of tissue progenitors is of great relevance for the emerging methodologies for cell-based therapies and regenerative medicine. The present article provides an overview of studies addressing the physiological significance and diverse modes of stem and progenitor cell trafficking in adult mammalian organs, discusses the major microenvironmental cues regulating cell migration, and describes the implementation of live imaging approaches for the exploration of stem cell movement in tissues and the factors dictating the motility of endogenous and transplanted cells with regenerative potential. PMID:27209167

  8. Robotic inguinal hernia repair.

    PubMed

    Escobar Dominguez, Jose E; Gonzalez, Anthony; Donkor, Charan

    2015-09-01

    Inguinal hernias have been described throughout the history of medicine with many efforts to achieve the cure. Currently, with the advantages of minimally invasive surgery, new questions arise: what is going to be the best approach for inguinal hernia repair? Is there a real benefit with the robotic approach? Should minimally invasive hernia surgery be the standard of care? In this report we address these questions by describing our experience with robotic inguinal hernia repair. PMID:26153353

  9. Human DNA repair genes.

    PubMed

    Wood, R D; Mitchell, M; Sgouros, J; Lindahl, T

    2001-02-16

    Cellular DNA is subjected to continual attack, both by reactive species inside cells and by environmental agents. Toxic and mutagenic consequences are minimized by distinct pathways of repair, and 130 known human DNA repair genes are described here. Notable features presently include four enzymes that can remove uracil from DNA, seven recombination genes related to RAD51, and many recently discovered DNA polymerases that bypass damage, but only one system to remove the main DNA lesions induced by ultraviolet light. More human DNA repair genes will be found by comparison with model organisms and as common folds in three-dimensional protein structures are determined. Modulation of DNA repair should lead to clinical applications including improvement of radiotherapy and treatment with anticancer drugs and an advanced understanding of the cellular aging process. PMID:11181991

  10. Therapies for neovascular age-related macular degeneration: current approaches and pharmacologic agents in development.

    PubMed

    Hanout, Mostafa; Ferraz, Daniel; Ansari, Mehreen; Maqsood, Natasha; Kherani, Saleema; Sepah, Yasir J; Rajagopalan, Nithya; Ibrahim, Mohamed; Do, Diana V; Nguyen, Quan Dong

    2013-01-01

    As one of the leading causes of blindness, age-related macular degeneration (AMD) has remained at the epicenter of clinical research in ophthalmology. During the past decade, focus of researchers has ranged from understanding the role of vascular endothelial growth factor (VEGF) in the angiogenic cascades to developing new therapies for retinal vascular diseases. Anti-VEGF agents such as ranibizumab and aflibercept are becoming increasingly well-established therapies and have replaced earlier approaches such as laser photocoagulation or photodynamic therapy. Many other new therapeutic agents, which are in the early phase clinical trials, have shown promising results. The purpose of this paper is to briefly review the available treatment modalities for neovascular AMD and then focus on promising new therapies that are currently in various stages of development.

  11. Therapies for Neovascular Age-Related Macular Degeneration: Current Approaches and Pharmacologic Agents in Development

    PubMed Central

    Ferraz, Daniel; Kherani, Saleema; Sepah, Yasir J.; Rajagopalan, Nithya; Ibrahim, Mohamed; Do, Diana V.; Nguyen, Quan Dong

    2013-01-01

    As one of the leading causes of blindness, age-related macular degeneration (AMD) has remained at the epicenter of clinical research in ophthalmology. During the past decade, focus of researchers has ranged from understanding the role of vascular endothelial growth factor (VEGF) in the angiogenic cascades to developing new therapies for retinal vascular diseases. Anti-VEGF agents such as ranibizumab and aflibercept are becoming increasingly well-established therapies and have replaced earlier approaches such as laser photocoagulation or photodynamic therapy. Many other new therapeutic agents, which are in the early phase clinical trials, have shown promising results. The purpose of this paper is to briefly review the available treatment modalities for neovascular AMD and then focus on promising new therapies that are currently in various stages of development. PMID:24319688

  12. Conscientiousness and public health: synthesizing current research to promote healthy aging.

    PubMed

    Reiss, David; Eccles, Jacquelynne S; Nielsen, Lisbeth

    2014-05-01

    In this special section, 9 studies and 6 commentaries make a unique contribution to the study of personality. They focus on the five-factor model and, in particular, one of those 5: conscientiousness. This trait has had astonishing success in the actuarial prediction of adaptive outcomes in adulthood and aging, but we have little understanding of the mechanisms that account for this actuarial success. The current studies and comments marshal current knowledge of conscientiousness to advance a mechanistic understanding of these predictions and to exploit that understanding toward interventions to enhance robust adult development and healthy aging. In this introductory article, we underscore the strategy we used to invite presentations and commentary. First, we sought a clearer definition of conscientiousness and a review of its assessment. Second, we sought a review of how the components of this complex trait develop in childhood and are assembled across development. Third, we sought an understanding of how mechanisms linking conscientiousness and health might be transformed across the life span. Fourth, we scrutinized naturally occurring factors that moderate the links between conscientiousness and health for clues to successful interventions. Finally, we sought ways to pull these analyses together to outline the framework for a program of interventions that, collectively, might be applicable at specific points across the life span. Six commentaries place this project in sharp relief. They remind us that the causal status of the associations between conscientiousness and health, reported throughout our 9 studies, are uncertain at best. Second, they remind us that the concept of conscientiousness is still too spare: It fails to embody the social skills required for conscientious behavior, the moral judgment of self or other implicit in its assessment, or the neurobiological mechanisms that might account for differences among individuals. Third, they raise a potent

  13. DNA repair in cultured keratinocytes

    SciTech Connect

    Liu, S.C.; Parsons, S.; Hanawalt, P.C.

    1983-07-01

    Most of our understanding of DNA repair mechanisms in human cells has come from the study of these processes in cultured fibroblasts. The unique properties of keratinocytes and their pattern of terminal differentiation led us to a comparative examination of their DNA repair properties. The relative repair capabilities of the basal cells and the differentiated epidermal keratinocytes as well as possible correlations of DNA repair capacity with respect to age of the donor have been examined. In addition, since portions of human skin are chronically exposed to sunlight, the repair response to ultraviolet (UV) irradiation (254 nm) when the cells are conditioned by chronic low-level UV irradiation has been assessed. The comparative studies of DNA repair in keratinocytes from infant and aged donors have revealed no significant age-related differences for repair of UV-induced damage to DNA. Sublethal UV conditioning of cells from infant skin had no appreciable effect on either the repair or normal replication response to higher, challenge doses of UVL. However, such conditioning resulted in attenuated repair in keratinocytes from adult skin after UV doses above 25 J/m2. In addition, a surprising enhancement in replication was seen in conditioned cells from adult following challenge UV doses.

  14. Weakest solar wind of the space age and the current 'MINI' solar maximum

    SciTech Connect

    McComas, D. J.; Angold, N.; Elliott, H. A.; Livadiotis, G.; Schwadron, N. A.; Smith, C. W.; Skoug, R. M.

    2013-12-10

    The last solar minimum, which extended into 2009, was especially deep and prolonged. Since then, sunspot activity has gone through a very small peak while the heliospheric current sheet achieved large tilt angles similar to prior solar maxima. The solar wind fluid properties and interplanetary magnetic field (IMF) have declined through the prolonged solar minimum and continued to be low through the current mini solar maximum. Compared to values typically observed from the mid-1970s through the mid-1990s, the following proton parameters are lower on average from 2009 through day 79 of 2013: solar wind speed and beta (∼11%), temperature (∼40%), thermal pressure (∼55%), mass flux (∼34%), momentum flux or dynamic pressure (∼41%), energy flux (∼48%), IMF magnitude (∼31%), and radial component of the IMF (∼38%). These results have important implications for the solar wind's interaction with planetary magnetospheres and the heliosphere's interaction with the local interstellar medium, with the proton dynamic pressure remaining near the lowest values observed in the space age: ∼1.4 nPa, compared to ∼2.4 nPa typically observed from the mid-1970s through the mid-1990s. The combination of lower magnetic flux emergence from the Sun (carried out in the solar wind as the IMF) and associated low power in the solar wind points to the causal relationship between them. Our results indicate that the low solar wind output is driven by an internal trend in the Sun that is longer than the ∼11 yr solar cycle, and they suggest that this current weak solar maximum is driven by the same trend.

  15. Weakest Solar Wind of the Space Age and the Current "Mini" Solar Maximum

    NASA Astrophysics Data System (ADS)

    McComas, D. J.; Angold, N.; Elliott, H. A.; Livadiotis, G.; Schwadron, N. A.; Skoug, R. M.; Smith, C. W.

    2013-12-01

    The last solar minimum, which extended into 2009, was especially deep and prolonged. Since then, sunspot activity has gone through a very small peak while the heliospheric current sheet achieved large tilt angles similar to prior solar maxima. The solar wind fluid properties and interplanetary magnetic field (IMF) have declined through the prolonged solar minimum and continued to be low through the current mini solar maximum. Compared to values typically observed from the mid-1970s through the mid-1990s, the following proton parameters are lower on average from 2009 through day 79 of 2013: solar wind speed and beta (~11%), temperature (~40%), thermal pressure (~55%), mass flux (~34%), momentum flux or dynamic pressure (~41%), energy flux (~48%), IMF magnitude (~31%), and radial component of the IMF (~38%). These results have important implications for the solar wind's interaction with planetary magnetospheres and the heliosphere's interaction with the local interstellar medium, with the proton dynamic pressure remaining near the lowest values observed in the space age: ~1.4 nPa, compared to ~2.4 nPa typically observed from the mid-1970s through the mid-1990s. The combination of lower magnetic flux emergence from the Sun (carried out in the solar wind as the IMF) and associated low power in the solar wind points to the causal relationship between them. Our results indicate that the low solar wind output is driven by an internal trend in the Sun that is longer than the ~11 yr solar cycle, and they suggest that this current weak solar maximum is driven by the same trend.

  16. Cobbler's Technique for Iridodialysis Repair

    PubMed Central

    Pandav, Surinder Singh; Gupta, Parul Chawla; Singh, Rishi Raj; Das, Kalpita; Kaushik, Sushmita; Raj, Srishti; Ram, Jagat

    2016-01-01

    We describe a novel “Cobbler's technique” for iridodialysis repair in the right eye of a patient aged 18 years, with a traumatic iridodialysis secondary to open globe injury with an iron rod. Our technique is simple with easy surgical maneuvers, that is, effective for repairing iridodialysis. The “Cobbler's technique” allows a maximally functional and cosmetic result for iridodialysis. PMID:26957855

  17. Cobbler's Technique for Iridodialysis Repair.

    PubMed

    Pandav, Surinder Singh; Gupta, Parul Chawla; Singh, Rishi Raj; Das, Kalpita; Kaushik, Sushmita; Raj, Srishti; Ram, Jagat

    2016-01-01

    We describe a novel "Cobbler's technique" for iridodialysis repair in the right eye of a patient aged 18 years, with a traumatic iridodialysis secondary to open globe injury with an iron rod. Our technique is simple with easy surgical maneuvers, that is, effective for repairing iridodialysis. The "Cobbler's technique" allows a maximally functional and cosmetic result for iridodialysis. PMID:26957855

  18. DNA repair in cultured keratinocytes.

    PubMed

    Liu, S C; Parsons, S; Hanawalt, P C

    1983-07-01

    Most of our understanding of DNA repair mechanisms in human cells has come from the study of these processes in cultured fibroblasts. The unique properties of keratinocytes and their pattern of terminal differentiation led us to a comparative examination of their DNA repair properties. We have examined the relative repair capabilities of the basal cells and the differentiated epidermal keratinocytes as well as possible correlations of DNA repair capacity with respect to age of the donor. In addition, since portions of human skin are chronically exposed to sunlight, we have assessed the repair response to ultraviolet (UV) irradiation (254 nm) when the cells are conditioned by chronic low-level UV irradiation. The methods of Liu and Karasek were used to grow pure keratinocytes on collagen gels following their isolation from abdominal skin of newborns and adults at autopsy. Density labeling with 5-bromodeoxyuridine was used to resolve repair replication from the semiconservative mode. We found similar repair characteristics in human epidermal keratinocytes to those previously reported for cultured fibroblasts. However, the DNA repair response in basal cells was much greater than that in differentiated cells from the same skin preparation. Our comparative studies of DNA repair in keratinocytes from infant and aged donors have revealed no significant age-related differences for repair of UV-induced damage to DNA. Sublethal UV conditioning of cells from infant skin had no appreciable effect on either the repair or normal replication response to higher, challenge doses of UVL. However, such conditioning resulted in attenuated repair in keratinocytes from adult skin after UV doses above 25 J/m2. In addition, a surprising enhancement in replication was seen in conditioned cells from adult following challenge UV doses.

  19. EUVL Mask Blank Repair

    SciTech Connect

    Barty, A; Mirkarimi, P; Stearns, D G; Sweeney, D; Chapman, H N; Clift, M; Hector, S; Yi, M

    2002-05-22

    EUV mask blanks are fabricated by depositing a reflective Mo/Si multilayer film onto super-polished substrates. Small defects in this thin film coating can significantly alter the reflected field and introduce defects in the printed image. Ideally one would want to produce defect-free mask blanks; however, this may be very difficult to achieve in practice. One practical way to increase the yield of mask blanks is to effectively repair multilayer defects, and to this effect they present two complementary defect repair strategies for use on multilayer-coated EUVL mask blanks. A defect is any area on the mask which causes unwanted variations in EUV dose in the aerial image obtained in a printing tool, and defect repair is correspondingly defined as any strategy that renders a defect unprintable during exposure. The term defect mitigation can be adopted to describe any strategy which renders a critical defect non-critical when printed, and in this regard a non-critical defect is one that does not adversely affect device function. Defects in the patterned absorber layer consist of regions where metal, typically chrome, is unintentionally added or removed from the pattern leading to errors in the reflected field. There currently exists a mature technology based on ion beam milling and ion beam assisted deposition for repairing defects in the absorber layer of transmission lithography masks, and it is reasonable to expect that this technology will be extended to the repair of absorber defects in EUVL masks. However, techniques designed for the repair of absorber layers can not be directly applied to the repair of defects in the mask blank, and in particular the multilayer film. In this paper they present for the first time a new technique for the repair of amplitude defects as well as recent results on the repair of phase defects.

  20. Large-scale genomic analyses link reproductive ageing to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair

    PubMed Central

    Lunetta, Kathryn L.; Pervjakova, Natalia; Chasman, Daniel I.; Stolk, Lisette; Finucane, Hilary K.; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D.; Elks, Cathy E.; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A.; Franke, Lude L.; Huffman, Jennifer E.; Keller, Margaux F.; McArdle, Patrick F.; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M.; Schick, Ursula M.; Smith, Jennifer A.; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V.; Tanaka, Toshiko; Abecasis, Goncalo; Andrulis, Irene L.; Anton-Culver, Hoda; Antoniou, Antonis C.; Arndt, Volker; Arnold, Alice M.; Barbieri, Caterina; Beckmann, Matthias W.; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J.; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Borresen-Dale, Anne-Lise; Boutin, Thibaud S; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J.; Chapman, J. Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J.; Coviello, Andrea D.; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W.; Dennis, Joe; Devilee, Peter; Dörk, Thilo; dos-Santos-Silva, Isabel; Dunning, Alison M.; Eicher, John D.; Fasching, Peter A.; Faul, Jessica D.; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E.; García-Closas, Montserrat; Giles, Graham G.; Girotto, Giorgia G.; Goldberg, Mark S.; González-Neira, Anna; Goodarzi, Mark O.; Grove, Megan L.; Gudbjartsson, Daniel F.; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A.; Hall, Per; Hamann, Ute; Henderson, Brian E.; Hocking, Lynne J.; Hofman, Albert; Homuth, Georg; Hooning, Maartje J.; Hopper, John L.; Hu, Frank B.; Huang, Jinyan; Humphreys, Keith; Hunter, David J.; Jakubowska, Anna; Jones, Samuel E.; Kabisch, Maria; Karasik, David; Knight, Julia A.; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian’an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G.; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L.; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Ben M.; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B.; Nordestgaard, Børge G.; Olson, Janet E.; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D.P.; Pirastu, Nicola N.; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M.; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J.; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Ruggiero, Daniela; Sala, Cinzia F.; Sanna, Serena; Sawyer, Elinor J.; Schlessinger, David; Schmidt, Marjanka K.; Schmidt, Frank; Schmutzler, Rita K.; Schoemaker, Minouk J.; Scott, Robert A.; Seynaeve, Caroline M.; Simard, Jacques; Sorice, Rossella; Southey, Melissa C.; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D.; Thorsteinsdottir, Unnur; Toland, Amanda E.; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T.; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F.; Winqvist, Robert; Wolffenbuttel, Bruce B.H.R.; Wright, Alan F.; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I.; Buring, Julie E.; Ferrucci, Luigi; Montgomery, Grant W.; Gudnason, Vilmundur; Spector, Tim D.; van Duijn, Cornelia M; Alizadeh, Behrooz Z.; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F.; Gasparini, Paolo P.; Gieger, Christian; Harris, Tamara B.; Hayward, Caroline; Kardia, Sharon L.R.; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C.; Reiner, Alex P.; Ridker, Paul M.; Rotter, Jerome I.; Toniolo, Daniela; Uitterlinden, André G.; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J.; Weir, David R.; Yerges-Armstrong, Laura M.; Price, Alkes L.; Stefansson, Kari; Visser, Jenny A.; Ong, Ken K.; Chang-Claude, Jenny; Murabito, Joanne M.; Perry, John R.B.; Murray, Anna

    2015-01-01

    Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ~70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two harbouring additional rare missense alleles of large effect. We found enrichment of signals in/near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses revealed a major association with DNA damage-response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomisation analyses supported a causal effect of later ANM on breast cancer risk (~6% risk increase per-year, P=3×10−14), likely mediated by prolonged sex hormone exposure, rather than DDR mechanisms. PMID:26414677

  1. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

    PubMed

    Day, Felix R; Ruth, Katherine S; Thompson, Deborah J; Lunetta, Kathryn L; Pervjakova, Natalia; Chasman, Daniel I; Stolk, Lisette; Finucane, Hilary K; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D; Elks, Cathy E; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A; Franke, Lude L; Huffman, Jennifer E; Keller, Margaux F; McArdle, Patrick F; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M; Schick, Ursula M; Smith, Jennifer A; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V; Tanaka, Toshiko; Abecasis, Gonçalo R; Andrulis, Irene L; Anton-Culver, Hoda; Antoniou, Antonis C; Arndt, Volker; Arnold, Alice M; Barbieri, Caterina; Beckmann, Matthias W; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Borresen-Dale, Anne-Lise; Boutin, Thibaud S; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J; Chapman, J Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J; Coviello, Andrea D; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dunning, Alison M; Eicher, John D; Fasching, Peter A; Faul, Jessica D; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E; García-Closas, Montserrat; Giles, Graham G; Girotto, Giorgia G; Goldberg, Mark S; González-Neira, Anna; Goodarzi, Mark O; Grove, Megan L; Gudbjartsson, Daniel F; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A; Hall, Per; Hamann, Ute; Henderson, Brian E; Hocking, Lynne J; Hofman, Albert; Homuth, Georg; Hooning, Maartje J; Hopper, John L; Hu, Frank B; Huang, Jinyan; Humphreys, Keith; Hunter, David J; Jakubowska, Anna; Jones, Samuel E; Kabisch, Maria; Karasik, David; Knight, Julia A; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian'an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Benjamin M; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B; Nordestgaard, Børge G; Olson, Janet E; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D P; Pirastu, Nicola N; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Ruggiero, Daniela; Sala, Cinzia F; Sanna, Serena; Sawyer, Elinor J; Schlessinger, David; Schmidt, Marjanka K; Schmidt, Frank; Schmutzler, Rita K; Schoemaker, Minouk J; Scott, Robert A; Seynaeve, Caroline M; Simard, Jacques; Sorice, Rossella; Southey, Melissa C; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D; Thorsteinsdottir, Unnur; Toland, Amanda E; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F; Winqvist, Robert; Wolffenbuttel, Bruce B H R; Wright, Alan F; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I; Buring, Julie E; Ferrucci, Luigi; Montgomery, Grant W; Gudnason, Vilmundur; Spector, Tim D; van Duijn, Cornelia M; Alizadeh, Behrooz Z; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F; Gasparini, Paolo P; Gieger, Christian; Harris, Tamara B; Hayward, Caroline; Kardia, Sharon L R; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C; Reiner, Alex P; Ridker, Paul M; Rotter, Jerome I; Toniolo, Daniela; Uitterlinden, André G; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J; Weir, David R; Yerges-Armstrong, Laura M; Price, Alkes L; Stefansson, Kari; Visser, Jenny A; Ong, Ken K; Chang-Claude, Jenny; Murabito, Joanne M; Perry, John R B; Murray, Anna

    2015-11-01

    Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms. PMID:26414677

  2. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

    PubMed

    Day, Felix R; Ruth, Katherine S; Thompson, Deborah J; Lunetta, Kathryn L; Pervjakova, Natalia; Chasman, Daniel I; Stolk, Lisette; Finucane, Hilary K; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D; Elks, Cathy E; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A; Franke, Lude L; Huffman, Jennifer E; Keller, Margaux F; McArdle, Patrick F; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M; Schick, Ursula M; Smith, Jennifer A; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V; Tanaka, Toshiko; Abecasis, Gonçalo R; Andrulis, Irene L; Anton-Culver, Hoda; Antoniou, Antonis C; Arndt, Volker; Arnold, Alice M; Barbieri, Caterina; Beckmann, Matthias W; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Borresen-Dale, Anne-Lise; Boutin, Thibaud S; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J; Chapman, J Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J; Coviello, Andrea D; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dunning, Alison M; Eicher, John D; Fasching, Peter A; Faul, Jessica D; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E; García-Closas, Montserrat; Giles, Graham G; Girotto, Giorgia G; Goldberg, Mark S; González-Neira, Anna; Goodarzi, Mark O; Grove, Megan L; Gudbjartsson, Daniel F; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A; Hall, Per; Hamann, Ute; Henderson, Brian E; Hocking, Lynne J; Hofman, Albert; Homuth, Georg; Hooning, Maartje J; Hopper, John L; Hu, Frank B; Huang, Jinyan; Humphreys, Keith; Hunter, David J; Jakubowska, Anna; Jones, Samuel E; Kabisch, Maria; Karasik, David; Knight, Julia A; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian'an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Benjamin M; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B; Nordestgaard, Børge G; Olson, Janet E; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D P; Pirastu, Nicola N; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Ruggiero, Daniela; Sala, Cinzia F; Sanna, Serena; Sawyer, Elinor J; Schlessinger, David; Schmidt, Marjanka K; Schmidt, Frank; Schmutzler, Rita K; Schoemaker, Minouk J; Scott, Robert A; Seynaeve, Caroline M; Simard, Jacques; Sorice, Rossella; Southey, Melissa C; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D; Thorsteinsdottir, Unnur; Toland, Amanda E; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F; Winqvist, Robert; Wolffenbuttel, Bruce B H R; Wright, Alan F; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I; Buring, Julie E; Ferrucci, Luigi; Montgomery, Grant W; Gudnason, Vilmundur; Spector, Tim D; van Duijn, Cornelia M; Alizadeh, Behrooz Z; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F; Gasparini, Paolo P; Gieger, Christian; Harris, Tamara B; Hayward, Caroline; Kardia, Sharon L R; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C; Reiner, Alex P; Ridker, Paul M; Rotter, Jerome I; Toniolo, Daniela; Uitterlinden, André G; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J; Weir, David R; Yerges-Armstrong, Laura M; Price, Alkes L; Stefansson, Kari; Visser, Jenny A; Ong, Ken K; Chang-Claude, Jenny; Murabito, Joanne M; Perry, John R B; Murray, Anna

    2015-11-01

    Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

  3. [Aging of residents of St. Petersburg: current status and near-future prospects].

    PubMed

    Safarova, G L

    2002-01-01

    Population ageing, an increase in the proportion of elderly, is a worldwide process. Having numerous economic, social and political consequences, population ageing has now risen to the top of developed nations' agendas. The evolution of ageing characteristics during 1970-2000 for Saint-Petersburg and their future trends have been considered. Comparisons with characteristics of ageing for Russia have been done. Special attention has been paid to gender disparities of ageing characteristics.

  4. Age of First Use as a Predictor of Current Alcohol and Marijuana Use among College-Bound Emerging Adults

    ERIC Educational Resources Information Center

    Bergen-Cico, Dessa K.; Lape, Megan E.

    2013-01-01

    Background: Alcohol and marijuana are the most commonly used psychoactive substances; however, the sequencing and relationship between age of first use and continued current problematic use among college-bound emerging adults is not well understood. Methods: This is a cross-sectional study of current and historical alcohol and marijuana use among…

  5. [Neovascular form of age-related macular degeneration --current management in Poland and in Europe].

    PubMed

    Teper, Sławomir; Nowińska, Anna; Lyssek-Boroń, Anita; Wylegała, Edward

    2014-07-01

    Currently in Poland neovascular form of age-related macular degeneration (AMD) is treated with vascular endothelial growth factor (VEGF) inhibitors--ranibizumab, aflibercept and bevacizumab. Photodynamic therapy is still refunded, although it is very rarely used. It can be estimated that only small minority (about 5-10%) of cases are properly treated due to mainly refunding restrictions in Poland. In countries with wider access to treatment 50% reduction in AMD-related blindness incidence was noted. Low-cost off-label anti-VEGF agent bevacizumab is almost inaccessible in Polish public health system because of law regulations. In order to increase availability of anti-VEGF injections vials of all mentioned drugs are divided which raises safety concerns. Despite new potent drug in the market aflibercept, cost of treatment remains very high. The optimal treatment regimen includes three monthly injections, after which is usually used pro re nata therapy based primarily on the outcome of macular optical coherence tomography. Routinely recommended antibiotic prophylaxis of injection-related endophthalmitis probably has no meaning apart from the generation of resistance.

  6. Endovascular abdominal aortic aneurysm repair

    PubMed Central

    Norwood, M G A; Lloyd, G M; Bown, M J; Fishwick, G; London, N J; Sayers, R D

    2007-01-01

    The operative mortality following conventional abdominal aortic aneurysm (AAA) repair has not fallen significantly over the past two decades. Since its inception in 1991, endovascular aneurysm repair (EVAR) has provided an alternative to open AAA repair and perhaps an opportunity to improve operative mortality. Two recent large randomised trials have demonstrated the short and medium term benefit of EVAR over open AAA repair, although data on the long term efficacy of the technique are still lacking. This review aimed at providing an overview of EVAR and a discussion of the potential benefits and current limitations of the technique. PMID:17267674

  7. Craniosynostosis repair

    MedlinePlus

    ... will be asleep and will not feel pain. Traditional surgery is called open repair. It includes these ... helps keep the swelling down. Talking, singing, playing music, and telling stories may help soothe your child. ...

  8. Current and emerging therapies for the treatment of age-related macular degeneration.

    PubMed

    Emerson, M Vaughn; Lauer, Andreas K

    2008-06-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the industrialized world. In the last few decades, the mainstay of treatment for choroidal neovascularization (CNV) due to AMD has been thermal laser photocoagulation. In the last decade, photodynamic therapy with verteporfin extended treatment for more patients. While both of these treatments have prevented further vision loss in a subset of patients, improvement in visual acuity is rare. Anti-vascular endothelial growth factor A (VEGF) therapy has revolutionized the treatment of AMD-related CNV. Pegaptanib, an anti-VEGF aptamer prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment and bevacizumab, a full-length humanized monoclonal antibody against VEGF have both shown promising results with improvements in visual acuity with either agent. VEGF trap, a modified soluble VEGF receptor analogue, binds VEGF more tightly than all other anti-VEGF agents and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering ribonucleic acid (RNA) to inhibit VEGF production and VEGF receptor production. Steroids, including anecortave acetate in the treatment and prevention of CNV, have shown promise in controlled trials. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Other growth factors, including pigment epithelium-derived growth factor that has been administered via an adenoviral vector has shown promising initial results. In some patients ciliary neurotrophic factor is currently being studied for the inhibition of progression of geographic atrophy. Combination therapy has been

  9. [An overview of current research of the effect of foods on aging and stress].

    PubMed

    Takahashi, Ryoya; Odera, Keiko

    2015-01-01

      The aging process is largely influenced by dietary factors. For example, caloric restriction can slow age-related functional deterioration and the onset or progression of age-related diseases, as well as prolong mean and maximum life span in laboratory animals. However, the dietary factors that affect the aging process comprise not only calories, but also various nutrients, such as proteins, carbohydrates, fats, and vitamins. Phytochemicals, which are found in plants, are non-nutritive, yet many phytochemicals are known to act as antioxidants and prevent diseases associated with free radical production. Furthermore, certain phytochemicals can help prevent or reduce the risk of cancer, inflammation, and cardiovascular disease by alteration of several signal transduction pathways in cells. Therefore, much focus is being placed on the effects of dietary phytochemicals on aging and stress response. This paper reviews recent advances in the study of two major dietary phytochemicals, resveratrol and curcumin, on aging and stress response.

  10. Evolution of crystal imperfections during current-stress ageing tests of green InGaN light-emitting diodes

    NASA Astrophysics Data System (ADS)

    Lin, Yue; Peng, Zhangbao; Zhu, Lihong; Yan, Wei; Shih, Tien-mo; Wu, Tingzhu; Lu, Yijun; Gao, Yulin; Chen, Zhong; Guo, Ziquan; Liu, Zhuguang

    2016-09-01

    We perform ageing tests under high current on several green InGaN light-emitting diodes and compare the luminous homogeneities of chip surfaces, shapes of external quantum efficiency (EQE) curves, and electroluminescence spectra during different ageing stages. By curve fittings to the EQE curves, with the ABC and two-level models, we discover that a high injection current density can modify the defect configuration in quantum wells even at room temperature, as high-temperature annealing can. For In-rich devices, the removal of localization centers is another origin of luminous intensity decay in addition to the formation of point defects.

  11. Pectus excavatum repair

    MedlinePlus

    Funnel chest repair; Chest deformity repair; Sunken chest repair; Cobbler's chest repair; Nuss repair; Ravitch repair ... There are two types of surgery to repair this condition -- open surgery ... surgery is done while the child is in a deep sleep and pain- ...

  12. Relationship of Intraoperative Cerebral Oxygen Saturation to Neurodevelopmental Outcome and Brain MRI at One Year of Age in Infants Undergoing Biventricular Repair

    PubMed Central

    Kussman, Barry D.; Wypij, David; Laussen, Peter C.; Soul, Janet S.; Bellinger, David C.; DiNardo, James A.; Robertson, Richard; Pigula, Frank A.; Jonas, Richard A.; Newburger, Jane W.

    2010-01-01

    Background Near-infrared spectroscopy (NIRS) monitoring of cerebral oxygen saturation (rSO2) has become routine in many centers, but no studies have reported the relationship of intraoperative NIRS to long-term neurodevelopmental outcomes after cardiac surgery. Methods and Results Of 104 infants undergoing biventricular repair without aortic arch reconstruction, 89 (86%) returned for neurodevelopmental testing at age 1 year. The primary NIRS variable was the integrated rSO2 (area under the curve) for rSO2 ≤ 45%; secondary variables were the average and minimum rSO2 by perfusion phase and at specific time points. Psychomotor (PDI) and Mental Development Indexes of the Bayley Scales, head circumference, neurologic examination, and abnormalities on brain MRI did not differ between subjects according to a threshold level for rSO2 of 45%. Lower PDI scores were modestly associated with lower average (r=0.23; P=0.03) and minimum rSO2 (r=0.22; P=0.04) during the 60 minute period following cardiopulmonary bypass (CPB), but not with other perfusion phases. Hemosiderin foci on brain MRI were associated with lower average rSO2 from post-induction to 60 minutes post-CPB (71±10 vs. 78±6%; P=0.01), and lower average rSO2 during the rewarming phase (72±12 vs. 83±9%; P=0.003) and during the 60 minute period following CPB (65±11 vs. 75±10%; P=0.009). In regression analyses adjusting for age ≤ 30 days, PDI score (P=0.02) and brain hemosiderin (P=0.04) remained significantly associated with rSO2 during the 60 minute period following CPB. Conclusions Perioperative periods of diminished cerebral oxygen delivery, as indicated by rSO2, are associated with one-year PDI and brain MRI abnormalities among infants undergoing reparative heart surgery. Clinical Trial Registration Information http://clinicaltrials.gov/ct2/show/NCT00006183 PMID:20606124

  13. Femoral hernia repair

    MedlinePlus

    Femorocele repair; Herniorrhaphy; Hernioplasty - femoral ... During surgery to repair the hernia, the bulging tissue is pushed back in. The weakened area is sewn closed or strengthened. This repair ...

  14. Undescended testicle repair

    MedlinePlus

    Orchidopexy; Inguinal orchidopexy; Orchiopexy; Repair of undescended testicle; Cryptorchidism repair ... first year of life without treatment. Undescended testicle repair surgery is recommended for patients whose testicles do ...

  15. Mammalian DNA Repair. Final Report

    SciTech Connect

    2003-01-24

    The Gordon Research Conference (GRC) on Mammalian DNA Repair was held at Harbortown Resort, Ventura Beach, CA. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  16. Mechanisms and consequences of injury and repair in older organ transplants.

    PubMed

    Slegtenhorst, Bendix R; Dor, Frank J M F; Elkhal, Abdala; Rodriguez, Hector; Yang, Xiaoyong; Edtinger, Karoline; Quante, Markus; Chong, Anita S; Tullius, Stefan G

    2014-06-15

    Donor organ scarcity remains a significant clinical challenge in transplantation. Older organs, increasingly utilized to meet the growing demand for donor organs, have been linked to inferior transplant outcomes. Susceptibility to organ injury, reduced repair capacity, and increased immunogenicity are interrelated and impacted by physiological and pathological aging processes. Insights into the underlying mechanisms are needed to develop age-specific interventional strategies with regards to organ preservation, immunosuppression, and allocation. In this overview, we summarize current knowledge of injury and repair mechanisms and the effects of aging relevant to transplantation.

  17. Are childhood abuse and neglect related to age of first homelessness episode among currently homeless adults?

    PubMed

    Mar, Marissa Y; Linden, Isabelle A; Torchalla, Iris; Li, Kathy; Krausz, Michael

    2014-01-01

    This study investigates 500 homeless adults and the associations between childhood maltreatment types and the age of first reported homelessness episode. Those first experiencing homelessness in youth (age 24 years or younger; 46%) were compared with those first experiencing homelessness at a later age (older than age 24 years). In individual models, physical abuse, emotional abuse, and emotional neglect were associated with first experiencing homelessness during youth (p < .02 for all types of maltreatment). In the simultaneous model, only emotional abuse remained significantly associated (p = .002). In addition, increasing numbers of maltreatment were associated with becoming homeless during youth (p < .0001). These results highlight the unique associations between childhood maltreatment types and becoming homeless earlier in life and support the need for early interventions with at-risk families.

  18. Current tobacco use and secondhand smoke exposure among women of reproductive age--14 countries, 2008-2010.

    PubMed

    2012-11-01

    Tobacco use and secondhand smoke (SHS) exposure in reproductive-aged women can cause adverse reproductive health outcomes, such as pregnancy complications, fetal growth restriction, preterm delivery, stillbirths, and infant death. Data on tobacco use and SHS exposure among reproductive-aged women in low- and middle-income countries are scarce. To examine current tobacco use and SHS exposure in women aged 15-49 years, data were analyzed from the 2008-2010 Global Adult Tobacco Survey (GATS) from 14 low- and middle-income countries: Bangladesh, Brazil, China, Egypt, India, Mexico, Philippines, Poland, Russia, Thailand, Turkey, Ukraine, Uruguay, and Vietnam. The results of this analysis indicated that, among reproductive-aged women, current tobacco smoking ranged from 0.4% in Egypt to 30.8% in Russia, current smokeless tobacco use was <1% in most countries, but common in Bangladesh (20.1%) and India (14.9%), and SHS exposure at home was common in all countries, ranging from 17.8% in Mexico to 72.3% in Vietnam. High tobacco smoking prevalence in some countries suggests that strategies promoting cessation should be a priority, whereas low prevalence in other countries suggests that strategies should focus on preventing smoking initiation. Promoting cessation and preventing initiation among both men and women would help to reduce the exposure of reproductive-aged women to SHS.

  19. Evolution and advances in laparoscopic ventral and incisional hernia repair

    PubMed Central

    Vorst, Alan L; Kaoutzanis, Christodoulos; Carbonell, Alfredo M; Franz, Michael G

    2015-01-01

    Primary ventral hernias and ventral incisional hernias have been a challenge for surgeons throughout the ages. In the current era, incisional hernias have increased in prevalence due to the very high number of laparotomies performed in the 20th century. Even though minimally invasive surgery and hernia repair have evolved rapidly, general surgeons have yet to develop the ideal, standardized method that adequately decreases common postoperative complications, such as wound failure, hernia recurrence and pain. The evolution of laparoscopy and ventral hernia repair will be reviewed, from the rectoscopy of the 4th century to the advent of laparoscopy, from suture repair to the evolution of mesh reinforcement. The nuances of minimally invasive ventral and incisional hernia repair will be summarized, from preoperative considerations to variations in intraoperative practice. New techniques have become increasingly popular, such as primary defect closure, retrorectus mesh placement, and concomitant component separation. The advent of robotics has made some of these repairs more feasible, but only time and well-designed clinical studies will tell if this will be a durable modality for ventral and incisional hernia repair. PMID:26649152

  20. Final report [DNA Repair and Mutagenesis - 1999

    SciTech Connect

    Walker, Graham C.

    2001-05-30

    The meeting, titled ''DNA Repair and Mutagenesis: Mechanism, Control, and Biological Consequences'', was designed to bring together the various sub-disciplines that collectively comprise the field of DNA Repair and Mutagenesis. The keynote address was titled ''Mutability Doth Play Her Cruel Sports to Many Men's Decay: Variations on the Theme of Translesion Synthesis.'' Sessions were held on the following themes: Excision repair of DNA damage; Transcription and DNA excision repair; UmuC/DinB/Rev1/Rad30 superfamily of DNA polymerases; Cellular responses to DNA damage, checkpoints, and damage tolerance; Repair of mismatched bases, mutation; Genome-instability, and hypermutation; Repair of strand breaks; Replicational fidelity, and Late-breaking developments; Repair and mutation in challenging environments; and Defects in DNA repair: consequences for human disease and aging.

  1. Age- and Sex-Related Characteristics of Tonic Gaba Currents in the Rat Substantia Nigra Pars Reticulata

    PubMed Central

    Hasson, H.; Bojar, M.; Moshé, S. L.; Galanopoulou, A. S.

    2015-01-01

    Previous studies have shown that the pharmacologic effects of GABAergic drugs and the postsynaptic phasic GABAAergic inhibitory responses in the anterior part of the rat substantia nigra pars reticulata (SNRA) are age- and sex-specific. Here, we investigate whether there are age- and sex-related differences in the expression of the δ GABAA receptor (GABAAR) subunit and GABAAR mediated tonic currents. We have used δ-specific immunochemistry and whole cell patch clamp to study GABAAR mediated tonic currents in the SNRA of male and female postnatal day (PN) PN5-9, PN11-16, and PN25-32 rats. We observed age-related decline, but no sex-specific changes, in bicuculline (BIM) sensitive GABAAR tonic current density, which correlated with the decline in δ subunit in the SNRA between PN15 and 30. Furthermore, we show that the GABAAR tonic currents can be modified by muscimol (GABAAR agonist; partial GABACR agonist), THIP (4,5,6,7-tetrahydroisoxazolo (5,4-c)pyridin-3-ol: α4β3δ GABAARs agonist and GABACR antagonist), and zolpidem (α1-subunit selective GABAAR agonist) in age-and sex-dependent manner specific for each drug. We propose that the emergence of the GABAAR-sensitive anticonvulsant effects of the rat SNRA during development may depend upon the developmental decline in tonic GABAergic inhibition of the activity of rat SNRA neurons, although other sex-specific factors are also involved. PMID:25645446

  2. Heterogeneity of the definition of elderly age in current orthopaedic research.

    PubMed

    Sabharwal, Sanjeeve; Wilson, Helen; Reilly, Peter; Gupte, Chinmay M

    2015-01-01

    Medical research often defines a person as elderly when they are 65 years of age or above, however defining elderly age by chronology alone has its limitations. Moreover, potential variability in definitions of elderly age can make interpretation of the collective body of evidence within a particular field of research confusing. Our research goals were to (1) evaluate published orthopaedic research and determine whether there is variability in proposed definitions of an elderly person, and (2) to determine whether variability exists within the important research sub-group of hip fractures. A defined search protocol was used within PubMed, EMBASE and the Cochrane Library that identified orthopaedic research articles published in 2012 that stated within their objective, intent to examine an intervention in an elderly population. 80 studies that included 271,470 patients were identified and subject to analysis. Four (5 %) studies failed to define their elderly population. The remaining 76 (95 %) studies all defined elderly age by chronology alone. Definitions of an elderly person ranged from 50 to 80 years and above. The most commonly used age to define an elderly person was 65, however this accounted for only 38 (47.5 %) of studies. Orthopedic research appears to favor defining elderly age by chronology alone, and there is considerable heterogeneity amongst these definitions. This may confuse interpretation of the evidence base in areas of orthopaedic research that focus on elderly patients. The findings of this study underline the importance of future research in orthopaedics adopting validated frailty index measures so that population descriptions in older patients are more uniform and clinically relevant. PMID:26405636

  3. Intestinal obstruction repair

    MedlinePlus

    Repair of volvulus; Intestinal volvulus - repair; Bowel obstruction - repair ... Intestinal obstruction repair is done while you are under general anesthesia . This means you are asleep and DO NOT feel pain. ...

  4. Motorcycle Repair.

    ERIC Educational Resources Information Center

    Hein, Jim; Bundy, Mike

    This motorcycle repair curriculum guide contains the following ten areas of study: brake systems, clutches, constant mesh transmissions, final drives, suspension, mechanical starting mechanisms, electrical systems, fuel systems, lubrication systems, and overhead camshafts. Each area consists of one or more units of instruction. Each instructional…

  5. Outboard Repair.

    ERIC Educational Resources Information Center

    Hardway, Jack

    This consortium-developed instructor's manual for small engine repair (with focus on outboard motors) consists of the following nine instructional units: electrical remote control assembly, mechanical remote control assembly, tilt assemblies, exhaust housing, propeller and trim tabs, cooling system, mechanical gearcase, electrical gearcase, and…

  6. Snowmobile Repair.

    ERIC Educational Resources Information Center

    Helbling, Wayne

    This guide is designed to provide and/or improve instruction for occupational training in the area of snowmobile repair, and includes eight areas. Each area consists of one or more units of instruction, with each instructional unit including some or all of the following basic components: Performance objectives, suggested activities for teacher and…

  7. Diminishing risk for age related macular degeneration with nutrition: A current view

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies because they are more affordable...

  8. Conscientiousness and Public Health: Synthesizing Current Research to Promote Healthy Aging

    ERIC Educational Resources Information Center

    Reiss, David; Eccles, Jacquelynne S.; Nielsen, Lisbeth

    2014-01-01

    In this special section, 9 studies and 6 commentaries make a unique contribution to the study of personality. They focus on the five-factor model and, in particular, one of those 5: conscientiousness. This trait has had astonishing success in the actuarial prediction of adaptive outcomes in adulthood and aging, but we have little understanding of…

  9. Turbine repair process, repaired coating, and repaired turbine component

    SciTech Connect

    Das, Rupak; Delvaux, John McConnell; Garcia-Crespo, Andres Jose

    2015-11-03

    A turbine repair process, a repaired coating, and a repaired turbine component are disclosed. The turbine repair process includes providing a turbine component having a higher-pressure region and a lower-pressure region, introducing particles into the higher-pressure region, and at least partially repairing an opening between the higher-pressure region and the lower-pressure region with at least one of the particles to form a repaired turbine component. The repaired coating includes a silicon material, a ceramic matrix composite material, and a repaired region having the silicon material deposited on and surrounded by the ceramic matrix composite material. The repaired turbine component a ceramic matrix composite layer and a repaired region having silicon material deposited on and surrounded by the ceramic matrix composite material.

  10. Past and current body size affect validity of reported energy intake among middle-aged Danish men.

    PubMed

    Nielsen, Birgit M; Nielsen, Marie M; Toubro, Søren; Pedersen, Oluf; Astrup, Arne; Sørensen, Thorkild I A; Jess, Tine; Heitmann, Berit L

    2009-12-01

    Our objectives were to estimate the degree of misreporting energy intake (EI) and analyze associations with previous BMI, current BMI, or both. The study was part of the Adiposity and Genetics Study follow-up study including 309 Danish men (age 40-65 y) originally sampled from the obligatory draft board examination. Height and weight were measured at the mean ages of 20 (draft board), 33, 44, and 49 y (current age). Obesity was categorized as BMI >or= 31 kg/m(2). Dietary intake for 7 d and physical activity (PA) level (PAL) were self-reported. Resting metabolic rate (RMR) was measured in a ventilated hood system. By comparing EI with energy expenditure and assuming energy balance, reporting accuracy (RA) was estimated as EI/(RMR.PAL). A plausibility interval was calculated to encompass specific variation components of EI, RMR, and PAL; the specific 95% plausibility interval was 1.00 +/- 0.35. Participants were categorized as underreporters (RA 1.35) of EI. The relation between RA and BMI was studied through linear regression analysis. Overall, the RA was (mean +/- SE) 0.76 +/- 0.01. Of 309 participants, 35% underreported and 7% overreported. Whether stratified for current BMI or draft board BMI, the obese men were more likely to underreport than those who were not obese. Among those currently not obese, underreporting was more prevalent among those who were obese at the draft board examination (44%) than among those who were not (21%). Regression analysis showed that both previous and current BMI and their combination were significantly associated with RA. Thus, underreporting of dietary intake seems to be associated with not only current BMI but also with current BMI in combination with previous BMI.

  11. Current asthma contributes as much as smoking to chronic bronchitis in middle age: a prospective population-based study

    PubMed Central

    Dharmage, Shyamali C; Perret, Jennifer L; Burgess, John A; Lodge, Caroline J; Johns, David P; Thomas, Paul S; Giles, Graham G; Hopper, John L; Abramson, Michael J; Walters, E Haydn; Matheson, Melanie C

    2016-01-01

    Background and objective Personal smoking is widely regarded to be the primary cause of chronic bronchitis (CB) in adults, but with limited knowledge of contributions by other factors, including current asthma. We aimed to estimate the independent and relative contributions to adult CB from other potential influences spanning childhood to middle age. Methods The population-based Tasmanian Longitudinal Health Study cohort, people born in 1961, completed respiratory questionnaires and spirometry in 1968 (n=8,583). Thirty-seven years later, in 2004, two-thirds responded to a detailed postal survey (n=5,729), from which the presence of CB was established in middle age. A subsample (n=1,389) underwent postbronchodilator spirometry between 2006 and 2008 for the assessment of chronic airflow limitation, from which nonobstructive and obstructive CB were defined. Multivariable and multinomial logistic regression models were used to estimate relevant associations. Results The prevalence of CB in middle age was 6.1% (95% confidence interval [CI]: 5.5, 6.8). Current asthma and/or wheezy breathing in middle age was independently associated with adult CB (odds ratio [OR]: 6.2 [95% CI: 4.6, 8.4]), and this estimate was significantly higher than for current smokers of at least 20 pack-years (OR: 3.0 [95% CI: 2.1, 4.3]). Current asthma and smoking in middle age were similarly associated with obstructive CB, in contrast to the association between allergy and nonobstructive CB. Childhood predictors included allergic history (OR: 1.3 [95% CI: 1.1, 1.7]), current asthma (OR: 1.8 [95% CI: 1.3, 2.7]), “episodic” childhood asthma (OR: 2.3 [95% CI: 1.4, 3.9]), and parental bronchitis symptoms (OR: 2.5 [95% CI: 1.6, 4.1]). Conclusion The strong independent association between current asthma and CB in middle age suggests that this condition may be even more influential than personal smoking in a general population. The independent associations of childhood allergy and asthma, though not

  12. Small Rayed Crater Ejecta Retention Age Calculated from Current Crater Production Rates on Mars

    NASA Technical Reports Server (NTRS)

    Calef, F. J. III; Herrick, R. R.; Sharpton, V. L.

    2011-01-01

    Ejecta from impact craters, while extant, records erosive and depositional processes on their surfaces. Estimating ejecta retention age (Eret), the time span when ejecta remains recognizable around a crater, can be applied to estimate the timescale that surface processes operate on, thereby obtaining a history of geologic activity. However, the abundance of sub-kilometer diameter (D) craters identifiable in high resolution Mars imagery has led to questions of accuracy in absolute crater dating and hence ejecta retention ages (Eret). This research calculates the maximum Eret for small rayed impact craters (SRC) on Mars using estimates of the Martian impactor flux adjusted for meteorite ablation losses in the atmosphere. In addition, we utilize the diameter-distance relationship of secondary cratering to adjust crater counts in the vicinity of the large primary crater Zunil.

  13. Diminishing risk for age-related macular degeneration with nutrition: a current view.

    PubMed

    Schleicher, Molly; Weikel, Karen; Garber, Caren; Taylor, Allen

    2013-07-02

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies, because they are more affordable than clinical therapies, do not require specialists for administration and many studies suggest a benefit of micro- and macro-nutrients with respect to AMD with few, if any, adverse effects. The goal of this review is to provide information from recent literature on the value of various nutrients, particularly omega-3 fatty acids, lower glycemic index diets and, perhaps, some carotenoids, with regard to diminishing risk for onset or progression of AMD. Results from the upcoming Age-Related Eye Disease Study (AREDS) II intervention trial should be particularly informative.

  14. Conversational Repair Strategies in Response to Requests for Clarification in Typically Developing Jordanian Children Ages 4;0-6;0 Years

    ERIC Educational Resources Information Center

    Kamal, Sana M.; Haj-Tas, Maisa A.

    2014-01-01

    Conversational repairs are an important pragmatic language skill. We identified types of responses to requests for clarification and their frequencies in typically developing 4;0-6;0-year-old Jordanian children. This study was motivated by the fact that there are no Arabic data regarding this issue and by the limited range of forms of requests for…

  15. Age-Associated Skin Conditions and Diseases: Current Perspectives and Future Options.

    PubMed

    Blume-Peytavi, Ulrike; Kottner, Jan; Sterry, Wolfram; Hodin, Michael W; Griffiths, Tamara W; Watson, Rachel E B; Hay, Roderick J; Griffiths, Christopher E M

    2016-04-01

    The International League of Dermatological Societies (ILDS), a global, not-for-profit organization representing 157 dermatological societies worldwide, has identified the consequences of skin aging as one of the most important grand challenges in global skin health. Reduced functional capacity and increased susceptibility of the skin with development of dermatoses such as dry skin, itching, ulcers, dyspigmentation, wrinkles, fungal infections, as well as benign and malignant tumors are the most common skin conditions in aged populations worldwide. Environmental (e.g., pollution) and lifestyle factors (e.g., smoking, sunbed use) negatively affect skin health. In turn altered appearance, dry skin, chronic wounds, and other conditions decrease general health and reduce the likelihood for healthy and active aging. Preventive skin care includes primary, secondary, and tertiary interventions. Continuous sun protection from early childhood onward is most important, to avoid extrinsic skin damage and skin cancer. Exposure to irritants, allergens, or other molecules damaging the skin must be avoided or reduced to a minimum. Public health approaches are needed to implement preventive and basic skin care worldwide to reach high numbers of dermatological patients and care receivers. Education of primary caregivers and implementation of community dermatology are successful strategies in resource-poor countries. Besides specialist physicians, nurses and other health care professionals play important roles in preventing and managing age-related skin conditions in developing as well as in developed countries. Healthy skin across the life course leads to better mental and emotional health, positive impact on social engagement, and healthier, more active, and productive lives.

  16. Ultrasound determination of rotator cuff tear repairability

    PubMed Central

    Tse, Andrew K; Lam, Patrick H; Walton, Judie R; Hackett, Lisa

    2015-01-01

    Background Rotator cuff repair aims to reattach the torn tendon to the greater tuberosity footprint with suture anchors. The present study aimed to assess the diagnostic accuracy of ultrasound in predicting rotator cuff tear repairability and to assess which sonographic and pre-operative features are strongest in predicting repairability. Methods The study was a retrospective analysis of measurements made prospectively in a cohort of 373 patients who had ultrasounds of their shoulder and underwent rotator cuff repair. Measurements of rotator cuff tear size and muscle atrophy were made pre-operatively by ultrasound to enable prediction of rotator cuff repairability. Tears were classified following ultrasound as repairable or irreparable, and were correlated with intra-operative repairability. Results Ultrasound assessment of rotator cuff tear repairability has a sensitivity of 86% (p < 0.0001) and a specificity of 67% (p < 0.0001). The strongest predictors of rotator cuff repairability were tear size (p < 0.001) and age (p = 0.004). Sonographic assessments of tear size ≥4 cm2 or anteroposterior tear length ≥25 mm indicated an irreparable rotator cuff tear. Conclusions Ultrasound assessment is accurate in predicting rotator cuff tear repairability. Tear size or anteroposterior tear length and age were the best predictors of repairability. PMID:27582996

  17. Population ageing in Lebanon: current status, future prospects and implications for policy.

    PubMed Central

    Sibai, Abla Mehio; Sen, Kasturi; Baydoun, May; Saxena, Prem

    2004-01-01

    During the past three decades, fast declines in fertility and mortality in Lebanon have created a compressed demographic transition, a growing trend towards survival into later life, and a larger proportion of elderly people in the population. Projections show that people aged 65 years and over are expected to constitute 10.2% of the population by 2025. Nevertheless, changes to the structure and composition of the population remain unmatched by any corresponding increase in support measures either through formal channels such as pension plans or through health or socioeconomic security measures such as the provision of subsidies for health care, home help or any form of nursing care. This means that an older person is forced to be dependent upon family support if it exists. We examine demographic trends of population ageing in Lebanon between 1970 and 1995 and provide projections until 2025. Variations in population ageing within the country are also considered. We also assess health care and social policy implications of demographic changes in the context of health and economic sector reforms initiated recently by the state, and explore their impact upon the expanding population of elderly people. PMID:15112011

  18. Current concepts in age-related hearing loss: Epidemiology and mechanistic pathways

    PubMed Central

    Yamasoba, Tatsuya; Lin, Frank R.; Someya, Shinichi; Kashio, Akinori; Sakamoto, Takashi; Kondo, Kenji

    2013-01-01

    Age-related hearing loss (AHL), also known as presbycusis, is a universal feature of mammalian aging and is characterized by a decline of auditory function, such as increased hearing thresholds and poor frequency resolution. The primary pathology of AHL includes the hair cells, stria vascularis, and afferent spiral ganglion neurons as well as the central auditory pathways. A growing body of evidence in animal studies has suggested that cumulative effect of oxidative stress could induce damage to macromolecules such as mitochondrial DNA (mtDNA) and that the resulting accumulation of mtDNA mutations/deletions and decline of mitochondrial function play an important role in inducing apoptosis of the cochlear cells, thereby the development of AHL. Epidemiological studies have demonstrated four categories of risk factors of AHL in humans: cochlear aging, environment such as noise exposure, genetic predisposition, and health co-morbidities such as cigarette smoking and atherosclerosis. Genetic investigation has identified several putative associating genes, including those related to antioxidant defense and atherosclerosis. Exposure to noise is known to induce excess generation of reactive oxygen species (ROS) in the cochlea, and cumulative oxidative stress can be enhanced by relatively hypoxic situations resulting from the impaired homeostasis of cochlear blood supply due to atherosclerosis, which could be accelerated by genetic and co-morbidity factors. Antioxidant defense system may also be influenced by genetic backgrounds. These may explain the large variations of the onset and extent of AHL among elderly subjects. PMID:23422312

  19. The needs, current knowledge, and attitudes of care staff toward the implementation of palliative care in old age homes.

    PubMed

    Lo, Raymond S K; Kwan, Bonnie H F; Lau, Kay P K; Kwan, Cecilia W M; Lam, L M; Woo, Jean

    2010-06-01

    This study aims to explore in depth the needs, current knowledge, and attitudes of all ranks of old age home staff. A large-scale qualitative study with 13 semistructured focus groups was conducted in Hong Kong. Key themes were extracted by framework analysis. Three major themes were extracted, including role as a service provider, current knowledge, and attitude toward palliative care. There was a marked difference in familiarity with the concept of ''palliative care'' between different groups of staff, yet both shared the motivation for enhancement. The biggest concerns for the staff were elderly residents' readiness to accept palliative care, manpower, and resources. Care staff, regardless of rank, seemed to welcome and be ready to adopt a palliative care approach in caring for old age home residents, though not without worries and concerns. PMID:19959840

  20. Transportation for School-Age Child Care: Current Status in Westchester County.

    ERIC Educational Resources Information Center

    Child Care Council of Westchester, Inc., White Plains, NY.

    Based on countywide interviews with transportation and child care personnel in Westchester County, New York, this report describes current practices, legislation, and issues related to the transportation of elementary school children to and from child care providers. Following a brief introduction, the report discusses various regulated and…

  1. Effect of thermal aging on the tensile bond strength at reduced areas of seven current adhesives.

    PubMed

    Baracco, Bruno; Fuentes, M Victoria; Garrido, Miguel A; González-López, Santiago; Ceballos, Laura

    2013-07-01

    The purpose of this study was to determine the micro-tensile bond strength (MTBS) to dentin of seven adhesive systems (total and self-etch adhesives) after 24 h and 5,000 thermocycles. Dentin surfaces of human third molars were exposed and bonded with two total-etch adhesives (Adper Scotchbond 1 XT and XP Bond), two two-step self-etch adhesives (Adper Scotchbond SE and Filtek Silorane Adhesive System) and three one-step self-etch adhesives (G-Bond, Xeno V and Bond Force). All adhesive systems were applied following manufacturers' instructions. Composite buildups were constructed and the bonded teeth were then stored in water (24 h, 37 °C) or thermocycled (5,000 cycles) before being sectioned and submitted to MTBS test. Two-way ANOVA and subsequent comparison tests were applied at α = 0.05. Characteristic de-bonded specimens were analyzed using scanning electron microscopy (SEM). After 24 h water storage, MTBS values were highest with XP Bond, Adper Scotchbond 1 XT, Filtek Silorane Adhesive System and Adper Scotchbond SE and lowest with the one-step self-etch adhesives Bond Force, Xeno V and G-Bond. After thermocycling, MTBS values were highest with XP Bond, followed by Filtek Silorane Adhesive System, Adper Scotchbond SE and Adper Scotchbond 1 XT and lowest with the one-step self-etch adhesives Bond Force, Xeno V and G-Bond. Thermal aging induced a significant decrease in MTBS values with all adhesives tested. The resistance of resin-dentin bonds to thermal-aging degradation was material dependent. One-step self-etch adhesives obtained the lowest MTBS results after both aging treatments, and their adhesive capacity was significantly reduced after thermocycling.

  2. Effect of thermal aging on the tensile bond strength at reduced areas of seven current adhesives.

    PubMed

    Baracco, Bruno; Fuentes, M Victoria; Garrido, Miguel A; González-López, Santiago; Ceballos, Laura

    2013-07-01

    The purpose of this study was to determine the micro-tensile bond strength (MTBS) to dentin of seven adhesive systems (total and self-etch adhesives) after 24 h and 5,000 thermocycles. Dentin surfaces of human third molars were exposed and bonded with two total-etch adhesives (Adper Scotchbond 1 XT and XP Bond), two two-step self-etch adhesives (Adper Scotchbond SE and Filtek Silorane Adhesive System) and three one-step self-etch adhesives (G-Bond, Xeno V and Bond Force). All adhesive systems were applied following manufacturers' instructions. Composite buildups were constructed and the bonded teeth were then stored in water (24 h, 37 °C) or thermocycled (5,000 cycles) before being sectioned and submitted to MTBS test. Two-way ANOVA and subsequent comparison tests were applied at α = 0.05. Characteristic de-bonded specimens were analyzed using scanning electron microscopy (SEM). After 24 h water storage, MTBS values were highest with XP Bond, Adper Scotchbond 1 XT, Filtek Silorane Adhesive System and Adper Scotchbond SE and lowest with the one-step self-etch adhesives Bond Force, Xeno V and G-Bond. After thermocycling, MTBS values were highest with XP Bond, followed by Filtek Silorane Adhesive System, Adper Scotchbond SE and Adper Scotchbond 1 XT and lowest with the one-step self-etch adhesives Bond Force, Xeno V and G-Bond. Thermal aging induced a significant decrease in MTBS values with all adhesives tested. The resistance of resin-dentin bonds to thermal-aging degradation was material dependent. One-step self-etch adhesives obtained the lowest MTBS results after both aging treatments, and their adhesive capacity was significantly reduced after thermocycling. PMID:22790477

  3. Did the 18 Drinking Age Promote High School Dropout? Implications for Current Policy

    PubMed Central

    Plunk, Andrew D.; Agrawal, Arpana; Tate, William F.; Cavazos-Rehg, Patricia; Bierut, Laura J.; Grucza, Richard A.

    2015-01-01

    Objective: Disagreement exists over whether permissive minimum legal drinking age (MLDA) laws affected underage adolescents (e.g., those age 17 years with the MLDA of 18). We used MLDA changes during the 1970s and 1980s as a natural experiment to investigate how underage exposure to permissive MLDA affected high school dropout. Method: MLDA exposure was added to two data sets: (a) the 5% public use microdata samples of the 1990 and 2000 censuses (n = 3,671,075), and (b) a combined data set based on the 1991–1992 National Longitudinal Alcohol Epidemiological Survey (NLAES) and the 2001–2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC; n = 16,331). We used logistic regression to model different thresholds of MLDA on high school dropout. We also estimated models conditioned on demographic variables and familial risk of developing alcohol problems. Results: Only the MLDA of 18 predicted high school dropout. Exposure was associated with 4% and 13% higher odds of high school dropout for the census and NLAES/NESARC samples, respectively. We noted greater impact on women (5%–18%), Blacks (5%–19%), and Hispanics (6%). Self-report of parental alcohol problems was associated with 40% higher odds, which equals a 4.14-point increase in dropout rate for that population. Conclusions: The MLDA of 18 likely had a large impact on high school dropout rates, suggesting that the presence of legal-aged peers in a high school setting increased access to alcohol for younger students. Our results also suggest that policy can promote less dangerous drinking behavior even when familial risk of alcohol use disorders is high. PMID:26402348

  4. A national survey of Rett syndrome: age, clinical characteristics, current abilities, and health.

    PubMed

    Cianfaglione, Rina; Clarke, Angus; Kerr, Mike; Hastings, Richard P; Oliver, Chris; Felce, David

    2015-07-01

    As part of a wider study to investigate the behavioral phenotype of a national sample of girls and women with Rett syndrome (RTT) in comparison to a well-chosen contrast group and its relationship to parental well-being, the development, clinical severity, current abilities and health of 91 participants were analyzed in relation to diagnostic, clinical and genetic mutation categories. Early truncating mutations or large deletions were associated with greater severity. Early regression was also associated with greater severity. All three were associated with lower current abilities. Epilepsy and weight, gastrointestinal and bowel problems were common co-morbidities. Participants with classic RTT had greater health problems than those with atypical RTT. A substantial minority of respondents reported fairly frequent signs of possible pain experienced by their relative with RTT. Overall, the study provides new data on the current abilities and general health of people with RTT and adds to the evidence that the severity of the condition and variation of subsequent disability, albeit generally within the profound range, may be related to gene mutation. The presence of certain co-morbidities represents a substantial ongoing need for better health. The experience of pain requires further investigation. PMID:25820775

  5. A national survey of Rett syndrome: age, clinical characteristics, current abilities, and health.

    PubMed

    Cianfaglione, Rina; Clarke, Angus; Kerr, Mike; Hastings, Richard P; Oliver, Chris; Felce, David

    2015-07-01

    As part of a wider study to investigate the behavioral phenotype of a national sample of girls and women with Rett syndrome (RTT) in comparison to a well-chosen contrast group and its relationship to parental well-being, the development, clinical severity, current abilities and health of 91 participants were analyzed in relation to diagnostic, clinical and genetic mutation categories. Early truncating mutations or large deletions were associated with greater severity. Early regression was also associated with greater severity. All three were associated with lower current abilities. Epilepsy and weight, gastrointestinal and bowel problems were common co-morbidities. Participants with classic RTT had greater health problems than those with atypical RTT. A substantial minority of respondents reported fairly frequent signs of possible pain experienced by their relative with RTT. Overall, the study provides new data on the current abilities and general health of people with RTT and adds to the evidence that the severity of the condition and variation of subsequent disability, albeit generally within the profound range, may be related to gene mutation. The presence of certain co-morbidities represents a substantial ongoing need for better health. The experience of pain requires further investigation.

  6. Age, body mass index, current smoking history, and serum insulin-like growth factor-I levels associated with bone mineral density in middle-aged Korean men.

    PubMed

    Rhee, Eun-Jung; Oh, Ki-Won; Lee, Won-Young; Kim, Sun-Woo; Oh, Eun-Sook; Baek, Ki-Hyun; Kang, Moo-Il; Park, Cheol-Young; Choi, Moon-Gi; Yoo, Hyung-Joon; Park, Sung-Woo

    2004-01-01

    Osteoporosis is a growing health problem in women and in men. This cross-sectional study examined the association of anthropometric, lifestyle, and hormonal factors with bone mineral density (BMD) in 152 healthy Korean middle-aged men. Smoking habits and alcohol consumption were assessed by interview. Serum testosterone and insulin-like growth factor-I (IGF-I) levels were measured by radioimmunoassay, and serum growth hormone (GH) levels were measured by immunoradiometric assay. GH stimulation tests were performed after the ingestion of 500 mg of L-dopa. BMD was measured at the lumbar spine and at the femoral neck by dual-energy X-ray absorptiometry. Of the middle-aged men, 3.9% were osteoporotic and 28.3% were osteopenic at the lumbar spine site, and 5.9% were osteoporotic and 45.4% were osteopenic at the femoral neck site. Lumbar spine BMD correlated significantly with body mass index (BMI), and femoral neck BMD correlated significantly with age, BMI, and serum IGF-I levels. The lowest quartile group for serum IGF-I levels showed the lowest femoral neck BMD. Osteoporotic men by lumbar spine BMD showed significant differences from the normal BMD group in terms of BMI and smoking habits. Also, osteoporotic men by femoral neck BMD were significantly different for mean age, BMI, and serum IGF-I levels compared with the normal BMD group. On multiple regression analysis, BMI was found to be the only independent predictor of lumbar spine BMD, whereas both BMI and serum IGF-I levels were found to be the independent predictors of femoral neck BMD. Overall, 28.3%-45.4% of middle-aged Korean men were osteopenic. We suggest that higher age, a lower BMI, current smoking history, and lower serum IGF-I levels are risk factors for lower BMD in middle-aged Korean men; however, serum testosterone levels and GH secretory capacity were not found to be correlated with BMD.

  7. Prenatal factors associated with birth weight and length and current nutritional status of hospitalized children aged 4-24 months.

    PubMed

    Mariante Giesta, Juliana; Ramón da Rosa, Suélen; Moura Pessoa, Juliana Salino; Lúcia Bosa, Vera

    2015-06-01

    The objective of the present study was to investigate the associations of prenatal factors with birth weight and length, as well as current nutritional status, of children hospitalized in southern Brazil. We conducted a cross-sectional study of 300 child-mother pairs. Children were between 4 and 24 months old. They were at the inpatient unit or pediatric emergency department of the Hospital de Clínicas de Porto Alegre. Anthropometric data were collected, and a questionnaire on gestational data was answered by the children's mothers. Maternal variables of interest were: prepregnancy body mass index (BMI), gestational weight gain, smoking and/or use of alcohol, use of illicit drugs, gestational diabetes and/ or high blood pressure. Children's variables of interest were: sex, gestational age, birth weight (BW) and birth length (BL), and current anthropometric data [body mass index for age (BMI/A), height for age (H/A), and weight for age (W/A)]. The gestational weight gain and smoking were associated with BW. We also found that H/A was associated with BW and BL, W/A was associated with BW, and BMI/A was associated with BL. The gestational weight gain was associated with BL, diabetes was associated with BW and BL, and high blood pressure was associated with low height in the first two years of life. We concluded that prenatal factors may have an influence on both BW and BL, causing the birth of small and large for gestational age children, and thus affecting their growth rate during the first years of life.

  8. A brief history of cancer: age-old milestones underlying our current knowledge database.

    PubMed

    Faguet, Guy B

    2015-05-01

    This mini-review chronicles the history of cancer ranging from cancerous growths discovered in dinosaur fossils, suggestions of cancer in Ancient Egyptian papyri written in 1500-1600 BC, and the first documented case of human cancer 2,700 years ago, to contributions by pioneers beginning with Hippocrates and ending with the originators of radiation and medical oncology. Fanciful notions that soon fell into oblivion are mentioned such as Paracelsus and van Helmont substituting Galen's black bile by mysterious ens or archeus systems. Likewise, unfortunate episodes such as Virchow claiming Remak's hypotheses as his own remind us that human shortcomings can affect otherwise excellent scientists. However, age-old benchmark observations, hypotheses, and practices of historic and scientific interest are underscored, excerpts included, as precursors of recent discoveries that shaped modern medicine. Examples include: Petit's total mastectomy with excision of axillary glands for breast cancer; a now routine practice, Peyrilhe's ichorous matter a cancer-causing factor he tested for transmissibility one century before Rous confirmed the virus-cancer link, Hill's warning of the dangers of tobacco snuff; heralding today's cancer pandemic caused by smoking, Pott reporting scrotum cancer in chimney sweepers; the first proven occupational cancer, Velpeau's remarkable foresight that a yet unknown subcellular element would have to be discovered in order to define the nature of cancer; a view confirmed by cancer genetics two centuries later, ending with Röntgen and the Curies, and Gilman et al. ushering radiation (1896, 1919) and medical oncology (1942), respectively.

  9. A brief history of cancer: age-old milestones underlying our current knowledge database.

    PubMed

    Faguet, Guy B

    2015-05-01

    This mini-review chronicles the history of cancer ranging from cancerous growths discovered in dinosaur fossils, suggestions of cancer in Ancient Egyptian papyri written in 1500-1600 BC, and the first documented case of human cancer 2,700 years ago, to contributions by pioneers beginning with Hippocrates and ending with the originators of radiation and medical oncology. Fanciful notions that soon fell into oblivion are mentioned such as Paracelsus and van Helmont substituting Galen's black bile by mysterious ens or archeus systems. Likewise, unfortunate episodes such as Virchow claiming Remak's hypotheses as his own remind us that human shortcomings can affect otherwise excellent scientists. However, age-old benchmark observations, hypotheses, and practices of historic and scientific interest are underscored, excerpts included, as precursors of recent discoveries that shaped modern medicine. Examples include: Petit's total mastectomy with excision of axillary glands for breast cancer; a now routine practice, Peyrilhe's ichorous matter a cancer-causing factor he tested for transmissibility one century before Rous confirmed the virus-cancer link, Hill's warning of the dangers of tobacco snuff; heralding today's cancer pandemic caused by smoking, Pott reporting scrotum cancer in chimney sweepers; the first proven occupational cancer, Velpeau's remarkable foresight that a yet unknown subcellular element would have to be discovered in order to define the nature of cancer; a view confirmed by cancer genetics two centuries later, ending with Röntgen and the Curies, and Gilman et al. ushering radiation (1896, 1919) and medical oncology (1942), respectively. PMID:25113657

  10. Nucleotide Excision Repair in Caenorhabditis elegans

    PubMed Central

    Lans, Hannes; Vermeulen, Wim

    2011-01-01

    Nucleotide excision repair (NER) plays an essential role in many organisms across life domains to preserve and faithfully transmit DNA to the next generation. In humans, NER is essential to prevent DNA damage-induced mutation accumulation and cell death leading to cancer and aging. NER is a versatile DNA repair pathway that repairs many types of DNA damage which distort the DNA helix, such as those induced by solar UV light. A detailed molecular model of the NER pathway has emerged from in vitro and live cell experiments, particularly using model systems such as bacteria, yeast, and mammalian cell cultures. In recent years, the versatility of the nematode C. elegans to study DNA damage response (DDR) mechanisms including NER has become increasingly clear. In particular, C. elegans seems to be a convenient tool to study NER during the UV response in vivo, to analyze this process in the context of a developing and multicellular organism, and to perform genetic screening. Here, we will discuss current knowledge gained from the use of C. elegans to study NER and the response to UV-induced DNA damage. PMID:22091407

  11. Functional repair with neural stem cells.

    PubMed

    Sinden, J D; Stroemer, P; Grigoryan, G; Patel, S; French, S J; Hodges, H

    2000-01-01

    Approval to commence phase I/II clinical trials with neural stem cells requires proof of concept in well-accepted animal models of human neurological disease or injury. We initially showed that the conditionally immortal MHP36 line of hippocampal origin (derived from the H-2Kb-tsA58 transgenic mouse) was effective in repopulating CA1 neurons in models of global ischaemia and repairing cognitive function, and have now shown that this line is multifunctional. MHP36 cells are effective in restoring spatial memory deficits in rats after excitotoxic lesions of the cholinergic projections to cortex and hippocampus and in rats showing cognitive impairments due to normal ageing. Moreover, grafts of MHP36 cells are effective in reversing sensory and motor deficits and reducing lesion volume as a consequence of occlusion of the middle cerebral artery, the major cause of stroke. In contrast, MHP36 cell grafts were unable to repair motor asymmetries in rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal dopamine system, the prototype rodent model of Parkinson's disease. These data show that conditionally immortal neuroepithelial stem cells are multifunctional, being able to repair diverse types of brain damage. However, there are limitations to this multifunctionality, suggesting that lines from different regions of the developing brain will be required to treat different brain diseases. ReNeuron is currently developing human neuroepithelial stem cell lines from different brain regions and with similar reparative properties to our murine lines. PMID:11131543

  12. Current status of vascular endothelial growth factor inhibition in age-related macular degeneration.

    PubMed

    Mousa, Shaker A; Mousa, Shaymaa S

    2010-06-01

    Angiogenesis, the process by which new vessels are created from pre-existing vasculature, has become the subject of intense research in recent years. Increased rates of angiogenesis are associated with several disease states, including cancer, age-related macular degeneration (AMD), psoriasis, rheumatoid arthritis, and diabetic retinopathy. Vascular endothelial growth factor (VEGF) is an important modulator of angiogenesis, and has been implicated in the pathology of a number of conditions, including AMD, diabetic retinopathy, and cancer. AMD is a progressive disease of the macula and the third major cause of blindness worldwide. If not treated appropriately, AMD can progress to involve both eyes. Until recently, the treatment options for AMD have been limited, with photodynamic therapy (PDT) the mainstay of treatment. Although PDT is effective at slowing disease progression, it rarely results in improved vision. Several therapies have been or are now being developed for neovascular AMD, with the goal of inhibiting VEGF. These VEGF inhibitors include the RNA aptamer pegaptanib, partial and full-length antibodies ranibizumab and bevacizumab, the VEGF receptor decoy aflibercept, small interfering RNA-based therapies bevasiranib and AGN 211745, sirolimus, and tyrosine kinase inhibitors, including vatalanib, pazopanib, TG 100801, TG 101095, AG 013958, and AL 39324. At present, established therapies have met with great success in reducing the vision loss associated with neovascular AMD, whereas those still under investigation offer the potential for further advances. In AMD patients, these therapies slow the rate of vision loss and in some cases increase visual acuity. Although VEGF-inhibitor therapies are a milestone in the treatment of these disease states, several concerns need to be addressed before their impact can be fully realized. PMID:20210371

  13. Interacting effects of age, density, and weather on survival and current reproduction for a large mammal

    PubMed Central

    Richard, Emmanuelle; Simpson, Steven E; Medill, Sarah A; McLoughlin, Philip D

    2014-01-01

    Individual-based study of natural populations allows for accurate and precise estimation of fitness components and the extent to which they might vary with ecological conditions. By tracking the fates of all 701 horses known to have lived on Sable Island, Canada, from 2009 to 2013 (where there is no predation, human interference, or interspecific competition for food), we present a detailed analysis of structured population dynamics with focus on interacting effects of intraspecific competition and weather on reproduction and survival. Annual survival of adult females (0.866 ± 0.107 [ ± SE]) was lower than that of 3-year-olds (0.955 ± 0.051), although annual fecundity (producing a foal in a year that was observed during our census) was higher in adults (0.616 ± 0.023) compared to 3-year-olds (0.402 ± 0.054). Milder winters and lower densities during gestation increased fecundity. Density negatively impacted survival for all age and sex categories; however, highest adult female survival was observed during high-density years coupled with a harsh winter, the result expected if pregnancy loss during winter or loss of foals in spring improved survival. Three-year-old females, which reproduced at lower rates, experienced higher survival than adults. Our results contrast with a previous study of feral horses that suggested recently feral ungulates might be artificially selected to reproduce even when costs to survival are high. In part, this may be because of the comparably long history of feralization (250 years; at least 25 generations) for Sable Island horses. PMID:25614799

  14. Branch age and light conditions determine leaf-area-specific conductivity in current shoots of Scots pine.

    PubMed

    Grönlund, Leila; Hölttä, Teemu; Mäkelä, Annikki

    2016-08-01

    Shoot size and other shoot properties more or less follow the availability of light, but there is also evidence that the topological position in a tree crown has an influence on shoot development. Whether the hydraulic properties of new shoots are more regulated by the light or the position affects the shoot acclimation to changing light conditions and thereby to changing evaporative demand. We investigated the leaf-area-specific conductivity (and its components sapwood-specific conductivity and Huber value) of the current-year shoots of Scots pine (Pinus sylvestris L.) in relation to light environment and topological position in three different tree classes. The light environment was quantified in terms of simulated transpiration and the topological position was quantified by parent branch age. Sample shoot measurements included length, basal and tip diameter, hydraulic conductivity of the shoot, tracheid area and density, and specific leaf area. In our results, the leaf-area-specific conductivity of new shoots declined with parent branch age and increased with simulated transpiration rate of the shoot. The relation to transpiration demand seemed more decisive, since it gave higher R(2) values than branch age and explained the differences between the tree classes. The trend of leaf-area-specific conductivity with simulated transpiration was closely related to Huber value, whereas the trend of leaf-area-specific conductivity with parent branch age was related to a similar trend in sapwood-specific conductivity. PMID:27217528

  15. Branch age and light conditions determine leaf-area-specific conductivity in current shoots of Scots pine.

    PubMed

    Grönlund, Leila; Hölttä, Teemu; Mäkelä, Annikki

    2016-08-01

    Shoot size and other shoot properties more or less follow the availability of light, but there is also evidence that the topological position in a tree crown has an influence on shoot development. Whether the hydraulic properties of new shoots are more regulated by the light or the position affects the shoot acclimation to changing light conditions and thereby to changing evaporative demand. We investigated the leaf-area-specific conductivity (and its components sapwood-specific conductivity and Huber value) of the current-year shoots of Scots pine (Pinus sylvestris L.) in relation to light environment and topological position in three different tree classes. The light environment was quantified in terms of simulated transpiration and the topological position was quantified by parent branch age. Sample shoot measurements included length, basal and tip diameter, hydraulic conductivity of the shoot, tracheid area and density, and specific leaf area. In our results, the leaf-area-specific conductivity of new shoots declined with parent branch age and increased with simulated transpiration rate of the shoot. The relation to transpiration demand seemed more decisive, since it gave higher R(2) values than branch age and explained the differences between the tree classes. The trend of leaf-area-specific conductivity with simulated transpiration was closely related to Huber value, whereas the trend of leaf-area-specific conductivity with parent branch age was related to a similar trend in sapwood-specific conductivity.

  16. The golden age of minimally invasive cardiothoracic surgery: current and future perspectives.

    PubMed

    Iribarne, Alexander; Easterwood, Rachel; Chan, Edward Y H; Yang, Jonathan; Soni, Lori; Russo, Mark J; Smith, Craig R; Argenziano, Michael

    2011-05-01

    Over the past decade, minimally invasive cardiothoracic surgery (MICS) has grown in popularity. This growth has been driven, in part, by a desire to translate many of the observed benefits of minimal access surgery, such as decreased pain and reduced surgical trauma, to the cardiac surgical arena. Initial enthusiasm for MICS was tempered by concerns over reduced surgical exposure in highly complex operations and the potential for prolonged operative times and patient safety. With innovations in perfusion techniques, refinement of transthoracic echocardiography and the development of specialized surgical instruments and robotic technology, cardiac surgery was provided with the necessary tools to progress to less invasive approaches. However, much of the early literature on MICS focused on technical reports or small case series. The safety and feasibility of MICS have been demonstrated, yet questions remain regarding the relative efficacy of MICS over traditional sternotomy approaches. Recently, there has been a growth in the body of published literature on MICS long-term outcomes, with most reports suggesting that major cardiac operations that have traditionally been performed through a median sternotomy can be performed through a variety of minimally invasive approaches with equivalent safety and durability. In this article, we examine the technological advancements that have made MICS possible and provide an update on the major areas of cardiac surgery where MICS has demonstrated the most growth, with consideration of current and future directions.

  17. Aging Reduces L-Type Calcium Channel Current and the Vasodilatory Response of Small Mesenteric Arteries to Calcium Channel Blockers

    PubMed Central

    Albarwani, Sulayma A.; Mansour, Fathi; Khan, Abdul Aleem; Al-Lawati, Intisar; Al-Kaabi, Abdulla; Al-Busaidi, Al-Manar; Al-Hadhrami, Safa; Al-Husseini, Isehaq; Al-Siyabi, Sultan; Tanira, Musbah O.

    2016-01-01

    Calcium channel blockers (CCBs) are widely used to treat cardiovascular disease (CVD) including hypertension. As aging is an independent risk factor for CVD, the use of CCBs increases with increasing age. Hence, this study was designed to evaluate the effect of aging on the sensitivity of small mesenteric arteries to L-type voltage-gated calcium channel (LTCC) blockers and also to investigate whether there was a concomitant change in calcium current density. Third order mesenteric arteries from male F344 rats, aged 2.5–3 months (young) and 22–26 months (old) were mounted on wire myograph to measure the tension during isometric contraction. Arteries were contracted with 100 mM KCl and were then relaxed in a cumulative concentration-response dependent manner with nifedipine (0.1 nM–1 μM), verapamil (0.1 nM–10 μM), or diltiazem (0.1 nM–10 μM). Relaxation-concentration response curves produced by cumulative concentrations of three different CCBs in arteries of old rats were shifted to the right with statistically significant IC50s. pIC50 ± s.e.m: (8.37 ± 0.06 vs. 8.04 ± 0.05, 7.40 ± 0.07 vs. 6.81 ± 0.04, and 6.58 ± 0.07 vs. 6.34 ± 0.06) in young vs. old. It was observed that the maximal contractions induced by phenylephrine and reversed by sodium nitroprusside were not different between young and old groups. However, Bay K 8644 (1 μM) increased resting tension by 23 ± 4.8% in young arteries and 4.7 ± 1.6% in old arteries. LTCC current density were also significantly lower in old arteries (−2.77 ± 0.45 pA/pF) compared to young arteries (−4.5 ± 0.40 pA/pF); with similar steady-state activation and inactivation curves. Parallel to this reduction, the expression of Cav1.2 protein was reduced by 57 ± 5% in arteries from old rats compared to those from young rats. In conclusion, our results suggest that aging reduces the response of small mesenteric arteries to the vasodilatory effect of the CCBs and this may be due to, at least in part, reduced

  18. Brain aneurysm repair

    MedlinePlus

    ... aneurysm repair; Dissecting aneurysm repair; Endovascular aneurysm repair - brain; Subarachnoid hemorrhage - aneurysm ... Your scalp, skull, and the coverings of the brain are opened. A metal clip is placed at ...

  19. Current Treatment Limitations in Age-Related Macular Degeneration and Future Approaches Based on Cell Therapy and Tissue Engineering

    PubMed Central

    Fernández-Robredo, P.; Sancho, A.; Johnen, S.; Recalde, S.; Gama, N.; Thumann, G.; Groll, J.; García-Layana, A.

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. With an ageing population, it is anticipated that the number of AMD cases will increase dramatically, making a solution to this debilitating disease an urgent requirement for the socioeconomic future of the European Union and worldwide. The present paper reviews the limitations of the current therapies as well as the socioeconomic impact of the AMD. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options show several side effects, are of high cost, and only treat the consequence, not the cause of the pathology. For that reason, many options involving cell therapy mainly based on retinal and iris pigment epithelium cells as well as stem cells are being tested. Moreover, tissue engineering strategies to design and manufacture scaffolds to mimic Bruch's membrane are very diverse and under investigation. Both alternative therapies are aimed to prevent and/or cure AMD and are reviewed herein. PMID:24672707

  20. Current treatment limitations in age-related macular degeneration and future approaches based on cell therapy and tissue engineering.

    PubMed

    Fernández-Robredo, P; Sancho, A; Johnen, S; Recalde, S; Gama, N; Thumann, G; Groll, J; García-Layana, A

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. With an ageing population, it is anticipated that the number of AMD cases will increase dramatically, making a solution to this debilitating disease an urgent requirement for the socioeconomic future of the European Union and worldwide. The present paper reviews the limitations of the current therapies as well as the socioeconomic impact of the AMD. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options show several side effects, are of high cost, and only treat the consequence, not the cause of the pathology. For that reason, many options involving cell therapy mainly based on retinal and iris pigment epithelium cells as well as stem cells are being tested. Moreover, tissue engineering strategies to design and manufacture scaffolds to mimic Bruch's membrane are very diverse and under investigation. Both alternative therapies are aimed to prevent and/or cure AMD and are reviewed herein. PMID:24672707

  1. College women who had sexual intercourse when they were underage minors (13-15): age of their male partners, relation to current adjustment, and statutory rape implications.

    PubMed

    Leitenberg, Harold; Saltzman, Heidi

    2003-04-01

    In a survey of 1,439 female college students, 24% reported that they had what they considered consensual sexual intercourse between ages 13 and 15 (2% at age 13, 7% at age 14, and 15% at age 15). Contrary to the impression left by studies of teenage mothers, the majority of their male sexual partners were not substantially older than them but instead were more typically "somewhat older" (2-4 years apart) or similar aged (less than 2 years apart). The percentage of "much older" partners (5 or more years older) was 31% for those who had intercourse at age 13, 17% for those who had intercourse at age 14, and 13% for those who had intercourse at age 15. Women who had intercourse at age 13 endorsed more current symptoms of psychological distress than those who first had intercourse at age 14 or 15. There were no significant differences between the groups in current levels of sexual satisfaction. Partner's age difference was not significantly associated with current levels of either psychological distress or sexual satisfaction. The implications of these results were discussed in light of recent calls in the United States for more strict and rigorous enforcement of statutory rape laws.

  2. [Mechanisms of repair after renal injury].

    PubMed

    Menè, P; Polci, R; Festuccia, F

    2003-01-01

    Recovery from kidney injury through repair mechanisms often linked to inflammation is conditioned by nature and severity of the insult. In the assessment of kidney repair, functional recovery should be kept distinct from structural repair: compensatory hypertrophy/function of intact nephrons often masks the inability of the kidney to heal or replace damaged structures. The mechanisms of repair reflect three degrees of injury, differently handled by the kidney. First, repair of DNA damage is accomplished through proofreading DNA polymerases, along with other controls for sequence misalignment / nucleotide replacement. If DNA cannot be repaired, cells carrying mutation(s) are disposed of through apoptosis, which is also critical to clearing damaged kidney cells and infiltrating leukocytes in acute and chronic ischemic, immunological, or chemical damage. A second mechanism of repair is linked to proliferation of surviving cells. At least 5 types of reparative proliferation are known to occur, some of which implicate stem cell immigration from distant reservoirs, followed by in situ differentiation. A third mode of repair could be referred to as structural repair, indeed limited in the human kidney by the absence of postnatal nephrogenesis. Recovery from acute tubular necrosis involves remodelling of the proximal tubule, with a strict requirement for integrity of the basement membrane. Contrary to the current dogma that only acute injury can be repaired, whereas chronic damage leads to irreversible loss of nephrons, evidence is emerging that some degree of renal remodelling occurs even in chronic renal disease, despite the occurrence of stabilized structural changes.

  3. Book Repair Manual.

    ERIC Educational Resources Information Center

    Milevski, Robert J.

    1995-01-01

    This book repair manual developed for the Illinois Cooperative Conservation Program includes book structure and book problems, book repair procedures for 4 specific problems, a description of adhesive bindings, a glossary, an annotated list of 11 additional readings, book repair supplies and suppliers, and specifications for book repair kits. (LRW)

  4. Current pattern of Ponderal Indices of term small-for-gestational age in a population of Nigerian babies

    PubMed Central

    2013-01-01

    Background Small-for-gestational age (SGA) newborns constitute a special group of neonates who may have suffered varying degrees of intrauterine insults and deprivation. Variations in birth weight, length and Ponderal Index (PI) depend on the type and degree of intrauterine insults the babies were exposed to. The objective of the study was to determine the current prevalence of term SGA births in a Nigerian Tertiary Hospital and the current pattern of Ponderal Indices among term SGA in a population of Nigerian babies. Methods Subjects comprised of consecutive term singleton mother-baby pairs in the first 24 hours of life. It was a cross sectional study. The anthropometric parameters of each baby were recorded and the PI was also determined. Results Out of 1,052 live births during the study period (September to December, 2009), 825 were term, singleton babies. Five hundred and eight-one babies (70.4%) fall into the upper socio-economic classes 1 and II, 193 (23.4%) in the middle class and 51 (6.2%) were of the lower classes IV and V. None of the mothers indicated ingestion of alcohol or smoking of cigarette. Fifty-nine babies (7.2%) were small-for gestational age (SGA). Of the 59 SGA subjects, 26 (44.1%) were symmetrical SGA while 33 (55.9%) were asymmetrical SGA. There was no significant sex or socioeconomic predilection for either symmetrical or asymmetrical growth (p = 0.59, 0.73 respectively). Conclusion The findings showed that proportionality in SGA fetuses is a continuum, with the PI depending on the duration of intrauterine insult and the extent of its effects on weight and length before delivery. PMID:23875695

  5. An experimental double-blind irradiation study of a novel topical product (TPF 50) compared to other topical products with DNA repair enzymes, antioxidants, and growth factors with sunscreens: implications for preventing skin aging and cancer.

    PubMed

    Emanuele, Enzo; Spencer, James M; Braun, Martin

    2014-03-01

    The exposure to ultraviolet radiation (UVR) is a major risk factor for skin aging and the development of non-melanoma skin cancer (NMSC). Although traditional sunscreens remain the mainstay for the prevention of UVR-induced skin damage, they cannot ensure a complete protection against the whole spectrum of molecular lesions associated with UVR exposure. The formation of helix-distorting photoproducts such as cyclobutane pyrimidine dimers (CPD), as well as oxidative damage to DNA bases, including the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8OHdG) are among the key DNA lesions associated with photoaging and tumorigenesis. Besides DNA lesions, UVR-induced formation of free radicals can result in protein carbonylation (PC), a major form of irreversible protein damage that inactivates their biological function. This study compares a complex novel topical product (TPF50) consisting of three actives, ie, 1) traditional physical sunscreens (SPF 50), 2) a liposome-encapsulated DNA repair enzymes complex (photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]), and 3) a potent antioxidant complex (carnosine, arazine, ergothionine) to existing products. Specifically, we assessed the ability of TFP50 vs those of DNA repair and antioxidant and growth factor topical products used with SPF 50 sunscreens in preventing CPD, 8OHdG, and PC formation in human skin biopsies after experimental irradiations. In head-to-head comparison studies, TPF50 showed the best efficacy in reducing all of the three molecular markers. The results indicated that the three TPF50 components had a synergistic effect in reducing CPD and PC, but not 8OHdG. Taken together, our results indicate that TPF50 improves the genomic and proteomic integrity of skin cells after repeated exposure to UVR, ultimately reducing the risk of skin aging and NMSC.

  6. Does transcranial direct current stimulation enhance cognitive and motor functions in the ageing brain? A systematic review and meta- analysis.

    PubMed

    Summers, Jeffery J; Kang, Nyeonju; Cauraugh, James H

    2016-01-01

    The use of transcranial direct current stimulation (tDCS) to enhance cognitive and motor functions has enjoyed a massive increase in popularity. Modifying neuroplasticity via non-invasive cortical stimulation has enormous potential to slow or even reverse declines in functions associated with ageing. The current meta-analysis evaluated the effects of tDCS on cognitive and motor performance in healthy older adults. Of the 81 studies identified, 25 qualified for inclusion. A random effects model meta-analysis revealed a significant overall standardized mean difference equal to 0.53 (SE=0.09; medium heterogeneity: I(2)=57.08%; and high fail-safe: N=448). Five analyses on moderator variables indicated significant tDCS beneficial effects: (a) on both cognitive and motor task performances, (b) across a wide-range of cognitive tasks, (c) on specific brain areas, (d) stimulation offline (before) or online (during) the cognitive and motor tasks. Although the meta-analysis revealed robust support for enhancing both cognitive and motor performance, we outline a number of caveats on the use of tDCS.

  7. Development of a Remote External Repair Tool for Damaged or Defective Polyethylene Pipe

    SciTech Connect

    Kenneth H. Green; Willie E. Rochefort; Nick Wannenmacher; John A. Clark; Kevin Harris

    2006-06-30

    Current procedures for repairing polyethylene (PE) gas pipe require excavation, isolation, and removal of the damaged section of pipe followed by fusing a new section of pipe into place. These techniques are costly and very disruptive. An alternative repair method was developed at Timberline Tool with support from Oregon State University (OSU) and funding by the U. S. Department of Energy National Energy Technology Laboratory (DOE/NETL). This project was undertaken to design, develop and test a tool and method for repairing damaged PE pipe remotely and externally in situ without squeezing off the flow of gas, eliminating the need for large-scale excavations. Through an iterative design and development approach, a final engineered prototype was developed that utilizes a unique thermo-chemical and mechanical process to apply a permanent external patch to repair small nicks, gouges and punctures under line pressure. The project identified several technical challenges during the design and development process. The repair tool must be capable of being installed under live conditions and operate in an 18-inch keyhole. This would eliminate the need for extensive excavations thus reducing the cost of the repair. Initially, the tool must be able to control the leak by encapsulating the pipe and apply slight pressure at the site of damage. Finally, the repair method must be permanent at typical operating pressures. The overall results of the project have established a permanent external repair method for use on damaged PE gas pipe in a safe and cost-effective manner. The engineered prototype was subjected to comprehensive testing and evaluation to validate the performance. Using the new repair tool, samples of 4-inch PE pipe with simulated damage were successfully repaired under line pressure to the satisfaction of DOE/NETL and the following natural gas companies: Northwest Natural; Sempra Energy, Southwest Gas Corporation, Questar, and Nicor. However, initial results of

  8. DNA Triplet Repeat Expansion and Mismatch Repair

    PubMed Central

    Iyer, Ravi R.; Pluciennik, Anna; Napierala, Marek; Wells, Robert D.

    2016-01-01

    DNA mismatch repair is a conserved antimutagenic pathway that maintains genomic stability through rectification of DNA replication errors and attenuation of chromosomal rearrangements. Paradoxically, mutagenic action of mismatch repair has been implicated as a cause of triplet repeat expansions that cause neurological diseases such as Huntington disease and myotonic dystrophy. This mutagenic process requires the mismatch recognition factor MutSβ and the MutLα (and/or possibly MutLγ) endonuclease, and is thought to be triggered by the transient formation of unusual DNA structures within the expanded triplet repeat element. This review summarizes the current knowledge of DNA mismatch repair involvement in triplet repeat expansion, which encompasses in vitro biochemical findings, cellular studies, and various in vivo transgenic animal model experiments. We present current mechanistic hypotheses regarding mismatch repair protein function in mediating triplet repeat expansions and discuss potential therapeutic approaches targeting the mismatch repair pathway. PMID:25580529

  9. [Cell therapy in cartilage repair: cellular and molecular bases].

    PubMed

    Corvol, Marie-Thérèse; Tahiri, Khadija; Montembault, Alexandra; Daumard, Alain; Savouret, Jean-François; Rannou, François

    2008-01-01

    The destruction of articular cartilage represents the outcome of most inflammatory and degenerative rheumatic diseases and leads to severe disability. Articular cartilage being unable to repair spontaneously, alterations of the joint surface often results in end-stage osteoarthritis, requiring surgical intervention and total joint replacement. This makes damaged tissues repair a major challenge in our aging society. Cartilage harbors only one cell type, the chondrocyte, which synthesizes and secretes specific matrix proteins such as type II collagen and high molecular weight proteoglycans. Matrix proteins are responsible for the conservation of the chondrocyte phenotype and the maintenance of the mechanical functions of cartilage. Development of therapeutic strategies for cartilage repair should thus comprise not only the replacement of lost cartilage cells but also that of extracellular matrix with cartilage-like properties. Different protocols are under investigation. The most commonly employed materials include transplantation of autologous osteochondral tissue. More recently, cell-based therapies using autologous mature chondrocytes or pre-chondrogenic stem cells have drawn particular attention. Tissue-engineering procedures represent the actual trend in cartilage repair. This approach combines biodegradable polymeric three-dimensional matrixes and isolated prechondrogenic stem cells. The cells are seeded within the biocompatible matrix and then implanted into the joint. Numerous non-degradable and degradable polymers, which efficiently "mimic" the natural surroundings of cartilage cells, are currently under investigation.

  10. Pipeline incidents and emergency repair in the North Sea

    SciTech Connect

    Wood, G.D.

    1988-12-01

    The failures of submarine pipelines in the North Sea, and the response of pipeline operators are first discussed. Against this background, the methods currently available for submarine pipeline repairs are reviewed. The Emergency Pipeline Repair Services available are described, and some future developments in the field of submarine pipeline repair are briefly outlined.

  11. Proximal Rectus Femoris Avulsion Repair.

    PubMed

    Dean, Chase S; Arbeloa-Gutierrez, Lucas; Chahla, Jorge; Pascual-Garrido, Cecilia

    2016-06-01

    Proximal rectus femoris tendon avulsions are rare and occur mostly in male athletes. Currently, the standard of care for complete tendinous avulsions of the direct arm of the rectus femoris is nonoperative treatment. However, surgical repair may be considered in high-level athletes who have a high demand for repetitive hip flexion performed in an explosive manner or in patients in whom nonoperative treatment has failed. The purpose of this technical note is to describe the method for surgical repair of the proximal direct arm of the rectus femoris to its origin at the anterior inferior iliac spine using suture anchors. PMID:27656376

  12. Rapid road repair vehicle

    DOEpatents

    Mara, L.M.

    1998-05-05

    Disclosed is a rapid road repair vehicle capable of moving over a surface to be repaired at near normal posted traffic speeds to scan for and find at the high rate of speed, imperfections in the pavement surface, prepare the surface imperfection for repair by air pressure and vacuum cleaning, applying a correct amount of the correct patching material to effect the repair, smooth the resulting repaired surface, and catalog the location and quality of the repairs for maintenance records of the road surface. The rapid road repair vehicle can repair surface imperfections at lower cost, improved quality, at a higher rate of speed than was not heretofor possible, with significantly reduced exposure to safety and health hazards associated with this kind of road repair activities in the past. 2 figs.

  13. Rapid road repair vehicle

    DOEpatents

    Mara, Leo M.

    1998-01-01

    Disclosed is a rapid road repair vehicle capable of moving over a surface to be repaired at near normal posted traffic speeds to scan for and find an the high rate of speed, imperfections in the pavement surface, prepare the surface imperfection for repair by air pressure and vacuum cleaning, applying a correct amount of the correct patching material to effect the repair, smooth the resulting repaired surface, and catalog the location and quality of the repairs for maintenance records of the road surface. The rapid road repair vehicle can repair surface imperfections at lower cost, improved quality, at a higher rate of speed than was was heretofor possible, with significantly reduced exposure to safety and health hazards associated with this kind of road repair activities in the past.

  14. Shear Bond Strength of Repaired Composites Using Surface Treatments and Repair Materials: An In vitro Study

    PubMed Central

    Hemadri, M; Saritha, G; Rajasekhar, V; Pachlag, K Amit; Purushotham, R; Reddy, Veera Kishore Kumar

    2014-01-01

    Background: Enhancement of bond strength between new and old composite usually requires increased surface roughness of old composite to promote mechanical interlocking and subsequent coating with bonding agents to improve surface wetting and chemical bonding. So this study was carried out to evaluate and compare the effects of different surface treatments and repair materials on the shear bond strength (SBS) of composite repairs The mode of failure of repaired composites whether cohesive or adhesive was also evaluated. Materials and Methods: The substrates for 60 composite specimens were fabricated and aged with water treatment and subjected to various surface treatments. The surface treatment regimens used in the study were: No surface treatment, abraded with diamond bur, air abraded (sandblasted) with 50 µ aluminum oxide particles. Specimens were then repaired with fresh composite using either Clearfil™ repair or all-bond two adhesive systems. Specimens were water stored, thermocycled and tested for SBS using universal testing machine. Fractured specimens were then examined under stereomicroscope to determine the mode of failure. Results: It was clearly showed that surface roughening of the aged composite substrate with air abrasion, followed by the application of Clearfil™ repair adhesive system (Group IIIa) yielded the highest repair bond strength (32.3 ± 2.2 MPa). Conclusion: Surface treatment with air abrasion followed by bonding with Clearfil™ repair adhesive system can be attempted clinically for the repair of composite restorations. PMID:25628478

  15. Integrated Electrical Wire Insulation Repair System

    NASA Technical Reports Server (NTRS)

    Williams, Martha; Jolley, Scott; Gibson, Tracy; Parks, Steven

    2013-01-01

    An integrated system tool will allow a technician to easily and quickly repair damaged high-performance electrical wire insulation in the field. Low-melt polyimides have been developed that can be processed into thin films that work well in the repair of damaged polyimide or fluoropolymer insulated electrical wiring. Such thin films can be used in wire insulation repairs by affixing a film of this low-melt polyimide to the damaged wire, and heating the film to effect melting, flow, and cure of the film. The resulting repair is robust, lightweight, and small in volume. The heating of this repair film is accomplished with the use of a common electrical soldering tool that has been modified with a special head or tip that can accommodate the size of wire being repaired. This repair method can furthermore be simplified for the repair technician by providing replaceable or disposable soldering tool heads that have repair film already "loaded" and ready for use. The soldering tool heating device can also be equipped with a battery power supply that will allow its use in areas where plug-in current is not available

  16. DNA Mismatch Repair

    PubMed Central

    MARINUS, M. G.

    2014-01-01

    DNA mismatch repair functions to correct replication errors in newly synthesized DNA and to prevent recombination between related, but not identical (homeologous), DNA sequences. The mechanism of mismatch repair is best understood in Escherichia coli and is the main focus of this review. The early genetic studies of mismatch repair are described as a basis for the subsequent biochemical characterization of the system. The effects of mismatch repair on homologous and homeologous recombination are described. The relationship of mismatch repair to cell toxicity induced by various drugs is included. The VSP (Very Short Patch) repair system is described in detail. PMID:26442827

  17. Dorsal variant blister aneurysm repair.

    PubMed

    Couldwell, William T; Chamoun, Roukoz

    2012-01-01

    Dorsal variant proximal carotid blister aneurysms are treacherous lesions to manage. It is important to recognize this variant on preoperative angiographic imaging, in anticipation of surgical strategies for their treatment. Strategies include trapping the involved segment and revascularization if necessary. Other options include repair of the aneurysm rupture site directly. Given that these are not true berry aneurysms, repair of the rupture site involves wrapping or clip-grafting techniques. The case presented here was a young woman with a subarachnoid hemorrhage from a ruptured dorsal variant blister aneurysm. The technique used is demonstrated in the video and is a modified clip-wrap technique using woven polyester graft material. The patient was given aspirin preoperatively as preparation for the clip-wrap technique. It is the authors' current protocol to attempt a direct repair with clip-wrapping and leaving artery sacrifice with or without bypass as a salvage therapy if direct repair is not possible. Assessment of vessel patency after repair is performed by intraoperative Doppler and indocyanine green angiography. Intraoperative somatosensory and motor evoked potential monitoring is performed in all cases. The video can be found here: http://youtu.be/crUreWGQdGo.

  18. AGING & HEALTH Expectations About Future Use Of Long-Term Services And Supports Vary By CurrentLiving Arrangement

    PubMed Central

    Henning-Smith, Carrie; Shippee, Tetyana

    2014-01-01

    Most Americans know little about options for long-term services and supports and underestimate their likely future needs for such assistance. Using data from the 2012 National Health Interview Survey, we examined expectations about future use of long-term services and supports among adults ages 40–65 and how these expectations varied by current living arrangement. We found differences by living arrangement in expectations about both future need for long-term services and supports and who would provide such care if needed. Respondents living with minor children were the least likely to expect to need long-term services and supports and to require paid care if the need arose. In contrast, respondents living alone were the most likely to expect that it was “very likely” that they would need long-term services and supports and to rely on paid care. Overall, we found a disconnect between expectations of use and likely future reality: 60 percent of respondents believed that they were unlikely to need long-term services and supports in the future, whereas the evidence suggests that nearly 70 percent of older adults will need them at some point. These findings both underscore the need for programs that encourage people to plan for long-term services and supports and indicate that information about living arrangements can be useful in developing and targeting such programs. PMID:25561642

  19. Study of the adhesive properties versus stability/aging of hernia repair meshes after deposition of RF activated plasma polymerized acrylic acid coating.

    PubMed

    Rivolo, Paola; Nisticò, Roberto; Barone, Fabrizio; Faga, Maria Giulia; Duraccio, Donatella; Martorana, Selanna; Ricciardi, Serena; Magnacca, Giuliana

    2016-08-01

    In order to confer adhesive properties to commercial polypropylene (PP) meshes, a surface plasma-induced deposition of poly-(acrylic acid) (PPAA) is performed. Once biomaterials were functionalized, different post-deposition treatments (i.e. water washing and/or thermal treatments) were investigated with the aim of monitoring the coating degradation (and therefore the loss of adhesion) after 3months of aging in both humid/oxidant (air) and inert (nitrogen) atmospheres. A wide physicochemical characterization was carried out in order to evaluate the functionalization effectiveness and the adhesive coating homogeneity by means of static water drop shape analysis and several spectroscopies (namely, FTIR, UV-Visible and X-ray Photoemission Spectroscopy). The modification of the adhesion properties after post-deposition treatments as well as aging under different storage atmospheres were investigated by means of Atomic Force Microscopy (AFM) used in Force/Distance (F/D) mode. This technique confirms itself as a powerful tool for unveiling the surface adhesion capacity as well as the homogeneity of the functional coatings along the fibers. Results obtained evidenced that post-deposition treatments are mandatory in order to remove all oligomers produced during the plasma-treatment, whereas aging tests evidenced that these devices can be simply stored in presence of air for at least three months without a meaningful degradation of the original properties. PMID:27157754

  20. Study of the adhesive properties versus stability/aging of hernia repair meshes after deposition of RF activated plasma polymerized acrylic acid coating.

    PubMed

    Rivolo, Paola; Nisticò, Roberto; Barone, Fabrizio; Faga, Maria Giulia; Duraccio, Donatella; Martorana, Selanna; Ricciardi, Serena; Magnacca, Giuliana

    2016-08-01

    In order to confer adhesive properties to commercial polypropylene (PP) meshes, a surface plasma-induced deposition of poly-(acrylic acid) (PPAA) is performed. Once biomaterials were functionalized, different post-deposition treatments (i.e. water washing and/or thermal treatments) were investigated with the aim of monitoring the coating degradation (and therefore the loss of adhesion) after 3months of aging in both humid/oxidant (air) and inert (nitrogen) atmospheres. A wide physicochemical characterization was carried out in order to evaluate the functionalization effectiveness and the adhesive coating homogeneity by means of static water drop shape analysis and several spectroscopies (namely, FTIR, UV-Visible and X-ray Photoemission Spectroscopy). The modification of the adhesion properties after post-deposition treatments as well as aging under different storage atmospheres were investigated by means of Atomic Force Microscopy (AFM) used in Force/Distance (F/D) mode. This technique confirms itself as a powerful tool for unveiling the surface adhesion capacity as well as the homogeneity of the functional coatings along the fibers. Results obtained evidenced that post-deposition treatments are mandatory in order to remove all oligomers produced during the plasma-treatment, whereas aging tests evidenced that these devices can be simply stored in presence of air for at least three months without a meaningful degradation of the original properties.

  1. [Stress and optimal ageing].

    PubMed

    Gogol, Manfred

    2015-08-01

    Stress is a stimulus or incident which has an exogenic or endogenic influence on an organism and leads to a biological and/or psychological adaptation from the organism by adaptation. Stressors can be differentiated by the temporal impact (e.g. acute, chronic or acute on chronic), strength and quality. The consequences of stress exposure and adaptation can be measured at the cellular level and as (sub) clinical manifestations, where this process can be biologically seen as a continuum. Over the course of life there is an accumulation of stress incidents resulting in a diminution of the capability for adaptation and repair mechanisms. By means of various interventions it is possible to improve the individual capability for adaptation but it is not currently definitively possible to disentangle alterations due to ageing and the development of diseases. As a consequence the term "healthy ageing" should be replaced by the concept of "optimal ageing". PMID:26208575

  2. Arthroscopic biceps tenodesis compared with repair of isolated type II SLAP lesions in patients older than 35 years.

    PubMed

    Denard, Patrick J; Lädermann, Alexandre; Parsley, B K; Burkhart, Stephen S

    2014-03-01

    This study compared arthroscopic biceps tenodesis with biceps repair for isolated type II superior labrum anterior and posterior (SLAP) lesions in patients older than 35 years. The authors identified isolated type II SLAP lesions that were surgically managed over a 5-year period. Minimum 2-year follow-up data were available for 22 patients who underwent biceps repair (repair group) and for 15 patients who underwent a primary biceps tenodesis (tenodesis group). Mean age at surgery was 45.2±5.5 years in the repair group and 52.0±8.0 years in the tenodesis group. In the repair group, functional outcome improved from baseline to final follow-up using the American Shoulder and Elbow Surgeons (ASES) (47.5 to 87.4, respectively; P<.0001) and University of California, Los Angeles (UCLA) scores (18.5 to 31.2, respectively; P<.0001). In the tenodesis group, similar findings were observed for the ASES (43.4 to 89.9, respectively; P<.0001) and UCLA scores (19.0 to 32.7, respectively; P<.0001). No difference was found in functional outcome between the groups. Full range of motion recovery was delayed by approximately 3 months in the repair group compared with the tenodesis group (P=.0631). Two patients in the repair group required a secondary capsular release. Seventy-seven percent of patients in the repair group and 100% of patients in the tenodesis group were satisfied and returned to normal activity (P=.0673). In the current study, individuals older than 35 years with an isolated type II SLAP lesion had a shorter postoperative recovery, a more predictable functional outcome, and a higher rate of satisfaction and return to activity with a biceps tenodesis compared with a biceps repair. Based on these observations, biceps tenodesis is preferable to biceps repair for isolated type II SLAP lesions in nonoverhead athletes older than 35 years.

  3. DNA Damage and Repair in Eukaryotic Cells

    PubMed Central

    Painter, R. B.

    1974-01-01

    Damage in DNA after irradiation can be classified into five kinds: base damage, single-strand breaks, double-strand breaks, DNA–DNA cross-linking, and DNA-protein cross-linking. Of these, repair of base damage is the best understood. In eukaryotes, at least three repair systems are known that can deal with base damage: photoreactivation, excision repair, and post-replication repair. Photoreactivation is specific for UV-induced damage and occurs widely throughout the biosphere, although it seems to be absent from placental mammals. Excision repair is present in prokaryotes and in animals but does not seem to be present in plants. Post-replication repair is poorly understood. Recent reports indicate that growing points in mammalian DNA simply skip past UV-induced lesions, leaving gaps in newly made DNA that are subsequently filled in by de novo synthesis. Evidence that this concept is oversimplified or incorrect is presented.—Single-strand breaks are induced by ionizing radiation but most cells can rapidly repair most or all of them, even after supralethal doses. The chemistry of the fragments formed when breaks are induced by ionizing radiation is complex and poorly understood. Therefore, the intermediate steps in the repair of single-strand breaks are unknown. Double-strand breaks and the two kinds of cross-linking have been studied very little and almost nothing is known about their mechanisms for repair.—The role of mammalian DNA repair in mutations is not known. Although there is evidence that defective repair can lead to cancer and/or premature aging in humans, the relationship between the molecular defects and the diseased state remains obscure. PMID:4442699

  4. Laparoscopic Inguinal Hernia Repair

    MedlinePlus

    ... Some hernia repairs are performed using a small telescope known as a laparoscope. If your surgeon has ... in the abdominal wall (muscle) using small incisions, telescopes and a patch (mesh). Laparoscopic repair offers a ...

  5. Eye muscle repair - discharge

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000111.htm Eye muscle repair - discharge To use the sharing features on ... enable JavaScript. You or your child had eye muscle repair surgery to correct eye muscle problems that ...

  6. Hydrocele repair - series (image)

    MedlinePlus

    ... vaginalis into the scrotum. This is called an inguinal hernia. If a hydrocele persists past the first six ... months of life, it should be surgically repaired. Inguinal hernia in infants is usually repaired within the first ...

  7. Phenotypic Transitions of Macrophages Orchestrate Tissue Repair

    PubMed Central

    Novak, Margaret L.; Koh, Timothy J.

    2014-01-01

    Macrophages are essential for the efficient healing of numerous tissues, and they contribute to impaired healing and fibrosis. Tissue repair proceeds through overlapping phases of inflammation, proliferation, and remodeling, and macrophages are present throughout this progression. Macrophages exhibit transitions in phenotype and function as tissue repair progresses, although the precise factors regulating these transitions remain poorly defined. In efficiently healing injuries, macrophages present during a given stage of repair appear to orchestrate transition into the next phase and, in turn, can promote debridement of the injury site, cell proliferation and angiogenesis, collagen deposition, and matrix remodeling. However, dysregulated macrophage function can contribute to failure to heal or fibrosis in several pathological situations. This review will address current knowledge of the origins and functions of macrophages during the progression of tissue repair, with emphasis on skin and skeletal muscle. Dysregulation of macrophages in disease states and therapies targeting macrophage activation to promote tissue repair are also discussed. PMID:24091222

  8. Effects of aging on the structural, mechanical, and thermal properties of the silicone rubber current transformer insulation bushing for a 500 kV substation.

    PubMed

    Wang, Zhigao; Zhang, Xinghai; Wang, Fangqiang; Lan, Xinsheng; Zhou, Yiqian

    2016-01-01

    In order to analyze the cracking and aging reason of the silicone rubber current transformer (CT) insulation bushing used for 8 years from a 500 kV alternating current substation, characteristics including Fourier transform infrared (FTIR) spectroscopy, mechanical properties analysis, hardness, and thermo gravimetric analysis have been carried out. The FTIR results indicated that the external surface of the silicone rubber CT insulation bushing suffered from more serious aging than the internal part, fracture of side chain Si-C bond was much more than the backbone. Mechanical properties and thermal stability results illustrated that the main aging reasons were the breakage of side chain Si-C bond and the excessive cross-linking reaction of the backbone. This study can provide valuable basis for evaluating degradation mechanism and aging state of the silicone rubber insulation bushing in electric power field.

  9. Effects of aging on the structural, mechanical, and thermal properties of the silicone rubber current transformer insulation bushing for a 500 kV substation.

    PubMed

    Wang, Zhigao; Zhang, Xinghai; Wang, Fangqiang; Lan, Xinsheng; Zhou, Yiqian

    2016-01-01

    In order to analyze the cracking and aging reason of the silicone rubber current transformer (CT) insulation bushing used for 8 years from a 500 kV alternating current substation, characteristics including Fourier transform infrared (FTIR) spectroscopy, mechanical properties analysis, hardness, and thermo gravimetric analysis have been carried out. The FTIR results indicated that the external surface of the silicone rubber CT insulation bushing suffered from more serious aging than the internal part, fracture of side chain Si-C bond was much more than the backbone. Mechanical properties and thermal stability results illustrated that the main aging reasons were the breakage of side chain Si-C bond and the excessive cross-linking reaction of the backbone. This study can provide valuable basis for evaluating degradation mechanism and aging state of the silicone rubber insulation bushing in electric power field. PMID:27390631

  10. Self-repairing composites for airplane components

    NASA Astrophysics Data System (ADS)

    Dry, Carolyn

    2008-03-01

    Durability and damage tolerance criteria drives the design of most composite structures. Those criteria could be altered by developing structure that repairs itself from impact damage. This is a technology for increasing damage tolerance for impact damage. Repaired damage would enable continued function and prevent further degradation to catastrophic failure in the case of an aircraft application. Further, repaired damage would enable applications to be utilized without reduction in performance due to impacts. Self repairing structures are designed to incorporate hollow fibers, which will release a repairing agent when the structure is impacted, so that the repairing agent will fill delaminations, voids and cracks in les than one minute, thus healing matrix voids. The intent is to modify the durability and damage tolerance criteria by incorporation of self-healing technologies to reduce overall weight: The structure will actually remain lighter than current conventional design procedures allow. Research objective(s) were: Prove that damage can be repaired to within 80-90% of original flexural strength in less than one minute, in laminates that are processed at 300-350F typical for aircraft composites. These were successfully met. The main focus was on testing of elements in compression after impact and a larger component in shear at Natural Process Design, Inc. Based on these results the advantages purposes are assessed. The results show potential; with self repairing composites, compressive strength is maintained sufficiently so that less material can be used as per durability and damage tolerance, yielding a lighter structure.

  11. Pectoralis Major Tendon Repair

    PubMed Central

    Cordasco, Frank A.; Degen, Ryan; Mahony, Gregory Thomas; Tsouris, Nicholas

    2016-01-01

    Objectives: Systematic reviews of the literature have identified 365 reported cases of Pectoralis Major Tendon (PMT) injuries. While surgical treatment has demonstrated improved outcomes compared to non-operative treatment, there is still relatively limited data on the functional outcome, return to sport and need for 2nd surgery in athletes following PMT repair. This study comprises the largest series of athletes following PMT repair reported to date. The Objective is to report on the functional outcomes, return to sport and need for 2nd surgery in a consecutive series of PMT tears. Methods: From 2009, 81 patients with PMT tears were enrolled in this prospective series. Baseline evaluation included patient demographics, mechanism of injury, physical examination and PMT specific MRI for confirmation of the diagnosis and analysis of the extent of injury. Each patient underwent surgical repair by the senior author utilizing a previously published surgical technique. Patients were then followed at 2 weeks, 6 weeks, 3 months and 6 months and further follow-up was conducted annually thereafter with functional outcome scores and adduction strength testing. The return to sport and incidence of 2nd surgery data were recorded. This study includes the first 40 athletes to reach the 2-year post-operative period. Results: All athletes were male, with an average age of 34.4 years (range 23-59). The patient cohort consisted of 4 professional NFL players and 36 recreational athletes. Average follow-up duration was 2.5 years (range 2 - 6.0 years). The most common mechanisms of injury occurred during the bench press (n=26) and contact sport participation (n=14). Sixteen injuries were complete avulsions involving both the clavicular and sternocostal heads, while 24 were isolated sternocostal head avulsions. Average pre-injury bench press of 396 lbs (range 170-500 lbs) was restored to 241 lbs post-operatively (range 140-550 lbs). Single Assessment Numeric Evaluation (SANE) scores

  12. Intimate partner violence and current tobacco smoking in low- to middle-income countries: Individual participant meta-analysis of 231,892 women of reproductive age.

    PubMed

    Caleyachetty, Rishi; Echouffo-Tcheugui, Justin B; Stephenson, Rob; Muennig, Peter

    2014-01-01

    Research on the health impact of intimate partner violence (IPV) has primarily focused on gynaecological and sexual health outcomes or psychiatric disorders. Much less is known about the association between IPV and tobacco smoking among women of reproductive age in low- to middle-income countries. This study examines the association between exposure to IPV and current tobacco smoking among women of reproductive age from low- to middle-income countries. We used data from Demographic and Health Surveys from 29 countries (231,892 women, aged 15-49) to examine the association between exposure to IPV and current tobacco smoking. Data were pooled using random-effects meta-analysis. There was a significant association between IPV and current tobacco smoking (pooled adjusted odds ratio [OR] = 1.58; 95% CI: 1.38-1.79) after controlling for age, education, occupation, household wealth, religion and pregnancy status across countries. The association was moderately consistent across the 29 countries (I(2) = 55.3%, p < 0.0001). These findings suggest that exposure to IPV is associated with an increased likelihood of current tobacco smoking among women of reproductive age in low- to middle-income countries. Future research on the association between exposure to IPV and tobacco smoking in prospective cohort studies is warranted.

  13. Comet assay to measure DNA repair: approach and applications

    PubMed Central

    Azqueta, Amaya; Slyskova, Jana; Langie, Sabine A. S.; O’Neill Gaivão, Isabel; Collins, Andrew

    2014-01-01

    Cellular repair enzymes remove virtually all DNA damage before it is fixed; repair therefore plays a crucial role in preventing cancer. Repair studied at the level of transcription correlates poorly with enzyme activity, and so assays of phenotype are needed. In a biochemical approach, substrate nucleoids containing specific DNA lesions are incubated with cell extract; repair enzymes in the extract induce breaks at damage sites; and the breaks are measured with the comet assay. The nature of the substrate lesions defines the repair pathway to be studied. This in vitro DNA repair assay has been modified for use in animal tissues, specifically to study the effects of aging and nutritional intervention on repair. Recently, the assay was applied to different strains of Drosophila melanogaster proficient and deficient in DNA repair. Most applications of the repair assay have been in human biomonitoring. Individual DNA repair activity may be a marker of cancer susceptibility; alternatively, high repair activity may result from induction of repair enzymes by exposure to DNA-damaging agents. Studies to date have examined effects of environment, nutrition, lifestyle, and occupation, in addition to clinical investigations. PMID:25202323

  14. Comet assay to measure DNA repair: approach and applications.

    PubMed

    Azqueta, Amaya; Slyskova, Jana; Langie, Sabine A S; O'Neill Gaivão, Isabel; Collins, Andrew

    2014-01-01

    Cellular repair enzymes remove virtually all DNA damage before it is fixed; repair therefore plays a crucial role in preventing cancer. Repair studied at the level of transcription correlates poorly with enzyme activity, and so assays of phenotype are needed. In a biochemical approach, substrate nucleoids containing specific DNA lesions are incubated with cell extract; repair enzymes in the extract induce breaks at damage sites; and the breaks are measured with the comet assay. The nature of the substrate lesions defines the repair pathway to be studied. This in vitro DNA repair assay has been modified for use in animal tissues, specifically to study the effects of aging and nutritional intervention on repair. Recently, the assay was applied to different strains of Drosophila melanogaster proficient and deficient in DNA repair. Most applications of the repair assay have been in human biomonitoring. Individual DNA repair activity may be a marker of cancer susceptibility; alternatively, high repair activity may result from induction of repair enzymes by exposure to DNA-damaging agents. Studies to date have examined effects of environment, nutrition, lifestyle, and occupation, in addition to clinical investigations.

  15. Dental materials for cleft palate repair.

    PubMed

    Sharif, Faiza; Ur Rehman, Ihtesham; Muhammad, Nawshad; MacNeil, Sheila

    2016-04-01

    Numerous bone and soft tissue grafting techniques are followed to repair cleft of lip and palate (CLP) defects. In addition to the gold standard surgical interventions involving the use of autogenous grafts, various allogenic and xenogenic graft materials are available for bone regeneration. In an attempt to discover minimally invasive and cost effective treatments for cleft repair, an exceptional growth in synthetic biomedical graft materials have occurred. This study gives an overview of the use of dental materials to repair cleft of lip and palate (CLP). The eligibility criteria for this review were case studies, clinical trials and retrospective studies on the use of various types of dental materials in surgical repair of cleft palate defects. Any data available on the surgical interventions to repair alveolar or palatal cleft, with natural or synthetic graft materials was included in this review. Those datasets with long term clinical follow-up results were referred to as particularly relevant. The results provide encouraging evidence in favor of dental and other related biomedical materials to fill the gaps in clefts of lip and palate. The review presents the various bones and soft tissue replacement strategies currently used, tested or explored for the repair of cleft defects. There was little available data on the use of synthetic materials in cleft repair which was a limitation of this study. In conclusion although clinical trials on the use of synthetic materials are currently underway the uses of autologous implants are the preferred treatment methods to date.

  16. Temporal variations in the strength of the Antarctic coastal current from the provenance and comminution ages of Weddell Sea sediments

    NASA Astrophysics Data System (ADS)

    Torfstein, A.; McManus, J. F.

    2012-12-01

    The location and geometric setting of the Weddell Sea, one of the large marginal seas of Antarctica, make it a sensitive recorder of the input of subglacial erosion products from Antarctica. We present evidence for variability in the sources and temporal fluxes of Antarctic continental erosion products, based on Pb, Sr and Nd isotopic compositions, U-decay series and trace element concnetrations of sediments deposited over the last ~250 kyrs in the East and deep-North Weddell Sea, at sites PS1388 and PS1170, respectively. Each sediment sample was separated into three grain size fractions of authigenic-free material (>20um, 20-2um, <2um). Significant differences are observed in sediment composition from the two studied regions as well as between grain size fractions within each sample. Lead isotopic compositions show a clear distinction between both sites with 206Pb/204Pb ratios at sites PS1388 and PS1170 ranging between 17.958-18.307 and 18.655-18.939, repsectively. The isotopic composition of Sr is generally similar at both sites, in the range of 0.715-0.723, except for <2um particles from PS1170 that display significantly higher values in the range of 0.726-0.734. The latter also display the strongest 234U-depletion with typical (234U/238U) ratios around 0.8. These observations imply that the clay size fraction in the North Weddell Sea originates from a distant region, most likely East Antarctica, and that it was exposed to more intense weathering and transport processes relative to the coarser particles. Hence, secular variations in 87Sr/86Sr and (234U/238U) ratios provide a sensitive recorder of the the sediments comminution ages (i.e., their time of transport between source and sink) and the intensity of weathering processes they were exposed to. The combined evidence supports enhanced rates of sediment transport by the Antarctic coastal current from the East Antarctic sector to the Weddell Sea during interglacial stages compared to glacial times, with

  17. Development of bonded composite doublers for the repair of oil recovery equipment.

    SciTech Connect

    Roach, David W.; Rackow, Kirk A.

    2005-06-01

    An unavoidable by-product of a metallic structure's use is the appearance of crack and corrosion flaws. Economic barriers to the replacement of these structures have created an aging infrastructure and placed even greater demands on efficient and safe repair methods. In the past decade, an advanced composite repair technology has made great strides in commercial aviation use. Extensive testing and analysis, through joint programs between the Sandia Labs FAA Airworthiness Assurance Center and the aviation industry, have proven that composite materials can be used to repair damaged aluminum structure. Successful pilot programs have produced flight performance history to establish the durability of bonded composite patches as a permanent repair on commercial aircraft structures. With this foundation in place, this effort is adapting bonded composite repair technology to civil structures. The use of bonded composite doublers has the potential to correct the difficulties associated with current repair techniques and the ability to be applied where there are no rehabilitation options. It promises to be cost-effective with minimal disruption to the users of the structure. This report concludes a study into the application of composite patches on thick steel structures typically used in mining operations. Extreme fatigue, temperature, erosive, and corrosive environments induce an array of equipment damage. The current weld repair techniques for these structures provide a fatigue life that is inferior to that of the original plate. Subsequent cracking must be revisited on a regular basis. The use of composite doublers, which do not have brittle fracture problems such as those inherent in welds, can help extend the structure's fatigue life and reduce the equipment downtime. Two of the main issues for adapting aircraft composite repairs to civil applications are developing an installation technique for carbon steel and accommodating large repairs on extremely thick structures

  18. Age-friendly primary health care: an assessment of current service provision for older adults in Hong Kong.

    PubMed

    Woo, Jean; Mak, Benise; Yeung, Fannie

    2013-01-01

    There has been no study evaluating whether primary care services are sufficiently oriented towards the older population in Hong Kong, particularly those with increasing frailty. Since primary care is a key first interface in promotion and maintenance of health in older people, an assessment of the age-friendliness of service provisions is of critical importance in optimizing the health of aging populations. The age-friendliness of primary care services for older people was assessed using focus groups of elderly people and also of service providers who care for them. Discussion content was based on the WHO guidelines for age-friendly primary care in the following areas: Information, education and training, community-based health care management systems, and the physical environment. Desirable improvements were identified in all domains. The findings underscore the need for wider dissemination of health care needs of older people in the primary care setting.

  19. Systems Maintenance Automated Repair Tasks (SMART)

    NASA Technical Reports Server (NTRS)

    Schuh, Joseph; Mitchell, Brent; Locklear, Louis; Belson, Martin A.; Al-Shihabi, Mary Jo Y.; King, Nadean; Norena, Elkin; Hardin, Derek

    2010-01-01

    SMART is a uniform automated discrepancy analysis and repair-authoring platform that improves technical accuracy and timely delivery of repair procedures for a given discrepancy (see figure a). SMART will minimize data errors, create uniform repair processes, and enhance the existing knowledge base of engineering repair processes. This innovation is the first tool developed that links the hardware specification requirements with the actual repair methods, sequences, and required equipment. SMART is flexibly designed to be useable by multiple engineering groups requiring decision analysis, and by any work authorization and disposition platform (see figure b). The organizational logic creates the link between specification requirements of the hardware, and specific procedures required to repair discrepancies. The first segment in the SMART process uses a decision analysis tree to define all the permutations between component/ subcomponent/discrepancy/repair on the hardware. The second segment uses a repair matrix to define what the steps and sequences are for any repair defined in the decision tree. This segment also allows for the selection of specific steps from multivariable steps. SMART will also be able to interface with outside databases and to store information from them to be inserted into the repair-procedure document. Some of the steps will be identified as optional, and would only be used based on the location and the current configuration of the hardware. The output from this analysis would be sent to a work authoring system in the form of a predefined sequence of steps containing required actions, tools, parts, materials, certifications, and specific requirements controlling quality, functional requirements, and limitations.

  20. Demographic Aspects of Aging and the Older Population in the United States. Current Population Reports, Special Studies, Series P-23, No. 59.

    ERIC Educational Resources Information Center

    Siegel, Jacob S.; And Others

    This report presents a statistical portrait of the demographic aspects of aging and the older population in the Unites States. Most of the estimates are based on data from decennial censuses, the program of nonsurvey population estimates and projections carried out by the U.S. Bureau of the Census, the Current Population Survey, and other census…

  1. The dynamics of certain indicators of nuclein metabolism during hypokinesia in rats of different ages under the influence of sinusoidal modulated currents and measured physical load

    NASA Technical Reports Server (NTRS)

    Sokolova, Z. A.

    1980-01-01

    The influence of sinusoidal modulated currents was studied and physical loads on the nucleic acid content and the nucleotide composition of the total RNA in muscles of rats of various ages under conditions of hypodynamia were measured. Methodology utilized is described and conclusions are presented.

  2. Current sensor

    DOEpatents

    Yakymyshyn, Christopher Paul; Brubaker, Michael Allen; Yakymyshyn, Pamela Jane

    2007-01-16

    A current sensor is described that uses a plurality of magnetic field sensors positioned around a current carrying conductor. The sensor can be hinged to allow clamping to a conductor. The current sensor provides high measurement accuracy for both DC and AC currents, and is substantially immune to the effects of temperature, conductor position, nearby current carrying conductors and aging.

  3. [How traumatized are the children of World War II? The relationship of age during flight and forced displacement and current posttraumatic stress symptoms].

    PubMed

    Wendt, Carolin; Freitag, Simone; Schmidt, Silke

    2012-08-01

    Traumatic events experienced in childhood can be reactivated in older age. The present study investigates the relation of age during flight and forced displacement within World War II (WWII; 2-7 years, 8-13 years, 14-20 years) and the current occurrence of posttraumatic stress disorder (PTSD). Traumatic events and current posttraumatic stress symptoms were assessed by the Harvard Trauma Questionnaire and the Impact of Event Scale-revised. Mean age of participants (N=169) was 73.76 years (SD=4.18). The eldest group reported most war-related traumatic events. In each age group a one-week-prevalence for a full PTSD of 10-11% was found. The prevalence for both full and subthreshold PTSD was higher for the age group 14-20 years (60.5%) compared to the younger age groups (33-35%). People, who experienced WWII as adolescents, show a dose-response-effect indicated by a higher prevalence for subthreshold PTSD.

  4. Hypospadias Repair: A Single Centre Experience

    PubMed Central

    Majeed, Abdul; Ullah, Hidayat; Naz, Shazia; Shah, Syed Asif; Tahmeed, Tahmeedullah; Yousaf, Kanwal; Tahir, Muhammad

    2014-01-01

    Objectives. To determine the demographics and analyze the management and factors influencing the postoperative complications of hypospadias repair. Settings. Hayatabad Medical Complex Peshawar, Pakistan, from January 2007 to December 2011. Material and Methods. All male patients presenting with hypospadias irrespective of their ages were included in the study. The data were acquired from the hospital's database and analyzed with Statistical Package for Social Sciences (SPSS). Results. A total of 428 patients with mean age of 8.12 ± 5.04 SD presented for hypospadias repair. Midpenile hypospadias were the most common. Chordee, meatal abnormalities, cryptorchidism, and inguinal hernias were observed in 74.3%, 9.6%, 2.8%, and 2.1% cases, respectively. Two-stage (Bracka) and TIP (tubularized incised urethral plate) repairs were performed in 76.2% and 20.8% of cases, respectively. The most common complications were edema and urethrocutaneous fistula (UCF). The complications were significantly lower in the hands of specialists than residents (P-value = 0.0086). The two-stage hypospadias repair resulted in higher complications frequency than single-stage repair (P value = 0.0001). Conclusion. Hypospadias surgery has a long learning curve because it requires a great deal of temperament, surgical skill and acquaintance with magnifications. Single-stage repair should be encouraged wherever applicable due to its lower postoperative complications. PMID:24579043

  5. Primary unilateral cleft lip repair

    PubMed Central

    Adenwalla, H. S.; Narayanan, P. V.

    2009-01-01

    The unilateral cleft lip is a complex deformity. Surgical correction has evolved from a straight repair through triangular and quadrilateral repairs to the Rotation Advancement Technique of Millard. The latter is the technique followed at our centre for all unilateral cleft lip patients. We operate on these at five to six months of age, do not use pre-surgical orthodontics, and follow a protocol to produce a notch-free vermillion. This is easy to follow even for trainees. We also perform closed alar dissection and extensive primary septoplasty in all these patients. This has improved the overall result and has no long-term deleterious effect on the growth of the nose or of the maxilla. Other refinements have been used for prevention of a high-riding nostril, and correction of the vestibular web. PMID:19884683

  6. Mountain Plains Learning Experience Guide: Electric Motor Repair.

    ERIC Educational Resources Information Center

    Ziller, T.

    This Electric Motor Repair Course is designed to provide the student with practical information for winding, repairing, and troubleshooting alternating current and direct current motors, and controllers. The course is comprised of eight units: (1) Electric Motor Fundamentals, (2) Rewinding, (3) Split-phase Induction Motors, (4) Capacitor Motors,…

  7. Age distribution patterns of patients with conventional ductal adenocarcinoma of the pancreas. A single-institution study of 580 cases re-evaluated using current histopathological diagnostic criteria.

    PubMed

    Liszka, Łukasz; Pająk, Jacek; Mrowiec, Sławomir; Zielińska-Pająk, Ewa; Lampe, Paweł; Gołka, Dariusz

    2010-01-01

    There are a few studies concerning epidemiology of pancreatic ductal adenocarcinoma (PDAC) in the Polish population. Analysis of age distribution patterns of patients with different types of cancer may be useful for studying their specific biology. In the present study we aimed to describe age distribution patterns of 580 patients with PDAC diagnosed in one centre during a 25-year period. All the histopathological diagnoses were re-reviewed using current histopathological diagnostic criteria. Age distributions of selected subpopulations of patients (defined based on gender, potential tumour resectability and type of the surgery) were compared using mean values, medians, age frequency density plots and logarithmic plots of age-specific frequencies. The mean and median values of patients' age were 60.8 y and 61.0 y, respectively. Females were approximately 2 y older than males at the time of PDAC diagnosis. Females with non-resectable PDAC were approximately 2 y older than females with resectable tumours. Mean age values of males with non-resectable and resectable PDAC were similar. Patients treated with pancreaticoduodenectomy were approximately 2 y older than patients undergoing other types of resections. Age distribution density plots showed that some subgroups of patients studied were somewhat heterogeneous and might include several yet poorly recognized clinico-pathological entities. Logarithmic plots of age-specific frequencies showed that PDAC epidemiology is in concordance with a multistage theory of carcinogenesis. PDAC is an age-dependent cancer. Single-institutional pathology-oriented cancer epidemiological databases may add some information to population-based cancer registries.

  8. Oxidative DNA Damage and Nucleotide Excision Repair

    PubMed Central

    Melis, Joost P.M.; Luijten, Mirjam

    2013-01-01

    Abstract Significance: Oxidative DNA damage is repaired by multiple, overlapping DNA repair pathways. Accumulating evidence supports the hypothesis that nucleotide excision repair (NER), besides base excision repair (BER), is also involved in neutralizing oxidative DNA damage. Recent Advances: NER includes two distinct sub-pathways: transcription-coupled NER (TC-NER) and global genome repair (GG-NER). The CSA and CSB proteins initiate the onset of TC-NER. Recent findings show that not only CSB, but also CSA is involved in the repair of oxidative DNA lesions, in the nucleus as well as in mitochondria. The XPG protein is also of importance for the removal of oxidative DNA lesions, as it may enhance the initial step of BER. Substantial evidence exists that support a role for XPC in NER and BER. XPC deficiency not only results in decreased repair of oxidative lesions, but has also been linked to disturbed redox homeostasis. Critical Issues: The role of NER proteins in the regulation of the cellular response to oxidative (mitochondrial and nuclear) DNA damage may be the underlying mechanism of the pathology of accelerated aging in Cockayne syndrome patients, a driving force for internal cancer development in XP-A and XP-C patients, and a contributor to the mixed exhibited phenotypes of XP-G patients. Future Directions: Accumulating evidence indicates that DNA repair factors can be involved in multiple DNA repair pathways. However, the distinct detailed mechanism and consequences of these additional functions remain to be elucidated and can possibly shine a light on clinically related issues. Antioxid. Redox Signal. 18, 2409–2419. PMID:23216312

  9. Magnetic Resonance Imaging of Cartilage Repair

    PubMed Central

    Trattnig, Siegfried; Winalski, Carl S.; Marlovits, Stephan; Jurvelin, Jukka S.; Welsch, Goetz H.; Potter, Hollis G.

    2011-01-01

    Articular cartilage lesions are a common pathology of the knee joint, and many patients may benefit from cartilage repair surgeries that offer the chance to avoid the development of osteoarthritis or delay its progression. Cartilage repair surgery, no matter the technique, requires a noninvasive, standardized, and high-quality longitudinal method to assess the structure of the repair tissue. This goal is best fulfilled by magnetic resonance imaging (MRI). The present article provides an overview of the current state of the art of MRI of cartilage repair. In the first 2 sections, preclinical and clinical MRI of cartilage repair tissue are described with a focus on morphological depiction of cartilage and the use of functional (biochemical) MR methodologies for the visualization of the ultrastructure of cartilage repair. In the third section, a short overview is provided on the regulatory issues of the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) regarding MR follow-up studies of patients after cartilage repair surgeries. PMID:26069565

  10. Informal Social Networks of People with Profound Intellectual and Multiple Disabilities: Relationship with Age, Communicative Abilities and Current Living Arrangements

    ERIC Educational Resources Information Center

    Kamstra, A.; van der Putten, A. A. J.; Post, W. J.; Vlaskamp, C.

    2015-01-01

    Background: People with profound intellectual and multiple disabilities (PIMD) have limited informal social contacts. Research to determine the factors which can positively influence establishing sound informal social contacts is required. Materials and Methods: Regression analysis for 200 people with PIMD was used to analyse how age,…

  11. The relevance of age in female human reproduction--current situation in Switzerland and pathophysiological background from a comparative perspective.

    PubMed

    Leeners, Brigitte; Geraedts, Kirsten; Imthurn, Bruno; Stiller, Ruth

    2013-07-01

    During recent years women tend to postpone childbirth to ages when fertility declines. Consequently, an increasing number of women experiences reproductive difficulties and seeks help by assisted reproductive techniques (ART). To investigate the dynamics of age-related fertility in Switzerland we evaluated data from the nationwide FIVNAT-CH statistics on ART as well as from a subsample receiving ART at the Division of Reproductive Endocrinology, University Hospital Zurich. Since 2000 the average age of women receiving ART increased from 34.9 to 36.3 years in Switzerland and since 2006 numbers of annual ART cycles augmented steadily. The percentage of women ≥40 increased from 17.2% in 2007 to 19.6% in 2011. In the Zurich cohort AMH, the number of oocytes retrieved, the number of fertilized oocytes with two pronuclei, the number of embryos with an adequate cell number, clinical pregnancy rates as well as life birth/ongoing pregnancy rates were lower in the age group ≥40 years, especially when compared to 33 year-old women. In the nationwide sample pregnancy rates decreased from about 45% at the age of 30 to less than 3% at the age of 45; delivery rates declined from about 38% to nearly 0%. In the Zurich cohort percentages of clinical pregnancies declined from 46% in women ≤34 years to 21% in women ≥40 years. In the national sample as well as in the Zurich cohort the percentage of miscarriages increased dramatically from 15.4% and 22% in women ≤34 years to 38.6% and 33% in women ≥40 years, respectively. Even in a country with high health standards such as Switzerland fertility is declining with age and ART does not succeed to improve reduced fertility. Rodent and primate models enrich our knowledge on the pathophysiological mechanisms underlying reproductive senescence. As non-infertility specialist physicians as well as the general public are not sufficiently aware of the dramatic reduction of chances for life births in women ≥40 years, medical

  12. Animal models of cartilage repair

    PubMed Central

    Cook, J. L.; Hung, C. T.; Kuroki, K.; Stoker, A. M.; Cook, C. R.; Pfeiffer, F. M.; Sherman, S. L.; Stannard, J. P.

    2014-01-01

    Cartilage repair in terms of replacement, or regeneration of damaged or diseased articular cartilage with functional tissue, is the ‘holy grail’ of joint surgery. A wide spectrum of strategies for cartilage repair currently exists and several of these techniques have been reported to be associated with successful clinical outcomes for appropriately selected indications. However, based on respective advantages, disadvantages, and limitations, no single strategy, or even combination of strategies, provides surgeons with viable options for attaining successful long-term outcomes in the majority of patients. As such, development of novel techniques and optimisation of current techniques need to be, and are, the focus of a great deal of research from the basic science level to clinical trials. Translational research that bridges scientific discoveries to clinical application involves the use of animal models in order to assess safety and efficacy for regulatory approval for human use. This review article provides an overview of animal models for cartilage repair. Cite this article: Bone Joint Res 2014;4:89–94. PMID:24695750

  13. Arthroscopic Repair of Posterior Meniscal Root Tears

    PubMed Central

    Matheny, Lauren; Moulton, Samuel G.; Dean, Chase S.; LaPrade, Robert F.

    2016-01-01

    Objectives: The purpose of this study was to compare subjective clinical outcomes in patients requiring arthroscopic transtibial pullout repair for posterior meniscus root tears of the medial and lateral menisci. We hypothesized that improvement in function and activity level would be similar among patients undergoing lateral and medial meniscal root repairs. Methods: This study was IRB approved. All patients who underwent posterior meniscal root repair by a single orthopaedic surgeon were included in this study. Detailed operative data were documented at surgery. Patients completed a subjective questionnaire, including Lysholm score, Tegner activity scale, WOMAC, SF-12 and patient satisfaction with outcome, which were collected preoperatively and at a minimum of two years postoperatively. Failure was defined as any patient who underwent revision meniscal root repair or partial meniscectomy following the index surgery. Results: There were 50 patients (16 females, 34 males) with a mean age of 37.8 years (range, 16.6-65.7) and a mean BMI of 27.3 (range, 20.5-49.2) included in this study. Fifteen patients underwent lateral meniscus root repair and 35 patients underwent medial meniscus root repair. Three patients who underwent lateral meniscus root repair required revision meniscus root repair surgery, while no patients who underwent medial meniscus root repair required revision surgery (p=0.26). There was a significant difference in preoperative and postoperative Lysholm score (53 vs. 78) (p<0.001), Tegner activity scale (2.0 vs. 4.0) (p=0.03), SF-12 physical component subscale (38 vs. 50) (p=0.001) and WOMAC (36 vs. 8) (p<0.001) for the total population. Median patient satisfaction with outcome was 9 (range, 1-10). There was no significant difference in mean age between lateral and medial root repair groups (32 vs. 40) (p=0.12) or gender (p=0.19). There was no significant difference in gender between lateral and medial root repair groups (p=0.95). There was a

  14. Targeting Endogenous Repair Pathways after AKI.

    PubMed

    Humphreys, Benjamin D; Cantaluppi, Vincenzo; Portilla, Didier; Singbartl, Kai; Yang, Li; Rosner, Mitchell H; Kellum, John A; Ronco, Claudio

    2016-04-01

    AKI remains a highly prevalent disease associated with poor short- and long-term outcomes and high costs. Although significant advances in our understanding of repair after AKI have been made over the last 5 years, this knowledge has not yet been translated into new AKI therapies. A consensus conference held by the Acute Dialysis Quality Initiative was convened in April of 2014 and reviewed new evidence on successful kidney repair to identify the most promising pathways that could be translated into new treatments. In this paper, we provide a summary of current knowledge regarding successful kidney repair and offer a framework for conceptualizing the therapeutic targeting that may facilitate this process. We outline gaps in knowledge and suggest a research agenda to more efficiently bring new discoveries regarding repair after AKI to the clinic.

  15. Further Evolution of Composite Doubler Aircraft Repairs Through a Focus on Niche Applications

    SciTech Connect

    ROACH,DENNIS P.

    2000-07-15

    The number of commercial airframes exceeding twenty years of service continues to grow. A typical aircraft can experience over 2,000 fatigue cycles (cabin pressurizations) and even greater flight hours in a single year. An unavoidable by-product of aircraft use is that crack and corrosion flaws develop throughout the aircraft's skin and substructure elements. Economic barriers to the purchase of new aircraft have created an aging aircraft fleet and placed even greater demands on efficient and safe repair methods. The use of bonded composite doublers offers the airframe manufacturers and aircraft maintenance facilities a cost effective method to safety extend the lives of their aircraft. Instead of riveting multiple steel or aluminum plates to facilitate an aircraft repair, it is now possible to bond a single Boron-Epoxy composite doubler to the damaged structure. The FAA's Airworthiness Assurance Center at Sandia National Labs (AANC) is conducting a program with Boeing and Federal Express to validate and introduce composite doubler repair technology to the US commercial aircraft industry. This project focuses on repair of DC-10 structure and builds on the foundation of the successful L-1011 door corner repair that was completed by the AANC, Lockheed-Martin, and Delta Air Lines. The L-1011 composite doubler repair was installed in 1997 and has not developed any flaws in over three years of service, As a follow-on effort, this DC-1O repair program investigated design, analysis, performance (durability, flaw containment, reliability), installation, and nondestructive inspection issues. Current activities are demonstrating regular use of composite doubler repairs on commercial aircraft. The primary goal of this program is to move the technology into niche applications and to streamline the design-to-installation process. Using the data accumulated to date, the team has designed, analyzed, and developed inspection techniques for an array of composite doubler repairs

  16. Participation of DNA repair in the response to 5-fluorouracil

    PubMed Central

    Wyatt, Michael D.; Wilson, David M.

    2008-01-01

    The anti-metabolite 5-fluorouracil (5-FU) is employed clinically to manage solid tumors including colorectal and breast cancer. Intracellular metabolites of 5-FU can exert cytotoxic effects via inhibition of thymidylate synthetase, or through incorporation into RNA and DNA, events that ultimately activate apoptosis. In this review, we cover the current data implicating DNA repair processes in cellular responsiveness to 5-FU treatment. Evidence points to roles for base excision repair (BER) and mismatch repair (MMR). However, mechanistic details remain unexplained, and other pathways have not been exhaustively interrogated. Homologous recombination is of particular interest, because it resolves unrepaired DNA intermediates not properly dealt with by BER or MMR. Furthermore, crosstalk among DNA repair pathways and S-phase checkpoint signaling has not been examined. Ongoing efforts aim to design approaches and reagents that (i) approximate repair capacity and (ii) mediate strategic regulation of DNA repair in order to improve the efficacy of current anti-cancer treatments. PMID:18979208

  17. Laparoscopic lumbar hernia repair.

    PubMed

    Madan, Atul K; Ternovits, Craig A; Speck, Karen E; Pritchard, F Elizabeth; Tichansky, David S

    2006-04-01

    Lumbar hernias are rare clinical entities that often pose a challenge for repair. Because of the surrounding anatomy, adequate surgical herniorraphy is often difficult. Minimally invasive surgery has become an option for these hernias. Herein, we describe two patients with lumbar hernias (one with a recurrent traumatic hernia and one with an incisional hernia). Both of these hernias were successfully repaired laparoscopically.

  18. Snowmobile Repair. Teacher Edition.

    ERIC Educational Resources Information Center

    Hennessy, Stephen S.; Conrad, Rex

    This teacher's guide contains 14 units on snowmobile repair: (1) introduction to snowmobile repair; (2) skis, front suspension, and steering; (3) drive clutch; (4) drive belts; (5) driven clutch; (6) chain drives; (7) jackshafts and axles; (8) rear suspension; (9) tracks; (10) shock absorbers; (11) brakes; (12) engines; (13) ignition and…

  19. INTERNAL REPAIR OF PIPELINES

    SciTech Connect

    Bill Bruce; Nancy Porter; George Ritter; Matt Boring; Mark Lozev; Ian Harris; Bill Mohr; Dennis Harwig; Robin Gordon; Chris Neary; Mike Sullivan

    2005-07-20

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without

  20. Design, manufacture, development, test, and evaluation of boron/aluminum structural components for space shuttle. Volume 4: Repairability

    NASA Technical Reports Server (NTRS)

    Miller, M. F.; Christian, J. L.; Doyal, F. H.

    1974-01-01

    The repairability of boron/aluminum structural components was investigated. It was demonstrated that metal matrix composite material, damaged in service, can be repaired by techniques that are not very different from those currently in use for conventional materials. A list of repair guidelines was prepared to aid in determining the proper repair techniques for a given structure. The guidelines include specifying types of repair material and their applicability, corrosion prevention procedures, design criteria, and inspection criteria. Boron/aluminum structural components were repaired and tested to compare as-fabricated and repaired performance. All but one set of specimens, when repaired, exceeded the strength of the original specimens.

  1. Properties of BK-type Ca(+) (+)-dependent K(+) channel currents in medial prefrontal cortex pyramidal neurons in rats of different ages.

    PubMed

    Książek, Aneta; Ladno, Wioletta; Szulczyk, Bartłomiej; Grzelka, Katarzyna; Szulczyk, Paweł

    2013-01-01

    The medial prefrontal cortex (PFC) is involved in cognitive functions, which undergo profound changes during adolescence. This alteration of the PFC function derives from neuron activity, which, in turn, may depend on age-dependent properties and the expression of neuronal ion channels. BK-type channels are involved in controlling both the Ca(+) (+) ion concentration in the cell interior and cell excitability. The purpose of this study was to test the properties of BK currents in the medial PFC pyramidal neurons of young (18- to 22-day-old), adolescent (38- to 42-day-old), and adult (60- to 65-day-old) rats. Whole-cell currents evoked by depolarizing voltage steps were recorded from dispersed medial PFC pyramidal neurons. A selective BK channel blocker - paxilline (10 μM) - irreversibly decreased the non-inactivating K(+) current in neurons that were isolated from the young and adult rats. This current was not significantly affected by paxilline in the neurons obtained from adolescent rats. The properties of single-channel K(+) currents were recorded from the soma of dispersed medial PFC pyramidal neurons in the cell-attached configuration. Of the K(+) channel currents that were recorded, ~90% were BK and leak channel currents. The BK-type channel currents were dependent on the Ca(+) (+) concentration and the voltage and were inhibited by paxilline. The biophysical properties of the BK channel currents did not differ among the pyramidal neurons isolated from young, adolescent, and adult rats. Among all of the recorded K(+) channel currents, 38.9, 12.7, and 21.1% were BK-type channel currents in the neurons isolated from the young, adolescent, and adult rats, respectively. Furthermore, application of paxilline effectively prolonged the half-width of the action potential in pyramidal neurons in slices isolated from young and adult rats but not in neurons isolated from adolescent rats. We conclude that the availability of BK channel currents decreases in medial PFC

  2. Properties of BK-type Ca++-dependent K+ channel currents in medial prefrontal cortex pyramidal neurons in rats of different ages

    PubMed Central

    Książek, Aneta; Ładno, Wioletta; Szulczyk, Bartłomiej; Grzelka, Katarzyna; Szulczyk, Paweł

    2013-01-01

    The medial prefrontal cortex (PFC) is involved in cognitive functions, which undergo profound changes during adolescence. This alteration of the PFC function derives from neuron activity, which, in turn, may depend on age-dependent properties and the expression of neuronal ion channels. BK-type channels are involved in controlling both the Ca++ ion concentration in the cell interior and cell excitability. The purpose of this study was to test the properties of BK currents in the medial PFC pyramidal neurons of young (18- to 22-day-old), adolescent (38- to 42-day-old), and adult (60- to 65-day-old) rats. Whole-cell currents evoked by depolarizing voltage steps were recorded from dispersed medial PFC pyramidal neurons. A selective BK channel blocker – paxilline (10 μM) – irreversibly decreased the non-inactivating K+ current in neurons that were isolated from the young and adult rats. This current was not significantly affected by paxilline in the neurons obtained from adolescent rats. The properties of single-channel K+ currents were recorded from the soma of dispersed medial PFC pyramidal neurons in the cell-attached configuration. Of the K+ channel currents that were recorded, ~90% were BK and leak channel currents. The BK-type channel currents were dependent on the Ca++ concentration and the voltage and were inhibited by paxilline. The biophysical properties of the BK channel currents did not differ among the pyramidal neurons isolated from young, adolescent, and adult rats. Among all of the recorded K+ channel currents, 38.9, 12.7, and 21.1% were BK-type channel currents in the neurons isolated from the young, adolescent, and adult rats, respectively. Furthermore, application of paxilline effectively prolonged the half-width of the action potential in pyramidal neurons in slices isolated from young and adult rats but not in neurons isolated from adolescent rats. We conclude that the availability of BK channel currents decreases in medial PFC pyramidal

  3. INTERNAL REPAIR OF PIPELINES

    SciTech Connect

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; George Ritter; Bill Mohr; Matt Boring; Nancy Porter; Mike Sullivan; Chris Neary

    2004-12-31

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without

  4. Mechanical characterization of composite repairs for fiberglass wind turbine blades

    NASA Astrophysics Data System (ADS)

    Chawla, Tanveer Singh

    While in service, wind turbine blades experience various modes of loading. An example is impact loading in the form of hail or bird strikes, which might lead to localized damage or formation of cracks a few plies deep on the blade surface. One of the methods to conduct repairs on wind turbine blades that are damaged while in service is hand lay-up of the repair part after grinding out the damaged portion and some of its surrounding area. The resin used for such repairs usually differs from the parent plate resin in composition and properties such as gel time, viscosity, etc. As a result the properties of the repaired parts are not the same as that of the undamaged blades. Subsequent repetitive loading can be detrimental to weak repairs to such an extent so as to cause delamination at the parent-repair bondline causing the repairs to eventually fall off the blade. Thus the strength and toughness of the repair are of critical importance. Initial part of this work consists of an effort to increase repair strength by identifying an optimum hand layup repair resin for fiberglass wind turbine blades currently being manufactured by a global company. As delamination of the repair from the parent blade is a major concern and unidirectional glass fibers along with a polymer resin are used to manufacture blades under consideration, testing method detailed in ASTM D 5528 (Test Method for Mode I Interlaminar Fracture Toughness of Unidirectional Fiber-Reinforced Polymer Matrix Composites) was followed to determine propagation fracture toughness values of the prospective vinyl ester repair resin candidates. These values were compared to those for a base polyester repair resin used by the company. Experimental procedure and results obtained from the above mentioned testing using double cantilever beam (DCB) specimens are detailed. Three new repair resins were shortlisted through mode I testing. It was also found that variation in the depth of the ground top ply of the parent part

  5. Multiple functions of gingival and mucoperiosteal fibroblasts in oral wound healing and repair.

    PubMed

    Chiquet, Matthias; Katsaros, Christos; Kletsas, Dimitris

    2015-06-01

    Fibroblasts are cells of mesenchymal origin. They are responsible for the production of most extracellular matrix in connective tissues and are essential for wound healing and repair. In recent years, it has become clear that fibroblasts from different tissues have various distinct traits. Moreover, wounds in the oral cavity heal under very special environmental conditions compared with skin wounds. Here, we reviewed the current literature on the various interconnected functions of gingival and mucoperiosteal fibroblasts during the repair of oral wounds. The MEDLINE database was searched with the following terms: (gingival OR mucoperiosteal) AND fibroblast AND (wound healing OR repair). The data gathered were used to compare oral fibroblasts with fibroblasts from other tissues in terms of their regulation and function during wound healing. Specifically, we sought answers to the following questions: (i) what is the role of oral fibroblasts in the inflammatory response in acute wounds; (ii) how do growth factors control the function of oral fibroblasts during wound healing; (iii) how do oral fibroblasts produce, remodel and interact with extracellular matrix in healing wounds; (iv) how do oral fibroblasts respond to mechanical stress; and (v) how does aging affect the fetal-like responses and functions of oral fibroblasts? The current state of research indicates that oral fibroblasts possess unique characteristics and tightly controlled specific functions in wound healing and repair. This information is essential for developing new strategies to control the intraoral wound-healing processes of the individual patient.

  6. Repair of Electronics for Long Duration Spaceflight

    NASA Technical Reports Server (NTRS)

    Pettegrew, Richard D.; Easton, John; Struk, Peter

    2007-01-01

    To reduce mission risk, long duration spaceflight and exploration activities will require greater degrees of self-sufficiency with regards to repair capability than have ever been employed before in space exploration. The current repair paradigm of replacing Orbital Replacement Units (ORUs) of malfunctioning avionics and electronic hardware will be impractical, since carrying all of the spares that could possibly be needed for a long duration mission would require upmass and volume at unprecedented and unacceptable levels. A strategy of component-level repair for electronics, however, could significantly reduce the mass and volume necessary for spares and enhance mission safety via a generic contingency capability. This approach is already used to varying degrees by the U.S. Navy, where vessels at sea experience some similar constraints such as the need for self sufficiency for moderately long time periods, and restrictions on volume of repair spares and infrastructure. The concept of conducting component-level repairs of electronics in spacecraft requires the development of design guidelines for future avionics (to enable repair), development of diagnostic techniques to allow an astronaut to pinpoint the faulty component aboard a vastly complex vehicle, and development of tools and methodologies for dealing with the physical processes of replacing the component. This physical process includes tasks such as conformal coating removal and replacement, component removal, replacement, and alignment--all in the difficulty of a reduced gravity environment. Further, the gravitational effects on the soldering process must be characterized and accounted for to ensure reliability of the newly repaired components. The Component-Level Electronics-Assembly Repair (CLEAR) project under the NASA Supportability program was established to develop and demonstrate the practicality of this repair approach. CLEAR involves collaborative efforts between NASA s Glenn Research Center

  7. Proficiency of Surgeons in Inguinal Hernia Repair

    PubMed Central

    Neumayer, Leigh A.; Gawande, Atul A.; Wang, Jia; Giobbie-Hurder, Anita; Itani, Kamal M. F.; Fitzgibbons, Robert J.; Reda, Domenic; Jonasson, Olga

    2005-01-01

    Objectives: We examined the influence of surgeon age and other factors on proficiency in laparoscopic or open hernia repair. Summary Background Data: In a multicenter, randomized trial comparing open and laparoscopic herniorrhaphies, conducted in Veterans Administration hospitals (CSP 456), we reported significant differences in recurrence rates (RR) for the laparoscopic procedure as a result of surgeons’ experience. We have also reported significant differences in RR for the open procedure related to resident postgraduate year (PGY) level. Methods: We analyzed data from unilateral laparoscopic and open herniorrhaphies from CSP 456 (n = 1629). Surgeon's experience (experienced ≥250 procedures; inexperienced <250), surgeon's age, median PGY level of the participating resident, operation time, and hospital observed-to-expected (O/E) ratios for mortality were potential independent predictors of RR. Results: Age was dichotomized into older (≥45 years) and younger (<45 years). Surgeon's inexperience and older age were significant predictors of recurrence in laparoscopic herniorrhaphy. The odds of recurrence for an inexperienced surgeon aged 45 years or older was 1.72 times that of a younger inexperienced surgeon. For open repairs, although surgeon's age and operation time appeared to be related to recurrence, only median PGY level of <3 was a significant independent predictor. Conclusion: This analysis demonstrates that surgeon's age of 45 years and older, when combined with inexperience in laparoscopic inguinal herniorrhaphies, increases risk of recurrence. For open repairs, only a median PGY level of <3 was a significant risk factor. PMID:16135920

  8. Durability of laparoscopic repair of paraesophageal hernia.

    PubMed Central

    Edye, M B; Canin-Endres, J; Gattorno, F; Salky, B A

    1998-01-01

    OBJECTIVES: To define a method of primary repair that would minimize hernia recurrence and to report medium-term follow-up of patients who underwent laparoscopic repair of paraesophageal hernia to verify durability of the repair and to assess the effect of inclusion of an antireflux procedure. SUMMARY BACKGROUND DATA: Primary paraesophageal hernia repair was completed laparoscopically in 55 patients. There were five recurrences within 6 months when the sac was not excised (20%). After institution of a technique of total sac excision in 30 subsequent repairs, no early recurrences were observed. METHODS: Inclusion of an antireflux procedure, incidence of subsequent hernia recurrence, dysphagia, and gastroesophageal reflux symptoms were recorded in clinical follow-up of patients who underwent a laparoscopic procedure. RESULTS: Mean length of follow-up was 29 months. Forty-nine patients were available for follow-up, and one patient had died of lung cancer. Mean age at surgery was 68 years. The surgical morbidity rate in elderly patients was no greater than in younger patients. Eleven patients (22%) had symptoms of mild to moderate reflux, and 15 were taking acid-reduction medication for a variety of dyspeptic complaints. All but 2 of these 15 had undergone 360 degrees fundoplication at initial repair. Two patients (4%) had late recurrent hernia, each small, demonstrated by esophagram or endoscopy. CONCLUSIONS: Laparoscopic repair in the medium term appeared durable. The incidence of postsurgical reflux symptoms was unrelated to inclusion of an antireflux procedure. In the absence of motility data, partial fundoplication was preferred, although dysphagia after floppy 360 degrees wrap was rare. With the low morbidity rate of this procedure, correction of symptomatic paraesophageal hernia appears indicated in patients regardless of age. Images Figure 1. PMID:9790342

  9. Inguinal hernia repair: toward Asian guidelines.

    PubMed

    Lomanto, Davide; Cheah, Wei-Keat; Faylona, Jose Macario; Huang, Ching Shui; Lohsiriwat, Darin; Maleachi, Andy; Yang, George Pei Cheung; Li, Michael Ka-Wai; Tumtavitikul, Sathien; Sharma, Anil; Hartung, Rolf Ulrich; Choi, Young Bai; Sutedja, Barlian

    2015-02-01

    Groin hernias are very common, and surgical treatment is usually recommended. In fact, hernia repair is the most common surgical procedure performed worldwide. In countries such as the USA, China, and India, there may easily be over 1 million repairs every year. The need for this surgery has become an important socioeconomic problem and may affect health-care providers, especially in aging societies. Surgical repair using mesh is recommended and widely employed in Western countries, but in many developing countries, tissue-to-tissue repair is still the preferred surgical procedure due to economic constraints. For these reason, the development and implementation of guidelines, consensus, or recommendations may aim to clarify issues related to best practices in inguinal hernia repair in Asia. A group of Asian experts in hernia repair gathered together to debate inguinal hernia treatments in Asia in an attempt to reach some consensus or develop recommendations on best practices in the region. The need for recommendations or guidelines was unanimously confirmed to help overcome the discrepancy in clinical practice between countries; the experts decided to focus mainly on the technical aspects of open repair, which is the most common surgery for hernia in our region. After the identification of 12 main topics for discussion (indication, age, and sex; symptomatic and asymptomatic hernia: type of hernia; type of treatment; hospital admission; preoperative care; anesthesia; surgical technique; perioperative care; postoperative care; early complications; and long-term complications), a search of the literature was carried out according to the five levels of the Oxford Classification of Evidence and the four grades of recommendation.

  10. INTERNAL REPAIR OF PIPELINES

    SciTech Connect

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; George Ritter; Bill Mohr; Matt Boring; Nancy Porter; Mike Sullivan; Chris Neary

    2004-08-17

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without liners

  11. Molecular Regulation of UV-Induced DNA Repair

    PubMed Central

    Shah, Palak; He, Yu-Ying

    2014-01-01

    Ultraviolet (UV) radiation from sunlight is a major etiologic factor for skin cancer, the most prevalent cancer in the U.S., as well as premature skin aging. In particular, UVB radiation causes formation of specific DNA damage photoproducts between pyrimidine bases. These DNA damage photoproducts are repaired by a process called nucleotide excision repair, also known as UV-induced DNA repair. When left unrepaired, UVB-induced DNA damage leads to accumulation of mutations, predisposing people to carcinogenesis as well as to premature aging. Genetic loss of nucleotide excision repair leads to severe disorders, namely, xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne syndrome (CS), which are associated with predisposition to skin carcinogenesis at a young age as well as developmental and neurological conditions. Regulation of nucleotide excision repair is an attractive avenue to preventing or reversing these detrimental consequences of impaired nucleotide excision repair. Here we review recent studies on molecular mechanisms regulating nucleotide excision repair by extracellular cues and intracellular signaling pathways, with a special focus on the molecular regulation of individual repair factors. PMID:25534312

  12. Deficient DNA repair in the human progeroid disorder, Werner syndrome.

    PubMed

    Bohr, Vilhelm A

    2005-09-01

    The study of how DNA repair mechanisms change with aging is central to our understanding of the aging process. Here, I review the molecular functions of a key aging protein, Werner protein (WRN), which is deficient in the premature aging disorder, Werner syndrome (WS). This protein plays a significant role in DNA repair, particularly in base excision repair and in recombination. WRN may be a key regulatory factor in these processes and may also play a role in coordinating them. WRN belongs to the RecQ helicase family of proteins, often referred to as the guardians of the genome. These proteins appear to integrate with the more classic DNA repair pathways and proteins.

  13. Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects

    PubMed Central

    Danis, Ronald P; Lavine, Jeremy A; Domalpally, Amitha

    2015-01-01

    Geographic atrophy (GA) of the retinal pigment epithelium (RPE) is a devastating complication of age-related macular degeneration (AMD). GA may be classified as drusen-related (drusen-associated GA) or neovascularization-related (neovascular-associated GA). Drusen-related GA remains a large public health concern due to the burden of blindness it produces, but pathophysiology of the condition is obscure and there are no proven treatment options. Genotyping, cell biology, and clinical imaging point to upregulation of parainflammatory pathways, oxidative stress, and choroidal sclerosis as contributors, among other factors. Onset and monitoring of progression is accomplished through clinical imaging instrumentation such as optical coherence tomography, photography, and autofluorescence, which are the tools most helpful in determining end points for clinical trials at present. A number of treatment approaches with diverse targets are in development at this time, some of which are in human clinical trials. Neovascular-associated GA is a consequence of RPE loss after development of neovascular AMD. The neovascular process leads to a plethora of cellular stresses such as ischemia, inflammation, and dramatic changes in cell environment that further taxes RPE cells already dysfunctional from drusen-associated changes. GA may therefore develop secondary to the neovascular process de novo or preexisting drusen-associated GA may continue to worsen with the development of neovascular AMD. Neovascular-associated GA is a prominent cause of continued vision loss in patients with otherwise successfully treated neovascular AMD. Clearly, treatment with vascular endothelial growth factor (VEGF) inhibitors early in the course of the neovascular disease is of great clinical benefit. However, there is a rationale and some suggestive evidence that anti-VEGF agents themselves could be toxic to RPE and enhance neovascular-associated GA. The increasing prevalence of legal blindness from this

  14. Rapid road repair vehicle

    SciTech Connect

    Mara, L.M.

    1999-09-07

    Disclosed are improvements to a rapid road repair vehicle comprising an improved cleaning device arrangement, two dispensing arrays for filling defects more rapidly and efficiently, an array of pre-heaters to heat the road way surface in order to help the repair material better bond to the repaired surface, a means for detecting, measuring, and computing the number, location and volume of each of the detected surface imperfection, and a computer means schema for controlling the operation of the plurality of vehicle subsystems. The improved vehicle is, therefore, better able to perform its intended function of filling surface imperfections while moving over those surfaces at near normal traffic speeds.

  15. Rapid road repair vehicle

    DOEpatents

    Mara, Leo M.

    1999-01-01

    Disclosed are improvments to a rapid road repair vehicle comprising an improved cleaning device arrangement, two dispensing arrays for filling defects more rapidly and efficiently, an array of pre-heaters to heat the road way surface in order to help the repair material better bond to the repaired surface, a means for detecting, measuring, and computing the number, location and volume of each of the detected surface imperfection, and a computer means schema for controlling the operation of the plurality of vehicle subsystems. The improved vehicle is, therefore, better able to perform its intended function of filling surface imperfections while moving over those surfaces at near normal traffic speeds.

  16. Cell therapy for bone repair.

    PubMed

    Rosset, P; Deschaseaux, F; Layrolle, P

    2014-02-01

    When natural bone repair mechanisms fail, autologous bone grafting is the current standard of care. The osteogenic cells and bone matrix in the graft provide the osteo-inductive and osteo-conductive properties required for successful bone repair. Bone marrow (BM) mesenchymal stem cells (MSCs) can differentiate into osteogenic cells. MSC-based cell therapy holds promise for promoting bone repair. The amount of MSCs available from iliac-crest aspirates is too small to be clinically useful, and either concentration or culture must therefore be used to expand the MSC population. MSCs can be administered alone via percutaneous injection or implanted during open surgery with a biomaterial, usually biphasic hydroxyapatite/β-calcium-triphosphate granules. Encouraging preliminary results have been obtained in patients with delayed healing of long bone fractures or avascular necrosis of the femoral head. Bone tissue engineering involves in vitro MSC culturing on biomaterials to obtain colonisation of the biomaterial and differentiation of the cells. The biomaterial-cell construct is then implanted into the zone to be treated. Few published data are available on bone tissue engineering. Much work remains to be done before determining whether this method is suitable for the routine filling of bone tissue defects. Increasing cell survival and promoting implant vascularisation are major challenges. Improved expertise with culturing techniques, together with the incorporation of regulatory requirements, will open the way to high-quality clinical trials investigating the usefulness of cell therapy as a method for achieving bone repair. Cell therapy avoids the drawbacks of autologous bone grafting, preserving the bone stock and diminishing treatment invasiveness.

  17. Regulatory Challenges for Cartilage Repair Technologies.

    PubMed

    McGowan, Kevin B; Stiegman, Glenn

    2013-01-01

    In the United States, few Food and Drug Administration (FDA)-approved options exist for the treatment of focal cartilage and osteochondral lesions. Developers of products for cartilage repair face many challenges to obtain marketing approval from the FDA. The objective of this review is to discuss the necessary steps for FDA application and approval for a new cartilage repair product. FDA Guidance Documents, FDA Panel Meetings, scientific organization recommendations, and clinicaltrials.gov were reviewed to demonstrate the current thinking of FDA and the scientific community on the regulatory process for cartilage repair therapies. Cartilage repair therapies can receive market approval from FDA as medical devices, drugs, or biologics, and the specific classification of product can affect the nonclinical, clinical, and regulatory strategy to bring the product to market. Recent FDA guidance gives an outline of the required elements to bring a cartilage repair product to market, although these standards are often very general. As a result, companies have to carefully craft their study patient population, comparator group, and clinical endpoint to best showcase their product's attributes. In addition, regulatory strategy and manufacturing process validation need to be considered early in the clinical study process to allow for timely product approval following the completion of clinical study. Although the path to regulatory approval for a cartilage repair therapy is challenging and time-consuming, proper clinical trial planning and attention to the details can eventually save companies time and money by bringing a product to the market in the most expeditious process possible.

  18. Social behavior in the "Age of Empathy"?-A social scientist's perspective on current trends in the behavioral sciences.

    PubMed

    Matusall, Svenja

    2013-01-01

    Recently, several behavioral sciences became increasingly interested in investigating biological and evolutionary foundations of (human) social behavior. In this light, prosocial behavior is seen as a core element of human nature. A central role within this perspective plays the "social brain" that is not only able to communicate with the environment but rather to interact directly with other brains via neuronal mind reading capacities such as empathy. From the perspective of a sociologist, this paper investigates what "social" means in contemporary behavioral and particularly brain sciences. It will be discussed what "social" means in the light of social neuroscience and a glance into the history of social psychology and the brain sciences will show that two thought traditions come together in social neuroscience, combining an individualistic and an evolutionary notion of the "social." The paper concludes by situating current research on prosocial behavior in broader social discourses about sociality and society, suggesting that to naturalize prosocial aspects in human life is a current trend in today's behavioral sciences and beyond.

  19. Clinical outcomes for Conduits and Scaffolds in peripheral nerve repair

    PubMed Central

    Gerth, David J; Tashiro, Jun; Thaller, Seth R

    2015-01-01

    The gold standard of peripheral nerve repair is nerve autograft when tensionless repair is not possible. Use of nerve autograft has several shortcomings, however. These include limited availability of donor tissue, sacrifice of a functional nerve, and possible neuroma formation. In order to address these deficiencies, researchers have developed a variety of biomaterials available for repair of peripheral nerve gaps. We review the clinical studies published in the English literature detailing outcomes and reconstructive options. Regardless of the material used or the type of nerve repaired, outcomes are generally similar to nerve autograft in gaps less than 3 cm. New biomaterials currently under preclinical evaluation may provide improvements in outcomes. PMID:25685760

  20. Nerve repair and cable grafting for facial paralysis.

    PubMed

    Humphrey, Clinton D; Kriet, J David

    2008-05-01

    Facial nerve injury and facial paralysis are devastating for patients. Although imperfect, primary repair is currently the best option to restore facial nerve function. Cable, or interposition, nerve grafting is an acceptable alternative when primary repair is not possible. Several donor nerves are at the surgeon's disposal. Great auricular, sural, or medial and lateral antebrachial cutaneous nerves are all easily obtained. Both primary repair and interposition grafting typically result in better facial function than do other dynamic and static rehabilitation strategies. Proficient anastomotic technique and, when necessary, selection of an appropriate interposition graft will optimize patient outcomes. Promising research is under way that will enhance future nerve repair and grafting efforts.

  1. Repairing Thermal Tiles

    NASA Technical Reports Server (NTRS)

    Mccain, C. R., Jr.; Feiler, C. W.

    1984-01-01

    Small chips and depression in surfaces of surface insulation tiles repaired using Ludox colloidal silica solution and silica powder. No waiting time necessary between mixing filler and using it. Patch cures quickly without heat being applied.

  2. Easily repairable networks

    NASA Astrophysics Data System (ADS)

    Fink, Thomas

    2015-03-01

    We introduce a simple class of distribution networks which withstand damage by being repairable instead of redundant. Instead of asking how hard it is to disconnect nodes through damage, we ask how easy it is to reconnect nodes after damage. We prove that optimal networks on regular lattices have an expected cost of reconnection proportional to the lattice length, and that such networks have exactly three levels of structural hierarchy. We extend our results to networks subject to repeated attacks, in which the repairs themselves must be repairable. We find that, in exchange for a modest increase in repair cost, such networks are able to withstand any number of attacks. We acknowledge support from the Defense Threat Reduction Agency, BCG and EU FP7 (Growthcom).

  3. INTERNAL REPAIR OF PIPELINES

    SciTech Connect

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; Nancy Porter; Mike Sullivan; Chris Neary

    2004-04-12

    The two broad categories of deposited weld metal repair and fiber-reinforced composite liner repair technologies were reviewed for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Preliminary test programs were developed for both deposited weld metal repair and for fiber-reinforced composite liner repair. Evaluation trials have been conducted using a modified fiber-reinforced composite liner provided by RolaTube and pipe sections without liners. All pipe section specimens failed in areas of simulated damage. Pipe sections containing fiber-reinforced composite liners failed at pressures marginally greater than the pipe sections without liners. The next step is to evaluate a liner material with a modulus of elasticity approximately 95% of the modulus of elasticity for steel. Preliminary welding parameters were developed for deposited weld metal repair in preparation of the receipt of Pacific Gas & Electric's internal pipeline welding repair system (that was designed specifically for 559 mm (22 in.) diameter pipe) and the receipt of 559 mm (22 in.) pipe sections from Panhandle Eastern. The next steps are to transfer welding parameters to the PG&E system and to pressure test repaired pipe sections to failure. A survey of pipeline operators was conducted to better understand the needs and performance requirements of the natural gas transmission industry regarding internal repair. Completed surveys contained the following principal conclusions: (1) Use of internal weld repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling (HDD) when a new bore must be created to

  4. Imperforate anus repair - slideshow

    MedlinePlus

    ... presentations/100030.htm Imperforate anus repair - series—Normal anatomy To use the sharing features on this page, ... of 4 Overview In individuals with a normal anatomy, the large intestine (colon) empties into a pouch- ...

  5. Timpani Repair and Maintenance.

    ERIC Educational Resources Information Center

    Combs, F. Michael

    1980-01-01

    Rather than focusing on specific brands of timpani, these guidelines for repair cover mechanical problems of a general nature: pedals, dents, unclear tone, and squeaking. Preventive maintenance is discussed. (Author/SJL)

  6. Eye muscle repair - slideshow

    MedlinePlus

    ... page: //medlineplus.gov/ency/presentations/100062.htm Eye muscle repair - series—Normal anatomy To use the sharing ... the eyeball to the eye socket. The external muscles of the eye are found behind the conjunctiva. ...

  7. Laparoscopic Ventral Hernia Repair

    MedlinePlus

    ... the likelihood of a hernia including persistent coughing, difficulty with bowel movements or urination, or frequent need for straining. What are the Advantages of Laparoscopic Ventral Hernia Repair? Keep reading... Page 1 of 2 1 2 » Brought to ...

  8. Planning Maintenance and Repairs.

    ERIC Educational Resources Information Center

    Fitzemeyer, Ted

    2001-01-01

    Discusses the use of school facility design as an aid to efficiently repairing and maintaining facility systems. Also presents details on facility design's influence in properly maintaining mechanical and electrical systems. (GR)

  9. Patent urachus repair

    MedlinePlus

    Patent urachal tube repair ... belly. Next, the surgeon will find the urachal tube and remove it. The bladder opening will be ... surgeon uses the tools to remove the urachal tube and close off the bladder and area where ...

  10. Achilles tendon repair

    MedlinePlus

    Achilles tendon rupture-surgery; Percutaneous Achilles tendon rupture repair ... To fix your torn Achilles tendon, the surgeon will: Make a cut down the back of your heel Make several small cuts rather than one large cut ...

  11. Repairing ceramic insulating tiles

    NASA Technical Reports Server (NTRS)

    Dunn, B. R.; Laymance, E. L.

    1980-01-01

    Fused-silica tiles containing large voids or gauges are repaired without adhesives by plug insertion method. Tiles are useful in conduits for high-temperature gases, in furnaces, and in other applications involving heat insulation.

  12. The Aging Stress Response

    PubMed Central

    Haigis, Marcia C.; Yankner, Bruce A.

    2010-01-01

    Aging is the outcome of a balance between damage and repair. The rate of aging and the appearance of age-related pathology are modulated by stress response and repair pathways that gradually decline, including the proteostasis and DNA damage repair networks and mitochondrial respiratory metabolism. Highly conserved insulin/IGF-1, TOR, and sirtuin signaling pathways in turn, control these critical cellular responses. The coordinated action of these signaling pathways maintains cellular and organismal homeostasis in the face of external perturbations, such as changes in nutrient availability, temperature and oxygen level, as well as internal perturbations, such as protein misfolding and DNA damage. Studies in model organisms suggest that changes in signaling can augment these critical stress response systems, increasing lifespan and reducing age-related pathology. The systems biology of stress response signaling thus provides a new approach to the understanding and potential treatment of age-related diseases. PMID:20965426

  13. Hypospadias repair using laser tissue soldering (LTS): preliminary results of a prospective randomized study

    NASA Astrophysics Data System (ADS)

    Kirsch, Andrew J.; Cooper, Christopher S.; Canning, Douglas A.; Snyder, Howard M., III; Zderic, Stephen A.

    1998-07-01

    Purpose: The purpose of this study was to evaluate laser tissue soldering using an 808 nm diode laser and wavelength- matched human albumin solder for urethral surgery in children. Methods: Currently, 30 boys, ages 3 months to 8 years were randomized to standard suturing (n equals 22) or 'sutureless' laser hypospadias repair (n equals 18). Laser soldering was performed with a human albumin solder doped with indocyanine green dye (2.5 mg/ml) using a laser power output of 0.5 W, pulse duration of 0.5 sec, and interval of 0.1 sec. Power density was approximately 16 W/cm2. In the laser group, sutures were used for tissue alignment only. At the time of surgery, neourethral and penile lengths, operative time for urethral repair, and number of sutures/throws were measured. Postoperatively, patients were examined for complications of wound healing, stricture, or fistula formation. Results: Mean age, severity of urethral defect, type of repair, and neourethra length were equivalent between the two groups. Operative time was significantly faster for laser soldering in both simple (1.6 plus or minus 0.21 min, p less than 0.001) and complex (5.4 plus or minus 0.28 min, p less than 0.0001) hypospadias repairs compared to controls (10.6 plus or minus 1.4 min and 27.8 plus or minus 2.9 min, respectively). The mean number of sutures used in the laser group for simple and complex repairs (3.3 plus or minus 0.3 and 8.1 plus or minus 0.64, respectively) were significantly (p less than 0.0001) less than for controls (8.2 plus or minus 0.84 and 20 plus or minus 2.3, respectively). Followup was between 3 months and 14 months. The overall complication rate in the laser group (11%) was lower than the controls (23%). However, statistical significance (p less than 0.05) was achieved only for the subgroup of patients undergoing simple repairs (LTS, 100% success versus suturing, 69% success). Conclusions: These preliminary results indicate that laser tissue soldering for hypospadias repair

  14. Control of excessive lead exposure in radiator repair workers.

    PubMed

    1991-03-01

    In 1988, 83 automotive repair workers with blood lead levels (BLLs) greater than 25 micrograms/dL were reported to state health departments in the seven states that collaborated with CDC's National Institute for Occupational Safety and Health (NIOSH) in maintaining registries of elevated BLLs in adults. In 18 (22%) of these 83 persons, BLLs were greater than 50 micrograms/dL. Among automotive repair workers for whom a job category was specified, radiator repair work was the principal source of lead exposure. The major sources of exposure for radiator repair workers are lead fumes generated during soldering and lead dust produced during radiator cleaning. This report summarizes current BLL surveillance data for radiator repair workers and describes three control technologies that are effective in reducing lead exposures in radiator repair shops.

  15. Repairing Foam Insulation

    NASA Technical Reports Server (NTRS)

    Corbin, J.; Buras, D.

    1986-01-01

    Large holes in polyurethane foam insulation repaired reliably by simple method. Little skill needed to apply method, used for overhead repairs as well as for those in other orientations. Plug positioned in hole to be filled and held in place with mounting fixture. Fresh liquid foam injected through plug to bond it in place. As foam cures and expands, it displaces plug outward. Protrusion later removed.

  16. Regenerative biology of tendon: mechanisms for renewal and repair

    PubMed Central

    Dyment, Nathaniel A.; Galloway, Jenna L.

    2015-01-01

    Understanding the molecular and cellular mechanisms underlying tissue turnover and repair are essential towards addressing pathologies in aging, injury and disease. Each tissue has distinct means of maintaining homeostasis and healing after injury. For some, resident stem cell populations mediate both of these processes. These stem cells, by definition, are self renewing and give rise to all the differentiated cells of that tissue. However, not all organs fit with this traditional stem cell model of regeneration, and some do not appear to harbor somatic stem or progenitor cells capable of multilineage in vivo reconstitution. Despite recent progress in tendon progenitor cell research, our current knowledge of the mechanisms regulating tendon cell homeostasis and injury response is limited. Understanding the role of resident tendon cell populations is of great importance for regenerative medicine based approaches to tendon injuries and disease. The goal of this review is to bring to light our current knowledge regarding tendon progenitor cells and their role in tissue maintenance and repair. We will focus on pressing questions in the field and the new tools, including model systems, available to address them. PMID:26389023

  17. Current Cigarette Smoking, Access, and Purchases from Retail Outlets Among Students Aged 13-15 Years - Global Youth Tobacco Survey, 45 Countries, 2013 and 2014.

    PubMed

    D'Angelo, Denise; Ahluwalia, Indu B; Pun, Eugene; Yin, Shaoman; Palipudi, Krishna; Mbulo, Lazarous

    2016-01-01

    Tobacco use is a leading preventable cause of morbidity and mortality, with nearly 6 million deaths caused by tobacco use worldwide every year (1). Cigarette smoking is the most common form of tobacco use in most countries, and the majority of adult smokers initiate smoking before age 18 years (2,3). Limiting access to cigarettes among youths is an effective strategy to curb the tobacco epidemic by preventing smoking initiation and reducing the number of new smokers (3,4). CDC used the Global Youth Tobacco Survey (GYTS) data from 45 countries to examine the prevalence of current cigarette smoking, purchase of cigarettes from retail outlets, and type of cigarette purchases made among school students aged 13-15 years. The results are presented by the six World Health Organization (WHO) regions: African Region (AFR); Eastern Mediterranean Region (EMR); European Region (EUR); Region of the Americas (AMR); South-East Asian Region (SEAR); and Western Pacific Region (WPR). Across all 45 countries, the median overall current cigarette smoking prevalence among students aged 13-15 years was 6.8% (range = 1.7% [Kazakhstan]-28.9% [Timor-Leste]); the median prevalence among boys was 9.7% (2.0% [Kazakhstan]-53.5% [Timor-Leste]), and among girls was 3.5% (0.0% [Bangladesh]-26.3% [Italy]). The proportion of current cigarette smokers aged 13-15 years who reported purchasing cigarettes from a retail outlet such as a store, street vendor, or kiosk during the past 30 days ranged from 14.9% [Latvia] to 95.1% [Montenegro], and in approximately half the countries, exceeded 50%. In the majority of countries assessed in AFR and SEAR, approximately 40% of cigarette smokers aged 13-15 years reported purchasing individual cigarettes. Approximately half of smokers in all but one country assessed in EUR reported purchasing cigarettes in packs. These findings could be used by countries to inform tobacco control strategies in the retail environment to reduce and prevent marketing and sales of

  18. Current Cigarette Smoking, Access, and Purchases from Retail Outlets Among Students Aged 13-15 Years - Global Youth Tobacco Survey, 45 Countries, 2013 and 2014.

    PubMed

    D'Angelo, Denise; Ahluwalia, Indu B; Pun, Eugene; Yin, Shaoman; Palipudi, Krishna; Mbulo, Lazarous

    2016-09-02

    Tobacco use is a leading preventable cause of morbidity and mortality, with nearly 6 million deaths caused by tobacco use worldwide every year (1). Cigarette smoking is the most common form of tobacco use in most countries, and the majority of adult smokers initiate smoking before age 18 years (2,3). Limiting access to cigarettes among youths is an effective strategy to curb the tobacco epidemic by preventing smoking initiation and reducing the number of new smokers (3,4). CDC used the Global Youth Tobacco Survey (GYTS) data from 45 countries to examine the prevalence of current cigarette smoking, purchase of cigarettes from retail outlets, and type of cigarette purchases made among school students aged 13-15 years. The results are presented by the six World Health Organization (WHO) regions: African Region (AFR); Eastern Mediterranean Region (EMR); European Region (EUR); Region of the Americas (AMR); South-East Asian Region (SEAR); and Western Pacific Region (WPR). Across all 45 countries, the median overall current cigarette smoking prevalence among students aged 13-15 years was 6.8% (range = 1.7% [Kazakhstan]-28.9% [Timor-Leste]); the median prevalence among boys was 9.7% (2.0% [Kazakhstan]-53.5% [Timor-Leste]), and among girls was 3.5% (0.0% [Bangladesh]-26.3% [Italy]). The proportion of current cigarette smokers aged 13-15 years who reported purchasing cigarettes from a retail outlet such as a store, street vendor, or kiosk during the past 30 days ranged from 14.9% [Latvia] to 95.1% [Montenegro], and in approximately half the countries, exceeded 50%. In the majority of countries assessed in AFR and SEAR, approximately 40% of cigarette smokers aged 13-15 years reported purchasing individual cigarettes. Approximately half of smokers in all but one country assessed in EUR reported purchasing cigarettes in packs. These findings could be used by countries to inform tobacco control strategies in the retail environment to reduce and prevent marketing and sales of

  19. Laparoscopic repair of iatrogenic vesicovaginal and rectovaginal fistula

    PubMed Central

    Chu, Lei; Wang, Jian-Jun; Li, Li; Tong, Xiao-Wen; Fan, Bo-Zhen; Guo, Yi; Li, Huai-Fang

    2015-01-01

    Objective: To investigate the clinical efficacy of laparoscopic repair of iatrogenic vesicovaginal fistulas (VVF) and rectovaginal fistulas. Methods: Seventeen female patients with iatrogenic fistulas (11 cases of VVF and 6 cases of high rectovaginal fistulas) were included. All patients were hospitalized and underwent laparoscopic fistula repair in our hospital between 2008 and 2012. The mean age of the patients was 44.8 ± 9.1 years. The fistulas and scar tissue were completely excised by laparoscopy, orifices were tension-free closed using absorbable sutures, omental flaps were interposed between the vagina and the bladder or rectum, and drainage was kept after repair. Results: Laparoscopic repair of fistulas was successful in all 17 patients. No complication was found during or after repair. No reoperation was needed after the repair. The operative time was 80.2 ± 30.0 minutes (range 50-140 minutes). The blood loss was 229.4 ± 101.6 ml (range 100-400 ml). The double J catheters were placed in 7 patients and removed 1-2 months after repair. Eight VVF patients underwent cystoscopy 3 months after laparoscopic repair and there were no abnormal findings. The follow-up time was 17.1 ± 6.5 months (range 8-29 months). Conclusion: Laparoscopic repair of VVF and rectovaginal fistulas is a safe and an effective minimally invasive procedure for treatment of iatrogenic fistula. PMID:25932174

  20. Plasma Membrane Repair in Health and Disease.

    PubMed

    Demonbreun, Alexis R; McNally, Elizabeth M

    2016-01-01

    Since an intact membrane is required for normal cellular homeostasis, membrane repair is essential for cell survival. Human genetic studies, combined with the development of novel animal models and refinement of techniques to study cellular injury, have now uncovered series of repair proteins highly relevant for human health. Many of the deficient repair pathways manifest in skeletal muscle, where defective repair processes result in myopathies or other forms of muscle disease. Dysferlin is a membrane-associated protein implicated in sarcolemmal repair and also linked to other membrane functions including the maintenance of transverse tubules in muscle. MG53, annexins, and Eps15 homology domain-containing proteins interact with dysferlin to form a membrane repair complex and similarly have roles in membrane trafficking in muscle. These molecular features of membrane repair are not unique to skeletal muscle, but rather skeletal muscle, due to its high demands, is more dependent on an efficient repair process. Phosphatidylserine and phosphatidylinositol 4,5-bisphosphate, as well as Ca(2+), are central regulators of membrane organization during repair. Given the importance of muscle health in disease and in aging, these pathways are targets to enhance muscle function and recovery from injury. PMID:26781830

  1. Plasma Membrane Repair in Health and Disease.

    PubMed

    Demonbreun, Alexis R; McNally, Elizabeth M

    2016-01-01

    Since an intact membrane is required for normal cellular homeostasis, membrane repair is essential for cell survival. Human genetic studies, combined with the development of novel animal models and refinement of techniques to study cellular injury, have now uncovered series of repair proteins highly relevant for human health. Many of the deficient repair pathways manifest in skeletal muscle, where defective repair processes result in myopathies or other forms of muscle disease. Dysferlin is a membrane-associated protein implicated in sarcolemmal repair and also linked to other membrane functions including the maintenance of transverse tubules in muscle. MG53, annexins, and Eps15 homology domain-containing proteins interact with dysferlin to form a membrane repair complex and similarly have roles in membrane trafficking in muscle. These molecular features of membrane repair are not unique to skeletal muscle, but rather skeletal muscle, due to its high demands, is more dependent on an efficient repair process. Phosphatidylserine and phosphatidylinositol 4,5-bisphosphate, as well as Ca(2+), are central regulators of membrane organization during repair. Given the importance of muscle health in disease and in aging, these pathways are targets to enhance muscle function and recovery from injury.

  2. Smoking after the age of 65 years: a qualitative exploration of older current and former smokers' views on smoking, stopping smoking, and smoking cessation resources and services.

    PubMed

    Kerr, Susan; Watson, Hazel; Tolson, Debbie; Lough, Murray; Brown, Malcolm

    2006-11-01

    The aim of this study was to explore older current/former smokers' views on smoking, stopping smoking, and smoking cessation resources and services. Despite the fact that older smokers have been identified as a priority group, there is currently a dearth of age-related smoking cessation research to guide practice. The study adopted a qualitative approach and used the health belief model as a conceptual framework. Twenty current and former smokers aged>or=65 years were recruited through general practices and a forum for older adults in the West of Scotland. Data were collected using a semistructured interview schedule. The audio-taped interviews were transcribed and then analysed using content analysis procedures. Current smokers reported many positive associations with smoking, which often prevented a smoking cessation attempt. The majority were aware that smoking had damaged their health; however, some were not convinced of the association. A common view was that 'the damage was done', and therefore, there was little point in attempting to stop smoking. When suggesting a cessation attempt, while some health professionals provided good levels of support, others were reported as providing very little. Some of the participants reported that they had never been advised to stop smoking. Knowledge of local smoking cessation services was generally poor. Finally, concern was voiced regarding the perceived health risks of using nicotine replacement therapy. The main reasons why the former smokers had stopped smoking were health-related. Many had received little help and support from health professionals when attempting to stop smoking. Most of the former smokers believed that stopping smoking in later life had been beneficial to their health. In conclusion, members of the primary care team have a key role to play in encouraging older people to stop smoking. In order to function effectively, it is essential that they take account of older smokers' health beliefs and that

  3. Fracture repair: general aspects and influence of osteoporosis and anti-osteoporosis treatment.

    PubMed

    Féron, Jean-Marc; Mauprivez, Raphaël

    2016-01-01

    Bone differs from other tissues in its capacity to self-repair after a fracture. The low bone mass and structural deterioration of bone associated with osteoporosis increases the risk of fragility fracture compared with healthy individuals. The intention of this article is to review the complex process of fracture repair and essential requirements for a successful fracture healing response summarized as the "diamond concept" in terms of aging and osteoporosis. The current preclinical and clinical evidence for a beneficial or harmful influence of anti-osteoporosis medications such as bisphosphonates, parathyroid hormone (PTH), strontium ranelate and antibodies of Wnt-inhibiting signaling proteins on bone healing is presented and discussed. Literature suggests that there are no detrimental consequences of such therapeutics on fracture repair processes. Following a fragility fracture, it seems that early start of preventive anti-osteoporotic treatment right after surgery does not delay the union of the fracture, except perhaps in the case of very rigidly fixed fracture requiring direct bone healing. There is some promising experimental and clinical evidence for possible enhancement of the bone repair process via administration of systemic agents. Further well designed studies in humans are necessary to accumulate more evidence on the positive effects and to translate this knowledge into valid therapeutic applications. PMID:26768282

  4. Microglia during development and aging.

    PubMed

    Harry, G Jean

    2013-09-01

    Microglia are critical nervous system-specific cells influencing brain development, maintenance of the neural environment, response to injury, and repair. They contribute to neuronal proliferation and differentiation, pruning of dying neurons, synaptic remodeling and clearance of debris and aberrant proteins. Colonization of the brain occurs during gestation with an expansion following birth with localization stimulated by programmed neuronal death, synaptic pruning, and axonal degeneration. Changes in microglia phenotype relate to cellular processes including specific neurotransmitter, pattern recognition, or immune-related receptor activation. Upon activation, microglia cells have the capacity to release a number of substances, e.g., cytokines, chemokines, nitric oxide, and reactive oxygen species, which could be detrimental or beneficial to the surrounding cells. With aging, microglia shift their morphology and may display diminished capacity for normal functions related to migration, clearance, and the ability to shift from a pro-inflammatory to an anti-inflammatory state to regulate injury and repair. This shift in microglia potentially contributes to increased susceptibility and neurodegeneration as a function of age. In the current review, information is provided on the colonization of the brain by microglia, the expression of various pattern recognition receptors to regulate migration and phagocytosis, and the shift in related functions that occur in normal aging.

  5. Microglia During Development and Aging

    PubMed Central

    Harry, G. Jean

    2013-01-01

    Microglia are critical nervous system-specific cells influencing brain development, maintenance of the neural environment, response to injury, and repair. They contribute to neuronal proliferation and differentiation, pruning of dying neurons, synaptic remodeling and clearance of debris and aberrant proteins. Colonization of the brain occurs during gestation with an expansion following birth with localization stimulated by programmed neuronal death, synaptic pruning, andaxonal degeneration. Changes inmicroglia phenotype relate to cellular processes including specific neurotransmitter, pattern recognition, or immune-related receptor activation. Upon activation, microglia cells have the capacity to release a number of substances, e.g., cytokines, chemokines, nitric oxide, and reactive oxygen species, which could be detrimental or beneficial to the surrounding cells. With aging, microglia shift their morphology and may display diminished capacity for normal functions related to migration, clearance, and the ability to shift from a pro-inflammatory to an anti-inflammatory state to regulate injury and repair. This shift in microgliapotentially contributes to increased susceptibility and neurodegeneration as a function of age. In the current review, information is provided on the colonization of the brain by microglia, the expression of various pattern recognition receptors to regulate migration and phagocytosis, and the shift in related functions that occur in normal aging. PMID:23644076

  6. 40 CFR 51.369 - Improving repair effectiveness.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... not currently available, shall insure that training is made available to all interested individuals in...) The application of emission control theory and diagnostic data to the diagnosis and repair of...

  7. Ontology Alignment Repair through Modularization and Confidence-Based Heuristics.

    PubMed

    Santos, Emanuel; Faria, Daniel; Pesquita, Catia; Couto, Francisco M

    2015-01-01

    Ontology Matching aims at identifying a set of semantic correspondences, called an alignment, between related ontologies. In recent years, there has been a growing interest in efficient and effective matching methods for large ontologies. However, alignments produced for large ontologies are often logically incoherent. It was only recently that the use of repair techniques to improve the coherence of ontology alignments began to be explored. This paper presents a novel modularization technique for ontology alignment repair which extracts fragments of the input ontologies that only contain the necessary classes and relations to resolve all detectable incoherences. The paper presents also an alignment repair algorithm that uses a global repair strategy to minimize both the degree of incoherence and the number of mappings removed from the alignment, while overcoming the scalability problem by employing the proposed modularization technique. Our evaluation shows that our modularization technique produces significantly small fragments of the ontologies and that our repair algorithm produces more complete alignments than other current alignment repair systems, while obtaining an equivalent degree of incoherence. Additionally, we also present a variant of our repair algorithm that makes use of the confidence values of the mappings to improve alignment repair. Our repair algorithm was implemented as part of AgreementMakerLight, a free and open-source ontology matching system. PMID:26710335

  8. Ontology Alignment Repair through Modularization and Confidence-Based Heuristics

    PubMed Central

    Santos, Emanuel; Faria, Daniel; Pesquita, Catia; Couto, Francisco M.

    2015-01-01

    Ontology Matching aims at identifying a set of semantic correspondences, called an alignment, between related ontologies. In recent years, there has been a growing interest in efficient and effective matching methods for large ontologies. However, alignments produced for large ontologies are often logically incoherent. It was only recently that the use of repair techniques to improve the coherence of ontology alignments began to be explored. This paper presents a novel modularization technique for ontology alignment repair which extracts fragments of the input ontologies that only contain the necessary classes and relations to resolve all detectable incoherences. The paper presents also an alignment repair algorithm that uses a global repair strategy to minimize both the degree of incoherence and the number of mappings removed from the alignment, while overcoming the scalability problem by employing the proposed modularization technique. Our evaluation shows that our modularization technique produces significantly small fragments of the ontologies and that our repair algorithm produces more complete alignments than other current alignment repair systems, while obtaining an equivalent degree of incoherence. Additionally, we also present a variant of our repair algorithm that makes use of the confidence values of the mappings to improve alignment repair. Our repair algorithm was implemented as part of AgreementMakerLight, a free and open-source ontology matching system. PMID:26710335

  9. Chromatin modifications and DNA repair: beyond double-strand breaks

    PubMed Central

    House, Nealia C. M.; Koch, Melissa R.; Freudenreich, Catherine H.

    2014-01-01

    DNA repair must take place in the context of chromatin, and chromatin modifications and DNA repair are intimately linked. The study of double-strand break repair has revealed numerous histone modifications that occur after induction of a DSB, and modification of the repair factors themselves can also occur. In some cases the function of the modification is at least partially understood, but in many cases it is not yet clear. Although DSB repair is a crucial activity for cell survival, DSBs account for only a small percentage of the DNA lesions that occur over the lifetime of a cell. Repair of single-strand gaps, nicks, stalled forks, alternative DNA structures, and base lesions must also occur in a chromatin context. There is increasing evidence that these repair pathways are also regulated by histone modifications and chromatin remodeling. In this review, we will summarize the current state of knowledge of chromatin modifications that occur during non-DSB repair, highlighting similarities and differences to DSB repair as well as remaining questions. PMID:25250043

  10. Variation in Base Excision Repair Capacity

    PubMed Central

    Wilson, David M.; Kim, Daemyung; Berquist, Brian R.; Sigurdson, Alice J.

    2010-01-01

    The major DNA repair pathway for coping with spontaneous forms of DNA damage, such as natural hydrolytic products or oxidative lesions, is base excision repair (BER). In particular, BER processes mutagenic and cytotoxic DNA lesions such as non-bulky base modifications, abasic sites, and a range of chemically distinct single-strand breaks. Defects in BER have been linked to cancer predisposition, neurodegenerative disorders, and immunodeficiency. Recent data indicate a large degree of sequence variability in DNA repair genes and several studies have associated BER gene polymorphisms with disease risk, including cancer of several sites. The intent of this review is to describe the range of BER capacity among individuals and the functional consequences of BER genetic variants. We also discuss studies that associate BER deficiency with disease risk and the current state of BER capacity measurement assays. PMID:21167187

  11. Induced pluripotent stem cells in cartilage repair

    PubMed Central

    Lietman, Steven A

    2016-01-01

    Articular cartilage repair techniques are challenging. Human embryonic stem cells and induced pluripotent stem cells (iPSCs) theoretically provide an unlimited number of specialized cells which could be used in articular cartilage repair. However thus far chondrocytes from iPSCs have been created primarily by viral transfection and with the use of cocultured feeder cells. In addition chondrocytes derived from iPSCs have usually been formed in condensed cell bodies (resembling embryoid bodies) that then require dissolution with consequent substantial loss of cell viability and phenotype. All of these current techniques used to derive chondrocytes from iPSCs are problematic but solutions to these problems are on the horizon. These solutions will make iPSCs a viable alternative for articular cartilage repair in the near future. PMID:27004161

  12. Induced pluripotent stem cells in cartilage repair.

    PubMed

    Lietman, Steven A

    2016-03-18

    Articular cartilage repair techniques are challenging. Human embryonic stem cells and induced pluripotent stem cells (iPSCs) theoretically provide an unlimited number of specialized cells which could be used in articular cartilage repair. However thus far chondrocytes from iPSCs have been created primarily by viral transfection and with the use of cocultured feeder cells. In addition chondrocytes derived from iPSCs have usually been formed in condensed cell bodies (resembling embryoid bodies) that then require dissolution with consequent substantial loss of cell viability and phenotype. All of these current techniques used to derive chondrocytes from iPSCs are problematic but solutions to these problems are on the horizon. These solutions will make iPSCs a viable alternative for articular cartilage repair in the near future. PMID:27004161

  13. Aging, anti-aging, and hormesis.

    PubMed

    Rattan, Suresh I S

    2004-04-01

    As a result of almost 50 years of efforts in collecting descriptive data, biogerontologists are now able to construct general principles of aging and to explore possibilities of gerontomodulation. Most of the data indicate that aging is characterized by a stochastic accumulation of molecular damage and a progressive failure of maintenance and repair, and the genes involved in homeodynamic pathways are the most likely candidate virtual gerontogenes. Several approaches are being tried and tested to modulate aging in a wide variety of organisms, but with the ultimate aim of improving the quality of human life in old age. These approaches include gene therapy, hormonal supplementation, nutritional modulation, and intervention by antioxidants and other molecules. A recent approach is that of applying hormesis in aging research and therapy, which is based on the principle of stimulation of maintenance and repair pathways by repeated exposure to mild stress.

  14. Repair of DNA Double-Strand Breaks

    NASA Astrophysics Data System (ADS)

    Falk, Martin; Lukasova, Emilie; Kozubek, Stanislav

    The genetic information of cells continuously undergoes damage induced by intracellular processes including energy metabolism, DNA replication and transcription, and by environmental factors such as mutagenic chemicals and UV and ionizing radiation. This causes numerous DNA lesions, including double strand breaks (DSBs). Since cells cannot escape this damage or normally function with a damaged genome, several DNA repair mechanisms have evolved. Although most "single-stranded" DNA lesions are rapidly removed from DNA without permanent damage, DSBs completely break the DNA molecule, presenting a real challenge for repair mechanisms, with the highest risk among DNA lesions of incorrect repair. Hence, DSBs can have serious consequences for human health. Therefore, in this chapter, we will refer only to this type of DNA damage. In addition to the biochemical aspects of DSB repair, which have been extensively studied over a long period of time, the spatio-temporal organization of DSB induction and repair, the importance of which was recognized only recently, will be considered in terms of current knowledge and remaining questions.

  15. Rescheduling with iterative repair

    NASA Technical Reports Server (NTRS)

    Zweben, Monte; Davis, Eugene; Daun, Brian; Deale, Michael

    1992-01-01

    This paper presents a new approach to rescheduling called constraint-based iterative repair. This approach gives our system the ability to satisfy domain constraints, address optimization concerns, minimize perturbation to the original schedule, produce modified schedules, quickly, and exhibits 'anytime' behavior. The system begins with an initial, flawed schedule and then iteratively repairs constraint violations until a conflict-free schedule is produced. In an empirical demonstration, we vary the importance of minimizing perturbation and report how fast the system is able to resolve conflicts in a given time bound. We also show the anytime characteristics of the system. These experiments were performed within the domain of Space Shuttle ground processing.

  16. Aging characteristics of blue InGaN micro-light emitting diodes at an extremely high current density of 3.5 kA cm-2

    NASA Astrophysics Data System (ADS)

    Tian, Pengfei; Althumali, Ahmad; Gu, Erdan; Watson, Ian M.; Dawson, Martin D.; Liu, Ran

    2016-04-01

    The aging characteristics of blue InGaN micro-light emitting diodes (micro-LEDs) with different sizes have been studied at an extremely high current density 3.5 kA cm-2 for emerging micro-LED applications including visible light communication (VLC), micro-LED pumped organic lasers and optogenetics. The light output power of micro-LEDs first increases and then decreases due to the competition of Mg activation in p-GaN layer and defect generation in the active region. The smaller micro-LEDs show less light output power degradation compared with larger micro-LEDs, which is attributed to the lower junction temperature of smaller micro-LEDs. It is found that the high current density without additional junction temperature cannot induce significant micro-LED degradation at room temperature but the combination of the high current density and high junction temperature leads to strong degradation. Furthermore, the cluster LEDs, composed of a micro-LED array, have been developed with both high light output power and less light output degradation for micro-LED applications in solid state lighting and VLC.

  17. Signaling Pathways in Cartilage Repair

    PubMed Central

    Mariani, Erminia; Pulsatelli, Lia; Facchini, Andrea

    2014-01-01

    In adult healthy cartilage, chondrocytes are in a quiescent phase characterized by a fine balance between anabolic and catabolic activities. In ageing, degenerative joint diseases and traumatic injuries of cartilage, a loss of homeostatic conditions and an up-regulation of catabolic pathways occur. Since cartilage differentiation and maintenance of homeostasis are finely tuned by a complex network of signaling molecules and biophysical factors, shedding light on these mechanisms appears to be extremely relevant for both the identification of pathogenic key factors, as specific therapeutic targets, and the development of biological approaches for cartilage regeneration. This review will focus on the main signaling pathways that can activate cellular and molecular processes, regulating the functional behavior of cartilage in both physiological and pathological conditions. These networks may be relevant in the crosstalk among joint compartments and increased knowledge in this field may lead to the development of more effective strategies for inducing cartilage repair. PMID:24837833

  18. Circadian clock regulation of skeletal muscle growth and repair.

    PubMed

    Chatterjee, Somik; Ma, Ke

    2016-01-01

    Accumulating evidence indicates that the circadian clock, a transcriptional/translational feedback circuit that generates ~24-hour oscillations in behavior and physiology, is a key temporal regulatory mechanism involved in many important aspects of muscle physiology. Given the clock as an evolutionarily-conserved time-keeping mechanism that synchronizes internal physiology to environmental cues, locomotor activities initiated by skeletal muscle enable entrainment to the light-dark cycles on earth, thus ensuring organismal survival and fitness. Despite the current understanding of the role of molecular clock in preventing age-related sarcopenia, investigations into the underlying molecular pathways that transmit clock signals to the maintenance of skeletal muscle growth and function are only emerging. In the current review, the importance of the muscle clock in maintaining muscle mass during development, repair and aging, together with its contribution to muscle metabolism, will be discussed. Based on our current understandings of how tissue-intrinsic muscle clock functions in the key aspects muscle physiology, interventions targeting the myogenic-modulatory activities of the clock circuit may offer new avenues for prevention and treatment of muscular diseases. Studies of mechanisms underlying circadian clock function and regulation in skeletal muscle warrant continued efforts. PMID:27540471

  19. Circadian clock regulation of skeletal muscle growth and repair

    PubMed Central

    Chatterjee, Somik; Ma, Ke

    2016-01-01

    Accumulating evidence indicates that the circadian clock, a transcriptional/translational feedback circuit that generates ~24-hour oscillations in behavior and physiology, is a key temporal regulatory mechanism involved in many important aspects of muscle physiology. Given the clock as an evolutionarily-conserved time-keeping mechanism that synchronizes internal physiology to environmental cues, locomotor activities initiated by skeletal muscle enable entrainment to the light-dark cycles on earth, thus ensuring organismal survival and fitness. Despite the current understanding of the role of molecular clock in preventing age-related sarcopenia, investigations into the underlying molecular pathways that transmit clock signals to the maintenance of skeletal muscle growth and function are only emerging. In the current review, the importance of the muscle clock in maintaining muscle mass during development, repair and aging, together with its contribution to muscle metabolism, will be discussed. Based on our current understandings of how tissue-intrinsic muscle clock functions in the key aspects muscle physiology, interventions targeting the myogenic-modulatory activities of the clock circuit may offer new avenues for prevention and treatment of muscular diseases. Studies of mechanisms underlying circadian clock function and regulation in skeletal muscle warrant continued efforts. PMID:27540471

  20. Bone fracture repair - series (image)

    MedlinePlus

    The three main treatment options for bone fractures are: Casting Open reduction, and internal fixation- this involves a surgery to repair the fracture-frequently, metal rods, screws or plates are used to repair the ...

  1. Cleft lip and palate repair

    MedlinePlus

    Orofacial cleft; Craniofacial birth defect repair; Cheiloplasty; Cleft rhinoplasty; Palatoplasty; Tip rhinoplasty ... these conditions at birth. Most times, cleft lip repair is done when the child is 6 to ...

  2. Electric motor model repair specifications

    SciTech Connect

    1995-08-01

    These model repair specifications list the minimum requirements for repair and overhaul of polyphase AC squireel cage induction motors. All power ranges, voltages, and speeds of squirrel cage motors are covered.

  3. Base excision repair: a critical player in many games.

    PubMed

    Wallace, Susan S

    2014-07-01

    This perspective reviews the many dimensions of base excision repair from a 10,000 foot vantage point and provides one person's view on where the field is headed. Enzyme function is considered under the lens of X-ray diffraction and single molecule studies. Base excision repair in chromatin and telomeres, regulation of expression and the role of posttranslational modifications are also discussed in the context of enzyme activities, cellular localization and interacting partners. The specialized roles that base excision repair play in transcriptional activation by active demethylation and targeted oxidation as well as how base excision repair functions in the immune processes of somatic hypermutation and class switch recombination and its possible involvement in retroviral infection are also discussed. Finally the complexities of oxidative damage and its repair and its link to neurodegenerative disorders, as well as the role of base excision repair as a tumor suppressor are examined in the context of damage, repair and aging. By outlining the many base excision repair-related mysteries that have yet to be unraveled, hopefully this perspective will stimulate further interest in the field.

  4. Base excision repair: A critical player in many games

    PubMed Central

    Wallace, Susan S.

    2014-01-01

    This perspective reviews the many dimensions of base excision repair from a 10,000 foot vantage point and provides one person’s view on where the field is headed. Enzyme function is considered under the lens of X-ray diffraction and single molecule studies. Base excision repair in chromatin and telomeres, regulation of expression and the role of posttranslational modifications are also discussed in the context of enzyme activities, cellular localization and interacting partners. The specialized roles that base excision repair play in transcriptional activation by active demethylation and targeted oxidation as well as how base excision repair functions in the immune processes of somatic hypermutation and class switch recombination and its possible involvement in retroviral infection are also discussed. Finally the complexities of oxidative damage and its repair and its link to neurodegenerative disorders, as well as the role of base excision repair as a tumor suppressor are examined in the context of damage, repair and aging. By outlining the many base excision repair-related mysteries that have yet to be unraveled, hopefully this perspective will stimulate further interest in the field. PMID:24780558

  5. Targeting Microtubules for Wound Repair

    PubMed Central

    Charafeddine, Rabab A.; Nosanchuk, Joshua D.; Sharp, David J.

    2016-01-01

    Significance: Fast and seamless healing is essential for both deep and chronic wounds to restore the skin and protect the body from harmful pathogens. Thus, finding new targets that can both expedite and enhance the repair process without altering the upstream signaling milieu and causing serious side effects can improve the way we treat wounds. Since cell migration is key during the different stages of wound healing, it presents an ideal process and intracellular structural machineries to target. Recent Advances and Critical Issues: The microtubule (MT) cytoskeleton is rising as an important structural and functional regulator of wound healing. MTs have been reported to play different roles in the migration of the various cell types involved in wound healing. Specific microtubule regulatory proteins (MRPs) can be targeted to alter a section or subtype of the MT cytoskeleton and boost or hinder cell motility. However, inhibiting intracellular components can be challenging in vivo, especially using unstable molecules, such as small interfering RNA. Nanoparticles can be used to protect these unstable molecules and topically deliver them to the wound. Utilizing this approach, we recently showed that fidgetin-like 2, an uncharacterized MRP, can be targeted to enhance cell migration and wound healing. Future Directions: To harness the full potential of the current MRP therapeutic targets, studies should test them with different delivery platforms, dosages, and skin models. Screening for new MT effectors that boost cell migration in vivo would also help find new targets for skin repair. PMID:27785378

  6. Regenerative Medicine Strategies for Esophageal Repair

    PubMed Central

    Londono, Ricardo

    2015-01-01

    Pathologies that involve the structure and/or function of the esophagus can be life-threatening. The esophagus is a complex organ comprising nonredundant tissue that does not have the ability to regenerate. Currently available interventions for esophageal pathology have limited success and are typically associated with significant morbidity. Hence, there is currently an unmet clinical need for effective methods of esophageal repair. The present article presents a review of esophageal disease along with the anatomic and functional consequences of each pathologic process, the shortcomings associated with currently available therapies, and the latest advancements in the field of regenerative medicine with respect to strategies for esophageal repair from benchtop to bedside. PMID:25813694

  7. New Materials for the Repair of Polyimide Electrical Wire Insulation

    NASA Technical Reports Server (NTRS)

    2008-01-01

    Two viable polyimide backbone materials have been identified that will allow the repair of polyimide electrical wire insulation found on the Space Shuttle and other aging aircraft. This identification is the outcome of ongoing efforts to assess the viability of using such polyimides and polyimide precursors (polyamic acids [PAAs]) as repair materials for aging polyimide electrical wire insulation. These repair materials were selected because they match the chemical makeup of the underlying wire insulation as closely as possible. This similarity allows for maximum compatibility, coupled with the outstanding physical properties of polyimides. The two polyimide backbone materials allow the polymer to be extremely flexible and to melt at low temperatures. A polymer chain end capping group that allows the polymer to crosslink into a nonflowable repair upon curing at around 200 C was also identified.

  8. Repair of proboscis lateralis.

    PubMed

    Uğurlu, Kemal; Karşidag, Semra; Ozçelik, Derya; Sadikoğlu, Buğra; Baş, Lütfü

    2005-01-01

    We report an 8-year-old girl presented with a proboscis on the right nasal nostril, right heminasal hypoplasia, hypertelorism, and cleft lip and palate on the other side. After repair of the cleft lip and palate and the hypertelorism, we successfully reconstructed the heminose with a V-Y advancement flap containing the proboscis tube. PMID:16019753

  9. Repairing cracked glass

    NASA Technical Reports Server (NTRS)

    Helman, D. D.; Holt, J. W.; Smiser, L. V.

    1979-01-01

    Filing procedure consisting of machined lightweight fused-silica tiles coated with thin-layer of borosilicate glass produces homogeneous seal in thin glass. Procedure is useful in repairing glass envelopes, X-ray tub windows, Dewar flasks, and similar thin glass objects.

  10. Automotive Body Repair Competencies.

    ERIC Educational Resources Information Center

    D'Armond, Jack; And Others

    Designed to provide a model curriculum and guidelines, this manual presents tasks that were identified by employers, employees, and teachers as important in a postsecondary auto body repair curriculum. The tasks are divided into ten major component areas of instruction: metalworking and fiberglass, painting, frame and suspension, glass and trim,…

  11. Patent urachus repair - slideshow

    MedlinePlus

    ... Drugs & Supplements Videos & Tools About MedlinePlus Show Search Search MedlinePlus GO GO About MedlinePlus Site Map FAQs Contact Us Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Patent urachus repair - series—Normal anatomy URL of this ...

  12. Aircraft Propeller Hub Repair

    SciTech Connect

    Muth, Thomas R.; Peter, William H.

    2015-02-13

    The team performed a literature review, conducted residual stress measurements, performed failure analysis, and demonstrated a solid state additive manufacturing repair technique on samples removed from a scrapped propeller hub. The team evaluated multiple options for hub repair that included existing metal buildup technologies that the Federal Aviation Administration (FAA) has already embraced, such as cold spray, high velocity oxy-fuel deposition (HVOF), and plasma spray. In addition the team helped Piedmont Propulsion Systems, LLC (PPS) evaluate three potential solutions that could be deployed at different stages in the life cycle of aluminum alloy hubs, in addition to the conventional spray coating method for repair. For new hubs, a machining practice to prevent fretting with the steel drive shaft was recommended. For hubs that were refurbished with some material remaining above the minimal material condition (MMC), a silver interface applied by an electromagnetic pulse additive manufacturing method was recommended. For hubs that were at or below the MMC, a solid state additive manufacturing technique using ultrasonic welding (UW) of thin layers of 7075 aluminum to the hub interface was recommended. A cladding demonstration using the UW technique achieved mechanical bonding of the layers showing promise as a viable repair method.

  13. Basic Book Repair Methods.

    ERIC Educational Resources Information Center

    Schechter, Abraham A.

    This book addresses some common preservation techniques that invariably become necessary in library and archival collections of any size. The procedures are described in chronological sequence, and photographs show the techniques from the viewpoint of the person actually doing the work. The recommended repair methods can be accomplished using…

  14. Comprehensive Small Engine Repair.

    ERIC Educational Resources Information Center

    Hires, Bill; And Others

    This curriculum guide contains the basic information needed to repair all two- and four-stroke cycle engines. The curriculum covers four areas, each consisting of one or more units of instruction that include performance objectives, suggested activities for teacher and students, information sheets, assignment sheets, job sheets, visual aids,…

  15. Targeting Nuclear Envelope Repair.

    PubMed

    2016-06-01

    Migrating cancer cells undergo repeated rupture of the protective nuclear envelope as they squeeze through small spaces in the surrounding tissue, compromising genomic integrity. Inhibiting both general DNA repair and the mechanism that seals these tears may enhance cell death and curb metastasis. PMID:27130435

  16. Repairing Holes in Pressure Walls

    NASA Technical Reports Server (NTRS)

    Mori, Paul Bruce Y.; Capriloa, Laurie J.; Corocado, Alexander R.; Gibbins, Martin N.; Horne, Robert B.

    1987-01-01

    Patches and easy-to-use tools yield pressure-tight seal. Repairer lifts patch from repair kit with hook-and-pile-tipped tool and positions it over puncture hole. With tool, even gloved repairer easily manipulates patch without damaging it.

  17. Lawn and Garden Equipment Repair.

    ERIC Educational Resources Information Center

    Hardway, Jack; And Others

    This publication is designed to supplement the Comprehensive Small Engine Rapair guide by covering in detail all aspects of lawn and garden equipment repair not included in general engine repair or the repair of other small engines. It consists of instructional materials for both teachers and students, written in terms of student performance using…

  18. Cleft lip repair - series (image)

    MedlinePlus

    ... the middle of the upper lip. A cleft palate is an opening in the roof of the mouth (palate). ... Cleft lip repair and cleft palate repair are indicated for: Repair of physical deformity Nursing, feeding, or speech problems resulting from cleft lip or palate

  19. Automotive Engine Maintenance and Repair.

    ERIC Educational Resources Information Center

    Marine Corps Inst., Washington, DC.

    This correspondence course, originally developed for the Marine Corps, is designed to provide students with an understanding of automotive engine maintenance and repair. The course contains six study units covering automotive engine maintenance and repair; design classification; engine malfunction, diagnosis, and repair; engine disassembly; engine…

  20. Small-for-gestational age and large-for-gestational age thresholds to predict infants at risk of adverse delivery and neonatal outcomes: are current charts adequate? An observational study from the Born in Bradford cohort

    PubMed Central

    Norris, T; Johnson, W; Farrar, D; Tuffnell, D; Wright, J; Cameron, N

    2015-01-01

    Objectives Construct an ethnic-specific chart and compare the prediction of adverse outcomes using this chart with the clinically recommended UK-WHO and customised birth weight charts using cut-offs for small-for-gestational age (SGA: birth weight <10th centile) and large-for-gestational age (LGA: birth weight >90th centile). Design Prospective cohort study. Setting Born in Bradford (BiB) study, UK. Participants 3980 White British and 4448 Pakistani infants with complete data for gestational age, birth weight, ethnicity, maternal height, weight and parity. Main outcome measures Prevalence of SGA and LGA, using the three charts and indicators of diagnostic utility (sensitivity, specificity and area under the receiver operating characteristic (AUROC)) of these chart-specific cut-offs to predict delivery and neonatal outcomes and a composite outcome. Results In White British and Pakistani infants, the prevalence of SGA and LGA differed depending on the chart used. Increased risk of SGA was observed when using the UK-WHO and customised charts as opposed to the ethnic-specific chart, while the opposite was apparent when classifying LGA infants. However, the predictive utility of all three charts to identify adverse clinical outcomes was poor, with only the prediction of shoulder dystocia achieving an AUROC>0.62 on all three charts. Conclusions Despite being recommended in national clinical guidelines, the UK-WHO and customised birth weight charts perform poorly at identifying infants at risk of adverse neonatal outcomes. Being small or large may increase the risk of an adverse outcome; however, size alone is not sensitive or specific enough with current detection to be useful. However, a significant amount of missing data for some of the outcomes may have limited the power needed to determine true associations. PMID:25783424

  1. The current status of community-acquired pneumonia management and prevention in children under 5 years of age in India: a review

    PubMed Central

    Yadav, Krishna Kumar; Awasthi, Shally

    2016-01-01

    India has the highest number of global deaths of children under 5 years of age. In the year 2015, it was reported that there were 5.9 million deaths of children under 5 years of age globally, of which 1.2 million (20%) occurred in India alone. Currently, India has an under 5 mortality rate of 48 per 1000 live births. Community-acquired pneumonia contributes to about one sixth of this mortality. Fast breathing is the key symptom of community-acquired pneumonia. The World Health Organization recently categorized community-acquired pneumonia in children under 5 years of age into two, pneumonia, and severe pneumonia. Fast breathing with or without chest in-drawing is categorized as pneumonia and fast breathing with any of danger signs as severe pneumonia. Because effective vaccines against two of the common organisms causing community-acquired pneumonia, namely Streptococcus pneumoniae and Haemophilus influenzae type b, are available, there should be urgent and phased introduction into the Indian Universal Immunization Programme. Several preventable risk factors of community-acquired pneumonia such as lack of exclusive breast feeding for first 6 months of life, inappropriate complimentary feeding, iron deficiency anemia, malnutrition, and indoor air pollution should be adequately addressed. The community should be aware about the signs and symptoms of community-acquired pneumonia and its danger signs so that delay in qualified care seeking can be avoided. To achieve the sustainable development goal of ⩽25 under five deaths per 1000 live births by 2030, a multipronged approach is the need of the hour. PMID:27536353

  2. The current status of community-acquired pneumonia management and prevention in children under 5 years of age in India: a review.

    PubMed

    Yadav, Krishna Kumar; Awasthi, Shally

    2016-06-01

    India has the highest number of global deaths of children under 5 years of age. In the year 2015, it was reported that there were 5.9 million deaths of children under 5 years of age globally, of which 1.2 million (20%) occurred in India alone. Currently, India has an under 5 mortality rate of 48 per 1000 live births. Community-acquired pneumonia contributes to about one sixth of this mortality. Fast breathing is the key symptom of community-acquired pneumonia. The World Health Organization recently categorized community-acquired pneumonia in children under 5 years of age into two, pneumonia, and severe pneumonia. Fast breathing with or without chest in-drawing is categorized as pneumonia and fast breathing with any of danger signs as severe pneumonia. Because effective vaccines against two of the common organisms causing community-acquired pneumonia, namely Streptococcus pneumoniae and Haemophilus influenzae type b, are available, there should be urgent and phased introduction into the Indian Universal Immunization Programme. Several preventable risk factors of community-acquired pneumonia such as lack of exclusive breast feeding for first 6 months of life, inappropriate complimentary feeding, iron deficiency anemia, malnutrition, and indoor air pollution should be adequately addressed. The community should be aware about the signs and symptoms of community-acquired pneumonia and its danger signs so that delay in qualified care seeking can be avoided. To achieve the sustainable development goal of ⩽25 under five deaths per 1000 live births by 2030, a multipronged approach is the need of the hour. PMID:27536353

  3. DNA repair mechanisms in eukaryotes: Special focus in Entamoeba histolytica and related protozoan parasites.

    PubMed

    López-Camarillo, César; Lopez-Casamichana, Mavil; Weber, Christian; Guillen, Nancy; Orozco, Esther; Marchat, Laurence A

    2009-12-01

    Eukaryotic cell viability highly relies on genome stability and DNA integrity maintenance. The cellular response to DNA damage mainly consists of six biological conserved pathways known as homologous recombination repair (HRR), non-homologous end-joining (NHEJ), base excision repair (BER), mismatch repair (MMR), nucleotide excision repair (NER), and methyltransferase repair that operate in a concerted way to minimize genetic information loss due to a DNA lesion. Particularly, protozoan parasites survival depends on DNA repair mechanisms that constantly supervise chromosomes to correct damaged nucleotides generated by cytotoxic agents, host immune pressure or cellular processes. Here we reviewed the current knowledge about DNA repair mechanisms in the most relevant human protozoan pathogens. Additionally, we described the recent advances to understand DNA repair mechanisms in Entamoeba histolytica with special emphasis in the use of genomic approaches based on bioinformatic analysis of parasite genome sequence and microarrays technology.

  4. Thoracoscopic repair of esophageal atresia with tracheoesophageal fistula: Basics of technique and its nuances

    PubMed Central

    Kanojia, Ravi Prakash; Bhardwaj, Neerja; Dwivedi, Deepak; Kumar, Raj; Joshi, Saajan; Samujh, Ram; Rao, K. L. N.

    2016-01-01

    Aim: To review the technique of thoracoscopic repair of esophageal atresia with tracheoesophageal fistula (TREAT) and results reported in literature and with authors’ experience. Patients and Methods: The technique of TREAT was reviewed in detail with evaluation in patients treated at authors’ institution. The patients were selected based on selection criteria and were followed postoperatively. The results available in literature were also reviewed. Results: A total of 29 patients (8 females) were operated by TREAT. Mean age was 2.8 days (range 2-6 days). Mean weight was 2.6 kg (range 1.8-3.2 kg). There was a leak in four patients, and two patients had to be diverted. They are now awaiting definitive repair. Twenty-one patients have completed a mean follow-up of 1.5 years and are doing well except for two patients who had a stricture and underwent serial esophageal dilatations. The results from current literature are provided in tabulated form. Conclusions: TREAT is now a well-established procedure and currently is the preferred approach wherever feasible. The avoidance of thoracotomy is a major advantage to the newborn and is proven to benefit the recovery in the postoperative patient. The technique demonstrated, and the tweaks reported make the procedure easy and is helpful to beginners. The outcome is very much comparable to the open repair as proven by various series. Various parameters like leak rate, anastomotic stricture are the same. The outcome is comparable if you TREAT these babies well. PMID:27365905

  5. Speech and Speech-Related Quality of Life After Late Palate Repair: A Patient's Perspective.

    PubMed

    Schönmeyr, Björn; Wendby, Lisa; Sharma, Mitali; Jacobson, Lia; Restrepo, Carolina; Campbell, Alex

    2015-07-01

    Many patients with cleft palate deformities worldwide receive treatment at a later age than is recommended for normal speech to develop. The outcomes after late palate repairs in terms of speech and quality of life (QOL) still remain largely unstudied. In the current study, questionnaires were used to assess the patients' perception of speech and QOL before and after primary palate repair. All of the patients were operated at a cleft center in northeast India and had a cleft palate with a normal lip or with a cleft lip that had been previously repaired. A total of 134 patients (7-35 years) were interviewed preoperatively and 46 patients (7-32 years) were assessed in the postoperative survey. The survey showed that scores based on the speech handicap index, concerning speech and speech-related QOL, did not improve postoperatively. In fact, the questionnaires indicated that the speech became more unpredictable (P < 0.01) and that nasal regurgitation became worse (P < 0.01) for some patients after surgery. A total of 78% of the patients were still satisfied with the surgery and all of the patients reported that their self-confidence had improved after the operation. Thus, the majority of interviewed patients who underwent late primary palate repair were satisfied with the surgery. At the same time, speech and speech-related QOL did not improve according to the speech handicap index-based survey. Speech predictability may even become worse and nasal regurgitation may increase after late palate repair, according to these results.

  6. Gene Therapy for Cartilage Repair

    PubMed Central

    Madry, Henning; Orth, Patrick; Cucchiarini, Magali

    2011-01-01

    The concept of using gene transfer strategies for cartilage repair originates from the idea of transferring genes encoding therapeutic factors into the repair tissue, resulting in a temporarily and spatially defined delivery of therapeutic molecules to sites of cartilage damage. This review focuses on the potential benefits of using gene therapy approaches for the repair of articular cartilage and meniscal fibrocartilage, including articular cartilage defects resulting from acute trauma, osteochondritis dissecans, osteonecrosis, and osteoarthritis. Possible applications for meniscal repair comprise meniscal lesions, meniscal sutures, and meniscal transplantation. Recent studies in both small and large animal models have demonstrated the applicability of gene-based approaches for cartilage repair. Chondrogenic pathways were stimulated in the repair tissue and in osteoarthritic cartilage using genes for polypeptide growth factors and transcription factors. Although encouraging data have been generated, a successful translation of gene therapy for cartilage repair will require an ongoing combined effort of orthopedic surgeons and of basic scientists. PMID:26069580

  7. Oxidative stress response and Nrf2 signaling in aging

    PubMed Central

    Zhang, Hongqiao; Davies, Kelvin J. A.; Forman, Henry Jay

    2015-01-01

    Increasing oxidative stress, a major characteristic of aging, has been implicated in variety of age-related pathologies. In aging, oxidant production from several sources is increased while antioxidant enzymes, the primary lines of defense, are decreased. Repair systems, including the proteasomal degradation of damaged proteins also declines. Importantly, the adaptive response to oxidative stress declines with aging. Nrf2/EpRE signaling regulates the basal and inducible expression of many antioxidant enzymes and the proteasome. Nrf2/EpRE activity is regulated at several levels including transcription, post-translation, and interaction with other proteins. This review summarizes current studies on age-related impairment of Nrf2/EpRE function and discusses the change of Nrf2 regulatory mechanisms with aging. PMID:26066302

  8. Self sensing composites with emi shielding and self repair

    NASA Astrophysics Data System (ADS)

    Dry, Carolyn

    2015-04-01

    Emi shielding provided by metal coating on repair fibers and conductive repair chemical maintained overall emi resistance of structural panels as well as provided the basis for eddy current and ultrasonic sensing/monitoring of structural panels. The sensing/repair system was easily inserted into composite processing and survived the heat and pressure of VARTM, resin infusion /pressing and pultrusion processing. The panels were tested with a commercial emi test lab, a commercial non-destructive testing lab, and a structural testing lab, The results were positive and will be presented in the paper.

  9. An artificial intelligence-based structural health monitoring system for aging aircraft

    NASA Technical Reports Server (NTRS)

    Grady, Joseph E.; Tang, Stanley S.; Chen, K. L.

    1993-01-01

    To reduce operating expenses, airlines are now using the existing fleets of commercial aircraft well beyond their originally anticipated service lives. The repair and maintenance of these 'aging aircraft' has therefore become a critical safety issue, both to the airlines and the Federal Aviation Administration. This paper presents the results of an innovative research program to develop a structural monitoring system that will be used to evaluate the integrity of in-service aerospace structural components. Currently in the final phase of its development, this monitoring system will indicate when repair or maintenance of a damaged structural component is necessary.

  10. Endovascular Repair of Blunt Popliteal Arterial Injuries

    PubMed Central

    Zhong, Shan; Chen, Zhong; Dong, Peng; Sun, Yequan; Zhu, Wei; Pan, Xiaolin; Qi, Deming

    2016-01-01

    Objective To evaluate the feasibility and effectiveness of endovascular repair for blunt popliteal arterial injuries. Materials and Methods A retrospective analysis of seven patients with clinical suspicion of popliteal arterial injuries that were confirmed by arteriography was performed from September 2009 to July 2014. Clinical data included demographics, mechanism of injury, type of injury, location of injury, concomitant injuries, time of endovascular procedures, time interval from trauma to blood flow restoration, instrument utilized, and follow-up. All patients were male (mean age of 35.9 ± 10.3 years). The type of lesion involved intimal injury (n = 1), partial transection (n = 2), complete transection (n = 2), arteriovenous fistula (n = 1), and pseudoaneurysm (n = 1). All patients underwent endovascular repair of blunt popliteal arterial injuries. Results Technical success rate was 100%. Intimal injury was treated with a bare-metal stent. Pseudoaneurysm and popliteal artery transections were treated with bare-metal stents. Arteriovenous fistula was treated with bare-metal stent and coils. No perioperative death and procedure-related complication occurred. The average follow-up was 20.9 ± 2.3 months (range 18–24 months). One patient underwent intra-arterial thrombolysis due to stent thrombosis at 18 months after the procedure. All limbs were salvaged. Stent migration, deformation, or fracture was not found during the follow-up. Conclusion Endovascular repair seems to be a viable approach for patients with blunt popliteal arterial injuries, especially on an emergency basis. Endovascular repair may be effective in the short-term. Further studies are required to evaluate the long-term efficacy of endovascular repair. PMID:27587969

  11. A biomechanical study of pediatric flexor profundus tendon repair

    PubMed Central

    Al-Thunayan, Turki A.; Al-Zahrani, Mohammed T.; Hakeem, Ahmad A.; Al-Zahrani, Fahad M.; Al-Qattan, Mohammad M.

    2016-01-01

    Objectives: To investigate the tensile strength of repaired flexor profundus tendons in young lambs, which would be equivalent to repairs in children older than 2 years of age. Methods: A comparative in-vitro experimental study conducted at King Saud University, Riyadh, Kingdom of Saudi Arabia from October 2014 to December 2015. We utilized 30 flexor profundus tendons of young lambs with a width of 4 mm. All tendons were repaired with a 4-strand repair technique using 4/0 polypropylene core sutures. In group I (n=10 tendons), 2 separate figure-of-eight sutures were applied. In group II (n=10 tendons), simple locking sutures were added to the corners of 2 separate figure-of-eight sutures. In group III (n=10 tendons), the locked cruciate repair was used. All tendon repairs were tested to single-cycle tensile failure. Results: There was no significant difference between groups II and III with regards to gap and breaking forces; and all forces of these 2 groups were significantly higher than the forces in group I. Conclusion: It was concluded that 4 mm-wide pediatric flexor tendons allow a 4-strand repair and the use of 4/0 sutures. The use of locking sutures increases the tensile strength to values that may allow protective mobilization in children. PMID:27570850

  12. Strengths of balloon films with flaws and repairs

    NASA Technical Reports Server (NTRS)

    Portanova, M. A.

    1989-01-01

    The effects of manufacture flaws and repairs in high altitude scientific balloons was examined. A right circular cylinder was used to induce a biaxial tension-tension stress field in the polyethlene film used to manufacture these balloons. A preliminary investigation of the effect that cylinder geometry has on stress rate as a function of inflation rate was conducted. The ultimate goal was to rank, by order of degrading effects, the flaws and repairs commonly found in current high altitude balloons.

  13. Stem cells in cardiac repair.

    PubMed

    Henning, Robert J

    2011-01-01

    Myocardial infarction is the leading cause of death among people in industrialized nations. Although the heart has some ability to regenerate after infarction, myocardial restoration is inadequate. Consequently, investigators are currently exploring the use of human embryonic stem cells (hESCs), skeletal myoblasts and adult bone marrow stem cells to limit infarct size. hESCs are pluripotent cells that can regenerate myocardium in infarcted hearts, attenuate heart remodeling and contribute to left ventricle (LV) systolic force development. Since hESCs can form heart teratomas, investigators are differentiating hESCs toward cardiac progenitor cells prior to transplantation into hearts. Large quantities of hESCs cardiac progenitor cells, however, must be generated, immune rejection must be prevented and grafts must survive over the long term to significantly improve myocardial performance. Transplanted autologous skeletal myoblasts can survive in infarcted myocardium in small numbers, proliferate, differentiate into skeletal myofibers and increase the LV ejection fraction. These cells, however, do not form electromechanical connections with host cardiomyocytes. Consequently, electrical re-entry can occur and cause cardiac arrhythmias. Autologous bone marrow mononuclear cells contain hematopoietic and mesenchymal stem cells. In several meta-analyses, patients with coronary disease who received autologous bone marrow cells by intracoronary injection show significant 3.7% (range: 1.9-5.4%) increases in LV ejection fraction, decreases in LV end-systolic volume of -4.8 ml (range: -1.4 to -8.2 ml) and reductions in infarct size of 5.5% (-1.9 to -9.1%), without experiencing arrhythmias. Bone marrow cells appear to release biologically active factors that limit myocardial damage. Unfortunately, bone marrow cells from patients with chronic diseases propagate poorly and can die prematurely. Substantial challenges must be addressed and resolved to advance the use of stem cells

  14. Current barriers to treatment for wet age-related macular degeneration (wAMD): findings from the wAMD patient and caregiver survey

    PubMed Central

    Varano, Monica; Eter, Nicole; Winyard, Steve; Wittrup-Jensen, Kim U; Navarro, Rafael; Heraghty, Julie

    2015-01-01

    Purpose A cross-sectional survey to evaluate the current management of wet age-related macular degeneration (wAMD) and to identify barriers to treatment from a patient and caregiver perspective. Methods An ophthalmologist-devised questionnaire was given to a global cohort of patients who were receiving (or had previously received) antivascular endothelial growth factor injections and to caregivers (paid and unpaid) to evaluate the impact of wAMD on their lives. Results Responders included 910 patients and 890 caregivers; wAMD was diagnosed in both eyes in 45% of patients, and 64% had been receiving injections for > 1 year. Many caregivers were a child/grandchild (47%) or partner (23%) of the patient; only 7% were professional caregivers. Most (73%) patients visited a health care professional within 1 month of experiencing vision changes and 54% began treatment immediately. Most patients and caregivers reported a number of obstacles in managing wAMD, including the treatment itself (35% and 39%, respectively). Sixteen percent of patients also missed a clinic visit. Conclusion Most patients seek medical assistance promptly for a change in vision; however, about a quarter of them do not. This highlights a lack of awareness surrounding eye health and the impact of a delayed diagnosis. Most patients and caregivers identified a number of obstacles in managing wAMD. PMID:26664038

  15. Impact of Diluted Pyroclastic Density Currents on Distal Settlements: A Case Study From the Bronze Age Eruption of Avellino, Somma-Vesuvius, Italy

    NASA Astrophysics Data System (ADS)

    di Vito, M. A.; Zanella, E.; Gurioli, L.; Lanza, R.; Sulpizio, R.; Evdokia, T.; Laforgia, E.

    2006-12-01

    During the ancient Bronze Age (Palma Campania Facies) a violent plinian eruption, known as the Avellino eruption, occurred at the Somma-Vesuvius, Italy. The eruption was characterised by two main phases: plinian and phreatomagmatic, respectively. The plinian phase dispersed fallout products across the Italian peninsula in a NE direction, while the phreatomagmatic one generated dilute, turbulent pyroclastic density currents (PDCs). The latter phase impacted the plain NNW of Vesuvius, from Naples to Nola, extending tens of kilometers from the volcano. This territory was densely occupied by human settlements. These currents emplaced dune-bedded and thinly stratified deposits that reached a maximum thickness of 8-10 m in the vent area located in the western sector of the edifice. These deposits thin with distance downstream across the northwestern plain, reaching a maximum runout of up to 25 km. The onset of the phreatomagmatic phase of the eruption, during which highly efficient magma-water interaction triggered highly energetic PDCs is marked by lithic rich, fine grained ash deposits. Across the northwestern and northeastern sectors several human settlements were covered by these deposits. Volcanological field investigations integrated with a detailed facies analysis revealed that the presence of village huts (of wood and straw) affected the distribution and accumulation of these dilute PDCs. A multidisciplinary approach was applied to constrain a number of parameters for the PDCs cropping out in the excavated villages. These include PDC temperature (from the Thermal Remnant Magnetization of the lithics and pottery fragments found within the deposits) and the flow directions (from the magnetic fabric of the fine matrix). These data show that the currents, even if diluted and distal, were still hot, with temperatures of at-least 240-280 °C. The first PDC was able to engulf the village, entering huts, as well as to being locally diverted by these structures. Small

  16. DNA repair: a changing geography? (1964-2008).

    PubMed

    Maisonobe, Marion; Giglia-Mari, Giuseppina; Eckert, Denis

    2013-07-01

    This article aims to explain the current state of DNA Repair studies' global geography by focusing on the genesis of the community. Bibliometric data is used to localize scientific activities related to DNA Repair at the city level. The keyword "DNA Repair" was introduced first by American scientists. It started to spread after 1964 that is to say, after P. Howard-Flanders (Yale University), P. Hanawalt (Stanford University) and R. Setlow (Oak Ridge Laboratories) found evidence for Excision Repair mechanisms. It was the first stage in the emergence of an autonomous scientific community. In this article, we will try to assess to what extent the geo-history of this scientific field is determinant in understanding its current geography. In order to do so, we will localize the places where the first "DNA Repair" publications were signed fifty years ago and the following spatial diffusion process, which led to the current geography of the field. Then, we will focus on the evolution of the research activity of "early entrants" in relation to the activity of "latecomers". This article is an opportunity to share with DNA Repair scientists some research results of a dynamic field in Science studies: spatial scientometrics.

  17. Nucleotide excision repair: new tricks with old bricks.

    PubMed

    Kamileri, Irene; Karakasilioti, Ismene; Garinis, George A

    2012-11-01

    Nucleotide excision repair (NER) is a major DNA repair pathway that ensures that the genome remains functionally intact and is faithfully transmitted to progeny. However, defects in NER lead, in addition to cancer and aging, to developmental abnormalities whose clinical heterogeneity and varying severity cannot be fully explained by the DNA repair deficiencies. Recent work has revealed that proteins in NER play distinct roles, including some that go well beyond DNA repair. NER factors are components of protein complexes known to be involved in nucleosome remodeling, histone ubiquitination, and transcriptional activation of genes involved in nuclear receptor signaling, stem cell reprogramming, and postnatal mammalian growth. Together, these findings add new pieces to the puzzle for understanding NER and the relevance of NER defects in development and disease.

  18. 76 FR 21425 - Rocky Mountain Railcar and Repair, Inc.-Acquisition and Operation Exemption-Line of Railroad in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-15

    ... Surface Transportation Board Rocky Mountain Railcar and Repair, Inc.--Acquisition and Operation Exemption--Line of Railroad in Tooele County, UT Rocky Mountain Railcar and Repair, Inc. (Rocky Mountain), a... line. \\1\\ Rocky Mountain states that it currently operates a railcar repair facility, but that it...

  19. Arthroscopic Transosseous Rotator Cuff Repair: Technical Note, Outcomes, and Complications

    PubMed Central

    Black, Eric M.; Lin, Albert; Srikumaran, Uma; Jain, Nitin; Freehill, Michael T.

    2016-01-01

    The goal of this study was to review the authors’ initial experience with arthroscopic transosseous rotator cuff repair. Thirty-one patients with full-thickness rotator cuff tears underwent arthroscopic transosseous rotator cuff repair over a 15-month period. Preoperatively, demographics and subjective scores were recorded. Postoperatively, pain levels, subjective shoulder values, satisfaction scores, American Shoulder and Elbow Surgeons (ASES) scores, complications, and reoperations were noted with a minimum 2-year follow-up. The relationships between pre- and intraoperative variables and outcome scores were determined with univariate analysis. Average patient age was 56 years, and 23 patients (74%) were men. Twenty patients (65%) underwent primary rotator cuff repair, and 11 patients (35%) underwent revision repair. Average time to follow-up was 26 months. Average preoperative pain level and subjective shoulder value were 5.1 of 10 and 35%, respectively. Average postoperative scores included pain level of 0.9 of 10, subjective shoulder value of 84%, satisfaction score of 90.6 of 100, and ASES score of 86.3 of 100. There were 3 (9.7%) major and 2 (6%) minor complications. Patients undergoing revision rotator cuff repair had significantly worse outcomes (pain level, subjective shoulder value, ASES score; P<.05) compared with those undergoing primary repair, and cortical augmentation did not significantly affect outcome. Overall, outcomes after arthroscopic transosseous rotator cuff repair are good, although patients undergoing revision repair do not have the same outcomes as those undergoing primary cuff repair. The procedure is not without complications (9.7% major, 6% minor complications). Cortical augmentation may be used to supplement fixation, although it does not necessarily affect outcomes. Patients without such augmentation may be at increased risk for suture cutout through the bone. PMID:25970360

  20. 49 CFR 193.2617 - Repairs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Repairs. 193.2617 Section 193.2617 Transportation...: FEDERAL SAFETY STANDARDS Maintenance § 193.2617 Repairs. (a) Repair work on components must be performed... repaired. (b) For repairs made while a component is operating, each operator shall include in...

  1. Revisiting the photosystem II repair cycle

    PubMed Central

    Theis, Jasmine; Schroda, Michael

    2016-01-01

    ABSTRACT The ability of photosystem (PS) II to catalyze the light-driven oxidation of water comes along with its vulnerability to oxidative damage, in particular of the D1 core subunit. Photodamaged PSII undergoes repair in a multi-step process involving (i) reversible phosphorylation of PSII core subunits; (ii) monomerization and lateral migration of the PSII core from grana to stroma thylakoids; (iii) partial disassembly of PSII; (iv) proteolytic degradation of damaged D1; (v) replacement of damaged D1 protein with a new copy; (vi) reassembly of PSII monomers and migration back to grana thylakoids for dimerization and supercomplex assembly. Here we review the current knowledge on the PSII repair cycle. PMID:27494214

  2. Revisiting the photosystem II repair cycle.

    PubMed

    Theis, Jasmine; Schroda, Michael

    2016-09-01

    The ability of photosystem (PS) II to catalyze the light-driven oxidation of water comes along with its vulnerability to oxidative damage, in particular of the D1 core subunit. Photodamaged PSII undergoes repair in a multi-step process involving (i) reversible phosphorylation of PSII core subunits; (ii) monomerization and lateral migration of the PSII core from grana to stroma thylakoids; (iii) partial disassembly of PSII; (iv) proteolytic degradation of damaged D1; (v) replacement of damaged D1 protein with a new copy; (vi) reassembly of PSII monomers and migration back to grana thylakoids for dimerization and supercomplex assembly. Here we review the current knowledge on the PSII repair cycle. PMID:27494214

  3. The mitochondrial theory of aging.

    PubMed

    Kowald, A

    2001-01-01

    Mitochondria are not only the main source of energy for most eukaryotic cells, but also the main source of free radicals. These reactive molecules can damage all components of a cell such as membranes, proteins and DNA. Therefore they have long been suspected to be involved in the biological aging process. The fact that mitochondria posses their own genetic material (mtDNA) and that they only have a limited arsenal of DNA repair processes makes them one of the prime targets for reactive oxygen species. The idea that genetically damaged mitochondria accumulate with time and are causally responsible for the aging phenotype via a disturbed energy budget is at the core of the so called mitochondrial theory of aging. In recent years this idea has gained impetus from the discovery of mitochondrial diseases and mtDNA deletions in old organisms. However, there are still many open questions regarding the mechanism of the accumulation of these deletions and their physiological relevance. This review is therefore intended to give an overview of the current state of the mitochondrial theory of aging and to discuss some recent experimental findings.

  4. Self-Repair of Speech by Four-Year-Old Finnish Children

    ERIC Educational Resources Information Center

    Salonen, Tuuli; Laakso, Minna

    2009-01-01

    The aim of this study was to examine what four-year-old children repair in their speech. For this purpose, conversational self-repairs (N = 316) made by two typically developing Finnish-speaking children (aged 4 ; 8 and 4 ; 11) were examined. The data comprised eight hours of natural interactions videotaped at the children's homes. The tapes were…

  5. The Use of Non-Verbal Repair Strategies by Children with Autism

    ERIC Educational Resources Information Center

    Keen, Deb

    2005-01-01

    This study examined possible links between the occurrence of prosodic changes to vocalizations and gestures and the use of problem behaviors by children with autism when attempting to repair communication breakdowns. The repair strategies of six children with autism aged 2-5 years and with fewer than 10 words or signs were analyzed. Mother-child…

  6. Biomaterial-mediated strategies targeting vascularization for bone repair.

    PubMed

    García, José R; García, Andrés J

    2016-04-01

    Repair of non-healing bone defects through tissue engineering strategies remains a challenging feat in the clinic due to the aversive microenvironment surrounding the injured tissue. The vascular damage that occurs following a bone injury causes extreme ischemia and a loss of circulating cells that contribute to regeneration. Tissue-engineered constructs aimed at regenerating the injured bone suffer from complications based on the slow progression of endogenous vascular repair and often fail at bridging the bone defect. To that end, various strategies have been explored to increase blood vessel regeneration within defects to facilitate both tissue-engineered and natural repair processes. Developments that induce robust vascularization will need to consolidate various parameters including optimization of embedded therapeutics, scaffold characteristics, and successful integration between the construct and the biological tissue. This review provides an overview of current strategies as well as new developments in engineering biomaterials to induce reparation of a functional vascular supply in the context of bone repair.

  7. Will our Current Data Rescue, Curation and Preservation Practices bring us out of the Digital Dark Ages and into the Renaissance of Multi-Source Science? (Invited)

    NASA Astrophysics Data System (ADS)

    Wyborn, L. A.

    2013-12-01

    evolutions of both hardware and software. The move to data intensive science has driven the realisation that we need to put more effort and resources into rescuing, curating and preserving data and properly preserved data sets are now being use to resolve the real world issues of today. However, as the capacity of computational systems increases relentlessly we need to question if our current efforts in data curation and preservation will scale to these ever growing systems. For Earth and Space Sciences to come out of the digital dark ages and into the renaissance of multi-source science, it is time to take stock and question our current data rescue, curation and preservation initiatives. Will the data store I am using be around in 50 years' time? What measures is this data store taking to avoid bit-rot and/or deal with software and hardware obsolescence. Is my data self-describing? Have I paid enough attention to cross domain data standards so my data can be reused and repurposed for the current decadal challenges? More importantly, as the capacity of computational systems scale beyond exascale to zettascale and yottascale, will my data sets that I have rescued, curated and preserved in my lifetime, no matter whether they are small or large, be able to contribute to addressing the decadal challenges that are as yet undefined.

  8. Comparison of Costs of Endovascular Repair versus Open Surgical Repair for Abdominal Aortic Aneurysm in Korea

    PubMed Central

    Min, Sang Il; Min, Seung-Kee; Ahn, Sanghyun; Kim, Suh Min; Park, Daedo; Park, Taejin; Chung, Jin Wook; Park, Jae Hyung; Ha, Jongwon; Kim, Sang Joon

    2012-01-01

    This study was designed to compare the hospital-related costs of elective abdominal aortic aneurysm (AAA) treatment and cost structure between endovascular aneurysm repair (EVAR) and open surgical repair (OSR) in Korean health care system. One hundred five primary elective AAA repairs (79 OSRs and 26 EVARs) performed in the Seoul National University Hospital from 2005 to 2009 were included. Patient characteristics were similar between two groups except for older age (P = 0.004) and more frequent history of malignancy (P = 0.031) in EVAR group. Thirty-day mortality rate was similar between two groups and there was no AAA-related mortality in both groups for 5 yr after repair. The total in-hospital costs for the index admission were significantly higher in EVAR patients (mean, KRW19,857,119) than OSR patients (mean KRW12,395,507) (P < 0.001). The reimbursement was also significantly higher in EVAR patients than OSR patients (mean, KRW14,071,081 vs KRW6,238,895, P < 0.001) while patients payments was comparable between two groups. EVAR patients showed higher follow-up cost up to 2 yr due to more frequent imaging studies and reinterventions for type II endoleaks (15.4%). In the perspective of cost-effectiveness, this study suggests that the determination of which method to be used in AAA treatment be more finely trimmed and be individualized. PMID:22468106

  9. We Are Ageing

    PubMed Central

    Kolovou, Genovefa D.; Kolovou, Vana; Mavrogeni, Sophie

    2014-01-01

    Ageing and longevity is unquestioningly complex. Several thoughts and mechanisms of ageing such as pathways involved in oxidative stress, lipid and glucose metabolism, inflammation, DNA damage and repair, growth hormone axis and insulin-like growth factor (GH/IGF), and environmental exposure have been proposed. Also, some theories of ageing were introduced. To date, the most promising leads for longevity are caloric restriction, particularly target of rapamycin (TOR), sirtuins, hexarelin and hormetic responses. This review is an attempt to analyze the mechanisms and theories of ageing and achieving longevity. PMID:25045704

  10. Membrane Repair: Mechanisms and Pathophysiology

    PubMed Central

    Cooper, Sandra T.; McNeil, Paul L.

    2015-01-01

    Eukaryotic cells have been confronted throughout their evolution with potentially lethal plasma membrane injuries, including those caused by osmotic stress, by infection from bacterial toxins and parasites, and by mechanical and ischemic stress. The wounded cell can survive if a rapid repair response is mounted that restores boundary integrity. Calcium has been identified as the key trigger to activate an effective membrane repair response that utilizes exocytosis and endocytosis to repair a membrane tear, or remove a membrane pore. We here review what is known about the cellular and molecular mechanisms of membrane repair, with particular emphasis on the relevance of repair as it relates to disease pathologies. Collective evidence reveals membrane repair employs primitive yet robust molecular machinery, such as vesicle fusion and contractile rings, processes evolutionarily honed for simplicity and success. Yet to be fully understood is whether core membrane repair machinery exists in all cells, or whether evolutionary adaptation has resulted in multiple compensatory repair pathways that specialize in different tissues and cells within our body. PMID:26336031

  11. Laparoscopic paracolostomy hernia mesh repair.

    PubMed

    Virzí, Giuseppe; Giuseppe, Virzí; Scaravilli, Francesco; Francesco, Scaravilli; Ragazzi, Salvatore; Salvatore, Ragazzi; Piazza, Diego; Diego, Piazza

    2007-12-01

    Paracolostomy hernia is a common occurrence, representing a late complication of stoma surgery. Different surgical techniques have been proposed to repair the wall defect, but the lowest recurrence rates are associated with the use of mesh. We present the case report of a patient in which laparoscopic paracolostomy hernia mesh repair has been successfully performed. PMID:18097321

  12. Major Appliance Repair. Teacher Edition.

    ERIC Educational Resources Information Center

    Smreker, Eugene; Calvert, King

    This module is a comprehensive text on basic appliance repair, designed to prepare students for entry-level jobs in this growing field. Ensuring a firm grounding in electrical knowledge, the module contains 13 instructional units that cover the following topics: (1) major appliance repair orientation; (2) safety and first aid; (3) fundamentals of…

  13. Instructional Guide for Autobody Repair.

    ERIC Educational Resources Information Center

    Virginia Polytechnic Inst. and State Univ., Blacksburg. Dept. of Education.

    The curriculum guide was developed to serve as a statewide model for Virginia auto body repair programs. The guide is designed to 1,080 hours of instruction in eleven blocks: orientation, introduction, welding and cutting, techniques of shaping metal, body filler and fiberglass repairs, body and frame, removing and replacing damaged parts, basic…

  14. Communication Repair and Response Classes

    ERIC Educational Resources Information Center

    Meadan, Hedda; Halle, James W.

    2004-01-01

    A communicative repair has been defined as the ability to persist in communication and to modify, repeat, or revise a signal when the initial communication attempt failed. From an operant perspective, initial communicative acts and communicative repairs can be considered members of a response class in which each response produces the same outcome.…

  15. Pipe inspection and repair system

    NASA Technical Reports Server (NTRS)

    Schempf, Hagen (Inventor); Mutschler, Edward (Inventor); Chemel, Brian (Inventor); Boehmke, Scott (Inventor); Crowley, William (Inventor)

    2004-01-01

    A multi-module pipe inspection and repair device. The device includes a base module, a camera module, a sensor module, an MFL module, a brush module, a patch set/test module, and a marker module. Each of the modules may be interconnected to construct one of an inspection device, a preparation device, a marking device, and a repair device.

  16. Final report on repair procedure of strong ground motion data from underground nuclear tests

    SciTech Connect

    Tunnell, T.W.

    1995-04-01

    Certain difficulties arise when recording close-in around motion from underground nuclear explosions. Data quality can be compromised by a variety of factors, including electromagnetic pulse, noise spikes, direct current effect, and gauge clipping and gauge tilt. From March 1988 through September 1994, EG&G Energy Measurements repaired strong round-motion data (acceleration data) from underground nuclear tests for the Los Alamos National Laboratory using, an automated repair procedure. The automated repair determined and implemented the required repairs based on user input and a consistent set of criteria. A log was kept of each repair so that the repair procedure could be duplicated. This relaxed the requirement to save the repaired data. Developed for the VAX system, the procedure allowed the user to stack up a large number of repairs, plot the repaired data, and obtain hard copies. The plotted data could then be reviewed for a given test to determine the consistency of repair for a given underground test. This feature released the user to perform other tasks while the data were being repaired.

  17. [Roll repair of nonconfluent pulmonary artery].

    PubMed

    Komiya, T; Yamazaki, K; Kohchi, K; Kanzaki, Y

    1995-11-01

    We reviewed the repair of nonconfluent pulmonary artery using a roll to clarify indication of this operation, operative technique (especially the material and the size of conduit) and possibility of total correction. Eleven patients (mean age: five years) and 13 operations including two reoperations were reviewed. The material of the roll was xenopericardium in nine and artificial graft in four operations. No operative death and late death occurred. Five patients required reoperations from three occlusion and two severe stenosis of the roll. Three of nine xenopericardial roll needed reoperations and in two reoperated cases, the roll had been placed behind the aorta. In contrast, one artificial graft needed reoperation. The diameter of the roll was compared with that of normal pulmonary artery estimated from the body surface area. If the roll was too large (more than 125% normal) or too small (less than 100% normal), the luminal diameter of the roll became significantly smaller than appropriate-sized roll (p = 0.002). The size of nonconfluent side of the pulmonary artery also affect the result of repair. In occluded or stenotic cases, the unilateral PA index was significantly smaller than good patent cases (p = 0.014). Total correction was possible in eight cases (73%) including four Rastelli operation, two right ventricular outflow patch enlargement, and two modified Fontan operations without operative death. Thus preoperative evaluation of the pulmonary artery size and anatomy, selection of roll material and size matching seemed to be important for successful roll repair of nonconfluent pulmonary artery.

  18. Arthroscopic Meniscus Repair: Clinical and Isokinetic Results

    PubMed Central

    Grosse, Carmen; Henche, Hans-Rudolph; De Koning, Bart

    1998-01-01

    The importance of the menisci for transmitting workloads in the knee joint to protect the articular cartilage is widely acknowledged. Therefore various techniques have been introduced to repair the damaged meniscus. We performed an arthroscopic meniscus repair with a modified outside-in technique on 29 patients (average 25 years) between 2/91 and 10/94. The average time between trauma and operation was 29 weeks (1–186) – the follow-up 16.3 months (4–49). All the patients were interviewed by phone – 23 were available for clinical respectively isokinetic examination, and categorized following the Lysholm and Lais scores. Twenty-eight patients were happy with the result of the procedure. Following the Lysholm score we found 78% good/excellent results (Lais score 74%). Isokinetic testing showed a muscular deficit of less than 20% in 91% of the cases for flexion (extension 69%). No significant influence neither of the age of the patient nor the time period between trauma and operation on the outcome of the procedure could be found. No complications were reported. Based on our results and well aware of the deleterious long term effects of total meniscectomy the arthroscopic menical repair performed by an experienced surgeon should be generous choice of therapy for the treatment of the ruptured meniscus. PMID:18493462

  19. Reliability-based lifetime maintenance of aging highway bridges

    NASA Astrophysics Data System (ADS)

    Enright, Michael P.; Frangopol, Dan M.

    2000-06-01

    As the nation's infrastructure continues to age, the cost of maintaining it at an acceptable safety level continues to increase. In the United States, about one of every three bridges is rated structurally deficient and/or functionally obsolete. It will require about 80 billion to eliminate the current backlog of bridge deficiencies and maintain repair levels. Unfortunately, the financial resources allocated for these activities fall extremely short of the demand. Although several existing and emerging NDT techniques are available to gather inspection data, current maintenance planning decisions for deficient bridges are based on data from subjective condition assessments and do not consider the reliability of bridge components and systems. Recently, reliability-based optimum maintenance planning strategies have been developed. They can be used to predict inspection and repair times to achieve minimum life-cycle cost of deteriorating structural systems. In this study, a reliability-based methodology which takes into account loading randomness and history, and randomness in strength and degradation resulting from aggressive environmental factors, is used to predict the time- dependent reliability of aging highway bridges. A methodology for incorporating inspection data into reliability predictions is also presented. Finally, optimal lifetime maintenance strategies are identified, in which optimal inspection/repair times are found based on minimum expected life-cycle cost under prescribed reliability constraints. The influence of discount rate on optimum solutions is evaluated.

  20. All-Endoscopic Single-Row Repair of Full-Thickness Gluteus Medius Tears

    PubMed Central

    Levy, David M.; Bogunovic, Ljiljana; Grzybowski, Jeffrey S.; Kuhns, Benjamin D.; Bush-Joseph, Charles A.; Nho, Shane J.

    2016-01-01

    Abductor tendon tears typically develop insidiously in middle-aged women and can lead to debilitating lateral hip pain and a Trendelenburg limp. The gluteus medius tendon is most commonly torn and may show fatty degeneration over time, similar to the rotator cuff muscles of the shoulder. Endoscopic repair offers a therapeutic alternative to traditional open techniques. This article describes the workup, examination, and endoscopic repair of a full-thickness gluteus medius tear presenting as lateral hip pain and weakness. The surgical repair for this case used a single-row suture anchor technique. In addition, the indications and technique for a double-row repair will be discussed. PMID:27073767

  1. Laparoscopic rectocele repair using polyglactin mesh.

    PubMed

    Lyons, T L; Winer, W K

    1997-05-01

    We assessed the efficacy of laparoscopic treatment of rectocele defect using a polyglactin mesh graft. From May 1, 1995, through September 30, 1995, we prospectively evaluated 20 women (age 38-74 yrs) undergoing pelvic floor reconstruction for symptomatic pelvic floor prolapse, with or without hysterectomy. Morbidity of the procedure was extremely low compared with standard transvaginal and transrectal approaches. Patients were followed at 3-month intervals for 1 year. Sixteen had resolution of symptoms. Laparoscopic application of polyglactin mesh for the repair of the rectocele defect is a viable option, although long-term follow-up is necessary. PMID:9154790

  2. Arthroscopic meniscal repair with two-year follow-up: a clinical review.

    PubMed

    Ryu, R K; Dunbar, W H

    1988-01-01

    The potential for healing of meniscal tissue has been historically underappreciated, but is currently more widely acknowledged. We have reviewed our experience with arthroscopic meniscal repair in 29 patients who had had a minimum of 2 years' follow-up. Between September 1983 and November 1986, 31 patients who had undergone arthroscopic meniscal repair with a minimum of 2-years' follow-up were identified. Of the 31 patients, 29 were available for additional follow-up. The patient population averaged 31 years of age, with 15 men and 14 women. Utilizing a closed arthroscopic cannulated technique, 16 lateral and 15 medial menisci were repaired. The majority of lesions were vertical bucket-handle tears involving the posterior horn and averaged 2.5 cm in length. Of the 31 tears, 29 were in the red-red or red-white zones. Clinical healing was present in 27 (87%) of the 31 repaired menisci. Nine patients underwent relook arthroscopy at which time healing was confirmed in eight, and a retear noted in one. Four reruptures occurred and the menisci required removal. Of the 29 patients, 16 had concomitant anterior cruciate ligament injuries ranging from partial tears to complete disruptions. Seven patients underwent immediate or delayed anterior cruciate ligament stabilization. Healing occurred in six of the seven patients whose anterior cruciate ligaments had been reconstructed. Among those patients with reruptures, chronic anterolateral rotatory instability was identified as a significant risk factor for rerupture. A complication rate of 13% was noted. Three patients underwent manipulation under anesthesia for postoperative ankylosis and one patient experienced a transient saphenous nerve neuropraxia.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. The ups and downs of DNA repair biomarkers for PARP inhibitor therapies

    PubMed Central

    Wang, XiaoZhe; Weaver, David T

    2011-01-01

    PARP inhibitors are emerging as a valuable new drug class in the treatment of cancer. Recent discoveries make a compelling case for the complexity of DNA repair biomarker evaluation and underscore the need to examine at multiple biomarkers in a relational manner. This review updates the current trends in DNA repair biomarker strategies in use for the PARP inhibitors and describes the impact of many DNA repair biomarkers on PARP inhibitor benefit in the cancer clinic. PMID:21968427

  4. Lin28 enhances tissue repair by reprogramming cellular metabolism

    PubMed Central

    Shyh-Chang, Ng; Zhu, Hao; de Soysa, T. Yvanka; Shinoda, Gen; Seligson, Marc T.; Tsanov, Kaloyan M.; Nguyen, Liem; Asara, John M.; Cantley, Lewis C.; Daley, George Q.

    2014-01-01

    SUMMARY Regeneration capacity declines with age, but why juvenile organisms show enhanced tissue repair remains unexplained. Lin28a, a highly-conserved RNA binding protein expressed during embryogenesis, plays roles in development, pluripotency and metabolism. To determine if Lin28a might influence tissue repair in adults, we engineered the reactivation of Lin28a expression in several models of tissue injury. Lin28a reactivation improved hair regrowth by promoting anagen in hair follicles, and accelerated regrowth of cartilage, bone and mesenchyme after ear and digit injuries. Lin28a inhibits let-7 microRNA biogenesis; however let-7 repression was necessary but insufficient to enhance repair. Lin28a bound to and enhanced the translation of mRNAs for several metabolic enzymes, thereby increasing glycolysis and oxidative phosphorylation (OxPhos). Lin28a-mediated enhancement of tissue repair was negated by OxPhos inhibition, whereas a pharmacologically-induced increase in OxPhos enhanced repair. Thus, Lin28a enhances tissue repair in some adult tissues by reprogramming cellular bioenergetics. PMID:24209617

  5. Should we think about wrist extensor after flexor tendon repair?

    PubMed Central

    Ferreira, Aline M; Tanaka, Denise M; Barbosa, Rafael I; Marcolino, Alexandre M; Elui, Valeria MC; Mazzer, Nilton

    2013-01-01

    Objective: To evaluate the activity of wrist extensor muscle, correlating with wrist motion during gripping after flexor tendon repair. Design: Cross-sectional clinical measurement study. Setting: Laboratory for biomechanics and rehabilitation. Subjects: A total of 11 patients submitted to rehabilitation by early passive motion of the fingers with wrist flexion position were evaluated after 8 weeks of fingers flexor tendon repair and 11 healthy volunteers, all ranging from 20 to 37 years of age. Intervention: Volunteers performed an isometric standardized gripping task. Main measures: We used electrogoniometry to analyze wrist range of motion and surface electromyography, considering 100% maximum voluntary contraction to represent the amplitude of electromyographic activity of the extensor carpi radialis and flexor digitorum superficialis. Results: Patients with flexor tendon repair showed co-activation deficit between wrist extensor (extensor carpi radialis) and flexor finger muscles (flexor digitorum superficialis) during gripping in the intermediate phase of rehabilitation, despite some recovering mobility for wrist extension (p ≤ 0.05). A moderate correlation between range of motion and extensor carpi radialis was present only for injured group (r = 0.32). Total active motion score, which represents finger active excursion, was regular or poor in 65% of cases, all with nerve repair associated. Conclusion: Wrist extensors have an important synergist role at handgrip, although some imbalance can be present after flexor tendon repair. These preliminary findings suggest that emphasis could be directed to add synergistic wrist motion in rehabilitation protocols after flexor tendon repair. Future studies with early active rehabilitation are necessary. PMID:26770674

  6. Ventricular septal defect: early against late surgical repair

    PubMed Central

    Siddiqui, Waqas J.; Iyer, Praneet; Amba, Samridhi; Muddassir, Salman; Cheboterav, Oleg

    2016-01-01

    Ventricular septal defect (VSD) is a rare complication of right ventricular infarction (RVI) which is associated with significant mortality, if not treated appropriately. It typically occurs within the first 10–14 days after myocardial infarction. Surgical repair has been shown to reduce in-hospital mortality from 90% to 33–45%. Early surgical VSD repair has also been associated with high 30-day operative mortality of 34–37%. Furthermore, after an acute MI the friable myocardium enhances the risk of recurrent VSD with early surgical repair. We present a case of a middle-aged woman who developed VSD after an RVI. Her surgical repair was delayed by 2 weeks due to development of Staphylococcus aureus bacteremia. During this period, she was managed medically and later on underwent percutaneous repair with an amplatzer VSD occluder device. Keeping this patient encounter in mind, we would like to emphasize on the limited recommendations available for early against late surgical repair of VSD. PMID:26908387

  7. Wound repair in Pocillopora.

    PubMed

    Rodríguez-Villalobos, Jenny Carolina; Work, Thierry Martin; Calderon-Aguilera, Luis Eduardo

    2016-09-01

    Corals routinely lose tissue due to causes ranging from predation to disease. Tissue healing and regeneration are fundamental to the normal functioning of corals, yet we know little about this process. We described the microscopic morphology of wound repair in Pocillopora damicornis. Tissue was removed by airbrushing fragments from three healthy colonies, and these were monitored daily at the gross and microscopic level for 40days. Grossly, corals healed by Day 30, but repigmentation was not evident at the end of the study (40d). On histology, from Day 8 onwards, tissues at the lesion site were microscopically indistinguishable from adjacent normal tissues with evidence of zooxanthellae in gastrodermis. Inflammation was not evident. P. damicornis manifested a unique mode of regeneration involving projections of cell-covered mesoglea from the surface body wall that anastomosed to form gastrovascular canals. PMID:27397755

  8. Wound repair in Pocillopora

    USGS Publications Warehouse

    Rodríguez-Villalobos, Jenny Carolina; Work, Thierry M.; Calderon-Aguileraa, Luis Eduardo

    2016-01-01

    Corals routinely lose tissue due to causes ranging from predation to disease. Tissue healing and regeneration are fundamental to the normal functioning of corals, yet we know little about this process. We described the microscopic morphology of wound repair in Pocillopora damicornis. Tissue was removed by airbrushing fragments from three healthy colonies, and these were monitored daily at the gross and microscopic level for 40 days. Grossly, corals healed by Day 30, but repigmentation was not evident at the end of the study (40 d). On histology, from Day 8 onwards, tissues at the lesion site were microscopically indistinguishable from adjacent normal tissues with evidence of zooxanthellae in gastrodermis. Inflammation was not evident. P. damicornis manifested a unique mode of regeneration involving projections of cell-covered mesoglea from the surface body wall that anastomosed to form gastrovascular canals.

  9. Wound repair in Pocillopora.

    PubMed

    Rodríguez-Villalobos, Jenny Carolina; Work, Thierry Martin; Calderon-Aguilera, Luis Eduardo

    2016-09-01

    Corals routinely lose tissue due to causes ranging from predation to disease. Tissue healing and regeneration are fundamental to the normal functioning of corals, yet we know little about this process. We described the microscopic morphology of wound repair in Pocillopora damicornis. Tissue was removed by airbrushing fragments from three healthy colonies, and these were monitored daily at the gross and microscopic level for 40days. Grossly, corals healed by Day 30, but repigmentation was not evident at the end of the study (40d). On histology, from Day 8 onwards, tissues at the lesion site were microscopically indistinguishable from adjacent normal tissues with evidence of zooxanthellae in gastrodermis. Inflammation was not evident. P. damicornis manifested a unique mode of regeneration involving projections of cell-covered mesoglea from the surface body wall that anastomosed to form gastrovascular canals.

  10. Coal bunker repairs

    SciTech Connect

    Emmons, M.H.; Hoffman, M.G. )

    1992-01-01

    Detroit Edison's St. Clair Power Plant (STCPP) Units 1 through 4 are 1950's vintage fossil fueled units with an average capacity of 163 megawatt per unit. Each unit had identical 2190 ton bunkers. The Unit No. 1 bunker had been experiencing noticeable exterior deterioration at the lower level internal support system. An internal bunker inspection revealed large deflections in the network of beams supporting the bunker side walls. A complete collapse of the internal support beams was imminent. Failure of these beams would have transferred the coal pressure loads to the bunker skin and external stiffeners which were not capable of sustaining the load and were also showing signs of distress. This paper presents the temporary repair installed immediately after inspection, the redesign of the lower internal support system and construction procedures involved in bringing the bunker back into operating condition.

  11. TPS Inspection and Repair

    NASA Technical Reports Server (NTRS)

    Parazynski, Scott

    2012-01-01

    Dr. Scott Parazynski provided a retrospective on the EVA tools and procedures efforts NASA went through in the aftermath of Columbia for the Shuttle Thermal Protection System (TPS) inspection and repair. He describes his role as the lead astronaut on this effort, and covered all of the Neutral Buoyancy Lab (NBL), KC 135 (reduced gravity aircraft), Precision Air Bearing Floor (PABF), vacuum chamber and 1 G testing that was done in order to develop the tools and techniques that were flown. Parazynski also discusses how the EVA community worked together to resolve a huge safety issue, and how his work in the spacesuit was critical to overcoming a design limitation of the Space Shuttle.

  12. Total Percutaneous Aortic Repair: Midterm Outcomes

    SciTech Connect

    Bent, Clare L. Fotiadis, Nikolas; Renfrew, Ian; Walsh, Michael; Brohi, Karim; Kyriakides, Constantinos; Matson, Matthew

    2009-05-15

    The purpose of this study was to examine the immediate and midterm outcomes of percutaneous endovascular repair of thoracic and abdominal aortic pathology. Between December 2003 and June 2005, 21 patients (mean age: 60.4 {+-} 17.1 years; 15 males, 6 females) underwent endovascular stent-graft insertion for thoracic (n = 13) or abdominal aortic (n = 8) pathology. Preprocedural computed tomographic angiography (CTA) was performed to assess the suitability of aorto-iliac and common femoral artery (CFA) anatomy, including the degree of CFA calcification, for total percutaneous aortic stent-graft repair. Percutaneous access was used for the introduction of 18- to 26-Fr delivery devices. A 'preclose' closure technique using two Perclose suture devices (Perclose A-T; Abbott Vascular) was used in all cases. Data were prospectively collected. Each CFA puncture site was assessed via clinical examination and CTA at 1, 6, and 12 months, followed by annual review thereafter. Minimum follow-up was 36 months. Outcome measures evaluated were rates of technical success, conversion to open surgical repair, complications, and late incidence of arterial stenosis at the site of Perclose suture deployment. A total of 58 Perclose devices were used to close 29 femoral arteriotomies. Outer diameters of stent-graft delivery devices used were 18 Fr (n = 5), 20 Fr (n = 3), 22 Fr (n = 4), 24 Fr (n = 15), and 26 Fr (n = 2). Percutaneous closure was successful in 96.6% (28/29) of arteriotomies. Conversion to surgical repair was required at one access site (3.4%). Mean follow-up was 50 {+-} 8 months. No late complications were observed. By CT criteria, no patient developed a >50% reduction in CFA caliber at the site of Perclose deployment during the study period. In conclusion, percutaneous aortic stent-graft insertion can be safely performed, with a low risk of both immediate and midterm access-related complications.

  13. Longevity and resistance to stress correlate with DNA repair capacity in Caenorhabditis elegans.

    PubMed

    Hyun, Moonjung; Lee, Jihyun; Lee, Kyungjin; May, Alfred; Bohr, Vilhelm A; Ahn, Byungchan

    2008-03-01

    DNA repair is an important mechanism by which cells maintain genomic integrity. Decline in DNA repair capacity or defects in repair factors are thought to contribute to premature aging in mammals. The nematode Caenorhabditis elegans is a good model for studying longevity and DNA repair because of key advances in understanding the genetics of aging in this organism. Long-lived C. elegans mutants have been identified and shown to be resistant to oxidizing agents and UV irradiation, suggesting a genetically determined correlation between DNA repair capacity and life span. In this report, gene-specific DNA repair is compared in wild-type C. elegans and stress-resistant C. elegans mutants for the first time. DNA repair capacity is higher in long-lived C. elegans mutants than in wild-type animals. In addition, RNAi knockdown of the nucleotide excision repair gene xpa-1 increased sensitivity to UV and reduced the life span of long-lived C. elegans mutants. These findings support that DNA repair capacity correlates with longevity in C. elegans.

  14. Does the light source affect the repairability of composite resins?

    PubMed

    Karaman, Emel; Gönülol, Nihan

    2014-01-01

    The aim of this study was to examine the effect of the light source on the microshear bond strength of different composite resins repaired with the same substrate. Thirty cylindrical specimens of each composite resin--Filtek Silorane, Filtek Z550 (3M ESPE), Gradia Direct Anterior (GC), and Aelite Posterior (BISCO)--were prepared and light-cured with a QTH light curing unit (LCU). The specimens were aged by thermal cycling and divided into three subgroups according to the light source used--QTH, LED, or PAC (n = 10). They were repaired with the same substrate and a Clearfil Repair Kit (Kuraray). The specimens were light-cured and aged for 1 week in distilled water at 37 °C. The microshear bond strength and failure modes were assessed. There was no significant difference in the microshear bond strength values among the composite resins, except for the Filtek Silorane group that showed significantly lower bond strength values when polymerized with the PAC unit compared to the QTH or LED unit. In conclusion, previously placed dimethacrylate-based composites can be repaired with different light sources; however, if the composite to be repaired is silorane-based, then using a QTH or LED device may be the best option. PMID:25098825

  15. Component Repair Experiment-1: An Experiment Evaluating Electronic Component-Level Repair During Spaceflight

    NASA Technical Reports Server (NTRS)

    Easton, John W.; Struk, Peter M.

    2012-01-01

    The Component Repair Experiment-1 (CRE-1) examines the capability for astronauts to perform electronics repair tasks in space. The goal is to determine the current capabilities and limits for the crew, and to make recommendations to improve and expand the range of work that astronauts may perform. CRE-1 provided two-layer, functional circuit boards and replacement components, a small tool kit, written and video training materials, and 1 hr of hands on training for the crew slated to perform the experiment approximately 7 months prior to the mission. Astronauts Michael Fincke and Sandra Magnus performed the work aboard the International Space Station (ISS) in February and March 2009. The astronauts were able to remove and replace components successfully, demonstrating the feasibility of performing component-level electronics repairs within a spacecraft. Several unsuccessful tasks demonstrated areas in need of improvement. These include improved and longer training prior to a mission, an improved soldering iron with a higher operating temperature and steady power source, video training and practice boards for refresher work or practice before a repair, and improved and varied hand tools and containment system.

  16. LWR Sustainability: Assessment of Aging of Nuclear Power Plant Safety Related Concrete Strutures

    SciTech Connect

    Graves III, Herman; Naus, Dan J

    2013-01-01

    Current regulatory testing and inspection requirements are reviewed and a summary of degradation experience is presented. Techniques commonly used to inspect NPP concrete structures to assess and quantify age-related degradation are summarized. An approach for conduct of condition assessments of structures in NPPs is presented. Criteria, based primarily on visual indications, are provided for use in classification and assessment of concrete degradation. Materials and techniques for repair of degraded structures are generally discussed.

  17. DNA repair in Chromobacterium violaceum.

    PubMed

    Duarte, Fábio Teixeira; Carvalho, Fabíola Marques de; Bezerra e Silva, Uaska; Scortecci, Kátia Castanho; Blaha, Carlos Alfredo Galindo; Agnez-Lima, Lucymara Fassarella; Batistuzzo de Medeiros, Silvia Regina

    2004-03-31

    Chromobacterium violaceum is a Gram-negative beta-proteobacterium that inhabits a variety of ecosystems in tropical and subtropical regions, including the water and banks of the Negro River in the Brazilian Amazon. This bacterium has been the subject of extensive study over the last three decades, due to its biotechnological properties, including the characteristic violacein pigment, which has antimicrobial and anti-tumoral activities. C. violaceum promotes the solubilization of gold in a mercury-free process, and has been used in the synthesis of homopolyesters suitable for the production of biodegradable polymers. The complete genome sequence of this organism has been completed by the Brazilian National Genome Project Consortium. The aim of our group was to study the DNA repair genes in this organism, due to their importance in the maintenance of genomic integrity. We identified DNA repair genes involved in different pathways in C. violaceum through a similarity search against known sequences deposited in databases. The phylogenetic analyses were done using programs of the PHILYP package. This analysis revealed various metabolic pathways, including photoreactivation, base excision repair, nucleotide excision repair, mismatch repair, recombinational repair, and the SOS system. The similarity between the C. violaceum sequences and those of Neisserie miningitidis and Ralstonia solanacearum was greater than that between the C. violaceum and Escherichia coli sequences. The peculiarities found in the C. violaceum genome were the absence of LexA, some horizontal transfer events and a large number of repair genes involved with alkyl and oxidative DNA damage.

  18. Designing ideal conduits for peripheral nerve repair

    PubMed Central

    de Ruiter, Godard C. W.; Malessy, Martijn J. A.; Yaszemski, Michael J.; Windebank, Anthony J.; Spinner, Robert J.

    2010-01-01

    Nerve tubes, guides, or conduits are a promising alternative for autologous nerve graft repair. The first biodegradable empty single lumen or hollow nerve tubes are currently available for clinical use and are being used mostly in the repair of small-diameter nerves with nerve defects of < 3 cm. These nerve tubes are made of different biomaterials using various fabrication techniques. As a result these tubes also differ in physical properties. In addition, several modifications to the common hollow nerve tube (for example, the addition of Schwann cells, growth factors, and internal frameworks) are being investigated that may increase the gap that can be bridged. This combination of chemical, physical, and biological factors has made the design of a nerve conduit into a complex process that demands close collaboration of bioengineers, neuroscientists, and peripheral nerve surgeons. In this article the authors discuss the different steps that are involved in the process of the design of an ideal nerve conduit for peripheral nerve repair. PMID:19435445

  19. Influence of calorie reduction on DNA repair capacity of human peripheral blood mononuclear cells.

    PubMed

    Matt, Katja; Burger, Katharina; Gebhard, Daniel; Bergemann, Jörg

    2016-03-01

    Caloric restrictive feeding prolongs the lifespan of a variety of model organisms like rodents and invertebrates. It has been shown that caloric restriction reduces age-related as well as overall-mortality, reduces oxidative stress and influences DNA repair ability positively. There are numerous studies underlining this, but fewer studies involving humans exist. To contribute to a better understanding of the correlation of calorie reduction and DNA repair in humans, we adapted the host cell reactivation assay to an application with human peripheral blood mononuclear cells. Furthermore, we used this reliable and reproducible assay to research the influence of a special kind of calorie reduction, namely F. X. Mayr therapy, on DNA repair capacity. We found a positive effect in all persons with low pre-existing DNA repair capacity. In individuals with normal pre-existing DNA repair capacity, no effect on DNA repair capacity was detectable. Decline of DNA repair, accumulation of oxidative DNA damages, mitochondrial dysfunction, telomere shortening as well as caloric intake are widely thought to contribute to aging. With regard to that, our results can be considered as a strong indication that calorie reduction may support DNA repair processes and thus contribute to a healthier aging.

  20. DNA repair in Mycoplasma gallisepticum

    PubMed Central

    2013-01-01

    Background DNA repair is essential for the maintenance of genome stability in all living beings. Genome size as well as the repertoire and abundance of DNA repair components may vary among prokaryotic species. The bacteria of the Mollicutes class feature a small genome size, absence of a cell wall, and a parasitic lifestyle. A small number of genes make Mollicutes a good model for a “minimal cell” concept. Results In this work we studied the DNA repair system of Mycoplasma gallisepticum on genomic, transcriptional, and proteomic levels. We detected 18 out of 22 members of the DNA repair system on a protein level. We found that abundance of the respective mRNAs is less than one per cell. We studied transcriptional response of DNA repair genes of M. gallisepticum at stress conditions including heat, osmotic, peroxide stresses, tetracycline and ciprofloxacin treatment, stationary phase and heat stress in stationary phase. Conclusions Based on comparative genomic study, we determined that the DNA repair system M. gallisepticum includes a sufficient set of proteins to provide a cell with functional nucleotide and base excision repair and mismatch repair. We identified SOS-response in M. gallisepticum on ciprofloxacin, which is a known SOS-inducer, tetracycline and heat stress in the absence of established regulators. Heat stress was found to be the strongest SOS-inducer. We found that upon transition to stationary phase of culture growth transcription of DNA repair genes decreases dramatically. Heat stress does not induce SOS-response in a stationary phase. PMID:24148612

  1. Ulnar Collateral Ligament Repair with Internal Brace Augmentation

    PubMed Central

    Walters, Brian L.; Cain, E. Lyle; Emblom, Benton A.; Frantz, Jamie T.; Dugas, Jeffrey R.

    2016-01-01

    Objectives: Objective: Our purpose is to describe a novel surgical technique for Ulnar Collateral Ligament repair in the young adolescent, and present the clinical results of a retrospective cohort of patients. We hypothesized that using an internal brace to augment the repair of the native ulnar collateral ligament would allow for a more aggressive physical therapy protocol and ultimately facilitate both an expeditious return to sport and a high level of patient satisfaction. Methods: Methods: After obtaining IRB approval for this study, our institutional electronic database was utilized to identify all patients who had undergone our novel technique for UCL repair between the years 2013-2014. An orthopedic fellow conducted phone surveys and the KJOC questionnaire was administered. Primary outcome measures included KJOC scores at 6 and 12 months, time to initiation of a plyometrics regimen, an interval throwing program and return to sports. Secondary measures including patient satisfaction, level of competition achieved and percent return to normal were also collected. Results: Results: Twenty-two patients (19 male/3 female, average age 17.8 years) underwent surgery between 2013-2014. All patients were high school level athletes at the time of injury and included nineteen baseball players (13 pitchers), two football players, a javelin thrower and a cheerleader. Injury patterns included seven proximal tears, one mid substance, thirteen distal and four avulsions. Nine patients underwent ulnar transposition at the time of surgery, one had undergone prior transposition and the remainder of the patient’s ulnar nerves were left in situ. At six and twelve months the average KJOC scores respectively were 88.3 and 93. Patients that underwent transposition had KJOC scores of 78.3 at six months and 97.5 at twelve while patients that were left in-situ scored 82 and 91. These differences were not significant. The average number of weeks until initiation of plyometrics was

  2. Inspection of aging aircraft: A manufacturer's perspective

    NASA Technical Reports Server (NTRS)

    Hagemaier, Donald J.

    1992-01-01

    Douglas, in conjunction with operators and regulators, has established interrelated programs to identify and address issues regarding inspection of aging aircraft. These inspection programs consist of the following: Supplemental Inspection Documents; Corrosion Prevention and Control Documents; Repair Assessment Documents; and Service Bulletin Compliance Documents. In addition, airframe manufacturers perform extended airframe fatigue tests to deal with potential problems before they can develop in the fleet. Lastly, nondestructive inspection (NDI) plays a role in all these programs through the detection of cracks, corrosion, and disbonds. However, improved and more cost effective NDI methods are needed. Some methods such as magneto-optic imaging, electronic shearography, Diffractor-Sight, and multi-parameter eddy current testing appear viable for near-term improvements in NDI of aging aircraft.

  3. Brain repair after stroke--a novel neurological model.

    PubMed

    Small, Steven L; Buccino, Giovanni; Solodkin, Ana

    2013-12-01

    Following stroke, patients are commonly left with debilitating motor and speech impairments. This article reviews the state of the art in neurological repair for stroke and proposes a new model for the future. We suggest that stroke treatment--from the time of the ictus itself to living with the consequences--must be fundamentally neurological, from limiting the extent of injury at the outset, to repairing the consequent damage. Our model links brain and behaviour by targeting brain circuits, and we illustrate the model though action observation treatment, which aims to enhance brain network connectivity. The model is based on the assumptions that the mechanisms of neural repair inherently involve cellular and circuit plasticity, that brain plasticity is a synaptic phenomenon that is largely stimulus-dependent, and that brain repair required both physical and behavioural interventions that are tailored to reorganize specific brain circuits. We review current approaches to brain repair after stroke and present our new model, and discuss the biological foundations, rationales, and data to support our novel approach to upper-extremity and language rehabilitation. We believe that by enhancing plasticity at the level of brain network interactions, this neurological model for brain repair could ultimately lead to a cure for stroke.

  4. DNA repair in cancer: emerging targets for personalized therapy

    PubMed Central

    Abbotts, Rachel; Thompson, Nicola; Madhusudan, Srinivasan

    2014-01-01

    Genomic deoxyribonucleic acid (DNA) is under constant threat from endogenous and exogenous DNA damaging agents. Mammalian cells have evolved highly conserved DNA repair machinery to process DNA damage and maintain genomic integrity. Impaired DNA repair is a major driver for carcinogenesis and could promote aggressive cancer biology. Interestingly, in established tumors, DNA repair activity is required to counteract oxidative DNA damage that is prevalent in the tumor microenvironment. Emerging clinical data provide compelling evidence that overexpression of DNA repair factors may have prognostic and predictive significance in patients. More recently, DNA repair inhibition has emerged as a promising target for anticancer therapy. Synthetic lethality exploits intergene relationships where the loss of function of either of two related genes is nonlethal, but loss of both causes cell death. Exploiting this approach by targeting DNA repair has emerged as a promising strategy for personalized cancer therapy. In the current review, we focus on recent advances with a particular focus on synthetic lethality targeting in cancer. PMID:24600246

  5. Purification of mammalian DNA repair protein XRCC1

    SciTech Connect

    Chen, I.

    1995-11-01

    Malfunctioning DNA repair systems lead to cancer mutations, and cell death. XRCC1 (X-ray Repair Cross Complementing) is a human DNA repair gene that has been found to fully correct the x-ray repair defect in Chinese hamster ovary (CHO) cell mutant EM9. The corresponding protein (XRCC1) encoded by this gene has been linked to a DNA repair pathway known as base excision repair, and affects the activity of DNA ligase III. Previously, an XRCC1 cDNA minigene (consisting of the uninterrupted coding sequence for XRCC1 protein followed by a decahistidine tag) was constructed and cloned into vector pET-16b for the purpose of: (1) overproduction of XRCC1 in both prokaryotic and eukaryotic cells; and (2) to facilitate rapid purification of XRCC1 from these systems. A vector is basically a DNA carrier that allows recombinant protein to be cloned and overexpressed in host cells. In this study, XRCC1 protein was overexpressed in E. coli and purified by immobilized metal affinity chromatography. Currently, the XRCC1 minigene is being inserted into a new vector [pET-26b(+)] in hopes to increase overexpression and improve purification. Once purified XRCC1 can be crystallized for structural studies, or studied in vitro for its biological function.

  6. Contemporary Concepts for the Bilateral Cleft Lip and Nasal Repair

    PubMed Central

    Khosla, Rohit K.; McGregor, Jyoti; Kelley, Patrick K.; Gruss, Joseph S.

    2012-01-01

    The bilateral cleft lip and nasal deformity presents a complex challenge for repair. Surgical techniques continue to evolve and are focused on primary anatomic realignment of the tissues. This can be accomplished in a single-stage or two-stage repair early in infancy to provide a foundation for future growth of the lip and nasal tissue. Most cleft surgeons currently perform a single-stage repair for simplifying patient care. Certain institutions utilize presurgical orthopedics for alignment of the maxillary segments and nasal shaping. Methods for the bilateral cleft lip repair are combined with various open and closed rhinoplasty techniques to achieve improved correction of the primary nasal deformity. There is recent focus on shaping the nose for columellar and tip support, as well as alar contour and alar base position. The authors will present a new technique for closure of the nasal floor to prevent the alveolar cleft fistula. Although the alveolar fistula is closed, alveolar bone grafting is still required at the usual time in dental development to fuse the maxilla. It is paramount to try and minimize the stigmata of secondary deformities that historically have been characteristic of the repaired bilateral cleft lip. A properly planned and executed repair reduces the number of revisions and can spare a child from living with secondary deformities. PMID:24179448

  7. Structural aging program -- a summary of activities, results, and conclusions

    SciTech Connect

    Naus, D.J.; Oland, C.B.; Ellingwood, B.R.

    1997-01-01

    Research has been conducted by the Oak Ridge National Laboratory to address aging management of nuclear power plant concrete structures. The purpose was to identify potential structural safety issues and acceptance criteria for use in continued service assessments. Primary program accomplishments have included formulation of a Structural Materials Information Center that contains data and information on the time variation of material properties under the influence of pertinent environmental stressors and aging factors for 144 materials, an aging assessment methodology to identify critical structures and degradation factors that can potentially impact their performance, guidelines and evaluation criteria for use in condition assessments of reinforced concrete structures, and a reliability-based methodology for current condition assessments and estimations of future performance of reinforced concrete nuclear power plant structures. In addition, the Structural Aging Program conducted in-depth evaluations of several nondestructive evaluation and repair-related technologies to develop guidance on their applicability.

  8. Current evidence for the clinical use of long-chain polyunsaturated n-3 fatty acids to prevent age-related cognitive decline and Alzheimer's disease.

    PubMed

    Dacks, P A; Shineman, D W; Fillit, H M

    2013-03-01

    An NIH State of the Science Conference panel concluded in 2010 that insufficient evidence is available to recommend the use of any primary prevention therapy for Alzheimer's disease or cognitive decline with age. Despite the insufficient evidence, candidate therapies with varying levels of evidence for safety and efficacy are taken by the public and discussed in the media. One example is the long-chain n-3 (omega-3) polyunsaturated fatty acids (n-3 LC-PUFA), DHA and EPA, found in some fish and dietary supplements. With this report, we seek to provide a practical overview and rating of the level and type of available evidence that n-3 LC-PUFA supplements are safe and protective against cognitive aging and Alzheimer's disease, with additional discussion of the evidence for effects on quality of life, vascular aging, and the rate of aging. We discuss available sources, dose, bioavailability, and variables that may impact the response to n-3 LC-PUFA treatment such as baseline n-3 LC-PUFA status, APOE ε4 genotype, depression, and background diet. Lastly, we list ongoing clinical trials and propose next research steps to validate these fatty acids for primary prevention of cognitive aging and dementia. Of particular relevance, epidemiology indicates a higher risk of cognitive decline in people in the lower quartile of n-3 LC-PUFA intake or blood levels but these populations have not been specifically targeted by RCTs. PMID:23459977

  9. Current evidence for the clinical use of long-chain polyunsaturated n-3 fatty acids to prevent age-related cognitive decline and Alzheimer's disease.

    PubMed

    Dacks, P A; Shineman, D W; Fillit, H M

    2013-03-01

    An NIH State of the Science Conference panel concluded in 2010 that insufficient evidence is available to recommend the use of any primary prevention therapy for Alzheimer's disease or cognitive decline with age. Despite the insufficient evidence, candidate therapies with varying levels of evidence for safety and efficacy are taken by the public and discussed in the media. One example is the long-chain n-3 (omega-3) polyunsaturated fatty acids (n-3 LC-PUFA), DHA and EPA, found in some fish and dietary supplements. With this report, we seek to provide a practical overview and rating of the level and type of available evidence that n-3 LC-PUFA supplements are safe and protective against cognitive aging and Alzheimer's disease, with additional discussion of the evidence for effects on quality of life, vascular aging, and the rate of aging. We discuss available sources, dose, bioavailability, and variables that may impact the response to n-3 LC-PUFA treatment such as baseline n-3 LC-PUFA status, APOE ε4 genotype, depression, and background diet. Lastly, we list ongoing clinical trials and propose next research steps to validate these fatty acids for primary prevention of cognitive aging and dementia. Of particular relevance, epidemiology indicates a higher risk of cognitive decline in people in the lower quartile of n-3 LC-PUFA intake or blood levels but these populations have not been specifically targeted by RCTs.

  10. Motor Vehicle and Machinery Repairers. Reprinted from the Occupational Outlook Handbook, 1978-79 Edition.

    ERIC Educational Resources Information Center

    Bureau of Labor Statistics (DOL), Washington, DC.

    Focusing on motor vehicle and machinery repairers, this document is one in a series of forty-one reprints from the Occupational Outlook Handbook providing current information and employment projections for individual occupations and industries through 1985. The specific occupations covered in this document include automobile body repairers,…

  11. Is Surgical Repair of the Fallopian Tubes Ever Appropriate?

    PubMed Central

    Sotrel, Ginter

    2009-01-01

    The overall median prevalence of infertility, defined as no conception after more than 12 months of unprotected intercourse with the husband or cohabiting partner in women aged 15 to 44 years, is approximately 9%. About 25% to 33% of female infertility is the result of tubal disease and endometriosis. In view of very successful alternative treatment of tubal factor infertility, the surgical repair of the fallopian tubes is all but obsolete and has been replaced with assisted reproductive technology. This article reviews situations in which surgical repair of the fallopian tubes may facilitate conception. PMID:19826575

  12. Vascular smooth muscle progenitor cells: building and repairing blood vessels.

    PubMed

    Majesky, Mark W; Dong, Xiu Rong; Regan, Jenna N; Hoglund, Virginia J

    2011-02-01

    Molecular pathways that control the specification, migration, and number of available smooth muscle progenitor cells play key roles in determining blood vessel size and structure, capacity for tissue repair, and progression of age-related disorders. Defects in these pathways produce malformations of developing blood vessels, depletion of smooth muscle progenitor cell pools for vessel wall maintenance and repair, and aberrant activation of alternative differentiation pathways in vascular disease. A better understanding of the molecular mechanisms that uniquely specify and maintain vascular smooth muscle cell precursors is essential if we are to use advances in stem and progenitor cell biology and somatic cell reprogramming for applications directed to the vessel wall.

  13. 40 CFR 63.1005 - Leak repair.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... successful repair of the leak. (3) Maximum instrument reading measured by Method 21 of 40 CFR part 60... 40 Protection of Environment 11 2012-07-01 2012-07-01 false Leak repair. 63.1005 Section 63.1005... Standards for Equipment Leaks-Control Level 1 § 63.1005 Leak repair. (a) Leak repair schedule. The owner...

  14. 40 CFR 63.1024 - Leak repair.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... reading measured by Method 21 of 40 CFR part 60, appendix A at the time the leak is successfully repaired... 40 Protection of Environment 11 2012-07-01 2012-07-01 false Leak repair. 63.1024 Section 63.1024... Standards for Equipment Leaks-Control Level 2 Standards § 63.1024 Leak repair. (a) Leak repair schedule....

  15. 40 CFR 63.1024 - Leak repair.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... reading measured by Method 21 of 40 CFR part 60, appendix A at the time the leak is successfully repaired... 40 Protection of Environment 11 2014-07-01 2014-07-01 false Leak repair. 63.1024 Section 63.1024... Standards for Equipment Leaks-Control Level 2 Standards § 63.1024 Leak repair. (a) Leak repair schedule....

  16. 40 CFR 63.1005 - Leak repair.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... successful repair of the leak. (3) Maximum instrument reading measured by Method 21 of 40 CFR part 60... 40 Protection of Environment 11 2014-07-01 2014-07-01 false Leak repair. 63.1005 Section 63.1005... Standards for Equipment Leaks-Control Level 1 § 63.1005 Leak repair. (a) Leak repair schedule. The owner...

  17. Wnt Signaling During Fracture Repair

    PubMed Central

    Secreto, Frank J.; Hoeppner, Luke H.; Westendorf, Jennifer J.

    2010-01-01

    Bone is one of the few tissues in the body with the capacity to regenerate and repair itself. In most cases, fractures are completely repaired in a relatively short period of time; however, in a small percentage of cases, healing never occurs and non-union is the result. Fracture repair and bone regeneration require the localized re-activation of signaling cascades that are crucial for skeletal development. The Wnt/β-catenin signaling pathway is one such developmental pathway whose role in bone formation and regeneration has been recently appreciated. During the last decade, much has learned about how Wnt pathways regulate bone mass. Small molecules and biologics aimed at this pathway are now being tested as potential new anabolic agents. Here we review recent data demonstrating that Wnt pathways are active during fracture repair and that increasing the activities of Wnt pathway components accelerates bone regeneration. PMID:19631031

  18. Nucleotide excision repair in humans.

    PubMed

    Spivak, Graciela

    2015-12-01

    The demonstration of DNA damage excision and repair replication by Setlow, Howard-Flanders, Hanawalt and their colleagues in the early 1960s, constituted the discovery of the ubiquitous pathway of nucleotide excision repair (NER). The serial steps in NER are similar in organisms from unicellular bacteria to complex mammals and plants, and involve recognition of lesions, adducts or structures that disrupt the DNA double helix, removal of a short oligonucleotide containing the offending lesion, synthesis of a repair patch copying the opposite undamaged strand, and ligation, to restore the DNA to its original form. The transcription-coupled repair (TCR) subpathway of NER, discovered nearly two decades later, is dedicated to the removal of lesions from the template DNA strands of actively transcribed genes. In this review I will outline the essential factors and complexes involved in NER in humans, and will comment on additional factors and metabolic processes that affect the efficiency of this important process. PMID:26388429

  19. Nuclear compartmentalization of DNA repair.

    PubMed

    Kalousi, Alkmini; Soutoglou, Evi

    2016-04-01

    The continuous threats on genome integrity by endogenous and exogenous sources have rendered cells competent to overcome these challenges by activating DNA repair pathways. A complex network of proteins and their modifications participate in orchestrated signaling cascades, which are induced in response to DNA damage and may determine the choice of repair pathway. In this review, we summarize recent findings in the field of DNA Double Strand Break repair with regard to the positioning of the break in the highly compartmentalized nucleus. We aim to highlight the importance of chromatin state along with the nuclear position of the DNA lesions on the choice of DNA repair pathway and maintenance of genome integrity. PMID:27266837

  20. Rotator cuff repair - series (image)

    MedlinePlus

    ... shoulder and arm bones. The tendons can be torn from overuse or injury. ... Surgery to repair a torn rotator cuff is usually very successful at relieving pain in the shoulder. The procedure is less predictable at returning strength ...

  1. Precision Instrument and Equipment Repairers.

    ERIC Educational Resources Information Center

    Wyatt, Ian

    2001-01-01

    Explains the job of precision instrument and equipment repairers, who work on cameras, medical equipment, musical instruments, watches and clocks, and industrial measuring devices. Discusses duties, working conditions, employment and earnings, job outlook, and skills and training. (JOW)

  2. How the brain repairs stuttering.

    PubMed

    Kell, Christian A; Neumann, Katrin; von Kriegstein, Katharina; Posenenske, Claudia; von Gudenberg, Alexander W; Euler, Harald; Giraud, Anne-Lise

    2009-10-01

    Stuttering is a neurodevelopmental disorder associated with left inferior frontal structural anomalies. While children often recover, stuttering may also spontaneously disappear much later after years of dysfluency. These rare cases of unassisted recovery in adulthood provide a model of optimal brain repair outside the classical windows of developmental plasticity. Here we explore what distinguishes this type of recovery from less optimal repair modes, i.e. therapy-induced assisted recovery and attempted compensation in subjects who are still affected. We show that persistent stuttering is associated with mobilization of brain regions contralateral to the structural anomalies for compensation attempt. In contrast, the only neural landmark of optimal repair is activation of the left BA 47/12 in the orbitofrontal cortex, adjacent to a region where a white matter anomaly is observed in persistent stutterers, but normalized in recovered subjects. These findings show that late repair of neurodevelopmental stuttering follows the principles of contralateral and perianomalous reorganization.

  3. Endovascular repair or open repair for ruptured abdominal aortic aneurysm: a Cochrane systematic review

    PubMed Central

    Badger, S A; Harkin, D W; Blair, P H; Ellis, P K; Kee, F; Forster, R

    2016-01-01

    Objectives Emergency endovascular aneurysm repair (eEVAR) may improve outcomes for patients with ruptured abdominal aortic aneurysm (RAAA). The study aim was to compare the outcomes for eEVAR with conventional open surgical repair for the treatment of RAAA. Setting A systematic review of relevant publications was performed. Randomised controlled trials (RCTs) comparing eEVAR with open surgical repair for RAAA were included. Participants 3 RCTs were included, with a total of 761 patients with RAAA. Interventions Meta-analysis was performed with fixed-effects models with ORs and 95% CIs for dichotomous data and mean differences with 95% CIs for continuous data. Primary and secondary outcome measures Primary outcome was short-term mortality. Secondary outcome measures included aneurysm-specific and general complication rates, quality of life and economic analysis. Results Overall risk of bias was low. There was no difference between the 2 interventions on 30-day (or in-hospital) mortality, OR 0.91 (95% CI 0.67 to 1.22; p=0.52). 30-day complications included myocardial infarction, stroke, composite cardiac complications, renal complications, severe bowel ischaemia, spinal cord ischaemia, reoperation, amputation and respiratory failure. Reporting was incomplete, and no robust conclusion was drawn. For complication outcomes that did include at least 2 studies in the meta-analysis, there was no clear evidence to support a difference between eEVAR and open repair. Longer term outcomes and cost per patient were evaluated in only a single study, thus precluding definite conclusions. Conclusions Outcomes between eEVAR and open repair, specifically 30-day mortality, are similar. However, further high-quality trials are required, as the paucity of data currently limits the conclusions. PMID:26873043

  4. Comparative proteomic analysis of primordial follicles from ovaries of immature and aged rats.

    PubMed

    Govindaraj, Vijayakumar; Rao, A Jagannadha

    2015-01-01

    Age related decline in reproductive performance in women is well documented and apoptosis has been considered as one of the reasons for the decline of primordial follicle reserve. Recently we observed a decline in the efficiency of DNA repair ability in aged rat primordial follicles as demonstrated by decreased mRNA levels of DNA repair genes BRCA1 and H2AX. In the present study, a two-dimensional electrophoresis (2DE) proteomic approach was employed to identify differentially expressed proteins in primordial follicles isolated from ovaries of immature (∼20 days) and aged (∼400-450 days) rats. Using MALDI-TOF/TOF MS, we identified 13 differentially expressed proteins (p < 0.05) which included seven up-regulated and six down-regulated proteins in aged primordial follicles. These proteins are involved in a wide range of biological functions including apoptosis, DNA repair, and the immune system. Interestingly, the differentially expressed proteins such as FIGNL1 (DNA repair) and BOK (apoptotic protein) have not been previously reported in the rat primordial follicles and these proteins can be related to some common features of ovarian aging such as loss of follicle reserve and genome integrity. The quantitative differences of two important proteins BOK and FIGNL1 observed by the proteomic analysis were correlated with the transcript levels, as determined by semi-quantitative RT-PCR. Our results improve the current knowledge about protein factors associated with molecular changes in rat primordial follicles as a function of aging and our understanding of the proteomic processes involved in degenerative changes observed in aging primordial follicles. PMID:26391928

  5. Effects of hyperthermia on DNA repair pathways: one treatment to inhibit them all.

    PubMed

    Oei, Arlene L; Vriend, Lianne E M; Crezee, Johannes; Franken, Nicolaas A P; Krawczyk, Przemek M

    2015-01-01

    The currently available arsenal of anticancer modalities includes many DNA damaging agents that can kill malignant cells. However, efficient DNA repair mechanisms protect both healthy and cancer cells against the effects of treatment and contribute to the development of drug resistance. Therefore, anti-cancer treatments based on inflicting DNA damage can benefit from inhibition of DNA repair. Hyperthermia - treatment at elevated temperature - considerably affects DNA repair, among other cellular processes, and can thus sensitize (cancer) cells to DNA damaging agents. This effect has been known and clinically applied for many decades, but how heat inhibits DNA repair and which pathways are targeted has not been fully elucidated. In this review we attempt to summarize the known effects of hyperthermia on DNA repair pathways relevant in clinical treatment of cancer. Furthermore, we outline the relationships between the effects of heat on DNA repair and sensitization of cells to various DNA damaging agents. PMID:26245485

  6. Aircraft Metal Skin Repair and Honeycomb Structure Repair; Sheet Metal Work 3: 9857.02.

    ERIC Educational Resources Information Center

    Dade County Public Schools, Miami, FL.

    The course helps students determine types of repairs, compute repair sizes, and complete the repair through surface protection. Course content includes goals, specific objectives, protection of metals, repairs to metal skin, and honeycomb structure repair. A bibliography and post-test are appended. A prerequisite for this course is mastery of the…

  7. Repair Integrity and Clinical Outcomes Following Arthroscopic Rotator Cuff Repair

    PubMed Central

    Williams, Ariel A.; Mark, P.; DiVenere, Jessica Megan; Klinge, Stephen Austin; Arciero, Robert A.; Mazzocca, Augustus D.

    2016-01-01

    Objectives: To prospectively evaluate the effect of early versus delayed motion on repair integrity on 6-month postoperative magnetic resonance imaging (MRI) scans following rotator cuff repair, and to correlate repair integrity with clinical and functional outcomes. We hypothesized that repair integrity would differ between the early and delayed groups and that patients with repair failures would have worse clinical and functional outcomes. Methods: This was a prospective, randomized, single blinded clinical trial comparing an early motion (post-op day 2-3) to a delayed motion (post-op day 28) rehabilitation protocol following arthroscopic repair of isolated supraspinatus tears. All patients underwent MRI at 6 months post-operatively as part of the study protocol. A blinded board-certified and fellowship-trained orthopaedic surgeon (not part of the surgical team) reviewed operative photos and video to confirm the presence of a full thickness supraspinatus tear and to ensure an adequate and consistent repair. The same surgeon along with a blinded sports medicine fellowship-trained musculoskeletal radiologist independently reviewed all MRIs to determine whether the repair was intact at 6 months. Outcome measures were collected by independent evaluators who were also blinded to group assignment. These included the Western Ontario Rotator Cuff (WORC) index, Single Assessment Numeric Evaluation (SANE) ratings, pain scores, sling use, and physical exam data. Enrolled patients were followed at 6 weeks, 6 months, and 1 year. Results: From October 2008 to April 2012, 73 patients met all inclusion criteria and were willing to participate. 36 patients were randomized to delayed motion and 37 were randomized to early motion. The final study group at 6 months consisted of 58 study participants. Postoperative MRIs were obtained on all of these patients at 6 months regardless of whether or not they were progressing as expected. These MRIs demonstrated an overall failure rate of

  8. Challenges and complexities in estimating both the functional impact and the disease risk associated with the extensive genetic variation in human DNA repair genes.

    PubMed

    Mohrenweiser, Harvey W; Wilson, David M; Jones, Irene M

    2003-05-15

    Individual risk and the population incidence of disease result from the interaction of genetic susceptibility and exposure. DNA repair is an example of a cellular process where genetic variation in families with extreme predisposition is documented to be associated with high disease likelihood, including syndromes of premature aging and cancer. Although the identification and characterization of new genes or variants in cancer families continues to be important, the focus of this paper is the current status of efforts to define the impact of polymorphic amino acid substitutions in DNA repair genes on individual and population cancer risk. There is increasing evidence that mild reductions in DNA repair capacity, assumed to be the consequence of common genetic variation, affect cancer predisposition. The extensive variation being found in the coding regions of DNA repair genes and the large number of genes in each of the major repair pathways results in complex genotypes with potential to impact cancer risk in the general population. The implications of this complexity for molecular epidemiology studies, as well as concepts that may make these challenges more manageable, are discussed. The concepts include both experimental and computational approaches that could be employed to develop predictors of disease susceptibility based on DNA repair genotype, focusing initially on studies to assess functional impact on individual proteins and pathways and then on molecular epidemiology studies to assess exposure-dependent health risk. In closing, we raise some of the non-technical challenges to the utilization of the full richness of the genetic variation to reduce disease occurrence and ultimately improve health care. PMID:12714187

  9. Exploration Challenges: Transferring Ground Repair Techniques to Space Flight Application

    NASA Technical Reports Server (NTRS)

    McLemore, Carole A.; Kennedy, James P.; Rose, Frederick A.; Evans, Brian W.

    2007-01-01

    Fulfilling NASA's Vision for Space Exploration will demand an extended presence in space at distances from our home planet that exceed our current experience in space logistics and maintenance. The ability to perform repairs in lieu of the customary Orbital Replacement Unit (ORU) process where a faulty part is replaced will be elevated from contingency to routine to sustain operations. The use and cost effectiveness of field repairs for ground based operations in industry and the military have advanced with the development of technology in new materials, new repair techniques and new equipment. The unique environments, accessibility constraints and Extra Vehicular Activity (EVA) issues of space operations will require extensive assessment and evolution of these technologies to provide an equivalent and expected level of assurance to mission success. Challenges include the necessity of changes in design philosophy and policy, extremes in thermal cycling, disruptive forces (such as static charge and wind entrainment) on developed methods for control of materials, dramatically increased volatility of chemicals for cleaning and other compounds due to extremely low pressures, the limits imposed on dexterity and maneuverability by current EVA equipment and practices, and the necessity of unique verification methodology. This paper describes these challenges in and discusses the effects on the established ground techniques for repair. The paper also describes the leading repair methodology candidates and their beneficial attributes for resolving these issues with the evolution of technology.

  10. Influence of Current Input-Output and Age of First Exposure on Phonological Acquisition in Early Bilingual Spanish-English-Speaking Kindergarteners

    ERIC Educational Resources Information Center

    Ruiz-Felter, Roxanna; Cooperson, Solaman J.; Bedore, Lisa M.; Peña, Elizabeth D.

    2016-01-01

    Background: Although some investigations of phonological development have found that segmental accuracy is comparable in monolingual children and their bilingual peers, there is evidence that language use affects segmental accuracy in both languages. Aims: To investigate the influence of age of first exposure to English and the amount of current…

  11. A Selective Intervention Program for Inhibited Preschool-Aged Children of Parents with an Anxiety Disorder: Effects on Current Anxiety Disorders and Temperament

    ERIC Educational Resources Information Center

    Kennedy, Susan J.; Rapee, Ronald M.; Edwards, Susan L.

    2009-01-01

    The efficacy of early intervention for preschool-aged children at risk of anxiety disorders is investigated. Brief early intervention delivered through parents can reduce anxiety and associated risk and may alter the developmental trajectory of anxiety in some young children.

  12. Comparative performance of current definitions of sarcopenia against the prospective incidence of falls among community dwelling seniors age 65 and older

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose: To compare the extent to which 7 available definitions of sarcopenia and 2 related definitions predict the prospective rate of falling. Methods: We studied a cohort of 445 seniors (mean age 71 years, 45% men) living in the community who were followed with a detailed fall assessment for 3 ...

  13. DNA repair mechanisms in dividing and non-dividing cells

    PubMed Central

    Iyama, Teruaki; Wilson, David M.

    2013-01-01

    DNA damage created by endogenous or exogenous genotoxic agents can exist in multiple forms, and if allowed to persist, can promote genome instability and directly lead to various human diseases, particularly cancer, neurological abnormalities, immunodeficiency and premature aging. To avoid such deleterious outcomes, cells have evolved an array of DNA repair pathways, which carry out what is typically a multiple-step process to resolve specific DNA lesions and maintain genome integrity. To fully appreciate the biological contributions of the different DNA repair systems, one must keep in mind the cellular context within they operate. For example, the human body is composed of non-dividing and dividing cell types, including, in the brain, neurons and glial cells. We describe herein the molecular mechanisms of the different DNA repair pathways, and review their roles in non-dividing and dividing cells, with an eye towards how these pathways may regulate the development of neurological disease. PMID:23684800

  14. DNA repair: front and center and not going away!

    PubMed

    Bohr, Vilhelm A

    2012-01-01

    This introduction to the book: DNA repair protocols: third edition, edited by Bjergbaek, discusses the history and more recent developments in the field of DNA repair. This research field started in the 1950 and developed from a small group of researchers interested in the damage caused to DNA by ultraviolet irradiation from the sun to become a large field of research today. DNA damage and its repair are now thought to play an important role in the etiologies of cancer, aging, and neurodegeneration and there is a great deal of interest in this venture. Thus, understanding of DNA processing is now a central field in molecular and cellular biology, and the field is still growing.

  15. The Multifaceted Role of the Vasculature in Endochondral Fracture Repair

    PubMed Central

    Bahney, Chelsea S.; Hu, Diane P.; Miclau, Theodore; Marcucio, Ralph S.

    2015-01-01

    Fracture healing is critically dependent upon an adequate vascular supply. The normal rate for fracture delayed or non-union is estimated to be between 10 and 15%, and annual fracture numbers are approximately 15 million cases per year. However, when there is decreased vascular perfusion to the fracture, incidence of impaired healing rises dramatically to 46%. Reduction in the blood supply to the fracture can be the result of traumatic injuries that physically disrupt the vasculature and damage supportive soft tissue, the result of anatomical location (i.e., distal tibia), or attributed to physiological conditions such as age, diabetes, or smoking. The role of the vasculature during repair is multifaceted and changes during the course of healing. In this article, we review recent insights into the role of the vasculature during fracture repair. Taken together these data highlight the need for an updated model for endochondral repair to facilitate improved therapeutic approaches to promote bone healing. PMID:25699016

  16. DNA repair mechanisms in dividing and non-dividing cells.

    PubMed

    Iyama, Teruaki; Wilson, David M

    2013-08-01

    DNA damage created by endogenous or exogenous genotoxic agents can exist in multiple forms, and if allowed to persist, can promote genome instability and directly lead to various human diseases, particularly cancer, neurological abnormalities, immunodeficiency and premature aging. To avoid such deleterious outcomes, cells have evolved an array of DNA repair pathways, which carry out what is typically a multiple-step process to resolve specific DNA lesions and maintain genome integrity. To fully appreciate the biological contributions of the different DNA repair systems, one must keep in mind the cellular context within which they operate. For example, the human body is composed of non-dividing and dividing cell types, including, in the brain, neurons and glial cells. We describe herein the molecular mechanisms of the different DNA repair pathways, and review their roles in non-dividing and dividing cells, with an eye toward how these pathways may regulate the development of neurological disease.

  17. Age to survive: DNA damage and aging.

    PubMed

    Schumacher, Björn; Garinis, George A; Hoeijmakers, Jan H J

    2008-02-01

    Aging represents the progressive functional decline and increased mortality risk common to nearly all metazoans. Recent findings experimentally link DNA damage and organismal aging: longevity-regulating genetic pathways respond to the accumulation of DNA damage and other stress conditions and conversely influence the rate of damage accumulation and its impact for cancer and aging. This novel insight has emerged from studies on human progeroid diseases and mouse models that have deficient DNA repair pathways. Here we discuss a unified concept of an evolutionarily conserved 'survival' response that shifts the organism's resources from growth to maintenance as an adaptation to stresses, such as starvation and DNA damage. This shift protects the organism from cancer and promotes healthy aging. PMID:18192065

  18. Clinical Results of Meniscal Repair Using Submeniscal Horizontal Sutures

    PubMed Central

    Navali, Amir Mohammad; Aslani, Hossein

    2015-01-01

    Background: Parts of the implants placed over the meniscus during meniscal repair can wear down the cartilage in the contact zones and cause chronic synovitis. Placing horizontal sutures under the meniscus may overcome this potential hazard. The purpose of this prospective study was to evaluate the midterm results of arthroscopic meniscal repair using submeniscally placed out-in horizontal sutures. Methods: One hundred and three meniscal repairs with submeniscal horizontal out-in technique in 103 patients were performed between 2009 and 2012. Our indications for meniscal repair were all longitudinal tear in red-red and red-white zone with acceptable tissue quality. Clinical evaluation included the Tegner and Lysholm knee scores and clinical success was defined as absence of joint-line tenderness, locking, swelling, and a negative McMurray test. Results: The average follow-up was 19 months (range, 14 to 40 months). The time interval from injury to meniscal repair ranged from 2 days to 390 days (median, 96 days). At the end of follow-up, the clinical success rate was 86.5%. Fourteen of 103 repaired menisci (13.5%) were considered failures according to Barrett’s criteria. The mean Lysholm score significantly improved from 39.6 preoperatively to 84.5 postoperatively (P<0.001). Eighty five patients (82.5%) had an excellent or good result according to Lysholm knee score. Tegner activity score improved significantly (P<0.01) from an average of 3.4 (range, 2-6) preoperatively to 5.9 (range, 5-8) postoperatively. Statistical analysis showed that age, simultaneous anterior cruciate ligament reconstruction, chronicity of injury did not affect the clinical outcome. Conclusion: Our results showed that acceptable midterm results are expected from submeniscal horizontal out-in repair technique. This technique is cheap, safe and has the advantage of avoiding chondral abrasion caused by solid implants and suture materials placed over the meniscus. PMID:26213701

  19. Single-Word Intelligibility in Speakers with Repaired Cleft Palate

    ERIC Educational Resources Information Center

    Whitehill, Tara L.; Chau, Cynthia H.-F.

    2004-01-01

    Many speakers with repaired cleft palate have reduced intelligibility, but there are limitations with current procedures for assessing intelligibility. The aim of this study was to construct a single-word intelligibility test for speakers with cleft palate. The test used a multiple-choice identification format, and was based on phonetic contrasts…

  20. Effect of Finishing Time on Microleakage at the Composite-Repair Interface

    PubMed Central

    Shafiei, Fereshteh; Berahman, Nazanin; Niazi, Elmira

    2016-01-01

    Background: Repair is a conservative treatment of defective composite restoration. Sealing the repair interface is a critical factor to achieve successful repaired restorations. Objective: The aim of this study was to evaluatethe effect of three finishing times on the microleakage at the composite-repair interface. Method: Eighty composite specimens (Z250) were made and aged for eight weeks in water. They were randomly divided into four groups. In the control group, repairing was done with no surface treatment and using bonding agent. In groups 2 to 4, the specimens were repaired following roughening, etching and use of Adper Single Bond, and finished immediately, after 20 minutes and after 24 hours, respectively. After thermocycling, the microleakage at the repair interface was assessed using dye-penetration technique. The results were analyzed using Kruskal-Wallis and Mann-Whitney tests (α=0.05). Results: There was a significant difference among the four groups (P<0.001). The control group with the highest leakage showed a significant difference with the other groups (P<0.05). Immediate finishing showed a significantly higher leakage compared to 20-minute and 24-hour delayed finishing time (P<0.001). The two latter groups had no difference. Conclusion: Immediate finishing of the repaired restorations negatively affect the sealing at the repair interface, while 20-minute and 24-hour delayed finishing had no adverse effect on the interface sealing. PMID:27733876

  1. Increased Production of Clusterin in Biopsies of Repair Tissue following Autologous Chondrocyte Implantation

    PubMed Central

    Malda, Jos; Richardson, James B.; Roberts, Sally

    2013-01-01

    Objective. To characterize the immunolocalization of clusterin in the repair cartilage of patients having undergone autologous chondrocyte implantation (ACI) and evaluate correlation to clinical outcome. Design. Full-depth core biopsies of repair tissue were obtained from 38 patients who had undergone ACI at an average of 18 ± 13 months previously (range 8-67 months). The biopsies were snap frozen, cryosectioned, and clusterin production immunolocalized using a specific monoclonal clusterin antibody and compared with normal and osteoarthritic cartilage. Clinical outcome was assessed from patients preoperatively, at the time of biopsy, and annually postoperatively. Results. Intensity of immunostaining for clusterin decreased with age in healthy cartilage tissue. Clusterin was detected to a variable degree in 37 of the 38 ACI cartilage biopsies, in single and clustered chondrocytes, in the pericellular capsule and the cartilage extracellular matrix, as well as the osteocytes and osteoid within the bone. Chondrocytes in hyaline repair tissue were significantly more immunopositive than those in fibrocartilage repair tissue. Clinical outcome improved significantly post-ACI, but did not correlate with the presence of clusterin in the repair tissue. Conclusions. These results demonstrate the presence of clusterin in actively repairing human cartilage and indicate a different distribution of clusterin in this tissue compared to normal cartilage. Variability in clusterin staining in the repair tissue could indicate different states of chondrogenic differentiation. The clinical significance of clusterin within repair tissue is difficult to assess, although the ideal functioning repair tissue morphology should resemble that of healthy adult cartilage. PMID:26069669

  2. Experimental Fatigue Study of Composite Patch Repaired Steel Plates with Cracks

    NASA Astrophysics Data System (ADS)

    Karatzas, Vasileios A.; Kotsidis, Elias A.; Tsouvalis, Nicholas G.

    2015-10-01

    Cracks are among the most commonly encountered defects in metallic structures operating at sea. Composite patch repairing is a repair method which is gaining popularity as it counters most of the problems faced by conventional renewal repairs. Extensive studies can be found in the literature addressing the efficiency of this novel repair method using techniques which meet higher performance and monitoring standards than these commonly found in naval applications. In this work the efficiency of practices widely used in the ship repair industry for the implementation of composite patch repairing is addressed. To this end, steel plates repaired with composite patches were tested under fatigue loading. The composite patches consisted of carbon fibers in epoxy matrix and were directly laminated to the steel surface using the vacuum infusion method. Two different surface preparation methods, namely grit-blasting and mechanical treatment with the use of a needle gun were studied. In addition, in order to account for the harsh environmental conditions during the operating life of the structure and to study its effect on the repair, two different aging scenarios were considered. Non-destructive evaluation of the patches was performed so as to assess the quality of the repair, and the evolution of debonding during testing.

  3. Rotator cuff repair

    MedlinePlus

    ... torn rotator cuff is usually successful in relieving pain in the shoulder. The procedure may not always return strength to ... may not fully heal. Stiffness, weakness, and chronic pain may still be ... are not followed. Older patients (over age 65). Smoking.

  4. On structural health monitoring of aircraft adhesively bonded repairs

    NASA Astrophysics Data System (ADS)

    Pavlopoulou, Sofia

    The recent interest in life extension of ageing aircraft and the need to address the repair challenges in the new age composite ones, led to the investigation of new repair methodologies such as adhesively bonded repair patches. The present thesis focuses on structural health monitoring aspects of the repairs, evaluating their performance with guided ultrasonic waves aiming to develop a monitoring strategy which would eliminate unscheduled maintenance and unnecessary inspection costs. To address the complex nature of the wave propagation phenomena, a finite element based model identified the existing challenges by exploring the interaction of the excitation waves with different levels of damage. The damage sensitivity of the first anti-symmetric mode was numerically investigated. An external bonded patch and a scarf repair, were further tested in static and dynamic loadings, and their performance was monitored with Lamb waves, excited by surface-bonded piezoelectric transducers.. The response was processed by means of advanced pattern recognition and data dimension reduction techniques such as novelty detection and principal component analysis. An optimisation of these tools enabled an accurate damage detection under complex conditions. The phenomena of mode isolation and precise arrival time determination under a noisy environment and the problem of inadequate training data were investigated and solved through appropriate transducer arrangements and advanced signal processing respectively. The applicability of the established techniques was demonstrated on an aluminium repaired helicopter tail stabilizer. Each case study utilised alternative non-destructive techniques for validation such as 3D digital image correlation, X-ray radiography and thermography. Finally a feature selection strategy was developed through the analysis of the instantaneous properties of guided waves for damage detection purposes..

  5. Endovascular abdominal aortic aneurysm repair in the octogenarian.

    PubMed

    Brinkman, William T; Terramani, Thomas T; Najibi, Sasan; Weiss, Victor J; Salam, Atef A; Dodson, Thomas F; Smith, Robert B; Chaikof, Elliot L

    2004-07-01

    The aim of this study was to analyze patient outcomes following endovascular repair of infrarenal abdominal aortic aneurysms (EAR) among patients 80 years of age or older. In this study, reporting standards of the Ad Hoc Committee for Standardized Reporting Practices for Endovascular Aortic Aneurysm Repair of the Society of Vascular Surgery/American Association for Vascular Surgery (SVS/AAVS) were followed. Between August 8, 1996 and February 12, 2001 EAR was performed in 31 patients (29 male and 2 female) with an average age of 83 +/- 3 years and an average maximum aneurysm diameter of 59 +/- 7 mm. Overall technical success was 90% (28/31) with a single acute conversion and a 6% (2/32) incidence of major morbidity. There were no in-hospital deaths, but two patients (6%) died within 30 days of intervention. Four endoleaks, two type I and two type II, were observed within the first 30 days after endograft implantation and three new type II endoleaks were noted after implant periods that exceeded 1 month. Average follow-up was 16 months, with a single aneurysm-related death that occurred after late conversion to open repair, 2 years following initial endovascular treatment. Kaplan-Meier analysis revealed 3-, 12-, and 24-month estimated survivals of 93% (+/-5), 75% (+/-8), and 68% (+/-10), respectively. Clinical success rates were 90% (+/-5), 90% (+/-5), and 72% (+/-17) at 12, 24, and 36 months, respectively. We conclude that, in the octogenarian with mild to moderate medical comorbidities, endovascular aneurysm repair provides an alternative to open AAA repair with low operative morbidity and good clinical success rates. Elevated SVS/AAVS medical comorbidity scores were not associated with increased operative mortality rates, but they did show a trend toward decreased mid-term survival. Careful consideration of life expectancy and the probability of rupture, as with traditional AAA repair, should dictate necessity for intervention. PMID:15175935

  6. Two Ports Laparoscopic Inguinal Hernia Repair in Children

    PubMed Central

    Ibrahim, Medhat M.

    2015-01-01

    Introduction. Several laparoscopic treatment techniques were designed for improving the outcome over the last decade. The various techniques differ in their approach to the inguinal internal ring, suturing and knotting techniques, number of ports used in the procedures, and mode of dissection of the hernia sac. Patients and Surgical Technique. 90 children were subjected to surgery and they undergone two-port laparoscopic repair of inguinal hernia in children. Technique feasibility in relation to other modalities of repair was the aim of this work. 90 children including 75 males and 15 females underwent surgery. Hernia in 55 cases was right-sided and in 15 left-sided. Two patients had recurrent hernia following open hernia repair. 70 (77.7%) cases were suffering unilateral hernia and 20 (22.2%) patients had bilateral hernia. Out of the 20 cases 5 cases were diagnosed by laparoscope (25%). The patients' median age was 18 months. The mean operative time for unilateral repairs was 15 to 20 minutes and bilateral was 21 to 30 minutes. There was no conversion. The complications were as follows: one case was recurrent right inguinal hernia and the second was stitch sinus. Discussion. The results confirm the safety and efficacy of two ports laparoscopic hernia repair in congenital inguinal hernia in relation to other modalities of treatment. PMID:25785196

  7. On the complex ageing characteristics of high-power LiFePO4/graphite battery cells cycled with high charge and discharge currents

    NASA Astrophysics Data System (ADS)

    Groot, Jens; Swierczynski, Maciej; Stan, Ana Irina; Kær, Søren Knudsen

    2015-07-01

    Li-ion batteries are known to undergo complex ageing processes, where the operating conditions have a profound and non-linear effect on both calendar life and cycle life. This is especially a challenge for the automotive industry, where the requirements on product lifetime and reliability are demanding. The aim of the present work is to quantify the ageing in terms of capacity fade and impedance growth as a function of operating conditions typical to high-power automotive applications; high charge and discharge rate, elevated temperatures and wide state-of-charge windows. The cycle life of 34 power-optimised LiFePO4/graphite cells was quantified by testing with charge and discharge rates between 1 and 4C-rate, temperatures between +23 °C and +53 °C, and a depth-of-discharge of either 100% or 60%. Although all cells show similar ageing pattern in general, the cycle life and the impedance growth is remarkably different for the tested cases. In addition, it is concluded that high charging rates, high temperatures or intensive cycling do not always lead to a shorter cycle life. One specifically interesting finding is that the combination of 1C-rate discharge in combination with 3.75C-rate charging was found to degrade the tested cells more rapidly than a symmetric cycle with 3.75C-rate in both directions.

  8. Evaluation of bisphenol E cyanate ester for the resin-injection repair of advanced composites

    NASA Astrophysics Data System (ADS)

    Lio, Wilber Yaote

    Polymer matrix composites (PMCs) are susceptible to impacts that often result in microcracks and delaminations that can greatly reduce their mechanical integrity. Current injection repair techniques are limited to low glass transition temperature (Tg) composites due to the temperature and viscosity limitations of current repair resins. Bisphenol E cyanate ester (BECy) has both a high Tg and low prepolymer viscosity that makes it an ideal resin for the injection repair of high temperature PMCs. In addition, alumina nanoparticles have been shown to increase the strengths of some adhesives as well as impart shear thinning properties in suspension; both of which are desirable effects for injection repair. Lap shear tests were performed to evaluate adhesive properties of BECy and BECy-alumina nanocomposites. Effects of substrate, temperature, nanoparticle loading, and moisture were investigated. A resin-injection process was developed and the efficiency of BECy in repairing bismaleimide-carbon fiber composite plates was studied through ultrasonic evaluation and compression-after-impact tests.

  9. In-Flight Manual Electronics Repair for Deep-Space Missions

    NASA Technical Reports Server (NTRS)

    Pettegrew, Richard; Easton, John; Struk, Peter; Anderson, Eric

    2007-01-01

    Severe limitations on mass and volume available for spares on long-duration spaceflight missions will require electronics repair to be conducted at the component level, rather than at the sub-assembly level (referred to as Orbital Replacement Unit, or 'ORU'), as is currently the case aboard the International Space Station. Performing reliable component-level repairs in a reduced gravity environment by crew members will require careful planning, and some specialty tools and systems. Additionally, spacecraft systems must be designed to enable such repairs. This paper is an overview of a NASA project which examines all of these aspects of component level electronic repair. Results of case studies that detail how NASA, the U.S. Navy, and a commercial company currently approach electronics repair are presented, along with results of a trade study examining commercial technologies and solutions which may be used in future applications. Initial design recommendations resulting from these studies are also presented.

  10. Use of a dynamic self-regulating prosthesis (P.A.D.) in inguinal hernia repair: our first experience in 214 patients.

    PubMed

    Ferranti, Fabrizio; Marzano, Marco; Quintiliani, Alberto

    2009-01-01

    Numerous techniques exist for inguinal hernia treatment. Currently, open mesh tension-free repair is regarded as the repair method of choice. In particular Lichtenstein repair is the most common procedure performed, although several articles have reported long-lasting postoperative pain and a higher recurrence rate than originally reported. This study describes the P.A.D. (Protesi Autoregolantesi Dinamica) prosthesis implantation technique and reports postoperative complications and long-term results. From June 2002 to May 2005 a total of 214 patients underwent P.A.D. prosthesis inguinal repair. All patients were male, with a mean age of 51 years. All hernias were treated via an open inguinal approach using the original technique described by Valenti, with slight modifications. A total of 171'patients (80%) were available to follow-up 3 years after surgery. Early postoperative complications occurred in 14 patients (8.4%). Four patients (12.1%), who had undergone regional anaesthesia, developed urinary retention. Wound infection occurred in 3 patients (1.4%). There were two direct recurrences (0.93%) whereas chronic postoperative inguinal pain was reported in 4.2% of patients. Within the limitations of a short follow-up, our results show that the P.A.D. prosthesis procedure is a reliable technique with a low recurrence rate and low postoperative morbidity.

  11. The cutting edges in DNA repair, licensing, and fidelity: DNA and RNA repair nucleases sculpt DNA to measure twice, cut once.

    PubMed

    Tsutakawa, Susan E; Lafrance-Vanasse, Julien; Tainer, John A

    2014-07-01

    To avoid genome instability, DNA repair nucleases must precisely target the correct damaged substrate before they are licensed to incise. Damage identification is a challenge for all DNA damage response proteins, but especially for nucleases that cut the DNA and necessarily create a cleaved DNA repair intermediate, likely more toxic than the initial damage. How do these enzymes achieve exquisite specificity without specific sequence recognition or, in some cases, without a non-canonical DNA nucleotide? Combined structural, biochemical, and biological analyses of repair nucleases are revealing their molecular tools for damage verification and safeguarding against inadvertent incision. Surprisingly, these enzymes also often act on RNA, which deserves more attention. Here, we review protein-DNA structures for nucleases involved in replication, base excision repair, mismatch repair, double strand break repair (DSBR), and telomere maintenance: apurinic/apyrimidinic endonuclease 1 (APE1), Endonuclease IV (Nfo), tyrosyl DNA phosphodiesterase (TDP2), UV Damage endonuclease (UVDE), very short patch repair endonuclease (Vsr), Endonuclease V (Nfi), Flap endonuclease 1 (FEN1), exonuclease 1 (Exo1), RNase T and Meiotic recombination 11 (Mre11). DNA and RNA structure-sensing nucleases are essential to life with roles in DNA replication, repair, and transcription. Increasingly these enzymes are employed as advanced tools for synthetic biology and as targets for cancer prognosis and interventions. Currently their structural biology is most fully illuminated for DNA repair, which is also essential to life. How DNA repair enzymes maintain genome fidelity is one of the DNA double helix secrets missed by James Watson and Francis Crick, that is only now being illuminated though structural biology and mutational analyses. Structures reveal motifs for repair nucleases and mechanisms whereby these enzymes follow the old carpenter adage: measure twice, cut once. Furthermore, to measure

  12. The cutting edges in DNA repair, licensing, and fidelity: DNA and RNA repair nucleases sculpt DNA to measure twice, cut once

    PubMed Central

    Lafrance-Vanasse, Julien

    2014-01-01

    To avoid genome instability, DNA repair nucleases must precisely target the correct damaged substrate before they are licensed to incise. Damage identification is a challenge for all DNA damage response proteins, but especially for nucleases that cut the DNA and necessarily create a cleaved DNA repair intermediate, likely more toxic than the initial damage. How do these enzymes achieve exquisite specificity without specific sequence recognition or, in some cases, without a non-canonical DNA nucleotide? Combined structural, biochemical, and biological analyses of repair nucleases are revealing their molecular tools for damage verification and safeguarding against inadvertent incision. Surprisingly, these enzymes also often act on RNA, which deserves more attention. Here, we review protein-DNA structures for nucleases involved in replication, base excision repair, mismatch repair, double strand break repair (DSBR), and telomere maintenance: apurinic/apyrimidinic endonuclease 1 (APE1), Endonuclease IV (Nfo), tyrosyl DNA phosphodiesterase (TDP2), UV Damage endonuclease (UVDE), very short patch repair endonuclease (Vsr), Endonuclease V (Nfi), Flap endonuclease 1 (FEN1), exonuclease 1 (Exo1), RNase T and Meiotic recombination 11 (Mre11). DNA and RNA structure-sensing nucleases are essential to life with roles in DNA replication, repair, and transcription. Increasingly these enzymes are employed as advanced tools for synthetic biology and as targets for cancer prognosis and interventions. Currently their structural biology is most fully illuminated for DNA repair, which is also essential to life. How DNA repair enzymes maintain genome fidelity is one of the DNA double helix secrets missed by Watson-Crick, that is only now being illuminated though structural biology and mutational analyses. Structures reveal motifs for repair nucleases and mechanisms whereby these enzymes follow the old carpenter adage: measure twice, cut once. Furthermore, to measure twice these nucleases

  13. Clinical outcomes after repair of quadriceps tendon rupture: a systematic review.

    PubMed

    Ciriello, Vincenzo; Gudipati, Suribabu; Tosounidis, Theodoros; Soucacos, P N; Giannoudis, Peter V

    2012-11-01

    The existing evidence regarding the management of quadriceps tendon rupture remains obscure. The aim of the current review is to investigate the characteristics, the different techniques employed and to analyse the clinical outcomes following surgical repair of quadriceps tendon rupture. An Internet based search of the English literature of the last 25 years was carried out. Case reports and non-clinical studies were excluded. The methodological quality of the included studies was assessed using the Coleman Methodology Score. All data regarding mechanism and site of rupture, type of treatment, time elapsed between diagnosis and repair, patients' satisfaction, clinical outcome, return to pre-injury activities, complications and recurrence rates were extracted and analysed. Out of 474 studies identified, 12 met the inclusion criteria. The average of Coleman Methodology Score was 50.46/100. In total 319 patients were analysed with a mean age of 57 years (16-85). The mean time of follow-up was 47.5 months (3 months to 24 years). The most common mechanism of injury was simple fall (61.5%). Spontaneous ruptures were reported in 3.2% of cases. The most common sites of tear were noted between 1cm and 2 cm of the superior pole of the patella and, in the older people, at the osseotendinous junction. The most frequently used repair technique was patella drill holes (50% of patients). Simple sutures were used in mid-substance ruptures. Several reinforcement techniques were employed in case of poor quality or retraction of the torn ends of tendon. The affected limb was immobilised in a cast for a period of 3-10 weeks. Quadriceps muscular atrophy and muscle strength deficit were present in most of the cases. Worst results were noted in delayed repairs. Reported complications included heterotopic ossifications in 6.9% of patients, deep venous thrombosis or pulmonary embolism in 2.5%, superficial infection in 1.2% and deep infection in 1.1%. It appears that the type of surgical

  14. DNA Repair Alterations in Children With Pediatric Malignancies: Novel Opportunities to Identify Patients at Risk for High-Grade Toxicities

    SciTech Connect

    Ruebe, Claudia E.

    2010-10-01

    Purpose: To evaluate, in a pilot study, the phosphorylated H2AX ({gamma}H2AX) foci approach for identifying patients with double-strand break (DSB) repair deficiencies, who may overreact to DNA-damaging cancer therapy. Methods and Materials: The DSB repair capacity of children with solid cancers was analyzed compared with that of age-matched control children and correlated with treatment-related normal-tissue responses (n = 47). Double-strand break repair was investigated by counting {gamma}H2AX foci in blood lymphocytes at defined time points after irradiation of blood samples. Results: Whereas all healthy control children exhibited proficient DSB repair, 3 children with tumors revealed clearly impaired DSB repair capacities, and 2 of these repair-deficient children developed life-threatening or even lethal normal-tissue toxicities. The underlying mutations affecting regulatory factors involved in DNA repair pathways were identified. Moreover, significant differences in mean DSB repair capacity were observed between children with tumors and control children, suggesting that childhood cancer is based on genetic alterations affecting DSB repair function. Conclusions: Double-strand break repair alteration in children may predispose to cancer formation and may affect children's susceptibility to normal-tissue toxicities. Phosphorylated H2AX analysis of blood samples allows one to detect DSB repair deficiencies and thus enables identification of children at risk for high-grade toxicities.

  15. Reprogramming Cells for Brain Repair

    PubMed Central

    Guarino, Alyx T.; McKinnon, Randall D.

    2013-01-01

    At present there are no clinical therapies that can repair traumatic brain injury, spinal cord injury or degenerative brain disease. While redundancy and rewiring of surviving circuits can recover some lost function, the brain and spinal column lack sufficient endogenous stem cells to replace lost neurons or their supporting glia. In contrast, pre-clinical studies have demonstrated that exogenous transplants can have remarkable efficacy for brain repair in animal models. Mesenchymal stromal cells (MSCs) can provide paracrine factors that repair damage caused by ischemic injury, and oligodendrocyte progenitor cell (OPC) grafts give dramatic functional recovery from spinal cord injury. These studies have progressed to clinical trials, including human embryonic stem cell (hESC)-derived OPCs for spinal cord repair. However, ESC-derived allografts are less than optimal, and we need to identify a more appropriate donor graft population. The cell reprogramming field has developed the ability to trans-differentiate somatic cells into distinct cell types, a technology that has the potential to generate autologous neurons and glia which address the histocompatibility concerns of allografts and the tumorigenicity concerns of ESC-derived grafts. Further clarifying how cell reprogramming works may lead to more efficient direct reprogram approaches, and possibly in vivo reprogramming, in order to promote brain and spinal cord repair. PMID:24961526

  16. Essentials of skin laceration repair.

    PubMed

    Forsch, Randall T

    2008-10-15

    Skin laceration repair is an important skill in family medicine. Sutures, tissue adhesives, staples, and skin-closure tapes are options in the outpatient setting. Physicians should be familiar with various suturing techniques, including simple, running, and half-buried mattress (corner) sutures. Although suturing is the preferred method for laceration repair, tissue adhesives are similar in patient satisfaction, infection rates, and scarring risk in low skin-tension areas and may be more cost-effective. The tissue adhesive hair apposition technique also is effective in repairing scalp lacerations. The sting of local anesthesia injections can be lessened by using smaller gauge needles, administering the injection slowly, and warming or buffering the solution. Studies have shown that tap water is safe to use for irrigation, that white petrolatum ointment is as effective as antibiotic ointment in postprocedure care, and that wetting the wound as early as 12 hours after repair does not increase the risk of infection. Patient education and appropriate procedural coding are important after the repair. PMID:18953970

  17. Adipose Stromal Cells Repair Pressure Ulcers in Both Young and Elderly Mice: Potential Role of Adipogenesis in Skin Repair

    PubMed Central

    Strong, Amy L.; Bowles, Annie C.; MacCrimmon, Connor P.; Frazier, Trivia P.; Lee, Stephen J.; Wu, Xiying; Katz, Adam J.; Gawronska-Kozak, Barbara; Bunnell, Bruce A.

    2015-01-01

    More than 2.5 million patients in the U.S. require treatment for pressure ulcers annually, and the elderly are at particularly high risk for pressure ulcer development. Current therapy for pressure ulcers consists of conservative medical management for shallow lesions and aggressive debridement and surgery for deeper lesions. The current study uses a murine model to address the hypothesis that adipose-derived stromal/stem cell (ASC) treatment would accelerate and enhance pressure ulcer repair. The dorsal skin of both young (2 months old [mo]) and old (20 mo) C57BL/6J female mice was sandwiched between external magnets for 12 hours over 2 consecutive days to initiate a pressure ulcer. One day following the induction, mice were injected with ASCs isolated from congenic mice transgenic for the green fluorescent protein under a ubiquitous promoter. Relative to phosphate-buffered saline-treated controls, ASC-treated mice displayed a cell concentration-dependent acceleration of wound closure, improved epidermal/dermal architecture, increased adipogenesis, and reduced inflammatory cell infiltration. The ASC-induced improvements occurred in both young and elderly recipients, although the expression profile of angiogenic, immunomodulatory, and reparative mRNAs differed as a function of age. The results are consistent with clinical reports that fat grafting improved skin architecture in thermal injuries; the authors of this published study have invoked ASC-based mechanisms to account for their clinical outcomes. Thus, the current proof-of-principle study sets the stage for clinical translation of autologous and/or allogeneic ASC treatment of pressure ulcers. Significance Adipose-derived stromal/stem cells (ASCs) promote the healing of pressure ulcer wounds in both young and old mice. ASCs enhance wound healing rates through adipogenic differentiation and regeneration of the underlying architecture of the skin. PMID:25900728

  18. Supporting Biomaterials for Articular Cartilage Repair

    PubMed Central

    Duarte Campos, Daniela Filipa; Drescher, Wolf; Rath, Björn; Tingart, Markus

    2012-01-01

    Orthopedic surgeons and researchers worldwide are continuously faced with the challenge of regenerating articular cartilage defects. However, until now, it has not been possible to completely mimic the biological and biochemical properties of articular cartilage using current research and development approaches. In this review, biomaterials previously used for articular cartilage repair research are addressed. Furthermore, a brief discussion of the state of the art of current cell printing procedures mimicking native cartilage is offered in light of their use as future alternatives for cartilage tissue engineering. Inkjet cell printing, controlled deposition cell printing tools, and laser cell printing are cutting-edge techniques in this context. The development of mimetic hydrogels with specific biological properties relevant to articular cartilage native tissue will support the development of improved, functional, and novel engineered tissue for clinical application. PMID:26069634

  19. Can ageing be slowed?

    PubMed Central

    Gaman, L; Stoian, I; Atanasiu, V

    2011-01-01

    Redox metabolism has long been considered to play important roles in aging and the development of age-related diseases. Both dietary and pharmacological manipulations of redox metabolism have been associated with the extension of lifespan. Increasing new evidence s also suggests that the process of aging may derive from imperfect clearance of oxidatively damaged material. The accumulation of this molecular “garbage”, relatively indigestible, further hinders cellular functions, induces progressive failure of maintenance and repair and increases the probability of death. One important trend in anti–aging strategy is, therefore, to prevent or even revert the accumulation of these oxidatively altered molecules by stimulating the maintenance and repair systems through hormesis. A promising approach for slowing down ageing and achieving a healthy senescence is represented by repeated exposure to various mild stresses (caloric restriction, moderate exercise, nutritional or pharmacological hormetins). This article reviews the potential therapeutic tools available to date for increasing longevity and obtaining and successful ageing from the redox and hormetic perspective. PMID:22514565

  20. The Repair of International Clefts in the Current Surgical Landscape.

    PubMed

    Persing, Sarah; Patel, Anup; Clune, James E; Steinbacher, Derek M; Persing, John A

    2015-06-01

    Cleft lip and palate (CLP) constitute a significant global disease burden. There are two general models that exist to deliver cleft care: surgical missions and comprehensive cleft centers (CCC). While surgical missions offer high quality surgical care to patients who would be unlikely to ever receive treatment, they may fail to provide sustainable solutions. The development of CCC is growing in popularity worldwide. CCC are permanent centers that offer a multidisciplinary team approach to the treatment of cleft lip and palate. Operation Smile has adopted the concept of specialized surgical care centers. These centers are shown to be safe, cost-effective, and provide sustainable solutions for cleft care. The authors discuss some of the benefits and drawbacks of the classic mission-based model and highlight why there may be a paradigm shift towards CCC. PMID:26080140

  1. Molecular Mechanisms of Biological Aging in Intervertebral Discs

    PubMed Central

    Vo, Nam V.; Hartman, Robert A.; Patil, Prashanti R.; Risbud, Makarand V.; Kletsas, Dimitris; Iatridis, James C.; Hoyland, Judith A.; Le Maitre, Christine L.; Sowa, Gwendolyn A.; Kang, James D.

    2016-01-01

    Advanced age is the greatest risk factor for the majority of human ailments, including spine-related chronic disability and back pain, which stem from age-associated intervertebral disc degeneration (IDD). Given the rapid global rise in the aging population, understanding the biology of intervertebral disc aging in order to develop effective therapeutic interventions to combat the adverse effects of aging on disc health is now imperative. Fortunately, recent advances in aging research have begun to shed light on the basic biological process of aging. Here we review some of these insights and organize the complex process of disc aging into three different phases to guide research efforts to understand the biology of disc aging. The objective of this review is to provide an overview of the current knowledge and the recent progress made to elucidate specific molecular mechanisms underlying disc aging. In particular, studies over the last few years have uncovered cellular senescence and genomic instability as important drivers of disc aging. Supporting evidence comes from DNA repair-deficient animal models that show increased disc cellular senescence and accelerated disc aging. Additionally, stress-induced senescent cells have now been well documented to secrete catabolic factors, which can negatively impact the physiology of neighboring cells and ECM. These along with other molecular drivers of aging are reviewed in depth to shed crucial insights into the underlying mechanisms of age-related disc degeneration. We also highlight molecular targets for novel therapies and emerging candidate therapeutics that may mitigate age-associated IDD. PMID:26890203

  2. Recommendations for Enabling Manual Component Level Electronic Repair for Future Space Missions

    NASA Technical Reports Server (NTRS)

    Struk, Peter M.; Easton, John W.; Funk, Gregory P.; Latta, Gary S.; Ganster, Andrew W.; Estes, Brett E.

    2011-01-01

    Long duration missions to the Moon and Mars pose a number of challenges to mission designers, controllers, and the crews. Among these challenges are planning for corrective maintenance actions which often require a repair. Current repair strategies on the International Space Station (ISS) rely primarily on the use of Orbital Replacement Units (ORUs), where a faulty unit is replaced with a spare, and the faulty unit typically returns to Earth for analysis and possible repair. The strategy of replace to repair has posed challenges even for the ISS program. Repairing faulty hardware at lower levels such as the component level can help maintain system availability in situations where no spares exist and potentially reduce logistic resupply mass.This report provides recommendations to help enable manual replacement of electronics at the component-level for future manned space missions. The recommendations include hardware, tools, containment options, and crew training. The recommendations are based on the work of the Component Level Electronics Assembly Repair (CLEAR) task of the Exploration Technology Development Program from 2006 to 2009. The recommendations are derived based on the experience of two experiments conducted by the CLEAR team aboard the International Space Station as well as a group of experienced Miniature/Microminiature (2M) electronics repair technicians and instructors from the U.S. Navy 2M Project Office. The emphasis of the recommendations is the physical repair. Fault diagnostics and post-repair functional test are discussed in other CLEAR reports.

  3. Brain necrosis after fractionated radiation therapy: Is the halftime for repair longer than we thought?

    SciTech Connect

    Bender, Edward T.

    2012-11-15

    Purpose: To derive a radiobiological model that enables the estimation of brain necrosis and spinal cord myelopathy rates for a variety of fractionation schemes, and to compare repair effects between brain and spinal cord. Methods: Sigmoidal dose response relationships for brain radiation necrosis and spinal cord myelopathy are derived from clinical data using nonlinear regression. Three different repair models are considered and the repair halftimes are included as regression parameters. Results: For radiation necrosis, a repair halftime of 38.1 (range 6.9-76) h is found with monoexponential repair, while for spinal cord myelopathy, a repair halftime of 4.1 (range 0-8) h is found. The best-fit alpha beta ratio is 0.96 (range 0.24-1.73)Conclusions: A radiobiological model that includes repair corrections can describe the clinical data for a variety of fraction sizes, fractionation schedules, and total doses. Modeling suggests a relatively long repair halftime for brain necrosis. This study suggests that the repair halftime for late radiation effects in the brain may be longer than is currently thought. If confirmed in future studies, this may lead to a re-evaluation of radiation fractionation schedules for some CNS diseases, particularly for those diseases where fractionated stereotactic radiation therapy is used.

  4. Stem cells: potential and challenges for kidney repair

    PubMed Central

    Herrera, Marcela

    2013-01-01

    Renal damage resulting from acute and chronic kidney injury poses an important problem to public health. Currently, patients with end-stage renal disease rely solely on kidney transplantation or dialysis for survival. Emerging therapies aiming to prevent and reverse kidney damage are thus in urgent need. Although the kidney was initially thought to lack the capacity for self-repair, several studies have indicated that this might not be the case; progenitor and stem cells appear to play important roles in kidney repair under various pathological conditions. In this review, we summarize recent findings on the role of progenitor/stem cells on kidney repair as well as discuss their potential as a therapeutic approach for kidney diseases. PMID:24197069

  5. Iterative Repair Planning for Spacecraft Operations Using the Aspen System

    NASA Technical Reports Server (NTRS)

    Rabideau, G.; Knight, R.; Chien, S.; Fukunaga, A.; Govindjee, A.

    2000-01-01

    This paper describes the Automated Scheduling and Planning Environment (ASPEN). ASPEN encodes complex spacecraft knowledge of operability constraints, flight rules, spacecraft hardware, science experiments and operations procedures to allow for automated generation of low level spacecraft sequences. Using a technique called iterative repair, ASPEN classifies constraint violations (i.e., conflicts) and attempts to repair each by performing a planning or scheduling operation. It must reason about which conflict to resolve first and what repair method to try for the given conflict. ASPEN is currently being utilized in the development of automated planner/scheduler systems for several spacecraft, including the UFO-1 naval communications satellite and the Citizen Explorer (CX1) satellite, as well as for planetary rover operations and antenna ground systems automation. This paper focuses on the algorithm and search strategies employed by ASPEN to resolve spacecraft operations constraints, as well as the data structures for representing these constraints.

  6. Practical aspects of coating repair

    SciTech Connect

    Munger, C.G.

    1980-02-01

    Detailed information is given concerning the types of coatings failures that are amenable to repair and materials and methods effective in making them. Coatings failure types are analyzed, and recommended surface preparation for several types of failure are described in detail. Consequences of improper surface preparation are emphasized. Precautions necessary for selection of materials and for application methods effective in applying coatings over old coatings are presented in detail. Characteristics and causes are given for pinpoint rusting, delamination, chalking, and undercutting by rust. Characteristics and causes of gas and liquid blisters are described and methods of repairing coating underneath them are detailed. Special attention is given to repairs on galvanizing and inorganic zinc-loaded coatings and the correct procedures of surface preparation and overcoating. Importance of time after start of failure to begin recoating is emphasized.

  7. Aging research in India.

    PubMed

    Ashok, Badithe T; Ali, Rashid

    2003-06-01

    Research on aging in India has been well documented since ancient times. As way back as 3000-1500 BC, the Indian medical system of Ayurveda was used as a means for the prevention of the effects of aging and generation of disease in organs or the whole organism, respectively. In recent years, the focus has been demographic studies on different aspects of aging and has been in isolation. Molecular aspects of aging have been addressed only by a few groups of scientists which has focused on regulation of gene expression, DNA damage and repair, development of immunochemical reagents to detect oxidative DNA damage and assessing the levels of circulating antibodies to reactive oxygen species modified DNA (ROS-DNA), etc. This review aims to recapitulate various research studies on aging since 3000 BC to date. PMID:12814794

  8. Shining Light on Nanotechnology to Help Repair and Regeneration

    PubMed Central

    Gupta, Asheesh; Avci, Pinar; Sadasivam, Magesh; Chandran, Rakkiyappan; Parizotto, Nivaldo; Vecchio, Daniela; Antunes-Melo, Wanessa C; Dai, Tianhong; Chiang, Long Y.; Hamblin, Michael R.

    2012-01-01

    Phototherapy can be used in two completely different but complementary therapeutic applications. While low level laser (or light) therapy (LLLT) uses red or near-infrared light alone to reduce inflammation, pain and stimulate tissue repair and regeneration, photodynamic therapy (PDT) uses the combination of light plus non-toxic dyes (called photosensitizers) to produce reactive oxygen species that can kill infectious microorganisms and cancer cells or destroy unwanted tissue (neo-vascularization in the choroid, atherosclerotic plaques in the arteries). The recent development of nanotechnology applied to medicine (nanomedicine) has opened a new front of advancement in the field of phototherapy and has provided hope for the development of nanoscale drug delivery platforms for effective killing of pathological cells and to promote repair and regeneration. Despite the well-known beneficial effects of phototherapy and nanomaterials in producing the killing of unwanted cells and promoting repair and regeneration, there are few reports that combine all three elements i.e. phototherapy, nanotechnology and, tissue repair and regeneration. However, these areas in all possible binary combinations have been addressed by many workers. The present review aims at highlighting the combined multi-model applications of phototherapy, nanotechnology and, reparative and regeneration medicine and outlines current strategies, future applications and limitations of nanoscale-assisted phototherapy for the management of cancers, microbial infections and other diseases, and to promote tissue repair and regeneration. PMID:22951919

  9. Aging management of containment structures in nuclear power plants

    SciTech Connect

    Naus, D.J.; Oland, C.B.; Ellingwood, B.R.; Graves, H.L. III; Norris, W.E.

    1994-12-31

    Research is being conducted by ORNL under US Nuclear Regulatory Commission (USNRC) sponsorship to address aging management of nuclear power plant containment and other safety-related structures. Documentation is being prepared to provide the USNRC with potential structural safety issues and acceptance criteria for use in continued service evaluations of nuclear power plants. Accomplishments include development of a Structural Materials Information Center containing data and information on the time variation of 144 material properties under the influence of pertinent environmental stressors or aging factors, evaluation of models for potential concrete containment degradation factors, development of a procedure to identify critical structures and degradation factors important to aging management, evaluations of nondestructive evaluation techniques. assessments of European and North American repair practices for concrete, review of parameters affecting corrosion of metals embedded in concrete, and development of methodologies for making current condition assessments and service life predictions of new or existing reinforced concrete structures in nuclear power plants.

  10. Developing miRNA therapeutics for cardiac repair in ischemic heart disease

    PubMed Central

    Zhu, Kai; Liu, Dingqian; Lai, Hao

    2016-01-01

    MicroRNAs (miRNAs) families have been found to be powerful regulators in a wide variety of diseases, which enables the possible use of miRNAs in therapeutic strategies for cardiac repair after ischemic heart disease. This review provides some general insights into miRNAs modulation for development of current molecular and cellular therapeutics in cardiac repair, including endogenous regeneration, endogenous repair, stem cells transplantation, and reprogramming. We also review the delivery strategies for miRNAs modulation, and briefly summarize the current bench and clinical efforts that are being made to explore miRNAs as the future therapeutic target. PMID:27747027

  11. Ginkgo biloba extract EGb 761® in the context of current developments in the diagnosis and treatment of age-related cognitive decline and Alzheimer's disease: a research perspective.

    PubMed

    Lautenschlager, Nicola T; Ihl, Ralf; Müller, Walter E

    2012-08-01

    In June 2011 a two-day expert meeting "The Ageing Brain" took place in Amsterdam, The Netherlands. The main aim was to discuss the available preclinical and clinical data on Ginkgo biloba special extract EGb 761® in the context of current developments in the diagnosis and treatment of age-related cognitive decline and Alzheimer's disease. 19 dementia experts covering the disciplines bio- and neurochemistry, gerontology, neurology, pharmacology, and psychiatry from Australia, Asia, Europe and North America reviewed available preclinical and clinical data for EGb 761® and identified core topics for future research. Based on a wide range of preclinical effects demonstrated for Ginkgo biloba, EGb 761® can be conceptualized as a multi-target compound with activity on distinct pathophysiological pathways in Alzheimer's disease (AD) and age-related cognitive decline. While symptomatic efficacy in dementia and mild cognitive impairment (MCI) has been demonstrated, interpretation of data from dementia prevention trials is complicated by important methodological issues. Bridging pre-clinical research and clinical research as well as deciding on suitable study designs for future trials with EGb 761® remain important questions. The participants of the "Ageing Brain" meeting on Ginkgo biloba special extract EGb 761® concluded that there is plenty of promising data, both pre-clinical and clinical, to consider future research with the compound targeting cognitive impairment in old age as a worthwhile activity.

  12. Diverless pipeline repair clamp: Phase 2

    SciTech Connect

    Miller, J.E.; Lane, B. )

    1992-04-01

    The objective of this project sponsored by the Pipeline Research Committee of the American Gas Association, is to develop a system suitable for repairing small leaks on deepwater pipelines. Phase I of the project, completed in 1990 by Stress Engineering Services, Inc. investigated the types of problems that would have to be overcome to effect a diverless clamp-type repair. Several repair systems were investigated and ten mechanisms were proposed that could be used to secure two clamp halves together. This current Phase 11 effort, is to take two most promising clamp concepts from Phase 1, further evaluate hardware and installation issues, develop conceptual designs, and determine which concept should be carried forward to detailed design. The two concepts evaluated were (1) a bolted split-sleeve clamp suited for ROV installation, and (2) a hydraulically self-actuating clamp requiring only placement on the pipe and actuation by ROV hydraulic hot stabs. Both concepts were evaluated for a 12-inch (324 mm) nominal pipe diameter with an ANSI 900 (15.3 mPa) pressure rating, presuming either system could be adapted to a wider range of pipe sizes and design pressures. Based on the results of this investigation a modified bolted split-sleeve clamp was recommended over the hydraulically self-actuating clamp. The main reasons are (1) the bolted split-sleeve clamp can be adapted to installation by a ROV, (2) sealing and clamping mechanisms borrow from available proven technology, (3) it would require less development effort than the hydraulically self-actuating clamp, and (4) the bolted split-sleeve clamp would probably result in a simpler, less costly design.

  13. Approach to In Situ Component Level Electronics Assembly Repair (CLEAR) for Constellation

    NASA Technical Reports Server (NTRS)

    Struk, Peter M.; Oeftering, Richard C.

    2010-01-01

    Maintenance resupply is a significant issue for long duration space missions. Currently, the International Space Station (ISS) approaches maintenance primarily around replaceable modules called Orbital Replacement Units (ORU). While swapping out ORUs has served the ISS well keeping crew time for maintenance to a minimum, this approach assumes a substantial logistics capacity to provide replacement ORUs and return ORUs to Earth for repair. The ORUs used for ISS require relatively large blocks of replacement hardware even though the actual failed component may be several orders of magnitude smaller. The Component Level Electronics Assembly Repair (CLEAR) task was created to explore electronics repair down to the component level for future space missions. From 2006 to 2009, CLEAR was an activity under the Supportability project of the Exploration Technology Development Program. This paper describes the activities of CLEAR including making a case for component-level electronics repair, examination of current terrestrial repair hardware, and potential repair needs. Based on those needs, the CLEAR team proposes an architecture for an in-situ repair capability aboard a spacecraft or habitat. Additionally, this paper discusses recent progress toward developing in-space repair capabilities--including two spaceflight experiments-- and presents technology concepts which could help enable or benefit the same.

  14. Techniques in Endovascular Aneurysm Repair

    PubMed Central

    Phade, Sachin V.; Garcia-Toca, Manuel; Kibbe, Melina R.

    2011-01-01

    Endovascular repair of infrarenal abdominal aortic aneurysms (EVARs) has revolutionized the treatment of aortic aneurysms, with over half of elective abdominal aortic aneurysm repairs performed endoluminally each year. Since the first endografts were placed two decades ago, many changes have been made in graft design, operative technique, and management of complications. This paper summarizes modern endovascular grafts, considerations in preoperative planning, and EVAR techniques. Specific areas that are addressed include endograft selection, arterial access, sheath delivery, aortic branch management, graft deployment, intravascular ultrasonography, pressure sensors, management of endoleaks and compressed limbs, and exit strategies. PMID:22121487

  15. The therapeutic potential of IGF-I in skeletal muscle repair

    PubMed Central

    Song, Yao-Hua; Song, Jenny L.; Delafontaine, Patrice; Godard, Michael P.

    2013-01-01

    Skeletal muscle loss due to aging, motor neuron degeneration, cancer, heart failure and ischemia is a serious condition for which currently there is no effective treatment. Insulin-like growth factor 1 (IGF-I) plays an important role in muscle maintenance and repair. Preclinical studies have shown that IGF-I is involved in increasing muscle mass and strength, reducing degeneration, inhibiting the prolonged and excessive inflammatory process due to toxin injury and increasing the proliferation potential of satellite cells. However, clinical trials have not been successful due to ineffective delivery method. Choosing the appropriate isoforms or peptides and developing targeted delivery techniques can resolve this issue. Here we discuss the latest development in the field with special emphasis on novel therapeutic approaches. PMID:23628587

  16. Mountain Plains Learning Experience Guide: Automotive Repair. Course: Engine Repair.

    ERIC Educational Resources Information Center

    Schramm, C.; Osland, Walt

    One of twelve individualized courses included in an automotive repair curriculum, this course covers theory and construction, inspection diagnoses, and service and overhaul of automotive engines. The course is comprised of five units: (1) Fundamentals of Four-Cycle Engines, (2) Engine Construction, (3) Valve Train, (4) Lubricating Systems, and (5)…

  17. Current research funding methods dumb down health care and rehabilitation for disabled people and aging population: a call for a change.

    PubMed

    Negrini, S; Padua, L; Kiekens, C; Michail, X; Boldrini, P

    2014-12-01

    Health care systems in Western societies are faced with two major challenges: aging populations and the growing burden of chronic conditions. This translates into more persons with disabilities and the need for more Physical and Rehabilitation Medicine (PRM) services. We raise the point of how these emerging needs are faced by the actual research funding. We briefly present the results of an analysis we made about research funding by the Italian National Health Service as an interesting case study, since it relates to Italy (the financer) and the United States, where National Institutes of Health (NIH) reviewers were identified according to their classification of research topics. The topics of potentially greatest interest for aging Western societies, like chronicity, disability and rehabilitation, were among those least often funded and considered in the traditional method of financing research projects. These results could be based on those PRM peculiarities that make the specialty different from all other classical biomedical specialties, namely the bio-psycho-social approach and its specific research methodologies. Moreover, PRM researchers are spread among the different topics as usually classified, and it is probable that PRM projects are judged by non-PRM reviewers. There are at least two possible ways in which research can be better placed to meet the emerging needs of Western societies (chronicity, disability and consequently also rehabilitation). One is to create specific keywords on these topics so as to improve the match between researchers and reviewers; the second is to allocate specific funds to research in these areas. In fact, the not coherence between emerging needs and research priorities have already been periodically addressed in the past with specific "political" and/or "social" initiatives, when researchers were forced to respond to new emergencies: some historical examples include cancer or HIV and viral diseases or the recent Ebola

  18. Endovascular Repair of Abdominal Aortic Aneurysms

    PubMed Central

    Chaikof, Elliot L.; Lin, Peter H.; Brinkman, William T.; Dodson, Thomas F.; Weiss, Victor J.; Lumsden, Alan B.; Terramani, Thomas T.; Najibi, Sasan; Bush, Ruth L.; Salam, Atef A.; Smith, Robert B.

    2002-01-01

    Objective The impact of co-morbid conditions on early and late clinical outcomes after endovascular treatment of abdominal aortic aneurysm (AAA) was assessed in concurrent cohorts of patients stratified with respect to risk for intervention. Summary Background Data As a minimally invasive strategy for the treatment of AAA, endovascular repair has been embraced with enthusiasm for all prospective patients who are suitable anatomical candidates because of the promise of achieving a durable result with a reduced risk of perioperative morbidity and mortality. Methods From April 1994 to March 2001, endovascular AAA repair was performed in 236 patients using commercially available systems. A subset of patients considered at increased risk for intervention (n = 123) were categorized, as such, based on a preexisting history of ischemic coronary artery disease, with documentation of myocardial infarction (60%) or congestive heart failure (35%), or due to the presence of chronic obstructive disease (21%), liver disease, or malignancy. Results Perioperative mortality (30-day) was 6.5% in the increased-risk patients as compared to 1.8% among those classified as low risk (P = NS). There was no difference between groups in age (74 ± 9 years vs. 72 ± 6 years; mean ± SD), surgical time (235 ± 95 minutes vs. 219 ± 84 minutes), blood loss (457 ± 432 mL vs. 351 ± 273 mL), postoperative hospital stay (4.8 ± 3.4 days vs. 4.0 ± 3.9 days), or days in the ICU (1.3 ± 1.8 days vs. 0.5 ± 1.6 days). Patients at increased risk of intervention had larger aneurysms than low-risk patients (59 ± 13 mm vs. 51 ± 14 mm;P < .05). Stent grafts were successfully implanted in 116 (95%) increased-risk versus 107 (95%) low-risk patients (P = NS). Conversion rates to open operative repair were similar in increased-risk and low-risk groups at 3% and 5%, respectively. The initial endoleak rate was 22% versus 20%, based on the first CT performed (either at discharge or 1 month;P = NS). To date

  19. Transcription-coupled and global genome repair in the Saccharomyces cerevisiae RPB2 gene at nucleotide resolution.

    PubMed Central

    Tijsterman, M; Tasseron-de Jong, J G; van de Putte, P; Brouwer, J

    1996-01-01

    Repair of UV-induced cyclobutane pyrimidine dimers (CPDs) was examined at single nucleotide resolution in the yeast Saccharomyces cerevisiae, using an improved protocol for genomic end-labelling. To obtain the sensitivity required for adduct detection in yeast, an oligonucleotide-directed enrichment step was introduced into the current methodology developed for adduct detection in Escherichia coli. With this method, heterogeneous repair of CPDs within the RPB2 locus is observed. Individual CPDs positioned in the transcribed strand are removed very efficiently with identical kinetics. This fast repair starts within 23 bases downstream of the transcription initiation site. The non-transcribed strand of the active gene exhibits slow repair without detectable repair variations between individual lesions. In contrast, CPDs positioned in the promoter region show profound repair heterogeneity. Here, CPDs at specific sites are removed very quickly, with comparable rates to CPDs positioned in the transcribed strand, while at other positions lesions are not repaired at all during the period studied. Interestingly, the fast repair in the promoter region is dependent on the RAD7 and RAD16 genes, as are the slowly repaired CPDs in this region and in the non-transcribed strand. This indicates that the global genome repair pathway is not intrinsically slow and at specific positions can be as efficient as the transcription-coupled repair pathway. PMID:8836174

  20. Social behavior in the “Age of Empathy”?—A social scientist's perspective on current trends in the behavioral sciences

    PubMed Central

    Matusall, Svenja

    2013-01-01

    Recently, several behavioral sciences became increasingly interested in investigating biological and evolutionary foundations of (human) social behavior. In this light, prosocial behavior is seen as a core element of human nature. A central role within this perspective plays the “social brain” that is not only able to communicate with the environment but rather to interact directly with other brains via neuronal mind reading capacities such as empathy. From the perspective of a sociologist, this paper investigates what “social” means in contemporary behavioral and particularly brain sciences. It will be discussed what “social” means in the light of social neuroscience and a glance into the history of social psychology and the brain sciences will show that two thought traditions come together in social neuroscience, combining an individualistic and an evolutionary notion of the “social.” The paper concludes by situating current research on prosocial behavior in broader social discourses about sociality and society, suggesting that to naturalize prosocial aspects in human life is a current trend in today's behavioral sciences and beyond. PMID:23755003