Prevalence, Comorbidities, and Risk of Perioperative Complications in Human Immunodeficiency Virus-Positive Patients Undergoing Cervical Spine Surgery.

PubMed

Lovy, Andrew J; Guzman, Javier Z; Skovrlj, Branko; Cho, Samuel K; Hecht, Andrew C; Qureshi, Sheeraz A

2015-11-01

Retrospective database analysis. To evaluate outcomes of human immunodeficiency virus (HIV) positive patients after cervical spine surgery. Highly active antiretroviral medications have qualitatively altered the natural history of HIV, thus increasing the number of HIV-positive patients seeking treatment for chronic degenerative conditions. Minimal data exist on HIV patients undergoing degenerative cervical spine surgery. The Nationwide Inpatient Sample was examined from 2002 to 2011. Hospitalizations were identified using International Classification of Diseases Ninth Revision, Clinical Modification (ICD-9-CM) procedural codes for cervical spine surgery and diagnoses codes for degenerative conditions of the cervical spine, and HIV. Statistical analysis was conducted to evaluate associations between HIV status and perioperative complications. A total of 1,602,129 patients underwent degenerative cervical spine surgery, of which 3700 patients (0.23%) had HIV. The prevalence of HIV increased over the study period from 0.19% to 0.33% (P < 0.001). Patients with HIV were younger (48.6 yrs vs. 53.4 yrs, P < 0.001) and more likely to be male (P < 0.001). HIV patients had significantly greater odds of having chronic pulmonary disease, liver disease, and drug abuse. Unadjusted analysis did not reveal increased rate of acute complications among HIV-positive patients compared with negative controls (3.8% vs. 3.7%, P = 0.62). Multivariate analysis did not identify HIV as a significant predictor of complication (odds ratio = 1.04, P = 0.84). HIV was associated with a 1.5 day increased length of stay AND 1.29 fold increase in median costs compared with controls ($14,551 vs. 18,846, P < 0.001). The prevalence of HIV patients undergoing degenerative cervical spine surgery is increasing. A diagnosis of HIV was not associated with an increased risk of perioperative complication among patients undergoing degenerative cervical spine surgery. Further clinical studies are needed to evaluate predictors of complications among HIV patients and long-term outcomes. 4.

Therapeutic effects of naringin on degenerative human nucleus pulposus cells for discogenic low back pain.

PubMed

Li, Nianhu; Whitaker, Camden; Xu, Zhanwang; Heggeness, Michael; Yang, Shang-You

2016-10-01

Over half the population of the world will suffer from moderate or severe low back pain (LBP) during their life span. Studies have shown that naringin, a major flavonoid in grapefruit and an active compound extracted from a Chinese herbal medicine (Rhizoma Drynariae) possesses many pharmacological effects. The aim of this study was to evaluate the influence of naringin on the growth of degenerative human nucleus pulposus (NP) cells, and its repair effects on protein and gene expressions of the cells. This was an in vitro investigation of the human NP cells isolated from degenerated intervertebral discs that were interacted with various concentrated of naringin. This study was exempted by the institutional Human Subjects Committee-2, University of Kansas School of Medicine-Wichita. Degenerative human NP cells were isolated from intervertebral discs of patients with discogenic LBP and cultured at 37°C with 5% CO 2 . The proliferation of NP cells was determined following treatment with various concentrations of naringin. The protein expressions of tumor necrosis factor-α (TNF-α) and Bone morphogenetic protein 2 (BMP-2) were tested using enzyme-linked immunosorbent assay. Aggrecan and type II collagen levels were measured by immunohistological staining. Further examination of the gene expression of aggrecan, Sox6, and MMP3 was performed after intervention with naringin for 3 days. The human NP cells were successfully propagated in culture and stained positive with toluidine blue staining. Naringin effectively enhanced the cell proliferation at an optimal concentration of 20 µg/mL. Naringin treatment resulted in significant inhibition of TNF-α, but elevated protein expressions of BMP-2, collagen II, and aggrecan. Naringin also increased disc matrix gene activity including aggrecan and Sox6, and decreased the gene expression of MMP3. Naringin effectively promotes the proliferation of degenerative human NP cells and improves the recuperation of the cells from degeneration by increasing expression of aggrecan, BMP-2, and Sox6 while inhibiting the expression of TNF-α and MMP3. This study suggests that naringin may represent an alternative therapeutic agent for disc degeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

Gene Expression in Human Meniscal Tears has Limited Association with Early Degenerative Changes in Knee Articular Cartilage

PubMed Central

Brophy, Robert H.; Sandell, Linda J.; Cheverud, James M.; Rai, Muhammad Farooq

2018-01-01

Purpose/Aim Meniscus tears are a common injury to the knee associated with the development of osteoarthritis. Gene expression in the injured meniscus may be associated with early degeneration in the articular cartilage. The purpose of this study was to test the hypothesis that gene expression in meniscus tears is associated with early degenerative changes in the articular cartilage at the time of partial meniscectomy. Materials and Methods Torn meniscus was removed at the time of partial meniscectomy in 63 patients without radiographic osteoarthritis. Meniscal mRNA expression was measured by quantitative PCR for multiple molecular markers of osteoarthritis and cartilage homeostasis. The presence of early degenerative changes in the knee was recorded by X-ray (N=63), magnetic resonance imaging (MRI, N=48) and arthroscopy (N=63). Gene expression was tested for correlation with the presence/absence of degenerative changes after adjusting for age, sex and body mass index. Results Overall gene expression varied significantly with degenerative changes based on X-ray (P=0.047) and MRI (P=0.018). The linear combination of gene variation was also significant. However, only adiponectin (ADIPOQ) (P=0.015) was expressed at a significantly lower level in patients with chondrosis on MRI while the expression of ADIPOQ (P=0.035) and resistin (RETN) (P=0.017) was higher in patients with early degenerative changes on X-ray. Conclusions There is an overall association of gene expression in meniscal tears to early degenerative changes in the knee, but only a limited number of specific genes demonstrate this relationship. The roles of adiponectin and resistin in knee injury and osteoarthritis deserve further study. PMID:27435997

Polyphenols from Root, Tubercles and Grains Cropped in Brazil: Chemical and Nutritional Characterization and Their Effects on Human Health and Diseases

PubMed Central

dos Santos Baião, Diego; Silva de Freitas, Cyntia; da Silva, Davi; Ribeiro Pereira, Patricia

2017-01-01

Throughout evolution, plants have developed the ability to produce secondary phenolic metabolites, which are important for their interactions with the environment, reproductive strategies and defense mechanisms. These (poly)phenolic compounds are a heterogeneous group of natural antioxidants found in vegetables, cereals and leguminous that exert beneficial and protective actions on human health, playing roles such as enzymatic reaction inhibitors and cofactors, toxic chemicals scavengers and biochemical reaction substrates, increasing the absorption of essential nutrients and selectively inhibiting deleterious intestinal bacteria. Polyphenols present in some commodity grains, such as soy and cocoa beans, as well as in other vegetables considered security foods for developing countries, including cassava, taro and beetroot, all of them cropped in Brazil, have been identified and quantified in order to point out their bioavailability and the adequate dietary intake to promote health. The effects of the flavonoid and non-flavonoid compounds present in these vegetables, their metabolism and their effects on preventing chronic and degenerative disorders like cancers, diabetes, osteoporosis, cardiovascular and neurological diseases are herein discussed based on recent epidemiological studies. PMID:28930173

Recent Advances towards the Clinical Application of Stem Cells for Retinal Regeneration

PubMed Central

Becker, Silke; Jayaram, Hari; Limb, G. Astrid

2012-01-01

Retinal degenerative diseases constitute a major cause of irreversible blindness in the world. Stem cell-based therapies offer hope for these patients at risk of or suffering from blindness due to the deterioration of the neural retina. Various sources of stem cells are currently being investigated, ranging from human embryonic stem cells to adult-derived induced pluripotent stem cells as well as human Müller stem cells, with the first clinical trials to investigate the safety and tolerability of human embryonic stem cell-derived retinal pigment epithelium cells having recently commenced. This review aims to summarize the latest advances in the development of stem cell strategies for the replacement of retinal neurons and their supportive cells, the retinal pigment epithelium (RPE) affected by retinal degenerative conditions. Particular emphasis will be given to the advances in stem cell transplantation and the challenges associated with their translation into clinical practice. PMID:24710533

SHOULDER ARTHROPLASTY RECORDS

PubMed Central

Filho, Geraldo Motta; Galvão, Marcus Vinicius; Monteiro, Martim; Cohen, Marcio; Brandão, Bruno

2015-01-01

The study's objective is to evaluate the characteristics and problems of patients who underwent shoulder arthroplasties between July 2004 and November 2006. Methodology: During the period of the study, 145 shoulder arthroplasties were performed. A prospective protocol was used for every patient; demographic, clinical and surgical procedure data were collected. All gathered data were included in the data base. The patients were divided in three major groups: fractures, degenerative diseases and trauma sequels. Information obtained from the data base was correlated in order to determine patients' epidemiologic, injuries, and surgical procedure profiles. Results: Of the 145 shoulder arthroplasties performed, 37% presented trauma sequels, 30% degenerative diseases, and 33% proximal humerus fracture. 12% of the cases required total arthroplasties and 88% partial arthroplasties. Five major complications were observed on early postoperative period. Conclusion: Shoulder arthroplasties have become a common procedure in orthopaedic practice. Surgical records are important in evidencing progressive evolution and in enabling future clinical outcomes evaluation. PMID:26998463

Cyclic impacts on heel strike: a possible biomechanical factor in the etiology of degenerative disease of the human locomotor system.

PubMed

Folman, Y; Wosk, J; Voloshin, A; Liberty, S

1986-01-01

The cyclic impacts induced by heel strike when walking were studied using both a high-resonance-frequency force plate and a low-mass skin-mounted accelerometer. The data were computer analyzed. The results showed that during normal human walking, the locomotor system is subjected to repetitive impact loads at heel strike, lasting about 5 ms and consisting of frequency spectra up to and above 100 Hz. The natural shock-absorbing structures in the musculoskeletal system have viscoelastic time-dependent mechanical behavior, which is relatively ineffective in withstanding sudden impulsive loads. Degenerative joint diseases may thus be seen as a late clinical result of fatigue failure of the natural shock absorbers, submitted to deleterious impacts over a period of time.

A fully organic retinal prosthesis restores vision in a rat model of degenerative blindness

NASA Astrophysics Data System (ADS)

Maya-Vetencourt, José Fernando; Ghezzi, Diego; Antognazza, Maria Rosa; Colombo, Elisabetta; Mete, Maurizio; Feyen, Paul; Desii, Andrea; Buschiazzo, Ambra; di Paolo, Mattia; di Marco, Stefano; Ticconi, Flavia; Emionite, Laura; Shmal, Dmytro; Marini, Cecilia; Donelli, Ilaria; Freddi, Giuliano; Maccarone, Rita; Bisti, Silvia; Sambuceti, Gianmario; Pertile, Grazia; Lanzani, Guglielmo; Benfenati, Fabio

2017-06-01

The degeneration of photoreceptors in the retina is one of the major causes of adult blindness in humans. Unfortunately, no effective clinical treatments exist for the majority of retinal degenerative disorders. Here we report on the fabrication and functional validation of a fully organic prosthesis for long-term in vivo subretinal implantation in the eye of Royal College of Surgeons rats, a widely recognized model of retinitis pigmentosa. Electrophysiological and behavioural analyses reveal a prosthesis-dependent recovery of light sensitivity and visual acuity that persists up to 6-10 months after surgery. The rescue of the visual function is accompanied by an increase in the basal metabolic activity of the primary visual cortex, as demonstrated by positron emission tomography imaging. Our results highlight the possibility of developing a new generation of fully organic, highly biocompatible and functionally autonomous photovoltaic prostheses for subretinal implants to treat degenerative blindness.

A fully organic retinal prosthesis restores vision in a rat model of degenerative blindness

PubMed Central

Antognazza, Maria Rosa; Colombo, Elisabetta; Mete, Maurizio; Feyen, Paul; Desii, Andrea; Buschiazzo, Ambra; Di Paolo, Mattia; Di Marco, Stefano; Ticconi, Flavia; Emionite, Laura; Shmal, Dmytro; Marini, Cecilia; Donelli, Ilaria; Freddi, Giuliano; Maccarone, Rita; Bisti, Silvia; Sambuceti, Gianmario; Pertile, Grazia; Lanzani, Guglielmo; Benfenati, Fabio

2017-01-01

The degeneration of photoreceptors in the retina is one of the major causes of adult blindness in humans. Unfortunately, no effective clinical treatments exist for the majority of retinal degenerative disorders. Here we report on the fabrication and functional validation of a fully organic prosthesis for long-term in vivo subretinal implantation in the eye of Royal College of Surgeons rats, a widely recognized model of Retinitis pigmentosa. Electrophysiological and behavioral analyses reveal a prosthesis-dependent recovery of light-sensitivity and visual acuity that persists up to 6-10 months after surgery. The rescue of the visual function is accompanied by an increase in the basal metabolic activity of the primary visual cortex, as demonstrated by positron emission tomography imaging. Our results highlight the possibility of developing a new generation of fully organic, highly biocompatible and functionally autonomous photovoltaic prostheses for subretinal implants to treat degenerative blindness. PMID:28250420

Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues.

PubMed

Foldager, Casper Bindzus; Toh, Wei Seong; Gomoll, Andreas H; Olsen, Bjørn Reino; Spector, Myron

2014-04-01

The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti-collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins, normally associated with BM.

Photoreceptor Outer Segment-like Structures in Long-Term 3D Retinas from Human Pluripotent Stem Cells.

PubMed

Wahlin, Karl J; Maruotti, Julien A; Sripathi, Srinivasa R; Ball, John; Angueyra, Juan M; Kim, Catherine; Grebe, Rhonda; Li, Wei; Jones, Bryan W; Zack, Donald J

2017-04-10

The retinal degenerative diseases, which together constitute a leading cause of hereditary blindness worldwide, are largely untreatable. Development of reliable methods to culture complex retinal tissues from human pluripotent stem cells (hPSCs) could offer a means to study human retinal development, provide a platform to investigate the mechanisms of retinal degeneration and screen for neuroprotective compounds, and provide the basis for cell-based therapeutic strategies. In this study, we describe an in vitro method by which hPSCs can be differentiated into 3D retinas with at least some important features reminiscent of a mature retina, including exuberant outgrowth of outer segment-like structures and synaptic ribbons, photoreceptor neurotransmitter expression, and membrane conductances and synaptic vesicle release properties consistent with possible photoreceptor synaptic function. The advanced outer segment-like structures reported here support the notion that 3D retina cups could serve as a model for studying mature photoreceptor development and allow for more robust modeling of retinal degenerative disease in vitro.

Cardiovascular disease resulting from a diet and lifestyle at odds with our Paleolithic genome: how to become a 21st-century hunter-gatherer.

PubMed

O'Keefe, James H; Cordain, Loren

2004-01-01

Our genetic make-up, shaped through millions of years of evolution, determines our nutritional and activity needs. Although the human genome has remained primarily unchanged since the agricultural revolution 10,000 years ago, our diet and lifestyle have become progressively more divergent from those of our ancient ancestors. Accumulating evidence suggests that this mismatch between our modern diet and lifestyle and our Paleolithic genome is playing a substantial role in the ongoing epidemics of obesity, hypertension, diabetes, and atherosclerotic cardiovascular disease. Until 500 generations ago, all humans consumed only wild and unprocessed food foraged and hunted from their environment. These circumstances provided a diet high in lean protein, polyunsaturated fats (especially omega-3 [omega-3] fatty acids), monounsaturated fats, fiber, vitamins, minerals, antioxidants, and other beneficial phytochemicals. Historical and anthropological studies show hunter-gatherers generally to be healthy, fit, and largely free of the degenerative cardiovascular diseases common in modern societies. This review outlines the essence of our hunter-gatherer genetic legacy and suggests practical steps to re-align our modern milieu with our ancient genome in an effort to improve cardiovascular health.

Transcription factor EB: from master coordinator of lysosomal pathways to candidate therapeutic target in degenerative storage diseases.

PubMed

Sardiello, Marco

2016-05-01

The lysosome is the main catabolic hub of the cell. Owing to its role in fundamental processes such as autophagy, plasma membrane repair, mTOR signaling, and maintenance of cellular homeostasis, the lysosome has a profound influence on cellular metabolism and human health. Indeed, inefficient or impaired lysosomal function has been implicated in the pathogenesis of a number of degenerative diseases affecting various organs and tissues, most notably the brain, liver, and muscle. The discovery of the coordinated lysosomal expression and regulation (CLEAR) genetic program and its master controller, transcription factor EB (TFEB), has provided an unprecedented tool to study and manipulate lysosomal function. Most lysosome-based processes-including macromolecule degradation, autophagy, lysosomal exocytosis, and proteostasis-are under the transcriptional control of TFEB. Interestingly, impaired TFEB signaling has been suggested to be a contributing factor in the pathogenesis of several degenerative storage diseases. Preclinical studies based on TFEB exogenous expression to reinstate TFEB activity or promote CLEAR network-based lysosomal enhancement have highlighted TFEB as a candidate therapeutic target for the treatment of various degenerative storage diseases. © 2016 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

Degenerative disease affecting the nervous system.

PubMed

Eadie, M J

1974-03-01

The term "degenerative disease" is one which is rather widely used in relation to the nervous system and yet one which is rarely formally and carefully defined. The term appears to be applied to disorders of the nervous system which often occur in later life and which are of uncertain cause. In the Shorter Oxford Dictionary the word degeneration is defined as "a change of structure by which an organism, or an organ, assumes the form of a lower type". However this is not quite the sense in which the word is applied in human neuropathology, where it is conventional to restrict the use of the word to those organic disorders which are of uncertain or poorly understood cause and in which there is a deterioration or regression in the level of functioning of the nervous system. The concept of degenerative disorder is applied to other organs as well as to the brain, and as disease elsewhere in the body may affect the nervous system, it seems reasonable to include within the topic of degenerative disorder affecting the nervous system those conditions in which the nervous system is involved as a result of primary degenerations in other parts of the body. Copyright © 1974 Australian Physiotherapy Association. Published by . All rights reserved.

Adversity, Adaptive Calibration, and Health: The Case of Disadvantaged Families.

PubMed

de Baca, Tomás Cabeza; Wahl, Richard A; Barnett, Melissa A; Figueredo, Aurelio José; Ellis, Bruce J

2016-06-01

Epidemiologists and medical researchers often employ an allostatic load model that focuses on environmental and lifestyle factors, together with biological vulnerabilities, to explain the deterioration of human physiological systems and chronic degenerative disease. Although this perspective has informed medicine and public health, it is agnostic toward the functional significance of pathophysiology and health deterioration. Drawing on Life History (LH) theory, the current paper reviews the literature on disadvantaged families to serve as a conceptual model of stress-health relationships in which the allocation of reproductive effort is instantiated in the LH strategies of individuals and reflects the bioenergetic and material resource tradeoffs . We propose that researchers interested in health disparities reframe chronic degenerative diseases as outcomes resulting from strategic calibration of physiological systems to best adapt, survive, and reproduce in response to demands of specific developmental contexts. These effects of adversity on later-age degenerative disease are mediated, in part, by socioemotional and cognitive mechanisms expressed in different life history strategies.

Adversity, Adaptive Calibration, and Health: The Case of Disadvantaged Families

PubMed Central

de Baca, Tomás Cabeza; Wahl, Richard A.; Barnett, Melissa A.; Figueredo, Aurelio José; Ellis, Bruce J.

2016-01-01

Epidemiologists and medical researchers often employ an allostatic load model that focuses on environmental and lifestyle factors, together with biological vulnerabilities, to explain the deterioration of human physiological systems and chronic degenerative disease. Although this perspective has informed medicine and public health, it is agnostic toward the functional significance of pathophysiology and health deterioration. Drawing on Life History (LH) theory, the current paper reviews the literature on disadvantaged families to serve as a conceptual model of stress-health relationships in which the allocation of reproductive effort is instantiated in the LH strategies of individuals and reflects the bioenergetic and material resource tradeoffs. We propose that researchers interested in health disparities reframe chronic degenerative diseases as outcomes resulting from strategic calibration of physiological systems to best adapt, survive, and reproduce in response to demands of specific developmental contexts. These effects of adversity on later-age degenerative disease are mediated, in part, by socioemotional and cognitive mechanisms expressed in different life history strategies. PMID:27175327

Features specific to retinal pigment epithelium cells derived from three-dimensional human embryonic stem cell cultures - a new donor for cell therapy.

PubMed

Wu, Wei; Zeng, Yuxiao; Li, Zhengya; Li, Qiyou; Xu, Haiwei; Yin, Zheng Qin

2016-04-19

Retinal pigment epithelium (RPE) transplantation is a particularly promising treatment of retinal degenerative diseases affecting RPE-photoreceptor complex. Embryonic stem cells (ESCs) provide an abundant donor source for RPE transplantation. Herein, we studied the time-course characteristics of RPE cells derived from three-dimensional human ESCs cultures (3D-RPE). We showed that 3D-RPE cells possessed morphology, ultrastructure, gene expression profile, and functions of authentic RPE. As differentiation proceeded, 3D-RPE cells could mature gradually with decreasing proliferation but increasing functions. Besides, 3D-RPE cells could form polarized monolayer with functional tight junction and gap junction. When grafted into the subretinal space of Royal College of Surgeons rats, 3D-RPE cells were safe and efficient to rescue retinal degeneration. This study showed that 3D-RPE cells were a new donor for cell therapy of retinal degenerative diseases.

[Drinking water hardness and chronic degenerative diseases. I. Analysis of epidemiological research].

PubMed

Nardi, G; Donato, F; Monarca, S; Gelatti, U

2003-01-01

For many years a causal relation between drinking water hardness and cardiovascular or other chronic degenerative diseases in humans has been hypothesized. In order to evaluate the association between the concentration of minerals (calcium and magnesium) responsible for the hardness of drinking water and human health, a review of all the articles published on the subject from 1980 up to today has been carried out. The retrieved articles have been divided into 4 categories: geographic correlation studies, cross-sectional studies, case-control and cohort studies, and clinical trials. The methods for the selection of the articles and the extraction and analysis of the data are detailed in this paper. Epidemiological studies have been reviewed critically, and some conclusions have been drawn taking into account the research in basic sciences and experimental studies. However, a formal meta-analysis has not been performed, due to the heterogeneity of measures of effect among the different studies.

PLURIPOTENT STEM CELL APPLICATIONS FOR REGENERATIVE MEDICINE

PubMed Central

Angelos, Mathew G.; Kaufman, Dan S.

2015-01-01

Purpose of Review In this review, we summarize the current status of clinical trials using therapeutic cells produced from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). We also discuss combined cell and gene therapy via correction of defined mutations in human pluripotent stem cells and provide commentary on key obstacles facing wide-scale clinical adoption of pluripotent stem cell-based therapy. Recent Findings Initial data suggest hESC/hiPSC-derived cell products used for retinal repair and spinal cord injury are safe for human use. Early stage studies for treatment of cardiac injury and diabetes are also in progress. However, there remain key concerns regarding the safety and efficacy of these cells that need to be addressed in additional well-designed clinical trials. Advances using the CRISPR/Cas9 gene-editing system offer an improved tool for more rapid and on-target gene correction of genetic diseases. Combined gene and cell therapy using human pluripotent stem cells may provide an additional curative approach for disabling or lethal genetic and degenerative diseases where there are currently limited therapeutic opportunities. Summary Human pluripotent stem cells are emerging as a promising tool to produce cells and tissues suitable for regenerative therapy for a variety of genetic and degenerative diseases. PMID:26536430

OrthoIllustrated Web Based Orthopaedic Sports Medicine Registry

ClinicalTrials.gov

2018-04-06

Degenerative and Traumatic Pathology of the Knee; Degenerative and Traumatic Pathology of the Shoulder and Elbow; Degenerative and Traumatic Pathology of the Foot and Ankle; Degenerative and Traumatic Pathology of the Hand and Wrist; Degenerative and Traumatic Pathology of the Hip

Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues

PubMed Central

Toh, Wei Seong; Gomoll, Andreas H.; Olsen, Bjørn Reino; Spector, Myron

2014-01-01

Objective: The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Design: Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti–collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. Results: When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. Conclusions: We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins, normally associated with BM. PMID:26069692

Fatal degenerative neurologic illnesses in men who participated in wild game feasts--Wisconsin, 2002.

PubMed

2003-02-21

Creutzfeldt-Jakob disease (CJD) is a fatal neurologic disorder in humans. CJD is one of a group of conditions known as transmissible spongiform encephalopathies (TSEs), or prion diseases, that are believed to be caused by abnormally configured, host-encoded prion proteins that accumulate in the central nervous tissue. CJD has an annual incidence of approximately 1 case per million population in the United States and occurs in three forms: sporadic, genetically determined, and acquired by infection. In the latter form, the incubation period is measured typically in years. Recent evidence that prion infection can cross the species barrier between humans and cattle has raised increasing public health concerns about the possible transmission to humans of a TSE among deer and elk known as chronic wasting disease (CWD). During 1993-1999, three men who participated in wild game feasts in northern Wisconsin died of degenerative neurologic illnesses. This report documents the investigation of these deaths, which was initiated in August 2002 and which confirmed the death of only one person from CJD. Although no association between CWD and CJD was found, continued surveillance of both diseases remains important to assess the possible risk for CWD transmission to humans.

Past and future corollaries of theories on causes of metabolic syndrome and obesity related co-morbidities part 2: a composite unifying theory review of human-specific co-adaptations to brain energy consumption.

PubMed

McGill, Anne-Thea

2014-01-01

Metabolic syndrome (MetS) predicts type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer, and their rates have escalated over the last few decades. Obesity related co-morbidities also overlap the concept of the metabolic syndrome (MetS). However, understanding of the syndrome's underlying causes may have been misapprehended. The current paper follows on from a theory review by McGill, A-T in Archives of Public Health, 72: 30. This accompanying paper utilises research on human evolution and new biochemistry to theorise on why MetS and obesity arise and how they affect the population. The basis of this composite unifying theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A 'dual system' is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals. In humans who consume a nutritious diet, the NRF2 system has become highly energy efficient. Other relevant human-specific co-adaptations are explored. In order to 'test' this composite unifying theory it is important to show that the hypothesis and sub-theories pertain throughout the whole of human evolution and history up till the current era. Corollaries of the composite unifying theory of MetS are examined with respect to past under-nutrition and malnutrition since agriculture began 10,000 years ago. The effects of man-made pollutants on degenerative change are examined. Projections are then made from current to future patterns on the state of 'insufficient micronutrient and/or unbalanced high energy malnutrition with central obesity and metabolic dysregulation' or 'malnubesity'. Forecasts on human health are made on positive, proactive strategies using the composite unifying theory, and are extended to the wider human ecology of food production. A comparison is made with the outlook for humans if current assumptions and the status quo on causes and treatments are maintained. Areas of further research are outlined. A table of suggestions for possible public health action is included.

[Dreams in normal and pathological aging].

PubMed

Guénolé, Fabian; Marcaggi, Geoffrey; Baleyte, Jean-Marc; Garma, Lucile

2010-06-01

Although most of scientific knowledge in dream research is based on young adult studies, this article provides a review of the effects of normal and pathological aging on dream psychology. It starts with preliminary comments about epistemological and methodological principles of dream research, its singularities in aged persons, and the modifications of sleep physiology with age. The whole literature agrees that dream recall progressively decreases from the beginning of adulthood - not in old age - and that dream reports become less intense, perceptually and emotionally. This evolution occurs faster in men than women, with gender differences in the content of dreams. The chronological modifications could be explained partly by changes in lifestyle and attitude towards dreams in early adulthood, but mainly by modifications of sleep physiology, particularly the decrease and qualitative changes of rapid eye movement (REM) sleep. Dreams have usually little subjective importance in the mental life of aged persons. However, working with dreams can be a valuable tool for psychotherapy in the aged. According to the few existing data, patients suffering degenerative dementia dream much less than healthy aged persons. In Alzheimer's disease, this could be linked to the decrease of REM sleep, and atrophy of associative sensory areas of the cerebral cortex. Most studied aspects of dreaming in degenerative cognitive disorders are REM sleep behavior disorders, and nightmares induced by cholinesterase inhibitors. More studies are needed to better characterize the evolution of dreams with age, particularly studies performed in sleep laboratory.

Biology and therapy of inherited retinal degenerative disease: insights from mouse models

PubMed Central

Veleri, Shobi; Lazar, Csilla H.; Chang, Bo; Sieving, Paul A.; Banin, Eyal; Swaroop, Anand

2015-01-01

Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases. PMID:25650393

Cloning of aged animals: a medical model for tissue and organ regeneration.

PubMed

Tian, X C; Kubota, C; Yang, X

2001-11-01

Cloning by nuclear transfer has great potential application in pharmaceutical protein production, xeno-transplantation, and perhaps most excitingly, therapeutic cloning. In therapeutic cloning a patient's own skin cells can be used to generate cloned embryos from which embryonic stem cells are isolated. Through targeted differentiation, embryonic stem cells can be directed to develop into the desired tissues/organs for replacement. The combination of homologous recombination of genes and nuclear transfer also offers the promise of correcting defective genes in humans. Demonstration of the successful cloning of aged animals is important for these future medical applications because degenerative diseases often afflict older adults. Our studies have demonstrated that skin fibroblast cells from aged adults, even after prolonged culture, provide nuclear donors equally as competent for cloning as cells from young adults or fetuses. These findings have paved the way for medically treating degenerative diseases of aged humans by tissue regeneration technologies made possible through cloning and homologous recombination.

Evidence Report: Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure

NASA Technical Reports Server (NTRS)

Patel, Zarana; Huff, Janice; Saha, Janapriya; Wang, Minli; Blattnig, Steve; Wu, Honglu; Cucinotta, Francis

2015-01-01

Occupational radiation exposure from the space environment may result in non-cancer or non-CNS degenerative tissue diseases, such as cardiovascular disease, cataracts, and respiratory or digestive diseases. However, the magnitude of influence and mechanisms of action of radiation leading to these diseases are not well characterized. Radiation and synergistic effects of radiation cause DNA damage, persistent oxidative stress, chronic inflammation, and accelerated tissue aging and degeneration, which may lead to acute or chronic disease of susceptible organ tissues. In particular, cardiovascular pathologies such as atherosclerosis are of major concern following gamma-ray exposure. This provides evidence for possible degenerative tissue effects following exposures to ionizing radiation in the form of the GCR or SPEs expected during long-duration spaceflight. However, the existence of low dose thresholds and dose-rate and radiation quality effects, as well as mechanisms and major risk pathways, are not well-characterized. Degenerative disease risks are difficult to assess because multiple factors, including radiation, are believed to play a role in the etiology of the diseases. As additional evidence is pointing to lower, space-relevant thresholds for these degenerative effects, particularly for cardiovascular disease, additional research with cell and animal studies is required to quantify the magnitude of this risk, understand mechanisms, and determine if additional protection strategies are required.The NASA PEL (Permissive Exposure Limit)s for cataract and cardiovascular risks are based on existing human epidemiology data. Although animal and clinical astronaut data show a significant increase in cataracts following exposure and a reassessment of atomic bomb (A-bomb) data suggests an increase in cardiovascular disease from radiation exposure, additional research is required to fully understand and quantify these adverse outcomes at lower doses (less than 0.5 gray (SI unit for ionizing radiation dosage, i.e. one joule of radiation energy per one kilogram of matter)) to facilitate risk prediction. This risk has considerable uncertainty associated with it, and no acceptable model for projecting degenerative tissue risk is currently available. In particular, risk factors such as obesity, alcohol, and tobacco use can act as confounding factors that contribute to the large uncertainties. The PELs could be violated under certain scenarios, including following a large SPE (solar proton event) or long-term GCR (galactic cosmic ray) exposure. Specifically, for a Mars mission, the accumulated dose is sufficiently high that epidemiology data and preliminary risk estimates suggest a significant risk for cardiovascular disease. Ongoing research in this area is intended to provide the evidence base for accurate risk quantification to determine criticality for extended duration missions. Data specific to the space radiation environment must be compiled to quantify the magnitude of this risk to decrease the uncertainty in current PELs and to determine if additional protection strategies are required. New research results could lead to estimates of cumulative radiation risk from CNS and degenerative tissue diseases that, when combined with the cancer risk, may have major negative impacts on mission design, costs, schedule, and crew selection. The current report amends an earlier report (Human Research Program Requirements Document, HRP-47052, Rev. C, dated Jan 2009) in order to provide an update of evidence since 2009.

An ultra-sensitive biophysical risk assessment of light effect on skin cells.

PubMed

Bennet, Devasier; Viswanath, Buddolla; Kim, Sanghyo; An, Jeong Ho

2017-07-18

The aim of this study was to analyze photo-dynamic and photo-pathology changes of different color light radiations on human adult skin cells. We used a real-time biophysical and biomechanics monitoring system for light-induced cellular changes in an in vitro model to find mechanisms of the initial and continuous degenerative process. Cells were exposed to intermittent, mild and intense (1-180 min) light with On/Off cycles, using blue, green, red and white light. Cellular ultra-structural changes, damages, and ECM impair function were evaluated by up/down-regulation of biophysical, biomechanical and biochemical properties. All cells exposed to different color light radiation showed significant changes in a time-dependent manner. Particularly, cell growth, stiffness, roughness, cytoskeletal integrity and ECM proteins of the human dermal fibroblasts-adult (HDF-a) cells showed highest alteration, followed by human epidermal keratinocytes-adult (HEK-a) cells and human epidermal melanocytes-adult (HEM-a) cells. Such changes might impede the normal cellular functions. Overall, the obtained results identify a new insight that may contribute to premature aging, and causes it to look aged in younger people. Moreover, these results advance our understanding of the different color light-induced degenerative process and help the development of new therapeutic strategies.

Macrophage Depletion Ameliorates Peripheral Neuropathy in Aging Mice.

PubMed

Yuan, Xidi; Klein, Dennis; Kerscher, Susanne; West, Brian L; Weis, Joachim; Katona, Istvan; Martini, Rudolf

2018-05-09

Aging is known as a major risk factor for the structure and function of the nervous system. There is urgent need to overcome such deleterious effects of age-related neurodegeneration. Here we show that peripheral nerves of 24-month-old aging C57BL/6 mice of either sex show similar pathological alterations as nerves from aging human individuals, whereas 12-month-old adult mice lack such alterations. Specifically, nerve fibers showed demyelination, remyelination and axonal lesion. Moreover, in the aging mice, neuromuscular junctions showed features typical for dying-back neuropathies, as revealed by a decline of presynaptic markers, associated with α-bungarotoxin-positive postsynapses. In line with these observations were reduced muscle strengths. These alterations were accompanied by elevated numbers of endoneurial macrophages, partially comprising the features of phagocytosing macrophages. Comparable profiles of macrophages could be identified in peripheral nerve biopsies of aging persons. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by applying an orally administered CSF-1R specific kinase (c-FMS) inhibitor. The 6-month-lasting treatment started before development of degenerative changes at 18 months and reduced macrophage numbers in mice by ∼70%, without side effects. Strikingly, nerve structure was ameliorated and muscle strength preserved. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may pave the way for treating degeneration in the aging peripheral nervous system by targeting macrophages, leading to reduced weakness, improved mobility, and eventually increased quality of life in the elderly. SIGNIFICANCE STATEMENT Aging is a major risk factor for the structure and function of the nervous system. Here we show that peripheral nerves of 24-month-old aging mice show similar degenerative alterations as nerves from aging human individuals. Both in mice and humans, these alterations were accompanied by endoneurial macrophages. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by blocking a cytokine receptor, essential for macrophage survival. The treatment strongly reduced macrophage numbers and substantially improved nerve structure and muscle strength. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may be helpful for treatment weakness and reduced mobility in the elderly. Copyright © 2018 the authors 0270-6474/18/384610-11$15.00/0.

Assessment of berry fruit's effects on mobility and cognition in aging

USDA-ARS?s Scientific Manuscript database

Changes in aging, in both animals and humans, include parallel decrements in mobility and cognition, even in the absence of degenerative disorders such as Parkinson’s or Alzheimer’s diseases. Diet has long been known to influence aging; however, specific whole foods are now being investigated for t...

Can Xanthophyll-Membrane Interactions Explain Their Selective Presence in the Retina and Brain?

PubMed Central

Widomska, Justyna; Zareba, Mariusz; Subczynski, Witold Karol

2016-01-01

Epidemiological studies demonstrate that a high dietary intake of carotenoids may offer protection against age-related macular degeneration, cancer and cardiovascular and neurodegenerative diseases. Humans cannot synthesize carotenoids and depend on their dietary intake. Major carotenoids that have been found in human plasma can be divided into two groups, carotenes (nonpolar molecules, such as β-carotene, α-carotene or lycopene) and xanthophylls (polar carotenoids that include an oxygen atom in their structure, such as lutein, zeaxanthin and β-cryptoxanthin). Only two dietary carotenoids, namely lutein and zeaxanthin (macular xanthophylls), are selectively accumulated in the human retina. A third carotenoid, meso-zeaxanthin, is formed directly in the human retina from lutein. Additionally, xanthophylls account for about 70% of total carotenoids in all brain regions. Some specific properties of these polar carotenoids must explain why they, among other available carotenoids, were selected during evolution to protect the retina and brain. It is also likely that the selective uptake and deposition of macular xanthophylls in the retina and brain are enhanced by specific xanthophyll-binding proteins. We hypothesize that the high membrane solubility and preferential transmembrane orientation of macular xanthophylls distinguish them from other dietary carotenoids, enhance their chemical and physical stability in retina and brain membranes and maximize their protective action in these organs. Most importantly, xanthophylls are selectively concentrated in the most vulnerable regions of lipid bilayer membranes enriched in polyunsaturated lipids. This localization is ideal if macular xanthophylls are to act as lipid-soluble antioxidants, which is the most accepted mechanism through which lutein and zeaxanthin protect neural tissue against degenerative diseases. PMID:27030822

Molecular evolution of the HoxA cluster in the three major gnathostome lineages

PubMed Central

Chiu, Chi-hua; Amemiya, Chris; Dewar, Ken; Kim, Chang-Bae; Ruddle, Frank H.; Wagner, Günter P.

2002-01-01

The duplication of Hox clusters and their maintenance in a lineage has a prominent but little understood role in chordate evolution. Here we examined how Hox cluster duplication may influence changes in cluster architecture and patterns of noncoding sequence evolution. We sequenced the entire duplicated HoxAa and HoxAb clusters of zebrafish (Danio rerio) and extended the 5′ (posterior) part of the HoxM (HoxA-like) cluster of horn shark (Heterodontus francisci) containing the hoxa11 and hoxa13 orthologs as well as intergenic and flanking noncoding sequences. The duplicated HoxA clusters in zebrafish each house considerably fewer genes and are dramatically shorter than the single HoxA clusters of human and horn shark. We compared the intergenic sequences of the HoxA clusters of human, horn shark, zebrafish (Aa, Ab), and striped bass and found extensive conservation of noncoding sequence motifs, i.e., phylogenetic footprints, between the human and horn shark, representing two of the three gnathostome lineages. These are putative cis-regulatory elements that may play a role in the regulation of the ancestral HoxA cluster. In contrast, homologous regions of the duplicated HoxAa and HoxAb clusters of zebrafish and the HoxA cluster of striped bass revealed a striking loss of conservation of these putative cis-regulatory sequences in the 3′ (anterior) segment of the cluster, where zebrafish only retains single representatives of group 1, 3, 4, and 5 (HoxAa) and group 2 (HoxAb) genes and in the 5′ part of the clusters, where zebrafish retains two copies of the group 13, 11, and 9 genes, i.e., AbdB-like genes. In analyzing patterns of cis-sequence evolution in the 5′ part of the clusters, we explicitly looked for evidence of complementary loss of conserved noncoding sequences, as predicted by the duplication-degeneration-complementation model in which genetic redundancy after gene duplication is resolved because of the fixation of complementary degenerative mutations. Our data did not yield evidence supporting this prediction. We conclude that changes in the pattern of cis-sequence conservation after Hox cluster duplication are more consistent with being the outcome of adaptive modification rather than passive mechanisms that erode redundancy created by the duplication event. These results support the view that genome duplications may provide a mechanism whereby master control genes undergo radical modifications conducive to major alterations in body plan. Such genomic revolutions may contribute significantly to the evolutionary process. PMID:11943847

Monoamine neurons in the human brain stem: anatomy, magnetic resonance imaging findings, and clinical implications.

PubMed

Sasaki, Makoto; Shibata, Eri; Tohyama, Koujiro; Kudo, Kohsuke; Endoh, Jin; Otsuka, Kotaro; Sakai, Akio

2008-11-19

By using high-resolution, conventional, and neuromelanin-sensitive magnetic resonance imaging techniques, we reviewed the normal anatomy of the nuclei consisting of monoamine neurons such as dopaminergic, noradrenergic, and serotoninergic neurons and noted the changes in these nuclei that occur in some degenerative and psychiatric disorders. Multimodal MR images can directly or indirectly help in identifying the substantia nigra, locus ceruleus, and raphe nuclei that contain monoamine neurons. Neuromelanin-sensitive magnetic resonance imaging can detect signal alterations in the substantia nigra pars compacta and/or locus ceruleus that occur in Parkinson's disease and psychiatric disorders such as depression and schizophrenia. This technique seems to be promising for the noninvasive evaluation of the pathological or functional changes in the monoamine system that occur in degenerative and psychiatric disorders.

Deep Space Gateway as a Platform to Study Synergistic Radiation and Microgravity-Induced Tissue Degeneration Using the Bioculture System Single Cassette Hardware Design

NASA Astrophysics Data System (ADS)

Almeida, E. A. C.

2018-02-01

A major unknown for human exploration of deep space is the question of how the degenerative effects of microgravity unloading of cells and tissues may synergize with radiation. Here we describe cell culture hardware to study those combined effects.

Effects of Focal Basal Ganglia Lesions on Timing and Force Control

ERIC Educational Resources Information Center

Aparicio, P.; Diedrichsen, J.; Ivry, R.B.

2005-01-01

Studies of basal ganglia dysfunction in humans have generally involved patients with degenerative disorders, notably Parkinson's disease. In many instances, the performance of these patients is compared to that of patients with focal lesions of other brain structures such as the cerebellum. In the present report, we studied the performance of…

Antioxidant Effect of trans-Resveratrol, Pterostilbene, Quercetin and Their Combinations in Human Erythrocytes In Vitro

USDA-ARS?s Scientific Manuscript database

There is evidence that a diet rich in fruit and vegetables may reduce the risk of cancer and other degenerative diseases. Most natural chemopreventive agents display antioxidant activity. However, the potential health impact of the bioactive phytochemicals is limited by their low amount and relative...

Probiotic Species in the Modulation of Gut Microbiota: An Overview

PubMed Central

Sarker, Manobendro

2018-01-01

Probiotics are microbial strains that are beneficial to health, and their potential has recently led to a significant increase in research interest in their use to modulate the gut microbiota. The animal gut is a complex ecosystem of host cells, microbiota, and available nutrients, and the microbiota prevents several degenerative diseases in humans and animals via immunomodulation. The gut microbiota and its influence on human nutrition, metabolism, physiology, and immunity are addressed, and several probiotic species and strains are discussed to improve the understanding of modulation of gut microbiota. This paper provides a broad review of several Lactobacillus spp., Bifidobacterium spp., and other coliform bacteria as the most promising probiotic species and their role in the prevention of degenerative diseases, such as obesity, diabetes, cancer, cardiovascular diseases, malignancy, liver disease, and inflammatory bowel disease. This review also discusses a recent study of Saccharomyces spp. in which inflammation was prevented by promotion of proinflammatory immune function via the production of short-chain fatty acids. A summary of gut microbiota alteration with future perspectives is also provided. PMID:29854813

Probiotic Species in the Modulation of Gut Microbiota: An Overview.

PubMed

Azad, Md Abul Kalam; Sarker, Manobendro; Li, Tiejun; Yin, Jie

2018-01-01

Probiotics are microbial strains that are beneficial to health, and their potential has recently led to a significant increase in research interest in their use to modulate the gut microbiota. The animal gut is a complex ecosystem of host cells, microbiota, and available nutrients, and the microbiota prevents several degenerative diseases in humans and animals via immunomodulation. The gut microbiota and its influence on human nutrition, metabolism, physiology, and immunity are addressed, and several probiotic species and strains are discussed to improve the understanding of modulation of gut microbiota. This paper provides a broad review of several Lactobacillus spp., Bifidobacterium spp., and other coliform bacteria as the most promising probiotic species and their role in the prevention of degenerative diseases, such as obesity, diabetes, cancer, cardiovascular diseases, malignancy, liver disease, and inflammatory bowel disease. This review also discusses a recent study of Saccharomyces spp. in which inflammation was prevented by promotion of proinflammatory immune function via the production of short-chain fatty acids. A summary of gut microbiota alteration with future perspectives is also provided.

Inclusion body myositis.

PubMed

Dimachkie, Mazen M; Barohn, Richard J

2014-08-01

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare disorders that share many similarities. In addition to sporadic inclusion body myositis (IBM), these include dermatomyositis, polymyositis, and autoimmune necrotizing myopathy. IBM is the most common IIM after age 50 years. Muscle histopathology shows endomysial inflammatory exudates surrounding and invading nonnecrotic muscle fibers often accompanied by rimmed vacuoles and protein deposits. It is likely that IBM is has a prominent degenerative component. This article reviews the evolution of knowledge in IBM, with emphasis on recent developments in the field, and discusses ongoing clinical trials. Copyright © 2014 Elsevier Inc. All rights reserved.

Detection of suspicious pain regions on a digital infrared thermal image using the multimodal function optimization.

PubMed

Lee, Junghoon; Lee, Joosung; Song, Sangha; Lee, Hyunsook; Lee, Kyoungjoung; Yoon, Youngro

2008-01-01

Automatic detection of suspicious pain regions is very useful in the medical digital infrared thermal imaging research area. To detect those regions, we use the SOFES (Survival Of the Fitness kind of the Evolution Strategy) algorithm which is one of the multimodal function optimization methods. We apply this algorithm to famous diseases, such as a foot of the glycosuria, the degenerative arthritis and the varicose vein. The SOFES algorithm is available to detect some hot spots or warm lines as veins. And according to a hundred of trials, the algorithm is very fast to converge.

Angiotensin Converting Enzyme (ACE) Inhibitor Extends Caenorhabditis elegans Life Span

PubMed Central

Kumar, Sandeep; Dietrich, Nicholas; Kornfeld, Kerry

2016-01-01

Animal aging is characterized by progressive, degenerative changes in many organ systems. Because age-related degeneration is a major contributor to disability and death in humans, treatments that delay age-related degeneration are desirable. However, no drugs that delay normal human aging are currently available. To identify drugs that delay age-related degeneration, we used the powerful Caenorhabdtitis elegans model system to screen for FDA-approved drugs that can extend the adult lifespan of worms. Here we show that captopril extended mean lifespan. Captopril is an angiotensin-converting enzyme (ACE) inhibitor used to treat high blood pressure in humans. To explore the mechanism of captopril, we analyzed the acn-1 gene that encodes the C. elegans homolog of ACE. Reducing the activity of acn-1 extended the mean life span. Furthermore, reducing the activity of acn-1 delayed age-related degenerative changes and increased stress resistance, indicating that acn-1 influences aging. Captopril could not further extend the lifespan of animals with reduced acn-1, suggesting they function in the same pathway; we propose that captopril inhibits acn-1 to extend lifespan. To define the relationship with previously characterized longevity pathways, we analyzed mutant animals. The lifespan extension caused by reducing the activity of acn-1 was additive with caloric restriction and mitochondrial insufficiency, and did not require sir-2.1, hsf-1 or rict-1, suggesting that acn-1 functions by a distinct mechanism. The interactions with the insulin/IGF-1 pathway were complex, since the lifespan extensions caused by captopril and reducing acn-1 activity were additive with daf-2 and age-1 but required daf-16. Captopril treatment and reducing acn-1 activity caused similar effects in a wide range of genetic backgrounds, consistent with the model that they act by the same mechanism. These results identify a new drug and a new gene that can extend the lifespan of worms and suggest new therapeutic strategies for addressing age-related degenerative changes. PMID:26918946

Noncanonical Wnt5a-Ca(2+) -NFAT signaling axis in pesticide induced bone marrow aplasia mouse model: A study to explore the novel mechanism of pesticide toxicity.

PubMed

Chattopadhyay, Sukalpa; Chatterjee, Ritam; Law, Sujata

2016-10-01

According to case-control studies, long-term pesticide exposure can cause bone marrow aplasia like hematopoietic degenerative disease leading to impaired hematopoiesis and increased risk of aplastic anemia in human subjects. However, the exact mechanism of pesticide mediated hematotoxicity still remains elusive. In this study, we investigated the role of noncanonical Wnt signaling pathway, a crucial regulator of adult hematopoiesis, in pesticide induced bone marrow aplasia mouse model. Aplasia mouse model was developed following inhalation and dermal exposure of 5% aqueous mixture of common agriculturally used pesticides for 6 h/day for 5 days a week up to 90 days. After that, blood hemogram, marrow smear, cellularity, scanning electron microscopy, extramedullary hematopoiesis and flowcytometric expression analysis of noncanonical Wnt signaling components, such as Wnt 5a, fzd5, NFAT, IFN-γ, intracellular Ca(2+) level were evaluated in the bone marrow hematopoietic stem/progenitor compartment of the control and pesticide induced aplasia groups of animals. Results showed that pesticide exposed mice were anemic with peripheral blood pancytopenia, hypocellular degenerative marrow, and extramedullary hematopoiesis in the spleen. Upon pesticide exposure, Wnt 5a expression was severely downregulated with a decline in intracellular Ca(2+) level. Moreover, downstream of Wnt5a, we observed sharp downregulation of NFATc2 transcription factor expression, the major target of pesticide toxicity and its target molecule IFN-γ. Taken together, our result suggests that deregulation of Wnt5a-Ca(2+) -NFAT signaling axis in the hematopoietic stem/progenitor compartment plays a crucial role behind the pathogenesis of pesticide mediated bone marrow aplasia by limiting primitive hematopoietic stem cells' ability to maintain hematopoietic homeostasis and reconstitution mechanism in vivo during xenobiotic stress leading to ineffective hematopoiesis and evolution of bone marrow aplasia. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1163-1175, 2016. © 2015 Wiley Periodicals, Inc.

Canine degenerative myelopathy: a model of human amyotrophic lateral sclerosis.

PubMed

Nardone, Raffaele; Höller, Yvonne; Taylor, Alexandra C; Lochner, Piergiorgio; Tezzon, Frediano; Golaszewski, Stefan; Brigo, Francesco; Trinka, Eugen

2016-02-01

Canine degenerative myelopathy (CDM) represents a unique naturally occurring animal model for human amyotrophic lateral sclerosis (ALS) because of similar clinical signs, neuropathologic findings, and involvement of the superoxide dismutase 1 (SOD1) mutation. A definitive diagnosis can only be made postmortem through microscopic detection of axonal degeneration, demyelination and astroglial proliferation, which is more severe in the dorsal columns of the thoracic spinal cord and in the dorsal portion of the lateral funiculus. Interestingly, the muscle acetylcholine receptor complexes are intact in CDM prior to functional impairment, thus suggesting that muscle atrophy in CDM does not result from physical denervation. Moreover, since sensory involvement seems to play an important role in CDM progression, a more careful investigation of the sensory pathology in ALS is also warranted. The importance of SOD1 expression remains unclear, while oxidative stress and denatured ubiquinated proteins appear to play a crucial role in the pathogenesis of CDM. In this updated narrative review we performed a systematic search of the published studies on CDM that may shed light on the pathophysiological mechanisms of human ALS. A better understanding of the factors that determine the disease progression in CDM may be beneficial for the development of effective treatments for ALS. Copyright © 2015 Elsevier GmbH. All rights reserved.

Effects of Fe particle irradiation on human endothelial barrier structure and function

NASA Astrophysics Data System (ADS)

Sharma, Preety; Guida, Peter; Grabham, Peter

2014-07-01

Space travel involves exposure to biologically effective heavy ion radiation and there is consequently a concern for possible degenerative disorders in humans. A significant target for radiation effects is the microvascular system, which is crucial to healthy functioning of the tissues. Its pathology is linked to disrupted endothelial barrier function and is not only a primary event in a range of degenerative diseases but also an important influencing factor in many others. Thus, an assessment of the effects of heavy ion radiation on endothelial barrier function would be useful for estimating the risks of space travel. This study was aimed at understanding the effects of high LET Fe particles (1 GeV/n) and is the first investigation of the effects of charged particles on the function of the human endothelial barrier. We used a set of established and novel endpoints to assess barrier function after exposure. These include, trans-endothelial electrical resistance (TEER), morphological effects, localization of adhesion and cell junction proteins (in 2D monolayers and in 3D tissue models), and permeability of molecules through the endothelial barrier. A dose of 0.50 Gy was sufficient to cause a progressive reduction in TEER measurements that were significant 48 hours after exposure. Concurrently, there were morphological changes and a 14% loss of cells from monolayers. Gaps also appeared in the normally continuous cell-border localization of the tight junction protein - ZO-1 but not the Platelet endothelial cell adhesion molecule (PECAM-1) in both monolayers and in 3D vessel models. Disruption of barrier function was confirmed by increased permeability to 3 kDa and 10 kDa dextran molecules. A dose of 0.25 Gy caused no detectible change in cell number, morphology, or TEER, but did cause barrier disruption since there were gaps in the cell border localization of ZO-1 and an increased permeability to 3 kDa dextran. These results indicate that Fe particles potently have impact on human endothelial barrier function and represent a risk for degenerative diseases in the space environment.

[Bilateral spontaneously reattached rhegmatogenous retinal detachment. Case report and differential diagnosis with pigmentary retinopathies].

PubMed

García-Guzmán, Jorge Guillermo; Franco-Yáñez, Yasmín; Lima-Gómez, Virgilio

2014-01-01

A dark pigmentation of the ocular fundus presents in degenerative diseases such as retinitis pigmentosa; this disease must be distinguished from others whose evolution is not progressive, in order to estimate the functional prognosis of the patient. To analyze the features which distinguish spontaneously reattached retinal detachment from other causes of ocular fundus pigmentation, in order to be able to identify it even in bilateral cases. A case of a female with chronic visual loss is presented, who was referred for evaluation with the diagnosis of a pigmented retinopathy. Clinical exploration discarded causes as retinitis pigmentosa, retinal inflammatory diseases or trauma. Based on the clinical features, on the topography of pigmentation and in the information provided by electroretinography, a bilateral spontaneous reattachment of rhegmatogenous retinal detachment was diagnosed made. Clinical features of this entity are discussed, as well as the diagnostic approach to distinguish it from other pigment retinopathies. Clinical features of spontaneously reattached retinal detachment allow the explorer to distinguish it from other causes of bilateral pigmentation, despite presenting bilaterally. Since the prognosis of the attached retina is better than that of a degenerative disease, the correct diagnosis makes rehabilitation easier.

Will immediate postoperative imbalance improve in patients with thoracolumbar/lumbar degenerative kyphoscoliosis? A comparison between Smith-Petersen osteotomy and pedicle subtraction osteotomy with an average 4 years of follow-up.

PubMed

Bao, Hongda; He, Shouyu; Liu, Zhen; Zhu, Zezhang; Qiu, Yong; Zhu, Feng

2015-03-01

A retrospective radiographical study. To compare compensatory behavior of coronal and sagittal alignment after pedicle subtraction osteotomy (PSO) and Smith-Petersen osteotomy (SPO) for degenerative kyphoscoliosis. There was a paucity of literature paying attention to the postoperative imbalance after PSO or SPO and natural evolution of the imbalance. A retrospective study was performed on 68 consecutive patients with degenerative kyphoscoliosis treated by lumbar PSO (25 patients) or SPO (43 patients) procedures at a single institution. Long-cassette standing radiographs were taken preoperatively, postoperatively, and at the last follow-up and radiographical parameters were measured. The lower instrumented vertebral level and level of osteotomy were compared between the patients with and without improvement. Negative sagittal vertical axis (SVA) was observed in the PSO group postoperatively, implying an overcorrection of SVA. This negative SVA improved spontaneously during follow-up (P < 0.05). Coronal balance was found to worsen immediately postoperatively in the SPO group (P < 0.05). At the last follow-up, spontaneous improvement was observed in 15 patients and the average coronal balance decreased to 16.35 mm. For the 15 patients with improved coronal balance, fusion at L5 or above was more common compared with the 11 patients with persisted postoperative imbalance (P = 0.027), whereas no difference in term of levels of osteotomy was found (P > 0.05). The overcorrection of SVA is more often seen in the PSO group. The coronal imbalance is more likely to occur in the SPO group. The postoperative sagittal imbalance often spontaneously improves with time. Lower instrumented vertebra at S1 or with pelvic fixation should be regarded as potential risk factors for persistent coronal imbalance in patients with SPO. 3.

Degenerative joint disease in weight-lifters. Fact or fiction?

PubMed Central

Fitzgerald, B.; McLatchie, G. R.

1980-01-01

A clinical and radiological study of upper and lower limb joints was carried out on 25 experienced weight-lifters to identify the extent of degenerative joint disease (Osteoarthrosis) produced by this sport. Although significant degenerative changes were found in five lifters (20%). This figure is not greater than that found in the general population within the age group studied. There were more degenerative changes found in Olympic style weight-lifters (30.7%) than in power lifters (8.3%). The significance of these figures is discussed. The upper limb joints were almost completely free of degenerative changes. Images p97-a p97-b PMID:7407459

Antiobesity Effects of Anthocyanins in Preclinical and Clinical Studies

PubMed Central

Giacometti, Jasminka

2017-01-01

The natural phytochemicals present in foods, including anthocyanins, might play a role in attenuating obesity by producing a decrease in weight and adipose tissue. This review focused on current knowledge about anthocyanins' role in obesity and its related comorbidities reported in animal models and humans. We summarized their target identification and mechanism of action through several pathways and their final effects on health and well-being. Into consideration of ongoing researches, we highlighted the following key points: a healthy relationship between anthocyanin supplementation and antiobesity effects suffers of the same pros and cons evidenced when the beneficial responses to other phytochemical treatments towards different degenerative diseases have been considered; the different dosage applied in animal versus clinical studies; the complex metabolism and biotransformation to which anthocyanins and phytochemicals are subjected in the intestine and tissues; the possibility that different components present in the supplemented mixtures can interact generating antagonistic, synergistic, or additive effects difficult to predict, and the difference between prevention and therapy. The evolution of the field must seriously consider the need to establish new and adequate cellular and animal models which may, in turn, allow the design of more efficient and prevention-targeted clinical studies. PMID:28785373

Antiobesity Effects of Anthocyanins in Preclinical and Clinical Studies.

PubMed

Azzini, Elena; Giacometti, Jasminka; Russo, Gian Luigi

2017-01-01

The natural phytochemicals present in foods, including anthocyanins, might play a role in attenuating obesity by producing a decrease in weight and adipose tissue. This review focused on current knowledge about anthocyanins' role in obesity and its related comorbidities reported in animal models and humans. We summarized their target identification and mechanism of action through several pathways and their final effects on health and well-being. Into consideration of ongoing researches, we highlighted the following key points: a healthy relationship between anthocyanin supplementation and antiobesity effects suffers of the same pros and cons evidenced when the beneficial responses to other phytochemical treatments towards different degenerative diseases have been considered; the different dosage applied in animal versus clinical studies; the complex metabolism and biotransformation to which anthocyanins and phytochemicals are subjected in the intestine and tissues; the possibility that different components present in the supplemented mixtures can interact generating antagonistic, synergistic, or additive effects difficult to predict, and the difference between prevention and therapy. The evolution of the field must seriously consider the need to establish new and adequate cellular and animal models which may, in turn, allow the design of more efficient and prevention-targeted clinical studies.

Familial Amyotrophic Lateral Sclerosis-linked Mutations in Profilin 1 Exacerbate TDP-43-induced Degeneration in the Retina of Drosophila melanogaster through an Increase in the Cytoplasmic Localization of TDP-43.

PubMed

Matsukawa, Koji; Hashimoto, Tadafumi; Matsumoto, Taisei; Ihara, Ryoko; Chihara, Takahiro; Miura, Masayuki; Wakabayashi, Tomoko; Iwatsubo, Takeshi

2016-11-04

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive and selective loss of motor neurons. Causative genes for familial ALS (fALS), e.g. TARDBP or FUS/TLS, have been found, among which mutations within the profilin 1 (PFN1) gene have recently been identified in ALS18. To elucidate the mechanism whereby PFN1 mutations lead to neuronal death, we generated transgenic Drosophila melanogaster overexpressing human PFN1 in the retinal photoreceptor neurons. Overexpression of wild-type or fALS mutant PFN1 caused no degenerative phenotypes in the retina. Double overexpression of fALS mutant PFN1 and human TDP-43 markedly exacerbated the TDP-43-induced retinal degeneration, i.e. vacuolation and thinning of the retina, whereas co-expression of wild-type PFN1 did not aggravate the degenerative phenotype. Notably, co-expression of TDP-43 with fALS mutant PFN1 increased the cytoplasmic localization of TDP-43, the latter remaining in nuclei upon co-expression with wild-type PFN1, whereas co-expression of TDP-43 lacking the nuclear localization signal with the fALS mutant PFN1 did not aggravate the retinal degeneration. Knockdown of endogenous Drosophila PFN1 did not alter the degenerative phenotypes of the retina in flies overexpressing wild-type TDP-43 These data suggest that ALS-linked PFN1 mutations exacerbate TDP-43-induced neurodegeneration in a gain-of-function manner, possibly by shifting the localization of TDP-43 from nuclei to cytoplasm. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Past and future corollaries of theories on causes of metabolic syndrome and obesity related co-morbidities part 2: a composite unifying theory review of human-specific co-adaptations to brain energy consumption

PubMed Central

2014-01-01

Forward A composite unifying theory on causes of obesity related-MetS has been formulated and published in an accompanying article (1). In the current article, the historical and recent past, present and future corollaries of this theory are discussed. By presenting this composite theory and corollaries, it is hoped that human evolution and physiology will be viewed and studied from a new vantage point. The politics of management of ecological farming and nutrition will change, a profound reconfiguration of scientific theory generation and advancement in a ‘high-tech’ world can be made, and pathways for solutions recognised. Metabolic syndrome (MetS) predicts type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer, and their rates have escalated over the last few decades. Obesity related co-morbidities also overlap the concept of the metabolic syndrome (MetS). However, understanding of the syndrome’s underlying causes may have been misapprehended. The current paper follows on from a theory review by McGill, A-T in Archives of Public Health, 72: 30. This accompanying paper utilises research on human evolution and new biochemistry to theorise on why MetS and obesity arise and how they affect the population. The basis of this composite unifying theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A ‘dual system’ is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals. In humans who consume a nutritious diet, the NRF2 system has become highly energy efficient. Other relevant human-specific co-adaptations are explored. In order to ‘test’ this composite unifying theory it is important to show that the hypothesis and sub-theories pertain throughout the whole of human evolution and history up till the current era. Corollaries of the composite unifying theory of MetS are examined with respect to past under-nutrition and malnutrition since agriculture began 10,000 years ago. The effects of man-made pollutants on degenerative change are examined. Projections are then made from current to future patterns on the state of ‘insufficient micronutrient and/or unbalanced high energy malnutrition with central obesity and metabolic dysregulation’ or ‘malnubesity’. Forecasts on human health are made on positive, proactive strategies using the composite unifying theory, and are extended to the wider human ecology of food production. A comparison is made with the outlook for humans if current assumptions and the status quo on causes and treatments are maintained. Areas of further research are outlined. A table of suggestions for possible public health action is included. PMID:25708599

An Unusual Splice Defect in the Mitofusin 2 Gene (MFN2) Is Associated with Degenerative Axonopathy in Tyrolean Grey Cattle

PubMed Central

Drögemüller, Cord; Reichart, Ursula; Seuberlich, Torsten; Oevermann, Anna; Baumgartner, Martin; Kühni Boghenbor, Kathrin; Stoffel, Michael H.; Syring, Claudia; Meylan, Mireille; Müller, Simone; Müller, Mathias; Gredler, Birgit

2011-01-01

Tyrolean Grey cattle represent a local breed with a population size of ∼5000 registered cows. In 2003, a previously unknown neurological disorder was recognized in Tyrolean Grey cattle. The clinical signs of the disorder are similar to those of bovine progressive degenerative myeloencephalopathy (weaver syndrome) in Brown Swiss cattle but occur much earlier in life. The neuropathological investigation of an affected calf showed axonal degeneration in the central nervous system (CNS) and femoral nerve. The pedigrees of the affected calves suggested a monogenic autosomal recessive inheritance. We localized the responsible mutation to a 1.9 Mb interval on chromosome 16 by genome-wide association and haplotype mapping. The MFN2 gene located in this interval encodes mitofusin 2, a mitochondrial membrane protein. A heritable human axonal neuropathy, Charcot-Marie-Tooth disease-2A2 (CMT2A2), is caused by MFN2 mutations. Therefore, we considered MFN2 a positional and functional candidate gene and performed mutation analysis in affected and control Tyrolean Grey cattle. We did not find any non-synonymous variants. However, we identified a perfectly associated silent SNP in the coding region of exon 20 of the MFN2 gene. This SNP is located within a putative exonic splice enhancer (ESE) and the variant allele leads to partial retention of the entire intron 19 and a premature stop codon in the aberrant MFN2 transcript. Thus we have identified a highly unusual splicing defect, where an exonic single base exchange leads to the retention of the preceding intron. This splicing defect represents a potential explanation for the observed degenerative axonopathy. Marker assisted selection can now be used to eliminate degenerative axonopathy from Tyrolean Grey cattle. PMID:21526202

An unusual splice defect in the mitofusin 2 gene (MFN2) is associated with degenerative axonopathy in Tyrolean Grey cattle.

PubMed

Drögemüller, Cord; Reichart, Ursula; Seuberlich, Torsten; Oevermann, Anna; Baumgartner, Martin; Kühni Boghenbor, Kathrin; Stoffel, Michael H; Syring, Claudia; Meylan, Mireille; Müller, Simone; Müller, Mathias; Gredler, Birgit; Sölkner, Johann; Leeb, Tosso

2011-04-15

Tyrolean Grey cattle represent a local breed with a population size of ∼5000 registered cows. In 2003, a previously unknown neurological disorder was recognized in Tyrolean Grey cattle. The clinical signs of the disorder are similar to those of bovine progressive degenerative myeloencephalopathy (weaver syndrome) in Brown Swiss cattle but occur much earlier in life. The neuropathological investigation of an affected calf showed axonal degeneration in the central nervous system (CNS) and femoral nerve. The pedigrees of the affected calves suggested a monogenic autosomal recessive inheritance. We localized the responsible mutation to a 1.9 Mb interval on chromosome 16 by genome-wide association and haplotype mapping. The MFN2 gene located in this interval encodes mitofusin 2, a mitochondrial membrane protein. A heritable human axonal neuropathy, Charcot-Marie-Tooth disease-2A2 (CMT2A2), is caused by MFN2 mutations. Therefore, we considered MFN2 a positional and functional candidate gene and performed mutation analysis in affected and control Tyrolean Grey cattle. We did not find any non-synonymous variants. However, we identified a perfectly associated silent SNP in the coding region of exon 20 of the MFN2 gene. This SNP is located within a putative exonic splice enhancer (ESE) and the variant allele leads to partial retention of the entire intron 19 and a premature stop codon in the aberrant MFN2 transcript. Thus we have identified a highly unusual splicing defect, where an exonic single base exchange leads to the retention of the preceding intron. This splicing defect represents a potential explanation for the observed degenerative axonopathy. Marker assisted selection can now be used to eliminate degenerative axonopathy from Tyrolean Grey cattle.

On the Relative Relevance of Subject-Specific Geometries and Degeneration-Specific Mechanical Properties for the Study of Cell Death in Human Intervertebral Disk Models

PubMed Central

Malandrino, Andrea; Pozo, José M.; Castro-Mateos, Isaac; Frangi, Alejandro F.; van Rijsbergen, Marc M.; Ito, Keita; Wilke, Hans-Joachim; Dao, Tien Tuan; Ho Ba Tho, Marie-Christine; Noailly, Jérôme

2015-01-01

Capturing patient- or condition-specific intervertebral disk (IVD) properties in finite element models is outmost important in order to explore how biomechanical and biophysical processes may interact in spine diseases. However, disk degenerative changes are often modeled through equations similar to those employed for healthy organs, which might not be valid. As for the simulated effects of degenerative changes, they likely depend on specific disk geometries. Accordingly, we explored the ability of continuum tissue models to simulate disk degenerative changes. We further used the results in order to assess the interplay between these simulated changes and particular IVD morphologies, in relation to disk cell nutrition, a potentially important factor in disk tissue regulation. A protocol to derive patient-specific computational models from clinical images was applied to different spine specimens. In vitro, IVD creep tests were used to optimize poro-hyperelastic input material parameters in these models, in function of the IVD degeneration grade. The use of condition-specific tissue model parameters in the specimen-specific geometrical models was validated against independent kinematic measurements in vitro. Then, models were coupled to a transport-cell viability model in order to assess the respective effects of tissue degeneration and disk geometry on cell viability. While classic disk poro-mechanical models failed in representing known degenerative changes, additional simulation of tissue damage allowed model validation and gave degeneration-dependent material properties related to osmotic pressure and water loss, and to increased fibrosis. Surprisingly, nutrition-induced cell death was independent of the grade-dependent material properties, but was favored by increased diffusion distances in large IVDs. Our results suggest that in situ geometrical screening of IVD morphology might help to anticipate particular mechanisms of disk degeneration. PMID:25717471

Selection and Investigation of a Primate Model of Spontaneous Degenerative Knee Osteoarthritis, the Cynomolgus Monkey (Macaca Fascicularis).

PubMed

Liu, Gang; Zhang, Lei; Zhou, Xin; Zhang, Bao L; Guo, Guang X; Xu, Ping; Wang, Guo Y; Fu, Shi J

2018-07-01

BACKGROUND The aim of this study was to identify a primate model of degenerative knee osteoarthritis (KOA) that may be more relevant for research studies on degenerative KOA in humans. MATERIAL AND METHODS Sixteen specific-pathogen-free (SPF) male cynomolgus monkeys (Macaca fascicularis) were divided into group A (n=8), an old group (22.0-25.3 years of age), and group B (n=8), a young group (3.0-5.2 years of age). For each primate, the behavior was observed, knee circumference was measured, knee joint X-rays were performed, and peripheral blood white blood cell (WBC) counts were measured, and the Kellgren and Lawrence (K-L) system was used for the classification of osteoarthritis. An enzyme-linked immunoassay (ELISA) was performed on knee joint fluid to measure levels of interleukin (IL)-1β, transforming growth factor (TGF)-β1, and matrix metalloproteinase (MMP)13. Changes in articular cartilage were evaluated using the Brittberg score and the Mankin histopathology grading score, respectively. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot were used to measure the expression of the NOTCH3, JAG1, and ACAN genes in knee cartilage specimens, and the findings in the two groups of primates were compared. RESULTS Seven old aged primates in group A were compared with group B, and showed significant differences in WBC count, synovial fluid IL-1β, TGF-β1, and MMP13 levels, expression levels of the NOTCH3, JAG1, and ACAN genes in knee cartilage specimens, and in the Brittberg and Mankin scores (all, P<0.05). CONCLUSIONS Cynomolgus monkeys (Macaca fascicularis) might be a model for age-related degenerative KOA.

78 FR 65450 - Agency Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

...-Degenerative Arthritis (Including Inflammatory, Autoimmune, Crystalline and Infectious Arthritis) and Dysbaric... Control No. 2900- NEW (Non-Degenerative Arthritis (including inflammatory, autoimmune, crystalline and infectious arthritis) and Dysbaric Osteonecrosis Disability Benefits Questionnaire)'' in any correspondence...

Multifractal detrended cross correlation analysis of neuro-degenerative diseases-An in depth study

NASA Astrophysics Data System (ADS)

Dutta, Srimonti; Ghosh, Dipak; Chatterjee, Sucharita

2018-02-01

This work revisits our previous study on human gait diseases, (Dutta et al., 2013) where we have studied the autocorrelation of human gait pattern in normal and diseased set. Significant difference in results was observed for normal and diseased set. However we were not able to distinguish between sets of Parkinson's and Huntington's disease. In this paper we attempt to study whether cross correlations between two feet of human gait pattern can help to distinguish between different diseased set. The results reveal that study of cross correlations can help to distinguish between Parkinson's and Huntington's disease.

MRI features of cervical articular process degenerative joint disease in Great Dane dogs with cervical spondylomyelopathy.

PubMed

Gutierrez-Quintana, Rodrigo; Penderis, Jacques

2012-01-01

Cervical spondylomyelopathy or Wobbler syndrome commonly affects the cervical vertebral column of Great Dane dogs. Degenerative changes affecting the articular process joints are a frequent finding in these patients; however, the correlation between these changes and other features of cervical spondylomyelopathy are uncertain. We described and graded the degenerative changes evident in the cervical articular process joints from 13 Great Danes dogs with cervical spondylomyelopathy using MR imaging, and evaluated the relationship between individual features of cervical articular process joint degeneration and the presence of spinal cord compression, vertebral foraminal stenosis, intramedullary spinal cord changes, and intervertebral disc degenerative changes. Degenerative changes affecting the articular process joints were common, with only 13 of 94 (14%) having no degenerative changes. The most severe changes were evident between C4-C5 and C7-T1 intervertebral spaces. Reduction or loss of the hyperintense synovial fluid signal on T2-weighted MR images was the most frequent feature associated with articular process joint degenerative changes. Degenerative changes of the articular process joints affecting the synovial fluid or articular surface, or causing lateral hypertrophic tissue, were positively correlated with lateral spinal cord compression and vertebral foraminal stenosis. Dorsal hypertrophic tissue was positively correlated with dorsal spinal cord compression. Disc-associated spinal cord compression was recognized less frequently. © 2011 Veterinary Radiology & Ultrasound.

Degenerative Changes of Spine in Helicopter Pilots

PubMed Central

Byeon, Joo Hyeon; Kim, Jung Won; Jeong, Ho Joong; Sim, Young Joo; Kim, Dong Kyu; Choi, Jong Kyoung; Im, Hyoung June

2013-01-01

Objective To determine the relationship between whole body vibration (WBV) induced helicopter flights and degenerative changes of the cervical and lumbar spine. Methods We examined 186 helicopter pilots who were exposed to WBV and 94 military clerical workers at a military hospital. Questionnaires and interviews were completed for 164 of the 186 pilots (response rate, 88.2%) and 88 of the 94 clerical workers (response rate, 93.6%). Radiographic examinations of the cervical and the lumbar spines were performed after obtaining informed consent in both groups. Degenerative changes of the cervical and lumbar spines were determined using four radiographs per subject, and diagnosed by two independent, blinded radiologists. Results There was no significant difference in general and work-related characteristics except for flight hours and frequency between helicopter pilots and clerical workers. Degenerative changes in the cervical spine were significantly more prevalent in the helicopter pilots compared with control group. In the cervical spine multivariate model, accumulated flight hours (per 100 hours) was associated with degenerative changes. And in the lumbar spine multivariate model, accumulated flight hours (per 100 hours) and age were associated with degenerative changes. Conclusion Accumulated flight hours were associated with degenerative changes of the cervical and lumbar spines in helicopter pilots. PMID:24236259

Zebrafish models for the functional genomics of neurogenetic disorders.

PubMed

Kabashi, Edor; Brustein, Edna; Champagne, Nathalie; Drapeau, Pierre

2011-03-01

In this review, we consider recent work using zebrafish to validate and study the functional consequences of mutations of human genes implicated in a broad range of degenerative and developmental disorders of the brain and spinal cord. Also we present technical considerations for those wishing to study their own genes of interest by taking advantage of this easily manipulated and clinically relevant model organism. Zebrafish permit mutational analyses of genetic function (gain or loss of function) and the rapid validation of human variants as pathological mutations. In particular, neural degeneration can be characterized at genetic, cellular, functional, and behavioral levels. Zebrafish have been used to knock down or express mutations in zebrafish homologs of human genes and to directly express human genes bearing mutations related to neurodegenerative disorders such as spinal muscular atrophy, ataxia, hereditary spastic paraplegia, amyotrophic lateral sclerosis (ALS), epilepsy, Huntington's disease, Parkinson's disease, fronto-temporal dementia, and Alzheimer's disease. More recently, we have been using zebrafish to validate mutations of synaptic genes discovered by large-scale genomic approaches in developmental disorders such as autism, schizophrenia, and non-syndromic mental retardation. Advances in zebrafish genetics such as multigenic analyses and chemical genetics now offer a unique potential for disease research. Thus, zebrafish hold much promise for advancing the functional genomics of human diseases, the understanding of the genetics and cell biology of degenerative and developmental disorders, and the discovery of therapeutics. This article is part of a Special Issue entitled Zebrafish Models of Neurological Diseases. Copyright © 2010 Elsevier B.V. All rights reserved.

Use of transfer learning to detect diffuse degenerative hepatic diseases from ultrasound images in dogs: A methodological study.

PubMed

Banzato, T; Bonsembiante, F; Aresu, L; Gelain, M E; Burti, S; Zotti, A

2018-03-01

The aim of this methodological study was to develop a deep convolutional neural network (DNN) to detect degenerative hepatic disease from ultrasound images of the liver in dogs and to compare the diagnostic accuracy of the newly developed DNN with that of serum biochemistry and cytology on the same samples, using histopathology as a standard. Dogs with suspected hepatic disease that had no prior history of neoplastic disease, no hepatic nodular pathology, no ascites and ultrasonography performed 24h prior to death were included in the study (n=52). Ultrasonography and serum biochemistry were performed as part of the routine clinical evaluation. On the basis of histopathology, dogs were categorised as 'normal' (n=8), or having 'vascular abnormalities'(n=8), or 'inflammatory'(n=0), 'neoplastic' (n=4) or 'degenerative'(n=32) disease; dogs with 'neoplastic' disease were excluded from further analysis. On cytological evaluation, dogs were categorised as 'normal' (n=11), or having 'inflammatory' (n=0), 'neoplastic' (n=4) or 'degenerative' (n=37) disease. Dogs were categorised as having 'degenerative' (n=32) or 'non-degenerative' (n=16) liver disease for analysis due to the limited sample size. The DNN was developed using a transfer learning methodology on a pre-trained neural network that was retrained and fine-tuned to our data set. The resultant DNN had a high diagnostic accuracy for degenerative liver disease (area under the curve 0.91; sensitivity 100%; specificity 82.8%). Cytology and serum biochemical markers (alanine transaminase and aspartate transaminase) had poor diagnostic accuracy in the detection of degenerative liver disease. The DNN outperformed all the other non-invasive diagnostic tests in the detection of degenerative liver disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

Javamide-I-O-methyl ester increases p53 acetylation and induces cell death via activating caspase 3/7 in monocytic THP-1 cells

USDA-ARS?s Scientific Manuscript database

Our previous study suggested that javamide-II found in coffee could inhibit sirtuin1/2, thereby potentially beneficial in some human diseases such as neuronal degenerative diseases and cancer. In fact, coffee is reported to contain javamide-I, in addition to javamide-II. However, potential effects o...

Slowly progressive aphasia associated with surface dyslexia.

PubMed

Chiacchio, L; Grossi, D; Stanzione, M; Trojano, L

1993-03-01

We report an Italian patient affected by slowly progressive aphasia (SPA) lasting since four years when he first came to our observation. During the successive four years, we documented a progressive language decline resembling transcortical sensory aphasia, associated with a reading disorder corresponding to surface dyslexia, a form extremely rare in patients with native transparent language. His performance at standard intelligence tasks remained in the normal range, without any variation. CT scan showed left temporal atrophy. We emphasize the heterogeneity of the syndrome of SPA and suggest that it can represent one of the pictures of focal cortical degenerative disease, with variable onset, progression, and evolution.

Distribution of lactate dehydrogenase in healthy and degenerative canine stifle joint cartilage.

PubMed

Walter, Eveline L C; Spreng, David; Schmöckel, Hugo; Schawalder, Peter; Tschudi, Peter; Friess, Armin E; Stoffel, Michael H

2007-07-01

In dogs, degenerative joint diseases (DJD) have been shown to be associated with increased lactate dehydrogenase (LDH) activity in the synovial fluid. The goal of this study was to examine healthy and degenerative stifle joints in order to clarify the origin of LDH in synovial fluid. In order to assess the distribution of LDH, cartilage samples from healthy and degenerative knee joints were investigated by means of light and transmission electron microscopy in conjunction with immunolabeling and enzyme cytochemistry. Morphological analysis confirmed DJD. All techniques used corroborated the presence of LDH in chondrocytes and in the interterritorial matrix of healthy and degenerative stifle joints. Although enzymatic activity of LDH was clearly demonstrated in the territorial matrix by means of the tetrazolium-formazan reaction, immunolabeling for LDH was missing in this region. With respect to the distribution of LDH in the interterritorial matrix, a striking decrease from superficial to deeper layers was present in healthy dogs but was missing in affected joints. These results support the contention that LDH in synovial fluid of degenerative joints originates from cartilage. Therefore, we suggest that (1) LDH is transferred from chondrocytes to ECM in both healthy dogs and dogs with degenerative joint disease and that (2) in degenerative joints, LDH is released from chondrocytes and the ECM into synovial fluid through abrasion of cartilage as well as through enhanced diffusion as a result of increased water content and degradation of collagen.

Label-free characterization of degenerative changes in articular cartilage by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Oshima, Yusuke; Akehi, Mayu; Kiyomatsu, Hiroshi; Miura, Hiromasa

2017-04-01

Osteoarthritis (OA) is very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. We generated an animal OA model surgically induced by knee joint instability and performed Raman spectroscopic analysis for the articular cartilage. In the result, Raman spectral data of the articular cartilage showed drastic changes in comparison between OA and control side. The relative intensity of phosphate band increases in the degenerative cartilage.

Bovine Progressive Degenerative Myeloencephalopathy (Weaver Syndrome) in Brown Swiss Cattle in Canada: A Literature Review and Case Report

PubMed Central

Baird, John D.; Sarmiento, Ulla M.; Basrur, Parvathi K.

1988-01-01

A 15-month-old purebred Brown Swiss heifer was presented because of posterior paresis and ataxia. Histopathological examination of the brain and spinal cord showed evidence of a mild diffuse degenerative myeloencephalopathy. The most severe degenerative lesions were located in the white matter of the thoracic spinal cord. We believe this to be the first documented case of bovine progressive degenerative myeloencephalopathy (“weaver syndrome”) in Canada. ImagesFigure 1.Figure 2., Figure 3., Figure 4.Figure 5. PMID:17423028

Contribution of Microglia-Mediated Neuroinflammation to Retinal Degenerative Diseases

PubMed Central

Madeira, Maria H.; Boia, Raquel; Santos, Paulo F.; Ambrósio, António F.; Santiago, Ana R.

2015-01-01

Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microglia-mediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy. PMID:25873768

Influence of artificial shock absorbers on human gait.

PubMed

Voloshin, A; Wosk, J

1981-10-01

The effect of artificial shock absorbers on the human gait and the technique for its quantitative evaluation have been studied. The results obtained have shown that viscoelastic inserts reduced the amplitude of the incoming shock waves bearing upon the musculoskeletal system as a result of the heel strike, by 42 percent (mean value). Conservative treatment, using such inserts for patients with different clinical symptoms of degenerative joint diseases, has shown excellent results. Seventy-eight percent of the clinical symptoms disappeared, while satisfactory improvement was reported in 17 percent of the subjects.

Induced pluripotent stem cells (iPSC)-derived retinal cells in disease modeling and regenerative medicine.

PubMed

Rathod, Reena; Surendran, Harshini; Battu, Rajani; Desai, Jogin; Pal, Rajarshi

2018-02-12

Retinal degenerative disorders are a leading cause of the inherited, irreversible and incurable vision loss. While various rodent model systems have provided crucial information in this direction, lack of disease-relevant tissue availability and species-specific differences have proven to be a major roadblock. Human induced pluripotent stem cells (iPSC) have opened up a whole new avenue of possibilities not just in understanding the disease mechanism but also potential therapeutic approaches towards a cure. In this review, we have summarized recent advances in the methods of deriving retinal cell types from iPSCs which can serve as a renewable source of disease-relevant cell population for basic as well as translational studies. We also provide an overview of the ongoing efforts towards developing a suitable in vitro model for modeling retinal degenerative diseases. This basic understanding in turn has contributed to advances in translational goals such as drug screening and cell-replacement therapies. Furthermore we discuss gene editing approaches for autologous repair of genetic disorders and allogeneic transplantation of stem cell-based retinal derivatives for degenerative disorders with an ultimate goal to restore vision. It is pertinent to note however, that these exciting new developments throw up several challenges that need to be overcome before their full clinical potential can be realized. Copyright © 2018 Elsevier B.V. All rights reserved.

Label-free characterization of articular cartilage in osteoarthritis model mice by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Oshima, Yusuke; Akehi, Mayu; Kiyomatsu, Hiroshi; Miura, Hiromasa

2017-02-01

Osteoarthritis (OA) is very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Cartilage contains mostly type II collagen and proteoglycans, so it is difficult to access the quality and morphology of cartilage tissue in situ by conventional diagnostic tools (X-ray, MRI and echography) directly or indirectly. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. In this study, we generated an animal OA model surgically induced by knee joint instability, and the femurs were harvested at two weeks after the surgery. We performed Raman spectroscopic analysis for the articular cartilage of distal femurs in OA side and unaffected side in each mouse. In the result, there is no gross findings in the surface of the articular cartilage in OA. On the other hand, Raman spectral data of the articular cartilage showed drastic changes in comparison between OA and control side. The major finding of this study is that the relative intensity of phosphate band (960 cm-1) increases in the degenerative cartilage. This may be the result of exposure of subchondral bone due to thinning of the cartilage layer. In conclusion, Raman spectroscopic technique is sufficient to characterize articular cartilage in OA as a pilot study for Raman application in cartilage degeneration and regeneration using animal models and human subjects.

Degenerative changes of the canine cervical spine after discectomy procedures, an in vivo study.

PubMed

Grunert, Peter; Moriguchi, Yu; Grossbard, Brian P; Ricart Arbona, Rodolfo J; Bonassar, Lawrence J; Härtl, Roger

2017-06-23

Discectomies are a common surgical treatment for disc herniations in the canine spine. However, the effect of these procedures on intervertebral disc tissue is not fully understood. The objective of this study was to assess degenerative changes of cervical spinal segments undergoing discectomy procedures, in vivo. Discectomies led to a 60% drop in disc height and 24% drop in foraminal height. Segments did not fuse but showed osteophyte formation as well as endplate sclerosis. MR imaging revealed terminal degenerative changes with collapse of the disc space and loss of T2 signal intensity. The endplates showed degenerative type II Modic changes. Quantitative MR imaging revealed that over 95% of Nucleus Pulposus tissue was extracted and that the nuclear as well as overall disc hydration significantly decreased. Histology confirmed terminal degenerative changes with loss of NP tissue, loss of Annulus Fibrosus organization and loss of cartilage endplate tissue. The bony endplate displayed sclerotic changes. Discectomies lead to terminal degenerative changes. Therefore, these procedures should be indicated with caution specifically when performed for prophylactic purposes.

Association between disk position and degenerative bone changes of the temporomandibular joints: an imaging study in subjects with TMD.

PubMed

Cortés, Daniel; Sylvester, Daniel Cortés; Exss, Eduardo; Marholz, Carlos; Millas, Rodrigo; Moncada, Gustavo

2011-04-01

The aim of this study was to determine the frequency and relationship between disk position and degenerative bone changes in the temporomandibular joints (TMJ), in subjects with internal derangement (ID). MRI and CT scans of 180 subjects with temporomandibular disorders (TMD) were studied. Different image parameters or characteristics were observed, such as disk position, joint effusion, condyle movement, degenerative bone changes (flattened, cortical erosions and irregularities), osteophytes, subchondral cysts and idiopathic condyle resorption. The present study concluded that there is a significant association between disk displacement without reduction and degenerative bone changes in patients with TMD. The study also found a high probability of degenerative bone changes when disk displacement without reduction is present. No association was found between TMD and condyle range of motion, joint effusion and/or degenerative bone changes. The following were the most frequent morphological changes observed: flattening of the anterior surface of the condyle; followed by erosions and irregularities of the joint surfaces; flattening of the articular surface of the temporal eminence, subchondral cysts, osteophytes; and idiopathic condyle resorption, in decreasing order.

Detection of degenerative change in lateral projection cervical spine x-ray images

NASA Astrophysics Data System (ADS)

Jebri, Beyrem; Phillips, Michael; Knapp, Karen; Appelboam, Andy; Reuben, Adam; Slabaugh, Greg

2015-03-01

Degenerative changes to the cervical spine can be accompanied by neck pain, which can result from narrowing of the intervertebral disc space and growth of osteophytes. In a lateral x-ray image of the cervical spine, degenerative changes are characterized by vertebral bodies that have indistinct boundaries and limited spacing between vertebrae. In this paper, we present a machine learning approach to detect and localize degenerative changes in lateral x-ray images of the cervical spine. Starting from a user-supplied set of points in the center of each vertebral body, we fit a central spline, from which a region of interest is extracted and image features are computed. A Random Forest classifier labels regions as degenerative change or normal. Leave-one-out cross-validation studies performed on a dataset of 103 patients demonstrates performance of above 95% accuracy.

CRISPR Epigenome Editing of AKAP150 in DRG Neurons Abolishes Degenerative IVD-Induced Neuronal Activation.

PubMed

Stover, Joshua D; Farhang, Niloofar; Berrett, Kristofer C; Gertz, Jason; Lawrence, Brandon; Bowles, Robby D

2017-09-06

Back pain is a major contributor to disability and has significant socioeconomic impacts worldwide. The degenerative intervertebral disc (IVD) has been hypothesized to contribute to back pain, but a better understanding of the interactions between the degenerative IVD and nociceptive neurons innervating the disc and treatment strategies that directly target these interactions is needed to improve our understanding and treatment of back pain. We investigated degenerative IVD-induced changes to dorsal root ganglion (DRG) neuron activity and utilized CRISPR epigenome editing as a neuromodulation strategy. By exposing DRG neurons to degenerative IVD-conditioned media under both normal and pathological IVD pH levels, we demonstrate that degenerative IVDs trigger interleukin (IL)-6-induced increases in neuron activity to thermal stimuli, which is directly mediated by AKAP and enhanced by acidic pH. Utilizing this novel information on AKAP-mediated increases in nociceptive neuron activity, we developed lentiviral CRISPR epigenome editing vectors that modulate endogenous expression of AKAP150 by targeted promoter histone methylation. When delivered to DRG neurons, these epigenome-modifying vectors abolished degenerative IVD-induced DRG-elevated neuron activity while preserving non-pathologic neuron activity. This work elucidates the potential for CRISPR epigenome editing as a targeted gene-based pain neuromodulation strategy. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Degenerative phenotypes caused by the combined deficiency of murine HIP1 and HIP1r are rescued by human HIP1.

PubMed

Bradley, Sarah V; Hyun, Teresa S; Oravecz-Wilson, Katherine I; Li, Lina; Waldorff, Erik I; Ermilov, Alexander N; Goldstein, Steven A; Zhang, Claire X; Drubin, David G; Varela, Kate; Parlow, Al; Dlugosz, Andrzej A; Ross, Theodora S

2007-06-01

The members of the huntingtin-interacting protein-1 (HIP1) family, HIP1 and HIP1-related (HIP1r), are multi-domain proteins that interact with inositol lipids, clathrin and actin. HIP1 is over-expressed in a variety of cancers and both HIP1 and HIP1r prolong the half-life of multiple growth factor receptors. To better understand the physiological importance of the HIP1 family in vivo, we have analyzed a large cohort of double Hip1/Hip1r knockout (DKO) mice. All DKO mice were dwarfed, afflicted with severe vertebral defects and died in early adulthood. These phenotypes were not observed during early adulthood in the single Hip1 or Hip1r knockouts, indicating that HIP1 and HIP1r compensate for one another. Despite the ability of HIP1 and HIP1r to modulate growth factor receptor levels when over-expressed, studies herein using DKO fibroblasts indicate that the HIP1 family is not necessary for endocytosis but is necessary for the maintenance of diverse adult tissues in vivo. To test if human HIP1 can function similar to mouse HIP1, transgenic mice with 'ubiquitous' expression of the human HIP1 cDNA were generated and crossed with DKO mice. Strikingly, the compound human HIP1 transgenic DKO mice were completely free from dwarfism and spinal defects. This successful rescue demonstrates that the human HIP1 protein shares some interchangeable functions with both HIP1 and HIP1r in vivo. In addition, we conclude that the degenerative phenotypes seen in the DKO mice are due mainly to HIP1 and HIP1r protein deficiency rather than altered expression of neighboring genes or disrupted intronic elements.

Inherited Retinal Degenerative Clinical Trial Network

DTIC Science & Technology

2009-10-01

ending in blindness. In the United States, the total number of individuals affected by retinitis pigmentosa (RP) and other forms of rare inherited...AD_________________ AWARD NUMBER: W81XWH-07-1-0720 TITLE: Inherited Retinal Degenerative...Final 3. DATES COVERED 27 Sep 2007 – 29 Sep 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Inherited Retinal Degenerative Clinical Trial Network

The Coracohumeral Distance in Shoulders With Traumatic and Degenerative Subscapularis Tendon Tears.

PubMed

Balke, Maurice; Banerjee, Marc; Greshake, Oliver; Hoeher, Juergen; Bouillon, Bertil; Liem, Dennis

2016-01-01

A reduced coracohumeral distance (CHD) is thought to be responsible for subcoracoid impingement. This only accounts for degenerative tendon tears. In traumatic tears, the subcoracoid space should be normal. The CHD in patients with traumatic subscapularis tendon tears is larger than that in patients with degenerative tears and does not differ from patients with an intact subscapularis tendon. Cohort study; Level of evidence, 3. A total of 83 patients with arthroscopically certified subscapularis tendon tears were included in the study. Forty-four patients had degenerative causes (group 1), and 39 had traumatic causes (group 2). The control group consisted of 20 patients with traumatic supraspinatus tendon tears and arthroscopically proven, intact subscapularis tendons (group 3). On preoperative axial magnetic resonance imaging, the distance between the CHD was measured, and the values of the 3 groups were compared using the t test. The mean (±SD) CHD in patients with degenerative subscapularis tendon tears was 8.6 ± 2.0 mm (range, 4.0-13.2 mm) and was significantly (P = .0003) smaller than that in patients with traumatic tears (10.2 ± 2.0 mm; range, 6.6-16.2 mm) or controls (10.4 ± 1.8 mm; range, 6.8-14.0 mm). The CHD of controls and patients with traumatic tears did not differ significantly (P = .7875). A CHD of less than 6 mm only occurred in patients with degenerative subscapularis tendon tears. The hypothesis that the CHD in patients with degenerative subscapularis tendon tears is significantly smaller than that in patients with traumatic tears or intact subscapularis tendons was confirmed. The CHD in patients with traumatic tears does not differ from that in controls. A CHD of less than 6 mm only occurs in patients with degenerative subscapularis tendon tears. © 2015 The Author(s).

'Lumbar Degenerative Kyphosis' Is Not Byword for Degenerative Sagittal Imbalance: Time to Replace a Misconception.

PubMed

Lee, Chang-Hyun; Chung, Chun Kee; Jang, Jee-Soo; Kim, Sung-Min; Chin, Dong-Kyu; Lee, Jung-Kil

2017-03-01

Lumbar degenerative kyphosis (LDK) is a subgroup of the flat-back syndrome and is most commonly caused by unique life styles, such as a prolonged crouched posture during agricultural work and performing activities of daily living on the floor. Unfortunately, LDK has been used as a byword for degenerative sagittal imbalance, and this sometimes causes confusion. The aim of this review was to evaluate the exact territory of LDK, and to introduce another appropriate term for degenerative sagittal deformity. Unlike what its name suggests, LDK does not only include sagittal balance disorder of the lumbar spine and kyphosis, but also sagittal balance disorder of the whole spine and little lordosis of the lumbar spine. Moreover, this disease is closely related to the occupation of female farmers and an outdated Asian life style. These reasons necessitate a change in the nomenclature of this disorder to prevent misunderstanding. We suggest the name "primary degenerative sagittal imbalance" (PDSI), which encompasses degenerative sagittal misalignments of unknown origin in the whole spine in older-age patients, and is associated with back muscle wasting. LDK may be regarded as a subgroup of PDSI related to an occupation in agriculture. Conservative treatments such as exercise and physiotherapy are recommended as first-line treatments for patients with PDSI, and surgical treatment is considered only if conservative treatments failed. The measurement of spinopelvic parameters for sagittal balance is important prior to deformity corrective surgery. LDK can be considered a subtype of PDSI that is more likely to occur in female farmers, and hence the use of LDK as a global term for all degenerative sagittal imbalance disorders is better avoided. To avoid confusion, we recommend PDSI as a newer, more accurate diagnostic term instead of LDK.

‘Lumbar Degenerative Kyphosis’ Is Not Byword for Degenerative Sagittal Imbalance: Time to Replace a Misconception

PubMed Central

Lee, Chang-Hyun; Chung, Chun Kee; Jang, Jee-Soo; Kim, Sung-Min; Chin, Dong-Kyu; Lee, Jung-Kil

2017-01-01

Lumbar degenerative kyphosis (LDK) is a subgroup of the flat-back syndrome and is most commonly caused by unique life styles, such as a prolonged crouched posture during agricultural work and performing activities of daily living on the floor. Unfortunately, LDK has been used as a byword for degenerative sagittal imbalance, and this sometimes causes confusion. The aim of this review was to evaluate the exact territory of LDK, and to introduce another appropriate term for degenerative sagittal deformity. Unlike what its name suggests, LDK does not only include sagittal balance disorder of the lumbar spine and kyphosis, but also sagittal balance disorder of the whole spine and little lordosis of the lumbar spine. Moreover, this disease is closely related to the occupation of female farmers and an outdated Asian life style. These reasons necessitate a change in the nomenclature of this disorder to prevent misunderstanding. We suggest the name “primary degenerative sagittal imbalance” (PDSI), which encompasses degenerative sagittal misalignments of unknown origin in the whole spine in older-age patients, and is associated with back muscle wasting. LDK may be regarded as a subgroup of PDSI related to an occupation in agriculture. Conservative treatments such as exercise and physiotherapy are recommended as first-line treatments for patients with PDSI, and surgical treatment is considered only if conservative treatments failed. The measurement of spinopelvic parameters for sagittal balance is important prior to deformity corrective surgery. LDK can be considered a subtype of PDSI that is more likely to occur in female farmers, and hence the use of LDK as a global term for all degenerative sagittal imbalance disorders is better avoided. To avoid confusion, we recommend PDSI as a newer, more accurate diagnostic term instead of LDK. PMID:28264231

Radiofrequency neurotomy for treatment of low back pain in patients with minor degenerative spondylolisthesis.

PubMed

Klessinger, Stephan

2012-01-01

Degenerative spondylolisthesis is one of the major causes for low back pain. Morphological abnormalities of the zygapophysial joints are a predisposing factor in the development of degenerative spondylolisthesis. Therefore, radiofrequency neurotomy seems to be a rational therapy. To determine if radiofrequency neurotomy is effective for patients with low back pain and degenerative spondylolisthesis. Retrospective practice audit. Single spine center Charts of all patients with degenerative spondylolisthesis who underwent treatment with radiofrequency neurotomy during a time period of 3 years were reviewed. Only patients with magnetic resonance imaging confirming the diagnosis were included. Patients with a lumbar spine operation in their history, patients with neurological deficits, and patients with a follow-up less than 3 months were excluded. Patients were treated with lumbar radiofrequency neurotomy. Positive treatment response was defined as at least a 50% reduction in pain. A radiofrequency neurotomy was only performed after positive diagnostic medial branch blocks. During a time period of 3 years, 1,490 patients were treated with lumbar radiofrequency neurotomy. Forty of these patients with degenerative spondylolisthesis were included. A significant pain reduction was achieved in 65 % of the patients. This audit is retrospective and observational, and therefore does not represent a high level of evidence. However, to our knowledge, since this information has not been previously reported and no specific nonoperative treatment for lumbar pain in patients with degenerative spondylolisthesis exists, it appears to be the best available research upon which to recommend treatment and to plan higher quality studies. Zygapophysial joints are a possible source of pain in patients with spondylolisthesis. Radiofrequency neurotomy is a rational, specific nonoperative therapy in addition to other nonoperative therapy methods with a success rate of 65%. This is the first study to determine the effect of radiofrequency neurotomy in patients with minor degenerative spondylolisthesis.

Novel paramyxoviruses in Australian flying-fox populations support host-virus co-evolution.

PubMed

Vidgen, Miranda E; de Jong, Carol; Rose, Karrie; Hall, Jane; Field, Hume E; Smith, Craig S

2015-07-01

Understanding the diversity of henipaviruses and related viruses is important in determining the viral ecology within flying-fox populations and assessing the potential threat posed by these agents. This study sought to identify the abundance and diversity of previously unknown paramyxoviruses (UPVs) in Australian flying-fox species (Pteropus alecto, Pteropus scapulatus, Pteropus poliocephalus and Pteropus conspicillatus) and in the Christmas Island species Pteropus melanotus natalis. Using a degenerative reverse transcription-PCR specific for the L gene of known species of the genus Henipavirus and two closely related paramyxovirus genera Respirovirus and Morbillivirus, we identified an abundance and diversity of previously UPVs, with a representative 31 UPVs clustering in eight distinct groups (100 UPVs/495 samples). No new henipaviruses were identified. The findings were consistent with a hypothesis of co-evolution of paramyxoviruses and their flying-fox hosts. Quantification of the degree of co-speciation between host and virus (beyond the scope of this study) would strengthen this hypothesis.

Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly.

PubMed

Aramillo Irizar, Peer; Schäuble, Sascha; Esser, Daniela; Groth, Marco; Frahm, Christiane; Priebe, Steffen; Baumgart, Mario; Hartmann, Nils; Marthandan, Shiva; Menzel, Uwe; Müller, Julia; Schmidt, Silvio; Ast, Volker; Caliebe, Amke; König, Rainer; Krawczak, Michael; Ristow, Michael; Schuster, Stefan; Cellerino, Alessandro; Diekmann, Stephan; Englert, Christoph; Hemmerich, Peter; Sühnel, Jürgen; Guthke, Reinhard; Witte, Otto W; Platzer, Matthias; Ruppin, Eytan; Kaleta, Christoph

2018-01-30

Disease epidemiology during ageing shows a transition from cancer to degenerative chronic disorders as dominant contributors to mortality in the old. Nevertheless, it has remained unclear to what extent molecular signatures of ageing reflect this phenomenon. Here we report on the identification of a conserved transcriptomic signature of ageing based on gene expression data from four vertebrate species across four tissues. We find that ageing-associated transcriptomic changes follow trajectories similar to the transcriptional alterations observed in degenerative ageing diseases but are in opposite direction to the transcriptomic alterations observed in cancer. We confirm the existence of a similar antagonism on the genomic level, where a majority of shared risk alleles which increase the risk of cancer decrease the risk of chronic degenerative disorders and vice versa. These results reveal a fundamental trade-off between cancer and degenerative ageing diseases that sheds light on the pronounced shift in their epidemiology during ageing.

Real efficiency of ambulatory laser treatment at the patients with different rheumatic diseases

NASA Astrophysics Data System (ADS)

Sidenco, Elena-Luminita; Ristache, Sanda; Belu, Luminita

2001-06-01

We consulted 189 patients, with different locomotory diseases: degenerative, posttraumatic and chronic inflammatory rheumatic diseases. We followed the main clinical parameters: pain, limitation of mobility, affected function, inflammation and disorders of sensitivity. We applied an infrared LASER source of 100 mW (BTL), daily, for 5 days. The tolerance of the patients at the LASER treatment was excellent (100%). The evolution of the clinical parameters was variated, but inflammation, limitation of mobility and the affected function significantly improved (30-50%). We found a significant diminution of pain (27- 39%). We believe the LASER treatment in ambulatory conditions is essential for the function of the patients with different locomotory diseases.

Early, asymptomatic stage of degenerative joint disease in canine hip joints.

PubMed

Lust, G; Summers, B A

1981-11-01

The early stages of degenerative joint disease were investigated in coxofemoral joints from dogs with a hereditary predisposition to hip dysplasia. Alterations observed included mild nonsuppurative synovitis, increased volume of both synovial fluid and the ligamentum teres, and focal degenerative articular cartilage lesions. On radiologic examination, subluxation of the femoral head was seen, but only in the most severely affected joints. Synovial inflammation with increased synovial fluid and ligament volumes were indicators of early degenerative joint disease in dogs. These changes seemed to coincide with, or perhaps to precede, microscopic evidence for articular cartilage degeneration and occurred before radiologic abnormalities were detected.

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

PubMed Central

Ames, Bruce N.

2006-01-01

Inadequate dietary intakes of vitamins and minerals are widespread, most likely due to excessive consumption of energy-rich, micronutrient-poor, refined food. Inadequate intakes may result in chronic metabolic disruption, including mitochondrial decay. Deficiencies in many micronutrients cause DNA damage, such as chromosome breaks, in cultured human cells or in vivo. Some of these deficiencies also cause mitochondrial decay with oxidant leakage and cellular aging and are associated with late onset diseases such as cancer. I propose DNA damage and late onset disease are consequences of a triage allocation response to micronutrient scarcity. Episodic shortages of micronutrients were common during evolution. Natural selection favors short-term survival at the expense of long-term health. I hypothesize that short-term survival was achieved by allocating scarce micronutrients by triage, in part through an adjustment of the binding affinity of proteins for required micronutrients. If this hypothesis is correct, micronutrient deficiencies that trigger the triage response would accelerate cancer, aging, and neural decay but would leave critical metabolic functions, such as ATP production, intact. Evidence that micronutrient malnutrition increases late onset diseases, such as cancer, is discussed. A multivitamin-mineral supplement is one low-cost way to ensure intake of the Recommended Dietary Allowance of micronutrients throughout life. PMID:17101959

Application of stem cell-derived retinal pigmented epithelium in retinal degenerative diseases: present and future.

PubMed

Luo, Mingyue; Chen, Youxin

2018-01-01

As a constituent of blood-retinal barrier and retinal outer segment (ROS) scavenger, retinal pigmented epithelium (RPE) is fundamental to normal function of retina. Malfunctioning of RPE contributes to the onset and advance of retinal degenerative diseases. Up to date, RPE replacement therapy is the only possible method to completely reverse retinal degeneration. Transplantation of human RPE stem cell-derived RPE (hRPESC-RPE) has shown some good results in animal models. With promising results in terms of safety and visual improvement, human embryonic stem cell-derived RPE (hESC-RPE) can be expected in clinical settings in the near future. Despite twists and turns, induced pluripotent stem cell-derived RPE (iPSC-RPE) is now being intensely investigated to overcome genetic and epigenetic instability. By far, only one patient has received iPSC-RPE transplant, which is a hallmark of iPSC technology development. During follow-up, no major complications such as immunogenicity or tumorigenesis have been observed. Future trials should keep focusing on the safety of stem cell-derived RPE (SC-RPE) especially in long period, and better understanding of the nature of stem cell and the molecular events in the process to generate SC-RPE is necessary to the prosperity of SC-RPE clinical application.

Lumbar paraspinal muscle transverse area and symmetry in dogs with and without degenerative lumbosacral stenosis.

PubMed

Henderson, A L; Hecht, S; Millis, D L

2015-10-01

To investigate whether dogs with degenerative lumbosacral stenosis have decreased lumbar paraspinal muscle transverse area and symmetry compared with control dogs. Retrospective cross-sectional study comparing muscles in transverse T2-weighted magnetic resonance images for nine dogs with and nine dogs without degenerative -lumbosacral stenosis. Mean transverse area was measured for the lumbar multifidus and sacrocaudalis dorsalis lateralis muscles bilaterally and the L7 vertebral body at the level of the caudal endplate. Transverse areas of both muscle groups relative to L7 and asymmetry indices were compared between study populations using independent t tests. Mean muscle-to-L7 transverse area ratios were significantly smaller in the degenerative lumbosacral stenosis group compared with those in the control group in both lumbar multifidus (0·84 ±0·26 versus 1·09 ±0·25; P=0·027) and sacrocaudalis dorsalis lateralis (0·5 ±0·15 versus 0·68 ±0·12; P=0·005) muscles. Mean asymmetry indices were higher for both muscles in the group with degenerative lumbosacral stenosis than in the control group, but highly variable and the difference was not statistically significant. These findings suggest that dogs with degenerative lumbosacral stenosis have decreased lumbar paraspinal muscle mass that may be a cause or consequence of the -syndrome. Understanding altered paraspinal muscle characteristics may improve understanding of the -pathophysiology and management options for degenerative lumbosacral stenosis. © 2015 British Small Animal Veterinary Association.

Antioxidant activity of puha (Sonchus oleraceus L.) as assessed by the cellular antioxidant activity (CAA) assay.

PubMed

McDowell, Arlene; Thompson, Scott; Stark, Mirjam; Ou, Zong-Quan; Gould, Kevin S

2011-12-01

There is considerable interest in antioxidant dietary components that can be protective against degenerative diseases in humans. Puha (Sonchus oleraceus L.) is a rich source of polyphenols, and exhibits strong antioxidant activity as measured by the 2,2-diphenylpicrylhydrazyl (DPPH) assay. However, the potential of puha to protect against degenerative diseases requires that low molecular weight antioxidants (LMWA) are absorbed by, and active in, human cells. The cellular antioxidant activity (CAA) assay was used to investigate the antioxidant activity of puha leaf extracts. Preparation methods of freezing and freeze-drying reduced the total polyphenolic content compared with fresh puha, but did not affect the LMWA potential as determined by the DPPH assay. The IC(50) values were 0.012 ± 0.003 mg/mL and 0.010 ± 0.005 mg/mL for freeze-dried and fresh puha leaves, respectively. Using the CAA assay, it was shown that LMWAs from foliar extracts of puha were effectively absorbed into HepG2 cells, and exerted antioxidant activity at levels comparable to those of extracts from blueberry fruits, the much-touted antioxidant superfood. Methylene blue staining of HepG2 cells indicated that puha extracts were not cytotoxic at concentrations below 100 mg DW/mL. The data indicate the potential of puha as a nutraceutical supplement for human health. Copyright © 2011 John Wiley & Sons, Ltd.

Deriving excitatory neurons of the neocortex from pluripotent stem cells

PubMed Central

Hansen, David V.; Rubenstein, John L.R.; Kriegstein, Arnold R.

2011-01-01

The human cerebral cortex is an immensely complex structure that subserves critical functions that can be disrupted in developmental and degenerative disorders. Recent innovations in cellular reprogramming and differentiation techniques have provided new ways to study the cellular components of the cerebral cortex. Here we discuss approaches to generate specific subtypes of excitatory cortical neurons from pluripotent stem cells. We review spatial and temporal aspects of cortical neuron specification that can guide efforts to produce excitatory neuron subtypes with increased resolution. Finally, we discuss distinguishing features of human cortical development and their translational ramifications for cortical stem cell technologies. PMID:21609822

The structure and material composition of ossified aortic valves identified using a set of scientific methods

NASA Astrophysics Data System (ADS)

Zeman, Antonín; Šmíd, Michal; Havelcová, Martina; Coufalová, Lucie; Kučková, Štěpánka; Velčovská, Martina; Hynek, Radovan

2013-11-01

Degenerative aortic stenosis has become a common and dangerous disease in recent decades. This disease leads to the mineralization of aortic valves, their gradual thickening and loss of functionality. We studied the detailed assessment of the proportion and composition of inorganic and organic components in the ossified aortic valve, using a set of analytical methods applied in science: polarized light microscopy, scanning electron microscopy, X-ray fluorescence, X-ray diffraction, gas chromatography/mass spectrometry and liquid chromatography-tandem mass spectrometry. The sample valves showed the occurrence of phosphorus and calcium in the form of phosphate and calcium carbonate, hydroxyapatite, fluorapatite and hydroxy-fluorapatite, with varying content of inorganic components from 65 to 90 wt%, and with phased development of degenerative disability. The outer layers of the plaque contained an organic component with peptide bonds, fatty acids, proteins and cholesterol. The results show a correlation between the formation of fluorapatite in aortic valves and in other parts of the human bodies, associated with the formation of bones.

Dietary polyphenols increase fecal mucin and immunoglobulin A and ameliorate the disturbance in gut microbiota caused by a high fat diet.

PubMed

Taira, Toshio; Yamaguchi, Sayori; Takahashi, Azusa; Okazaki, Yukako; Yamaguchi, Akihiro; Sakaguchi, Hirohide; Chiji, Hideyuki

2015-11-01

The effects of dietary polyphenols on human health have mainly been discussed in the context of preventing degenerative diseases, particularly cardiovascular diseases and cancer. The antioxidant properties of polyphenols have been widely studied, but it has become clear that the mechanism of action of polyphenols extends beyond the modulation of oxidative stress, as they are poorly absorbed from the digestive tract. The purpose of this study was to clarify the effects of polyphenols on the colonic environment, intestinal barrier function, and gut microbiota. We demonstrated that dietary polyphenols derived from aronia, haskap, and bilberry, markedly elevated the amount of fecal mucin and immunoglobulin A (IgA) as an intestinal barrier function and ameliorated the disturbance in gut microbiota caused by a high fat diet in rats. These results suggest that dietary polyphenols play a significant role in the prevention of degenerative diseases through improvement of the colonic environment without any absorption from the digestive tract.

Dietary polyphenols increase fecal mucin and immunoglobulin A and ameliorate the disturbance in gut microbiota caused by a high fat diet

PubMed Central

Taira, Toshio; Yamaguchi, Sayori; Takahashi, Azusa; Okazaki, Yukako; Yamaguchi, Akihiro; Sakaguchi, Hirohide; Chiji, Hideyuki

2015-01-01

The effects of dietary polyphenols on human health have mainly been discussed in the context of preventing degenerative diseases, particularly cardiovascular diseases and cancer. The antioxidant properties of polyphenols have been widely studied, but it has become clear that the mechanism of action of polyphenols extends beyond the modulation of oxidative stress, as they are poorly absorbed from the digestive tract. The purpose of this study was to clarify the effects of polyphenols on the colonic environment, intestinal barrier function, and gut microbiota. We demonstrated that dietary polyphenols derived from aronia, haskap, and bilberry, markedly elevated the amount of fecal mucin and immunoglobulin A (IgA) as an intestinal barrier function and ameliorated the disturbance in gut microbiota caused by a high fat diet in rats. These results suggest that dietary polyphenols play a significant role in the prevention of degenerative diseases through improvement of the colonic environment without any absorption from the digestive tract. PMID:26566306

[Drinking water hardness and chronic degenerative diseases. III. Tumors, urolithiasis, fetal malformations, deterioration of the cognitive function in the aged and atopic eczema].

PubMed

Donato, F; Monarca, S; Premi, S; Gelatti, U

2003-01-01

For several decades a causal relation has been hypothesised between drinking water hardness and cardiovascular and other chronic degenerative diseases in humans. Only recently some epidemiological studies also investigated the association between the concentration of the minerals responsible for the hardness of drinking water (calcium and magnesium) and other chronic diseases. Some case-control studies carried out in Taiwan using aggregated data showed a possible protective effect of water hardness toward the risk of dying from various neoplasms, though more research is needed on the issue, possibly based on individual data, to draw definitive conclusions. There is a substantial evidence that consumption of water with high levels of calcium does not increase, and maybe reduces the risk of developing urinary stones of the most common type in developed countries (calcium oxalate), on the contrary, there is no conclusive evidence on the relation between water hardness and foetal malformations, cognitive functions in old men, diabetes and eczema.

[Dynamic stabilisation and compression without fusion using Dynesys for the treatment of degenerative lumbar spondylolisthesis: a prospective series of 25 cases].

PubMed

Ricart, O; Serwier, J-M

2008-11-01

We used the Dynesys stabilization to treat degenerative lumber spondylolysis by decompression without fusion with the objective of decreasing the morbidity related to instrumented arthrodesis in older patients yet preventing progression of the displacement. This was a prospective study of 25 patients with symptomatic degenerative lumber spondylolysis associated with degenerative spinal canal stenosis documented by saccoradiculography. For inclusion, static anteroposterior intervertebral displacement had to be at least 3mm in the upright position, irrespective of the displacement on the stress films. The series included 19 women and six men, mean age 71 years (range 53-83). The level was L4-L5 in all 25 cases. Instrumentations involved a single level (L4-L5) or two levels (L3-L5). All patients were explored with computed tomography and saccoradiculography. An MRI was obtained in 12 patients. Pre- and postoperative stress images and views of the entire spinal column in the upright position were used to study pelvic parameters and sagittal spinal balance before and after surgery. Lumbar incidence and lordosis was used to divide the patients into three groups. Outcome was assessed with the Beaujon classification at minimal follow-up of 24 months, mean 34, range 24-72 months. Very good results were obtained in 72% of patients (relative gain greater than 70%) and good results in 28% (relative gain 40-70%). There were not outcomes considered fair or poor. There were two complications: aggravation of preoperative crural paresia with complete recovery and replacement of one neuroaggressive pedicular screw with no consequence thereafter. The stress films confirmed the residual mobility of the instrumented level when the preserved disc was of sufficient height. Postoperative pelvic parameters after Dynesys instrumentation showed improvement in sagittal tilt for T9 by accentuated suprajacent lordosis, even in the event of anterior spinal imbalance preoperatively. Theoretically, solicitation of the pedicular anchors of a rigid instrumentation on a poorly balanced spine would rapidly lead to failure, while fibrous non-union on a globally well balanced spine would be tolerated much longer or even definitively without development of clinical symptoms. In our opinion, the Dynesys instrumentation enables a real restabilization of the spine by adapting to the patients particular spinal balance intra-operatively and postoperatively without imposing a definitive curvature as would a rigid fixation. The ultimate objective is to accompany the aging spine without brutally changing the stress forces. This semi-rigid instrumentation without fusion enables an adapted evolution of the overall spinal degeneration without imposing excessive local forces, which could be sources of stenosis or junctional instability. The most logical indication for this instrumentation is the older subject aged at least 65 years with degenerative lumber spondylolysis and a predominantly self-reducible angular displacement and satisfactory disc height. This context (group 3 in our series) occurs in patients with a weak sacral slope and incidence, as well as minimal lordosis adapted to the pelvic parameters. The Dynesys instrumentation can be a palliative alternative to fusion for more advanced degenerative lumber spondylolysis occurring on spines with anterior imbalance where fusion would be technically difficult in terms of correction of the kyphosis or because of the general risk factors.

Chemometric evaluation of concentrations of trace elements in intervertebral disc tissue in patient with degenerative disc disease.

PubMed

Kubaszewski, Łukasz; Zioła-Frankowska, Anetta; Gasik, Zuzanna; Frankowski, Marcin; Dąbrowski, Mikołaj; Molisak, Bartłomiej; Kaczmarczyk, Jacek; Gasik, Robert

2017-12-23

The work is designed to uncover the pattern of mutual relation among trace elements and epidemiological data in the degenerated intervertebral disk tissue in humans. Hitherto the reason of the degenerative process is not fully understood. Trace elements are the basic components of the biological compound related both its metabolism as well as environmental exposure. The relation pattern among elements occurs gives new perspective in solving the cause of the disease. We have analysed trace elements content in the 30 intervertebral disc from 22 patients with degenerative disc disease. The concentrations of Al, Cu, Cd, Mo, Ni and Pb were determined with Atomic Absorption Spectrometry. To analyse the multidimentional relation between trace element concentration and epidemiological data the chemometric analysis was applied. The similarity have been shown in occurrence of following pairs: Cd-Mo as well as Mg-Zn. The second pair was correlated with Pb concentration. Pb levels are observed to be competitive to Cu concentration. Cd concentration was related to Zn and Mg deficiency. No single but rather cluster of epidemiological data show observable influence on the TE tissue variance. Zn and Cu was related to the male sex. Operation with orthopedic implants were related to combined Al, Mo and Zn concentration. This is the first chemometric analysis of trace elements in disk tissue. It shows multidimentional relations that are missed by the classical statistic. The analysis shows significant relation. The nature of the relations is the basis for further metabolic and environmental research.

Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and -9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases.

PubMed

Calabriso, Nadia; Massaro, Marika; Scoditti, Egeria; Pellegrino, Mariangela; Ingrosso, Ilaria; Giovinazzo, Giovanna; Carluccio, Maria Annunziata

2016-08-29

Matrix metalloproteinases (MMPs) are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases' activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5-25 μg/mL) of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively) or their specific components (0.5-25 μmol/L), before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases.

Proteomic profiling of early degenerative retina of RCS rats.

PubMed

Zhu, Zhi-Hong; Fu, Yan; Weng, Chuan-Huang; Zhao, Cong-Jian; Yin, Zheng-Qin

2017-01-01

To identify the underlying cellular and molecular changes in retinitis pigmentosa (RP). Label-free quantification-based proteomics analysis, with its advantages of being more economic and consisting of simpler procedures, has been used with increasing frequency in modern biological research. Dystrophic RCS rats, the first laboratory animal model for the study of RP, possess a similar pathological course as human beings with the diseases. Thus, we employed a comparative proteomics analysis approach for in-depth proteome profiling of retinas from dystrophic RCS rats and non-dystrophic congenic controls through Linear Trap Quadrupole - orbitrap MS/MS, to identify the significant differentially expressed proteins (DEPs). Bioinformatics analyses, including Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation and upstream regulatory analysis, were then performed on these retina proteins. Finally, a Western blotting experiment was carried out to verify the difference in the abundance of transcript factor E2F1. In this study, we identified a total of 2375 protein groups from the retinal protein samples of RCS rats and non-dystrophic congenic controls. Four hundred thirty-four significantly DEPs were selected by Student's t -test. Based on the results of the bioinformatics analysis, we identified mitochondrial dysfunction and transcription factor E2F1 as the key initiation factors in early retinal degenerative process. We showed that the mitochondrial dysfunction and the transcription factor E2F1 substantially contribute to the disease etiology of RP. The results provide a new potential therapeutic approach for this retinal degenerative disease.

Degenerative Nerve Diseases

MedlinePlus

... may include toxins, chemicals, and viruses. Sometimes the cause is not known. Degenerative nerve diseases include Alzheimer's disease Amyotrophic lateral sclerosis Friedreich's ataxia Huntington's disease ...

Dietary Phytochemicals: Natural Swords Combating Inflammation and Oxidation-Mediated Degenerative Diseases.

PubMed

Islam, Md Asiful; Alam, Fahmida; Solayman, Md; Khalil, Md Ibrahim; Kamal, Mohammad Amjad; Gan, Siew Hua

2016-01-01

Cumulatively, degenerative disease is one of the most fatal groups of diseases, and it contributes to the mortality and poor quality of life in the world while increasing the economic burden of the sufferers. Oxidative stress and inflammation are the major pathogenic causes of degenerative diseases such as rheumatoid arthritis (RA), diabetes mellitus (DM), and cardiovascular disease (CVD). Although a number of synthetic medications are used to treat these diseases, none of the current regimens are completely safe. Phytochemicals (polyphenols, carotenoids, anthocyanins, alkaloids, glycosides, saponins, and terpenes) from natural products such as dietary fruits, vegetables, and spices are potential sources of alternative medications to attenuate the oxidative stress and inflammation associated with degenerative diseases. Based on in vitro , in vivo , and clinical trials, some of these active compounds have shown good promise for development into novel agents for treating RA, DM, and CVD by targeting oxidative stress and inflammation. In this review, phytochemicals from natural products with the potential of ameliorating degenerative disease involving the bone, metabolism, and the heart are described.

Astrocytes and Müller Cell Alterations During Retinal Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa

PubMed Central

Fernández-Sánchez, Laura; Lax, Pedro; Campello, Laura; Pinilla, Isabel; Cuenca, Nicolás

2015-01-01

Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer (GCL) of P23H vs. SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina. PMID:26733810

Changes in rates of arthroscopy due to degenerative knee disease and traumatic meniscal tears in Finland and Sweden

PubMed Central

Mattila, Ville M; Sihvonen, Raine; Paloneva, Juha; Felländer-Tsai, Li

2016-01-01

Background and purpose Knee arthroscopy is commonly performed to treat degenerative knee disease symptoms and traumatic meniscal tears. We evaluated whether the recent high-quality randomized control trials not favoring arthroscopic surgery for degenerative knee disease affected the procedure incidence and trends in Finland and Sweden. Patients and methods We conducted a bi-national registry-based study including all adult (aged ≥18 years) inpatient and outpatient arthroscopic surgeries performed for degenerative knee disease (osteoarthritis (OA) and degenerative meniscal tears) and traumatic meniscal tears in Finland between 1997 and 2012, and in Sweden between 2001 and 2012. Results In Finland, the annual number of operations was 16,389 in 1997, reached 20,432 in 2007, and declined to 15,018 in 2012. In Sweden, the number of operations was 9,944 in 2001, reached 11,711 in 2008, and declined to 8,114 in 2012. The knee arthroscopy incidence for OA was 124 per 105 person-years in 2012 in Finland and it was 51 in Sweden. The incidence of knee arthroscopies for meniscal tears coded as traumatic steadily increased in Finland from 64 per 105 person-years in 1997 to 97 per 105 person-years in 2012, but not in Sweden. Interpretation The incidence of arthroscopies for degenerative knee disease declined after 2008 in both countries. Remarkably, the incidence of arthroscopy for degenerative knee disease and traumatic meniscal tears is 2 to 4 times higher in Finland than in Sweden. Efficient implementation of new high-quality evidence in clinical practice could reduce the number of ineffective surgeries. PMID:26122621

Epigenetic control of vascular smooth muscle cells in Marfan and non-Marfan thoracic aortic aneurysms

PubMed Central

Gomez, Delphine; Coyet, Aurélie; Ollivier, Véronique; Jeunemaitre, Xavier; Jondeau, Guillaume; Michel, Jean-Baptiste; Vranckx, Roger

2011-01-01

Aims Human thoracic aortic aneurysms (TAAs) are characterized by extracellular matrix breakdown associated with progressive smooth muscle cell (SMC) rarefaction. These features are present in all types of TAA: monogenic forms [mainly Marfan syndrome (MFS)], forms associated with bicuspid aortic valve (BAV), and degenerative forms. Initially described in a mouse model of MFS, the transforming growth factor-β1 (TGF-β1)/Smad2 signalling pathway is now assumed to play a role in TAA of various aetiologies. However, the relation between the aetiological diversity and the common cell phenotype with respect to TGF-β signalling remains unexplained. Methods and results This study was performed on human aortic samples, including TAA [MFS, n = 14; BAV, n = 15; and degenerative, n = 19] and normal aortas (n = 10) from which tissue extracts and human SMCs and fibroblasts were obtained. We show that all types of TAA share a complex dysregulation of Smad2 signalling, independent of TGF-β1 in TAA-derived SMCs (pharmacological study, qPCR). The Smad2 dysregulation is characterized by an SMC-specific, heritable activation and overexpression of Smad2, compared with normal aortas. The cell specificity and heritability of this overexpression strongly suggest the implication of epigenetic control of Smad2 expression. By chromatin immunoprecipitation, we demonstrate that the increases in H3K9/14 acetylation and H3K4 methylation are involved in Smad2 overexpression in TAA, in a cell-specific and transcription start site-specific manner. Conclusion Our results demonstrate the heritability, the cell specificity, and the independence with regard to TGF-β1 and genetic backgrounds of the Smad2 dysregulation in human thoracic aneurysms and the involvement of epigenetic mechanisms regulating histone marks in this process. PMID:20829218

Pedicle screw-rod fixation: a feasible treatment for dogs with severe degenerative lumbosacral stenosis.

PubMed

Tellegen, Anna R; Willems, Nicole; Tryfonidou, Marianna A; Meij, Björn P

2015-12-07

Degenerative lumbosacral stenosis is a common problem in large breed dogs. For severe degenerative lumbosacral stenosis, conservative treatment is often not effective and surgical intervention remains as the last treatment option. The objective of this retrospective study was to assess the middle to long term outcome of treatment of severe degenerative lumbosacral stenosis with pedicle screw-rod fixation with or without evidence of radiological discospondylitis. Twelve client-owned dogs with severe degenerative lumbosacral stenosis underwent pedicle screw-rod fixation of the lumbosacral junction. During long term follow-up, dogs were monitored by clinical evaluation, diagnostic imaging, force plate analysis, and by using questionnaires to owners. Clinical evaluation, force plate data, and responses to questionnaires completed by the owners showed resolution (n = 8) or improvement (n = 4) of clinical signs after pedicle screw-rod fixation in 12 dogs. There were no implant failures, however, no interbody vertebral bone fusion of the lumbosacral junction was observed in the follow-up period. Four dogs developed mild recurrent low back pain that could easily be controlled by pain medication and an altered exercise regime. Pedicle screw-rod fixation offers a surgical treatment option for large breed dogs with severe degenerative lumbosacral stenosis with or without evidence of radiological discospondylitis in which no other treatment is available. Pedicle screw-rod fixation alone does not result in interbody vertebral bone fusion between L7 and S1.

Dietary Phytochemicals: Natural Swords Combating Inflammation and Oxidation-Mediated Degenerative Diseases

PubMed Central

2016-01-01

Cumulatively, degenerative disease is one of the most fatal groups of diseases, and it contributes to the mortality and poor quality of life in the world while increasing the economic burden of the sufferers. Oxidative stress and inflammation are the major pathogenic causes of degenerative diseases such as rheumatoid arthritis (RA), diabetes mellitus (DM), and cardiovascular disease (CVD). Although a number of synthetic medications are used to treat these diseases, none of the current regimens are completely safe. Phytochemicals (polyphenols, carotenoids, anthocyanins, alkaloids, glycosides, saponins, and terpenes) from natural products such as dietary fruits, vegetables, and spices are potential sources of alternative medications to attenuate the oxidative stress and inflammation associated with degenerative diseases. Based on in vitro, in vivo, and clinical trials, some of these active compounds have shown good promise for development into novel agents for treating RA, DM, and CVD by targeting oxidative stress and inflammation. In this review, phytochemicals from natural products with the potential of ameliorating degenerative disease involving the bone, metabolism, and the heart are described. PMID:27721914

Ecological transition predictably associated with gene degeneration.

PubMed

Wessinger, Carolyn A; Rausher, Mark D

2015-02-01

Gene degeneration or loss can significantly contribute to phenotypic diversification, but may generate genetic constraints on future evolutionary trajectories, potentially restricting phenotypic reversal. Such constraints may manifest as directional evolutionary trends when parallel phenotypic shifts consistently involve gene degeneration or loss. Here, we demonstrate that widespread parallel evolution in Penstemon from blue to red flowers predictably involves the functional inactivation and degeneration of the enzyme flavonoid 3',5'-hydroxylase (F3'5'H), an anthocyanin pathway enzyme required for the production of blue floral pigments. Other types of genetic mutations do not consistently accompany this phenotypic shift. This pattern may be driven by the relatively large mutational target size of degenerative mutations to this locus and the apparent lack of associated pleiotropic effects. The consistent degeneration of F3'5'H may provide a mechanistic explanation for the observed asymmetry in the direction of flower color evolution in Penstemon: Blue to red transitions are common, but reverse transitions have not been observed. Although phenotypic shifts in this system are likely driven by natural selection, internal constraints may generate predictable genetic outcomes and may restrict future evolutionary trajectories. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Emergence of Physiology and Form: Natural Selection Revisited

PubMed Central

Torday, John S.

2016-01-01

Natural Selection describes how species have evolved differentially, but it is descriptive, non-mechanistic. What mechanisms does Nature use to accomplish this feat? One known way in which ancient natural forces affect development, phylogeny and physiology is through gravitational effects that have evolved as mechanotransduction, seen in the lung, kidney and bone, linking as molecular homologies to skin and brain. Tracing the ontogenetic and phylogenetic changes that have facilitated mechanotransduction identifies specific homologous cell-types and functional molecular markers for lung homeostasis that reveal how and why complex physiologic traits have evolved from the unicellular to the multicellular state. Such data are reinforced by their reverse-evolutionary patterns in chronic degenerative diseases. The physiologic responses of model organisms like Dictyostelium and yeast to gravity provide deep comparative molecular phenotypic homologies, revealing mammalian Target of Rapamycin (mTOR) as the final common pathway for vertical integration of vertebrate physiologic evolution; mTOR integrates calcium/lipid epistatic balance as both the proximate and ultimate positive selection pressure for vertebrate physiologic evolution. The commonality of all vertebrate structure-function relationships can be reduced to calcium/lipid homeostatic regulation as the fractal unit of vertebrate physiology, demonstrating the primacy of the unicellular state as the fundament of physiologic evolution. PMID:27534726

Pathophysiology of Degenerative Mitral Regurgitation: New 3-Dimensional Imaging Insights.

PubMed

Antoine, Clemence; Mantovani, Francesca; Benfari, Giovanni; Mankad, Sunil V; Maalouf, Joseph F; Michelena, Hector I; Enriquez-Sarano, Maurice

2018-01-01

Despite its high prevalence, little is known about mechanisms of mitral regurgitation in degenerative mitral valve disease apart from the leaflet prolapse itself. Mitral valve is a complex structure, including mitral annulus, mitral leaflets, papillary muscles, chords, and left ventricular walls. All these structures are involved in physiological and pathological functioning of this valvuloventricular complex but up to now were difficult to analyze because of inherent limitations of 2-dimensional imaging. The advent of 3-dimensional echocardiography, computed tomography, and cardiac magnetic resonance imaging overcoming these limitations provides new insights into mechanistic analysis of degenerative mitral regurgitation. This review will detail the contribution of quantitative and qualitative dynamic analysis of mitral annulus and mitral leaflets by new imaging methods in the understanding of degenerative mitral regurgitation pathophysiology. © 2018 American Heart Association, Inc.

DNA linkage studies of degenerative retinal diseases.

PubMed

Daiger, S P; Heckenlively, J R; Lewis, R A; Pelias, M Z

1987-01-01

DNA linkage studies of human genetic diseases have led to rapid characterization of a number of otherwise intractable disease loci. Detection of a linked DNA marker, the first step in "reverse genetics", has permitted cloning of the genes for Duchenne muscular dystrophy, retinoblastoma and chronic granulomatosis disease, among others. Thus, the case for applying these techniques to retinitis pigmentosa and related diseases, and the urgency in capitalizing on molecular developments, is justified and compelling. The first major success regarding RP was in demonstrating linkage of the DNA marker DXS7 (L1.28) to XRP. For autosomal forms of the disease, conventional linkage studies have provided tentative evidence for linkage of ADRP to the Rh blood group on chromosome lp and for linkage of Usher's syndrome to Gc and 4q. These provisional assignments are, at least, an important starting point for DNA analysis. The Support Program for DNA Linkage Studies of Degenerative Retinal Diseases was established to provide access for the scientific community to appropriate families, using the resources of the Human Genetic Mutant Cell Repository to prepare, store and distribute lymphoblast lines. To date, two extensive, well-characterized families are included in the program: the autosomal dominant RP family UCLA-RP01, and the Usher's syndrome families LSU-US01. It is highly likely that rapid progress will be made in mapping and characterizing the inherited retinal dystrophies. We believe the support program will facilitate this progress.

Proteomic profiling of early degenerative retina of RCS rats

PubMed Central

Zhu, Zhi-Hong; Fu, Yan; Weng, Chuan-Huang; Zhao, Cong-Jian; Yin, Zheng-Qin

2017-01-01

AIM To identify the underlying cellular and molecular changes in retinitis pigmentosa (RP). METHODS Label-free quantification-based proteomics analysis, with its advantages of being more economic and consisting of simpler procedures, has been used with increasing frequency in modern biological research. Dystrophic RCS rats, the first laboratory animal model for the study of RP, possess a similar pathological course as human beings with the diseases. Thus, we employed a comparative proteomics analysis approach for in-depth proteome profiling of retinas from dystrophic RCS rats and non-dystrophic congenic controls through Linear Trap Quadrupole - orbitrap MS/MS, to identify the significant differentially expressed proteins (DEPs). Bioinformatics analyses, including Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation and upstream regulatory analysis, were then performed on these retina proteins. Finally, a Western blotting experiment was carried out to verify the difference in the abundance of transcript factor E2F1. RESULTS In this study, we identified a total of 2375 protein groups from the retinal protein samples of RCS rats and non-dystrophic congenic controls. Four hundred thirty-four significantly DEPs were selected by Student's t-test. Based on the results of the bioinformatics analysis, we identified mitochondrial dysfunction and transcription factor E2F1 as the key initiation factors in early retinal degenerative process. CONCLUSION We showed that the mitochondrial dysfunction and the transcription factor E2F1 substantially contribute to the disease etiology of RP. The results provide a new potential therapeutic approach for this retinal degenerative disease. PMID:28730077

Swallowing Disorders

MedlinePlus

... most common cause of dysphagia); traumatic brain injury; cerebral palsy; Parkinson disease and other degenerative neurological disorders such ... most common cause of dysphagia); traumatic brain injury; cerebral palsy; Parkinson disease and other degenerative neurological disorders such ...

Acceptance of evolutionary explanations as they are applied to plants, animals, and humans

NASA Astrophysics Data System (ADS)

Thanukos, Anastasia

In four investigations using Likert-scale questionnaires and think-aloud protocols with 173 university students in total, the willingness to accept evolutionary explanations regarding plant, animal, and human characteristics was examined. Participants were presented with evolutionary explanations for features and behaviors and were asked to rate how much they agreed with evolution as an explanation for each scenario. Some were also asked to explain their reasoning in think-aloud protocols or to discuss item ratings with one another. Overall, participants thought evolutionary explanations appropriate, with median ratings in the upper quarter of the rating scale. They were slightly more willing to ascribe evolutionary explanations to plant than to human phenomena; however, this general effect was mediated by more specific aspects of the evolutionary scenarios in question. Participants who were generally negative regarding evolution were particularly negative towards human evolution. Those who were positive or neutral towards evolution in general were more willing to accept human evolution, but were more likely to use evolution to explain similarities between humans and other species than to explain particular human adaptations. For example, they were more likely to agree that evolution is responsible for the DNA similarities between humans and chimpanzees than that evolution is responsible for human behavioral characteristics, such as the fight or flight response. Think-aloud protocols suggest that, while people are more familiar with human evolutionary relationships than plant evolutionary relationships, they may be less likely to see human characteristics as adaptively valuable. One plausible explanation for these patterns is that an evolutionary explanation is judged jointly by its availability in an individual's memory and its plausibility (i.e., its congruence with the individual's worldview). Popular media coverage, with its focus on controversy and litigation, makes it likely that awareness of human evolution is high, compared with plant evolution (which may not even "enter the radar screen" when most people think of evolution). Some aspects of human evolution, such as the basic relationship between all primates, may have become so pedestrian that they do not threaten many individuals' worldviews. However, even for those positively disposed towards evolution, extending the ramifications of human evolution by suggesting that evolution shapes our behaviors and physical traits may pose a threat to their sense of personal agency. This threat is not associated with plant evolution.

Artificial chordae for degenerative mitral valve disease: critical analysis of current techniques

PubMed Central

Ibrahim, Michael; Rao, Christopher; Athanasiou, Thanos

2012-01-01

The surgical repair of degenerative mitral valve disease involves a number of technical points of importance. The use of artificial chordae for the repair of degenerative disease has increased as a part of the move from mitral valve replacement to repair of the mitral valve. The use of artificial chordae provides an alternative to the techniques pioneered by Carpentier (including the quadrangular resection, transfer of native chordae and papillary muscle shortening/plasty), which can be more technically difficult. Despite a growth in their uptake and the indications for their use, a number of challenges remain for the use of artificial chordae in mitral valve repair, particularly in the determination of the correct length to ensure optimal leaflet coaptation. Here, we analyse over 40 techniques described for artificial chordae mitral valve repair in the setting of degenerative disease. PMID:22962321

Linkage of early-onset osteoarthritis and chondrocalcinosis to human chromosome 8q

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baldwin, C.T.; Farrer, L.A.; Adair, R.

Calcium pyrophosphate-deposition disease (CPDD), also called {open_quotes}chondrocalcinosis{close_quotes} or {open_quotes}pseudogout{close_quotes}, is a disorder characterized by the deposition of calcium-containing crystals in joint tissue, which leads to arthritis-like symptoms. The presence of these crystals in joint tissue is a common finding in the elderly, and, in this population, there is a poor correlation with joint pain. In contrast, early-onset CPDD has been described in several large families in which the disease progresses to severe degenerative osteoarthritis (OA). In these families, an autosomal dominant mode of inheritance is observed, with an age at onset between the 2nd and 5th decades of life. Inmore » this report, we describe a large New England family with early-onset CPDD and severe degenerative OA. We found genetic linkage between the disease in this family and chromosome 8q, with a multipoint lod score of 4.06. These results suggest that a defective gene at this location causes the disease in this family. 29 refs., 2 figs., 1 tab.« less

Glutaminolysis is Essential for Energy Production and Ion Transport in Human Corneal Endothelium.

PubMed

Zhang, Wenlin; Li, Hongde; Ogando, Diego G; Li, Shimin; Feng, Matthew; Price, Francis W; Tennessen, Jason M; Bonanno, Joseph A

2017-02-01

Corneal endothelium (CE) is among the most metabolically active tissues in the body. This elevated metabolic rate helps the CE maintain corneal transparency by its ion and fluid transport properties, which when disrupted, leads to visual impairment. Here we demonstrate that glutamine catabolism (glutaminolysis) through TCA cycle generates a large fraction of the ATP needed to maintain CE function, and this glutaminolysis is severely disrupted in cells deficient in NH 3 :H + cotransporter Solute Carrier Family 4 Member 11 (SLC4A11). Considering SLC4A11 mutations leads to corneal endothelial dystrophy and sensorineural deafness, our results indicate that SLC4A11-associated developmental and degenerative disorders result from altered glutamine catabolism. Overall, our results describe an important metabolic mechanism that provides CE cells with the energy required to maintain high level transport activity, reveal a direct link between glutamine metabolism and developmental and degenerative neuronal diseases, and suggest an approach for protecting the CE during ophthalmic surgeries. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Pulmonary artery dissection causing haemothorax in a cat: potential role of Dirofilaria immitis infection and literature review.

PubMed

Biasato, I; Tursi, M; Zanet, S; Longato, E; Capucchio, M T

2017-02-01

A 7-year-old male castrated domestic short-haired cat suddenly died. Gross examination revealed severe right-sided haemothorax with blood clots, four adult filarial nematodes in the blood clots and the caudal vena cava and haemorrhage dissecting into the tunica media of the right pulmonary artery. Histopathological investigation showed fibrosis of the tunica intima and disorganization/fragmentation of the elastic fibres accompanied by fibrous tissue deposition in the tunica media of both branches of pulmonary artery. Degenerative vasculopathy (intimal fibromuscular hyperplasia and medial hypertrophy/hyperplasia) involving pulmonary arteries was also observed. The polymerase chain reaction amplification and sequencing confirmed the identification of the parasite as Dirofilaria immitis. A diagnosis of pulmonary artery dissection with haemothorax and concomitant heartworm disease was formulated. Degenerative processes of the tunica media have been reported to cause pulmonary artery dissection in both humans and animals. Pulmonary artery remodelling induced by heartworms may be considered the underlying cause in the first case of feline pulmonary artery dissection, herein described. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of Low-Level Laser Therapy in Neurorehabilitation

PubMed Central

Hashmi, Javad T.; Huang, Ying-Ying; Osmani, Bushra Z.; Sharma, Sulbha K.; Naeser, Margaret A.; Hamblin, Michael R.

2011-01-01

This year marks the 50th anniversary of the discovery of the laser. The development of lasers for medical use, which became known as low-level laser therapy (LLLT) or photobiomodulation, followed in 1967. In recent years, LLLT has become an increasingly mainstream modality, especially in the areas of physical medicine and rehabilitation. At first used mainly for wound healing and pain relief, the medical applications of LLLT have broadened to include diseases such as stroke, myocardial infarction, and degenerative or traumatic brain disorders. This review will cover the mechanisms of LLLT that operate both on a cellular and a tissue level. Mitochondria are thought to be the principal photoreceptors, and increased adenosine triphosphate, reactive oxygen species, intracellular calcium, and release of nitric oxide are the initial events. Activation of transcription factors then leads to expression of many protective, anti-apoptotic, anti-oxidant, and pro-proliferation gene products. Animal studies and human clinical trials of LLLT for indications with relevance to neurology, such as stroke, traumatic brain injury, degenerative brain disease, spinal cord injury, and peripheral nerve regeneration, will be covered. PMID:21172691

cGMP production of patient-specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness

PubMed Central

Wiley, Luke A.; Burnight, Erin R.; DeLuca, Adam P.; Anfinson, Kristin R.; Cranston, Cathryn M.; Kaalberg, Emily E.; Penticoff, Jessica A.; Affatigato, Louisa M.; Mullins, Robert F.; Stone, Edwin M.; Tucker, Budd A.

2016-01-01

Immunologically-matched, induced pluripotent stem cell (iPSC)-derived photoreceptor precursor cells have the potential to restore vision to patients with retinal degenerative diseases like retinitis pigmentosa. The purpose of this study was to develop clinically-compatible methods for manufacturing photoreceptor precursor cells from adult skin in a non-profit cGMP environment. Biopsies were obtained from 35 adult patients with inherited retinal degeneration and fibroblast lines were established under ISO class 5 cGMP conditions. Patient-specific iPSCs were then generated, clonally expanded and validated. Post-mitotic photoreceptor precursor cells were generated using a stepwise cGMP-compliant 3D differentiation protocol. The recapitulation of the enhanced S-cone phenotype in retinal organoids generated from a patient with NR2E3 mutations demonstrated the fidelity of these protocols. Transplantation into immune compromised animals revealed no evidence of abnormal proliferation or tumor formation. These studies will enable clinical trials to test the safety and efficiency of patient-specific photoreceptor cell replacement in humans. PMID:27471043

Interpreting Evidence: An Approach to Teaching Human Evolution in the Classroom

ERIC Educational Resources Information Center

DeSilva, Jeremy

2004-01-01

Paleoanthropology, which is the study of human evolution through fossil records, can be used as a tool for teaching human evolution in the classrooms. An updated approach to teaching human evolution and a model for explaining what is science and how it is done, is presented.

Functional insights from the distribution and role of homopeptide repeat-containing proteins

PubMed Central

Faux, Noel G.; Bottomley, Stephen P.; Lesk, Arthur M.; Irving, James A.; Morrison, John R.; de la Banda, Maria Garcia; Whisstock, James C.

2005-01-01

Expansion of “low complex” repeats of amino acids such as glutamine (Poly-Q) is associated with protein misfolding and the development of degenerative diseases such as Huntington's disease. The mechanism by which such regions promote misfolding remains controversial, the function of many repeat-containing proteins (RCPs) remains obscure, and the role (if any) of repeat regions remains to be determined. Here, a Web-accessible database of RCPs is presented. The distribution and evolution of RCPs that contain homopeptide repeats tracts are considered, and the existence of functional patterns investigated. Generally, it is found that while polyamino acid repeats are extremely rare in prokaryotes, several eukaryote putative homologs of prokaryote RCP—involved in important housekeeping processes—retain the repetitive region, suggesting an ancient origin for certain repeats. Within eukarya, the most common uninterrupted amino acid repeats are glutamine, asparagines, and alanine. Interestingly, while poly-Q repeats are found in vertebrates and nonvertebrates, poly-N repeats are only common in more primitive nonvertebrate organisms, such as insects and nematodes. We have assigned function to eukaryote RCPs using Online Mendelian Inheritance in Man (OMIM), the Human Reference Protein Database (HRPD), FlyBase, and Wormpep. Prokaryote RCPs were annotated using BLASTp searches and Gene Ontology. These data reveal that the majority of RCPs are involved in processes that require the assembly of large, multiprotein complexes, such as transcription and signaling. PMID:15805494

Long-term Outcomes of Mitral Valve Repair Versus Replacement for Degenerative Disease: A Systematic Review

PubMed Central

McNeely, Christian A; Vassileva, Christina M

2015-01-01

The short-term advantage of mitral valve repair versus replacement for degenerative disease has been extensively documented. These advantages include lower operative mortality, improved survival, better preservation of left-ventricular function, shorter post-operative hospital stay, lower total costs, and fewer valve-related complications, including thromboembolism, anticoagulation-related bleeding events and late prosthetic dysfunction. More recent written data are available indicating the long-term advantage of repair versus replacement. While at some institutions, the repair rate for degenerative disease may exceed 90%, the national average in 2007 was only 69%. Making direct comparisons between mitral valve repair and replacement using the available studies does present some challenges however, as there are often differences in baseline characteristics between patient groups as well as other dissimilarities between studies. The purpose of this review is to systematically summarize the long-term survival and reoperation data of mitral valve repair versus replacement for degenerative disease. A PubMed search was done and resulted in 12 studies that met our study criteria for comparing mitral valve repair versus replacement for degenerative disease. A systematic review was then conducted abstracting survival and reoperation data. PMID:25158683

Short-term results of physiotherapy in patients with newly diagnosed degenerative cervical spine disease.

PubMed

Hey, H W; Lau, P H; Hee, H T

2012-03-01

Degenerative cervical spine diseases are common, and physiotherapy is widely used as an initial form of treatment. We aimed to analyse the effects of the initial sessions of physiotherapy for patients who were newly diagnosed with degenerative cervical spine disorders. A prospective series of 30 patients with newly diagnosed degenerative cervical spine disease were referred to our department and followed up for the initial two sessions of physiotherapy. The patients were assessed after each session. Outcome parameters studied included pain using a visual analogue scale (VAS), neck range of movements and activities of daily living (ADL). Our study subjects comprised mainly females (60%) in their fifties (46.7%) who worked as clerks or secretaries (53.3%). There was an improvement in the patients' pain score (VAS) from a median of 8 to 4 after two visits to the physiotherapists. Slight improvement in the neck range of movements was also observed. Marked improvement was seen in ADL, especially in the ability to carry heavy objects. Physiotherapy is an effective initial option for patients with newly presented degenerative cervical spine disease. The results of this study can be used to advise patients on the short-term benefits of physiotherapy.

Degenerative Cervical Myelopathy: A Spectrum of Related Disorders Affecting the Aging Spine.

PubMed

Tetreault, Lindsay; Goldstein, Christina L; Arnold, Paul; Harrop, James; Hilibrand, Alan; Nouri, Aria; Fehlings, Michael G

2015-10-01

Cervical spinal cord dysfunction can result from either traumatic or nontraumatic causes, including tumors, infections, and degenerative changes. In this article, we review the range of degenerative spinal disorders resulting in progressive cervical spinal cord compression and propose the adoption of a new term, degenerative cervical myelopathy (DCM). DCM comprises both osteoarthritic changes to the spine, including spondylosis, disk herniation, and facet arthropathy (collectively referred to as cervical spondylotic myelopathy), and ligamentous aberrations such as ossification of the posterior longitudinal ligament and hypertrophy of the ligamentum flavum. This review summarizes current knowledge of the pathophysiology of DCM and describes the cascade of events that occur after compression of the spinal cord, including ischemia, destruction of the blood-spinal cord barrier, demyelination, and neuronal apoptosis. Important features of the diagnosis of DCM are discussed in detail, and relevant clinical and imaging findings are highlighted. Furthermore, this review outlines valuable assessment tools for evaluating functional status and quality of life in these patients and summarizes the advantages and disadvantages of each. Other topics of this review include epidemiology, the prevalence of degenerative changes in the asymptomatic population, the natural history and rates of progression, risk factors of diagnosis (clinical, imaging and genetic), and management strategies.

Plasma and tissue oxidative stress index in patients with rheumatic and degenerative heart valve disease.

PubMed

Rabus, Murat; Demirbağ, Recep; Sezen, Yusuf; Konukoğlu, Oğuz; Yildiz, Ali; Erel, Ozcan; Zeybek, Rahmi; Yakut, Cevat

2008-12-01

We investigated whether patients with rheumatic and degenerative heart valve disease (HVD) differed with regard to plasma and tissue oxidative stress index (OSI). The study included 56 patients who underwent valve replacement due to rheumatic (n=32; 15 males; mean age 47+/-10 years) and degenerative (n=24; 13 males; mean age 55+/-12 years) HVD. Plasma and tissue total oxidative status (TOS) and total antioxidative capacity (TAC) levels were measured and OSI was calculated. Patients with degenerative HVD had significantly higher age, increased interventricular septum thickness, and higher frequency of aortic stenosis, whereas the incidence of mitral stenosis was higher in patients with rheumatic HVD (p<0.05). Plasma oxidative characteristics did not differ between the two HVD groups (p>0.05). Tissue TAC was significantly lower in patients with rheumatic HVD (p=0.027), whereas tissue TOS and OSI were similar between the two HVD groups (p>0.05). In bivariate analysis, plasma OSI did not show any correlation with clinical, laboratory, and echocardiographic variables (p>0.05). Our data show that plasma and tissue OSI levels are similar in patients with rheumatic and degenerative HVD.

Major transitions in human evolution.

PubMed

Foley, Robert A; Martin, Lawrence; Mirazón Lahr, Marta; Stringer, Chris

2016-07-05

Evolutionary problems are often considered in terms of 'origins', and research in human evolution seen as a search for human origins. However, evolution, including human evolution, is a process of transitions from one state to another, and so questions are best put in terms of understanding the nature of those transitions. This paper discusses how the contributions to the themed issue 'Major transitions in human evolution' throw light on the pattern of change in hominin evolution. Four questions are addressed: (1) Is there a major divide between early (australopithecine) and later (Homo) evolution? (2) Does the pattern of change fit a model of short transformations, or gradual evolution? (3) Why is the role of Africa so prominent? (4) How are different aspects of adaptation-genes, phenotypes and behaviour-integrated across the transitions? The importance of developing technologies and approaches and the enduring role of fieldwork are emphasized.This article is part of the themed issue 'Major transitions in human evolution'. © 2016 The Author(s).

Are animal models useful for studying human disc disorders/degeneration?

PubMed Central

Eisenstein, Stephen M.; Ito, Keita; Little, Christopher; Kettler, A. Annette; Masuda, Koichi; Melrose, James; Ralphs, Jim; Stokes, Ian; Wilke, Hans Joachim

2007-01-01

Intervertebral disc (IVD) degeneration is an often investigated pathophysiological condition because of its implication in causing low back pain. As human material for such studies is difficult to obtain because of ethical and government regulatory restriction, animal tissue, organs and in vivo models have often been used for this purpose. However, there are many differences in cell population, tissue composition, disc and spine anatomy, development, physiology and mechanical properties, between animal species and human. Both naturally occurring and induced degenerative changes may differ significantly from those seen in humans. This paper reviews the many animal models developed for the study of IVD degeneration aetiopathogenesis and treatments thereof. In particular, the limitations and relevance of these models to the human condition are examined, and some general consensus guidelines are presented. Although animal models are invaluable to increase our understanding of disc biology, because of the differences between species, care must be taken when used to study human disc degeneration and much more effort is needed to facilitate research on human disc material. PMID:17632738

Anterior Cervical Spine Surgery for Degenerative Disease: A Review

PubMed Central

SUGAWARA, Taku

Anterior cervical spine surgery is an established surgical intervention for cervical degenerative disease and high success rate with excellent long-term outcomes have been reported. However, indications of surgical procedures for certain conditions are still controversial and severe complications to cause neurological dysfunction or deaths may occur. This review is focused mainly on five widely performed procedures by anterior approach for cervical degenerative disease; anterior cervical discectomy, anterior cervical discectomy and fusion, anterior cervical corpectomy and fusion, anterior cervical foraminotomy, and arthroplasty. Indications, procedures, outcomes, and complications of these surgeries are discussed. PMID:26119899

C-reactive protein in degenerative aortic valve stenosis

PubMed Central

Sanchez, Pedro L; Mazzone, AnnaMaria

2006-01-01

Degenerative aortic valve stenosis includes a range of disorder severity from mild leaflet thickening without valve obstruction, "aortic sclerosis", to severe calcified aortic stenosis. It is a slowly progressive active process of valve modification similar to atherosclerosis for cardiovascular risk factors, lipoprotein deposition, chronic inflammation, and calcification. Systemic signs of inflammation, as wall and serum C-reactive protein, similar to those found in atherosclerosis, are present in patients with degenerative aortic valve stenosis and may be expression of a common disease, useful in monitoring of stenosis progression. PMID:16774687

Quantitative analysis of 18F-NaF dynamic PET/CT cannot differentiate malignant from benign lesions in multiple myeloma

PubMed Central

Sachpekidis, Christos; Hillengass, Jens; Goldschmidt, Hartmut; Anwar, Hoda; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2017-01-01

A renewed interest has been recently developed for the highly sensitive bone-seeking radiopharmaceutical 18F-NaF. Aim of the present study is to evaluate the potential utility of quantitative analysis of 18F-NaF dynamic PET/CT data in differentiating malignant from benign degenerative lesions in multiple myeloma (MM). 80 MM patients underwent whole-body PET/CT and dynamic PET/CT scanning of the pelvis with 18F-NaF. PET/CT data evaluation was based on visual (qualitative) assessment, semi-quantitative (SUV) calculations, and absolute quantitative estimations after application of a 2-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD). In total 263 MM lesions were demonstrated on 18F-NaF PET/CT. Semi-quantitative and quantitative evaluations were performed for 25 MM lesions as well as for 25 benign, degenerative and traumatic lesions. Mean SUVaverage for MM lesions was 11.9 and mean SUVmax was 23.2. Respectively, SUVaverage and SUVmax for degenerative lesions were 13.5 and 20.2. Kinetic analysis of 18F-NaF revealed the following mean values for MM lesions: K1 = 0.248 (1/min), k3 = 0.359 (1/min), influx (Ki) = 0.107 (1/min), FD = 1.382, while the respective values for degenerative lesions were: K1 = 0.169 (1/min), k3 = 0.422 (1/min), influx (Ki) = 0.095 (1/min), FD = 1. 411. No statistically significant differences between MM and benign degenerative disease regarding SUVaverage, SUVmax, K1, k3 and influx (Ki) were demonstrated. FD was significantly higher in degenerative than in malignant lesions. The present findings show that quantitative analysis of 18F-NaF PET data cannot differentiate malignant from benign degenerative lesions in MM patients, supporting previously published results, which reflect the limited role of 18F-NaF PET/CT in the diagnostic workup of MM. PMID:28913153

Lumbar degenerative spinal deformity: Surgical options of PLIF, TLIF and MI-TLIF

PubMed Central

Hey, Hwee Weng Dennis; Hee, Hwan Tak

2010-01-01

Degenerative disease of the lumbar spine is common in ageing populations. It causes disturbing back pain, radicular symptoms and lowers the quality of life. We will focus our discussion on the surgical options of posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) and minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) for lumbar degenerative spinal deformities, which include symptomatic spondylolisthesis and degenerative scoliosis. Through a description of each procedure, we hope to illustrate the potential benefits of TLIF over PLIF. In a retrospective study of 53 ALIF/PLIF patients and 111 TLIF patients we found reduced risk of vessel and nerve injury in TLIF patients due to less exposure of these structures, shortened operative time and reduced intra-operative bleeding. These advantages could be translated to shortened hospital stay, faster recovery period and earlier return to work. The disadvantages of TLIF such as incomplete intervertebral disc and vertebral end-plate removal and potential occult injury to exiting nerve root when under experienced hands are rare. Hence TLIF remains the mainstay of treatment in degenerative deformities of the lumbar spine. However, TLIF being a unilateral transforaminal approach, is unable to decompress the opposite nerve root. This may require contralateral laminotomy, which is a fairly simple procedure. The use of minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) to treat degenerative lumbar spinal deformity is still in its early stages. Although the initial results appear promising, it remains a difficult operative procedure to master with a steep learning curve. In a recent study comparing 29 MI-TLIF patients and 29 open TLIF, MI-TLIF was associated with longer operative time, less blood loss, shorter hospital stay, with no difference in SF-36 scores at six months and two years. Whether it can replace traditional TLIF as the surgery of choice for degenerative lumbar deformity remains unknown and more studies are required to validate the safety and efficiency. PMID:20419002

Evolution education in Canada's museums: Where is human evolution?

NASA Astrophysics Data System (ADS)

Bean, Sarah

While an interest in the origin of human beings may be a cultural universal, there are various views and beliefs about how this event took place. In Canada, a recent (2010) Angus Reid survey revealed that only 61% of Canadians accepted that humans evolved over millions of years; 39% of the population either believed in creationism or did not accept evolution as a scientific fact. These statistics suggest that human evolution education is a topic that needs to be addressed. This thesis investigates the role of museums in public education about human evolution. Prior to this study, the number of Canadian museums with exhibits about this topic was unknown. Sixteen Canadian museums participated in this study, and the results demonstrated that only two had permanent exhibits on human evolution, and one creationist museum presented a biblically-based account of human origins. Here, it is argued that more of Canada's museums should consider incorporating human evolution education into their mandates.

The immediate effects of taping therapy on knee pain and depression in patients with degenerative arthritis.

PubMed

Han, Ji-Won; Lee, Dong-Kyu; Park, Chi-Bok

2018-05-01

[Purpose] This study aims to identify the immediate effects of taping therapy on knee pain and depression among patients with degenerative arthritis. [Subjects and Methods] In total, 32 patients with degenerative arthritis were randomly assigned to one of two groups: the experimental group that underwent taping therapy and the control group that underwent regular treatment (16 patients per group). In the experimental group, therapeutic tape was wrapped all around the knee joint. Pain and depression were measured using the visual analogue scale (VAS) and the Beck Depression Inventory (BDI), respectively. [Results] The intra-group comparison showed significant differences in VAS and BDI for the experimental group. The intergroup comparison showed that the differences in VAS and BDI within the experimental group appeared significant relative to the control group. [Conclusion] It was observed that taping therapy showed an immediate effect in decreasing knee pain and depression among patients with degenerative arthritis.

Synergistic Effect of High Charge and Energy Particle Radiation and Chronological Age on Biomarkers of Oxidative Stress and Tissue Degeneration: A Ground-Based Study Using the Vertebrate Laboratory Model Organism Oryzias latipes

PubMed Central

Zheng, Xuan; Zhang, Xinyan; Ding, Lingling; Lee, Jeffrey R.; Weinberger, Paul M.; Dynan, William S.

2014-01-01

High charge and energy (HZE) particles are a main hazard of the space radiation environment. Uncertainty regarding their health effects is a limiting factor in the design of human exploration-class space missions, that is, missions beyond low earth orbit. Previous work has shown that HZE exposure increases cancer risk and elicits other aging-like phenomena in animal models. Here, we investigate how a single exposure to HZE particle radiation, early in life, influences the subsequent age-dependent evolution of oxidative stress and appearance of degenerative tissue changes. Embryos of the laboratory model organism, Oryzias latipes (Japanese medaka fish), were exposed to HZE particle radiation at doses overlapping the range of anticipated human exposure. A separate cohort was exposed to reference γ-radiation. Survival was monitored for 750 days, well beyond the median lifespan. The population was also sampled at intervals and liver tissue was subjected to histological and molecular analysis. HZE particle radiation dose and aging contributed synergistically to accumulation of lipid peroxidation products, which are a marker of chronic oxidative stress. This was mirrored by a decline in PPARGC1A mRNA, which encodes a transcriptional co-activator required for expression of oxidative stress defense genes and for mitochondrial maintenance. Consistent with chronic oxidative stress, mitochondria had an elongated and enlarged ultrastructure. Livers also had distinctive, cystic lesions. Depending on the endpoint, effects of γ-rays in the same dose range were either lesser or not detected. Results provide a quantitative and qualitative framework for understanding relative contributions of HZE particle radiation exposure and aging to chronic oxidative stress and tissue degeneration. PMID:25375139

Synergistic Effect of High Charge and Energy Particle Radiation and Chronological Age on Biomarkers of Oxidative Stress and Tissue Degeneration: A Ground-Based Study Using the Vertebrate Laboratory Model Organism Oryzias latipes

DOE PAGES

Zheng, Xuan; Zhang, Xinyan; Ding, Lingling; ...

2014-11-06

High charge and energy (HZE) particles are a main hazard of the space radiation environment. Uncertainty regarding their health effects is a limiting factor in the design of human exploration-class space missions, that is, missions beyond low earth orbit. Previous work has shown that HZE exposure increases cancer risk and elicits other aging-like phenomena in animal models. Here, we investigate how a single exposure to HZE particle radiation, early in life, influences the subsequent age-dependent evolution of oxidative stress and appearance of degenerative tissue changes. Embryos of the laboratory model organism, Oryzias latipes (Japanese medaka fish), were exposed to HZEmore » particle radiation at doses overlapping the range of anticipated human exposure. A separate cohort was exposed to reference γ-radiation. Survival was monitored for 750 days, well beyond the median lifespan. The population was also sampled at intervals and liver tissue was subjected to histological and molecular analysis. HZE particle radiation dose and aging contributed synergistically to accumulation of lipid peroxidation products, which are a marker of chronic oxidative stress. This was mirrored by a decline in PPARGC1A mRNA, which encodes a transcriptional co-activator required for expression of oxidative stress defense genes and for mitochondrial maintenance. Consistent with chronic oxidative stress, mitochondria had an elongated and enlarged ultrastructure. Livers also had distinctive, cystic lesions. Depending on the endpoint, effects of γ-rays in the same dose range were either lesser or not detected. Results provide a quantitative and qualitative framework for understanding relative contributions of HZE particle radiation exposure and aging to chronic oxidative stress and tissue degeneration.« less

Maintaining the Brain: Insight into Human Neurodegeneration From Drosophila Mutants

PubMed Central

Lessing, Derek; Bonini, Nancy M.

2009-01-01

The fruit fly Drosophila melanogaster has brought significant advances to research in neurodegenerative disease, notably in the identification of genes that are required to maintain the structural integrity of the brain, defined by recessive mutations that cause adult-onset neurodegeneration. Here, we survey these genes in the fly and classify them according to five key cell biological processes. Over half of these genes have counterparts in mouse or human that are also associated with neurodegeneration. Fly genetics continues to be instrumental in the analysis of degenerative disease, with notable recent advances in our understanding of several inherited disorders, as well as Parkinson’s Disease and the central role of mitochondria in neuronal maintenance. PMID:19434080

Traditional Chinese medicine and the positive correlation with homeostatic evolution of human being: based on medical perspective.

PubMed

Wang, Jie-Hua

2012-08-01

Adaptation is an eternal theme of biological evolution. The paper aims at exploring the conception of positive correlation between traditional Chinese medicine (TCM) and human homeostatic evolution based on medical perspective. Discussions mainly involve TCM conforming to natural laws and natural evolution of life, spontaneous harmonization of yin and yang and operating system of human self-healing, modern human immunology and human endogenous immune function in TCM, self-homeostasis of human micro-ecological state and balance mechanism on regulating base in TCM, as well as adaptation-eternal theme of biological evolution and safeguarding adaptability-value of TCM. In perspective of medicine, theory and practice of TCM are in positive correlation with human homeostatic evolution, and what TCM tries to maintain is human intrinsic adaptive capability to disease and nature. Therefore, it is the core value of TCM, which is to be further studied, explored, realized and known to the world.

Comparative effectiveness of platelet-rich plasma injections for treating knee joint cartilage degenerative pathology: a systematic review and meta-analysis.

PubMed

Chang, Ke-Vin; Hung, Chen-Yu; Aliwarga, Fanny; Wang, Tyng-Guey; Han, Der-Sheng; Chen, Wen-Shiang

2014-03-01

To explore the effectiveness of platelet-rich plasma (PRP) in treating cartilage degenerative pathology in knee joints. Electronic databases, including PubMed and Scopus, were searched from the earliest record to September 2013. We included single-arm prospective studies, quasi-experimental studies, and randomized controlled trials that used PRP to treat knee chondral degenerative lesions. Eight single-arm studies, 3 quasi-experimental studies, and 5 randomized controlled trials were identified, comprising 1543 participants. We determined effect sizes for the selected studies by extracting changes in functional scales after the interventions and compared the PRP group pooled values with the pretreatment baseline and the groups receiving placebo or hyaluronic acid (HA) injections. PRP injections in patients with knee degenerative pathology showed continual efficacy for 12 months compared with their pretreatment condition. The effectiveness of PRP was likely better and more prolonged than that of HA. Injection doses ≤2, the use of a single-spinning approach, and lack of additional activators led to an uncertainty in the treatment effects. Patients with lower degrees of cartilage degeneration achieved superior outcomes as opposed to those affected by advanced osteoarthritis. PRP application improves function from basal evaluations in patients with knee joint cartilage degenerative pathology and tends to be more effective than HA administration. Discrepancy in the degenerative severity modifies the treatment responses, leading to participants with lower degrees of degeneration benefiting more from PRP injections. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Do the disc degeneration and osteophyte contribute to the curve rigidity of degenerative scoliosis?

PubMed

Zhu, Feng; Bao, Hongda; Yan, Peng; Liu, Shunan; Bao, Mike; Zhu, Zezhang; Liu, Zhen; Qiu, Yong

2017-03-29

The factors associated with lateral curve flexibility in degenerative scoliosis have not been well documented. Disc degeneration could result in significant change in stiffness and range of motion in lateral bending films. The osteophytes could be commonly observed in degenerative spine but the relationship between osteophyte formation and curve flexibility remains controversial. The aim of the current study is to clarify if the disc degeneration and osteophyte formation were both associated with curve flexibility of degenerative scoliosis. A total of 85 patients were retrospectively analyzed. The inclusion criteria were as follow: age greater than 45 years, diagnosed as degenerative scoliosis and coronal Cobb angle greater than 20°. Curve flexibility was calculated based on Cobb angle, and range of motion (ROM) was based on disc angle evaluation. Regional disc degeneration score (RDS) was obtained according to Pfirrmann classification and osteophyte formation score (OFS) was based on Nanthan classification. Spearman correlation was performed to analyze the relationship between curve flexibility and RDS as well as OFS. Moderate correlation was found between RDS and curve flexibility with a Spearman coefficient of -0.487 (P = 0.009). Similarly, moderate correlation was observed between curve flexibility and OFS with a Spearman coefficient of -0.429 (P = 0.012). Strong correlation was found between apical ROM and OFS compared to the relationship between curve flexibility and OFS with a Spearman coefficient of -0.627 (P < 0.001). Both disc degeneration and osteophytes formation correlated with curve rigidity. The pre-operative evaluation of both features may aid in the surgical decision-making in degenerative scoliosis patients.

Lumbar scoliosis associated with spinal stenosis in idiopathic and degenerative cases.

PubMed

Le Huec, J C; Cogniet, A; Mazas, S; Faundez, A

2016-10-01

Degenerative de novo scoliosis is commonly present in older adult patients. The degenerative process including disc bulging, facet arthritis, and ligamentum flavum hypertrophy contributes to the appearance of symptoms of spinal stenosis. Idiopathic scoliosis has also degenerative changes that can lead to spinal stenosis. The aetiology, prevalence, biomechanics, classification, symptomatology, and treatment of idiopathic and degenerative lumbar scoliosis in association with spinal stenosis are reviewed. Review study is based on a review of pertinent but non-exhaustive literature of the last 20 years in PubMed in English language. Retrospective analysis of studies focused on all parameters concerning scoliosis associated with stenosis. Very few publications have focused specifically on idiopathic scoliosis and stenosis, and this was before the advent of modern segmental instrumentation. On the other hand, many papers were found for degenerative scoliosis and stenosis with treatment methods based on aetiology of spinal canal stenosis and analysis of global sagittal and frontal parameters. Satisfactory clinical results after operative treatment range from 83 to 96 % but with increased percentage of complications. Recent literature analysed the importance of stabilizing or not the spine after decompression in such situation knowing the increasing risk of instability after facet resection. No prospective randomized studies were found to support short instrumentation. Long instrumentation and fusion to prevent distabilization after decompression were always associated with higher complication rates. Imbalance patients with unsatisfactory compensation capacities were at risk of complications. Operative treatment using newly proposed classification system of lumbar scoliosis with associated canal stenosis is useful. Sagittal balance and rotatory dislocation are the main parameters to analyse to determine the length of fusion.

Cartilage repair in the degenerative ageing knee

PubMed Central

Brittberg, Mats; Gomoll, Andreas H; Canseco, José A; Far, Jack; Lind, Martin; Hui, James

2016-01-01

Background and purpose Cartilage damage can develop due to trauma, resulting in focal chondral or osteochondral defects, or as more diffuse loss of cartilage in a generalized organ disease such as osteoarthritis. A loss of cartilage function and quality is also seen with increasing age. There is a spectrum of diseases ranging from focal cartilage defects with healthy surrounding cartilage to focal lesions in degenerative cartilage, to multiple and diffuse lesions in osteoarthritic cartilage. At the recent Aarhus Regenerative Orthopaedics Symposium (AROS) 2015, regenerative challenges in an ageing population were discussed by clinicians and basic scientists. A group of clinicians was given the task of discussing the role of tissue engineering in the treatment of degenerative cartilage lesions in ageing patients. We present the outcomes of our discussions on current treatment options for such lesions, with particular emphasis on different biological repair techniques and their supporting level of evidence. Results and interpretation Based on the studies on treatment of degenerative lesions and early OA, there is low-level evidence to suggest that cartilage repair is a possible treatment for such lesions, but there are conflicting results regarding the effect of advanced age on the outcome. We concluded that further improvements are needed for direct repair of focal, purely traumatic defects before we can routinely use such repair techniques for the more challenging degenerative lesions. Furthermore, we need to identify trigger mechanisms that start generalized loss of cartilage matrix, and induce subchondral bone changes and concomitant synovial pathology, to maximize our treatment methods for biological repair in degenerative ageing joints. PMID:27910738

21 CFR 888.3580 - Knee joint patellar (hemi-knee) metallic resurfacing uncemented prosthesis.

Code of Federal Regulations, 2012 CFR

2012-04-01

... degenerative and posttraumatic patellar arthritis. (2) Class III when intended for uses other than treatment of degenerative and posttraumatic patellar arthritis. (c) Date PMA or notice of completion of a PDP is required. A...

21 CFR 888.3580 - Knee joint patellar (hemi-knee) metallic resurfacing uncemented prosthesis.

Code of Federal Regulations, 2014 CFR

2014-04-01

... degenerative and posttraumatic patellar arthritis. (2) Class III when intended for uses other than treatment of degenerative and posttraumatic patellar arthritis. (c) Date PMA or notice of completion of a PDP is required. A...

21 CFR 888.3580 - Knee joint patellar (hemi-knee) metallic resurfacing uncemented prosthesis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... degenerative and posttraumatic patellar arthritis. (2) Class III when intended for uses other than treatment of degenerative and posttraumatic patellar arthritis. (c) Date PMA or notice of completion of a PDP is required. A...

21 CFR 888.3580 - Knee joint patellar (hemi-knee) metallic resurfacing uncemented prosthesis.

Code of Federal Regulations, 2013 CFR

2013-04-01

... degenerative and posttraumatic patellar arthritis. (2) Class III when intended for uses other than treatment of degenerative and posttraumatic patellar arthritis. (c) Date PMA or notice of completion of a PDP is required. A...

A Large Animal Model that Recapitulates the Spectrum of Human Intervertebral Disc Degeneration

PubMed Central

Gullbrand, Sarah E.; Malhotra, Neil R.; Schaer, Thomas P.; Zawacki, Zosia; Martin, John T.; Bendigo, Justin R.; Milby, Andrew H.; Dodge, George R.; Vresilovic, Edward J.; Elliott, Dawn M.; Mauck, Robert L.; Smith, Lachlan J.

2016-01-01

Objective The objective of this study was to establish a large animal model that recapitulates the spectrum of intervertebral disc degeneration that occurs in humans and which is suitable for pre-clinical evaluation of a wide range of experimental therapeutics. Design Degeneration was induced in the lumbar intervertebral discs of large frame goats by either intradiscal injection of chondroitinase ABC (ChABC) over a range of dosages (0.1U, 1U or 5U) or subtotal nucleotomy. Radiographs were used to assess disc height changes over 12 weeks. Degenerative changes to the discs and endplates were assessed via magnetic resonance imaging (MRI), semi-quantitative histological grading, micro-computed tomography (µCT), and measurement of disc biomechanical properties. Results Degenerative changes were observed for all interventions that ranged from mild (0.1U ChABC) to moderate (1U ChABC and nucleotomy) to severe (5U ChABC). All groups showed progressive reductions in disc height over 12 weeks. Histological scores were significantly increased in the 1U and 5U ChABC groups. Reductions in T2 and T1ρ, and increased Pfirrmann grade were observed on MRI. Resorption and remodeling of the cortical boney endplate adjacent to ChABC injected discs also occurred. Spine segment range of motion was greater and compressive modulus was lower in 1U ChABC and nucleotomy discs compared to intact. Conclusions A large animal model of disc degeneration was established that recapitulates the spectrum of structural, compositional and biomechanical features of human disc degeneration. This model may serve as a robust platform for evaluating the efficacy of therapeutics targeted towards varying degrees of disc degeneration. PMID:27568573

Intradiscal pressure study of percutaneous disc decompression with nucleoplasty in human cadavers.

PubMed

Chen, Yung C; Lee, Sang-heon; Chen, Darwin

2003-04-01

Intradiscal pressure was measured after percutaneous disc decompression by nucleoplasty in human cadavers with different degrees of disc degeneration. To assess intradiscal pressure change after disc decompression, and to analyze the influence of degeneration on the intradiscal pressure change. Partial removal of the nucleus has been shown to decompress herniated discs, relieving pressure on nerve roots and, in some cases, offering relief from disc pain. Nucleoplasty, a new minimally invasive procedure using patented Coblation technology, combines coagulation and ablation for partial removal of the nucleus. Coblated channels remove the tissue volume and may decrease the disc pressure. Three fresh human cadaver spinal specimens (T8-L5; age, 54-84 years; mean age, 70.7 years) were used in this investigation. The intradiscal pressure was measured at three points: before treatment, after each channel was created, and after treatment using a 25-guage 6-inch needle connected to a Merit Medical Systems Intellisystem Inflation Monitor. The needles were calibrated initially to approximately 30 pounds per square inch. For the control, the change in disc pressure was recorded by the same procedure without using Coblation energy. To evaluate the effectiveness of nucleoplasty, disc pressure changes were compared between treatment with and without Coblation energy. Intradiscal pressure was markedly reduced in the younger, healthy disc cadaver. In the older, degenerative disc cadavers, the change in intradiscal pressure after nucleoplasty was very small. There was an inverse correlation between the degree of disc degeneration and the change in intradiscal pressure. Pressure reduction through nucleoplasty is highly dependent on the degree of spine degeneration. Nucleoplasty markedly reduced intradiscal pressure in nondegenerative discs, but had a negligible effect on highly degenerative discs.

Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells

NASA Astrophysics Data System (ADS)

Yang, Ruifeng; Zheng, Ying; Burrows, Michelle; Liu, Shujing; Wei, Zhi; Nace, Arben; Guo, Wei; Kumar, Suresh; Cotsarelis, George; Xu, Xiaowei

2014-01-01

Epithelial stem cells (EpSCs) in the hair follicle bulge are required for hair follicle growth and cycling. The isolation and propagation of human EpSCs for tissue engineering purposes remains a challenge. Here we develop a strategy to differentiate human iPSCs (hiPSCs) into CD200+/ITGA6+ EpSCs that can reconstitute the epithelial components of the hair follicle and interfollicular epidermis. The hiPSC-derived CD200+/ITGA6+ cells show a similar gene expression signature as EpSCs directly isolated from human hair follicles. Human iPSC-derived CD200+/ITGA6+ cells are capable of generating all hair follicle lineages including the hair shaft, and the inner and outer root sheaths in skin reconstitution assays. The regenerated hair follicles possess a KRT15+ stem cell population and produce hair shafts expressing hair-specific keratins. These results suggest an approach for generating large numbers of human EpSCs for tissue engineering and new treatments for hair loss, wound healing and other degenerative skin disorders.

Intravitreal Autologous Bone Marrow CD34+ Cell Therapy for Ischemic and Degenerative Retinal Disorders: Preliminary Phase 1 Clinical Trial Findings

PubMed Central

Park, Susanna S.; Bauer, Gerhard; Abedi, Mehrdad; Pontow, Suzanne; Panorgias, Athanasios; Jonnal, Ravi; Zawadzki, Robert J.; Werner, John S.; Nolta, Jan

2015-01-01

Purpose. Because human bone marrow (BM) CD34+ stem cells home into damaged tissue and may play an important role in tissue repair, this pilot clinical trial explored the safety and feasibility of intravitreal autologous CD34+ BM cells as potential therapy for ischemic or degenerative retinal conditions. Methods. This prospective study enrolled six subjects (six eyes) with irreversible vision loss from retinal vascular occlusion, hereditary or nonexudative age-related macular degeneration, or retinitis pigmentosa. CD34+ cells were isolated under Good Manufacturing Practice conditions from the mononuclear cellular fraction of the BM aspirate using a CliniMACs magnetic cell sorter. After intravitreal CD34+ cell injection, serial ophthalmic examinations, microperimetry/perimetry, fluorescein angiography, electroretinography (ERG), optical coherence tomography (OCT), and adaptive optics OCT were performed during the 6-month follow-up. Results. A mean of 3.4 million (range, 1–7 million) CD34+ cells were isolated and injected per eye. The therapy was well tolerated with no intraocular inflammation or hyperproliferation. Best-corrected visual acuity and full-field ERG showed no worsening after 6 months. Clinical examination also showed no worsening during follow-up except among age-related macular degeneration subjects in whom mild progression of geographic atrophy was noted in both the study eye and contralateral eye at 6-month follow-up, concurrent with some possible decline on multifocal ERG and microperimetry. Cellular in vivo imaging using adaptive optics OCT showed changes suggestive of new cellular incorporation into the macula of the hereditary macular degeneration study eye. Conclusions. Intravitreal autologous BM CD34+ cell therapy appears feasible and well tolerated in eyes with ischemic or degenerative retinal conditions and merits further exploration. (ClinicalTrials.gov number, NCT01736059.) PMID:25491299

Degenerative Pannus Mimicking Clival Chordoma Resected via an Endoscopic Transnasal Approach.

PubMed

Khaldi, Ahmad; Griauzde, Julius; Duckworth, Edward A M

2011-05-01

Lesions of the lower clivus represent a technically challenging subset of skull base disease that requires careful treatment. A 75-year-old woman with tongue atrophy was referred for resection of a presumed clival chordoma. The lesion was resected via an endoscopic transnasal transclival approach with no complications. Pathology revealed only chronic inflammatory tissue consistent with a degenerative pannus. Degenerative pannus should be included in the differential diagnosis of lower clival extradural lesions. The endoscopic transnasal transclival corridor should be considered for resection of such lesions as an alternative to larger, more morbid, traditional skull base approaches.

Degenerative Pannus Mimicking Clival Chordoma Resected via an Endoscopic Transnasal Approach

PubMed Central

Khaldi, Ahmad; Griauzde, Julius; Duckworth, Edward A.M.

2011-01-01

Lesions of the lower clivus represent a technically challenging subset of skull base disease that requires careful treatment. A 75-year-old woman with tongue atrophy was referred for resection of a presumed clival chordoma. The lesion was resected via an endoscopic transnasal transclival approach with no complications. Pathology revealed only chronic inflammatory tissue consistent with a degenerative pannus. Degenerative pannus should be included in the differential diagnosis of lower clival extradural lesions. The endoscopic transnasal transclival corridor should be considered for resection of such lesions as an alternative to larger, more morbid, traditional skull base approaches. PMID:23984195

Motor Training in Degenerative Spinocerebellar Disease: Ataxia-Specific Improvements by Intensive Physiotherapy and Exergames

PubMed Central

2014-01-01

The cerebellum is essentially involved in movement control and plays a critical role in motor learning. It has remained controversial whether patients with degenerative cerebellar disease benefit from high-intensity coordinative training. Moreover, it remains unclear by which training methods and mechanisms these patients might improve their motor performance. Here, we review evidence from different high-intensity training studies in patients with degenerative spinocerebellar disease. These studies demonstrate that high-intensity coordinative training might lead to a significant benefit in patients with degenerative ataxia. This training might be based either on physiotherapy or on whole-body controlled videogames (“exergames”). The benefit shown in these studies is equal to regaining one or more years of natural disease progression. In addition, first case studies indicate that even subjects with advanced neurodegeneration might benefit from such training programs. For both types of training, the observed clinical improvements are paralleled by recoveries in ataxia-specific dysfunctions (e.g., multijoint coordination and dynamic stability). Importantly, for both types of training, the retention of the effects seems to depend on the frequency and continuity of training. Based on these studies, we here present preliminary recommendations for clinical practice, and articulate open questions that might guide future studies on neurorehabilitation in degenerative spinocerebellar disease. PMID:24877117

Characterization of Individuals with Sacroiliac Joint Bridging in a Skeletal Population: Analysis of Degenerative Changes in Spinal Vertebrae

PubMed Central

Imamura, Takeshi; Saiki, Kazunobu; Okamoto, Keishi; Maeda, Junichiro; Matsuo, Hiroaki; Wakebe, Tetsuaki; Ogami, Keiko; Tomita, Masato; Tagami, Atsushi; Shindo, Hiroyuki; Tsurumoto, Toshiyuki

2014-01-01

The aim of this study was to characterize the individuals with sacroiliac joint bridging (SIB) by analyzing the degenerative changes in their whole vertebral column and comparing them with the controls. A total of 291 modern Japanese male skeletons, with an average age at death of 60.8 years, were examined macroscopically. They were divided into two groups: individuals with SIB and those without bridging (Non-SIB). The degenerative changes in their whole vertebral column were evaluated, and marginal osteophyte scores (MOS) of the vertebral bodies and degenerative joint scores in zygapophyseal joints were calculated. SIB was recognized in 30 individuals from a total of 291 males (10.3%). The average of age at death in SIB group was significantly higher than that in Non-SIB group. The values of MOS in the thoracic spines, particularly in the anterior part of the vertebral bodies, were consecutively higher in SIB group than in Non-SIB group. Incidence of fused vertebral bodies intervertebral levels was obviously higher in SIB group than in Non-SIB group. SIB and marginal osteophyte formation in vertebral bodies could coexist in a skeletal population of men. Some systemic factors might act on these degenerative changes simultaneously both in sacroiliac joint and in vertebral column. PMID:25276825

Degenerative joint disease: multiple joint involvement in young and mature dogs.

PubMed

Olsewski, J M; Lust, G; Rendano, V T; Summers, B A

1983-07-01

Radiologic, pathologic, and ancillary methods were used to determine the occurrence of degenerative joint disease involving multiple joints of immature and adult dogs. Animals were selected for the development of hip joint dysplasia and chronic degenerative joint disease. Of disease-prone dogs, 82% (45 of 55 dogs) had radiologic changes, indicative of hip dysplasia, by 1 year of age. At necropsy, more abnormal joints were identified than by radiographic examination. Among 92 dogs between 3 to 11 months of age that had joint abnormalities, 71% had hip joint involvement; 38%, shoulder joint involvement; 22%, stifle joint involvement; and 40% had multiple joint involvement. Polyarthritis was asymptomatic and unexpected. Radiographic examination of older dogs also revealed evidence of degenerative joint disease in many joints. Multiple joint involvement was substantiated at necropsy of young and mature dogs. A similar pattern of polyarticular osteoarthritis was revealed in a survey (computer search) of necropsy reports from medical case records of 100 adult and elderly dogs. Usually, the joint disease was an incidental observation, unrelated to the clinical disease or to the cause of death. The frequent occurrence of degenerative changes in several joints of dogs aged 6 months to 17 years indicated that osteoarthritis may be progressive in these joints and raises the possibility that systemic factors are involved in the disease process.

Directed induction of functional motor neuron-like cells from genetically engineered human mesenchymal stem cells.

PubMed

Park, Hwan-Woo; Cho, Jung-Sun; Park, Chul-Kyu; Jung, Sung Jun; Park, Chang-Hwan; Lee, Shin-Jae; Oh, Seog Bae; Park, Young-Seok; Chang, Mi-Sook

2012-01-01

Cell replacement using stem cells is a promising therapeutic approach to treat degenerative motor neuron (MN) disorders, such as amyotrophic lateral sclerosis and spinal cord injury. Human bone marrow-derived mesenchymal stem cells (hMSCs) are a desirable cell source for autologous cell replacement therapy to treat nervous system injury due to their plasticity, low immunogenicity, and a lower risk of tumor formation than embryonic stem cells. However, hMSCs are inefficient with regards to differentiating into MN-like cells. To solve this limitation, we genetically engineered hMSCs to express MN-associated transcription factors, Olig2 and Hb9, and then treat the hMSCs expressing Olig2 and Hb9 with optimal MN induction medium (MNIM). This method of induction led to higher expression (>30% of total cells) of MN markers. Electrophysiological data revealed that the induced hMSCs had the excitable properties of neurons and were able to form functional connections with muscle fibers in vitro. Furthermore, when the induced hMSCs were transplanted into an injured organotypic rat spinal cord slice culture, an ex vivo model of spinal cord injury, they exhibited characteristics of MNs. The data strongly suggest that induced Olig2/Hb9-expressing hMSCs were clearly reprogrammed and directed toward a MN-like lineage. We propose that methods to induce Olig2 and Hb9, followed by further induction with MNIM have therapeutic potential for autologous cell replacement therapy to treat degenerative MN disorders.

Brief report: reconstruction of joint hyaline cartilage by autologous progenitor cells derived from ear elastic cartilage.

PubMed

Mizuno, Mitsuru; Kobayashi, Shinji; Takebe, Takanori; Kan, Hiroomi; Yabuki, Yuichiro; Matsuzaki, Takahisa; Yoshikawa, Hiroshi Y; Nakabayashi, Seiichiro; Ik, Lee Jeong; Maegawa, Jiro; Taniguchi, Hideki

2014-03-01

In healthy joints, hyaline cartilage covering the joint surfaces of bones provides cushioning due to its unique mechanical properties. However, because of its limited regenerative capacity, age- and sports-related injuries to this tissue may lead to degenerative arthropathies, prompting researchers to investigate a variety of cell sources. We recently succeeded in isolating human cartilage progenitor cells from ear elastic cartilage. Human cartilage progenitor cells have high chondrogenic and proliferative potential to form elastic cartilage with long-term tissue maintenance. However, it is unknown whether ear-derived cartilage progenitor cells can be used to reconstruct hyaline cartilage, which has different mechanical and histological properties from elastic cartilage. In our efforts to develop foundational technologies for joint hyaline cartilage repair and reconstruction, we conducted this study to obtain an answer to this question. We created an experimental canine model of knee joint cartilage damage, transplanted ear-derived autologous cartilage progenitor cells. The reconstructed cartilage was rich in proteoglycans and showed unique histological characteristics similar to joint hyaline cartilage. In addition, mechanical properties of the reconstructed tissues were higher than those of ear cartilage and equal to those of joint hyaline cartilage. This study suggested that joint hyaline cartilage was reconstructed from ear-derived cartilage progenitor cells. It also demonstrated that ear-derived cartilage progenitor cells, which can be harvested by a minimally invasive method, would be useful for reconstructing joint hyaline cartilage in patients with degenerative arthropathies. © AlphaMed Press.

Reflections about Osteoarthritis and Curcuma longa

PubMed Central

Akuri, Marina Cristina; Barbalho, Sandra Maria; Val, Raíssa Meira; Guiguer, Elen Landgraf

2017-01-01

Osteoarthritis (OA) is a chronic inflammatory degenerative process that affects joints such as the hands, hips, shoulders, feet, spine, and especially knees in millions of people worldwide. Some authors have shown that Curcuma longa components may exhibit benefic effects in the treatment of degenerative diseases as OA. This plant belongs to the family Zingiberaceae and it is popularly known as turmeric or saffron. This review intended to perform a retrospective search to identify studies involving humans and animal models. This review was based on articles linking OA and C. longa. Databases as Medline, Science Direct, and Lilacs were consulted and a retrospective search was carried out in order to identify studies involving humans and animal models. The curcuminoids from C. longa exhibit actions at different locations in the pathogenesis of OA once it may play an important role as anti-inflammatory, down-regulating enzymes as phospholipase A2, cyclooxygenase-2, and lipoxygenases, and reducing tumor necrosis factor-alpha-and interleukins such as interleukin-1β (IL-1β), IL-6, and IL-8. They also act as inducer of apoptosis in synoviocytes, decreasing the inflammation process and may also reduce the synthesis of reactive oxygen species. For these reasons, new pharmaceutical technology and pharmacological studies should be proposed to determine the dose, the best delivery vehicle, pharmaceutical formulation and route of administration of this plant so its use as an adjunct in the treatment of OA may become a reality in clinical practice. PMID:28503046

Genetic drift and mutational hazard in the evolution of salamander genomic gigantism.

PubMed

Mohlhenrich, Erik Roger; Mueller, Rachel Lockridge

2016-12-01

Salamanders have the largest nuclear genomes among tetrapods and, excepting lungfishes, among vertebrates as a whole. Lynch and Conery (2003) have proposed the mutational-hazard hypothesis to explain variation in genome size and complexity. Under this hypothesis, noncoding DNA imposes a selective cost by increasing the target for degenerative mutations (i.e., the mutational hazard). Expansion of noncoding DNA, and thus genome size, is driven by increased levels of genetic drift and/or decreased mutation rates; the former determines the efficiency with which purifying selection can remove excess DNA, whereas the latter determines the level of mutational hazard. Here, we test the hypothesis that salamanders have experienced stronger long-term, persistent genetic drift than frogs, a related clade with more typically sized vertebrate genomes. To test this hypothesis, we compared dN/dS and Kr/Kc values of protein-coding genes between these clades. Our results do not support this hypothesis; we find that salamanders have not experienced stronger genetic drift than frogs. Additionally, we find evidence consistent with a lower nucleotide substitution rate in salamanders. This result, along with previous work showing lower rates of small deletion and ectopic recombination in salamanders, suggests that a lower mutational hazard may contribute to genomic gigantism in this clade. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Causes of metabolic syndrome and obesity-related co-morbidities Part 1: A composite unifying theory review of human-specific co-adaptations to brain energy consumption.

PubMed

McGill, Anne-Thea

2014-01-01

The medical, research and general community is unable to effect significantly decreased rates of central obesity and related type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer. All conditions seem to be linked by the concept of the metabolic syndrome (MetS), but the underlying causes are not known. MetS markers may have been mistaken for causes, thus many treatments are destined to be suboptimal. The current paper aims to critique current paradigms, give explanations for their persistence, and to return to first principles in an attempt to determine and clarify likely causes of MetS and obesity related comorbidities. A wide literature has been mined, study concepts analysed and the basics of human evolution and new biochemistry reviewed. A plausible, multifaceted composite unifying theory is formulated. The basis of the theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A 'dual system' is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals, becoming highly energy efficient in humans. The still-evolving, complex human cortico-limbic-striatal system generates strong behavioural drives for energy dense food procurement, including motivating agricultural technologies and social system development. Addiction to such foods, leading to neglect of nutritious but less appetizing 'common or garden' food, appears to have occurred. Insufficient consumption of food micronutrients prevents optimal human NRF2 function. Inefficient oxidation of excess energy forces central and non-adipose cells to store excess toxic lipid. Oxidative stress and metabolic inflammation, or metaflammation, allow susceptibility to infectious, degenerative atherosclerotic cardiovascular, autoimmune, neurodegenerative and dysplastic diseases. Other relevant human-specific co-adaptations are examined, and encompass the unusual ability to store fat, certain vitamin pathways, the generalised but flexible intestine and microbiota, and slow development and longevity. This theory has significant past and future corollaries, which are explored in a separate article by McGill, A-T, in Archives of Public Health, 72: 31.

A new look at an old virus: patterns of mutation accumulation in the human H1N1 influenza virus since 1918

PubMed Central

2012-01-01

Background The H1N1 influenza A virus has been circulating in the human population for over 95 years, first manifesting itself in the pandemic of 1917–1918. Initial mortality was extremely high, but dropped exponentially over time. Influenza viruses have high mutation rates, and H1N1 has undergone significant genetic changes since 1918. The exact nature of H1N1 mutation accumulation over time has not been fully explored. Methods We have made a comprehensive historical analysis of mutational changes within H1N1 by examining over 4100 fully-sequenced H1N1 genomes. This has allowed us to examine the genetic changes arising within H1N1 from 1918 to the present. Results We document multiple extinction events, including the previously known extinction of the human H1N1 lineage in the 1950s, and an apparent second extinction of the human H1N1 lineage in 2009. These extinctions appear to be due to a continuous accumulation of mutations. At the time of its disappearance in 2009, the human H1N1 lineage had accumulated over 1400 point mutations (more than 10% of the genome), including approximately 330 non-synonymous changes (7.4% of all codons). The accumulation of both point mutations and non-synonymous amino acid changes occurred at constant rates (μ = 14.4 and 2.4 new mutations/year, respectively), and mutations accumulated uniformly across the entire influenza genome. We observed a continuous erosion over time of codon-specificity in H1N1, including a shift away from host (human, swine, and bird [duck]) codon preference patterns. Conclusions While there have been numerous adaptations within the H1N1 genome, most of the genetic changes we document here appear to be non-adaptive, and much of the change appears to be degenerative. We suggest H1N1 has been undergoing natural genetic attenuation, and that significant attenuation may even occur during a single pandemic. This process may play a role in natural pandemic cessation and has apparently contributed to the exponential decline in mortality rates over time, as seen in all major human influenza strains. These findings may be relevant to the development of strategies for managing influenza pandemics and strain evolution. PMID:23062055

Leveraging Human Insights by Combining Multi-Objective Optimization with Interactive Evolution

DTIC Science & Technology

2015-03-26

application, a program that used human selections to guide the evolution of insect -like images. He was able to demonstrate that humans provide key insights...LEVERAGING HUMAN INSIGHTS BY COMBINING MULTI-OBJECTIVE OPTIMIZATION WITH INTERACTIVE EVOLUTION THESIS Joshua R. Christman, Second Lieutenant, USAF...COMBINING MULTI-OBJECTIVE OPTIMIZATION WITH INTERACTIVE EVOLUTION THESIS Presented to the Faculty Department of Electrical and Computer Engineering

Guideline summary review: An evidence-based clinical guideline for the diagnosis and treatment of degenerative lumbar spondylolisthesis.

PubMed

Matz, Paul G; Meagher, R J; Lamer, Tim; Tontz, William L; Annaswamy, Thiru M; Cassidy, R Carter; Cho, Charles H; Dougherty, Paul; Easa, John E; Enix, Dennis E; Gunnoe, Bryan A; Jallo, Jack; Julien, Terrence D; Maserati, Matthew B; Nucci, Robert C; O'Toole, John E; Rosolowski, Karie; Sembrano, Jonathan N; Villavicencio, Alan T; Witt, Jens-Peter

2016-03-01

The North American Spine Society's (NASS) Evidence-Based Clinical Guideline for the Diagnosis and Treatment of Degenerative Lumbar Spondylolisthesis features evidence-based recommendations for diagnosing and treating degenerative lumbar spondylolisthesis. The guideline updates the 2008 guideline on this topic and is intended to reflect contemporary treatment concepts for symptomatic degenerative lumbar spondylolisthesis as reflected in the highest quality clinical literature available on this subject as of May 2013. The NASS guideline on this topic is the only guideline on degenerative lumbar spondylolisthesis included in the Agency for Healthcare Research and Quality's National Guideline Clearinghouse (NGC). The purpose of this guideline is to provide an evidence-based educational tool to assist spine specialists when making clinical decisions for patients with degenerative lumbar spondylolisthesis. This article provides a brief summary of the evidence-based guideline recommendations for diagnosing and treating patients with this condition. A systematic review of clinical studies relevant to degenerative spondylolisthesis was carried out. This NASS spondyolisthesis guideline is the product of the Degenerative Lumbar Spondylolisthesis Work Group of NASS' Evidence-Based Guideline Development Committee. The methods used to develop this guideline are detailed in the complete guideline and technical report available on the NASS website. In brief, a multidisciplinary work group of spine care specialists convened to identify clinical questions to address in the guideline. The literature search strategy was developed in consultation with medical librarians. Upon completion of the systematic literature search, evidence relevant to the clinical questions posed in the guideline was reviewed. Work group members used the NASS evidentiary table templates to summarize study conclusions, identify study strengths and weaknesses, and assign levels of evidence. Work group members participated in webcasts and in-person recommendation meetings to update and formulate evidence-based recommendations and incorporate expert opinion when necessary. The draft guidelines were submitted to an internal peer review process and ultimately approved by the NASS Board of Directors. Upon publication, the Degenerative Lumbar Spondylolisthesis guideline was accepted into the NGC and will be updated approximately every 5 years. Twenty-seven clinical questions were addressed in this guideline update, including 15 clinical questions from the original guideline and 12 new clinical questions. The respective recommendations were graded by strength of the supporting literature, which was stratified by levels of evidence. Twenty-one new or updated recommendations or consensus statements were issued and 13 recommendations or consensus statements were maintained from the original guideline. The clinical guideline was created using the techniques of evidence-based medicine and best available evidence to aid practitioners in the care of patients with degenerative lumbar spondylolisthesis. The entire guideline document, including the evidentiary tables, literature search parameters, literature attrition flow chart, suggestions for future research, and all of the references, is available electronically on the NASS website at https://www.spine.org/Pages/ResearchClinicalCare/QualityImprovement/ClinicalGuidelines.aspx and will remain updated on a timely schedule. Copyright © 2016 Elsevier Inc. All rights reserved.

First sternocostal degenerative arthritis with intrarticular fluid collection. A case report.

PubMed

Chalazonitis, Athanasios N; Condilis, Nicolas; Tilentzoglou, Anastasia C; Pontikis, John; Tzovara, Joannie

2006-01-01

A rare case with clinical condition of first sternocostal degenerative arthritis with intra-articular fluid collection that developed after long-lasting intense exercise (weight-lifting) for twenty years is reported. Imaging findings and differential diagnoses of the case are presented.

Biobanking of Human Retinas: The Next Big Leap for Eye Banks?

PubMed Central

Lužnik, Zala; Parekh, Mohit; Bertolin, Marina; Griffoni, Carlo; Ponzin, Diego

2015-01-01

Summary Retinal degenerative diseases are one of the main clinical causes of incurable and severe visional impairment. Thus, extensive research effort is put into the development of new causal therapeutic options. Promisingly, a number of studies showed regenerative capacity in specific retinal regions (the ciliary epithelium, retinal pigmented epithelium, iris, and Müller glia cells). However, most recent research studies are based on animal models or in vitro cultured cells, probably because of the limited availability of human posterior eye tissues (vitreous, retina, and choroid). To address this, we showed in our previous reports that eye banks with large numbers of globes collected yearly could set up biorepositories/biobanks where these precious tissues are isolated, quality controlled, and finally stored for scientists and clinicians wanting to access human tissues and test their own hypotheses. These precious human posterior eye tissues could be used for further research purposes, epidemiological studies, and target validation of newly developed drugs. In addition, this could be a promising and challenging option to retrieve potential retinal stem and progenitor cells from different parts of the retina and could be a breakthrough in the future delivery of ex vivo prepared customized (histocompatible) retinal tissue on scaffolds for transplantation purposes. In this Perspective, we will consider how the biorepositories could influence the future strategies for retinal stem cell therapies. Significance Retinal degenerative diseases are one of the main causes of severe vision impairment and regenerative medicine is attracting much attention as a potential therapy. Although highly desirable, the reactivation and proliferation of endogenous stem cells in vivo is not sufficient to generate enough cells to restore visual function after retinal injury. Thus, the replacement of exogenously derived normal donor cells is a promising solution. The challenge is to develop therapies with sufficient amounts of cells being harvested or expanded from donor tissues. Eye banks could overcome this issue by harvesting endogenous adult retinal stem cells from different donors. PMID:26032747

Genetics and recent human evolution.

PubMed

Templeton, Alan R

2007-07-01

Starting with "mitochondrial Eve" in 1987, genetics has played an increasingly important role in studies of the last two million years of human evolution. It initially appeared that genetic data resolved the basic models of recent human evolution in favor of the "out-of-Africa replacement" hypothesis in which anatomically modern humans evolved in Africa about 150,000 years ago, started to spread throughout the world about 100,000 years ago, and subsequently drove to complete genetic extinction (replacement) all other human populations in Eurasia. Unfortunately, many of the genetic studies on recent human evolution have suffered from scientific flaws, including misrepresenting the models of recent human evolution, focusing upon hypothesis compatibility rather than hypothesis testing, committing the ecological fallacy, and failing to consider a broader array of alternative hypotheses. Once these flaws are corrected, there is actually little genetic support for the out-of-Africa replacement hypothesis. Indeed, when genetic data are used in a hypothesis-testing framework, the out-of-Africa replacement hypothesis is strongly rejected. The model of recent human evolution that emerges from a statistical hypothesis-testing framework does not correspond to any of the traditional models of human evolution, but it is compatible with fossil and archaeological data. These studies also reveal that any one gene or DNA region captures only a small part of human evolutionary history, so multilocus studies are essential. As more and more loci became available, genetics will undoubtedly offer additional insights and resolutions of human evolution.

Does hybrid fixation prevent junctional disease after posterior fusion for degenerative lumbar disorders? A minimum 5-year follow-up study.

PubMed

Baioni, Andrea; Di Silvestre, Mario; Greggi, Tiziana; Vommaro, Francesco; Lolli, Francesco; Scarale, Antonio

2015-11-01

Medium- to long-term retrospective evaluation of clinical and radiographic outcome in the treatment of degenerative lumbar diseases with hybrid posterior fixation. Thirty patients were included with the mean age of 47.8 years (range 35 to 60 years). All patients underwent posterior lumbar instrumentation using hybrid fixation for lumbar stenosis with instability (13 cases), degenerative spondylolisthesis Meyerding grade I (6 cases), degenerative disc disease of one or more adjacent levels in six cases and mild lumbar degenerative scoliosis in five patients. Clinical outcomes were evaluated using Oswestry disability index (ODI), Roland and Morris disability questionnaire (RMDQ), and the visual analog scale (VAS) pain scores. All patients were assessed by preoperative, postoperative and follow-up standing plain radiographs and lateral X-rays with flexion and extension. Adjacent disc degeneration was also evaluated by magnetic resonance imaging (MRI) at follow-up. At a mean follow-up of 6.1 years, we observed on X-rays and/or MRI 3 cases of adjacent segment disease (10.0 %): two of them (6.6 %) presented symptoms and recurred a new surgery. The last patient (3.3 %) developed asymptomatic retrolisthesis of L3 not requiring revision surgery. The mean preoperative ODI score was 67.6, RMDQ score was 15.1, VAS back pain score was 9.5, and VAS leg pain score was 8.6. Postoperatively, these values improved to 28.1, 5.4, 3.1, and 2.9, respectively, and remained substantially unchanged at the final follow-up: (27.7, 5.2, 2.9, and 2.7, respectively). After 5-year follow-up, hybrid posterior lumbar fixation presented satisfying clinical outcomes in the treatment of degenerative disease.

Does restoration of focal lumbar lordosis for single level degenerative spondylolisthesis result in better patient-reported clinical outcomes? A systematic literature review.

PubMed

Rhee, Chanseok; Visintini, Sarah; Dunning, Cynthia E; Oxner, William M; Glennie, R Andrew

2017-10-01

It is controversial whether the surgical restoration of sagittal balance and spinopelvic angulation in a single level lumbar degenerative spondylolisthesis results in clinical improvements. The purpose of this study to systematically review the available literature to determine whether the surgical correction of malalignment in lumbar degenerative spondylolisthesis correlates with improvements in patient-reported clinical outcomes. Literature searches were performed via Ovid Medline, Embase, CENTRAL and Web of Science using search terms "lumbar," "degenerative/spondylolisthesis" and "surgery/surgical/surgeries/fusion". This resulted in 844 articles and after reviewing the abstracts and full-texts, 13 articles were included for summary and final analysis. There were two Level II articles, four Level III articles and five Level IV articles. Most commonly used patient-reported outcome measures (PROMs) were Oswestery disability index (ODI) and visual analogue scale (VAS). Four articles were included for the final statistical analysis. There was no statistically significant difference between the patient groups who achieved successful surgical correction of malalignment and those who did not for either ODI (mean difference -0.94, CI -8.89-7.00) or VAS (mean difference 1.57, CI -3.16-6.30). Two studies assessed the efficacy of manual reduction of lumbar degenerative spondylolisthesis and their clinical outcomes after the operation, and there was no statistically significant improvement. Overall, the restoration of focal lumbar lordosis and restoration of sagittal balance for single-level lumbar degenerative spondylolisthesis does not seem to yield clinical improvements but well-powered studies on this specific topic is lacking in the current literature. Future well-powered studies are needed for a more definitive conclusion. Copyright © 2017 Elsevier Ltd. All rights reserved.

How Can Diet Affect the Accumulation of Advanced Glycation End-Products in the Human Body?

PubMed

Guilbaud, Axel; Niquet-Leridon, Celine; Boulanger, Eric; Tessier, Frederic J

2016-12-06

The accumulation of advanced glycation end products (AGEs) is associated with the complications of diabetes, kidney disease, metabolic disorders and degenerative diseases. It is recognized that the pool of glycation products found in the human body comes not only from an endogenous formation, but also from a dietary exposure to exogenous AGEs. In recent years, the development of pharmacologically-active ingredients aimed at inhibiting endogenous glycation has not been successful. Since the accumulation of AGEs in the human body appears to be progressive throughout life, an early preventive action against glycation could be effective through dietary adjustments or supplementation with purified micronutrients. The present article provides an overview of current dietary strategies tested either in vitro, in vivo or both to reduce the endogenous formation of AGEs and to limit exposure to food AGEs.

How Can Diet Affect the Accumulation of Advanced Glycation End-Products in the Human Body?

PubMed Central

Guilbaud, Axel; Niquet-Leridon, Celine; Boulanger, Eric; Tessier, Frederic J.

2016-01-01

The accumulation of advanced glycation end products (AGEs) is associated with the complications of diabetes, kidney disease, metabolic disorders and degenerative diseases. It is recognized that the pool of glycation products found in the human body comes not only from an endogenous formation, but also from a dietary exposure to exogenous AGEs. In recent years, the development of pharmacologically-active ingredients aimed at inhibiting endogenous glycation has not been successful. Since the accumulation of AGEs in the human body appears to be progressive throughout life, an early preventive action against glycation could be effective through dietary adjustments or supplementation with purified micronutrients. The present article provides an overview of current dietary strategies tested either in vitro, in vivo or both to reduce the endogenous formation of AGEs and to limit exposure to food AGEs. PMID:28231179

Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders.

PubMed

Kaminsky, Natalie; Bihari, Ofer; Kanner, Sivan; Barzilai, Ari

2016-06-01

The DNA damage response (DDR) is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes). Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a "hostile" environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit. Copyright © 2016 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

Bilateral coxofemoral degenerative joint disease in a juvenile male yellow-eyed penguin (Megadyptes antipodes).

PubMed

Buckle, Kelly N; Alley, Maurice R

2011-08-01

A juvenile, male, yellow-eyed penguin (Megadyptes antipodes) with abnormal stance and decreased mobility was captured, held in captivity for approximately 6 weeks, and euthanized due to continued clinical signs. Radiographically, there was bilateral degenerative joint disease with coxofemoral periarticular osteophyte formation. Grossly, the bird had bilaterally distended, thickened coxofemoral joints with increased laxity, and small, roughened and angular femoral heads. Histologically, the left femoral articular cartilage and subchondral bone were absent, and the remaining femoral head consisted of trabecular bone overlain by fibrin and granulation tissue. There was no gross or histological evidence of infection. The historic, gross, radiographic, and histopathologic findings were most consistent with bilateral aseptic femoral head degeneration resulting in degenerative joint disease. Although the chronicity of the lesions masked the initiating cause, the probable underlying causes of aseptic bilateral femoral head degeneration in a young animal are osteonecrosis and osteochondrosis of the femoral head. To our knowledge, this is the first reported case of bilateral coxofemoral degenerative joint disease in a penguin.

The cervical spine of professional front-row rugby players: correlation between degenerative changes and symptoms.

PubMed

Hogan, B A; Hogan, N A; Vos, P M; Eustace, S J; Kenny, P J

2010-06-01

Injuries to the cervical spine (C-spine) are among the most serious in rugby and are well documented. Front-row players are particularly at risk due to repetitive high-intensity collisions in the scrum. This study evaluates degenerative changes of the C-spine and associated symptomatology in front-row rugby players. C-spine radiographs from 14 professional rugby players and controls were compared. Players averaged 23 years of playing competitive rugby. Two consultant radiologists performed a blind review of radiographs evaluating degeneration of disc spaces and apophyseal joints. Clinical status was assessed using a modified AAOS/NASS/COSS cervical spine outcomes questionnaire. Front-row rugby players exhibited significant radiographic evidence of C-spine degenerative changes compared to the non-rugby playing controls (P < 0.005). Despite these findings the rugby players did not exhibit increased symptoms. This highlights the radiologic degenerative changes of the C-spine of front-row rugby players. However, these changes do not manifest themselves clinically or affect activities of daily living.

Major transitions in human evolution

PubMed Central

Foley, Robert A.; Martin, Lawrence; Mirazón Lahr, Marta; Stringer, Chris

2016-01-01

Evolutionary problems are often considered in terms of ‘origins', and research in human evolution seen as a search for human origins. However, evolution, including human evolution, is a process of transitions from one state to another, and so questions are best put in terms of understanding the nature of those transitions. This paper discusses how the contributions to the themed issue ‘Major transitions in human evolution’ throw light on the pattern of change in hominin evolution. Four questions are addressed: (1) Is there a major divide between early (australopithecine) and later (Homo) evolution? (2) Does the pattern of change fit a model of short transformations, or gradual evolution? (3) Why is the role of Africa so prominent? (4) How are different aspects of adaptation—genes, phenotypes and behaviour—integrated across the transitions? The importance of developing technologies and approaches and the enduring role of fieldwork are emphasized. This article is part of the themed issue ‘Major transitions in human evolution’. PMID:27298461

Monogamy, strongly bonded groups, and the evolution of human social structure.

PubMed

Chapais, Bernard

2013-01-01

Human social evolution has most often been treated in a piecemeal fashion, with studies focusing on the evolution of specific components of human society such as pair-bonding, cooperative hunting, male provisioning, grandmothering, cooperative breeding, food sharing, male competition, male violence, sexual coercion, territoriality, and between-group conflicts. Evolutionary models about any one of those components are usually concerned with two categories of questions, one relating to the origins of the component and the other to its impact on the evolution of human cognition and social life. Remarkably few studies have been concerned with the evolution of the entity that integrates all components, the human social system itself. That social system has as its core feature human social structure, which I define here as the common denominator of all human societies in terms of group composition, mating system, residence patterns, and kinship structures. The paucity of information on the evolution of human social structure poses substantial problems because that information is useful, if not essential, to assess both the origins and impact of any particular aspect of human society. Copyright © 2013 Wiley Periodicals, Inc.

Level of Education as a Risk Factor for Extensive Prevalence of Cervical Intervertebral Disc Degenerative Changes and Chronic Neck Pain.

PubMed

Markotić, Vedran; Zubac, Damir; Miljko, Miro; Šimić, Goran; Zalihić, Amra; Bogdan, Gojko; Radančević, Dorijan; Šimić, Ana Dugandžić; Mašković, Josip

2017-09-01

The aim of this study was to document the prevalence of degenerative intervertebral disc changes in the patients who previously reported symptoms of neck pain and to determine the influence of education level on degenerative intervertebral disc changes and subsequent chronic neck pain. One hundred and twelve patients were randomly selected from the University Hospital in Mostar, Bosna and Herzegovina, (aged 48.5±12.7 years) and submitted to magnetic resonance imaging (MRI) of the cervical spine. MRI of 3.0 T (Siemens, Skyrim, Erlangen, Germany) was used to obtain cervical spine images. Patients were separated into two groups based on their education level: low education level (LLE) and high education level (HLE). Pfirrmann classification was used to document intervertebral disc degeneration, while self-reported chronic neck pain was evaluated using the previously validated Oswestry questionnaire. The entire logistic regression model containing all predictors was statistically significant, (χ 2 (3)=12.2, p=0.02), and was able to distinguish between respondents who had chronic neck pain and vice versa. The model explained between 10.0% (Cox-Snell R 2 ) and 13.8% (Nagelkerke R 2 ) of common variance with Pfirrmann classification, and it had the strength to discriminate and correctly classify 69.6% of patients. The probability of a patient being classified in the high or low group of degenerative disc changes according to the Pfirrmann scale was associated with the education level (Wald test: 5.5, p=0.02). Based on the Pfirrmann assessment scale, the HLE group was significantly different from the LLE group in the degree of degenerative changes of the cervical intervertebral discs (U=1,077.5, p=0.001). A moderate level of intervertebral disc degenerative changes (grade II and III) was equally matched among all patients, while the overall results suggest a higher level of education as a risk factor leading to cervical disc degenerative changes, regardless of age differences among respondents. Copyright© by the National Institute of Public Health, Prague 2017

Quantitative analysis of 18F-NaF dynamic PET/CT cannot differentiate malignant from benign lesions in multiple myeloma.

PubMed

Sachpekidis, Christos; Hillengass, Jens; Goldschmidt, Hartmut; Anwar, Hoda; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2017-01-01

A renewed interest has been recently developed for the highly sensitive bone-seeking radiopharmaceutical 18 F-NaF. Aim of the present study is to evaluate the potential utility of quantitative analysis of 18 F-NaF dynamic PET/CT data in differentiating malignant from benign degenerative lesions in multiple myeloma (MM). 80 MM patients underwent whole-body PET/CT and dynamic PET/CT scanning of the pelvis with 18 F-NaF. PET/CT data evaluation was based on visual (qualitative) assessment, semi-quantitative (SUV) calculations, and absolute quantitative estimations after application of a 2-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD). In total 263 MM lesions were demonstrated on 18 F-NaF PET/CT. Semi-quantitative and quantitative evaluations were performed for 25 MM lesions as well as for 25 benign, degenerative and traumatic lesions. Mean SUV average for MM lesions was 11.9 and mean SUV max was 23.2. Respectively, SUV average and SUV max for degenerative lesions were 13.5 and 20.2. Kinetic analysis of 18 F-NaF revealed the following mean values for MM lesions: K 1 = 0.248 (1/min), k 3 = 0.359 (1/min), influx (K i ) = 0.107 (1/min), FD = 1.382, while the respective values for degenerative lesions were: K 1 = 0.169 (1/min), k 3 = 0.422 (1/min), influx (K i ) = 0.095 (1/min), FD = 1. 411. No statistically significant differences between MM and benign degenerative disease regarding SUV average , SUV max , K 1 , k 3 and influx (K i ) were demonstrated. FD was significantly higher in degenerative than in malignant lesions. The present findings show that quantitative analysis of 18 F-NaF PET data cannot differentiate malignant from benign degenerative lesions in MM patients, supporting previously published results, which reflect the limited role of 18 F-NaF PET/CT in the diagnostic workup of MM.

The comparison of measurement between ultrasound and computed tomography for abnormal degenerative facet joints: A STROBE-compliant article.

PubMed

Shi, Wen; Tian, Dan; Liu, Da; Yin, Jing; Huang, Ying

2017-08-01

Besides the study on examining facet joints of lumbar spine by ultrasound in normal population, there has not been any related report about examining normal facet joints of lumbar spine by ultrasound so far. This study was aimed to explore the feasibility of ultrasound assessment of lumber spine facet joints by comparing ultrasound measure values of normal and degenerative lumber spine facet joints, and by comparing measure values of ultrasound and computed tomography (CT) of degenerative lumber spine facet joints.This study included 15 patients who had chronic low back pain because of degenerative change in lumbar vertebrae, and 19 volunteers who did not have low back pain or pain in the lower limb. The ultrasound measure values (height [H] and width [W]) of normal and degenerative lumber spine facet joints were compared. And the differentiation between measure values (H and W) of ultrasound and CT of degenerative lumber spine facet joints was also analyzed.The ultrasound clearly showed abnormal facet joints lesion, which was characterized by hyperostosis on the edge of joints, bone destruction under joints, and thinner or thicker articular cartilage. There were significant differences between the ultrasound measure values of the normal (H: 1.26 ± 0.03 cm, W: 0.18 ± 0.01 cm) and abnormal facet joints (H: 1.43 ± 0.05 cm, W: 0.15 ± 0.02 cm) (all P < .05). However, there were no significant differences between the measure values of the ultrasound (H: 1.43 ± 0.17 cm, W: 0.15 ± 0.03 cm) and CT (H: 1.42 ± 0.16, W: 0.14 ± 0.03) of the degenerative lumber spine facet joints (all P > .05).Ultrasound can clearly show the structure of facet joints of lumbar spine. It is precise and feasible to assess facet joints of lumbar spine by ultrasound. This study has important significance for the diagnosis of lumbar facet joint degeneration.

Surgical Treatment of Spinal Stenosis with and without Degenerative Spondylolisthesis: Cost-Effectiveness after 2 Years

PubMed Central

Tosteson, Anna N.A.; Lurie, Jon D.; Tosteson, Tor D.; Skinner, Jonathan S.; Herkowitz, Harry; Albert, Todd; Boden, Scott D.; Bridwell, Keith; Longley, Michael; Andersson, Gunnar B.; Blood, Emily A.; Grove, Margaret R.; Weinstein, James N.

2009-01-01

Background The SPORT (Spine Patient Outcomes Research Trial) reported favorable surgery outcomes over 2 years among patients with stenosis with and without degenerative spondylolisthesis, but the economic value of these surgeries is uncertain. Objective To assess the short-term cost-effectiveness of spine surgery relative to nonoperative care for stenosis alone and for stenosis with spondylolisthesis. Design Prospective cohort study. Data Sources Resource utilization, productivity, and EuroQol EQ-5D score measured at 6 weeks and at 3, 6, 12, and 24 months after treatment among SPORT participants. Target Population Patients with image-confirmed spinal stenosis, with and without degenerative spondylolisthesis. Time Horizon 2 years. Perspective Societal. Intervention Nonoperative care or surgery (primarily decompressive laminectomy for stenosis and decompressive laminectomy with fusion for stenosis associated with degenerative spondylolisthesis). Outcome Measures Cost per quality-adjusted life-year (QALY) gained. Results of Base-Case Analysis Among 634 patients with stenosis, 394 (62%) had surgery, most often decompressive laminectomy (320 of 394 [81%]). Stenosis surgeries improved health to a greater extent than nonoperative care (QALY gain, 0.17 [95% CI, 0.12 to 0.22]) at a cost of $77 600 (CI, $49 600 to $120 000) per QALY gained. Among 601 patients with degenerative spondylolisthesis, 368 (61%) had surgery, most including fusion (344 of 368 [93%]) and most with instrumentation (269 of 344 [78%]). Degenerative spondylolisthesis surgeries significantly improved health versus non-operative care (QALY gain, 0.23 [CI, 0.19 to 0.27]), at a cost of $115 600 (CI, $90 800 to $144 900) per QALY gained. Result of Sensitivity Analysis Surgery cost markedly affected the value of surgery. Limitation The study used self-reported utilization data, 2-year time horizon, and as-treated analysis to address treatment non-adherence among randomly assigned participants. Conclusion The economic value of spinal stenosis surgery at 2 years compares favorably with many health interventions. Degenerative spondylolisthesis surgery is not highly cost-effective over 2 years but could show value over a longer time horizon. PMID:19075203

Destructive discovertebral degenerative disease of the lumbar spine.

PubMed

Charran, A K; Tony, G; Lalam, R; Tyrrell, P N M; Tins, B; Singh, J; Eisenstein, S M; Balain, B; Trivedi, J M; Cassar-Pullicino, V N

2012-09-01

The uncommon variant of degenerative hip joint disease, termed rapidly progressive osteoarthritis, and highlighted by severe joint space loss and osteochondral disintegration, is well established. We present a similar unusual subset in the lumbar spine termed destructive discovertebral degenerative disease (DDDD) with radiological features of vertebral malalignment, severe disc resorption, and "bone sand" formation secondary to vertebral fragmentation. Co-existing metabolic bone disease is likely to promote the development of DDDD of the lumbar spine, which presents with back pain and sciatica due to nerve root compression by the "bone sand" in the epidural space. MRI and CT play a complimentary role in making the diagnosis.

Generation and expansion of highly pure motor neuron progenitors from human pluripotent stem cells.

PubMed

Du, Zhong-Wei; Chen, Hong; Liu, Huisheng; Lu, Jianfeng; Qian, Kun; Huang, CindyTzu-Ling; Zhong, Xiaofen; Fan, Frank; Zhang, Su-Chun

2015-03-25

Human pluripotent stem cells (hPSCs) have opened new opportunities for understanding human development, modelling disease processes and developing new therapeutics. However, these applications are hindered by the low efficiency and heterogeneity of cell types, such as motorneurons (MNs), differentiated from hPSCs as well as our inability to maintain the potency of lineage-committed progenitors. Here by using a combination of small molecules that regulate multiple signalling pathways, we develop a method to guide human embryonic stem cells to a near-pure population (>95%) of motor neuron progenitors (MNPs) in 12 days, and an enriched population (>90%) of functionally mature MNs in an additional 16 days. More importantly, the MNPs can be expanded for at least five passages so that a single MNP can be amplified to 1 × 10(4). This method is reproducible in human-induced pluripotent stem cells and is applied to model MN-degenerative diseases and in proof-of-principle drug-screening assays.

Yeast Prions and Human Prion-like Proteins: Sequence Features and Prediction Methods

PubMed Central

Cascarina, Sean; Ross, Eric D.

2014-01-01

Prions are self-propagating infectious protein isoforms. A growing number of prions have been identified in yeast, each resulting from the conversion of soluble proteins into an insoluble amyloid form. These yeast prions have served as a powerful model system for studying the causes and consequences of prion aggregation. Remarkably, a number of human proteins containing prion-like domains, defined as domains with compositional similarity to yeast prion domains, have recently been linked to various human degenerative diseases, including amyotrophic lateral sclerosis (ALS). This suggests that the lessons learned from yeast prions may help in understanding these human diseases. In this review, we examine what has been learned about the amino acid sequence basis for prion aggregation in yeast, and how this information has been used to develop methods to predict aggregation propensity. We then discuss how this information is being applied to understand human disease, and the challenges involved in applying yeast prediction methods to higher organisms. PMID:24390581

Yeast prions and human prion-like proteins: sequence features and prediction methods.

PubMed

Cascarina, Sean M; Ross, Eric D

2014-06-01

Prions are self-propagating infectious protein isoforms. A growing number of prions have been identified in yeast, each resulting from the conversion of soluble proteins into an insoluble amyloid form. These yeast prions have served as a powerful model system for studying the causes and consequences of prion aggregation. Remarkably, a number of human proteins containing prion-like domains, defined as domains with compositional similarity to yeast prion domains, have recently been linked to various human degenerative diseases, including amyotrophic lateral sclerosis. This suggests that the lessons learned from yeast prions may help in understanding these human diseases. In this review, we examine what has been learned about the amino acid sequence basis for prion aggregation in yeast, and how this information has been used to develop methods to predict aggregation propensity. We then discuss how this information is being applied to understand human disease, and the challenges involved in applying yeast prediction methods to higher organisms.

Evaluation of Electrospun Nanofiber-Anchored Silicone for the Degenerative Intervertebral Disc

PubMed Central

Riahanizad, S.

2017-01-01

The nucleus pulposus (NP) substitution by polymeric gel is one of the promising techniques for the repair of the degenerative intervertebral disc (IVD). Silicone gel is one of the potential candidates for a NP replacement material. Electrospun fiber anchorage to silicone disc, referred as ENAS disc, may not only improve the biomechanical performances of the gel but it can also improve restoration capability of the gel, which is unknown. This study successfully produced a novel process to anchor any size and shape of NP gel with electrospun fiber mesh. Viscoelastic properties of silicone and ENAS disc were measured using standard experimental techniques and compared with the native tissue properties. Ex vivo mechanical tests were conducted on ENAS disc-implanted rabbit tails to the compare the mechanical stability between intact and ENAS implanted spines. This study found that viscoelastic properties of ENAS disc are higher than silicone disc and comparable to the viscoelastic properties of human NP. The ex vivo studies found that the ENAS disc restore the mechanical functionality of rabbit tail spine, after discectomy of native NP and replacing the NP by ENAS disc. Therefore, the PCL ENF mesh anchoring technique to a NP implant can have clinical potential. PMID:29181144

A Comprehensive Review on Clinical Applications of Comet Assay

PubMed Central

Gunasekarana, Vidya; Chand, Parkash

2015-01-01

Increased levels of DNA damage and ineffective repair mechanisms are the underlying bio-molecular events in the pathogenesis of most of the life-threatening diseases like cancer and degenerative diseases. The sources of DNA damage can be either exogenous or endogenous in origin. Imbalance between the oxidants and antioxidants resulting in increased reactive oxygen species mostly accounts for the endogenously derived attacks on DNA. Among the various methods employed in the estimation of DNA damage, alkaline comet assay is proven to be a relatively simple and versatile tool in the assessment of DNA damage and also in determining the efficacy of DNA repair mechanism. The aim of this article is to review the application of comet assay in the field of medicine towards human biomonitoring, understanding the pathogenesis of cancer and progression of chronic and degenerative diseases, prediction of tumour radio & chemosensitivity and in male infertility. A standardized protocol and analysis system of various variants of comet assay in different types of cells, across the labs will be of useful and reliable clinical tool in the field of Medicine for the estimation of levels of DNA damage and repair mechanisms. PMID:25954633

Adult's Degenerative Scoliosis: Midterm Results of Dynamic Stabilization without Fusion in Elderly Patients—Is It Effective?

PubMed Central

Di Silvestre, Mario; Lolli, Francesco; Greggi, Tiziana; Vommaro, Francesco; Baioni, Andrea

2013-01-01

Study Design. A retrospective study. Purpose. Posterolateral fusion with pedicle screw instrumentation used for degenerative lumbar scoliosis can lead to several complications. In elderly patients without sagittal imbalance, dynamic stabilization could represent an option to avoid these adverse events. Methods. 57 patients treated by dynamic stabilization without fusion were included. All patients had degenerative lumbar de novo scoliosis (average Cobb angle 17.2°), without sagittal imbalance, associated in 52 cases (91%) with vertebral canal stenosis and in 24 (42%) with degenerative spondylolisthesis. Nineteen patients (33%) had previously undergone lumbar spinal surgery. Results. At an average followup of 77 months, clinical results improved with statistical significance. Scoliosis Cobb angle was 17.2° (range, 12° to 38°) before surgery and 11.3° (range, 4° to 26°) at last follow-up. In the patients with associated spondylolisthesis, anterior vertebral translation was 19.5% (range, 12% to 27%) before surgery, 16.7% (range, 0% to 25%) after surgery, and 17.5% (range, 0% to 27%) at followup. Complications incidence was low (14%), and few patients required revision surgery (4%). Conclusions. In elderly patients with mild degenerative lumbar scoliosis without sagittal imbalance, pedicle screw-based dynamic stabilization is an effective option, with low complications incidence, granting curve stabilization during time and satisfying clinical results. PMID:23781342

Prevalence of Late Functional Tricuspid Regurgitation in Degenerative Mitral Regurgitation Surgery.

PubMed

Vaturi, Mordehay; Kotler, Tali; Shapira, Yaron; Weisenberg, Daniel; Monakier, Daniel; Sagie, Alexander

2016-03-01

Although significant late tricuspid regurgitation (TR) may develop after surgery for degenerative mitral regurgitation (MR), the use of routine tricuspid annuloplasty is debatable. The study aim was to determine the prevalence and predictors of significant late TR after surgery for degenerative MR. A total of 112 patients who had undergone surgery for degenerative MR without concomitant tricuspid valve repair (average follow up 7.7 ± 4.0 years) was studied retrospectively. The prevalence of post-surgical TR and predictors of progression were determined. The majority of patients (97%) had non-significant TR (less than moderate) prior to surgery, although an overall trend of progression towards significant TR (grades 2 or 3) was noted in 17 patients (p = 0.0006). Of the 18 patients (16%) with late postoperative significant TR, only nine (8%) had severe TR with only a single referral to surgery. New-onset post-surgical atrial fibrillation was more common in patients who developed late significant TR (p = 0.002). Multivariate analysis of the pre-surgery variables, age >65 years and left ventricular dysfunction were shown to be independent predictors of late functional TR. Significant progression in TR after surgery for degenerative MR was rare in this patient cohort. The impact of older age and left ventricular dysfunction at the time of surgery showed a strong association with post-surgical atrial fibrillation.

New thinking: the evolution of human cognition

PubMed Central

Heyes, Cecilia

2012-01-01

Humans are animals that specialize in thinking and knowing, and our extraordinary cognitive abilities have transformed every aspect of our lives. In contrast to our chimpanzee cousins and Stone Age ancestors, we are complex political, economic, scientific and artistic creatures, living in a vast range of habitats, many of which are our own creation. Research on the evolution of human cognition asks what types of thinking make us such peculiar animals, and how they have been generated by evolutionary processes. New research in this field looks deeper into the evolutionary history of human cognition, and adopts a more multi-disciplinary approach than earlier ‘Evolutionary Psychology’. It is informed by comparisons between humans and a range of primate and non-primate species, and integrates findings from anthropology, archaeology, economics, evolutionary biology, neuroscience, philosophy and psychology. Using these methods, recent research reveals profound commonalities, as well striking differences, between human and non-human minds, and suggests that the evolution of human cognition has been much more gradual and incremental than previously assumed. It accords crucial roles to cultural evolution, techno-social co-evolution and gene–culture co-evolution. These have produced domain-general developmental processes with extraordinary power—power that makes human cognition, and human lives, unique. PMID:22734052

New thinking: the evolution of human cognition.

PubMed

Heyes, Cecilia

2012-08-05

Humans are animals that specialize in thinking and knowing, and our extraordinary cognitive abilities have transformed every aspect of our lives. In contrast to our chimpanzee cousins and Stone Age ancestors, we are complex political, economic, scientific and artistic creatures, living in a vast range of habitats, many of which are our own creation. Research on the evolution of human cognition asks what types of thinking make us such peculiar animals, and how they have been generated by evolutionary processes. New research in this field looks deeper into the evolutionary history of human cognition, and adopts a more multi-disciplinary approach than earlier 'Evolutionary Psychology'. It is informed by comparisons between humans and a range of primate and non-primate species, and integrates findings from anthropology, archaeology, economics, evolutionary biology, neuroscience, philosophy and psychology. Using these methods, recent research reveals profound commonalities, as well striking differences, between human and non-human minds, and suggests that the evolution of human cognition has been much more gradual and incremental than previously assumed. It accords crucial roles to cultural evolution, techno-social co-evolution and gene-culture co-evolution. These have produced domain-general developmental processes with extraordinary power-power that makes human cognition, and human lives, unique.

Mosaic evolution and the pattern of transitions in the hominin lineage.

PubMed

Foley, Robert A

2016-07-05

Humans are uniquely unique, in terms of the extreme differences between them and other living organisms, and the impact they are having on the biosphere. The evolution of humans can be seen, as has been proposed, as one of the major transitions in evolution, on a par with the origins of multicellular organisms or the eukaryotic cell (Maynard Smith & Szathmáry 1997 Major transitions in evolution). Major transitions require the evolution of greater complexity and the emergence of new evolutionary levels or processes. Does human evolution meet these conditions? I explore the diversity of evidence on the nature of transitions in human evolution. Four levels of transition are proposed-baseline, novel taxa, novel adaptive zones and major transitions-and the pattern of human evolution considered in the light of these. The primary conclusions are that changes in human evolution occur continuously and cumulatively; that novel taxa and the appearance of new adaptations are not clustered very tightly in particular periods, although there are three broad transitional phases (Pliocene, Plio-Pleistocene and later Quaternary). Each phase is distinctive, with the first based on ranging and energetics, the second on technology and niche expansion, and the third on cognition and cultural processes. I discuss whether this constitutes a 'major transition' in the context of the evolutionary processes more broadly; the role of behaviour in evolution; and the opportunity provided by the rich genetic, phenotypic (fossil morphology) and behavioural (archaeological) record to examine in detail major transitions and the microevolutionary patterns underlying macroevolutionary change. It is suggested that the evolution of the hominin lineage is consistent with a mosaic pattern of change.This article is part of the themed issue 'Major transitions in human evolution'. © 2016 The Author(s).

Statistical analysis of polarization interference images of biological fluids polycrystalline films in the tasks of optical anisotropy weak changes differentiation

NASA Astrophysics Data System (ADS)

Ushenko, Yu. O.; Dubolazov, O. V.; Ushenko, V. O.; Zhytaryuk, V. G.; Prydiy, O. G.; Pavlyukovich, N.; Pavlyukovich, O.

2018-01-01

In this paper, we present the results of a statistical analysis of polarization-interference images of optically thin histological sections of biological tissues and polycrystalline films of biological fluids of human organs. A new analytical parameter is introduced-the local contrast of the interference pattern in the plane of a polarizationinhomogeneous microscopic image of a biological preparation. The coordinate distributions of the given parameter and the sets of statistical moments of the first-fourth order that characterize these distributions are determined. On this basis, the differentiation of degenerative-dystrophic changes in the myocardium and the polycrystalline structure of the synovial fluid of the human knee with different pathologies is realized.

Force wave transmission through the human locomotor system.

PubMed

Voloshin, A; Wosk, J; Brull, M

1981-02-01

A method to measure the capability of the human shock absorber system to attenuate input dynamic loading during the gait is presented. The experiments were carried out with two groups: healthy subjects and subjects with various pathological conditions. The results of the experiments show a considerable difference in the capability of each group's shock absorbers to attenuate force transmitted through the locomotor system. Comparison shows that healthy subjects definitely possess a more efficient shock-absorbing capacity than do those subjects with joint disorders. Presented results show that degenerative changes in joints reduce their shock absorbing capacity, which leads to overloading of the next shock absorber in the locomotor system. So, the development of osteoarthritis may be expected to result from overloading of a shock absorber's functional capacity.

Homogentisate 1,2 dioxygenase is expressed in human osteoarticular cells: implications in alkaptonuria.

PubMed

Laschi, Marcella; Tinti, Laura; Braconi, Daniela; Millucci, Lia; Ghezzi, Lorenzo; Amato, Loredana; Selvi, Enrico; Spreafico, Adriano; Bernardini, Giulia; Santucci, Annalisa

2012-09-01

Alkaptonuria (AKU) results from defective homogentisate1,2-dioxygenase (HGD), causing degenerative arthropathy. The deposition of ochronotic pigment in joints is so far attributed to homogentisic acid produced by the liver, circulating in the blood and accumulating locally. Human normal and AKU osteoarticular cells were tested for HGD gene expression by RT-PCR, mono- and 2D-Western blotting. HGD gene expression was revealed in chondrocytes, synoviocytes, osteoblasts. Furthermore, HGD expression was confirmed by Western blotting, that also revealed the presence of five enzymatic molecular species. Our findings indicate that AKU osteoarticular cells produce the ochronotic pigment in loco and this may strongly contribute to induction of ochronotic arthropathy. Copyright © 2011 Wiley Periodicals, Inc.

Analysis of Brain Recurrence

NASA Astrophysics Data System (ADS)

Frilot, Clifton; Kim, Paul Y.; Carrubba, Simona; McCarty, David E.; Chesson, Andrew L.; Marino, Andrew A.

Analysis of Brain Recurrence (ABR) is a method for extracting physiologically significant information from the electroencephalogram (EEG), a non-stationary electrical output of the brain, the ultimate complex dynamical system. ABR permits quantification of temporal patterns in the EEG produced by the non-autonomous differential laws that govern brain metabolism. In the context of appropriate experimental and statistical designs, ABR is ideally suited to the task of interpreting the EEG. Present applications of ABR include discovery of a human magnetic sense, increased mechanistic understanding of neuronal membrane processes, diagnosis of degenerative neurological disease, detection of changes in brain metabolism caused by weak environmental electromagnetic fields, objective characterization of the quality of human sleep, and evaluation of sleep disorders. ABR has important beneficial implications for the development of clinical and experimental neuroscience.

Human niche construction in interdisciplinary focus

PubMed Central

Kendal, Jeremy; Tehrani, Jamshid J.; Odling-Smee, John

2011-01-01

Niche construction is an endogenous causal process in evolution, reciprocal to the causal process of natural selection. It works by adding ecological inheritance, comprising the inheritance of natural selection pressures previously modified by niche construction, to genetic inheritance in evolution. Human niche construction modifies selection pressures in environments in ways that affect both human evolution, and the evolution of other species. Human ecological inheritance is exceptionally potent because it includes the social transmission and inheritance of cultural knowledge, and material culture. Human genetic inheritance in combination with human cultural inheritance thus provides a basis for gene–culture coevolution, and multivariate dynamics in cultural evolution. Niche construction theory potentially integrates the biological and social aspects of the human sciences. We elaborate on these processes, and provide brief introductions to each of the papers published in this theme issue. PMID:21320894

[Attention and aging].

PubMed

Siéroff, Eric; Piquard, Ambre

2004-12-01

Due to progress in the cognitive theories in the last twenty years, the description of attentional deficits associated with normal or pathological aging has substantially improved. In this article, attentional deficits are presented according to Posner theory, which describes three sub-systems in a global network of attention: vigilance, selective attention, command. This theory not only characterizes the functions of these subsystems, but gives precise indications about their anatomical and neurochemical substrates. Several clinical tests can be described for each of these different subsystems. The main attentional deficits are presented in the second part of this paper: if some decline of the attentional command occurs in normal aging, a real deficit in this subsystem is found in most degenerative processes (frontotemporal dementia, Alzheimer and Parkinson diseases). Alzheimer disease is also frequently associated with a deficit of selective spatial attention, early in the evolution of the disease.

[Public health conceptual models and paradigms].

PubMed

Hernández-Girón, Carlos; Orozco-Núñez, Emanuel; Arredondo-López, Armando

2012-01-01

The epidemiological transition model proposed by Omhran at the beginning of the 1970s (decreased fecundity rate and increased life expectancy), together with modifications in lifestyles and diet, showed increased mortality due to chronically degenerative causes. This essay thus discusses and makes a comparative analysis of some currents of thought, taking as its common thread an analysis of epidemiological change identified in different eras or stages and relationships with some public health models or conceptual frameworks. Discussing public health paradigms leads to a historical recapitulation of conceptual models ranging from magical-religious conceptions to ecological and socio-medical models. M. Susser proposed 3 eras in this discipline's evolution in his speech on the future of the epidemiology. The epidemiological changes analysed through different approaches constitute elements of analysis that all models discussed in this essay include to delimit the contributions and variables so determining them.

Myelination, oligodendrocytes, and serious mental illness.

PubMed

Haroutunian, V; Katsel, P; Roussos, P; Davis, K L; Altshuler, L L; Bartzokis, G

2014-11-01

Historically, the human brain has been conceptually segregated from the periphery and further dichotomized into gray matter (GM) and white matter (WM) based on the whitish appearance of the exceptionally high lipid content of the myelin sheaths encasing neuronal axons. These simplistic dichotomies were unfortunately extended to conceptually segregate neurons from glia, cognition from behavior, and have been codified in the separation of clinical and scientific fields into medicine, psychiatry, neurology, pathology, etc. The discrete classifications have helped obscure the importance of continual dynamic communication between all brain cell types (neurons, astrocytes, microglia, oligodendrocytes, and precursor (NG2) cells) as well as between brain and periphery through multiple signaling systems. The signaling systems range from neurotransmitters to insulin, angiotensin, and multiple kinases such a glycogen synthase kinase 3 (GSK-3) that together help integrate metabolism, inflammation, and myelination processes and orchestrate the development, plasticity, maintenance, and repair that continually optimize function of neural networks. A more comprehensive, evolution-based, systems biology approach that integrates brain, body, and environmental interactions may ultimately prove more fruitful in elucidating the complexities of human brain function. The historic focus on neurons/GM is rebalanced herein by highlighting the importance of a systems-level understanding of the interdependent age-related shifts in both central and peripheral homeostatic mechanisms that can lead to remarkably prevalent and devastating neuropsychiatric diseases. Herein we highlight the role of glia, especially the most recently evolved oligodendrocytes and the myelin they produce, in achieving and maintaining optimal brain function. The human brain undergoes exceptionally protracted and pervasive myelination (even throughout its GM) and can thus achieve and maintain the rapid conduction and synchronous timing of neural networks on which optimal function depends. The continuum of increasing myelin vulnerability resulting from the human brain's protracted myelination underlies underappreciated communalities between different disease phenotypes ranging from developmental ones such as schizophrenia (SZ) and bipolar disorder (BD) to degenerative ones such as Alzheimer's disease (AD). These shared vulnerabilities also expose significant yet underexplored opportunities for novel treatment and prevention approaches that have the potential to considerably reduce the tremendous burden of neuropsychiatric disease. © 2014 Wiley Periodicals, Inc.

Skulls and Human Evolution: The Use of Casts of Anthropoid Skulls in Teaching Concepts of Human Evolution.

ERIC Educational Resources Information Center

Gipps, John

1991-01-01

Proposes the use of a series of 11 casts of fossil skulls as a method of teaching about the theory of human evolution. Students explore the questions of which skulls are "human" and which came first in Homo Sapien development, large brain or upright stance. (MDH)

Concurrent Use of Lumbar Total Disc Arthroplasty and Anterior Lumbar Interbody Fusion: The Lumbar Hybrid Procedure for the Treatment of Multilevel Symptomatic Degenerative Disc Disease: A Prospective Study.

PubMed

Scott-Young, Matthew; McEntee, Laurence; Schram, Ben; Rathbone, Evelyne; Hing, Wayne; Nielsen, David

2018-01-15

A prospective study. The aim of this study was to evaluate clinical and patient outcomes post combined total disc arthroplasty (TDA) and anterior lumbar interbody fusion (ALIF), known as hybrid surgery for the treatment of multilevel symptomatic degenerative disc disease (DDD). Class I studies comparing the treatment of one-level lumbar DDD with TDA and ALIF have confirmed the effectiveness of those treatments through clinical and patient outcomes. Although the success of single-level disease is well documented, the evidence relating to the treatment of multilevel DDD with these modalities is emerging. With the evolution of the TDA technology, a combined approach to multilevel disease has developed in the form of the hybrid procedure. A total of 617 patients underwent hybrid surgery for chronic back pain between July 1998 and February 2012. Visual Analog Pain Scale for the back and leg were recorded along with the Oswestry Disability Index and Roland Morris Disability Questionnaire. Both statistically and clinically significant (p < 0.005) reductions were seen in back and leg pain, which were sustained for at least 8 years postsurgery. In addition, significant improvements (P < 0.001) in self-rated disability and function were also maintained for at least 8 years. Patient satisfaction was rated as good or excellent in >90% of cases. The results of this research indicate that improvements in both back and leg pain and function can be achieved using the hybrid lumbar reconstructive technique. 4.

American Muslim Undergraduates' Views on Evolution

ERIC Educational Resources Information Center

Fouad, Khadija Engelbrecht

2016-01-01

A qualitative investigation into American Muslim undergraduates' views on evolution revealed three main positions on evolution: theistic evolution, a belief in special creation of all species, and a belief in special creation of humans with evolution for all non-human species. One can conceive of the manner in which respondents chose their…

Survival, differentiation, and neuroprotective mechanisms of human stem cells complexed with neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo model of Parkinson's disease.

PubMed

Daviaud, Nicolas; Garbayo, Elisa; Sindji, Laurence; Martínez-Serrano, Alberto; Schiller, Paul C; Montero-Menei, Claudia N

2015-06-01

Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson's disease (PD). We recently reported the repair and functional recovery after treatment with human marrow-isolated adult multilineage inducible (MIAMI) cells adhered to neurotrophin-3 (NT3) releasing pharmacologically active microcarriers (PAMs) in hemiparkinsonian rats. In order to comprehend this effect, the goal of the present work was to elucidate the survival, differentiation, and neuroprotective mechanisms of MIAMI cells and human neural stem cells (NSCs), both adhering to NT3-releasing PAMs in an ex vivo organotypic model of nigrostriatal degeneration made from brain sagittal slices. It was shown that PAMs led to a marked increase in MIAMI cell survival and neuronal differentiation when releasing NT3. A significant neuroprotective effect of MIAMI cells adhering to PAMs was also demonstrated. NSCs barely had a neuroprotective effect and differentiated mostly into dopaminergic neuronal cells when adhering to PAM-NT3. Moreover, those cells were able to release dopamine in a sufficient amount to induce a return to baseline levels. Reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay analyses identified vascular endothelial growth factor (VEGF) and stanniocalcin-1 as potential mediators of the neuroprotective effect of MIAMI cells and NSCs, respectively. It was also shown that VEGF locally stimulated tissue vascularization, which might improve graft survival, without excluding a direct neuroprotective effect of VEGF on dopaminergic neurons. These results indicate a prospective interest of human NSC/PAM and MIAMI cell/PAM complexes in tissue engineering for PD. Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson's disease (PD). The present work elucidates and compares the survival, differentiation, and neuroprotective mechanisms of marrow-isolated adult multilineage inducible cells and human neural stem cells both adhered to neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo organotypic model of PD made from brain sagittal slices. ©AlphaMed Press.

Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia.

PubMed

Duncombe, Jessica; Kitamura, Akihiro; Hase, Yoshiki; Ihara, Masafumi; Kalaria, Raj N; Horsburgh, Karen

2017-10-01

Increasing evidence suggests that vascular risk factors contribute to neurodegeneration, cognitive impairment and dementia. While there is considerable overlap between features of vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD), it appears that cerebral hypoperfusion is the common underlying pathophysiological mechanism which is a major contributor to cognitive decline and degenerative processes leading to dementia. Sustained cerebral hypoperfusion is suggested to be the cause of white matter attenuation, a key feature common to both AD and dementia associated with cerebral small vessel disease (SVD). White matter changes increase the risk for stroke, dementia and disability. A major gap has been the lack of mechanistic insights into the evolution and progress of VCID. However, this gap is closing with the recent refinement of rodent models which replicate chronic cerebral hypoperfusion. In this review, we discuss the relevance and advantages of these models in elucidating the pathogenesis of VCID and explore the interplay between hypoperfusion and the deposition of amyloid β (Aβ) protein, as it relates to AD. We use examples of our recent investigations to illustrate the utility of the model in preclinical testing of candidate drugs and lifestyle factors. We propose that the use of such models is necessary for tackling the urgently needed translational gap from preclinical models to clinical treatments. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Evolution of life in urban environments.

PubMed

Johnson, Marc T J; Munshi-South, Jason

2017-11-03

Our planet is an increasingly urbanized landscape, with over half of the human population residing in cities. Despite advances in urban ecology, we do not adequately understand how urbanization affects the evolution of organisms, nor how this evolution may affect ecosystems and human health. Here, we review evidence for the effects of urbanization on the evolution of microbes, plants, and animals that inhabit cities. Urbanization affects adaptive and nonadaptive evolutionary processes that shape the genetic diversity within and between populations. Rapid adaptation has facilitated the success of some native species in urban areas, but it has also allowed human pests and disease to spread more rapidly. The nascent field of urban evolution brings together efforts to understand evolution in response to environmental change while developing new hypotheses concerning adaptation to urban infrastructure and human socioeconomic activity. The next generation of research on urban evolution will provide critical insight into the importance of evolution for sustainable interactions between humans and our city environments. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Mosaic evolution and the pattern of transitions in the hominin lineage

PubMed Central

Foley, Robert A.

2016-01-01

Humans are uniquely unique, in terms of the extreme differences between them and other living organisms, and the impact they are having on the biosphere. The evolution of humans can be seen, as has been proposed, as one of the major transitions in evolution, on a par with the origins of multicellular organisms or the eukaryotic cell (Maynard Smith & Szathmáry 1997 Major transitions in evolution). Major transitions require the evolution of greater complexity and the emergence of new evolutionary levels or processes. Does human evolution meet these conditions? I explore the diversity of evidence on the nature of transitions in human evolution. Four levels of transition are proposed—baseline, novel taxa, novel adaptive zones and major transitions—and the pattern of human evolution considered in the light of these. The primary conclusions are that changes in human evolution occur continuously and cumulatively; that novel taxa and the appearance of new adaptations are not clustered very tightly in particular periods, although there are three broad transitional phases (Pliocene, Plio-Pleistocene and later Quaternary). Each phase is distinctive, with the first based on ranging and energetics, the second on technology and niche expansion, and the third on cognition and cultural processes. I discuss whether this constitutes a ‘major transition’ in the context of the evolutionary processes more broadly; the role of behaviour in evolution; and the opportunity provided by the rich genetic, phenotypic (fossil morphology) and behavioural (archaeological) record to examine in detail major transitions and the microevolutionary patterns underlying macroevolutionary change. It is suggested that the evolution of the hominin lineage is consistent with a mosaic pattern of change. This article is part of the themed issue ‘Major transitions in human evolution’. PMID:27298474

Diabetic neuropathy: electrophysiological and morphological study of peripheral nerve degeneration and regeneration in transgenic mice that express IFNbeta in beta cells.

PubMed

Serafín, Anna; Molín, Jessica; Márquez, Merce; Blasco, Ester; Vidal, Enric; Foradada, Laia; Añor, Sonia; Rabanal, Rosa M; Fondevila, Dolors; Bosch, Fàtima; Pumarola, Martí

2010-05-01

Diabetic neuropathy is one of the most frequent complications in diabetes but there are no treatments beyond glucose control, due in part to the lack of an appropriate animal model to assess an effective therapy. This study was undertaken to characterize the degenerative and regenerative responses of peripheral nerves after induced sciatic nerve damage in transgenic rat insulin I promoter / human interferon beta (RIP/IFNbeta) mice made diabetic with a low dose of streptozotocin (STZ) as an animal model of diabetic complications. In vivo, histological and immunohistological studies of cutaneous and sciatic nerves were performed after left sciatic crush. Functional tests, cutaneous innervation, and sciatic nerve evaluation showed pronounced neurological reduction in all groups 2 weeks after crush. All animals showed a gradual recovery but this was markedly slower in diabetic animals in comparison with normoglycemic animals. The delay in regeneration in diabetic RIP/IFNbeta mice resulted in an increase in active Schwann cells and regenerating neurites 8 weeks after surgery. These findings indicate that diabetic-RIP/IFNbeta animals mimic human diabetic neuropathy. Moreover, when these animals are submitted to nerve crush they have substantial deficits in nerve regrowth, similar to that observed in diabetic patients. When wildtype animals were treated with the same dose of STZ, no differences were observed with respect to nontreated animals, indicating that low doses of STZ and the transgene are not implicated in development of the degenerative and regenerative events observed in our study. All these findings indicate that RIP/IFNbeta transgenic mice are a good model for diabetic neuropathy.

Teaching Early Braille Literacy Skills within a Stimulus Equivalence Paradigm to Children with Degenerative Visual Impairments

ERIC Educational Resources Information Center

Toussaint, Karen A.; Tiger, Jeffrey H.

2010-01-01

Despite the need for braille literacy, there has been little attempt to systematically evaluate braille-instruction programs. The current study evaluated an instructive procedure for teaching early braille-reading skills with 4 school-aged children with degenerative visual impairments. Following a series of pretests, braille instruction involved…

The development of biomarkers for degenerative musculoskeletal conditions.

PubMed

Jayabalan, Prakash; Sowa, Gwendolyn A

2014-02-01

With an aging population, degenerative musculoskeletal conditions will become more prevalent with significantly increasing costs to society over the next several decades. The majority of these conditions are diagnosed radiographically, at which point the disease process is often more advanced and challenging to treat. The commonly available radiographic studies also do not adequately provide information as to the exact pain generator and findings often do not correlate either to patient symptoms or function. Personalized medicine involves formulating treatments based on a patient's own biology. The development of biological markers (biomarkers) pertaining to disease is a rapidly growing area within this field of medicine. For degenerative musculoskeletal conditions, biomarkers have the potential to provide an early non-invasive method of assessing the location and severity of tissue damage and presence of inflammation. By outlining mechanisms of disease they could allow the formulation of further treatment targets and through sub-categorizing patients into different groups based on their biomarker profile, one could provide more efficacious treatments for patients. The present article is a review of the development of biomarkers for these purposes specifically as they pertain to degenerative musculoskeletal conditions.

Two Dimensional Finite Element Analysis for the Effect of a Pressure Wave in the Human Brain

NASA Astrophysics Data System (ADS)

Ponce L., Ernesto; Ponce S., Daniel

2008-11-01

Brain injuries in people of all ages is a serious, world-wide health problem, with consequences as varied as attention or memory deficits, difficulties in problem-solving, aggressive social behavior, and neuro degenerative diseases such as Alzheimer's and Parkinson's. Brain injuries can be the result of a direct impact, but also pressure waves and direct impulses. The aim of this work is to develop a predictive method to calculate the stress generated in the human brain by pressure waves such as high power sounds. The finite element method is used, combined with elastic wave theory. The predictions of the generated stress levels are compared with the resistance of the arterioles that pervade the brain. The problem was focused to the Chilean mining where there are some accidents happen by detonations and high sound level. There are not formal medical investigation, however these pressure waves could produce human brain damage.

Stem cells in degenerative orthopaedic pathologies: effects of aging on therapeutic potential.

PubMed

Atesok, Kivanc; Fu, Freddie H; Sekiya, Ichiro; Stolzing, Alexandra; Ochi, Mitsuo; Rodeo, Scott A

2017-02-01

The purpose of this study was to summarize the current evidence on the use of stem cells in the elderly population with degenerative orthopaedic pathologies and to highlight the pathophysiologic mechanisms behind today's therapeutic challenges in stem cell-based regeneration of destructed tissues in the elderly patients with osteoarthritis (OA), degenerative disc disease (DDD), and tendinopathies. Clinical and basic science studies that report the use of stem cells in the elderly patients with OA, DDD, and tendinopathies were identified using a PubMed search. The studies published in English have been assessed, and the best and most recent evidence was included in the current study. Evidence suggests that, although short-term results regarding the effects of stem cell therapy in degenerative orthopaedic pathologies can be promising, stem cell therapies do not appear to reverse age-related tissue degeneration. Causes of suboptimal outcomes can be attributed to the decrease in the therapeutic potential of aged stem cell populations and the regenerative capacity of these cells, which might be negatively influenced in an aged microenvironment within the degenerated tissues of elderly patients with OA, DDD, and tendinopathies. Clinical protocols guiding the use of stem cells in the elderly patient population are still under development, and high-level randomized controlled trials with long-term outcomes are lacking. Understanding the consequences of age-related changes in stem cell function and responsiveness of the in vivo microenvironment to stem cells is critical when designing cell-based therapies for elderly patients with degenerative orthopaedic pathologies.

Restoring Segmental Biomechanics Through Nucleus Augmentation: An In Vitro Study.

PubMed

Pelletier, Matthew H; Cohen, Charles S; Ducheyne, Paul; Walsh, William R

2016-12-01

In vitro biomechanical laboratory study. The purpose of this study is to evaluate a mechanical treatment to create a degenerative motion segment and the ability of nucleus augmentation to restore biomechanics. In cases with an intact annulus fibrosus, the replacement or augmentation of the nucleus pulposus alone may provide a less invasive option to restore normal biomechanics and disk height when compared with spinal fusion or total disk replacement. Laboratory testing allows these changes to be fully characterized. However, without preexisting pathology, nucleus augmentation therapies are difficult to evaluate in vitro. The present study evaluated pure moment bending and compressive biomechanics in 3 states (n=6): (1) intact, (2) after creep loading and nucleus disruption to induce degenerative biomechanical changes, and (3) after nucleus augmentation through an injectable polymer (DiscCell). Neutral zone and ROM were increased in all modes of bending after the degenerative treatment. The most sensitive mode of bending was lateral bending, with intact ROM (20.0±2.9 degrees) increased to 22.3±2.6 degrees after degenerative treatment and reduced to 18.4±1.6 degrees after injection of the polymer. All bending ROM and NZ changes induced by the degenerative treatment were reversed by nucleus augmentation. This material was shown to be effective at altering motion segment biomechanics and restoring disk height during time zero tests. This technique may provide a model to examine the time zero performance of a nucleus augmentation device/material.

Correlation between degenerative spine disease and bone marrow density: a retrospective investigation.

PubMed

Grams, Astrid Ellen; Rehwald, Rafael; Bartsch, Alexander; Honold, Sarah; Freyschlag, Christian Franz; Knoflach, Michael; Gizewski, Elke Ruth; Glodny, Bernhard

2016-02-24

Spondylosis leads to an overestimation of bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA) but not with quantitative computed tomography (QCT). The correlation between degenerative changes of the spine and QCT-BMD was therefore investigated for the first time. One hundred thirty-four patients (66 female and 68 male) with a mean age of 49.0 ± 14.6 years (range: 19-88 years) who received a CT scan and QCT-BMD measurements of spine and hip were evaluated retrospectively. The occurrence and severity of spondylosis, osteochondrosis, and spondylarthrosis and the height of the vertebral bodies were assessed. A negative correlation was found between spinal BMD and number of spondylophytes (ρ = -0.35; p < 0.01), disc heights (r = -0.33; p < 0.01), number of discal air inclusions (ρ = -0.34; p < 0.01), the number of Schmorl nodules (ρ = -0.25; p < 0.01), the number (ρ = -0.219; p < 0.05) and the degree (ρ = -0.220; p < 0.05) of spondylarthrosis. Spinal and hip BMD correlated moderately, but the latter did not correlate with degenerative changes of the spine. In linear regression models age, osteochondrosis and spondylarthrosis were factors influencing spinal BMD. Degenerative spinal changes may be associated with reduced regional spinal mineralization. This knowledge could lead to a modification of treatment of degenerative spine disease with early treatment of osteopenia to prevent secondary fractures.

Human Origins: Problems in the Interpretation of New Evidence. Third Edition. AAAS Study Guides on Contemporary Problems.

ERIC Educational Resources Information Center

Almquist, Alan J.; Cronin, John E.

This Chautauqua-type short course in human evolution is divided into two parts: The Biochemical Evidence for Human Evolution, and the Fossil Evidence for Human Evolution. The first part covers the comparison of macromolecular differences between species. This includes comparison of DNA base-ratios and amino acid substitution in enzymes and other…

Reticulate evolution and the human past: an anthropological perspective.

PubMed

Winder, Isabelle C; Winder, Nick P

2014-01-01

The evidence is mounting that reticulate (web-like) evolution has shaped the biological histories of many macroscopic plants and animals, including non-human primates closely related to Homo sapiens, but the implications of this non-hierarchical evolution for anthropological enquiry are not yet fully understood. When they are understood, the result may be a paradigm shift in evolutionary anthropology. This paper reviews the evidence for reticulated evolution in the non-human primates and human lineage. Then it makes the case for extrapolating this sort of patterning to Homo sapiens and other hominins and explores the implications this would have for research design, method and understandings of evolution in anthropology. Reticulation was significant in human evolutionary history and continues to influence societies today. Anthropologists and human scientists-whether working on ancient or modern populations-thus need to consider the implications of non-hierarchic evolution, particularly where molecular clocks, mathematical models and simplifying assumptions about evolutionary processes are used. This is not just a problem for palaeoanthropology. The simple fact of different mating systems among modern human groups, for example, may demand that more attention is paid to the potential for complexity in human genetic and cultural histories.

The Effects of Anti-Dementia and Nootropic Treatments on the Mortality of Patients with Dementia: A Population-Based Cohort Study in Taiwan.

PubMed

Wu, Chen-Yi; Hu, Hsiao-Yun; Chow, Lok-Hi; Chou, Yiing-Jenq; Huang, Nicole; Wang, Pei-Ning; Li, Chung-Pin

2015-01-01

Few studies have examined the contribution of treatment on the mortality of dementia based on a population-based study. To investigate the effects of anti-dementia and nootropic treatments on the mortality of dementia using a population-based cohort study. 12,193 incident dementia patients were found from 2000 to 2010. Their data were compared with 12,193 age- and sex-matched non-dementia controls that were randomly selected from the same database. Dementia was classified into vascular (VaD) and degenerative dementia. Mortality incidence and hazard ratios (HRs) were calculated. The median survival time was 3.39 years (95% confidence interval [CI]: 2.88-3.79) for VaD without medication, 6.62 years (95% CI: 6.24-7.21) for VaD with nootropics, 3.01 years (95% CI: 2.85-3.21) for degenerative dementia without medication, 8.11 years (95% CI: 6.30-8.55) for degenerative dementia with anti-dementia medication, 6.00 years (95% CI: 5.73-6.17) for degenerative dementia with nootropics, and 9.03 years (95% CI: 8.02-9.87) for degenerative dementia with both anti-dementia and nootropic medications. Compared to the non-dementia group, the HRs among individuals with degenerative dementia were 2.69 (95% CI: 2.55-2.83) without medication, 1.46 (95% CI: 1.39-1.54) with nootropics, 1.05 (95% CI: 0.82-1.34) with anti-dementia medication, and 0.92 (95% CI: 0.80-1.05) with both nootropic and anti-dementia medications. VaD with nootropics had a lower mortality (HR: 1.25, 95% CI: 1.15-1.37) than VaD without medication (HR: 2.46, 95% CI: 2.22-2.72). Pharmacological treatments have beneficial effects for patients with dementia in prolonging their survival.

A 20-Year Prospective Longitudinal Study of Degeneration of the Cervical Spine in a Volunteer Cohort Assessed Using MRI: Follow-up of a Cross-Sectional Study.

PubMed

Daimon, Kenshi; Fujiwara, Hirokazu; Nishiwaki, Yuji; Okada, Eijiro; Nojiri, Kenya; Watanabe, Masahiko; Katoh, Hiroyuki; Shimizu, Kentaro; Ishihama, Hiroko; Fujita, Nobuyuki; Tsuji, Takashi; Nakamura, Masaya; Matsumoto, Morio; Watanabe, Kota

2018-05-16

Few studies have addressed in detail long-term degenerative changes in the cervical spine. In this study, we evaluated the progression of degenerative changes of the cervical spine that occurred over a 20-year period in an originally healthy cohort. We also sought to clarify the relationship between the progression of cervical degenerative changes and the development of clinical symptoms. For this prospective follow-up investigation, we recruited 193 subjects from an original cohort of 497 participants who had undergone magnetic resonance imaging (MRI) of the cervical spine between 1993 and 1996. The subjects were asked about the presence or absence of cervical spine-related symptoms. Degenerative changes of the cervical spine were assessed on MRI using an original numerical grading system. The relationship between the progression of degenerative changes and the onset of clinical symptoms was evaluated by logistic regression analysis. Degeneration in the cervical spine was found to have progressed in 95% of the subjects during the 20-year period. The finding of a decrease in signal intensity of the intervertebral disc progressed in a relatively high proportion of the subjects in all age groups and occurred with similar frequency (around 60%) at all intervertebral disc levels. The rate of progression of other structural failures on MRI increased with age and was highest at C5-C6. The progression of foraminal stenosis was associated with the onset of upper-limb pain (odds ratio, 4.71 [95% confidence interval, 1.02 to 21.7]). A progression of degenerative changes in the cervical spine on MRI over the 20-year period was detected in nearly all subjects. There was no relationship between the progression of degeneration on MRI and the development of clinical symptoms, with the exception of an association found between foraminal stenosis and upper-limb pain. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The change in the diffusion of water in normal and degenerative lumbar intervertebral discs following joint mobilization compared to prone lying.

PubMed

Beattie, Paul F; Donley, Jonathan W; Arnot, Cathy F; Miller, Ronald

2009-01-01

Prospective, repeated measures obtained under treatment and control conditions. The purposes of this study were to provide preliminary evidence regarding the immediate change in the diffusion of water in the nuclear region of normal and degenerative lumbar intervertebral discs (IVDs) following a single session of lumbar joint mobilization, and to compare these findings to the immediate change in the diffusion of water following a 10-minute session of prone lying. There is conflicting evidence regarding the effectiveness and efficacy of lumbar joint mobilization. Increased knowledge of the physiologic effects of lumbar joint mobilization can lead to refinement of its clinical application. A total of 24 people (15 males and 9 females), ranging in age from 22 to 58 years, participated in this study. All subjects had a history of activity-limiting low back pain. Diffusion-weighted magnetic resonance images (DW-MRIs) were obtained immediately before and after a 10-minute session of lumbar joint mobilization. At least 1 month later, a second session was performed in which DW-MRIs were obtained immediately before and after a 10-minute session of prone lying. Following lumbar joint mobilization, a significant increase (P = .002) in the mean values for diffusion of water was observed within degenerative IVDs at L5-S1 (22.2% increase; effect size, 0.97). Degenerative IVDs at L1-2 to L4-5 and normal IVDs at L1-2 to L5-S1 did not demonstrate a change in diffusion following joint mobilization. Prone lying was not associated with a change in diffusion for normal or degenerative IVDs. The stimulus provided by lumbar joint mobilization may influence the diffusion of water in degenerative IVDs at L5-S1; however, these are preliminary findings and the relationship of these findings to pain and function needs further investigation.

The Effects of Anti-Dementia and Nootropic Treatments on the Mortality of Patients with Dementia: A Population-Based Cohort Study in Taiwan

PubMed Central

Wu, Chen-Yi; Hu, Hsiao-Yun; Chow, Lok-Hi; Chou, Yiing-Jenq; Huang, Nicole; Wang, Pei-Ning; Li, Chung-Pin

2015-01-01

Background Few studies have examined the contribution of treatment on the mortality of dementia based on a population-based study. Objective To investigate the effects of anti-dementia and nootropic treatments on the mortality of dementia using a population-based cohort study. Methods 12,193 incident dementia patients were found from 2000 to 2010. Their data were compared with 12,193 age- and sex-matched non-dementia controls that were randomly selected from the same database. Dementia was classified into vascular (VaD) and degenerative dementia. Mortality incidence and hazard ratios (HRs) were calculated. Results The median survival time was 3.39 years (95% confidence interval [CI]: 2.88–3.79) for VaD without medication, 6.62 years (95% CI: 6.24–7.21) for VaD with nootropics, 3.01 years (95% CI: 2.85–3.21) for degenerative dementia without medication, 8.11 years (95% CI: 6.30–8.55) for degenerative dementia with anti-dementia medication, 6.00 years (95% CI: 5.73–6.17) for degenerative dementia with nootropics, and 9.03 years (95% CI: 8.02–9.87) for degenerative dementia with both anti-dementia and nootropic medications. Compared to the non-dementia group, the HRs among individuals with degenerative dementia were 2.69 (95% CI: 2.55–2.83) without medication, 1.46 (95% CI: 1.39–1.54) with nootropics, 1.05 (95% CI: 0.82–1.34) with anti-dementia medication, and 0.92 (95% CI: 0.80–1.05) with both nootropic and anti-dementia medications. VaD with nootropics had a lower mortality (HR: 1.25, 95% CI: 1.15–1.37) than VaD without medication (HR: 2.46, 95% CI: 2.22–2.72). Conclusion Pharmacological treatments have beneficial effects for patients with dementia in prolonging their survival. PMID:26098910

Descriptive analysis of spinal neuroaxial injections, surgical interventions and physical therapy utilization for degenerative lumbar spondylolisthesis within Medicare beneficiaries from 2000–2011

PubMed Central

Sclafani, Joseph A.; Constantin, Alexandra; Ho, Pei-Shu; Akuthota, Venu; Chan, Leighton

2016-01-01

Study Design Retrospective, observational study. Objective To determine the utilization of various treatment modalities in the management of degenerative spondylolisthesis within Medicare beneficiaries. Summary of Background Data Degenerative lumbar spondylolisthesis is a condition often identified in symptomatic low back pain. A variety of treatment algorithms including physical therapy and interventional techniques can be used to manage clinically significant degenerative spondylolisthesis. Methods This study utilized the 5% national sample of Medicare carrier claims from 2000 through 2011. A cohort of beneficiaries with a new ICD-9 diagnosis code for degenerative lumbar spondylolisthesis was identified. Current procedural terminology codes were used to identify the number of procedures performed each year by specialty on this cohort. Results A total of 95,647 individuals were included in the analysis. Average age at the time of initial diagnosis was 72.8 ± 9.8 years. Within this study cohort, spondylolisthesis was more prevalent in females (69%) than males and in Caucasians (88%) compared to other racial demographics. Over 40% of beneficiaries underwent at least one injection, approximately one third (37%) participated in physical therapy, one in five (22%) underwent spinal surgery, and one third (36%) did not utilize any of these interventions. Greater than half of all procedures (124,280/216,088) occurred within 2 years of diagnosis. The ratio of focal interventions (transforaminal and facet interventions) to less selective (interlaminar) procedures was greater for the specialty of Physical Medicine and Rehabilitation compared to the specialties of Anesthesiology, Interventional Radiology, Neurosurgery, and Orthopedic Surgery. The majority of physical therapy was dedicated to passive treatment modalities and range of motion exercises rather than active strengthening modalities within this cohort. Conclusion Interventional techniques and physical therapy are frequently used treatment modalities for symptomatic degenerative spondylolisthesis. Understanding utilization of these techniques is important to determine relative clinical efficacies and to optimize future health care expenditures. PMID:28207664

Comparison of 368 patients undergoing surgery for lumbar degenerative spondylolisthesis from the SPORT trial with 955 from the NSQIP database.

PubMed

Golinvaux, Nicholas S; Basques, Bryce A; Bohl, Daniel D; Yacob, Alem; Grauer, Jonathan N

2015-03-01

Retrospective cohort. To compare demographics and perioperative outcomes between the Spine Patient Outcomes Research Trial (SPORT) lumbar degenerative spondylolisthesis arm and a similar population from the National Surgical Quality Improvement Program (NSQIP) database. SPORT is a well-known surgical trial that investigated the benefits of surgical versus nonsurgical treatment in patients with various lumbar pathologies. However, the external validity of SPORT demographics and outcomes has not been fully established. Surgical degenerative spondylolisthesis cases were identified from NSQIP between 2010 and 2012. This population was then compared with the SPORT degenerative spondylolisthesis study. These comparisons were based on published data from SPORT and included analyses of demographics, perioperative factors, and complications. The 368 surgical patients with degenerative spondylolisthesis in SPORT were compared with 955 patients identified in NSQIP. Demographic comparisons were as follows: average age and race (no difference; P > 0.05 for each), sex (9.1% more female patients in SPORT; P = 0.002), smoking status (6.6% more smokers in NSQIP; P = 0.002), and average body mass index (1.1 kg/m greater in NSQIP; P = 0.005). Larger differences were noted in what surgical procedure was performed (P < 0.001), with the most notable difference being that the NSQIP population was much more likely to include interbody fusion than the SPORT population (52.4% vs. 12.5%). Most perioperative factors and complication rates were similar, including average operative time, wound infection, wound dehiscence, postoperative transfusion, and postoperative mortality (no differences; P > 0.05 for each). Average length of stay was shorter in NSQIP compared with SPORT (3.7 vs. 5.8 d; P = 0.042). Though important differences in the distribution of surgical procedures were identified, this study supports the greater generalizability of the surgical SPORT degenerative spondylolisthesis study based on similar demographics and perioperative outcomes when compared with patients from the NSQIP database. 3.

Genome-Wide Identification of Regulatory Sequences Undergoing Accelerated Evolution in the Human Genome

PubMed Central

Dong, Xinran; Wang, Xiao; Zhang, Feng; Tian, Weidong

2016-01-01

Accelerated evolution of regulatory sequence can alter the expression pattern of target genes, and cause phenotypic changes. In this study, we used DNase I hypersensitive sites (DHSs) to annotate putative regulatory sequences in the human genome, and conducted a genome-wide analysis of the effects of accelerated evolution on regulatory sequences. Working under the assumption that local ancient repeat elements of DHSs are under neutral evolution, we discovered that ∼0.44% of DHSs are under accelerated evolution (ace-DHSs). We found that ace-DHSs tend to be more active than background DHSs, and are strongly associated with epigenetic marks of active transcription. The target genes of ace-DHSs are significantly enriched in neuron-related functions, and their expression levels are positively selected in the human brain. Thus, these lines of evidences strongly suggest that accelerated evolution on regulatory sequences plays important role in the evolution of human-specific phenotypes. PMID:27401230

Surgical outcomes of degenerative spondylolisthesis with L5-S1 disc degeneration: comparison between lumbar floating fusion and lumbosacral fusion at a minimum 5-year follow-up.

PubMed

Liao, Jen-Chung; Chen, Wen-Jer; Chen, Lih-Hui; Niu, Chi-Chien; Keorochana, Gun

2011-09-01

A retrospective clinical and radiographic study was performed. The purpose of this study was to compare outcomes of patients with degenerative spondylolisthesis and a preexisting degenerative L5-S1 disc treated with a lumbar floating fusion (LFF) versus lumbosacral fusion (LSF). Fusion for treatment of degenerative spondylolisthesis often ends at the L5 level. These patients usually had a preexisting L5-S1 disc degeneration; however, no literature mentions the role of prophylactic LSF in degenerative spondylolisthesis associated with L5-S1 disc degeneration. A total of 107 patients with a minimum 5-year follow-up who had lumbosacral or LFF with pedicle instrumentation for degenerative spondylolisthesis were included. UCLA (University of California, Los Angeles) classification was used to evaluate the radiographic results of the L5-S1 segment. The Oswestry Disability Index (ODI) and modified Brodsky's criteria were used to evaluate patients' clinical results. The incidence of adjacent segment disease (ASD) (includes radiographic and clinical ASD) of both ends was recorded. There were no statistically significant differences in sex, age distribution, or amount of follow-up between the LFF and LSF groups. The LSF group had a higher percentage of patients that underwent total L5 laminectomy with loss of L5-S1 posterior ligament integrity (LSF = 92% vs. LFF = 67%, P = 0.019). The higher incidence of cephalic ASD in the LSF group was statistically significant (LSF = 25% vs. LFF = 9.7%, P = 0.049). Although no patient in the LSF group developed L5-S1 ASD, need for L5-S1 segment revision surgery was not prevented with LSF. Clinical outcomes on the basis of the success rate (LFF = 85.5% vs.LSF = 70.8%, P = 0.103) and ODI difference (LFF = 28.97 ± 15.82 vs. LSF = 23.04 ± 10.97, P = 0.109), there were no statistically significant difference between these two groups. Posterior instrumentation with posterolateral LFF for the treatment of degenerative spondylolisthesis with concomitant L5-S1 disc degeneration results in a high percentage of satisfactory clinical results. Extended fusion to the sacrum did not provide a better clinical result. LSF could not reduce the incidence of revision surgery at the L5-S1 segment and involved greater incidence of cephalic ASD.

Genome-Wide Identification of Regulatory Sequences Undergoing Accelerated Evolution in the Human Genome.

PubMed

Dong, Xinran; Wang, Xiao; Zhang, Feng; Tian, Weidong

2016-10-01

Accelerated evolution of regulatory sequence can alter the expression pattern of target genes, and cause phenotypic changes. In this study, we used DNase I hypersensitive sites (DHSs) to annotate putative regulatory sequences in the human genome, and conducted a genome-wide analysis of the effects of accelerated evolution on regulatory sequences. Working under the assumption that local ancient repeat elements of DHSs are under neutral evolution, we discovered that ∼0.44% of DHSs are under accelerated evolution (ace-DHSs). We found that ace-DHSs tend to be more active than background DHSs, and are strongly associated with epigenetic marks of active transcription. The target genes of ace-DHSs are significantly enriched in neuron-related functions, and their expression levels are positively selected in the human brain. Thus, these lines of evidences strongly suggest that accelerated evolution on regulatory sequences plays important role in the evolution of human-specific phenotypes. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Causes of metabolic syndrome and obesity-related co-morbidities Part 1: A composite unifying theory review of human-specific co-adaptations to brain energy consumption

PubMed Central

2014-01-01

One line summary Metabolic syndrome and obesity-related co-morbidities are largely explained by co-adaptations to the energy use of the large human brain in the cortico-limbic-striatal and NRF2 systems. The medical, research and general community is unable to effect significantly decreased rates of central obesity and related type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer. All conditions seem to be linked by the concept of the metabolic syndrome (MetS), but the underlying causes are not known. MetS markers may have been mistaken for causes, thus many treatments are destined to be suboptimal. The current paper aims to critique current paradigms, give explanations for their persistence, and to return to first principles in an attempt to determine and clarify likely causes of MetS and obesity related comorbidities. A wide literature has been mined, study concepts analysed and the basics of human evolution and new biochemistry reviewed. A plausible, multifaceted composite unifying theory is formulated. The basis of the theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A ‘dual system’ is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals, becoming highly energy efficient in humans. The still-evolving, complex human cortico-limbic-striatal system generates strong behavioural drives for energy dense food procurement, including motivating agricultural technologies and social system development. Addiction to such foods, leading to neglect of nutritious but less appetizing ‘common or garden’ food, appears to have occurred. Insufficient consumption of food micronutrients prevents optimal human NRF2 function. Inefficient oxidation of excess energy forces central and non-adipose cells to store excess toxic lipid. Oxidative stress and metabolic inflammation, or metaflammation, allow susceptibility to infectious, degenerative atherosclerotic cardiovascular, autoimmune, neurodegenerative and dysplastic diseases. Other relevant human-specific co-adaptations are examined, and encompass the unusual ability to store fat, certain vitamin pathways, the generalised but flexible intestine and microbiota, and slow development and longevity. This theory has significant past and future corollaries, which are explored in a separate article by McGill, A-T, in Archives of Public Health, 72: 31. PMID:25708524

Regional selection of the brain size regulating gene CASC5 provides new insight into human brain evolution.

PubMed

Shi, Lei; Hu, Enzhi; Wang, Zhenbo; Liu, Jiewei; Li, Jin; Li, Ming; Chen, Hua; Yu, Chunshui; Jiang, Tianzi; Su, Bing

2017-02-01

Human evolution is marked by a continued enlargement of the brain. Previous studies on human brain evolution focused on identifying sequence divergences of brain size regulating genes between humans and nonhuman primates. However, the evolutionary pattern of the brain size regulating genes during recent human evolution is largely unknown. We conducted a comprehensive analysis of the brain size regulating gene CASC5 and found that in recent human evolution, CASC5 has accumulated many modern human specific amino acid changes, including two fixed changes and six polymorphic changes. Among human populations, 4 of the 6 amino acid polymorphic sites have high frequencies of derived alleles in East Asians, but are rare in Europeans and Africans. We proved that this between-population allelic divergence was caused by regional Darwinian positive selection in East Asians. Further analysis of brain image data of Han Chinese showed significant associations of the amino acid polymorphic sites with gray matter volume. Hence, CASC5 may contribute to the morphological and structural changes of the human brain during recent evolution. The observed between-population divergence of CASC5 variants was driven by natural selection that tends to favor a larger gray matter volume in East Asians.

Rapid evolution of the cerebellum in humans and other great apes.

PubMed

Barton, Robert A; Venditti, Chris

2014-10-20

Humans' unique cognitive abilities are usually attributed to a greatly expanded neocortex, which has been described as "the crowning achievement of evolution and the biological substrate of human mental prowess". The human cerebellum, however, contains four times more neurons than the neocortex and is attracting increasing attention for its wide range of cognitive functions. Using a method for detecting evolutionary rate changes along the branches of phylogenetic trees, we show that the cerebellum underwent rapid size increase throughout the evolution of apes, including humans, expanding significantly faster than predicted by the change in neocortex size. As a result, humans and other apes deviated significantly from the general evolutionary trend for neocortex and cerebellum to change in tandem, having significantly larger cerebella relative to neocortex size than other anthropoid primates. These results suggest that cerebellar specialization was a far more important component of human brain evolution than hitherto recognized and that technical intelligence was likely to have been at least as important as social intelligence in human cognitive evolution. Given the role of the cerebellum in sensory-motor control and in learning complex action sequences, cerebellar specialization is likely to have underpinned the evolution of humans' advanced technological capacities, which in turn may have been a preadaptation for language. Copyright © 2014 Elsevier Ltd. All rights reserved.

Recent advances in understanding the role of nutrition in human genome evolution.

PubMed

Ye, Kaixiong; Gu, Zhenglong

2011-11-01

Dietary transitions in human history have been suggested to play important roles in the evolution of mankind. Genetic variations caused by adaptation to diet during human evolution could have important health consequences in current society. The advance of sequencing technologies and the rapid accumulation of genome information provide an unprecedented opportunity to comprehensively characterize genetic variations in human populations and unravel the genetic basis of human evolution. Series of selection detection methods, based on various theoretical models and exploiting different aspects of selection signatures, have been developed. Their applications at the species and population levels have respectively led to the identification of human specific selection events that distinguish human from nonhuman primates and local adaptation events that contribute to human diversity. Scrutiny of candidate genes has revealed paradigms of adaptations to specific nutritional components and genome-wide selection scans have verified the prevalence of diet-related selection events and provided many more candidates awaiting further investigation. Understanding the role of diet in human evolution is fundamental for the development of evidence-based, genome-informed nutritional practices in the era of personal genomics.

Induced pluripotent stem cells as custom therapeutics for retinal repair: progress and rationale.

PubMed

Wright, Lynda S; Phillips, M Joseph; Pinilla, Isabel; Hei, Derek; Gamm, David M

2014-06-01

Human pluripotent stem cells have made a remarkable impact on science, technology and medicine by providing a potentially unlimited source of human cells for basic research and clinical applications. In recent years, knowledge gained from the study of human embryonic stem cells and mammalian somatic cell reprogramming has led to the routine production of human induced pluripotent stem cells (hiPSCs) in laboratories worldwide. hiPSCs show promise for use in transplantation, high throughput drug screening, "disease-in-a-dish" modeling, disease gene discovery, and gene therapy testing. This review will focus on the first application, beginning with a discussion of methods for producing retinal lineage cells that are lost in inherited and acquired forms of retinal degenerative disease. The selection of appropriate hiPSC-derived donor cell type(s) for transplantation will be discussed, as will the caveats and prerequisite steps to formulating a clinical Good Manufacturing Practice (cGMP) product for clinical trials. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Induced pluripotent stem cells as custom therapeutics for retinal repair: Progress and rationale

PubMed Central

Wright, Lynda S.; Phillips, M. Joseph; Pinilla, Isabel; Hei, Derek; Gamm, David M.

2014-01-01

Human pluripotent stem cells have made a remarkable impact on science, technology and medicine by providing a potentially unlimited source of human cells for basic research and clinical applications. In recent years, knowledge gained from the study of human embryonic stem cells and mammalian somatic cell reprogramming has led to the routine production of human induced pluripotent stem cells (hiPSCs) in laboratories worldwide. hiPSCs show promise for use in transplantation, high throughput drug screening, “disease-in-a-dish” modeling, disease gene discovery, and gene therapy testing. This review will focus on the first application, beginning with a discussion of methods for producing retinal lineage cells that are lost in inherited and acquired forms of retinal degenerative disease. The selection of appropriate hiPSC-derived donor cell type(s) for transplantation will be discussed, as will the caveats and prerequisite steps to formulating a clinical Good Manufacturing Practice (cGMP) product for clinical trials. PMID:24534198

Progeroid syndromes: models for stem cell aging?

PubMed

Bellantuono, I; Sanguinetti, G; Keith, W N

2012-02-01

Stem cells are responsible for tissue repair and maintenance and it is assumed that changes observed in the stem cell compartment with age underlie the concomitant decline in tissue function. Studies in murine models have highlighted the importance of intrinsic changes occurring in stem cells with age. They have also drawn the attention to other factors, such as changes in the local or systemic environment as the primary cause of stem cell dysfunction. Whilst knowledge in murine models has been advancing rapidly there has been little translation of these data to human aging. This is most likely due to the difficulties of testing the regenerative capacity of human stem cells in vivo and to substantial differences in the aging phenotype within humans. Here we summarize evidence to show how progeroid syndromes, integrated with other models, can be valuable tools in addressing questions about the role of stem cell aging in human degenerative diseases of older age and the molecular pathways involved.

Inherited Retinal Degenerative Disease Clinical Trial Network

DTIC Science & Technology

2012-10-01

strategies can be designed , tested and adopted as standard care. 2 While repeat evaluation and study of affected patients are vital to rigorously...following document is a summary of our experience and research in testing retinal structure and function in eyes with degenerative retinal diseases...Network PRINCIPAL INVESTIGATOR: Patricia Zilliox, Ph.D. CONTRACTING ORGANIZATION: National Neurovision Research Institute Owings

Degenerative Changes of the Spine of Pilots of the RNLAF

DTIC Science & Technology

2000-08-01

views of the spine taken in standing 7-3 Table 2 Classification of disorders Disorder Levels General: Osteo-arthrosis / Spondylosis / Arthrosis...Deformans Cervical, thoracic, lumbar Scoliosis Cervical, thoracic, lumbar Abnormal alignment Cervical, lumbar Scheuermann’s disease / Enchondrosis Thoracic... lumbar Specific: Degenerative changes in the intervertebral disc / Discopathy Cervical, thoracic, lumbar Presence of Osteophyte’s / Osteophytic

Let There Be Light: Gene and Cell Therapy for Blindness.

PubMed

Dalkara, Deniz; Goureau, Olivier; Marazova, Katia; Sahel, José-Alain

2016-02-01

Retinal degenerative diseases are a leading cause of irreversible blindness. Retinal cell death is the main cause of vision loss in genetic disorders such as retinitis pigmentosa, Stargardt disease, and Leber congenital amaurosis, as well as in complex age-related diseases such as age-related macular degeneration. For these blinding conditions, gene and cell therapy approaches offer therapeutic intervention at various disease stages. The present review outlines advances in therapies for retinal degenerative disease, focusing on the progress and challenges in the development and clinical translation of gene and cell therapies. A significant body of preclinical evidence and initial clinical results pave the way for further development of these cutting edge treatments for patients with retinal degenerative disorders.

Let There Be Light: Gene and Cell Therapy for Blindness

PubMed Central

Dalkara, Deniz; Goureau, Olivier; Marazova, Katia; Sahel, José-Alain

2016-01-01

Retinal degenerative diseases are a leading cause of irreversible blindness. Retinal cell death is the main cause of vision loss in genetic disorders such as retinitis pigmentosa, Stargardt disease, and Leber congenital amaurosis, as well as in complex age-related diseases such as age-related macular degeneration. For these blinding conditions, gene and cell therapy approaches offer therapeutic intervention at various disease stages. The present review outlines advances in therapies for retinal degenerative disease, focusing on the progress and challenges in the development and clinical translation of gene and cell therapies. A significant body of preclinical evidence and initial clinical results pave the way for further development of these cutting edge treatments for patients with retinal degenerative disorders. PMID:26751519

Studies on carcinogenic and toxic effects of ochratoxin A in chicks.

PubMed

Stoev, Stoycho D

2010-04-01

Carcinogenic/toxic effects of ochratoxin A (OTA) in various internal organs of Plymouth Rock chicks were determined. The number of OTA-induced neoplasms was similar in chicks given 25 ppm L-β-phenylalanine (PHE) in addition to 5 ppm OTA compared to chicks given only 5 ppm OTA, which showed that PHE cannot be used as a real protector against the carcinogenic or toxic effects of OTA in chicks. OTA was found to provoke strong degenerative changes in liver and kidneys, degenerative changes and depletion of cells in lymphoid organs, oedematous and degenerative changes in the brain, muscular haemorrhages and fatty changes in the bone marrow. The target organs for carcinogenic effect of OTA in chicks were found to be kidneys and liver.

Homogentisate 1,2 Dioxygenase is Expressed in Human Osteoarticular Cells: Implications in Alkaptonuria

PubMed Central

Laschi, Marcella; Tinti, Laura; Braconi, Daniela; Millucci, Lia; Ghezzi, Lorenzo; Amato, Loredana; Selvi, Enrico; Spreafico, Adriano; Bernardini, Giulia; Santucci, Annalisa

2012-01-01

Alkaptonuria (AKU) results from defective homogentisate1,2-dioxygenase (HGD), causing degenerative arthropathy. The deposition of ochronotic pigment in joints is so far attributed to homogentisic acid produced by the liver, circulating in the blood and accumulating locally. Human normal and AKU osteoarticular cells were tested for HGD gene expression by RT-PCR, mono- and 2D-Western blotting. HGD gene expression was revealed in chondrocytes, synoviocytes, osteoblasts. Furthermore, HGD expression was confirmed by Western blotting, that also revealed the presence of five enzymatic molecular species. Our findings indicate that AKU osteoarticular cells produce the ochronotic pigment in loco and this may strongly contribute to induction of ochronotic arthropathy. J. Cell. Physiol. 227: 3254–3257, 2012. © 2011 Wiley Periodicals, Inc. PMID:22105303

Insights into human evolution from ancient and contemporary microbiome studies

PubMed Central

Schnorr, Stephanie L; Sankaranarayanan, Krithivasan; Lewis, Cecil M; Warinner, Christina

2017-01-01

Over the past decade, human microbiome research has energized the study of human evolution through a complete shift in our understanding of what it means to be human. The microbiome plays a pivotal role in human biology, performing key functions in digestion, mood and behavior, development and immunity, and a range of acute and chronic diseases. It is therefore critical to understand its evolution and changing ecology through time. Here we review recent findings on the microbiota of diverse human populations, non-human primates, and past human populations and discuss the implications of this research in formulating a deeper evolutionary understanding of the human holobiont. PMID:27507098

Adult Astrogenesis and the Etiology of Cortical Neurodegeneration

PubMed Central

Mohn, Tal C.; Koob, Andrew O.

2015-01-01

As more evidence points to a clear role for astrocytes in synaptic processing, synaptogenesis and cognition, continuing research on astrocytic function could lead to strategies for neurodegenerative disease prevention. Reactive astrogliosis results in astrocyte proliferation early in injury and disease states and is considered neuroprotective, indicating a role for astrocytes in disease etiology. This review describes the different types of human cortical astrocytes and the current evidence regarding adult cortical astrogenesis in injury and degenerative disease. A role for disrupted astrogenesis as a cause of cortical degeneration, with a focus on the tauopathies and synucleinopathies, will also be considered. PMID:26568684

Considerations of the ischemic basis and therapy of Alzheimer Disease.

PubMed

Niedermeyer, E

2007-01-01

A recently presented concept of Alzheimer disease (AD) is based on a primarily ischemic (rather than degenerative) type of brain disease. Etiologically, this new concept is presumed to be related to the human upright gait along with individual predisposition. The proposed treatment--head-down therapy (HDT) --is the centerpoint of this presentation: a simple and generally accessible type of therapy, with monitoring by neuropsychological questioning, electroencephalography, and transcranial Doppler. As a treatment of AD (limited to stage 1), HDT is expected to be helpful. It is possible, however, that its prophylactic use may be of even greater importance.

Systemic Problems: A perspective on stem cell aging and rejuvenation.

PubMed

Conboy, Irina M; Conboy, Michael J; Rebo, Justin

2015-10-01

This review provides balanced analysis of the advances in systemic regulation of young and old tissue stem cells and suggests strategies for accelerating development of therapies to broadly combat age-related tissue degenerative pathologies. Many highlighted recent reports on systemic tissue rejuvenation combine parabiosis with a "silver bullet" putatively responsible for the positive effects. Attempts to unify these papers reflect the excitement about this experimental approach and add value in reproducing previous work. At the same time, defined molecular approaches, which are "beyond parabiosis" for the rejuvenation of multiple old organs represent progress toward attenuating or even reversing human tissue aging.

Potential biomarkers of ageing.

PubMed

Simm, Andreas; Nass, Norbert; Bartling, Babett; Hofmann, Britt; Silber, Rolf-Edgar; Navarrete Santos, Alexander

2008-03-01

Life span in individual humans is very heterogeneous.Thus, the ageing rate, measured as the decline of functional capacity and stress resistance, is different in every individual. There have been attempts made to analyse this individual age, the so-called biological age, in comparison to chronological age. Biomarkers of ageing should help to characterise this biological age and, as age is a major risk factor in many degenerative diseases,could be subsequently used to identify individuals at high risk of developing age-associated diseases or disabilities. Markers based on oxidative stress, protein glycation,inflammation, cellular senescence and hormonal deregulation are discussed.

Antifibrotic effects of tocotrienols on human Tenon's fibroblasts.

PubMed

Tappeiner, Christoph; Meyenberg, Alexander; Goldblum, David; Mojon, Daniel; Zingg, Jean-Marc; Nesaretnam, Kalanithi; Kilchenmann, Monika; Frueh, Beatrice E

2010-01-01

To compare the antifibrotic effect of vitamin E isoforms alpha-, gamma-, and delta-tocotrienol on human Tenon's fibroblasts (hTf) to the antimetabolite mitomycin C. Antifibrotic effects of alpha- (40, 60, 80, 100, and 120 microM), gamma- (10, 20, 30, and 40 microM) and delta-tocotrienol (10, 20, 30, and 40 microM) on hTf cultures were evaluated by performing proliferation, migration and collagen synthesis assays. Whereas for vitamin E the exposure time was set to 7 days to mimic subconjunctival application, cultures were exposed only 5 min to mitomycin C 100 microg/ml to mimic intraoperative administration. Cell morphology (phase contrast microscopy) as an assessment for cytotoxicity and cell density by measuring DNA content in a fluorometric assay to determine proliferation inhibition was performed on day 0, 4, and 7. Migration ability and collagen synthesis of fibroblasts were measured. All tested tocotrienol isoforms were able to significantly inhibit hTf proliferation in a dose-dependent manner (maximal inhibitory effect without relevant morphological changes at day 4 for alpha-tocotrienol 80 microM with 36.7% and at day 7 for alpha-tocotrienol 80 microM with 42.6% compared to control). Degenerative cell changes were observed in cultures with concentrations above 80 microM for alpha- and above 30 microM for gamma- and delta-tocotrienol. The highest collagen synthesis inhibition has been found with 80 microM alpha-tocotrienol (62.4%) and no significant inhibition for mitomycin C (2.5%). Migration ability was significantly reduced in cultures exposed to 80 microM alpha- and 30 microM gamma-tocotrienol (inhibition of 82.2% and 79.5%, respectively, compared to control) and also after mitomycin C treatment (60.0%). Complete growth inhibition without significant degenerative cell changes could only be achieved with mitomycin C. In vitro, all tested tocotrienol isoforms were able to inhibit proliferation, migration and collagen synthesis of human Tenon's fibroblasts and therefore may have the potential as an anti-scarring agent in filtrating glaucoma surgery.

Intentional fatal metallic phosphide poisoning in a dog--a case report.

PubMed

Nagy, Andras-Laszlo; Bolfa, Pompei; Mihaiu, Marian; Catoi, Cornel; Oros, Adrian; Taulescu, Marian; Tabaran, Flaviu

2015-07-23

Metallic phosphides are extremely toxic pesticides that are regulated in their usage. Information concerning the impact of metallic phosphides on human health is abundant. Data regarding the clinical pathology of phosphide poisoning in humans or domestic and wild animals is largely incomplete with only a few cases of metallic phosphide poisoning being reported every year, especially in humans. For the majority of cases reported in dogs the data are vague or incomplete. Here we report a complete and detailed description of pathological changes in a case of intentional metallic phosphide poisoning in a dog including an exhaustive examination of the brain. A 1 year old, male, Belgian Shepherd crossbreed dog with a clean medical history and no observed clinical signs prior to death, was submitted for post mortem examination. The dog was found dead by the owner. Near the body a suspect mix of bread, fat and a blackish powder was found. The owner announced the authorities and submitted the animal and the possible bait for forensic examination. At necropsy, multisystemic necrotic and degenerative lesions were observed. Histological exam confirmed the presence of necrotic and degenerative lesions of variable severity in all of the examined organs. The toxicological forensic examination revealed the presence of the phosphine gas in the gastric content and the bait. Metallic phosphide poisoning is a rarely reported entity, since the diagnosis of intentional poisoning with these compounds is a great challenge for forensic pathologists and toxicologists. To our knowledge, this is the first study describing the lesions completely in veterinary forensic toxicology. We assume that the toxic shows systemic endotheliotropism and damage of the endothelial cells responsible for the hemorrhagic lesions and for the secondary ischemic necrosis in various organs. This report will contribute to a better understanding of the pathogenesis in cases of acute metallic phosphide exposure in animals.

A new in vivo animal model to create intervertebral disc degeneration characterized by MRI, radiography, CT/discogram, biochemistry, and histology.

PubMed

Zhou, HaoWei; Hou, ShuXun; Shang, WeiLin; Wu, WenWen; Cheng, Yao; Mei, Fang; Peng, BaoGan

2007-04-15

A new in vivo sheep model was developed that produced disc degeneration through the injection of 5-bromodeoxyuridine (BrdU) into the intervertebral disc. This process was studied using magnetic resonance imaging (MRI), radiography, CT/discogram, histology, and biochemistry. To develop a sheep model of intervertebral disc degeneration that more faithfully mimics the pathologic hallmarks of human intervertebral disc degeneration. Recent studies have shown age-related alterations in proteoglycan structure and organization in human intervertebral discs. An animal model that involves the use of age-related changes in disc cells can be beneficial over other more invasive degenerative models that involves directly damaging the matrix of disc tissue. Twelve sheep were injected with BrdU or vehicle (phosphate-buffered saline) into the central region of separate lumbar discs. Intact discs were used as controls. At the 2-, 6-, 10-, and 14-week time points, discs underwent MRI, radiography, histology, and biochemical analyses. A CT/discogram study was performed at the 14-week time point. MRI demonstrated a progressive loss of T2-weighted signal intensity at BrdU-injected discs over the 14-week study period. Radiograph findings included osteophyte and disc space narrowing formed by 10 weeks post-BrdU treatment. CT discography demonstrated internal disc disruption in several BrdU-treated discs at the 14-week time point. Histology showed a progressive loss of the normal architecture and cell density of discs from the 2-week time point to the 14-week time point. A progressive loss of cell proliferation capacity, water content, and proteoglycans was also documented. BrdU injection into the central region of sheep discs resulted in degeneration of intervertebral discs. This progressive, degenerative process was confirmed using MRI, histology, and by observing changes in biochemistry. Degeneration occurred in a manner that was similar to that observed in human disc degeneration.

Cis-regulatory Elements and Human Evolution

PubMed Central

Siepel, Adam

2014-01-01

Modification of gene regulation has long been considered an important force in human evolution, particularly through changes to cis-regulatory elements (CREs) that function in transcriptional regulation. For decades, however, the study of cis-regulatory evolution was severely limited by the available data. New data sets describing the locations of CREs and genetic variation within and between species have now made it possible to study CRE evolution much more directly on a genome-wide scale. Here, we review recent research on the evolution of CREs in humans based on large-scale genomic data sets. We consider inferences based on primate divergence, human polymorphism, and combinations of divergence and polymorphism. We then consider “new frontiers” in this field stemming from recent research on transcriptional regulation. PMID:25218861

Sequence-Level Mechanisms of Human Epigenome Evolution

PubMed Central

Prendergast, James G.D.; Chambers, Emily V.; Semple, Colin A.M.

2014-01-01

DNA methylation and chromatin states play key roles in development and disease. However, the extent of recent evolutionary divergence in the human epigenome and the influential factors that have shaped it are poorly understood. To determine the links between genome sequence and human epigenome evolution, we examined the divergence of DNA methylation and chromatin states following segmental duplication events in the human lineage. Chromatin and DNA methylation states were found to have been generally well conserved following a duplication event, with the evolution of the epigenome largely uncoupled from the total number of genetic changes in the surrounding DNA sequence. However, the epigenome at tissue-specific, distal regulatory regions was observed to be unusually prone to diverge following duplication, with particular sequence differences, altering known sequence motifs, found to be associated with divergence in patterns of DNA methylation and chromatin. Alu elements were found to have played a particularly prominent role in shaping human epigenome evolution, and we show that human-specific AluY insertion events are strongly linked to the evolution of the DNA methylation landscape and gene expression levels, including at key neurological genes in the human brain. Studying paralogous regions within the same sample enables the study of the links between genome and epigenome evolution while controlling for biological and technical variation. We show DNA methylation and chromatin divergence between duplicated regions are linked to the divergence of particular genetic motifs, with Alu elements having played a disproportionate role in the evolution of the epigenome in the human lineage. PMID:24966180

Chronic In Vivo Load Alteration Induces Degenerative Changes in the Rat Tibiofemoral Joint

PubMed Central

Roemhildt, M. L.; Beynnon, B. D.; Gauthier, A. E.; Gardner-Morse, M.; Ertem, F.; Badger, G. J.

2012-01-01

Objective We investigated the relationship between the magnitude and duration of sustained compressive load alteration and the development of degenerative changes in the rat tibiofemoral joint. Methods A varus loading device was attached to the left hind limb of mature rats to apply increased compression to the medial compartment and decreased compression to the lateral compartment of the tibiofemoral joint of either 0% or 100% body weight for 0, 6 or 20 weeks. Compartment-specific assessment of the tibial plateaus included biomechanical measures (articular cartilage aggregate modulus, permeability and Poisson’s ratio, and subchondral bone modulus) and histological assessments (articular cartilage, calcified cartilage, and subchondral bone thicknesses, degenerative scoring parameters, and articular cartilage cellularity). Results Increased compression in the medial compartment produced significant degenerative changes consistent with the development of osteoarthritis including a progressive decrease in cartilage aggregate modulus (43% and 77% at 6 and 20 weeks), diminished cellularity (38% and 51% at 6 and 20 weeks), and increased histological degeneration. At 20 weeks, medial compartment articular cartilage thickness deceased 30% while subchondral bone thickness increased 32% and subchondral bone modulus increased 99%. Decreased compression in the lateral compartment increased calcified cartilage thickness, diminished region-specific subchondral bone thickness and revealed trends for reduced cellularity and decreased articular cartilage thickness at 20 weeks. Conclusions Altered chronic joint loading produced degenerative changes consistent with those observed clinically with the development of osteoarthritis and may replicate the slow development of non-traumatic osteoarthritis in which mechanical loads play a primary etiological role. PMID:23123358

Human influences on evolution, and the ecological and societal consequences

PubMed Central

Hendry, Andrew P.; Svensson, Erik I.

2017-01-01

Humans have dramatic, diverse and far-reaching influences on the evolution of other organisms. Numerous examples of this human-induced contemporary evolution have been reported in a number of ‘contexts’, including hunting, harvesting, fishing, agriculture, medicine, climate change, pollution, eutrophication, urbanization, habitat fragmentation, biological invasions and emerging/disappearing diseases. Although numerous papers, journal special issues and books have addressed each of these contexts individually, the time has come to consider them together and thereby seek important similarities and differences. The goal of this special issue, and this introductory paper, is to promote and expand this nascent integration. We first develop predictions as to which human contexts might cause the strongest and most consistent directional selection, the greatest changes in evolutionary potential, the greatest genetic (as opposed to plastic) changes and the greatest effects on evolutionary diversification. We then develop predictions as to the contexts where human-induced evolutionary changes might have the strongest effects on the population dynamics of the focal evolving species, the structure of their communities, the functions of their ecosystems and the benefits and costs for human societies. These qualitative predictions are intended as a rallying point for broader and more detailed future discussions of how human influences shape evolution, and how that evolution then influences species traits, biodiversity, ecosystems and humans. This article is part of the themed issue ‘Human influences on evolution, and the ecological and societal consequences’. PMID:27920373

A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine

PubMed Central

Wallace, Douglas C.

2005-01-01

Life is the interplay between structure and energy, yet the role of energy deficiency in human disease has been poorly explored by modern medicine. Since the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary calories into usable energy, generating reactive oxygen species (ROS) as a toxic by-product, I hypothesize that mitochondrial dysfunction plays a central role in a wide range of age-related disorders and various forms of cancer. Because mitochondrial DNA (mtDNA) is present in thousands of copies per cell and encodes essential genes for energy production, I propose that the delayed-onset and progressive course of the age-related diseases results from the accumulation of somatic mutations in the mtDNAs of post-mitotic tissues. The tissue-specific manifestations of these diseases may result from the varying energetic roles and needs of the different tissues. The variation in the individual and regional predisposition to degenerative diseases and cancer may result from the interaction of modern dietary caloric intake and ancient mitochondrial genetic polymorphisms. Therefore the mitochondria provide a direct link between our environment and our genes and the mtDNA variants that permitted our forbears to energetically adapt to their ancestral homes are influencing our health today. PMID:16285865

Stem cells in drug discovery, tissue engineering, and regenerative medicine: emerging opportunities and challenges.

PubMed

Nirmalanandhan, Victor Sanjit; Sittampalam, G Sitta

2009-08-01

Stem cells, irrespective of their origin, have emerged as valuable reagents or tools in human health in the past 2 decades. Initially, a research tool to study fundamental aspects of developmental biology is now the central focus of generating transgenic animals, drug discovery, and regenerative medicine to address degenerative diseases of multiple organ systems. This is because stem cells are pluripotent or multipotent cells that can recapitulate developmental paths to repair damaged tissues. However, it is becoming clear that stem cell therapy alone may not be adequate to reverse tissue and organ damage in degenerative diseases. Existing small-molecule drugs and biologicals may be needed as "molecular adjuvants" or enhancers of stem cells administered in therapy or adult stem cells in the diseased tissues. Hence, a combination of stem cell-based, high-throughput screening and 3D tissue engineering approaches is necessary to advance the next wave of tools in preclinical drug discovery. In this review, the authors have attempted to provide a basic account of various stem cells types, as well as their biology and signaling, in the context of research in regenerative medicine. An attempt is made to link stem cells as reagents, pharmacology, and tissue engineering as converging fields of research for the next decade.

Oxidation Inhibits Iron-Induced Blood Coagulation

PubMed Central

Pretorius, Etheresia; Bester, Janette; Vermeulen, Natasha; Lipinski, Boguslaw

2013-01-01

Blood coagulation under physiological conditions is activated by thrombin, which converts soluble plasma fibrinogen (FBG) into an insoluble clot. The structure of the enzymatically-generated clot is very characteristic being composed of thick fibrin fibers susceptible to the fibrinolytic degradation. However, in chronic degenerative diseases, such as atherosclerosis, diabetes mellitus, cancer, and neurological disorders, fibrin clots are very different forming dense matted deposits (DMD) that are not effectively removed and thus create a condition known as thrombosis. We have recently shown that trivalent iron (ferric ions) generates hydroxyl radicals, which subsequently convert FBG into abnormal fibrin clots in the form of DMDs. A characteristic feature of DMDs is their remarkable and permanent resistance to the enzymatic degradation. Therefore, in order to prevent thrombotic incidences in the degenerative diseases it is essential to inhibit the iron-induced generation of hydroxyl radicals. This can be achieved by the pretreatment with a direct free radical scavenger (e.g. salicylate), and as shown in this paper by the treatment with oxidizing agents such as hydrogen peroxide, methylene blue, and sodium selenite. Although the actual mechanism of this phenomenon is not yet known, it is possible that hydroxyl radicals are neutralized by their conversion to the molecular oxygen and water, thus inhibiting the formation of dense matted fibrin deposits in human blood. PMID:23170793

[Partial nucleotomy of the ovine disc as an in vivo model for disc degeneration].

PubMed

Guder, E; Hill, S; Kandziora, F; Schnake, K J

2009-01-01

The aim of this study was to develop a suitable animal model for the clinical situation of progressive disc degeneration after microsurgical nucleotomy. Twenty sheep underwent standardised partial anterolateral nucleotomy at lumbar segment 3/4. After randomisation, 10 animals were sacrificed after 12 weeks (group 1). The remainder was sacrificed after 48 weeks (group 2). For radiological examination X-rays, MRI and post-mortem CT scans were performed. Lumbar discs L 3/4 with adjacent subchondral trabecular bone were harvested and analysed macroscopically and histologically. An image-analysing computer program was used to measure histomorphometric indices of bone structure. 17 segments could be evaluated. After 12 weeks (group 1) histological and radiological degenerative disc changes were noted. After 48 weeks (group 2), radiological signs in MRI reached statistical significance. Furthermore, group 2 showed significantly more osteophyte formations in CT scans. Histomorphometric changes of the disc and the adjacent vertebral bone structure suggest a significant progressive degenerative remodelling. The facet joints did not show any osteoarthrosis after 48 weeks. Partial nucleotomy of the ovine lumbar disc leads to radiological and histological signs of disc degeneration similar to those seen in humans after microsurgical nucleotomy. The presented in vivo model may be useful to evaluate new orthopaedic treatment strategies.

The ubiquitin-proteasome system in spongiform degenerative disorders

PubMed Central

Whatley, Brandi R.; Li, Lian; Chin, Lih-Shen

2008-01-01

Summary Spongiform degeneration is characterized by vacuolation in nervous tissue accompanied by neuronal death and gliosis. Although spongiform degeneration is a hallmark of prion diseases, this pathology is also present in the brains of patients suffering from Alzheimer's disease, diffuse Lewy body disease, human immunodeficiency virus (HIV) infection, and Canavan's spongiform leukodystrophy. The shared outcome of spongiform degeneration in these diverse diseases suggests that common cellular mechanisms must underlie the processes of spongiform change and neurodegeneration in the central nervous system. Immunohistochemical analysis of brain tissues reveals increased ubiquitin immunoreactivity in and around areas of spongiform change, suggesting the involvement of ubiquitin-proteasome system dysfunction in the pathogenesis of spongiform neurodegeneration. The link between aberrant ubiquitination and spongiform neurodegeneration has been strengthened by the discovery that a null mutation in the E3 ubiquitin-protein ligase mahogunin ring finger-1 (Mgrn1) causes an autosomal recessively inherited form of spongiform neurodegeneration in animals. Recent studies have begun to suggest that abnormal ubiquitination may alter intracellular signaling and cell functions via proteasome-dependent and proteasome-independent mechanisms, leading to spongiform degeneration and neuronal cell death. Further elucidation of the pathogenic pathways involved in spongiform neurodegeneration should facilitate the development of novel rational therapies for treating prion diseases, HIV infection, and other spongiform degenerative disorders. PMID:18790052

Osteoporosis in Cervical Spine Surgery.

PubMed

Guzman, Javier Z; Feldman, Zachary M; McAnany, Steven; Hecht, Andrew C; Qureshi, Sheeraz A; Cho, Samuel K

2016-04-01

Retrospective administrative database analysis. To investigate the effect of osteoporosis (OS) on complications and outcomes in patients undergoing cervical spine surgery. OS is the most prevalent degenerative human bone disease, and spine surgeons will inevitably perform procedures on patients with OS. These patients might present a difficult patient cohort because many fixation techniques depend on bone quality and adequate bone healing--both of which are compromised in OS. The nationwide inpatient sample was queried using the Ninth Revision, Clinical Modification procedural codes for cervical spine procedures and diagnosis codes for degenerative conditions of cervical spine from 2002 to 2011. Patients were separated into two cohorts, those patients with OS and those without OS. Demographics, hospital characteristics, and adjusted complication likelihood were analyzed. Multivariate regression analysis was performed to determine odds of revision surgery in patients with OS. Of all patients undergoing degenerative cervical spine surgery, 2% were identified as having OS (32,557 of a sample of 1,602,129 patients). Osteoporotic patients were more likely to undergo posterior cervical spine fusion when compared with those patients without OS (11.3% vs. 5.4%, P < 0.0001). Moreover, circumferential fusion was performed 3 times more frequently in the osteoporotic cohort. Adjusted complications showed increased odds for postoperative hemorrhage (odds ratio = 1.70, 95% confidence interval = 1.46-1.98, P < 0.0001). Patients with OS stayed in the hospital longer (3.5 vs. 2.5 days, P < 0.0001) and had 30% costlier hospitalizations. Multivariate for revision surgery indicated that osteoporotic patients had significantly increased odds of revision surgery (odds ratio = 1.54, P ≤ 0.0001) when referenced to non-osteoporotic patients undergoing cervical spine surgery. Osteoporotic patients were more likely to undergo revision surgery, have longer hospitalizations, and have higher hospitalization costs, than their non-osteoporotic counterparts. 3.

77 FR 23506 - Notice of Inventory Completion: U.S. Department of Interior, Bureau of Reclamation, Upper...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-19

... Arizona State University, School of Human Evolution and Social Change, Tempe, AZ AGENCY: National Park... University, School of Human Evolution and Social Change, Tempe, AZ, and under the control of the U.S... University, School of Human Evolution and Social Change. No known individuals were identified. No associated...

Does football cause an increase in degenerative disease of the lumbar spine?

PubMed

Gerbino, Peter G; d'Hemecourt, Pierre A

2002-02-01

Degenerative disease of the lumbar spine is exceedingly common. Whether any specific activity increases the likelihood of developing degenerative disc disease (DDD) or facet degeneration (FD) has enormous implications. Within the field of occupational medicine there are specific activities, occupations, and morphologic characteristics that have been related to low back pain. Several specific risk factors have been conclusively linked to low back pain, and in particular DDD and FD. Within the sport of American football, there has long been the feeling that many athletes have or will develop low back pain, DDD, and FD. Proving that certain risk factors present in football will predictably lead to an increase in LBP, DDD, and FD is more difficult. At this time, it can be said that football players, in general, increase their risk of developing low back pain, DDD, and FD as their years of involvement with their sport increase. Because specific spine injuries like fracture, disc herniation, and spondylolysis are more frequent in football players, the resulting DDD and FD are greater than that of the general population. The weightlifting and violent hyperextension that are part of American football are independent risk factors for degenerative spine disease.

Early clinical effects of the Dynesys system plus transfacet decompression through the Wiltse approach for the treatment of lumbar degenerative diseases

PubMed Central

Liu, Chao; Wang, Lei; Tian, Ji-wei

2014-01-01

Background This study investigated early clinical effects of Dynesys system plus transfacet decompression through the Wiltse approach in treating lumbar degenerative diseases. Material/Methods 37 patients with lumbar degenerative disease were treated with the Dynesys system plus transfacet decompression through the Wiltse approach. Results Results showed that all patients healed from surgery without severe complications. The average follow-up time was 20 months (9–36 months). Visual Analogue Scale and Oswestry Disability Index scores decreased significantly after surgery and at the final follow-up. There was a significant difference in the height of the intervertebral space and intervertebral range of motion (ROM) at the stabilized segment, but no significant changes were seen at the adjacent segments. X-ray scans showed no instability, internal fixation loosening, breakage, or distortion in the follow-up. Conclusions The Dynesys system plus transfacet decompression through the Wiltse approach is a therapeutic option for mild lumbar degenerative disease. This method can retain the structure of the lumbar posterior complex and the motion of the fixed segment, reduce the incidence of low back pain, and decompress the nerve root. PMID:24859831

Investigating Human Evolution Using Digital Imaging & Craniometry

ERIC Educational Resources Information Center

Robertson, John C.

2007-01-01

Human evolution is an important and intriguing area of biology. The significance of evolution as a component of biology curricula, at all levels, can not be overstated; the need to make the most of opportunities to effectively educate students in evolution as a central and unifying realm of biology is paramount. Developing engaging laboratory or…

Peking Man to Socialist Man: The Teaching of Human Evolution in China.

ERIC Educational Resources Information Center

Swetz, Frank J.

1986-01-01

Examines the content and methodology of the teaching of human evolution in the schools of the People's Republic of China. Reviews the aims and goals of science teaching and their effects on the teaching of evolution. Emphasizes evolution, compatibility with China's political doctrines, and includes illustrations of instructional materials. (ML)

The Evolution of Lineage-Specific Regulatory Activities in the Human Embryonic Limb

PubMed Central

Cotney, Justin; Leng, Jing; Yin, Jun; Reilly, Steven K.; DeMare, Laura E.; Emera, Deena; Ayoub, Albert E.; Rakic, Pasko; Noonan, James P.

2013-01-01

SUMMARY The evolution of human anatomical features likely involved changes in gene regulation during development. However, the nature and extent of human-specific developmental regulatory functions remain unknown. We obtained a genome-wide view of cis-regulatory evolution in human embryonic tissues by comparing the histone modification H3K27ac, which provides a quantitative readout of promoter and enhancer activity, during human, rhesus, and mouse limb development. Based on increased H3K27ac, we find that 13% of promoters and 11% of enhancers have gained activity on the human lineage since the human-rhesus divergence. These gains largely arose by modification of ancestral regulatory activities in the limb or potential co-option from other tissues and are likely to have heterogeneous genetic causes. Most enhancers that exhibit gain of activity in humans originated in mammals. Gains at promoters and enhancers in the human limb are associated with increased gene expression, suggesting they include molecular drivers of human morphological evolution. PMID:23827682

Newer knowledge in comparative virology--its contribution to human health research.

PubMed

Cabasso, J J

1975-06-28

Like other comparative sciences, and despite its recent beginning comparative virology has already contributed useful applications and observations to human health research. Teachings derived from the study of Marek's disease found application in that of Burkitt's lymphoma, and may lead to a possible vaccine against the human disease. Equally useful information came from the study of canine distemper in the development of a chorio-allantoic membrane attenuated measles vaccine, and in our knowledge of subacute sclerosing panencephalitis (SSPE) of humans; from the study of reovirus-like agents of infant mice and neonatal calves in that of an acute nonbacterial gastro-enteritis of infants and young children; and from that of the cancer-producing viruses of chickens, cats, and dogs to a better understanding of some human neoplasias. Finally, Aleutian mink disease may be an excellent natural model for the study of the collagen diseases of man, and scrapie of sheep one for that of a human chronic degenerative disease of the central nervous system of humans such as Kuru. Comparative virology has proved quite productive in a relatively short period, and is unlikely to be neglected in the future.

Elective frozen elephant trunk procedure using the E-Vita Open Plus prosthesis in 94 patients: a multicentre French registry.

PubMed

Verhoye, Jean-Philippe; Belhaj Soulami, Reda; Fouquet, Olivier; Ruggieri, Vito Giovanni; Kaladji, Adrien; Tomasi, Jacques; Sellin, Michel; Farhat, Fadi; Anselmi, Amedeo

2017-10-01

Our goal was to evaluate the operative outcomes of the frozen elephant trunk technique using the E-Vita Open Plus® hybrid prosthesis in chronic aortic arch diseases and report clinical and radiological outcomes at the 1-year follow-up. As determined from a prospective multicentre registry, 94 patients underwent frozen elephant trunk procedures using the E-Vita Open Plus hybrid device for the treatment of chronic aortic conditions, including 50% chronic aortic dissections, 40% degenerative aneurysms and 10% miscellaneous indications. Fifty percent of the cases were reoperations. The perioperative mortality rate was 11.7%. Spinal cord ischaemia and stroke rates were 4% and 9.6%, respectively. The mean cardiopulmonary bypass time was 252 ± 97 min, cardiac ischaemia time was 152 ± 53 min and cerebral perfusion time was 82 ± 22 min. Concomitant procedures were observed in 15% of patients. Among the 83 surviving patients, the survival rate after the 1-year follow-up was 98%. Eleven percent of patients underwent endovascular completion, whereas 4% of patients required aortic reintervention at 1 year. The E-Vita Open Plus hybrid device confirms the favourable short- and mid-term outcomes offered by its predecessor in frozen elephant trunk procedures in patients with chronic aortic arch disease. Implantation of the E-Vita Open Plus is associated with good 1-year survival rates, good rates of favourable aortic remodelling in both chronic dissection and degenerative aneurysms and a reproducible technique in a multicentre registry. Continued follow-up is required due to the risk of evolution at the downstream aorta. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Applications of CRISPR/Cas9 in retinal degenerative diseases

PubMed Central

Peng, Ying-Qian; Tang, Luo-Sheng; Yoshida, Shigeo; Zhou, Ye-Di

2017-01-01

Gene therapy is a potentially effective treatment for retinal degenerative diseases. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has been developed as a new genome-editing tool in ophthalmic studies. Recent advances in researches showed that CRISPR/Cas9 has been applied in generating animal models as well as gene therapy in vivo of retinitis pigmentosa (RP) and leber congenital amaurosis (LCA). It has also been shown as a potential attempt for clinic by combining with other technologies such as adeno-associated virus (AAV) and induced pluripotent stem cells (iPSCs). In this review, we highlight the main points of further prospect of using CRISPR/Cas9 in targeting retinal degeneration. We also emphasize the potential applications of this technique in treating retinal degenerative diseases. PMID:28503441

Management of Lumbar Conditions in the Elite Athlete.

PubMed

Hsu, Wellington K; Jenkins, Tyler James

2017-07-01

Lumbar disk herniation, degenerative disk disease, and spondylolysis are the most prevalent lumbar conditions that result in missed playing time. Lumbar disk herniation has a good prognosis. After recovery from injury, professional athletes return to play 82% of the time. Surgical management of lumbar disk herniation has been shown to be a viable option in athletes in whom nonsurgical measures have failed. Degenerative disk disease is predominately genetic but may be accelerated in athletes secondary to increased physiologic loading. Nonsurgical management is the standard of care for lumbar degenerative disk disease in the elite athlete. Spondylolysis is more common in adolescent athletes with back pain than in adult athletes. Nonsurgical management of spondylolysis is typically successful. However, if surgery is required, fusion or direct pars repair can allow the patient to return to sports.

Dynamic self-guiding analysis of Alzheimer's disease

PubMed Central

Kurakin, Alexei; Bredesen, Dale E.

2015-01-01

We applied a self-guiding evolutionary algorithm to initiate the synthesis of the Alzheimer's disease-related data and literature. A protein interaction network associated with amyloid-beta precursor protein (APP) and a seed model that treats Alzheimer's disease as progressive dysregulation of APP-associated signaling were used as dynamic “guides” and structural “filters” in the recursive search, analysis, and assimilation of data to drive the evolution of the seed model in size, detail, and complexity. Analysis of data and literature across sub-disciplines and system-scale discovery platforms suggests a key role of dynamic cytoskeletal connectivity in the stability, plasticity, and performance of multicellular networks and architectures. Chronic impairment and/or dysregulation of cell adhesions/synapses, cytoskeletal networks, and/or reversible epithelial-to-mesenchymal-like transitions, which enable and mediate the stable and coherent yet dynamic and reconfigurable multicellular architectures, may lead to the emergence and persistence of the disordered, wound-like pockets/microenvironments of chronically disconnected cells. Such wound-like microenvironments support and are supported by pro-inflammatory, pro-secretion, de-differentiated cellular phenotypes with altered metabolism and signaling. The co-evolution of wound-like microenvironments and their inhabitants may lead to the selection and stabilization of degenerated cellular phenotypes, via acquisition of epigenetic modifications and mutations, which eventually result in degenerative disorders such as cancer and Alzheimer's disease. PMID:26041885

Evolution of the diagnostic criteria for degenerative and cognitive disorders

PubMed Central

Lopez, Oscar L.; McDade, Eric; Riverol, Mario; Becker, James T.

2012-01-01

Purpose of review This review describes the evolution of the clinical criteria for Alzheimer’s disease over the past 25 years, with special emphasis on those recently published that have incorporated the use of biomarkers. Recent findings One of the most important advances in the knowledge of Alzheimer’s disease was the development of cerebrospinal fluid, PET and MRI biomarkers. These have shown that the Alzheimer’s disease is present in cognitively normal individuals, suggesting that there is a long incubation process that precedes the onset of the symptoms. Although there are diagnostic criteria for Alzheimer’s disease, the National Institute on Aging and the Alzheimer’s Association has proposed a set of diagnostic criteria oriented to provide a unified vision of the pathological process from preclinical, to mild cognitive impairment, and to full-blown dementia. These new criteria take advantage of different biomarkers to support the clinical diagnosis of the different stages of the disease. Summary The new guidelines provide a definition of the dementia syndrome and core diagnostic features to be used in research and clinical practice, although they caution about the use of biomarkers, since they still require validation, and the longitudinal interaction and dynamics of these biomarkers in relationship to the manifestation of the symptoms are not fully understood. PMID:22071334

A Novel, Extremely Elongated, and Endocellular Bacterial Symbiont Supports Cuticle Formation of a Grain Pest Beetle.

PubMed

Hirota, Bin; Okude, Genta; Anbutsu, Hisashi; Futahashi, Ryo; Moriyama, Minoru; Meng, Xian-Ying; Nikoh, Naruo; Koga, Ryuichi; Fukatsu, Takema

2017-09-26

The saw-toothed grain beetle, Oryzaephilus surinamensis (Silvanidae), is a cosmopolitan stored-product pest. Early studies on O. surinamensis in the 1930s described the presence of peculiar bacteriomes harboring endosymbiotic bacteria in the abdomen. Since then, however, the microbiological nature of the symbiont has been elusive. Here we investigated the endosymbiotic system of O. surinamensis in detail. In the abdomen of adults, pupae, and larvae, four oval bacteriomes were consistently identified, whose cytoplasm was full of extremely elongated tubular bacterial cells several micrometers wide and several hundred micrometers long. Molecular phylogenetic analysis identified the symbiont as a member of the Bacteroidetes , in which the symbiont was the most closely related to the endosymbiont of a grain pest beetle, Rhyzopertha dominica (Bostrichidae). The symbiont was detected in developing embryos, corroborating vertical symbiont transmission through host generations. The symbiont gene showed AT-biased nucleotide composition and accelerated molecular evolution, plausibly reflecting degenerative evolution of the symbiont genome. When the symbiont infection was experimentally removed, the aposymbiotic insects grew and reproduced normally, but exhibited a slightly but significantly more reddish cuticle and lighter body mass. These results indicate that the symbiont of O. surinamensis is not essential for the host's growth and reproduction but contributes to the host's cuticle formation. Symbiont genome sequencing and detailed comparison of fitness parameters between symbiotic and aposymbiotic insects under various environmental conditions will provide further insights into the symbiont's biological roles for the stored-product pest. IMPORTANCE Some beetles notorious as stored-product pests possess well-developed symbiotic organs called bacteriomes for harboring specific symbiotic bacteria, although their biological roles have been poorly understood. Here we report a peculiar endosymbiotic system of a grain pest beetle, Oryzaephilus surinamensis , in which four oval bacteriomes in the abdomen are full of extremely elongated tubular bacterial cells. Experimental symbiont elimination did not hinder the host's growth and reproduction, but resulted in emergence of reddish beetles, uncovering the symbiont's involvement in host's cuticle formation. We speculate that the extremely elongated symbiont cell morphology might be due to the degenerative symbiont genome deficient in bacterial cell division and/or cell wall formation, which highlights an evolutionary consequence of intimate host-symbiont coevolution. Copyright © 2017 Hirota et al.

Degenerative lumbar scoliosis in elderly patients: dynamic stabilization without fusion versus posterior instrumented fusion.

PubMed

Di Silvestre, Mario; Lolli, Francesco; Bakaloudis, Georgios

2014-01-01

Posterolateral fusion with pedicle screw instrumentation is currently the most widely accepted technique for degenerative lumbar scoliosis in elderly patients. However, a high incidence of complications has been reported in most series. Dynamic stabilization without fusion in patients older than 60 years has not previously been compared with the use of posterior fusion in degenerative lumbar scoliosis. To compare dynamic stabilization without fusion and posterior instrumented fusion in the treatment of degenerative lumbar scoliosis in elderly patients, in terms of perioperative findings, clinical outcomes, and adverse events. A retrospective study. Fifty-seven elderly patients were included. There were 45 women (78%) and 12 men (22%) with a mean age of 68.1 years (range, 61-78 years). All patients had degenerative de novo lumbar scoliosis, associated with vertebral canal stenosis in 51 cases (89.4%) and degenerative spondylolisthesis in 24 patients (42.1%). Clinical (Oswestry Disability Index, visual analog scale, Roland-Morris Disability Questionnaire) and radiological (scoliosis and lordosis corrections) outcomes as well as incidence of complications. Patients were divided into two groups: 32 patients (dynamic group) had dynamic stabilization without fusion and 25 patients (fusion group) underwent posterior instrumented fusion. All the patients' medical records and X-rays were reviewed. Preoperative, postoperative, and follow-up questionnaires were obtained to evaluate clinical outcomes. At an average follow-up of 64 months (range, 42-90 months), clinical results improved similarly in both groups of patients. Statistically superior scoliosis and final lordosis corrections were achieved with posterior fusion (56.9% vs. 37.3% and -46.8° vs. -35.8°, respectively). However, in the dynamic group, incidence of overall complications was lower (25% vs. 44%), and fewer patients required revision surgery (6.2% vs. 16%). Furthermore, lower average values of operative duration (190 vs. 240 minutes) and blood loss (950 vs. 1,400 cc) were observed in the dynamic group than in the fusion group. In elderly patients with degenerative lumbar scoliosis, pedicle screw-based dynamic stabilization was less invasive with shorter operative duration, less blood loss, and lower adverse event rates than instrumented posterior fusion. Scoliosis curve reduction and lumbar lordosis were superior after fusion; however, dynamic stabilization achieved satisfying values of both these parameters, and these results were stable after an average follow-up of more than 5 years. Furthermore, there was no difference between the two techniques in terms of functional clinical outcomes at the last follow-up. Copyright © 2014 Elsevier Inc. All rights reserved.

Relation of Mitral Valve Surgery Volume to Repair Rate, Durability, and Survival.

PubMed

Chikwe, Joanna; Toyoda, Nana; Anyanwu, Anelechi C; Itagaki, Shinobu; Egorova, Natalia N; Boateng, Percy; El-Eshmawi, Ahmed; Adams, David H

2017-04-24

Degenerative mitral valve repair rates remain highly variable, despite established benefits of repair over replacement. The contribution of surgeon-specific factors is poorly defined. This study evaluated the influence of surgeon case volume on degenerative mitral valve repair rates and outcomes. A mandatory New York State database was queried and 5,475 patients were identified with degenerative mitral disease who underwent mitral valve operations between 2002 and 2013. Mitral repair rates, mitral reoperations within 12 months of repair, and survival were analyzed using multivariable Cox modeling and restricted cubic spline function. Median annual surgeon volume of any mitral operations was 10 (range 1 to 230), with a mean repair rate of 55% (n = 20,797 of 38,128). In the subgroup of patients with degenerative disease, the mean repair rate was 67% (n = 3,660 of 5,475), with a range of 0% to 100%. Mean repair rates ranged from 48% (n = 179 of 370) for surgeons with total annual volumes of ≤10 mitral operations to 77% (n = 1,710 of 2,216) for surgeons with total annual volumes of >50 mitral operations (p < 0.001). Higher total annual surgeon volume was associated with increased repair rates of degenerative mitral valve disease (adjusted odds ratio [OR]: 1.13 for every additional 10 mitral operations; 95% confidence interval [CI]: 1.10 to 1.17; p < 0.001); a steady decrease in reoperation risk until 25 total mitral operations annually; and improved 1-year survival (adjusted hazard ratio: 0.95 for every additional 10 operations; 95% CI: 0.92 to 0.98; p = 0.001). For surgeons with a total annual volume of ≤25 mitral operations, repair rates were higher (63.8%; n = 180 of 282) if they operated in the same institution as a surgeon with total annual mitral volumes of >50 and degenerative mitral valve repair rates of >70%, compared with surgeons operating in the other institutions (51.3%; n = 580 of 1,130) (adjusted OR: 1.79; 95% CI: 1.24 to 2.60; p < 0.001). This study suggests that individual surgeon volume is a determinant of not only mitral repair rates, but also freedom from reoperation, and survival. The data from this study support the guideline's concept of reference referral to experienced mitral surgeons to improve outcomes in patients with degenerative mitral valve disease. Copyright © 2017. Published by Elsevier Inc.

Finnish Degenerative Meniscal Lesion Study (FIDELITY): a protocol for a randomised, placebo surgery controlled trial on the efficacy of arthroscopic partial meniscectomy for patients with degenerative meniscus injury with a novel ‘RCT within-a-cohort’ study design

PubMed Central

Sihvonen, Raine; Paavola, Mika; Malmivaara, Antti; Järvinen, Teppo L N

2013-01-01

Introduction Arthroscopic partial meniscectomy (APM) to treat degenerative meniscus injury is the most common orthopaedic procedure. However, valid evidence of the efficacy of APM is lacking. Controlling for the placebo effect of any medical intervention is important, but seems particularly pertinent for the assessment of APM, as the symptoms commonly attributed to a degenerative meniscal injury (medial joint line symptoms and perceived disability) are subjective and display considerable fluctuation, and accordingly difficult to gauge objectively. Methods and analysis A multicentre, parallel randomised, placebo surgery controlled trial is being carried out to assess the efficacy of APM for patients from 35 to 65 years of age with a degenerative meniscus injury. Patients with degenerative medial meniscus tear and medial joint line symptoms, without clinical or radiographic osteoarthritis of the index knee, were enrolled and then randomly assigned (1 : 1) to either APM or diagnostic arthroscopy (placebo surgery). Patients are followed up for 12 months. According to the prior power calculation, 140 patients were randomised. The two randomised patient groups will be compared at 12 months with intention-to-treat analysis. To safeguard against bias, patients, healthcare providers, data collectors, data analysts, outcome adjudicators and the researchers interpreting the findings will be blind to the patients’ interventions (APM/placebo). Primary outcomes are Lysholm knee score (a generic knee instrument), knee pain (using a numerical rating scale), and WOMET score (a disease-specific, health-related quality of life index). The secondary outcome is 15D (a generic quality of life instrument). Further, in one of the five centres recruiting patients for the randomised controlled trial (RCT), all patients scheduled for knee arthroscopy due to a degenerative meniscus injury are prospectively followed up using the same protocol as in the RCT to provide an external validation cohort. In this article, we present and discuss our study design, focusing particularly on the internal and external validity of our trial and the ethics of carrying out a placebo surgery controlled trial. Ethics and dissemination The protocol has been approved by the institutional review board of the Pirkanmaa Hospital District and the trial has been duly registered at ClinicalTrials.gov. The findings of this study will be disseminated widely through peer-reviewed publications and conference presentations. Trial registration ClinicalTrials.gov, number NCT00549172. PMID:23474796

Temperature and Evolutionary Novelty as Forces behind the Evolution of General Intelligence

ERIC Educational Resources Information Center

Kanazawa, Satoshi

2008-01-01

How did human intelligence evolve to be so high? Lynn [Lynn, R. (1991). The evolution of race differences in intelligence. Mankind Quarterly, 32, 99-173] and Rushton [Rushton, J.P. (1995). Race, evolution, and behavior: A life history perspective. New Brunswick: Transaction] suggest that the main forces behind the evolution of human intelligence…

The evolution of human and ape hand proportions.

PubMed

Almécija, Sergio; Smaers, Jeroen B; Jungers, William L

2015-07-14

Human hands are distinguished from apes by possessing longer thumbs relative to fingers. However, this simple ape-human dichotomy fails to provide an adequate framework for testing competing hypotheses of human evolution and for reconstructing the morphology of the last common ancestor (LCA) of humans and chimpanzees. We inspect human and ape hand-length proportions using phylogenetically informed morphometric analyses and test alternative models of evolution along the anthropoid tree of life, including fossils like the plesiomorphic ape Proconsul heseloni and the hominins Ardipithecus ramidus and Australopithecus sediba. Our results reveal high levels of hand disparity among modern hominoids, which are explained by different evolutionary processes: autapomorphic evolution in hylobatids (extreme digital and thumb elongation), convergent adaptation between chimpanzees and orangutans (digital elongation) and comparatively little change in gorillas and hominins. The human (and australopith) high thumb-to-digits ratio required little change since the LCA, and was acquired convergently with other highly dexterous anthropoids.

New genes contribute to genetic and phenotypic novelties in human evolution

PubMed Central

Zhang, Yong E.; Long, Manyuan

2014-01-01

New genes in human genomes have been found relevant in evolution and biology of humans. It was conservatively estimated that the human genome encodes more than 300 human-specific genes and 1,000 primate-specific genes. These new arrivals appear to be implicated in brain function and male reproduction. Surprisingly, increasing evidence indicates that they may also bring negative pleiotropic effects, while assuming various possible biological functions as sources of phenotypic novelties, suggesting a non-progressive route for functional evolution. Similar to these fixed new genes, polymorphic new genes were found to contribute to functional evolution within species, e.g. with respect to digestion or disease resistance, revealing that new genes can acquire new or diverged functions in its initial stage as prototypic genes. These progresses have provided new opportunity to explore the genetic basis of human biology and human evolutionary history in a new dimension. PMID:25218862

Evolutionary anthropology and genes: investigating the genetics of human evolution from excavated skeletal remains.

PubMed

Anastasiou, Evilena; Mitchell, Piers D

2013-10-01

The development of molecular tools for the extraction, analysis and interpretation of DNA from the remains of ancient organisms (paleogenetics) has revolutionised a range of disciplines as diverse as the fields of human evolution, bioarchaeology, epidemiology, microbiology, taxonomy and population genetics. The paper draws attention to some of the challenges associated with the extraction and interpretation of ancient DNA from archaeological material, and then reviews the influence of paleogenetics on the field of human evolution. It discusses the main contributions of molecular studies to reconstructing the evolutionary and phylogenetic relationships between extinct hominins (human ancestors) and anatomically modern humans. It also explores the evidence for evolutionary changes in the genetic structure of anatomically modern humans in recent millennia. This breadth of research has led to discoveries that would never have been possible using traditional approaches to human evolution. Copyright © 2013 Elsevier B.V. All rights reserved.

The evolution of human and ape hand proportions

PubMed Central

Almécija, Sergio; Smaers, Jeroen B.; Jungers, William L.

2015-01-01

Human hands are distinguished from apes by possessing longer thumbs relative to fingers. However, this simple ape-human dichotomy fails to provide an adequate framework for testing competing hypotheses of human evolution and for reconstructing the morphology of the last common ancestor (LCA) of humans and chimpanzees. We inspect human and ape hand-length proportions using phylogenetically informed morphometric analyses and test alternative models of evolution along the anthropoid tree of life, including fossils like the plesiomorphic ape Proconsul heseloni and the hominins Ardipithecus ramidus and Australopithecus sediba. Our results reveal high levels of hand disparity among modern hominoids, which are explained by different evolutionary processes: autapomorphic evolution in hylobatids (extreme digital and thumb elongation), convergent adaptation between chimpanzees and orangutans (digital elongation) and comparatively little change in gorillas and hominins. The human (and australopith) high thumb-to-digits ratio required little change since the LCA, and was acquired convergently with other highly dexterous anthropoids. PMID:26171589

Hydroxyl radical-modified fibrinogen as a marker of thrombosis: the role of iron.

PubMed

Lipinski, B; Pretorius, E

2012-07-01

Excessive free iron in blood and in organ tissues (so called iron overload) has been observed in degenerative diseases such as atherosclerosis, cancer, neurological, and certain autoimmune diseases, in which fibrin-like deposits are also found. Although most of the body iron is bound to hemoglobin and myoglobin in a divalent ferrous form, a certain amount of iron exists in blood as a trivalent (ferric) ion. This particular chemical state of iron has been shown to be toxic to the human body when not controlled by endogenous and/or dietary chelating agents. Experiments described in this paper show for the first time that ferric ions (Fe(3+)) can generate hydroxyl radicals without participation of any redox agent, thus making it a special case of the Fenton reaction. Ferric chloride was also demonstrated to induce aggregation of purified fibrinogen at the same molar concentrations that were used for the generation of hydroxyl radicals. Iron-aggregated fibrinogen, by contrast to native molecule, could not be dissociated into polypeptide subunit chains as shown in a polyacrylamide gel electrophoresis. The mechanism of this phenomenon is very likely based on hydroxyl radical-induced modification of fibrinogen tertiary structure with the formation of insoluble aggregates resistant to enzymatic and chemical degradations. Soluble modified fibrinogen species can be determined in blood of thrombotic patients by the reaction with protamine sulfate and/or by scanning electron microscopy. In view of these findings, it is postulated that iron-induced alterations in fibrinogen structure is involved in pathogenesis of certain degenerative diseases associated with iron overload and persistent thrombosis. It is concluded that the detection of hydroxyl radical-modified fibrinogen may be utilized as a marker of a thrombotic condition in human subjects.

Chondroprotective supplementation promotes the mechanical properties of injectable scaffold for human nucleus pulposus tissue engineering.

PubMed

Foss, Berit L; Maxwell, Thomas W; Deng, Ying

2014-01-01

A result of intervertebral disc (IVD) degeneration, the nucleus pulposus (NP) is no longer able to withstand applied load leading to pain and disability. The objective of this study is to fabricate a tissue-engineered injectable scaffold with chondroprotective supplementation in vitro to improve the mechanical properties of a degenerative NP. Tissue-engineered scaffolds were fabricated using different concentrations of alginate and calcium chloride and mechanically evaluated. Fabrication conditions were based on structural and mechanical resemblance to the native NP. Chondroprotective supplementation, glucosamine (GCSN) and chondroitin sulfate (CS), were added to scaffolds at concentrations of 0:0µg/mL (0:0-S), 125:100µg/mL (125:100-S), 250:200µg/mL (250:200-S), and 500:400µg/mL (500:400-S), GCSN and CS, respectively. Scaffolds were used to fabricate tissue-engineered constructs through encapsulation of human nucleus pulposus cells (HNPCs). The tissue-engineered constructs were collected at days 1, 14, and 28 for biochemical and biomechanical evaluations. Confocal microscopy showed HNPC viability and rounded morphology over the 28 day period. MTT analysis resulted in significant increases in cell proliferation for each group. Collagen type II ELISA quantification and compressive aggregate moduli (HA) showed increasing trends for both 250:200-S and the 500:400-S groups on Day 28 with significantly greater HA compared to 0:0-S group. Glycosaminoglycan and water content decreased for all groups. Results indicate the increased mechanical properties of the 250:200-S and the 500:400-S was due to production of a functional matrix. This study demonstrated potential for a chondroprotective supplemented injectable scaffold to restore biomechanical function of a degenerative disc through the production of a mechanically functional matrix. Copyright © 2013 Elsevier Ltd. All rights reserved.

Analysis of Recombinant Human Bone Morphogenetic Protein-2 Use in the Treatment of Lumbar Degenerative Spondylolisthesis.

PubMed

Yao, Qingqiang; Cohen, Jeremiah R; Buser, Zorica; Park, Jong-Beom; Brodke, Darrel S; Meisel, Hans-Joerg; Youssef, Jim A; Wang, Jeffrey C; Yoon, S Tim

2016-12-01

Study Design  Retrospective database review. Objective  To identify trends of the recombinant human bone morphogenetic protein-2 (rhBMP-2) use in the treatment of lumbar degenerative spondylolisthesis (LDS). Methods  PearlDiver Patient Record Database was used to identify patients who underwent lumbar fusion for LDS between 2005 and 2011. The distribution of bone morphogenetic protein use rate (BR) in various surgical procedures was recorded. Patient numbers, reoperation numbers, BR, and per year BR (PYBR) were stratified by geographic region, gender, and age. Results  There were 11,335 fusion surgeries, with 3,461 cases using rhBMP-2. Even though PYRB increased between 2005 and 2008, there was a significant decrease in 2010 for each procedure: 404 (34.5%) for posterior interbody fusion, 1,282 (34.3%) for posterolateral plus posterior interbody fusion (PLPIF), 1,477 (29.2%) for posterolateral fusion, and 335 (22.4%) for anterior lumbar interbody fusion. In patients using rhBMP-2, the reoperation rate was significantly lower than in patients not using rhBMP-2 (0.69% versus 1.07%, p  < 0.0001). Male patients had higher PYBR compared with female patients in 2008 and 2009 ( p  < 0.05). The West region and PLPIF had the highest BR and PYBR. Conclusions Our data shows that the revision rates were significantly lower in patients treated with rhBMP-2 compared with patients not treated with rhBMP-2. Furthermore, rhBMP-2 use in LDS varied by year, region, gender, and type of fusion technique. In the West region, the posterior approach and patients 65 to 69 years of age had the highest rate of rhBMP-2 use.

Analysis of Recombinant Human Bone Morphogenetic Protein-2 Use in the Treatment of Lumbar Degenerative Spondylolisthesis

PubMed Central

Yao, Qingqiang; Cohen, Jeremiah R.; Buser, Zorica; Park, Jong-Beom; Brodke, Darrel S.; Meisel, Hans-Joerg; Youssef, Jim A.; Wang, Jeffrey C.; Yoon, S. Tim

2016-01-01

Study Design Retrospective database review. Objective To identify trends of the recombinant human bone morphogenetic protein-2 (rhBMP-2) use in the treatment of lumbar degenerative spondylolisthesis (LDS). Methods PearlDiver Patient Record Database was used to identify patients who underwent lumbar fusion for LDS between 2005 and 2011. The distribution of bone morphogenetic protein use rate (BR) in various surgical procedures was recorded. Patient numbers, reoperation numbers, BR, and per year BR (PYBR) were stratified by geographic region, gender, and age. Results There were 11,335 fusion surgeries, with 3,461 cases using rhBMP-2. Even though PYRB increased between 2005 and 2008, there was a significant decrease in 2010 for each procedure: 404 (34.5%) for posterior interbody fusion, 1,282 (34.3%) for posterolateral plus posterior interbody fusion (PLPIF), 1,477 (29.2%) for posterolateral fusion, and 335 (22.4%) for anterior lumbar interbody fusion. In patients using rhBMP-2, the reoperation rate was significantly lower than in patients not using rhBMP-2 (0.69% versus 1.07%, p < 0.0001). Male patients had higher PYBR compared with female patients in 2008 and 2009 (p < 0.05). The West region and PLPIF had the highest BR and PYBR. Conclusions Our data shows that the revision rates were significantly lower in patients treated with rhBMP-2 compared with patients not treated with rhBMP-2. Furthermore, rhBMP-2 use in LDS varied by year, region, gender, and type of fusion technique. In the West region, the posterior approach and patients 65 to 69 years of age had the highest rate of rhBMP-2 use. PMID:27853658

Cytotoxic Effects of Nonionic Iodinated Contrast Agent on Human Adipose-derived Mesenchymal Stem Cells.

PubMed

Wu, Tao; Nie, Hai; Dietz, Allan B; Salek, David R; Smith, Jay; van Wijnen, Andre J; Qu, Wenchun

2018-05-31

Transplantation of mesenchymal stem cells (MSCs) is a promising therapy for degenerative spine conditions. However, cell therapy for painful spine degeneration presently requires use of contrast agents during fluoroscopy-guided injections and the effects of these agents on MSCs represents a gap in knowledge. To investigate the biological effects of contrast media that are co-injected with MSCs. Prospective observational study. Academic medical center. Patient-derived clinical-grade culture expanded MSCs. Iohexol(Omnipaque300) was reduced to 12.5%, 25%, 50% and 100% of the stock solution and incubated with MSCs for 30 minutes, 4 hours and 48 hours. We also used complete media and 12.5%, 25%, 50%, 100% of phosphate buffered saline (PBS) as control group. We examined cytotoxicity of Iohexol at different concentrations and exposure duration, as well as the potential for recovery over time. Cell counts, mitochondrial activity, and quantitative real time reverse-transcriptase polymerase chain reaction (qRT-PCR) of related genes were analyzed immediately after exposure (day 0) and after two days of exposure (day 2). Human MSCs exhibit a time- and concentration-dependent cytotoxic response to iodinated CM. A brief 30min exposure did not affect MSCs function and viability. However, extended treatment with iohexol for 4 hours at 50% or higher concentration had a significant impact on both viability and gene expression in MSCs. CM (Omnipaque300) is cytotoxic to MSCs in a time-and concentration-dependent manner. Hence, the concentration of CM that accompanies MSC injections should be carefully considered during mesenchymal stem cell therapy for disc degenerative diseases. Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

The Fallacy of the Longevity Elixir: Negligible Senescence May be Achieved, but Not by Using Something Physical.

PubMed

Kyriazis, Marios; Apostolides, Andreas

2015-01-01

The process of aging is a continuum of degeneration which eventually leads to loss of function and clinically manifest disease. Yet, in the purely therapeutic sense, there is a distinct clinical and practical separation between age-related degenerative diseases and the background process of aging itself. It is quite possible that biomedical technologies will prove invaluable in treating or alleviating the impact of distinct age-related degenerative diseases such as cardiovascular disease, arthritis or dementia. However, when it comes to addressing the fundamental, background stochastic nature of aging, it is unlikely that regenerative biotechnologies will have any appreciable impact in continually counteracting the process. In this paper we discuss some essential conceptual obstacles, both functional and translational, which will prove overwhelming and which preclude the notion that aging can be eliminated by using physical therapies. Our reasoning is two-fold: 1. Disruptive regenerative biotechnologies interfere with the complex, dynamic topological architecture of the human organism, in a manner that will render them unsuitable for clinical use against all age-related degeneration. 2. Even if some regenerative biotechnological treatments are developed in the laboratory, the translational issues will be insurmountable, and the treatments will thus be practically unusable by the general public at large. Predictions about the near or mid-term development of rejuvenating biotechnologies are not sufficiently grounded, and do not provide a framework for effective practical achievement of negligible senescence. Instead, the answer must lie in more global and abstract methods which align well with evolutionary mechanisms based on techno-cultural societal necessities. These are likely to operate in a way which ultimately may downgrade the importance of human aging and make it an evolutionarily unnecessary process.

Inherited Retinal Degenerative Disease Clinical Trial Network. Addendum

DTIC Science & Technology

2010-10-01

by retinitis pigmentosa (RP) and other forms of rare inherited retinal degenerative diseases is estimated at approximately 200,000 individuals. RP... Retinitis Pigmentosa ). NNRI is awaiting final protocol review and HRPO approval for NNRI and the three enrolling clinical sites- the CTEC site at...acid) in individuals with autosomal dominant retinitis pigmentosa , with the ability to expand the enrollment to individuals with autosomal recessive

[Analysis of the prevalence and risk factors of preoperative angiography confirmed coronary artery stenosis in patients with degenerative valvular heart disease].

PubMed

Xu, Z J; Pan, J; Zhou, Q; Wang, D J

2017-10-24

Objective: To estimate the prevalence and the risk factors of preoperative coronary angiography (CAG) confirmed coronary stenosis in patients with degenerative valvular heart disease. Methods: A total of 491 patients who underwent screening CAG before valvular surgery due to degenerative valvular heart disease were enrolled from January 2011 to September 2014 in our hospital, and clinical data were analyzed. According to CAG results, patients were divided into positive CAG result (PCAG) group or negative CAG (NCAG) group. Positive CAG result was defined as stenosis ≥50% of the diameter of the left main coronary artery or stenosis ≥70% of the diameter of left anterior descending, left circumflex artery, and right coronary artery.Risk factors of positive CAG result were analyzed by multivariable logistic regression analysis, and Bootstrap method was used to verify the results. Results: There were 47(9.57%)degenerative valvular heart disease patients with PCAG. Patients were older ((68.0±7.6)years vs.(62.6±7.1)years, P <0.001) and the prevalence of typical angina was significantly higher (14.89%(7/47)vs. 2.03%(9/444), P <0.001)in PCAG group than in NCAG group. Multivariable logistic regression analysis showed that age ( OR =1.118, 95% CI 1.067-1.172, P <0.001), typical angina ( OR =8.970, 95% CI 2.963-27.154, P <0.001), and serum concentration of apolipoprotein B ( OR =20.311, 95% CI 4.774-86.416, P <0.001) were the independent risk factors of PCAG in degenerative valvular heart disease patients. Bootstrap method revealed satisfactory repeatability of multivariable logistic regression analysis results (age: OR =1.118, 95% CI 1.068-1.178, P =0.001; typical angina: OR =8.970, 95% CI 2.338-35.891, P =0.001; serum concentration of apolipoprotein B: OR =20.311, 95% CI 4.639-91.977, P =0.001). Conclusions: A low prevalence of PCAG before valvular surgery is observed in degenerative valvular heart disease patients in this patient cohort. Age, typical angina, and serum concentration of apolipoprotein B are independent risk factors of PCAG in this patient cohort.

Osteitis pubis and adductor tendinopathy in athletes: a novel arthroscopic pubic symphysis curettage and adductor reattachment.

PubMed

Hopp, Sascha Jörg; Culemann, Ulf; Kelm, Jens; Pohlemann, Tim; Pizanis, Antonius

2013-07-01

Various surgical treatment options have been described in athletes with degenerative osteitis pubis who fail to respond to conservative treatment modalities. Although adductor longus tendinopathy often represents an additional pain generator in chronic groin pain associated with osteitis pubis, this has not been acknowledged in the surgical literature, to our knowledge. We present the results of a novel surgical technique for combined degenerative lesions of the pubic symphysis joint and the adjacent adductor longus tendon in a series of athletes with osteitis pubis. During 2009 and 2010, five competitive non-professional soccer players with considerable groin and pubic pain were referred to our clinic, after conservative therapy over a period of at least 12 months had failed. According to our clinical protocol for patients with groin pain, physical examination, pelvic radiographs and arthrography of the pubic symphysis to detect microlesions of the adjacent adductor longus tendons were performed. The patients diagnosed with degenerative osteitis pubis and concomitant lesion of the adductor longus origin were indicated for surgery. Surgery consisted of resection of the degenerative soft and bone tissue and subsequent reattachment with suture anchors. With regard to stability of the symphysis pubis, a two-portal arthroscopic curettage of the degenerative fibrocartilaginous disc tissue was performed. The patients were followed prospectively at medium term with assessment of general pain level (VAS score) and sport activity with pain (NIPPS score) pre- and postoperatively. All patients recovered to full activity sports after an average period of 14.4 weeks. VAS and NIPPS scores markedly improved and overall satisfaction with the postoperative result was high. One intraoperative bleeding occurred, needing revision surgery. None of the patients developed pubic instability due to pubic symphysis curettage in the sequel. This novel surgical technique combines successfully stability-preserving arthroscopic pubic symphysis curettage with adductor debridement and reattachment in well-selected cases of athletes suffering from degenerative osteitis pubis and concomitant adductor pathology, being refractory to conservative treatment. Diligent preoperative evaluation of the specific pathology will lead to successful outcome.

Fire Control and Human Evolution.

ERIC Educational Resources Information Center

Russell, Claire

1978-01-01

Briefly outlines some aspects of the discovery of fire control by primitive people, such as the preadaptation for speech, the evolution of the human brain, and natural selection for human nakedness or loss of hair. (CS)

Brain Evolution and Human Neuropsychology: The Inferential Brain Hypothesis

PubMed Central

Koscik, Timothy R.; Tranel, Daniel

2013-01-01

Collaboration between human neuropsychology and comparative neuroscience has generated invaluable contributions to our understanding of human brain evolution and function. Further cross-talk between these disciplines has the potential to continue to revolutionize these fields. Modern neuroimaging methods could be applied in a comparative context, yielding exciting new data with the potential of providing insight into brain evolution. Conversely, incorporating an evolutionary base into the theoretical perspectives from which we approach human neuropsychology could lead to novel hypotheses and testable predictions. In the spirit of these objectives, we present here a new theoretical proposal, the Inferential Brain Hypothesis, whereby the human brain is thought to be characterized by a shift from perceptual processing to inferential computation, particularly within the social realm. This shift is believed to be a driving force for the evolution of the large human cortex. PMID:22459075

Human influences on evolution, and the ecological and societal consequences.

PubMed

Hendry, Andrew P; Gotanda, Kiyoko M; Svensson, Erik I

2017-01-19

Humans have dramatic, diverse and far-reaching influences on the evolution of other organisms. Numerous examples of this human-induced contemporary evolution have been reported in a number of 'contexts', including hunting, harvesting, fishing, agriculture, medicine, climate change, pollution, eutrophication, urbanization, habitat fragmentation, biological invasions and emerging/disappearing diseases. Although numerous papers, journal special issues and books have addressed each of these contexts individually, the time has come to consider them together and thereby seek important similarities and differences. The goal of this special issue, and this introductory paper, is to promote and expand this nascent integration. We first develop predictions as to which human contexts might cause the strongest and most consistent directional selection, the greatest changes in evolutionary potential, the greatest genetic (as opposed to plastic) changes and the greatest effects on evolutionary diversification We then develop predictions as to the contexts where human-induced evolutionary changes might have the strongest effects on the population dynamics of the focal evolving species, the structure of their communities, the functions of their ecosystems and the benefits and costs for human societies. These qualitative predictions are intended as a rallying point for broader and more detailed future discussions of how human influences shape evolution, and how that evolution then influences species traits, biodiversity, ecosystems and humans.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'. © 2016 The Author(s).

Nursing review of diagnosis and treatment of lumbar degenerative spondylolisthesis

PubMed Central

Epstein, Nancy E.; Hollingsworth, Renee D.

2017-01-01

Background: In the lumbar spine, degenerative spondylolisthesis or degenerative (not traumatic) slippage of one vertebral body over another is divided into 4 grades – grade I (25%), grade II (50%), grade III (75%), and grade IV (100%). Dynamic X-rays, magnetic resonance (MR), and computed tomography (CT) scans document the slip secondary to arthritic changes of the facet joint plus stenosis, ossification of the yellow ligament, disc herniations, and synovial cysts. MR best demonstrates soft tissue pathology whereas CT better delineates ossific/calcified disease. Methods: Grade I degenerative spondylolisthesis, typically found at the L4–L5 level followed by L3–L4 and L5S1, is more common in females (ratio 2:1) over the age of 65. Symptoms include radiculopathy (root pain) and neurogenic claudication (e.g., pain with ambulation, requiring the patient to stop, rest, sit down). Symptoms/signs may include unilateral/bilateral radiculopathy and uni/multifocal motor, reflex, and sensory deficits in. Some may also present with a cauda equina syndrome (e.g., paraparesis/sphincter dysfunction). Results: Surgery for grade I-II spondylolisthesis may include laminectomy alone, laminectomy/noninstrumented fusion or with an instrumented fusion. Older patients with osteoporosis are more likely to have no fusion or a noninstrumented fusion. All fusions utilize autograft harvested from the laminectomy that may or may not be combined with a bone graft expander (to increase the fusion mass) combined with autogenous bone marrow aspirate. The fusion mass is placed over the transverse processes following decortication. Conclusions: Patients with multilevel spinal stenosis and degenerative spondylolisthesis may require decompressive lumbar laminectomies alone or in combination with noninstrumented or instrumented fusions. PMID:29119044

A comparison of film and computer workstation measurements of degenerative spondylolisthesis: intraobserver and interobserver reliability.

PubMed

Bolesta, Michael J; Winslow, Lauren; Gill, Kevin

2010-06-01

A comparison of measurements of degenerative spondylolisthesis made on film and on computer workstations. To determine whether the 2 methodologies are comparable in some of the parameters used to assess lumbar degenerative spondylolisthesis. Digital radiology has been replacing analog radiographs. In scoliosis, several studies have shown that measurements made on digital and analog films are similar and that they are also similar to those made on computer workstations. Such work has not been done in spondylolisthesis. Twenty-four cases of lumbar degenerative spondylolisthesis were identified from our clinic practice. Three observers measured anterior displacement, sagittal rotation, and lumbar lordosis on digital films using the same protractor and pencil. The same parameters were measured on the same studies at clinical workstations. All measurements were repeated 2 weeks later. A statistician determined the intra and interobserver reliability of the 2 measurement methods and the degree of agreement between the 2 methods. The differences between the first and second readings did reach statistical significance in some cases, but none of them were large enough to be clinically meaningful. The interclass correlation coefficients (ICCs) were >or=0.80 except for one (0.67). The difference among the 3 observers was similarly statistically significant in a few instances but not enough to influence clinical decisions and with good ICCs (0.67 and better). Similarly, the differences in the 2 methods were small, and ICCs ranged from 0.69 to 0.98. This study supports the use of computer workstation measurements in lumbar degenerative spondylolisthesis. The parameters used in this study were comparable, whether measured on film or at clinical workstations.

Prevalence of degenerative and spondyloarthritis-related magnetic resonance imaging findings in the spine and sacroiliac joints in patients with persistent low back pain.

PubMed

Arnbak, Bodil; Jensen, Tue S; Egund, Niels; Zejden, Anna; Hørslev-Petersen, Kim; Manniche, Claus; Jurik, Anne G

2016-04-01

To estimate the prevalence of degenerative and spondyloarthritis (SpA)-related magnetic resonance imaging (MRI) findings in the spine and sacroiliac joints (SIJs) and analyse their association with gender and age in persistent low back pain (LBP) patients. Degenerative and SpA-related MRI findings in the whole spine and SIJs were evaluated in Spine Centre patients aged 18-40 years with LBP. Among the 1,037 patients, the prevalence of disc degeneration, disc contour changes and vertebral endplate signal (Modic) changes were 87 % (±SEM 1.1), 82 % (±1.2) and 48 % (±1.6). All degenerative spinal findings were most frequent in men and patients aged 30-40 years. Spinal SpA-related MRI findings were rare. In the SIJs, 28 % (±1.4) had at least one MRI finding, with bone marrow oedema being the most common (21 % (±1.3)). SIJ erosions were most prevalent in patients aged 18-29 years and bone marrow oedema in patients aged 30-40 years. SIJ sclerosis and fatty marrow deposition were most common in women. SIJ bone marrow oedema, sclerosis and erosions were most frequent in women indicating pregnancy-related LBP. The high prevalence of SIJ MRI findings associated with age, gender, and pregnancy-related LBP need further investigation of their clinical importance in LBP patients. • The location of vertebral endplate signal changes supports a mechanical aetiology. • Several sacroiliac joint findings were associated with female gender and pregnancy-related back pain. • Sacroiliac joint bone marrow oedema was frequent and age-associated, indicating a possible degenerative aetiology. • More knowledge of the clinical importance of sacroiliac joint MRI findings is needed.

The effects of muscle weakness on degenerative spondylolisthesis: A finite element study.

PubMed

Zhu, Rui; Niu, Wen-Xin; Zeng, Zhi-Li; Tong, Jian-Hua; Zhen, Zhi-Wei; Zhou, Shuang; Yu, Yan; Cheng, Li-Ming

2017-01-01

Whether muscle weakness is a cause, or result, of degenerative spondylolisthesis is not currently well understood. Little biomechanical evidence is available to offer an explanation for the mechanism behind exercise therapy. Therefore, the aim of this study is to investigate the effects of back muscle weakness on degenerative spondylolisthesis and to tease out the biomechanical mechanism of exercise therapy. A nonlinear 3-D finite element model of L3-L5 was constructed. Forces representing global back muscles and global abdominal muscles, follower loads and an upper body weight were applied. The force of the global back muscles was reduced to 75%, 50% and 25% to simulate different degrees of back muscle weakness. An additional boundary condition which represented the loads from other muscles after exercise therapy was set up to keep the spine in a neutral standing position. Shear forces, intradiscal pressure, facet joint forces and von Mises equivalent stresses in the annuli were calculated. The intervertebral rotations of L3-L4 and L4-L5 were within the range of in vitro experimental data. The calculated intradiscal pressure of L4-L5 for standing was 0.57MPa, which is similar to previous in vivo data. With the back muscles were reduced to 75%, 50% and 25% force, the shear force moved increasingly in a ventral direction. Due to the additional stabilizing force and moment provided by boundary conditions, the shear force varied less than 15%. Reducing the force of global back muscles might lead to, or aggravate, degenerative spondylolisthesis with forward slipping from biomechanical point of view. Exercise therapy may improve the spinal biomechanical environment. However, the intrinsic correlation between back muscle weakness and degenerative spondylolisthesis needs more clinical in vivo study and biomechanical analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of lumbar segmental instability in degenerative diseases by using a new intraoperative measurement system.

PubMed

Hasegawa, Kazuhiro; Kitahara, Ko; Hara, Toshiaki; Takano, Ko; Shimoda, Haruka; Homma, Takao

2008-03-01

In vivo quantitative measurement of lumbar segmental stability has not been established. The authors developed a new measurement system to determine intraoperative lumbar stability. The objective of this study was to clarify the biomechanical properties of degenerative lumbar segments by using the new method. Twenty-two patients with a degenerative symptomatic segment were studied and their measurements compared with those obtained in normal or asymptomatic degenerative segments (Normal group). The measurement system produces cyclic flexion-extension through spinous process holders by using a computer-controlled motion generator with all ligamentous structures intact. The following biomechanical parameters were determined: stiffness, absorption energy (AE), and neutral zone (NZ). Discs with degeneration were divided into 2 groups based on magnetic resonance imaging grading: degeneration without collapse (Collapse[-]) and degeneration with collapse (Collapse[+]). Biomechanical parameters were compared among the groups. Relationships among the biomechanical parameters and age, diagnosis, or radiographic parameters were analyzed. The mean stiffness value in the Normal group was significantly greater than that in Collapse(-) or Collapse(+) group. There was no significant difference in the average AE value among the Normal, Collapse(-), and Collapse(+) groups. The NZ in the Collapse(-) was significantly higher than in the Normal or Collapse(+) groups. Stiffness was negatively and NZ was positively correlated with age. Stiffness demonstrated a significant negative and NZ a significant positive relationship with disc height, however. There were no significant differences in stiffness between spines in the Collapse(-) and Collapse(+) groups. The values of a more sensitive parameter, NZ, were higher in Collapse(-) than in Collapse(+) groups, demonstrating that degenerative segments with preserved disc height have a latent instability compared to segments with collapsed discs.

[3-Tesla MRI vs. arthroscopy for diagnostics of degenerative knee cartilage diseases: preliminary clinical results].

PubMed

von Engelhardt, L V; Schmitz, A; Burian, B; Pennekamp, P H; Schild, H H; Kraft, C N; von Falkenhausen, M

2008-09-01

The literature contains only a few studies investigating the magnetic resonance imaging (MRI) diagnostics of degenerative cartilage diseases. Studies on MRI diagnostics of the cartilage using field strengths of 3-Tesla demonstrate promising results. To assess the value of 3-Tesla MRI for decision making regarding conservative or operative treatment possibilities, this study focused on patients with degenerative cartilage diseases. Thirty-two patients with chronic knee pain, a minimum age of 40 years, a negative history of trauma, and at least grade II degenerative cartilage disease were included. Cartilage abnormalities detected at preoperative 3-Tesla MRI (axial/koronar/sagittal PD-TSE-SPAIR, axial/sagittal 3D-T1-FFE, axial T2-FFE; Intera 3.0T, Philips Medical Systems) were classified (grades I-IV) and compared with arthroscopic findings. Thirty-six percent (70/192) of the examined cartilage surfaces demonstrated no agreement between MRI and arthroscopic grading. In most of these cases, grades II and III cartilage lesions were confounded with each other. Regarding the positive predictive values, the probability that a positive finding in MRI would be exactly confirmed by arthroscopy was 39-72%. In contrast, specificities and negative predictive values of different grades of cartilage diseases were 85-95%. Regarding the high specificities and negative predictive values, 3-Tesla MRI is a reliable method for excluding even slight cartilage degeneration. In summary, in degenerative cartilage diseases, 3-Tesla MRI is a supportive, noninvasive method for clinical decision making regarding conservative or operative treatment possibilities. However, the value of diagnostic arthroscopy for a definitive assessment of the articular surfaces and for therapeutic planning currently cannot be replaced by 3-Tesla MRI. This applies especially to treatment options in which a differentiation between grade II and III cartilage lesions is of interest.

Relationship of individual scapular anatomy and degenerative rotator cuff tears.

PubMed

Moor, Beat K; Wieser, Karl; Slankamenac, Ksenija; Gerber, Christian; Bouaicha, Samy

2014-04-01

The etiology of rotator cuff disease is age related, as documented by prevalence data. Despite conflicting results, growing evidence suggests that distinct scapular morphologies may accelerate the underlying degenerative process. The purpose of the present study was to evaluate the predictive power of 5 commonly used radiologic parameters of scapular morphology to discriminate between patients with intact rotator cuff tendons and those with torn rotator cuff tendons. A pre hoc power analysis was performed to determine the sample size. Two independent readers measured the acromion index, lateral acromion angle, and critical shoulder angle on standardized anteroposterior radiographs. In addition, the acromial morphology according to Bigliani and the acromial slope were determined on true outlet views. Measurements were performed in 51 consecutive patients with documented degenerative rotator cuff tears and in an age- and sex-matched control group of 51 patients with intact rotator cuff tendons. Receiver operating characteristic analyses were performed to determine cutoff values and to assess the sensitivity and specificity of each parameter. Patients with degenerative rotator cuff tears demonstrated significantly higher acromion indices, smaller lateral acromion angles, and larger critical shoulder angles than patients with intact rotator cuffs. However, no difference was found between the acromial morphology according to Bigliani and the acromial slope. With an area under the receiver operating characteristic curve of 0.855 and an odds ratio of 10.8, the critical shoulder angle represented the strongest predictor for the presence of a rotator cuff tear. The acromion index, lateral acromion angle, and critical shoulder angle accurately predict the presence of degenerative rotator cuff tears. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

Intra-articular injections of HYADD4-G in male professional soccer players with traumatic or degenerative knee chondropathy. A pilot, prospective study.

PubMed

Tamburrino, Pasquale; Castellacci, Enrico

2016-12-01

Knee injuries are very common in some sports and particularly in soccer due to the highly repetitive loading of the mechanical stress involved in this practice. Knee-joint injuries account for 40% of all different kinds of lesions. Traumatic or degenerative patellofemoral or tibialfemoral chondropaties of knee cause disabling symptoms, joint pain and/or dysfunctions. The aim of the study was to evaluate the effects of HYADD4-G, a hydrogel based on a hyaluronic acid derivative, in professional soccer players affected by traumatic or degenerative knee chondropathy. Thirty male professional soccer players participants in the Italian League 2014-2015, affected by traumatic or degenerative knee patellofemoral (N.=12) or tibiofemoral (N.=18) chondropathy assessed through MRI and/or arthroscopy of knee joints and the ICRS staging (International Cartilage Repair Society ≤3a), were enrolled in this pilot prospective study. Patients underwent 2 intra-articular (IA) injections of HYADD4-G (3 mL of 8 mg/mL) at one week interval. Patients were prospectively evaluated at baseline and then at 1, 3 and 6 months after the treatment by the Osteoarthritis Outcome Score (KOOS) Score (main outcome) and by the Visual Analog Scale (VAS) to evaluate pain. A significant improvement in all clinical endpoints from pretreatment to different times of evaluation was found in all patients. ANOVA with repeated measure using the SPSS has showed significantly better results in term of KOOS and VAS scores at 1, 3 and 6 months compared to the pre-injection value (P<0.05). IA HYADD4-G is highly effective to improve resting and walking pain in professional male soccer players with traumatic or degenerative knee chondropathy.

The human genome and the human control of natural evolution.

PubMed

Sakamoto, H

2001-10-01

Recent advances in research on the Human Genome are provoking many critical problems in the global policy regarding the future status of human beings as well as in that of the whole life system on the earth, and consequently, these advances provoke the serious bioethical and philosophical questions. Firstly, how can we comprehend that we are going to have the complete technology to manipulate the system of the human genome and other non-human genomes? Though no science and technology can be complete, we will, I believe, take possession of an almost complete gene technology in the early stage of the next Century. Gene technology will soon fall into the hands of human beings instead of rendering in the province of God. Secondly, which gene technologies will we actually realize and utilize in the early stages of the 21st Century? Most probably, we will adopt these technologies to health care to treat some apparent bodily diseases, for instance, cancer, hemophilia, ADA deficiency, and so forth, and sooner or later we will adopt gene therapy to germ lines, which, in the long run, suggests the possibility of a future "artificial evolution" instead of the "natural evolution" of the past. Thirdly, how is the new concept of "artificial evolution" justified ethically? I believe this kind of manmade evolution is the only way for human beings to survive into the future global environment. There cannot be any serious ethical objection against the idea of artificial evolution. Fourthly, what is the background philosophy for the concept of "artificial evolution"? I will discuss the nature of modern European humanism with individual dignity and fundamental human rights which has led the philosophy of modern culture and modern society, and I will conclude by suggesting that we should abolish an essential part of modern humanism and newly devise some alternative philosophy to fit the new Millennium.

Grandmothering life histories and human pair bonding.

PubMed

Coxworth, James E; Kim, Peter S; McQueen, John S; Hawkes, Kristen

2015-09-22

The evolution of distinctively human life history and social organization is generally attributed to paternal provisioning based on pair bonds. Here we develop an alternative argument that connects the evolution of human pair bonds to the male-biased mating sex ratios that accompanied the evolution of human life history. We simulate an agent-based model of the grandmother hypothesis, compare simulated sex ratios to data on great apes and human hunter-gatherers, and note associations between a preponderance of males and mate guarding across taxa. Then we explore a recent model that highlights the importance of mating sex ratios for differences between birds and mammals and conclude that lessons for human evolution cannot ignore mammalian reproductive constraints. In contradiction to our claim that male-biased sex ratios are characteristically human, female-biased ratios are reported in some populations. We consider the likelihood that fertile men are undercounted and conclude that the mate-guarding hypothesis for human pair bonds gains strength from explicit links with our grandmothering life history.

Accelerated Evolution of the Pituitary Adenylate Cyclase-Activating Polypeptide Precursor Gene During Human Origin

PubMed Central

Wang, Yin-qiu; Qian, Ya-ping; Yang, Su; Shi, Hong; Liao, Cheng-hong; Zheng, Hong-Kun; Wang, Jun; Lin, Alice A.; Cavalli-Sforza, L. Luca; Underhill, Peter A.; Chakraborty, Ranajit; Jin, Li; Su, Bing

2005-01-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide abundantly expressed in the central nervous system and involved in regulating neurogenesis and neuronal signal transduction. The amino acid sequence of PACAP is extremely conserved across vertebrate species, indicating a strong functional constraint during the course of evolution. However, through comparative sequence analysis, we demonstrated that the PACAP precursor gene underwent an accelerated evolution in the human lineage since the divergence from chimpanzees, and the amino acid substitution rate in humans is at least seven times faster than that in other mammal species resulting from strong Darwinian positive selection. Eleven human-specific amino acid changes were identified in the PACAP precursors, which are conserved from murine to African apes. Protein structural analysis suggested that a putative novel neuropeptide might have originated during human evolution and functioned in the human brain. Our data suggested that the PACAP precursor gene underwent adaptive changes during human origin and may have contributed to the formation of human cognition. PMID:15834139

The contribution of mouse models to understanding the pathogenesis of spinal muscular atrophy

PubMed Central

Sleigh, James N.; Gillingwater, Thomas H.; Talbot, Kevin

2011-01-01

Spinal muscular atrophy (SMA), which is caused by inactivating mutations in the survival motor neuron 1 (SMN1) gene, is characterized by loss of lower motor neurons in the spinal cord. The gene encoding SMN is very highly conserved in evolution, allowing the disease to be modeled in a range of species. The similarities in anatomy and physiology to the human neuromuscular system, coupled with the ease of genetic manipulation, make the mouse the most suitable model for exploring the basic pathogenesis of motor neuron loss and for testing potential treatments. Therapies that increase SMN levels, either through direct viral delivery or by enhancing full-length SMN protein expression from the SMN1 paralog, SMN2, are approaching the translational stage of development. It is therefore timely to consider the role of mouse models in addressing aspects of disease pathogenesis that are most relevant to SMA therapy. Here, we review evidence suggesting that the apparent selective vulnerability of motor neurons to SMN deficiency is relative rather than absolute, signifying that therapies will need to be delivered systemically. We also consider evidence from mouse models suggesting that SMN has its predominant action on the neuromuscular system in early postnatal life, during a discrete phase of development. Data from these experiments suggest that the timing of therapy to increase SMN levels might be crucial. The extent to which SMN is required for the maintenance of motor neurons in later life and whether augmenting its levels could treat degenerative motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), requires further exploration. PMID:21708901

Gastrointestinal tract and the elderly: functional foods, gut microflora and healthy ageing.

PubMed

Saunier, K; Doré, J

2002-09-01

Advances in science and medicine as well as improved living standards have led to a steady increase in life expectancy. Yet ageing is associated with increased susceptibility to degenerative or infectious diseases, which may be exacerbated by a poor nutritional status. The intestinal microflora will mediate crucial events towards the protection or degradation of health. It is hence essential and timely that strategies of preventive nutrition aimed at maintaining or improving the quality of life of the ageing population be developed. "CROWNALIFE" is a newly funded EuropeanUnion project, so called because of its emphasis on the preservation of the period of independence of the elderly, recognised as the "crown of life". The project aims at assessing age-related alterations and exploring strategies to restore and maintain a balanced healthy intestinal environment. Current knowledge on the composition and function of the human intestinal microflora is still improving with the use of better methodologies and yet their evolution with ageing has not been investigated in detail. There have been a few reports that putatively protective lactic acid bacteria, in general, and bifidobacteria, in particular, seem less represented in the elderly faecal flora. We have also observed an increase in species diversity of the dominant faecal microflora with ageing. This certainly warrants confirmation and is being addressed by the investigation of age-related changes in the structure and function of the intestinal flora of the elderly in countries across Europe. Ensuing results will constitute a baseline for functional-food based strategies aimed at providing health benefits for the elderly.

Electromagnetic fields in the treatment of chronic lower back pain in patients with degenerative disc disease

PubMed Central

Arneja, Amarjit S; Kotowich, Alan; Staley, Doug; Summers, Randy; Tappia, Paramjit S

2016-01-01

Aim: To examine the effects of low-amplitude, low frequency electromagnetic field therapy (EMF) therapy in patients with persistent chronic lower back pain associated with degenerative disc disease. Design: Double-blind, randomized and placebo controlled. Intervention: EMF using a medical device resonator; control group underwent same procedures, except the device was turned off. Outcome measures: Pain reduction and mobility. Results: Improvements in overall physical health, social functioning and reduction in bodily pain were observed in the EMF group. The pain relief rating scale showed a higher level of pain relief at the target area in the EMF group. An increase in left lateral mobility was seen only in the EMF group. Conclusion: EMF treatment may be of benefit to patients with chronic nonresponsive lower back pain associated with degenerative disc disease. PMID:28031951

[Virtual clinical diagnosis support system of degenerative stenosis of the lumbar spinal canal].

PubMed

Shevelev, I N; Konovalov, N A; Cherkashov, A M; Molodchenkov, A A; Sharamko, T G; Asiutin, D S; Nazarenko, A G

2013-01-01

The aim of the study was to develop a virtual clinical diagnostic support system of degenerative lumbar spinal stenosis on database of spine registry. Choice of criteria's for diagnostic system was made on symptom analysis of 298 patients with lumbar spinal stenosis. Also was analysed a group of patient with disc herniation's for sensitivity and specify assessment of developed diagnostic support system. Represented clinical diagnostic support system allows identifying patients with degenerative lumbar spinal stenosis on stage of patient's primary visit. System sensitivity and specify are 90 and 71% respectively. "Online" mode of diagnostic system in structure of spine registry provides maximal availability for specialists, regardless of their locations. Development of tools "medicine 2.0" is the actual direction for carrying out further researches with which carrying out the centralized baea collection by means of specialized registers helps.

Accepting, understanding, teaching, and learning (human) evolution: Obstacles and opportunities.

PubMed

Pobiner, Briana

2016-01-01

Questions about our origin as a species are universal and compelling. Evolution-and in particular human evolution-is a subject that generates intense interest across the world, evidenced by the fact that fossil and DNA discoveries grace the covers of major science journals and magazines as well as other popular print and online media. However, virtually all national polls indicate that the majority of Americans strongly reject biological evolution as a fact-based, well-tested, and robust understanding of the history of life. In the popular mind, no topic in all of science is more contentious or polarizing than evolution and media sources often only serve to magnify this polarization by covering challenges to the teaching of evolution. In the realm of teaching, debates about evolution have shaped textbooks, curricula, standards, and policy. Challenges to accepting and understanding evolution include mistrust and denial of science, cognitive obstacles and misconceptions, language and terminology, and a religious worldview, among others. Teachers, who are on the front lines of these challenges, must be armed with the tools and techniques to teach evolution in formal education settings across grades K-16 in a straightforward, thorough, and sensitive way. Despite the potentially controversial topic of human evolution, growing research is demonstrating that a pedagogical focus on human examples is an effective and engaging way to teach core concepts of evolutionary biology. © 2016 Wiley Periodicals, Inc.

Within-Host Evolution of Human Influenza Virus.

PubMed

Xue, Katherine S; Moncla, Louise H; Bedford, Trevor; Bloom, Jesse D

2018-03-10

The rapid global evolution of influenza virus begins with mutations that arise de novo in individual infections, but little is known about how evolution occurs within hosts. We review recent progress in understanding how and why influenza viruses evolve within human hosts. Advances in deep sequencing make it possible to measure within-host genetic diversity in both acute and chronic influenza infections. Factors like antigenic selection, antiviral treatment, tissue specificity, spatial structure, and multiplicity of infection may affect how influenza viruses evolve within human hosts. Studies of within-host evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape influenza virus's global evolution. Copyright © 2018 Elsevier Ltd. All rights reserved.

Adult Degenerative Scoliosis with Spinal Stenosis Treated with Stand-Alone Cage via an Extreme Lateral Transpsoas Approach; a Case Report and Literature Review

PubMed Central

von Keudell, Arvind; Alimi, Marjan; Gebhard, Harry; Härtl, Roger

2015-01-01

We report the case of a 73-year-old female with severe degenerative scoliosis and back and leg pain that was successfully treated with stand- alone cages via an extreme lateral transpsoas approach. This patient had declined open surgery and instrumentation due to her advanced age concerns about potential side effects. PMID:26110180

Study of metabolism and energetics in hypogravity: Degenerative effects of prolonged hypogravity

NASA Technical Reports Server (NTRS)

Siegel, S. M.

1976-01-01

The role of gravity in the formation of rigid, lignified plant cell walls hence to the development of the erect land plant body is examined. An experiment was proposed with a general hypothesis that a chosen plant, a dwarf marigold, would display degenerative changes in mechanical supportive systems under hypogravity because normal lignin-cellulose wall structure fails to develop. Observational and experimental results are given.

Etiology impacts survival in patients with severe aortic regurgitation: results from a cohort of 756 patients.

PubMed

Varadarajan, Padmini; Patel, Reena; Turk, Rami; Kamath, Ashvin R; Sampath, Unnati; Khandhar, Sumit; Pai, Ramdas G

2013-01-01

Severe aortic regurgitation (AR) is caused by a variety of mechanisms, which include the degenerative process, bicuspid aortic valve (BAV), aortic root dilation, endocarditis or a combination of these. Their frequency in a contemporary clinical series, and their impact on survival, are currently unknown. The authors' echocardiographic database between 1993 and 2007 was screened for patients with severe AR, and yielded 756 patients. Detailed chart reviews were performed to acquire clinical and demographic data. Mortality data were obtained from the social security death index and analyzed as a function of the condition's etiology. The probable etiologies for AR were: degenerative in 29% of patients, BAV in 10%, aortic root pathology in 11%, endocarditis in 10%, and mixed or unclear mechanism in 40%. Survival was a function of the etiology (p < 0.0001), with degenerative mechanism having the worst prognosis and BAV the best. This differential impact on mortality remained significant after adjusting for age, gender, coronary artery disease, diabetes mellitus, renal insufficiency, left ventricular ejection fraction and aortic valve replacement, using the Cox regression model (p < 0.0001). Etiology has a significant independent impact on mortality in patients with severe AR, with the worst survival being seen in degenerative AR.

Effects of phototherapy on cartilage structure and inflammatory markers in an experimental model of osteoarthritis

NASA Astrophysics Data System (ADS)

Oliveira, Poliani; Santos, Anderson Amaro; Rodrigues, Tamara; Tim, Carla Roberta; Pinto, Karina Zambone; Magri, Angela Maria Paiva; Fernandes, Kelly Rossetti; Mattiello, Stela M.; Parizotto, Nivaldo Antonio; Anibal, Fernanda Freitas; Rennó, Ana Claudia Muniz

2013-12-01

The aim of this study was to evaluate the effects of laser phototherapy on the degenerative modifications on the articular cartilage after the anterior cruciate ligament transection (ACLT) in the knee of rats. Eighty male rats (Wistar) were distributed into four groups: intact control group (IG), injured control group (CG), injured laser treated group at 10 J/cm2 (L10), and injured laser treated group at 50 J/cm2 (L50). Animals were distributed into two subgroups, sacrificed in 5 and 8 weeks postsurgery. The ACLT was used to induce knee osteoarthritis in rats. After 2 weeks postsurgery, laser phototherapy initiated and it was performed for 15 and 30 sessions. The histological findings revealed that laser irradiation, especially at 10 J/cm2, modulated the progression of the degenerative process, showing a better cartilage structure and lower number of condrocytes compared to the other groups. Laser phototherapy was not able to decrease the degenerative process measured by Mankin score and prevent the increase of cartilage thickness related to the degenerative process. Moreover, it did not have any effect in the biomodulation of the expression of markers IL1β, tumor necrosis factor-α, and metalloprotein-13. Furthermore, laser irradiated animals, at 50 J/cm2 showed a lower amount of collagen type 1.

The prevalence of sacroiliac joint degeneration in asymptomatic adults.

PubMed

Eno, Jonathan-James T; Boone, Christopher R; Bellino, Michael J; Bishop, Julius A

2015-06-03

Degenerative changes of the sacroiliac joint have been implicated as a cause of lower back pain in adults. The purpose of this study was to determine the prevalence of sacroiliac joint degeneration in asymptomatic patients. Five hundred consecutive pelvic computed tomography (CT) scans, made at a tertiary-care medical center, of patients with no history of pain in the lower back or pelvic girdle were retrospectively reviewed and analyzed for degenerative changes of the sacroiliac joint. After exclusion criteria were applied, 373 CT scans (746 sacroiliac joints) were evaluated for degenerative changes. Regression analysis was used to determine the association between age and the degree of sacroiliac joint degeneration. The prevalence of sacroiliac joint degeneration was 65.1%, with substantial degeneration occurring in 30.5% of asymptomatic subjects. The prevalence steadily increased with age, with 91% of subjects in the ninth decade of life displaying degenerative changes. Radiographic evidence of sacroiliac joint degeneration is highly prevalent in the asymptomatic population and is associated with age. Caution must be exercised when attributing lower back or pelvic girdle pain to sacroiliac joint degeneration seen on imaging. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Identifying Degenerative Brain Disease Using Rough Set Classifier Based on Wavelet Packet Method.

PubMed

Cheng, Ching-Hsue; Liu, Wei-Xiang

2018-05-28

Population aging has become a worldwide phenomenon, which causes many serious problems. The medical issues related to degenerative brain disease have gradually become a concern. Magnetic Resonance Imaging is one of the most advanced methods for medical imaging and is especially suitable for brain scans. From the literature, although the automatic segmentation method is less laborious and time-consuming, it is restricted in several specific types of images. In addition, hybrid techniques segmentation improves the shortcomings of the single segmentation method. Therefore, this study proposed a hybrid segmentation combined with rough set classifier and wavelet packet method to identify degenerative brain disease. The proposed method is a three-stage image process method to enhance accuracy of brain disease classification. In the first stage, this study used the proposed hybrid segmentation algorithms to segment the brain ROI (region of interest). In the second stage, wavelet packet was used to conduct the image decomposition and calculate the feature values. In the final stage, the rough set classifier was utilized to identify the degenerative brain disease. In verification and comparison, two experiments were employed to verify the effectiveness of the proposed method and compare with the TV-seg (total variation segmentation) algorithm, Discrete Cosine Transform, and the listing classifiers. Overall, the results indicated that the proposed method outperforms the listing methods.

Global warming and neurodegenerative disorders: speculations on their linkage.

PubMed

Habibi, Laleh; Perry, George; Mahmoudi, Morteza

2014-01-01

Climate change is having considerable impact on biological systems. Eras of ice ages and warming shaped the contemporary earth and origin of creatures including humans. Warming forces stress conditions on cells. Therefore, cells evolved elaborate defense mechanisms, such as creation of heat shock proteins, to combat heat stress. Global warming is becoming a crisis and this process would yield an undefined increasing rate of neurodegenerative disorders in future decades. Since heat stress is known to have a degenerative effects on neurons and, conversely, cold conditions have protective effect on these cells, we hypothesize that persistent heat stress forced by global warming might play a crucial role in increasing neurodegenerative disorders.

Derivation of Functional Human Astrocytes from Cerebral Organoids

PubMed Central

Dezonne, Rômulo Sperduto; Sartore, Rafaela Costa; Nascimento, Juliana Minardi; Saia-Cereda, Verônica M.; Romão, Luciana Ferreira; Alves-Leon, Soniza Vieira; de Souza, Jorge Marcondes; Martins-de-Souza, Daniel; Rehen, Stevens Kastrup; Gomes, Flávia Carvalho Alcantara

2017-01-01

Astrocytes play a critical role in the development and homeostasis of the central nervous system (CNS). Astrocyte dysfunction results in several neurological and degenerative diseases. However, a major challenge to our understanding of astrocyte physiology and pathology is the restriction of studies to animal models, human post-mortem brain tissues, or samples obtained from invasive surgical procedures. Here, we report a protocol to generate human functional astrocytes from cerebral organoids derived from human pluripotent stem cells. The cellular isolation of cerebral organoids yielded cells that were morphologically and functionally like astrocytes. Immunolabelling and proteomic assays revealed that human organoid-derived astrocytes express the main astrocytic molecular markers, including glutamate transporters, specific enzymes and cytoskeletal proteins. We found that organoid-derived astrocytes strongly supported neuronal survival and neurite outgrowth and responded to ATP through transient calcium wave elevations, which are hallmarks of astrocyte physiology. Additionally, these astrocytes presented similar functional pathways to those isolated from adult human cortex by surgical procedures. This is the first study to provide proteomic and functional analyses of astrocytes isolated from human cerebral organoids. The isolation of these astrocytes holds great potential for the investigation of developmental and evolutionary features of the human brain and provides a useful approach to drug screening and neurodegenerative disease modelling. PMID:28345587

Human Resource Management and Human Resource Development: Evolution and Contributions

ERIC Educational Resources Information Center

Richman, Nicole

2015-01-01

Research agrees that a high performance organization (HPO) cannot exist without an elevated value placed on human resource management (HRM) and human resource development (HRD). However, a complementary pairing of HRM and HRD has not always existed. The evolution of HRD from its roots in human knowledge transference to HRM and present day HRD…

Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution.

PubMed

Mendizabal, Isabel; Shi, Lei; Keller, Thomas E; Konopka, Genevieve; Preuss, Todd M; Hsieh, Tzung-Fu; Hu, Enzhi; Zhang, Zhe; Su, Bing; Yi, Soojin V

2016-11-01

How do epigenetic modifications change across species and how do these modifications affect evolution? These are fundamental questions at the forefront of our evolutionary epigenomic understanding. Our previous work investigated human and chimpanzee brain methylomes, but it was limited by the lack of outgroup data which is critical for comparative (epi)genomic studies. Here, we compared whole genome DNA methylation maps from brains of humans, chimpanzees and also rhesus macaques (outgroup) to elucidate DNA methylation changes during human brain evolution. Moreover, we validated that our approach is highly robust by further examining 38 human-specific DMRs using targeted deep genomic and bisulfite sequencing in an independent panel of 37 individuals from five primate species. Our unbiased genome-scan identified human brain differentially methylated regions (DMRs), irrespective of their associations with annotated genes. Remarkably, over half of the newly identified DMRs locate in intergenic regions or gene bodies. Nevertheless, their regulatory potential is on par with those of promoter DMRs. An intriguing observation is that DMRs are enriched in active chromatin loops, suggesting human-specific evolutionary remodeling at a higher-order chromatin structure. These findings indicate that there is substantial reprogramming of epigenomic landscapes during human brain evolution involving noncoding regions. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The Molecular Basis of Human Brain Evolution.

PubMed

Enard, Wolfgang

2016-10-24

Humans are a remarkable species, especially because of the remarkable properties of their brain. Since the split from the chimpanzee lineage, the human brain has increased three-fold in size and has acquired abilities for vocal learning, language and intense cooperation. To better understand the molecular basis of these changes is of great biological and biomedical interest. However, all the about 16 million fixed genetic changes that occurred during human evolution are fully correlated with all molecular, cellular, anatomical and behavioral changes that occurred during this time. Hence, as humans and chimpanzees cannot be crossed or genetically manipulated, no direct evidence for linking particular genetic and molecular changes to human brain evolution can be obtained. Here, I sketch a framework how indirect evidence can be obtained and review findings related to the molecular basis of human cognition, vocal learning and brain size. In particular, I discuss how a comprehensive comparative approach, leveraging cellular systems and genomic technologies, could inform the evolution of our brain in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

From Darwinian to technological evolution: forgetting the human lottery.

PubMed

Tintino, Giorgio

2014-01-01

The GRIN technologies (-geno, -robo, -info, -nano) promise to change the inner constitution of human body and its own existence. This transformation involves the structure of our lives and represent a brave new world that we have to explore and to manage. In this sense, the traditional tools of humanism seems very inadequate to think the biotech century and there is a strong demand of a new thought for the evolution and the concrete history of life. The posthuman philosophy tries to take this new path of human existence in all of its novelty since GRIN technologies seem to promise new and unexpected paths of evolution to living beings and, above all, man. For this, the post-human thought, as we see, is a new anthropological overview on the concrete evolution of human being, an overview that involves an epistemological revolution of the categories that humanism uses to conceptualize the journey that divides the Homo sapiens from the man. But, is this right?

Evolution of the human-specific microRNA miR-941

PubMed Central

Hu, Hai Yang; He, Liu; Fominykh, Kseniya; Yan, Zheng; Guo, Song; Zhang, Xiaoyu; Taylor, Martin S.; Tang, Lin; Li, Jie; Liu, Jianmei; Wang, Wen; Yu, Haijing; Khaitovich, Philipp

2012-01-01

MicroRNA-mediated gene regulation is important in many physiological processes. Here we explore the roles of a microRNA, miR-941, in human evolution. We find that miR-941 emerged de novo in the human lineage, between six and one million years ago, from an evolutionarily volatile tandem repeat sequence. Its copy-number remains polymorphic in humans and shows a trend for decreasing copy-number with migration out of Africa. Emergence of miR-941 was accompanied by accelerated loss of miR-941-binding sites, presumably to escape regulation. We further show that miR-941 is highly expressed in pluripotent cells, repressed upon differentiation and preferentially targets genes in hedgehog- and insulin-signalling pathways, thus suggesting roles in cellular differentiation. Human-specific effects of miR-941 regulation are detectable in the brain and affect genes involved in neurotransmitter signalling. Taken together, these results implicate miR-941 in human evolution, and provide an example of rapid regulatory evolution in the human linage. PMID:23093182

Human-specific protein isoforms produced by novel splice sites in the human genome after the human-chimpanzee divergence.

PubMed

Kim, Dong Seon; Hahn, Yoonsoo

2012-11-13

Evolution of splice sites is a well-known phenomenon that results in transcript diversity during human evolution. Many novel splice sites are derived from repetitive elements and may not contribute to protein products. Here, we analyzed annotated human protein-coding exons and identified human-specific splice sites that arose after the human-chimpanzee divergence. We analyzed multiple alignments of the annotated human protein-coding exons and their respective orthologous mammalian genome sequences to identify 85 novel splice sites (50 splice acceptors and 35 donors) in the human genome. The novel protein-coding exons, which are expressed either constitutively or alternatively, produce novel protein isoforms by insertion, deletion, or frameshift. We found three cases in which the human-specific isoform conferred novel molecular function in the human cells: the human-specific IMUP protein isoform induces apoptosis of the trophoblast and is implicated in pre-eclampsia; the intronization of a part of SMOX gene exon produces inactive spermine oxidase; the human-specific NUB1 isoform shows reduced interaction with ubiquitin-like proteins, possibly affecting ubiquitin pathways. Although the generation of novel protein isoforms does not equate to adaptive evolution, we propose that these cases are useful candidates for a molecular functional study to identify proteomic changes that might bring about novel phenotypes during human evolution.

Construction of a plasmid for human brain-derived neurotrophic factor and its effect on retinal pigment epithelial cell viability

PubMed Central

Yan, Bo-jing; Wu, Zhi-zhong; Chong, Wei-hua; Li, Gen-lin

2016-01-01

Several studies have investigated the protective functions of brain-derived neurotrophic factor (BDNF) in retinitis pigmentosa. However, a BDNF-based therapy for retinitis pigmentosa is not yet available. To develop an efficient treatment for fundus disease, an eukaryotic expression plasmid was generated and used to transfect human 293T cells to assess the expression and bioactivity of BDNF on acute retinal pigment epithelial-19 (ARPE-19) cells, a human retinal epithelial cell line. After 96 hours of co-culture in a Transwell chamber, ARPE-19 cells exposed to BDNF secreted by 293T cells were more viable than ARPE-19 cells not exposed to secreted BDNF. Western blot assay showed that Bax levels were downregulated and that Bcl-2 levels were upregulated in human ARPE-19 cells exposed to BDNF. Furthermore, 293T cells transfected with the BDNF gene steadily secreted the protein. The powerful anti-apoptotic function of this BDNF may be useful for the treatment of retinitis pigmentosa and other retinal degenerative diseases. PMID:28197196

Polyphenol-Rich Dry Common Beans (Phaseolus vulgaris L.) and Their Health Benefits

PubMed Central

Ganesan, Kumar

2017-01-01

Polyphenols are plant metabolites with potent anti-oxidant properties, which help to reduce the effects of oxidative stress-induced dreaded diseases. The evidence demonstrated that dietary polyphenols are of emerging increasing scientific interest due to their role in the prevention of degenerative diseases in humans. Possible health beneficial effects of polyphenols are based on the human consumption and their bioavailability. Common beans (Phaseolus vulgaris L.) are a greater source of polyphenolic compounds with numerous health promoting properties. Polyphenol-rich dry common beans have potential effects on human health, and possess anti-oxidant, anti-diabetic, anti-obesity, anti-inflammatory and anti-mutagenic and anti-carcinogenic properties. Based on the studies, the current comprehensive review aims to provide up-to-date information on the nutritional compositions and health-promoting effect of polyphenol-rich common beans, which help to explore their therapeutic values for future clinical studies. Investigation of common beans and their impacts on human health were obtained from various library databases and electronic searches (Science Direct PubMed, and Google Scholar). PMID:29113066

Polyphenol-Rich Lentils and Their Health Promoting Effects.

PubMed

Ganesan, Kumar; Xu, Baojun

2017-11-10

Polyphenols are a group of plant metabolites with potent antioxidant properties, which protect against various chronic diseases induced by oxidative stress. Evidence showed that dietary polyphenols have emerged as one of the prominent scientific interests due to their role in the prevention of degenerative diseases in humans. Possible health beneficial effects of polyphenols are measured based on the human consumption and their bioavailability. Lentil ( Lens culinaris ; Family: Fabaceae) is a great source of polyphenol compounds with various health-promoting properties. Polyphenol-rich lentils have a potential effect on human health, possessing properties such as antioxidant, antidiabetic, anti-obesity, anti-hyperlipidemic, anti-inflammatory and anticancer. Based on the explorative study, the current comprehensive review aims to give up-to-date information on nutritive compositions, bioactive compounds and the health-promoting effect of polyphenol-rich lentils, which explores their therapeutic values for future clinical studies. All data of in vitro , in vivo and clinical studies of lentils and their impact on human health were collected from a library database and electronic search (Science Direct, PubMed and Google Scholar). Health-promoting information was gathered and orchestrated in the suitable place in the review.

Human myosin VIIA responsible for the Usher 1B syndrome: a predicted membrane-associated motor protein expressed in developing sensory epithelia.

PubMed

Weil, D; Levy, G; Sahly, I; Levi-Acobas, F; Blanchard, S; El-Amraoui, A; Crozet, F; Philippe, H; Abitbol, M; Petit, C

1996-04-16

The gene encoding human myosin VIIA is responsible for Usher syndrome type III (USH1B), a disease which associates profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. The reconstituted cDNA sequence presented here predicts a 2215 amino acid protein with a typical unconventional myosin structure. This protein is expected to dimerize into a two-headed molecule. The C terminus of its tail shares homology with the membrane-binding domain of the band 4.1 protein superfamily. The gene consists of 48 coding exons. It encodes several alternatively spliced forms. In situ hybridization analysis in human embryos demonstrates that the myosin VIIA gene is expressed in the pigment epithelium and the photoreceptor cells of the retina, thus indicating that both cell types may be involved in the USH1B retinal degenerative process. In addition, the gene is expressed in the human embryonic cochlear and vestibular neuroepithelia. We suggest that deafness and vestibular dysfunction in USH1B patients result from a defect in the morphogenesis of the inner ear sensory cell stereocilia.

Genetics and the making of Homo sapiens.

PubMed

Carroll, Sean B

2003-04-24

Understanding the genetic basis of the physical and behavioural traits that distinguish humans from other primates presents one of the great new challenges in biology. Of the millions of base-pair differences between humans and chimpanzees, which particular changes contributed to the evolution of human features after the separation of the Pan and Homo lineages 5-7 million years ago? How can we identify the 'smoking guns' of human genetic evolution from neutral ticks of the molecular evolutionary clock? The magnitude and rate of morphological evolution in hominids suggests that many independent and incremental developmental changes have occurred that, on the basis of recent findings in model animals, are expected to be polygenic and regulatory in nature. Comparative genomics, population genetics, gene-expression analyses and medical genetics have begun to make complementary inroads into the complex genetic architecture of human evolution.

Measuring and Understanding Public Opinion on Human Evolution

ERIC Educational Resources Information Center

Gwon, Misook

2012-01-01

The theory of evolution has long generated controversy in American society, but Americans' attitudes about human evolution are often neglected in studies of "culture wars" and the nature of mass belief systems more generally (Berkman and Plutzer 2010; Freeland and Houston 2009). Gallup and other survey organizations have polled…

Apes, Wolves, Birds, and Humans: Toward a Comparative Foundation for a Functional Theory of Language Evolution

ERIC Educational Resources Information Center

Hill, Jane H.

1977-01-01

This article reviews the possibilities that a comparative, functionally oriented view of communication evolution offers to a linguist interested in the evolution of human languages and suggests a wide variety of areas which might be further investigated with profit. (CFM)

Age-related carbonylation of fibrocartilage structural proteins drives tissue degenerative modification.

PubMed

Scharf, Brian; Clement, Cristina C; Yodmuang, Supansa; Urbanska, Aleksandra M; Suadicani, Sylvia O; Aphkhazava, David; Thi, Mia M; Perino, Giorgio; Hardin, John A; Cobelli, Neil; Vunjak-Novakovic, Gordana; Santambrogio, Laura

2013-07-25

Aging-related oxidative stress has been linked to degenerative modifications in different organs and tissues. Using redox proteomic analysis and illustrative tandem mass spectrometry mapping, we demonstrate oxidative posttranslational modifications in structural proteins of intervertebral discs (IVDs) isolated from aging mice. Increased protein carbonylation was associated with protein fragmentation and aggregation. Complementing these findings, a significant loss of elasticity and increased stiffness was measured in fibrocartilage from aging mice. Studies using circular dichroism and intrinsic tryptophan fluorescence revealed a significant loss of secondary and tertiary structures of purified collagens following oxidation. Collagen unfolding and oxidation promoted both nonenzymatic and enzymatic degradation. Importantly, induction of oxidative modification in healthy fibrocartilage recapitulated the biochemical and biophysical modifications observed in the aging IVD. Together, these results suggest that protein carbonylation, glycation, and lipoxidation could be early events in promoting IVD degenerative changes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Biological insight, high-throughput datasets and the nature of neuro-degenerative disorders.

PubMed

Valente, André X C N; Oliveira, Paulo J; Khaiboullina, Svetlana F; Palotás, András; Rizvanov, Albert A

2013-09-01

Life sciences are experiencing a historical shift towards a quantitative, data-rich regime. This transition has been associated with the advent of bio-informatics: mathematicians, physicists, computer scientists and statisticians are now commonplace in the field, working on the analysis of ever larger data-sets. An open question regarding what should drive scientific progress in this new era remains: will biological insight become increasingly irrelevant in a world of hypothesis-free, unbiased data analysis? This piece offers a different perspective, pin-pointing that biological thought is more-than-ever relevant in a data-rich setting. Some of the novel highthroughput information being acquired in the field of neuro-degenerative disorders is highlighted here. As but one example of how theory and experiment can interact in this new reality, our efforts in developing an idiopathic neuro-degenerative disease hematopoietic stemcell ageing theory are described.

The role of arthroscopy in ankle and subtalar degenerative joint disease.

PubMed

Cheng, J C; Ferkel, R D

1998-04-01

Treatment options for degenerative joint disease of the ankle and subtalar joints are limited. When conservative management fails, the only effective procedure is arthrodesis. With the advent of the small arthroscope and the development of better instrumentation and distraction techniques, small joint arthroscopy has gained popularity as an important diagnostic and therapeutic tool in the treatment of ankle and subtalar disorders. Although the benefits of arthroscopic ankle arthrodesis are well established, and arthroscopic subtalar arthrodesis has been described recently, the role of arthroscopic debridement for degenerative joint disease of the ankle and subtalar joints remains controversial. Traditionally, operative arthroscopy for ankle arthritis has not met with great success; however, recent studies have shown that it can provide an interim alternative to arthrodesis in early arthritis with preserved range of motion. Lesions associated with arthritis, such as impinging osteophytes and loose bodies, can be treated effectively with arthroscopy.

What progress has been made in the understanding and treatment of degenerative lumbosacral stenosis in dogs during the past 30 years?

PubMed

Jeffery, Nick D; Barker, Andrew; Harcourt-Brown, Tom

2014-07-01

An association between degenerative changes in the lumbosacral region of the vertebral column and clinical signs of pain and pelvic limb dysfunction has long been recognized in dogs and has become known as degenerative lumbosacral stenosis syndrome. Over the past two decades, methods of imaging this condition have advanced greatly, but definitive criteria for a reliable diagnosis using physical examination, imaging and electrodiagnostics remain elusive. Available treatment options have changed little over more than 30 years but, more importantly, there is a lack of comparative studies and little progress has been made in providing evidence-based recommendations for the treatment of affected dogs. This review provides an overview of the changes in diagnosis, understanding and treatment of lumbosacral disease in dogs over the past 30 years. Approaches to address the unanswered questions regarding treatment choice are also proposed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Factors affecting disability and physical function in degenerative lumbar spondylolisthesis of L4-5: evaluation with axially loaded MRI.

PubMed

Huang, Kuo-Yuan; Lin, Ruey-Mo; Lee, Yung-Ling; Li, Jenq-Daw

2009-12-01

Few studies have investigated the factors related to the disability and physical function in degenerative lumbar spondylolisthesis using axially loaded magnetic resonance imaging (MRI). Therefore, we aimed to investigate the effect of axial loading on the morphology of the spine and the spinal canal in patients with degenerative spondylolisthesis of L4-5 and to correlate morphologic changes to their disability and physical functions. From March 2003 to January 2004, 32 consecutive cases (26 females, 6 males) with degenerative L4-5 spondylolisthesis, grade 1-2, intermittent claudication, and low back pain without sciatica were included in this study. All patients underwent unloaded and axially loaded MRI of the lumbo-sacral spine in supine position to elucidate the morphological findings and to measure the parameters of MRI, including disc height (DH), sagittal translation (ST), segmental angulation (SA), dural sac cross-sectional area (DCSA) at L4-5, and lumbar lordotic angles (LLA) at L1-5 between the unloaded and axially loaded condition. Each patient's disability was evaluated by the Oswestry Disability Index (ODI) questionnaire, and physical functioning (PF) was evaluated by the Physical Function scale proposed by Stucki et al. (Spine 21:796-803, 1996). Three patients were excluded due to the presence of neurologic symptoms found with the axially loaded MRI. Finally, a total of 29 (5 males, 24 females) consecutive patients were included in this study. Comparisons and correlations were done to determine which parameters were critical to the patient's disability and PF. The morphologies of the lumbar spine changed after axially loaded MRI. In six of our patients, we observed adjacent segment degeneration (4 L3-L4 and 2 L5-S1) coexisting with degenerative spondylolisthesis of L4-L5 under axially loaded MRI. The mean values of the SA under pre-load and post-load were 7.14 degrees and 5.90 degrees at L4-L5 (listhetic level), respectively. The mean values of the LLA under pre-load and post-load were 37.03 degrees and 39.28 degrees , respectively. There were significant correlations only between the ODI, PF, and the difference of SA, and between PF and the post-loaded LLA. The changes in SA (L4-L5) during axial loading were well correlated to the ODI and PF scores. In addition, the LLA (L1-L5) under axial loading was well correlated to the PF of patients with degenerative L4-L5 spondylolisthesis. We suggest that the angular instability of the intervertebral disc may play a more important role than neurological compression in the pathogenesis of disability in degenerative lumbar spondylolisthesis.

Evolution and proximate expression of human paternal investment.

PubMed

Geary, D C

2000-01-01

In more than 95% of mammalian species, males provide little direct investment in the well-being of their offspring. Humans are one notable exception to this pattern and, to date, the factors that contributed to the evolution and the proximate expression of human paternal care are unexplained (T. H. Clutton-Brock, 1989). The nature, extent, and influence of human paternal investment on the physical and social well-being of children are reviewed in light of the social and ecological factors that are associated with paternal investment in other species. On the basis of this review, discussion of the evolution and proximate expression of human paternal investment is provided.

Inventing Homo gardarensis: prestige, pressure, and human evolution in interwar Scandinavia.

PubMed

Kjaergaard, Peter C

2014-06-01

In the 1920s there were still very few fossil human remains to support an evolutionary explanation of human origins. Nonetheless, evolution as an explanatory framework was widely accepted. This led to a search for ancestors in several continents with fierce international competition. With so little fossil evidence available and the idea of a Missing Link as a crucial piece of evidence in human evolution still intact, many actors participated in the scientific race to identify the human ancestor. The curious case of Homo gardarensis serves as an example of how personal ambitions and national pride were deeply interconnected as scientific concerns were sometimes slighted in interwar palaeoanthropology.

Social, moral, and temporal qualities: Pre-service teachers' considerations of evolution and creation

NASA Astrophysics Data System (ADS)

Hahn, Deirdre

The introduction of the theories of evolution into public education has created a history of misinterpretation and uncertainty about its application to understanding deep time and human origins. Conceptions about negative social and moral outcomes of evolution itself along with cognitive temporal constraints may be difficult for many individuals to uncouple from the scientific theory, serving to provoke the ongoing debate about the treatment of evolution in science education. This debate about teaching evolution is strongly influenced by groups who strive to add creationism to the science curriculum for a balanced treatment of human origins and to mediate implied negative social and moral outcomes of evolution. Individual conceptualization of evolution and creation may influence the choice of college students to teach science. This study is designed to examine if pre-service teachers' conceptualize an evolutionary and creationist process of human development using certain social, moral or temporal patterns; and if the patterns follow a negative conceptual theme. The pilot study explored 21 pre-service teachers' conceptual representation of an evolutionary process through personal narratives. Participants tended to link evolutionary changes with negative social and moral consequences and seemed to have difficulty envisioning change over time. The pilot study was expanded to include a quantitative examination of attribute patterns of an evolutionary and creationist developmental process. Seventy-three pre-service teachers participated in the second experiment and tended to fall evenly along a continuum of creationist and evolutionist beliefs about life. Using a chi-square and principle components analysis, participants were found to map concepts of evolution and creation onto each other using troubling attributes of development to distinguish negative change over time. A strong negative social and moral pattern of human development was found in the creation condition, though only a vague negative human developmental process was found for the evolution condition. Based on these results, pre-service teachers may not use evolution as a viable explanation of human origins, which may serve to contribute to evolution theory debates and discourage pre-service teachers' choice of being science instructors.

Is necroptosis a death pathway in aluminum-induced neuroblastoma cell demise?

PubMed

Zhang, Q L; Niu, Q; Ji, X L; Conti, P; Boscolo, P

2008-01-01

Besides being an aggravating factor secondary to major physiological alterations in degenerative diseases, aluminum has also been considered as a risk factor in the etiology. Although many in vivo and in vitro data are in favor of apoptosis and necrosis being involved in Al induced neurodegenerative processes, there is considerable evidence that very complex events may contribute to neural cell death. Necroptosis, a novel cell death pathway, was recently reported to contribute to ischemia brain injury. It is different from, but associated with, apoptosis and necrosis, the two common major pathways of cell demise. In the present study, SH-SY5Y cells were put under stress by Al, a potential degenerative cell death inducer. Nec-1, a specific inhibitor, was used to identify necroptosis. The characteristics observed in Nec-1 and Al treated SH-SY5Y cells showed that necrotic morphological changes were reduced, and a sharp decrease of necrotic rate was detected. Besides, there were Al-induced mitochondria membrane potential decreasing, reactive oxygen species remaining, and autophagosomes declining. The mechanism of Nec-1s effect on cell death may be related to caspases pathways. To our best knowledge, this is the pioneer report on necroptosis in mixed human neural cell death pathways, which might offer a novel therapeutic target for neurodegenerative diseases, and an extended window for neuroprotection.

Serum and synovial fluid C-reactive protein level variations in dogs with degenerative joint disease and their relationships with physiological parameters.

PubMed

Boal, S; Miguel Carreira, L

2015-09-01

Degenerative joint disease (DJD) is a progressive, chronic joint disease with an inflammatory component promoting an acute phase protein (APP) response. C-reactive protein (CRP) is one of the most important APPs, used as an inflammation marker in human, but not veterinary medicine. The study was developed in a sample of 48 dogs (n = 48) with DJD and aimed to: 1) identify and quantify the synovial fluid CRP (SFCRP) in these specimens using a validated ELISA test for serum CRP (SCRP) detection and quantification; and 2) to study the possible relationship between SCRP and SFCRP levels variations in DJD patients evaluating the influence of some physical parameters such as gender, body weight, pain level, DJD grade, and the physical activity (PA) of the patients. Statistical analysis considered the results significant for p values <0.05. Our study showed that it is possible to detect and quantify SFCRP levels in DJD patients using a previously validated canine SCRP ELISA test, allowing us to point out a preliminary reference value for SFCRP in patients with DJD. Although, individuals with DJD presents SCRP values within the normal reference range and the SFCRP levels were always lower. Obesity, pain, and the DJD grade presented by the patients are conditions which seem to influence the SCRP levels but not the SFCRP.

Prevalence of Age-Related Changes in Ovine Lumbar Intervertebral Discs during Computed Tomography and Magnetic Resonance Imaging

PubMed Central

Nisolle, Jean-François; Bihin, Benoît; Kirschvink, Nathalie; Neveu, Fabienne; Clegg, Peter; Dugdale, Alexandra; Wang, Xiaoqing; Vandeweerd, Jean-Michel

2016-01-01

Ovine models are used to study intervertebral disc (IVD) degeneration. The objective of the current study was to assess the naturally occurring age-related changes of the IVD that can be diagnosed by CT and MRI in the lumbar spine of sheep. We used CT and T2-weighted MR images to score the IVD (L6S1 to L1L2) in 41 sheep (age, 6 mo to 11 y) that were euthanized for reasons not related to musculoskeletal disease. T2 mapping and measurement of T2 time of L6S1 to L2L3 were performed in 22 of the sheep. Degenerative changes manifested as early as 2 y of age and occurred at every IVD level. Discs were more severely damaged in older sheep. The age effect of the L6S1 IVD was larger than the average age effect for the other IVD. The current study provides evidence that lesions similar to those encountered in humans can be identified by CT and MRI in lumbar spine of sheep. Ideally, research animals should be assessed at the initiation of preclinical trials to determine the extent of prevalent degenerative changes. The ovine lumbosacral disc seems particularly prone to degeneration and might be a favorable anatomic site for studying IVD degeneration. PMID:27538861

Smooth muscle membrane organization in the normal and dysfunctional human urinary bladder: a structural analysis.

PubMed

Burkhard, Fiona C; Monastyrskaya, Katia; Studer, Urs E; Draeger, Annette

2005-01-01

The decline in contractile properties is a characteristic feature of the dysfunctional bladder as a result of infravesical outlet obstruction. During clinical progression of the disease, smooth muscle cells undergo structural modifications. Since adaptations to constant changes in length require a high degree of structural organization within the sarcolemma, we have investigated the expression of several proteins, which are involved in smooth muscle membrane organization, in specimens derived from normal and dysfunctional organs. Specimen from patients with urodynamically normal/equivocal (n = 4), obstructed (n = 2), and acontractile (n = 2) bladders were analyzed relative to their structural features and sarcolemmal protein profile. Smooth muscle cells within the normal urinary bladder display a distinct sarcolemmal domain structure, characterized by firm actin-attachment sites, alternating with flexible "hinge" regions. In obstructed bladders, foci of cells displaying degenerative sarcolemmal changes alternate with areas of hypertrophic cells in which the membrane appears unaffected. In acontractile organs, the overall membrane structure remains intact, however annexin 6, a protein belonging to a family of Ca2+-dependent, "membrane-organizers," is downregulated. Degenerative changes in smooth muscle cells, which are chronically working against high resistance, are preferentially located within the actin-attachment sites. In acontractile bladders, the downregulation of annexin 6 might have a bearing on the fine-tuning of the plasma membrane during contraction/relaxation cycles. Copyright 2005 Wiley-Liss, Inc.

Etiology of lumbar lordosis and its pathophysiology: a review of the evolution of lumbar lordosis, and the mechanics and biology of lumbar degeneration.

PubMed

Sparrey, Carolyn J; Bailey, Jeannie F; Safaee, Michael; Clark, Aaron J; Lafage, Virginie; Schwab, Frank; Smith, Justin S; Ames, Christopher P

2014-05-01

The goal of this review is to discuss the mechanisms of postural degeneration, particularly the loss of lumbar lordosis commonly observed in the elderly in the context of evolution, mechanical, and biological studies of the human spine and to synthesize recent research findings to clinical management of postural malalignment. Lumbar lordosis is unique to the human spine and is necessary to facilitate our upright posture. However, decreased lumbar lordosis and increased thoracic kyphosis are hallmarks of an aging human spinal column. The unique upright posture and lordotic lumbar curvature of the human spine suggest that an understanding of the evolution of the human spinal column, and the unique anatomical features that support lumbar lordosis may provide insight into spine health and degeneration. Considering evolution of the skeleton in isolation from other scientific studies provides a limited picture for clinicians. The evolution and development of human lumbar lordosis highlight the interdependence of pelvic structure and lumbar lordosis. Studies of fossils of human lineage demonstrate a convergence on the degree of lumbar lordosis and the number of lumbar vertebrae in modern Homo sapiens. Evolution and spine mechanics research show that lumbar lordosis is dictated by pelvic incidence, spinal musculature, vertebral wedging, and disc health. The evolution, mechanics, and biology research all point to the importance of spinal posture and flexibility in supporting optimal health. However, surgical management of postural deformity has focused on restoring posture at the expense of flexibility. It is possible that the need for complex and costly spinal fixation can be eliminated by developing tools for early identification of patients at risk for postural deformities through patient history (genetics, mechanics, and environmental exposure) and tracking postural changes over time.

Pervasive genetic integration directs the evolution of human skull shape.

PubMed

Martínez-Abadías, Neus; Esparza, Mireia; Sjøvold, Torstein; González-José, Rolando; Santos, Mauro; Hernández, Miquel; Klingenberg, Christian Peter

2012-04-01

It has long been unclear whether the different derived cranial traits of modern humans evolved independently in response to separate selection pressures or whether they resulted from the inherent morphological integration throughout the skull. In a novel approach to this issue, we combine evolutionary quantitative genetics and geometric morphometrics to analyze genetic and phenotypic integration in human skull shape. We measured human skulls in the ossuary of Hallstatt (Austria), which offer a unique opportunity because they are associated with genealogical data. Our results indicate pronounced covariation of traits throughout the skull. Separate simulations of selection for localized shape changes corresponding to some of the principal derived characters of modern human skulls produced outcomes that were similar to each other and involved a joint response in all of these traits. The data for both genetic and phenotypic shape variation were not consistent with the hypothesis that the face, cranial base, and cranial vault are completely independent modules but relatively strongly integrated structures. These results indicate pervasive integration in the human skull and suggest a reinterpretation of the selective scenario for human evolution where the origin of any one of the derived characters may have facilitated the evolution of the others. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

Delayed Induction of Human NTE (PNPLA6) Rescues Neurodegeneration and Mobility Defects of Drosophila swiss cheese (sws) Mutants.

PubMed

Sujkowski, Alyson; Rainier, Shirley; Fink, John K; Wessells, Robert J

2015-01-01

Human PNPLA6 gene encodes Neuropathy Target Esterase protein (NTE). PNPLA6 gene mutations cause hereditary spastic paraplegia (SPG39 HSP), Gordon-Holmes syndrome, Boucher-Neuhäuser syndromes, Laurence-Moon syndrome, and Oliver-McFarlane syndrome. Mutations in the Drosophila NTE homolog swiss cheese (sws) cause early-onset, progressive behavioral defects and neurodegeneration characterized by vacuole formation. We investigated sws5 flies and show for the first time that this allele causes progressive vacuolar formation in the brain and progressive deterioration of negative geotaxis speed and endurance. We demonstrate that inducible, neuron-specific expression of full-length human wildtype NTE reduces vacuole formation and substantially rescues mobility. Indeed, neuron-specific expression of wildtype human NTE is capable of rescuing mobility defects after 10 days of adult life at 29°C, when significant degeneration has already occurred, and significantly extends longevity of mutants at 25°C. These results raise the exciting possibility that late induction of NTE function may reduce or ameliorate neurodegeneration in humans even after symptoms begin. In addition, these results highlight the utility of negative geotaxis endurance as a new assay for longitudinal tracking of degenerative phenotypes in Drosophila.

Inference of ecological and social drivers of human brain-size evolution.

PubMed

González-Forero, Mauricio; Gardner, Andy

2018-05-01

The human brain is unusually large. It has tripled in size from Australopithecines to modern humans 1 and has become almost six times larger than expected for a placental mammal of human size 2 . Brains incur high metabolic costs 3 and accordingly a long-standing question is why the large human brain has evolved 4 . The leading hypotheses propose benefits of improved cognition for overcoming ecological 5-7 , social 8-10 or cultural 11-14 challenges. However, these hypotheses are typically assessed using correlative analyses, and establishing causes for brain-size evolution remains difficult 15,16 . Here we introduce a metabolic approach that enables causal assessment of social hypotheses for brain-size evolution. Our approach yields quantitative predictions for brain and body size from formalized social hypotheses given empirical estimates of the metabolic costs of the brain. Our model predicts the evolution of adult Homo sapiens-sized brains and bodies when individuals face a combination of 60% ecological, 30% cooperative and 10% between-group competitive challenges, and suggests that between-individual competition has been unimportant for driving human brain-size evolution. Moreover, our model indicates that brain expansion in Homo was driven by ecological rather than social challenges, and was perhaps strongly promoted by culture. Our metabolic approach thus enables causal assessments that refine, refute and unify hypotheses of brain-size evolution.

Interrater and intrarater agreements of magnetic resonance imaging findings in the lumbar spine: significant variability across degenerative conditions.

PubMed

Fu, Michael C; Buerba, Rafael A; Long, William D; Blizzard, Daniel J; Lischuk, Andrew W; Haims, Andrew H; Grauer, Jonathan N

2014-10-01

Magnetic resonance imaging (MRI) is frequently used in the evaluation of degenerative conditions in the lumbar spine. The relative interrater and intrarater agreements of MRI findings across different pathologic conditions are underexplored, as most studies are focused on specific findings. The purpose of this study was to characterize the interrater and intrarater agreements of MRI findings used to assess the degenerative lumbar spine. A retrospective diagnostic study at a large academic medical center was undertaken with a panel of orthopedic surgeons and musculoskeletal radiologists to assess lumbar MRIs using standardized criteria. Seventy-five subjects who underwent routine lumbar spine MRI at our institution were included. Each MRI study was assessed for 10 lumbar degenerative findings using standardized criteria. Lumbar vertebral levels were assessed independently, where applicable, for a total of 52 data points collected per study. T2-weighted axial and sagittal MRI sequences were presented in random order to the four reviewers (two orthopedic spine surgeons and two musculoskeletal radiologists) independently to determine interrater agreement. The first 10 studies were reevaluated at the end to determine intrarater agreement. Images were assessed using standardized and pilot-tested criteria to assess disc degeneration, stenosis, and other degenerative changes. Interrater and intrarater absolute percent agreements were calculated. To highlight the most clinically important MRI disagreements, a modified agreement analysis was also performed (in which disagreements between the lowest two severity grades for applicable conditions were ignored). Fleiss kappa coefficients for interrater agreement were determined. The overall absolute and modified interrater agreements were 76.9% and 93.5%, respectively. The absolute and modified intrarater agreements were 81.3% and 92.7%, respectively. Average Fleiss kappa coefficient was 0.431, suggesting moderate overall agreement. However, when stratified by condition, absolute interrater agreement ranged from 65.1% to 92.0%. Disc hydration, disc space height, and bone marrow changes exhibited the lowest absolute interrater agreements. The absolute intrarater agreement had a narrower range, from 74.5% to 91.5%. Fleiss kappa coefficients ranged from fair-to-substantial agreement (0.282-0.618). Even in a study using standardized evaluation criteria, there was significant variability in the interrater and intrarater agreements of MRI in assessing different degenerative conditions of the lumbar spine. Clinicians should be aware of the condition-specific diagnostic limitations of MRI interpretation. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of Altered Gut Microbiota Composition on Aging and Aging-Related Diseases

PubMed Central

Choi, Jeonghyun; Hur, Tai-Young; Hong, Yonggeun

2018-01-01

The gut microbiota forms a large community that coexists with all species, including humans and rodents. Genome projects have been conducted by many researchers in nearly every country to better understand and treat diseases that lead to death in humans. However, the gut microbiota is known as a “second genome” because it includes microbes, genomic DNA, proteins, and metabolites. A large number of studies have revealed the importance of the gut microbiota. In elderly people, the diversity of the gut microbiota is reduced and there is an increased incidence of degenerative diseases, including Alzheimer’s and Parkinson’s, and decreased cognitive and memory functions. However, the administration of pre/probiotics can help to improve the symptoms of these diseases. Therefore, we believe that the gut microbiota is important for maintaining homeostasis and diversity, as well as for avoiding gastrointestinal tract-derived diseases and improving health in the elderly population. PMID:29581954

[Drinking water hardness and chronic degenerative diseases. II. Cardiovascular diseases].

PubMed

Monarca, S; Zerbini, I; Simonati, C; Gelatti, U

2003-01-01

Since the 1950s a causal relation between water hardness and cardiovascular diseases (CVD) in humans has been hypothesized. In order to evaluate the influence of calcium and magnesium, the minerals responsible for the hardness of drinking water, on human health, a review of all the articles published on the subject from 1980 up to today has been carried out. Many but not all geographic correlation studies showed an inverse association between water hardness and mortality for CVD. Most case-control and one cohort studies showed an inverse relation, statistically significant, between mortality from CVD and water levels of magnesium, but not calcium. Consumption of water containing high concentrations of magnesium seems to reduce of about 30-35% the mortality for CVD, but not the incidence. This inverse association is supported by clinical and experimental findings and is biologically plausible and in line with Hill's criteria for a cause-effect relationship.

Effects of ionizing radiation on bio-active plant extracts useful for preventing oxidative damages.

PubMed

Mulinacci, Nadia; Valletta, Alessio; Pasqualetti, Valentina; Innocenti, Marzia; Giuliani, Camilla; Bellumori, Maria; De Angelis, Giulia; Carnevale, Alessia; Locato, Vittoria; Di Venanzio, Cristina; De Gara, Laura; Pasqua, Gabriella

2018-04-02

Humans are exposed to ionizing radiations in medical radiodiagnosis and radiotherapy that cause oxidative damages and degenerative diseases. Airplane pilots, and even more astronauts, are exposed to a variety of potentially harmful factors, including cosmic radiations. Among the phytochemicals, phenols are particularly efficient in countering the oxidative stress. In the present study, different extracts obtained from plant food, plant by-products and dietary supplements, have been compared for their antioxidant properties before and after irradiation of 140 cGy, a dose absorbed during a hypothetical stay of three years in the space. All the dry extracts, characterized in terms of vitamin C and phenolic content, remained chemically unaltered and maintained their antioxidant capability after irradiation. Our results suggest the potential use of these extracts as nutraceuticals to protect humans from oxidative damages, even when these extracts must be stored in an environment exposed to cosmic radiations as in a space station.

Evolution of the Human Pelvis.

PubMed

Rosenberg, Karen R; DeSilva, Jeremy M

2017-05-01

No bone in the human postcranial skeleton differs more dramatically from its match in an ape skeleton than the pelvis. Humans have evolved a specialized pelvis, well-adapted for the rigors of bipedal locomotion. Precisely how this happened has been the subject of great interest and contention in the paleoanthropological literature. In part, this is because of the fragility of the pelvis and its resulting rarity in the human fossil record. However, new discoveries from Miocene hominoids and Plio-Pleistocene hominins have reenergized debates about human pelvic evolution and shed new light on the competing roles of bipedal locomotion and obstetrics in shaping pelvic anatomy. In this issue, 13 papers address the evolution of the human pelvis. Here, we summarize these new contributions to our understanding of pelvic evolution, and share our own thoughts on the progress the field has made, and the questions that still remain. Anat Rec, 300:789-797, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Morphological and population genomic evidence that human faces have evolved to signal individual identity.

PubMed

Sheehan, Michael J; Nachman, Michael W

2014-09-16

Facial recognition plays a key role in human interactions, and there has been great interest in understanding the evolution of human abilities for individual recognition and tracking social relationships. Individual recognition requires sufficient cognitive abilities and phenotypic diversity within a population for discrimination to be possible. Despite the importance of facial recognition in humans, the evolution of facial identity has received little attention. Here we demonstrate that faces evolved to signal individual identity under negative frequency-dependent selection. Faces show elevated phenotypic variation and lower between-trait correlations compared with other traits. Regions surrounding face-associated single nucleotide polymorphisms show elevated diversity consistent with frequency-dependent selection. Genetic variation maintained by identity signalling tends to be shared across populations and, for some loci, predates the origin of Homo sapiens. Studies of human social evolution tend to emphasize cognitive adaptations, but we show that social evolution has shaped patterns of human phenotypic and genetic diversity as well.

Human-specific protein isoforms produced by novel splice sites in the human genome after the human-chimpanzee divergence

PubMed Central

2012-01-01

Background Evolution of splice sites is a well-known phenomenon that results in transcript diversity during human evolution. Many novel splice sites are derived from repetitive elements and may not contribute to protein products. Here, we analyzed annotated human protein-coding exons and identified human-specific splice sites that arose after the human-chimpanzee divergence. Results We analyzed multiple alignments of the annotated human protein-coding exons and their respective orthologous mammalian genome sequences to identify 85 novel splice sites (50 splice acceptors and 35 donors) in the human genome. The novel protein-coding exons, which are expressed either constitutively or alternatively, produce novel protein isoforms by insertion, deletion, or frameshift. We found three cases in which the human-specific isoform conferred novel molecular function in the human cells: the human-specific IMUP protein isoform induces apoptosis of the trophoblast and is implicated in pre-eclampsia; the intronization of a part of SMOX gene exon produces inactive spermine oxidase; the human-specific NUB1 isoform shows reduced interaction with ubiquitin-like proteins, possibly affecting ubiquitin pathways. Conclusions Although the generation of novel protein isoforms does not equate to adaptive evolution, we propose that these cases are useful candidates for a molecular functional study to identify proteomic changes that might bring about novel phenotypes during human evolution. PMID:23148531

Factors influencing on retro-odontoid soft-tissue thickness: analysis by magnetic resonance imaging.

PubMed

Tojo, Shinjiro; Kawakami, Reina; Yonenaga, Takenori; Hayashi, Daichi; Fukuda, Kunihiko

2013-03-01

A retrospective, consecutive case series. To analyze the relationship between retro-odontoid soft-tissue thickness and patients' age, sex, and degenerative changes of cervical spine and to investigate the effect these factors have on retro-odontoid soft-tissue thickness. Thickening of the soft tissue posterior to the odontoid process can form a retro-odontoid pseudotumor causing symptoms of spinal cord compression. Rheumatoid arthritis and long-term dialysis have been reported as possible causes for this. However, there have been reports of retro-odontoid pseudotumors without coexisting diseases. Findings from a total of 503 cases of cervical spine magnetic resonance images were reviewed, and retro-odontoid soft-tissue thickness was measured. The values were matched for age, sex, presence of degenerative changes, rheumatoid arthritis, and dialysis and were analyzed for significance. Retro-odontoid soft tissue thickened with age, and this was also seen in male patients and patients with degenerative changes. Significant increase in thickness was also observed in patients undergoing dialysis and further increased with prolonged dialysis. There was no significant association with presence of rheumatoid arthritis. There is association between age, sex, degenerative cervical spine changes, and dialysis with retro-odontoid soft-tissue thickness. With dialysis, retro-odontoid soft-tissue thickness increases with increasing duration. Thus, reviewing magnetic resonance image from daily practice indicates that cervical spine degeneration is associated with the development of retro-odontoid pseudotumors.

Diagnostic accuracy of electrocardiographic P wave related parameters in the assessment of left atrial size in dogs with degenerative mitral valve disease.

PubMed

Soto-Bustos, Ángel; Caro-Vadillo, Alicia; Martínez-DE-Merlo, Elena; Alonso-Alegre, Elisa González

2017-10-07

The purpose of this research was to compare the accuracy of newly described P wave-related parameters (P wave area, Macruz index and mean electrical axis) with classical P wave-related parameters (voltage and duration of P wave) for the assessment of left atrial (LA) size in dogs with degenerative mitral valve disease. One hundred forty-six dogs (37 healthy control dogs and 109 dogs with degenerative mitral valve disease) were prospectively studied. Two-dimensional echocardiography examinations and a 6-lead ECG were performed prospectively in all dogs. Echocardiography parameters, including determination of the ratios LA diameter/aortic root diameter and LA area/aortic root area, were compared to P wave-related parameters: P wave area, Macruz index, mean electrical axis voltage and duration of P wave. The results showed that P wave-related parameters (classical and newly described) had low sensitivity (range=52.3 to 77%; median=60%) and low to moderate specificity (range=47.2 to 82.5%; median 56.3%) for the prediction of left atrial enlargement. The areas under the curve of P wave-related parameters were moderate to low due to poor sensitivity. In conclusion, newly P wave-related parameters do not increase the diagnostic capacity of ECG as a predictor of left atrial enlargement in dogs with degenerative mitral valve disease.

Diagnostic accuracy of electrocardiographic P wave related parameters in the assessment of left atrial size in dogs with degenerative mitral valve disease

PubMed Central

SOTO-BUSTOS, Ángel; CARO-VADILLO, Alicia; MARTÍNEZ-DE-MERLO, Elena; ALONSO-ALEGRE, Elisa González

2017-01-01

The purpose of this research was to compare the accuracy of newly described P wave-related parameters (P wave area, Macruz index and mean electrical axis) with classical P wave-related parameters (voltage and duration of P wave) for the assessment of left atrial (LA) size in dogs with degenerative mitral valve disease. One hundred forty-six dogs (37 healthy control dogs and 109 dogs with degenerative mitral valve disease) were prospectively studied. Two-dimensional echocardiography examinations and a 6-lead ECG were performed prospectively in all dogs. Echocardiography parameters, including determination of the ratios LA diameter/aortic root diameter and LA area/aortic root area, were compared to P wave-related parameters: P wave area, Macruz index, mean electrical axis voltage and duration of P wave. The results showed that P wave-related parameters (classical and newly described) had low sensitivity (range=52.3 to 77%; median=60%) and low to moderate specificity (range=47.2 to 82.5%; median 56.3%) for the prediction of left atrial enlargement. The areas under the curve of P wave-related parameters were moderate to low due to poor sensitivity. In conclusion, newly P wave-related parameters do not increase the diagnostic capacity of ECG as a predictor of left atrial enlargement in dogs with degenerative mitral valve disease. PMID:28845021

A descriptive study of potential effect of anterior tibial translation, femoral tunnel and anterior cruciate ligament graft inclination on clinical outcome and degenerative changes.

PubMed

Snoj, Žiga; Zupanc, Oskar; Stražar, Klemen; Salapura, Vladka

2017-04-01

There is no evidence that anatomically correct anterior cruciate ligament reconstruction (ACLR) offers lower rate of degenerative changes development or that it would lead to a better outcome. The significance and understanding of the abnormal anterior tibial translation (ATT) in ACLR patients is yet to be established. Sixty subjects (40 patients at 5.9 years after ACLR, 20 healthy controls) underwent 3 T MRI. Quantitative cartilage T2 mapping and morphological whole organ magnetic resonance imaging score (WORMS) evaluation was performed. Self-reported questionnaires were used for subjective clinical evaluation. Correlations were calculated with the following MRI measurements; femoral tunnel inclination, ACL graft inclination, lateral and medial compartment ATT. In the ACLR group positive correlation was found between the patellar cartilage T2 values and sagittal ACL graft inclination. In the ACLR group lateral compartment ATT showed negative correlation with ACL graft inclination and subjective clinical evaluation, and positive correlation with morphological degenerative changes. Femoral tunnel showed positive correlation with ACL graft inclination in the same plane. Increased ATT offers worse clinical outcome and increased rate of degenerative changes. Furthermore, ATT is affected by the ACL inclination. Inclination of the drilling tunnel affects ACL graft inclination; thereby independent drilling techniques provide superior results of anatomical ACL graft positioning.

The effects of extracorporeal shock wave therapy on the pain and function of patients with degenerative knee arthritis.

PubMed

Lee, Ji-Hyun; Lee, Sangyong; Choi, SeokJoo; Choi, Yoon-Hee; Lee, Kwansub

2017-03-01

[Purpose] The purpose of this study was to identify the effects of extracorporeal shock wave therapy on the pain and function of patients with degenerative knee arthritis. [Subjects and Methods] Twenty patients with degenerative knee arthritis were divided into a conservative physical therapy group (n=10) and an extracorporeal shock wave therapy group (n=10). Both groups received general conservative physical therapy, and the extracorporeal shock wave therapy was additionally treated with extracorporeal shock wave therapy after receiving conservative physical therapy. Both groups were treated three times a week over a four-week period. The visual analogue scale was used to evaluate pain in the knee joints of the subjects, and the Korean Western Ontario and McMaster Universities Osteoarthritis Index was used to evaluate the function of the subjects. [Results] The comparison of the visual analogue scale and Korean Western Ontario and McMaster Universities Osteoarthritis Index scores within each group before and after the treatment showed statistically significant declines in scores in both the conservative physical therapy group and extracorporeal shock wave therapy group. A group comparison after the treatment showed statistically significant differences in these scores in the extracorporeal shock wave therapy group and the conservative physical therapy group. [Conclusion] extracorporeal shock wave therapy may be a useful nonsurgical intervention for reducing the pain of patients with degenerative knee arthritis and improving these patients' function.

Prognostic indicators of the outcome of arthrocentesis with and without sodium hyaluronate injection for the treatment of disc displacement without reduction: a magnetic resonance imaging study.

PubMed

Aktas, I; Yalcin, S; Sencer, S

2010-11-01

This study analysed the prognostic factors for successful arthrocentesis with and without sodium hyaluronate (SH) injection for the treatment of temporomandibular joint (TMJ) disc displacement without reduction (DDwoR) using clinical and radiological results. 29 TMJs in 25 patients with DDwoR were included. Patients were treated with arthrocentesis or arthrocentesis followed by intra-articular (i.a.) injection of SH. Treatment was evaluated for postoperative range of maximum mouth opening and the degree of postoperative pain on a VAS. Prognostic factors analysed were age, sex, duration of locking, trauma history, previous TMJ treatment, depression, bruxism, malocclusion and missing teeth. Degenerative changes were evaluated as probable prognostic factors. After treatment, 24 joints (83%) fulfilled the criteria for success. Duration of locking and present preoperative degenerative changes were the most significant factors for treatment outcome. The results suggest it is sufficient to use only arthrocentesis in patients without preoperative degenerative changes and arthrocentesis with SH in patients with degenerative changes on their preoperative MRIs, but because there were some significant differences between the two groups preventing the authors from comparing them statistically, they cannot come to that conclusion. To clarify the use of SH in such cases, standardized study groups are necessary for future studies. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Evaluation of degenerative disease of the lumbar spine: MR/MR myelography versus conventional myelography/post-myelography CT.

PubMed

Shiban, Ehab; von Lehe, Marec; Simon, Matthias; Clusmann, Hans; Heinrich, Petra; Ringel, Florian; Wilhelm, Kai; Urbach, Horst; Meyer, Bernhard; Stoffel, Michael

2016-08-01

To compare the use of magnetic resonance (MR)/MR myelography (MRM) with conventional myelography/post-myelography CT (convM) for detailed surgery planning in degenerative lumbar disease. Twenty-six patients with suspected complex lumbar degenerative disease underwent MRM in addition to convM as preoperative workup. Surgery was planned based on convM-as usual at our department. Post hoc, surgical planning was repeated planned again-now based on MRM. Furthermore, the MRM-based planning was performed by six independent neurosurgeons (three groups) of different degrees of specialisation. In only 31 % of the patients, post hoc MRM-based planning resulted in the same surgical decision as originally performed, whereas in 69 % (n = 18) a different procedure was indicated. In patients with non-concurring convM- and MRM-based surgical plans, a less extended procedure was the result of MRM in six patients (23 %), a more extended one in five (19 %), and a related to side/level of decompression or nucleotomy different plan in six patients (23 %). In one patient (4 %), the MRM-based planning would have led to a completely different surgery compared to convM. Overall interobserver agreement on the MRM-based planning was substantial. Detailed planning of operative procedures for complex lumbar degenerative disease is highly dependent on the image modality used.

The Evolution of Human Intelligence and the Coefficient of Additive Genetic Variance in Human Brain Size

ERIC Educational Resources Information Center

Miller, Geoffrey F.; Penke, Lars

2007-01-01

Most theories of human mental evolution assume that selection favored higher intelligence and larger brains, which should have reduced genetic variance in both. However, adult human intelligence remains highly heritable, and is genetically correlated with brain size. This conflict might be resolved by estimating the coefficient of additive genetic…

Mechanisms for the Evolution of a Derived Function in the Ancestral Glucocorticoid Receptor

PubMed Central

Carroll, Sean Michael; Ortlund, Eric A.; Thornton, Joseph W.

2011-01-01

Understanding the genetic, structural, and biophysical mechanisms that caused protein functions to evolve is a central goal of molecular evolutionary studies. Ancestral sequence reconstruction (ASR) offers an experimental approach to these questions. Here we use ASR to shed light on the earliest functions and evolution of the glucocorticoid receptor (GR), a steroid-activated transcription factor that plays a key role in the regulation of vertebrate physiology. Prior work showed that GR and its paralog, the mineralocorticoid receptor (MR), duplicated from a common ancestor roughly 450 million years ago; the ancestral functions were largely conserved in the MR lineage, but the functions of GRs—reduced sensitivity to all hormones and increased selectivity for glucocorticoids—are derived. Although the mechanisms for the evolution of glucocorticoid specificity have been identified, how reduced sensitivity evolved has not yet been studied. Here we report on the reconstruction of the deepest ancestor in the GR lineage (AncGR1) and demonstrate that GR's reduced sensitivity evolved before the acquisition of restricted hormone specificity, shortly after the GR–MR split. Using site-directed mutagenesis, X-ray crystallography, and computational analyses of protein stability to recapitulate and determine the effects of historical mutations, we show that AncGR1's reduced ligand sensitivity evolved primarily due to three key substitutions. Two large-effect mutations weakened hydrogen bonds and van der Waals interactions within the ancestral protein, reducing its stability. The degenerative effect of these two mutations is extremely strong, but a third permissive substitution, which has no apparent effect on function in the ancestral background and is likely to have occurred first, buffered the effects of the destabilizing mutations. Taken together, our results highlight the potentially creative role of substitutions that partially degrade protein structure and function and reinforce the importance of permissive mutations in protein evolution. PMID:21698144

Mechanisms for the Evolution of a Derived Function in the Ancestral Glucocorticoid Receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carroll, Sean Michael; Ortlund, Eric A; Thornton, Joseph W.

2012-03-16

Understanding the genetic, structural, and biophysical mechanisms that caused protein functions to evolve is a central goal of molecular evolutionary studies. Ancestral sequence reconstruction (ASR) offers an experimental approach to these questions. Here we use ASR to shed light on the earliest functions and evolution of the glucocorticoid receptor (GR), a steroid-activated transcription factor that plays a key role in the regulation of vertebrate physiology. Prior work showed that GR and its paralog, the mineralocorticoid receptor (MR), duplicated from a common ancestor roughly 450 million years ago; the ancestral functions were largely conserved in the MR lineage, but the functionsmore » of GRs - reduced sensitivity to all hormones and increased selectivity for glucocorticoids - are derived. Although the mechanisms for the evolution of glucocorticoid specificity have been identified, how reduced sensitivity evolved has not yet been studied. Here we report on the reconstruction of the deepest ancestor in the GR lineage (AncGR1) and demonstrate that GR's reduced sensitivity evolved before the acquisition of restricted hormone specificity, shortly after the GR-MR split. Using site-directed mutagenesis, X-ray crystallography, and computational analyses of protein stability to recapitulate and determine the effects of historical mutations, we show that AncGR1's reduced ligand sensitivity evolved primarily due to three key substitutions. Two large-effect mutations weakened hydrogen bonds and van der Waals interactions within the ancestral protein, reducing its stability. The degenerative effect of these two mutations is extremely strong, but a third permissive substitution, which has no apparent effect on function in the ancestral background and is likely to have occurred first, buffered the effects of the destabilizing mutations. Taken together, our results highlight the potentially creative role of substitutions that partially degrade protein structure and function and reinforce the importance of permissive mutations in protein evolution.« less

Inclusion Body Myositis

PubMed Central

Barohn, Richard J.

2014-01-01

The idiopathic inflammatory myopathies (IIM) are a heterogenous group of rare disorders that share many similarities. In addition to sporadic inclusion body myositis (IBM), these include dematomyositis (DM), polymyositis (PM), and autoimmune necrotizing myopathy (NM). For discussion of later three disorders, the reader is referred to the IIM review in this issue. IBM is the most common IIM after age 50. It typically presents with chronic insidious proximal leg and/or distal arm asymmetric muscle weakness leading to recurrent falls and loss of dexterity. Creatine kinase (CK) is up to 15 times elevated in IBM and needle electromyograhy (EMG) mostly shows a chronic irritative myopathy. Muscle histopathology demonstrates endomysial inflammatory exudates surrounding and invading non-necrotic muscle fibers often times accompanied by rimmed vacuoles and protein deposits. Despite inflammatory muscle pathology suggesting similarity with PM, it likely that IBM is has a prominent degenerative component as supported by refractoriness to immunosuppressive therapy. We review the evolution of our knowledge in IBM with emphasis on recent developments in the field and discuss ongoing clinical trials. PMID:25037082

CALCIFIC AORTIC VALVE DISEASE: PART 1 – MOLECULAR PATHOGENETIC ASPECTS, HEMODYNAMICS AND ADAPTIVE FEEDBACKS

PubMed Central

Pasipoularides, Ares

2016-01-01

Aortic valvular stenosis (AVS), produced by calcific aortic valve disease (CAVD) causing reduced cusp opening, afflicts mostly older persons eventually requiring valve replacement. CAVD had been considered “degenerative,” but newer investigations implicate active mechanisms similar to atherogenesis—genetic predisposition and signaling pathways, lipoprotein deposits, chronic inflammation and calcification/osteogenesis. Consequently, CAVD may eventually be controlled/reversed by lifestyle and pharmacogenomics remedies. Its management should be comprehensive, embracing not only the valve but also the left ventricle and the arterial system with their interdependent morphomechanics/hemodynamics, which underlie the ensuing diastolic and systolic LV dysfunction. Compared to even a couple of decades ago, we now have an increased appreciation of genomic and cytomolecular pathogenetic mechanisms underlying CAVD. Future pluridisciplinary studies will characterize better and more completely its pathobiology, evolution and overall dynamics, encompassing intricate feedback processes involving specific signaling molecules and gene network cascades. They will herald more effective, personalized medicine treatments of CAVD/AVS. PMID:26891845

Degenerative jargon aphasia: unusual progression of logopenic/phonological progressive aphasia?

PubMed

Caffarra, Paolo; Gardini, Simona; Cappa, Stefano; Dieci, Francesca; Concari, Letizia; Barocco, Federica; Ghetti, Caterina; Ruffini, Livia; Prati, Guido Dalla Rosa

2013-01-01

Primary progressive aphasia (PPA) corresponds to the gradual degeneration of language which can occur as nonfluent/agrammatic PPA, semantic variant PPA or logopenic variant PPA. We describe the clinical evolution of a patient with PPA presenting jargon aphasia as a late feature. At the onset of the disease (ten years ago) the patient showed anomia and executive deficits, followed later on by phonemic paraphasias and neologisms, deficits in verbal short-term memory, naming, verbal and semantic fluency. At recent follow-up the patient developed an unintelligible jargon with both semantic and neologistic errors, as well as with severe deficit of comprehension which precluded any further neuropsychological assessment. Compared to healthy controls, FDG-PET showed a hypometabolism in the left angular and middle temporal gyri, precuneus, caudate, posterior cingulate, middle frontal gyrus, and bilaterally in the superior temporal and inferior frontal gyri. The clinical and neuroimaging profile seems to support the hypothesis that the patient developed a late feature of logopenic variant PPA characterized by jargonaphasia and associated with superior temporal and parietal dysfunction.

Direct Revascularization with Autotransplant Technique for a True Aneurysm of the Renal Artery 20 Years after Kidney Transplantation.

PubMed

Mezzetto, Luca; Boschiero, Luigino; Fior, Francesca; Nguefouet Momo, Rostand Emmanuel; Nacchia, Francesco; Eccher, Albino; Macrì, Marco; Veraldi, Gian Franco

2016-04-01

True degenerative aneurysm of renal artery represents a very rare evolution in kidney transplantation. The cases presented in the literature are usually perianastomotic or mycotic pseudoaneurysm related to surgical technical defects or local infections. Herewith, we present the case of a voluminous true aneurysm developed in a young patient transplanted at our hospital 20 years before. All follow-up ultrasounds were always normal until the last disclosing a voluminous aneurysm of the transplanted renal artery. The subsequent angio-CT-scan confirmed the presence of a 52-mm saccular dilatation of the renal artery. For the complex anatomy, the endovascular approach was excluded, and a surgical revascularization was staged. We treated this lesion with the autotransplant technique, preserving the transplanted kidney, resecting the aneurysm, and performing a direct anastomosis after cold perfusion of the kidney. The autotransplant technique demonstrated to be a safe and effective approach in this challenging and very unusual situation. Copyright © 2016 Elsevier Inc. All rights reserved.

Criterion Validation Testing of Clinical Metrology Instruments for Measuring Degenerative Joint Disease Associated Mobility Impairment in Cats

PubMed Central

Gruen, Margaret E.; Griffith, Emily H.; Thomson, Andrea E.; Simpson, Wendy; Lascelles, B. Duncan X.

2015-01-01

Introduction Degenerative joint disease and associated pain are common in cats, particularly in older cats. There is a need for treatment options, however evaluation of putative therapies is limited by a lack of suitable, validated outcome measures that can be used in the target population of client owned cats. The objectives of this study were to evaluate low-dose daily meloxicam for the treatment of pain associated with degenerative joint disease in cats, and further validate two clinical metrology instruments, the Feline Musculoskeletal Pain Index (FMPI) and the Client Specific Outcome Measures (CSOM). Methods Sixty-six client owned cats with degenerative joint disease and owner-reported impairments in mobility were screened and enrolled into a double-masked, placebo-controlled, randomized clinical trial. Following a run-in baseline period, cats were given either placebo or meloxicam for 21 days, then in a masked washout, cats were all given placebo for 21 days. Subsequently, cats were given the opposite treatment, placebo or meloxicam, for 21 days. Cats wore activity monitors throughout the study, owners completed clinical metrology instruments following each period. Results Activity counts were increased in cats during treatment with daily meloxicam (p<0.0001) compared to baseline. The FMPI results and activity count data offer concurrent validation for the FMPI, though the relationship between baseline activity counts and FMPI scores at baseline was poor (R2=0.034). The CSOM did not show responsiveness for improvement in this study, and the relationship between baseline activity counts and CSOM scores at baseline was similarly poor (R2=0.042). Conclusions Refinements to the FMPI, including abbreviation of the instrument and scoring as percent of possible score are recommended. This study offered further validation of the FMPI as a clinical metrology instrument for use in detecting therapeutic efficacy in cats with degenerative joint disease. PMID:26162101

Work-Related Biomechanical Exposure and Job Strain as Separate and Joint Predictors of Musculoskeletal Diseases: A 28-Year Prospective Follow-up Study.

PubMed

Prakash, K C; Neupane, Subas; Leino-Arjas, Päivi; von Bonsdorff, Mikaela B; Rantanen, Taina; von Bonsdorff, Monika E; Seitsamo, Jorma; Ilmarinen, Juhani; Nygård, Clas-Håkan

2017-12-01

We investigated how work-related biomechanical exposure and job strain in midlife separately and jointly predicted back and degenerative musculoskeletal diseases (MSDs). A total of 6,257 employees participated in the Finnish Longitudinal Study on Aging Municipal Employees (FLAME) in 1981 and were followed up for 28 years. Risk ratios and the relative excessive risk due to interaction and 95% confidence intervals were modeled for separate and joint prediction estimates, respectively. After adjustment for confounders, job strain predicted degenerative MSDs among women after 4 and 11 years of follow-up. After 11 years, both exposures predicted both types of MSDs among men. Joint exposure predicted both types of MSDs after 4 years among women (for back MSDs, risk ratio (RR) = 1.58, 95% confidence interval (CI): 1.15, 2.18; for degenerative MSDs, RR = 1.59, 95% CI: 1.21, 2.07) and men (for back MSDs, RR = 1.50, 95% CI: 1.05, 2.15; for degenerative MSDs, RR = 1.61, 95% CI: 1.16, 2.22) and both types of MSDs after 11 years (for back MSDs, RR = 1.72, 95% CI: 1.21, 2.43; for degenerative MSDs, RR = 1.68, 95% CI: 1.25, 2.46) among men only, but the relative excessive risk due to interaction was not significant throughout. However, after 28 years, the separate and joint exposures did not predict MSDs. Workplace interventions should be focused on reducing job strain along with biomechanical exposure for possible prevention of MSDs in working life and around the time of retirement, but there may be other pathways of onset of MSDs in old age. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mortality for chronic-degenerative diseases in Tuscany: Ecological study comparing neighboring areas with substantial differences in environmental pollution.

PubMed

Marabotti, Claudio; Piaggi, Paolo; Scarsi, Paolo; Venturini, Elio; Cecchi, Romina; Pingitore, Alessandro

2017-06-19

Environmental pollution is associated with morbidity and mortality for chronic-degenerative diseases. Recent data points out a relationship between proximity to industrial plants and mortality due to neoplasms. The aim of this study has been to compare mortality due to chronic-degenerative diseases in the area of Tuscany (Bassa Val di Cecina), Italy, characterized by the presence of 2 neighboring municipalities similar in terms of size but with substantial differences in industrial activities: Rosignano (the site of chemical, energy production and waste processing industries) and Cecina (with no polluting activity). Standardized mortality rates for the 2001-2010 decade were calculated; the data of the whole Tuscany was assumed as reference. Environmental levels of pollutants were obtained by databases of the Environmental Protection Agency of Tuscany Region (Agenzia Regionale per la Protezione Ambientale della Toscana - ARPAT). Maximum tolerated pollutant levels set by national laws were assumed as reference. In the whole Bassa Val di Cecina, significantly elevated standardized mortality rates due to mesothelioma, ischemic heart diseases, cerebrovascular diseases and Alzheimer and other degenerative diseases of nervous system were observed. In the municipality of Rosignano, a significant excess of mortality for all these groups of diseases was confirmed. On the contrary, the municipality of Cecina showed only significantly higher mortality rates for ischemic heart diseases. Elevated levels of heavy metals in sea water and of particulate matter which contains particles of diameter ≤ 10 mm (PM₁₀) and ozone in air were detected in Rosignano. This study shows an excess of mortality for chronic-degenerative diseases in the area with elevated concentration of polluting factories. Proximity to industrial plants seems to represent a risk factor for those diseases. Int J Occup Med Environ Health 2017;30(4):641-653. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Indications for spine surgery: validation of an administrative coding algorithm to classify degenerative diagnoses

PubMed Central

Lurie, Jon D.; Tosteson, Anna N.A.; Deyo, Richard A.; Tosteson, Tor; Weinstein, James; Mirza, Sohail K.

2014-01-01

Study Design Retrospective analysis of Medicare claims linked to a multi-center clinical trial. Objective The Spine Patient Outcomes Research Trial (SPORT) provided a unique opportunity to examine the validity of a claims-based algorithm for grouping patients by surgical indication. SPORT enrolled patients for lumbar disc herniation, spinal stenosis, and degenerative spondylolisthesis. We compared the surgical indication derived from Medicare claims to that provided by SPORT surgeons, the “gold standard”. Summary of Background Data Administrative data are frequently used to report procedure rates, surgical safety outcomes, and costs in the management of spinal surgery. However, the accuracy of using diagnosis codes to classify patients by surgical indication has not been examined. Methods Medicare claims were link to beneficiaries enrolled in SPORT. The sensitivity and specificity of three claims-based approaches to group patients based on surgical indications were examined: 1) using the first listed diagnosis; 2) using all diagnoses independently; and 3) using a diagnosis hierarchy based on the support for fusion surgery. Results Medicare claims were obtained from 376 SPORT participants, including 21 with disc herniation, 183 with spinal stenosis, and 172 with degenerative spondylolisthesis. The hierarchical coding algorithm was the most accurate approach for classifying patients by surgical indication, with sensitivities of 76.2%, 88.1%, and 84.3% for disc herniation, spinal stenosis, and degenerative spondylolisthesis cohorts, respectively. The specificity was 98.3% for disc herniation, 83.2% for spinal stenosis, and 90.7% for degenerative spondylolisthesis. Misclassifications were primarily due to codes attributing more complex pathology to the case. Conclusion Standardized approaches for using claims data to accurately group patients by surgical indications has widespread interest. We found that a hierarchical coding approach correctly classified over 90% of spine patients into their respective SPORT cohorts. Therefore, claims data appears to be a reasonably valid approach to classifying patients by surgical indication. PMID:24525995

A Multicenter Radiographic Evaluation of the Rates of Preoperative and Postoperative Malalignment in Degenerative Spinal Fusions.

PubMed

Leveque, Jean-Christophe A; Segebarth, Bradley; Schroerlucke, Samuel R; Khanna, Nitin; Pollina, John; Youssef, Jim A; Tohmeh, Antoine G; Uribe, Juan S

2018-07-01

Multicenter, retrospective, institutional-review-board -approved study at 18 institutions in the United States with 24 treating investigators. This study was designed to retrospectively assess the prevalence of spinopelvic malalignment in patients who underwent one- or two-level lumbar fusions for degenerative (nondeformity) indications and to assess the incidence of malalignment after fusion surgery as well as the rate of alignment preservation and/or correction in this population. Spinopelvic malalignment after lumbar fusion has been associated with lower postoperative health-related quality of life and elevated risk of adjacent segment failure. The prevalence of spinopelvic malalignment in short-segment degenerative lumbar fusion procedures from a large sample of patients is heretofore unreported and may lead to an under-appreciation of these factors in surgical planning and ultimate preservation or correction of alignment. Lateral preoperative and postoperative lumbar radiographs were retrospectively acquired from 578 one- or two-level lumbar fusion patients and newly measured for lumbar lordosis (LL), pelvic incidence (PI), and pelvic tilt. Patients were categorized at preop and postop time points as aligned if PI-LL < 10° or malaligned if PI-LL≥10°. Patients were grouped into categories based on their alignment progression from pre- to postoperative, with preserved (aligned to aligned), restored (malaligned to aligned), not corrected (malaligned to malaligned), and worsened (aligned to malaligned) designations. Preoperatively, 173 (30%) patients exhibited malalignment. Postoperatively, 161 (28%) of patients were malaligned. Alignment was preserved in 63%, restored in 9%, not corrected in 21%, and worsened in 7% of patients. This is the first multicenter study to evaluate the preoperative prevalence and postoperative incidence of spinopelvic malalignment in a large series of short-segment degenerative lumbar fusions, finding over 25% of patients out of alignment at both time points, suggesting that alignment preservation/restoration considerations should be incorporated into the decision-making of even degenerative lumbar spinal fusions. 3.

Suprascapular nerve block (using bupivacaine and methylprednisolone acetate) in chronic shoulder pain.

PubMed

Shanahan, E M; Ahern, M; Smith, M; Wetherall, M; Bresnihan, B; FitzGerald, O

2003-05-01

Shoulder pain from inflammatory arthritis and/or degenerative disease is a common cause of morbidity in the community. It is difficult to treat and there are limited data on the efficacy of most interventions. Suprascapular nerve block has shown promise in limited trials in reducing shoulder pain. There have been no large randomised placebo controlled trials examining the efficacy of suprascapular nerve block for shoulder pain in arthritis and/or degenerative disease using pain and disability end points. To perform a randomised, double blind, placebo controlled trial of the efficacy of suprascapular nerve block for shoulder pain in rheumatoid arthritis (RA) and/or degenerative disease of the shoulder. 83 people with chronic shoulder pain from degenerative disease or RA took part in the trial. If a person had two painful shoulders, these were randomised separately. A total of 108 shoulders were randomised. Patients in the group receiving active treatment had a single suprascapular nerve block following the protocol described by Dangoisse et al, while those in the other group received a placebo injection of normal saline administered subcutaneously. The patients were followed up for 12 weeks by an observer who was unaware of the randomisation and reviewed at weeks 1, 4, and 12 after the injection. Pain, disability, and range of movement data were gathered. Clinically and statistically significant improvements in all pain scores, all disability scores, and some range of movement scores in the shoulders receiving suprascapular nerve block compared with those receiving placebo were seen at weeks 1, 4, and 12. There were no significant adverse effects in either group. Suprascapular nerve block is a safe and efficacious treatment for the treatment of shoulder pain in degenerative disease and/or arthritis. It improves pain, disability, and range of movement at the shoulder compared with placebo. It is a useful adjunct treatment for the practising clinician to assist in the management of a difficult and common clinical problem.

Systematic Review of the Long-term Surgical Outcomes of Discoid Lateral Meniscus.

PubMed

Lee, Yong Seuk; Teo, Seow Hui; Ahn, Jin Hwan; Lee, O-Sung; Lee, Seung Hoon; Lee, Je Ho

2017-10-01

To evaluate the surgical treatment of the discoid lateral meniscus (DLM) with long-term follow-up and to search which factors are related to good clinical or radiological outcomes. Search was performed using a MEDLINE, EMBASE, and Cochrane database, and each of the selected studies was evaluated for methodological quality using a risk of bias (ROB) covering 7 criteria. Clinical and radiological outcomes with more than 5 years of follow-up were evaluated after surgical treatment of DLM. They were analyzed according to the age, follow-up period, kind of surgery, DLM type, and alignment. Eleven articles (422 DLM cases) were included in the final analysis. Among 7 criteria, 3 criteria showed little ROB in all studies. However, 4 criteria showed some ROB ("Yes" in 63.6% to 81.8%). The minimal follow-up period was 5.5 years (weighted mean follow-up: 9.1 years). Surgical procedures were performed with open or arthroscopic partial central meniscectomy, subtotal meniscectomy, total meniscectomy, or partial meniscectomy with repair. The majority of the studies showed good clinical results. Mild joint space narrowing was reported in the lateral compartment, but none of the knees demonstrated moderate or advanced degenerative changes. Increased age at surgery, longer follow-up period, and subtotal or total meniscectomy could be related to degenerative change. The majority of the complications was osteochondritis dissecans at the lateral femoral condyle (13 cases) and reoperation was performed by osteochondritis dissecans (4 cases), recurrent swelling (2 cases), residual symptom (1 case), stiffness (1 case), and popliteal stenosis (1 case). Good clinical results were obtained with surgical treatment of symptomatic DLM. The progression of degenerative change was minimal and none of the knees demonstrated moderate or advanced degenerative changes. Increased age at surgery, longer follow-up period, and subtotal or total meniscectomy were possible risk factors for degenerative changes. Level IV, systematic review of Level IV studies. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Random genetic drift, natural selection, and noise in human cranial evolution.

PubMed

Roseman, Charles C

2016-08-01

This study assesses the extent to which relationships among groups complicate comparative studies of adaptation in recent human cranial variation and the extent to which departures from neutral additive models of evolution hinder the reconstruction of population relationships among groups using cranial morphology. Using a maximum likelihood evolutionary model fitting approach and a mixed population genomic and cranial data set, I evaluate the relative fits of several widely used models of human cranial evolution. Moreover, I compare the goodness of fit of models of cranial evolution constrained by genomic variation to test hypotheses about population specific departures from neutrality. Models from population genomics are much better fits to cranial variation than are traditional models from comparative human biology. There is not enough evolutionary information in the cranium to reconstruct much of recent human evolution but the influence of population history on cranial variation is strong enough to cause comparative studies of adaptation serious difficulties. Deviations from a model of random genetic drift along a tree-like population history show the importance of environmental effects, gene flow, and/or natural selection on human cranial variation. Moreover, there is a strong signal of the effect of natural selection or an environmental factor on a group of humans from Siberia. The evolution of the human cranium is complex and no one evolutionary process has prevailed at the expense of all others. A holistic unification of phenome, genome, and environmental context, gives us a strong point of purchase on these problems, which is unavailable to any one traditional approach alone. Am J Phys Anthropol 160:582-592, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

High-expanding cortical regions in human development and evolution are related to higher intellectual abilities.

PubMed

Fjell, Anders M; Westlye, Lars T; Amlien, Inge; Tamnes, Christian K; Grydeland, Håkon; Engvig, Andreas; Espeseth, Thomas; Reinvang, Ivar; Lundervold, Astri J; Lundervold, Arvid; Walhovd, Kristine B

2015-01-01

Cortical surface area has tremendously expanded during human evolution, and similar patterns of cortical expansion have been observed during childhood development. An intriguing hypothesis is that the high-expanding cortical regions also show the strongest correlations with intellectual function in humans. However, we do not know how the regional distribution of correlations between intellectual function and cortical area maps onto expansion in development and evolution. Here, in a sample of 1048 participants, we show that regions in which cortical area correlates with visuospatial reasoning abilities are generally high expanding in both development and evolution. Several regions in the frontal cortex, especially the anterior cingulate, showed high expansion in both development and evolution. The area of these regions was related to intellectual functions in humans. Low-expanding areas were not related to cognitive scores. These findings suggest that cortical regions involved in higher intellectual functions have expanded the most during development and evolution. The radial unit hypothesis provides a common framework for interpretation of the findings in the context of evolution and prenatal development, while additional cellular mechanisms, such as synaptogenesis, gliogenesis, dendritic arborization, and intracortical myelination, likely impact area expansion in later childhood. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Science as a (TRANSITORY?) Phase in Human Evolution

NASA Astrophysics Data System (ADS)

Leibowitz, Elia

One of the key elements of human knowledge in the last 150 years is the recognition that the universe, as well as each of its components, are in a permanent stage of evolution. Mankind and human affairs are of course no exceptions. Human beings owe their biological supremacy to the possession of a form of inheritance quite unlike that of other animals: exogenetic heredity. They have a non genetic channel for transmitting information from one generation to another, namely, the entire apparatus of culture. As information is correlated with brain structure, culture is a non genetic means to create patterns in human brains. It therefore plays a major role in human evolution. This apparatus by itself is however also undergoing a process of evolution. Using examples of astronomical, cosmological and other cultural concepts and argumentations, I shall show that throughout recorded human history, 4 distinct phases can be recognized in the evolution of this non genetic apparatus. The latest phase, the beginning of which is symbolized by the life and work of Galileo, is the "scientific" era. At the turn of the millenium, humankind is possibly at a transition state, from the "scientific" towards a new phase that may be termed a "public relation" or "propaganda" era. Causes for this transition can be found among recent developments in mass media and communications. These, in turn, are correlated with modern, 20th century trends in economy, technology and sociology that are other dominants factors in this transition. The apparent decline of the "scientific" culture may have profound consequences on the future evolution of mankind.

On the Evolution of Human Language.

ERIC Educational Resources Information Center

Lieberman, Philip

Human linguistic ability depends, in part, on the gradual evolution of man's supralaryngeal vocal tract. The anatomic basis of human speech production is the result of a long evolutionary process in which the Darwinian process of natural selection acted to retain mutations. For auditory perception, the listener operates in terms of the acoustic…

Articular Cartilage of the Human Knee Joint: In Vivo Multicomponent T2 Analysis at 3.0 T

PubMed Central

Choi, Kwang Won; Samsonov, Alexey; Spencer, Richard G.; Wilson, John J.; Block, Walter F.; Kijowski, Richard

2015-01-01

Purpose To compare multicomponent T2 parameters of the articular cartilage of the knee joint measured by using multicomponent driven equilibrium single-shot observation of T1 and T2 (mcDESPOT) in asymptomatic volunteers and patients with osteoarthritis. Materials and Methods This prospective study was performed with institutional review board approval and with written informed consent from all subjects. The mcDESPOT sequence was performed in the knee joint of 13 asymptomatic volunteers and 14 patients with osteoarthritis of the knee. Single-component T2 (T2Single), T2 of the fast-relaxing water component (T2F) and of the slow-relaxing water component (T2S), and the fraction of the fast-relaxing water component (FF) of cartilage were measured. Wilcoxon rank-sum tests and multivariate linear regression models were used to compare mcDESPOT parameters between volunteers and patients with osteoarthritis. Receiver operating characteristic analysis was used to assess diagnostic performance with mcDESPOT parameters for distinguishing morphologically normal cartilage from morphologically degenerative cartilage identified at magnetic resonance imaging in eight cartilage subsections of the knee joint. Results Higher cartilage T2Single (P < .001), lower cartilage FF (P < .001), and similar cartilage T2F (P = .079) and T2S (P = .124) values were seen in patients with osteoarthritis compared with those in asymptomatic volunteers. Differences in T2Single and FF remained significant (P < .05) after consideration of age differences between groups of subjects. Diagnostic performance was higher with FF than with T2Single for distinguishing between normal and degenerative cartilage (P < .05), with greater areas under the curve at receiver operating characteristic analysis. Conclusion Patients with osteoarthritis of the knee had significantly higher cartilage T2Single and significantly lower cartilage FF than did asymptomatic volunteers, and receiver operating characteristic analysis results suggested that FF may allow greater diagnostic performance than that with T2Single for distinguishing between normal and degenerative cartilage. © RSNA, 2015 Online supplemental material is available for this article. PMID:26024307

Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes.

PubMed

Braidy, Nady; Berg, Jade; Clement, James; Khorshidi, Fatemeh; Poljak, Anne; Jayasena, Tharusha; Grant, Ross; Sachdev, Perminder

2018-05-11

Nicotinamide adenine dinucleotide (NAD + ) is an essential pyridine nucleotide that serves as an essential cofactor and substrate for a number of critical cellular processes involved in oxidative phosphorylation and ATP production, DNA repair, epigenetically modulated gene expression, intracellular calcium signaling, and immunological functions. NAD + depletion may occur in response to either excessive DNA damage due to free radical or ultraviolet attack, resulting in significant poly(ADP-ribose) polymerase (PARP) activation and a high turnover and subsequent depletion of NAD + , and/or chronic immune activation and inflammatory cytokine production resulting in accelerated CD38 activity and decline in NAD + levels. Recent studies have shown that enhancing NAD + levels can profoundly reduce oxidative cell damage in catabolic tissue, including the brain. Therefore, promotion of intracellular NAD + anabolism represents a promising therapeutic strategy for age-associated degenerative diseases in general, and is essential to the effective realization of multiple benefits of healthy sirtuin activity. The kynurenine pathway represents the de novo NAD + synthesis pathway in mammalian cells. NAD + can also be produced by the NAD + salvage pathway. Recent Advances: In this review, we describe and discuss recent insights regarding the efficacy and benefits of the NAD + precursors, nicotinamide (NAM), nicotinic acid (NA), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN), in attenuating NAD + decline in degenerative disease states and physiological aging. Results obtained in recent years have shown that NAD + precursors can play important protective roles in several diseases. However, in some cases, these precursors may vary in their ability to enhance NAD + synthesis via their location in the NAD + anabolic pathway. Increased synthesis of NAD + promotes protective cell responses, further demonstrating that NAD + is a regulatory molecule associated with several biochemical pathways. In the next few years, the refinement of personalized therapy for the use of NAD + precursors and improved detection methodologies allowing the administration of specific NAD + precursors in the context of patients' NAD + levels will lead to a better understanding of the therapeutic role of NAD + precursors in human diseases. Antioxid. Redox Signal. 00, 000-000.

Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution

PubMed Central

Mendizabal, Isabel; Shi, Lei; Keller, Thomas E.; Konopka, Genevieve; Preuss, Todd M.; Hsieh, Tzung-Fu; Hu, Enzhi; Zhang, Zhe; Su, Bing; Yi, Soojin V.

2016-01-01

How do epigenetic modifications change across species and how do these modifications affect evolution? These are fundamental questions at the forefront of our evolutionary epigenomic understanding. Our previous work investigated human and chimpanzee brain methylomes, but it was limited by the lack of outgroup data which is critical for comparative (epi)genomic studies. Here, we compared whole genome DNA methylation maps from brains of humans, chimpanzees and also rhesus macaques (outgroup) to elucidate DNA methylation changes during human brain evolution. Moreover, we validated that our approach is highly robust by further examining 38 human-specific DMRs using targeted deep genomic and bisulfite sequencing in an independent panel of 37 individuals from five primate species. Our unbiased genome-scan identified human brain differentially methylated regions (DMRs), irrespective of their associations with annotated genes. Remarkably, over half of the newly identified DMRs locate in intergenic regions or gene bodies. Nevertheless, their regulatory potential is on par with those of promoter DMRs. An intriguing observation is that DMRs are enriched in active chromatin loops, suggesting human-specific evolutionary remodeling at a higher-order chromatin structure. These findings indicate that there is substantial reprogramming of epigenomic landscapes during human brain evolution involving noncoding regions. PMID:27563052

Cervical Radiculopathy due to Cervical Degenerative Diseases : Anatomy, Diagnosis and Treatment

PubMed Central

Kim, Kyoung-Tae

2010-01-01

A cervical radiculopathy is the most common symptom of cervical degenerative disease and its natural course is generally favorable. With a precise diagnosis using appropriate tools, the majority of patients will respond well to conservative treatment. Cervical radiculopathy with persistent radicular pain after conservative treatment and progressive or profound motor weakness may require surgery. Options for surgical management are extensive. Each technique has strengths and weaknesses, so the choice will depend on the patient's clinical profile and the surgeon's judgment. PMID:21430971

The Degenerative Spine.

PubMed

Clarençon, Frédéric; Law-Ye, Bruno; Bienvenot, Peggy; Cormier, Évelyne; Chiras, Jacques

2016-08-01

Degenerative disease of the spine is a leading cause of back pain and radiculopathy, and is a frequent indication for spine MR imaging. Disc degeneration, disc protrusion/herniation, discarhtrosis, spinal canal stenosis, and facet joint arthrosis, as well as interspinous processes arthrosis, may require an MR imaging workup. This review presents the MR imaging patterns of these diseases and describes the benefit of the MR imaging in these indications compared with the other imaging modalities like plain radiographs or computed tomography scan. Copyright © 2016 Elsevier Inc. All rights reserved.

Evolution of mosquito preference for humans linked to an odorant receptor

PubMed Central

McBride, Carolyn S.; Baier, Felix; Omondi, Aman B.; Spitzer, Sarabeth A.; Lutomiah, Joel; Sang, Rosemary; Ignell, Rickard; Vosshall, Leslie B.

2014-01-01

Female mosquitoes are major vectors of human disease and the most dangerous are those that preferentially bite humans. A ‘domestic’ form of the mosquito Aedes aegypti has evolved to specialize in biting humans and is the major worldwide vector of dengue, yellow fever, and Chikungunya viruses. The domestic form coexists with an ancestral, animal-biting ‘forest’ form along the coast of Kenya. We collected the two forms, established laboratory colonies, and document striking divergence in preference for human versus animal odour. We further show that the evolution of preference for human odour in domestic mosquitoes is tightly linked to increases in the expression and ligand-sensitivity of the odorant receptor AaegOr4, which we found recognises a compound present at high levels in human odour. Our results provide a rare example of a gene contributing to behavioural evolution and provide insight into how disease-vectoring mosquitoes came to specialise on humans. PMID:25391959

An in vivo study of low back pain and shock absorption in the human locomotor system.

PubMed

Voloshin, A; Wosk, J

1982-01-01

In this second of three papers, the principles of a non-invasive in vivo method to quantitatively evaluate the shock absorbing capacity of the human musculoskeletal system and the correlation of this shock absorbing capacity with low back pain (LPB) symptoms are presented. The experiments involved patients suffering from low back pain (as well as other degenerative joint diseases) and healthy patients. The obtained results reveal that low back pain correlates with the reduced capacity of the human musculoskeletal system between the femoral condyle and the forehead to attenuate incoming shock waves. Examination of the absolute values of the amplitude of the propagated waves leads to the conclusion that the human locomotor system, which possesses reduced attenuation capacity, tries to prevent overloading of the head from insufficiently attenuated shock waves. Results of the present investigation support the idea that the repetitive loading resulting from gait generates intermittent waves that propagate through the entire human musculoskeletal system from the heel up to the head. These waves are gradually attenuated along this course by the natural shock absorbers (bone and soft tissues). Contemporary methods for examination of the human musculoskeletal system may by improved by using the proposed non-invasive in vivo technique for quantitative characterization of the locomotor system's shock absorbing capacity.

In silico study of the human rhodopsin and meta rhodopsin II/S-arrestin complexes: impact of single point mutations related to retina degenerative diseases.

PubMed

Mokarzel-Falcón, Leonardo; Padrón-García, Juan Alexander; Carrasco-Velar, Ramón; Berry, Colin; Montero-Cabrera, Luis A

2008-03-01

We propose two models of the human S-arrestin/rhodopsin complex in the inactive dark adapted rhodopsin and meta rhodopsin II form, obtained by homology modeling and knowledge based docking. First, a homology model for the human S-arrestin was built and validated by molecular dynamics, showing an average root mean square deviation difference from the pattern behavior of 0.76 A. Then, combining the human S-arrestin model and the modeled structure of the two human rhodopsin forms, we propose two models of interaction for the human S-arrestin/rhodopsin complex. The models involve two S-arrestin regions related to the N domain (residues 68-78; 170-182) and a third constituent of the C domain (248-253), with the rhodopsin C terminus (330-348). Of the 22 single point mutations related to retinitis pigmentosa and congenital night blindness located in the cytoplasmatic portion of rhodopsin or in S-arrestin, our models locate 16 in the interaction region and relate two others to possible dimer formation. Our calculations also predict that the light activated complex is more stable than the dark adapted rhodopsin and, therefore, of higher affinity to S-arrestin. 2008 Wiley-Liss, Inc.

Convergent Evolution of Human-Isolated H7N9 Avian Influenza A Viruses.

PubMed

Xiang, Dan; Shen, Xuejuan; Pu, Zhiqing; Irwin, David M; Liao, Ming; Shen, Yongyi

2018-05-05

Avian influenza A virus H7N9 has caused 5 epidemic waves of human infections in China since 2013. Avian influenza A viruses may face strong selection to adapt to novel conditions when establishing themselves in humans. In this study, we sought to determine whether adaptive evolution had occurred in human-isolated H7N9 viruses. We evaluated all available genomes of H7N9 avian influenza A virus. Maximum likelihood trees were separately reconstructed for all 8 genes. Signals of positive selection and convergent evolution were then detected on branches that lead to changes in host tropism (from avian to human). We found that 3 genes had significant signals of positive selection (all of them P < .05). In addition, we detected 34 sites having significant signals for parallel evolution in 8 genes (all of them P < .05), including 7 well-known sites (Q591K, E627K, and D701N in PB2 gene; R156K, V202A, and L244Q in HA; and R289K in NA) that play roles in crossing species barriers for avian influenza A viruses. Our study suggests that, during infection in humans, H7N9 viruses have undergone adaptive evolution to adapt to their new host environment and that the sites where parallel evolution occurred might play roles in crossing species barriers and respond to the new selection pressures arising from their new host environments.

Extraterrestrial intelligence? Not likely.

PubMed

DeVore, I

2001-12-01

The possibility that there exist extraterrestrial creatures with advanced intelligence is considered by examining major events in mammalian, primate, and human evolution on earth. The overwhelming evidence is that the evolution of intelligence in creatures elsewhere who have the capability to communicate with us is vanishingly small. The history of the evolution of advanced forms of life on this planet is so beset by adventitious, unpredictable events and multiple contingencies that the evolution of human-level intelligence is highly unlikely on any planet, including earth.

Language evolution and human-computer interaction

NASA Technical Reports Server (NTRS)

Grudin, Jonathan; Norman, Donald A.

1991-01-01

Many of the issues that confront designers of interactive computer systems also appear in natural language evolution. Natural languages and human-computer interfaces share as their primary mission the support of extended 'dialogues' between responsive entities. Because in each case one participant is a human being, some of the pressures operating on natural languages, causing them to evolve in order to better support such dialogue, also operate on human-computer 'languages' or interfaces. This does not necessarily push interfaces in the direction of natural language - since one entity in this dialogue is not a human, this is not to be expected. Nonetheless, by discerning where the pressures that guide natural language evolution also appear in human-computer interaction, we can contribute to the design of computer systems and obtain a new perspective on natural languages.

Role of Wnt signaling during inflammation and sepsis: A review of the literature.

PubMed

Houschyar, Khosrow Siamak; Chelliah, Malcolm P; Rein, Susanne; Maan, Zeshaan N; Weissenberg, Kristian; Duscher, Dominik; Branski, Ludwik K; Siemers, Frank

2018-05-01

Despite the development of modern intensive care and new antimicrobial agents, the mortality of patients with severe sepsis and septic shock remains high. Systemic inflammation is a consequence of activation of the innate immune system. It is characterized by the intravascular release of proinflammatory cytokines and other vasoactive mediators, with concurrent activation of innate immune cells. The Wnt signaling pathway plays a critical role in the development of multicellular organisms. Abnormal Wnt signaling has been associated with many human diseases, ranging from inflammation and degenerative diseases to cancer. This article reviews the accumulating evidence that the Wnt signaling pathway plays a distinct role in inflammation and sepsis.

NASA Strategy to Safely Live and Work in the Space Radiation Environment

NASA Technical Reports Server (NTRS)

Cucinotta, Francis; Wu, Honglu; Corbin, Barbara; Sulzman, Frank; Kreneck, Sam

2007-01-01

This viewgraph document reviews the radiation environment that is a significant potential hazard to NASA's goals for space exploration, of living and working in space. NASA has initiated a Peer reviewed research program that is charged with arriving at an understanding of the space radiation problem. To this end NASA Space Radiation Laboratory (NSRL) was constructed to simulate the harsh cosmic and solar radiation found in space. Another piece of the work was to develop a risk modeling tool that integrates the results from research efforts into models of human risk to reduce uncertainties in predicting risk of carcinogenesis, central nervous system damage, degenerative tissue disease, and acute radiation effects acute radiation effects.

First Do No Harm: Euthanasia of Patients with Dementia in Belgium

PubMed Central

Cohen-Almagor, Raphael

2016-01-01

In Memory of Ed Pellegrino Euthanasia in Belgium is not limited to terminally ill patients. It may be applied to patients with chronic degenerative diseases. Currently, people in Belgium wish to make it possible to euthanize incompetent patients who suffer from dementia. This article explains the Belgian law and then explores arguments for and against euthanasia of patients with dementia. It probes the dementia paradox by elucidating Dworkin’s distinction between critical and experiential interests, arguing that at the end-of-life this distinction is not clearcut. It argues against euthanasia for patients with dementia, for respecting patients’ humanity and for providing them with more care, compassion, and good doctoring. PMID:26661050

In the swim of things: recent insights to neurogenetic disorders from zebrafish.

PubMed

Kabashi, Edor; Champagne, Nathalie; Brustein, Edna; Drapeau, Pierre

2010-08-01

The advantage of zebrafish as a model to study human pathologies lies in the ease of manipulating gene expression in vivo. Here we focus on recent progress in our understanding of motor neuron diseases and neurodevelopmental disorders and discuss how novel technologies will permit further disease models to be developed. Together these advances set the stage for this simple functional model, with particular advantages for transgenesis, multigenic analyses and chemical biology, to become uniquely suited for advancing the functional genomics of neurological and possibly psychiatric diseases - from understanding the genetics and cell biology of degenerative and developmental disorders to the discovery of therapeutics. Copyright 2010 Elsevier Ltd. All rights reserved.

Inflammation in aging: cause, effect, or both?

PubMed

Jenny, Nancy S

2012-06-01

Aging is a progressive degenerative process tightly integrated with inflammation. Cause and effect are not clear. A number of theories have been developed that attempt to define the role of chronic inflammation in aging: redox stress, mitochondrial damage, immunosenescence, endocrinosenescence, epigenetic modifications, and age-related diseases. However, no single theory explains all aspects of aging; instead, it is likely that multiple processes contribute and that all are intertwined with inflammatory responses. Human immunodeficiency virus (HIV)-infected patients undergo a premature aging phenomenon which may provide clues to better elucidate the nature of inflammation in aging. Environmental and lifestyle effectors of inflammation may also contribute to modulation of both inflammation and age-related dysfunction.

The Status of RPE65 Gene Therapy Trials: Safety and Efficacy

PubMed Central

Pierce, Eric A.; Bennett, Jean

2015-01-01

Several groups have reported the results of clinical trials of gene augmentation therapy for Leber congenital amaurosis (LCA) because of mutations in the RPE65 gene. These studies have used subretinal injection of adeno-associated virus (AAV) vectors to deliver the human RPE65 cDNA to the retinal pigment epithelial (RPE) cells of the treated eyes. In all of the studies reported to date, this approach has been shown to be both safe and effective. The successful clinical trials of gene augmentation therapy for retinal degeneration caused by mutations in the RPE65 gene sets the stage for broad application of gene therapy to treat retinal degenerative disorders. PMID:25635059

Dual function of MG53 in membrane repair and insulin signaling

PubMed Central

Tan, Tao; Ko, Young-Gyu; Ma, Jianjie

2016-01-01

MG53 is a member of the TRIM-family protein that acts as a key component of the cell membrane repair machinery. MG53 is also an E3-ligase that ubiquinates insulin receptor substrate-1 and controls insulin signaling in skeletal muscle cells. Since its discovery in 2009, research efforts have been devoted to translate this basic discovery into clinical applications in human degenerative and metabolic diseases. This review article highlights the dual function of MG53 in cell membrane repair and insulin signaling, the mechanism that underlies the control of MG53 function, and the therapeutic value of targeting MG53 function in regenerative medicine. [BMB Reports 2016; 49(8): 414-423] PMID:27174502

Degenerative Changes in the Knee 2 Years After Anterior Cruciate Ligament Rupture and Related Risk Factors: A Prospective Observational Follow-up Study.

PubMed

van Meer, Belle L; Oei, Edwin H G; Meuffels, Duncan E; van Arkel, Ewoud R A; Verhaar, Jan A N; Bierma-Zeinstra, Sita M A; Reijman, Max

2016-06-01

Anterior cruciate ligament (ACL) rupture is a well-known risk factor for development of knee osteoarthritis. Early identification of those patients at risk and early identification of the process of ACL rupture leading to osteoarthritis may aid in preventing the onset or progression of osteoarthritis. To identify early degenerative changes as assessed on magnetic resonance imaging (MRI) after 2-year follow-up in patients with a recent ACL rupture and to evaluate which determinants are related to these changes. Cohort study; Level of evidence, 2. Included in this study were 154 adults aged between 18 and 45 years with acute ACL rupture diagnosed by physical examination and MRI, without previous knee trauma or surgery, and without osteoarthritic changes on radiographs. A total of 143 patients completed the 2-year follow-up, and the results in this study apply to these 143 patients. All patients were treated according to the Dutch guideline on ACL injury. Of the 143 patients, 50 patients were treated nonoperatively during the 2-year follow-up period. Main outcome was early degenerative changes assessed on MRI defined as progression of cartilage defects and osteophytes in tibiofemoral and patellofemoral compartments. Patient characteristics, activity level, functional instability, treatment type, and trauma-related variables were evaluated as determinants. The median time between MRI at baseline and MRI at 2-year follow-up was 25.9 months (interquartile range, 24.7-26.9 months). Progression of cartilage defects in the medial and lateral tibiofemoral compartments was present in 12% and 27% of patients, and progression of osteophytes in tibiofemoral and patellofemoral compartments was present in 10% and 8% of patients, respectively. The following determinants were positively significantly associated with early degenerative changes: male sex (odds ratio [OR], 4.43; 95% CI, 1.43-13.66; P = .010), cartilage defect in the medial tibiofemoral compartment at baseline (OR, 3.66; 95% CI, 1.04-12.95; P = .044), presence of bone marrow lesions in the medial tibiofemoral compartment 1 year after trauma (OR, 5.19; 95% CI, 1.56-17.25; P = .007), joint effusion 1 year after trauma (OR, 4.19; 95% CI, 1.05-16.72; P = .042), and presence of meniscal tears (OR, 6.37; 95% CI, 1.94-20.88; P = .002). When the patients were categorized into 3 treatment groups (nonoperative, reconstruction <6 months after ACL rupture, and reconstruction ≥6 months after ACL rupture), there was no significant relationship between the treatment options and the development of early degenerative changes. Two years after ACL rupture, early degenerative changes were assessed on MRI. Concomitant medial cartilage defect and meniscal injury, male sex, persistent bone marrow lesions in the medial tibiofemoral compartment, and joint effusion are risk factors for degenerative changes. © 2016 The Author(s).

Evidence of a Conserved Molecular Response to Selection for Increased Brain Size in Primates

PubMed Central

Harrison, Peter W.; Caravas, Jason A.; Raghanti, Mary Ann; Phillips, Kimberley A.; Mundy, Nicholas I.

2017-01-01

The adaptive significance of human brain evolution has been frequently studied through comparisons with other primates. However, the evolution of increased brain size is not restricted to the human lineage but is a general characteristic of primate evolution. Whether or not these independent episodes of increased brain size share a common genetic basis is unclear. We sequenced and de novo assembled the transcriptome from the neocortical tissue of the most highly encephalized nonhuman primate, the tufted capuchin monkey (Cebus apella). Using this novel data set, we conducted a genome-wide analysis of orthologous brain-expressed protein coding genes to identify evidence of conserved gene–phenotype associations and species-specific adaptations during three independent episodes of brain size increase. We identify a greater number of genes associated with either total brain mass or relative brain size across these six species than show species-specific accelerated rates of evolution in individual large-brained lineages. We test the robustness of these associations in an expanded data set of 13 species, through permutation tests and by analyzing how genome-wide patterns of substitution co-vary with brain size. Many of the genes targeted by selection during brain expansion have glutamatergic functions or roles in cell cycle dynamics. We also identify accelerated evolution in a number of individual capuchin genes whose human orthologs are associated with human neuropsychiatric disorders. These findings demonstrate the value of phenotypically informed genome analyses, and suggest at least some aspects of human brain evolution have occurred through conserved gene–phenotype associations. Understanding these commonalities is essential for distinguishing human-specific selection events from general trends in brain evolution. PMID:28391320

Cumulative role of rare and common putative functional genetic variants at NPAS3 in schizophrenia susceptibility.

PubMed

González-Peñas, Javier; Arrojo, Manuel; Paz, Eduardo; Brenlla, Julio; Páramo, Mario; Costas, Javier

2015-10-01

Schizophrenia may be considered a human-specific disorder arisen as a maladaptive by-product of human-specific brain evolution. Therefore, genetic variants involved in susceptibility to schizophrenia may be identified among those genes related to acquisition of human-specific traits. NPAS3, a transcription factor involved in central nervous system development and neurogenesis, seems to be implicated in the evolution of human brain, as it is the human gene with most human-specific accelerated elements (HAEs), i.e., .mammalian conserved regulatory sequences with accelerated evolution in the lineage leading to humans after human-chimpanzee split. We hypothesize that any nucleotide variant at the NPAS3 HAEs may lead to altered susceptibility to schizophrenia. Twenty-one variants at these HAEs detected by the 1000 genomes Project, as well as five additional variants taken from psychiatric genome-wide association studies, were genotyped in 538 schizophrenic patients and 539 controls from Galicia. Analyses at the haplotype level or based on the cumulative role of the variants assuming different susceptibility models did not find any significant association in spite of enough power under several plausible scenarios regarding direction of effect and the specific role of rare and common variants. These results suggest that, contrary to our hypothesis, the special evolution of the NPAS3 HAEs in Homo relaxed the strong constraint on sequence that characterized these regions during mammalian evolution, allowing some sequence changes without any effect on schizophrenia risk. © 2015 Wiley Periodicals, Inc.

Exploring Relations among Preservice Elementary Teachers' Ideas about Evolution, Understanding of Relevant Science Concepts, and College Science Coursework

ERIC Educational Resources Information Center

Rice, Diana C.; Kaya, Sibel

2012-01-01

This study investigated the relations among preservice elementary teachers' ideas about evolution, their understanding of basic science concepts and college science coursework. Forty-two percent of 240 participants did not accept the theory of human evolution, but held inconsistent ideas about related topics, such as co-existence of humans and…

Clearing the Highest Hurdle: Human-Based Case Studies Broaden Students' Knowledge of Core Evolutionary Concepts

ERIC Educational Resources Information Center

Werth, Alexander J.

2009-01-01

An anonymous survey instrument was used for a ten year study to gauge college student attitudes toward evolution. Results indicate that students are most likely to accept evolution as a historical process for change in physical features of non-human organisms. They are less likely to accept evolution as an ongoing process that shapes all traits…

Q&A: What is human language, when did it evolve and why should we care?

PubMed

Pagel, Mark

2017-07-24

Human language is unique among all forms of animal communication. It is unlikely that any other species, including our close genetic cousins the Neanderthals, ever had language, and so-called sign 'language' in Great Apes is nothing like human language. Language evolution shares many features with biological evolution, and this has made it useful for tracing recent human history and for studying how culture evolves among groups of people with related languages. A case can be made that language has played a more important role in our species' recent (circa last 200,000 years) evolution than have our genes.

Socio-hydrologic perspectives of the co-evolution of humans and water in the Tarim River Basin, Western China: the Taiji-Tire Model

NASA Astrophysics Data System (ADS)

Liu, Y.; Tian, F.; Hu, H.; Sivapalan, M.

2013-10-01

This paper presents a historical socio-hydrological analysis of the Tarim Basin, Xinjiang Province, Western China, from the time of the opening of the Silk Road to the present. The analysis is aimed at exploring the historical co-evolution of coupled human-water systems and at identifying common patterns or organizing principles underpinning socio-hydrological systems (SHS). As a self-organized entity, the evolution of the human-water system in the Tarim Basin reached stable states for long periods of time, then punctuated by sudden shifts due to internal or external disturbances. In this study, we discuss three steady periods (i.e. natural, human exploitation, and degradation and recovery) and transitions in between during the past 2000 yr. During the "natural" stage that existed pre-18th century, with small-scale human society and sound environment, evolution of the SHS was mainly driven by natural environmental changes such as river channel migration and climate change. During the human exploitation stage, especially in the 19th and 20th centuries, it experienced rapid population growth, massive land reclamation and fast socio-economic development, and humans became the principal players of system evolution. By the 1970s, the Tarim Basin had evolved into a new regime with a vulnerable eco-hydrological system seemingly populated beyond its carrying capacity, and a human society that began to suffer from serious water shortages, land salinization and desertification. With intensified deterioration of river health and increased recognition of unsustainability of traditional development pattern, human intervention and recovery measures have been adopted. Since then, the basin has shown a reverse regime shift towards some healing of the environmental damage. Spatio-temporal variations of historical socio-hydrological co-evolution are classified into four types: primitive agricultural, traditional agricultural, industrial agricultural and urban SHSs. These co-evolutionary changes have been summarized in terms of the Taiji-Tire Model, a refinement of a special concept in Chinese philosophy, relating to the co-evolution of a system because of interactions among its components.

Human development, heredity and evolution.

PubMed

Nishinakamura, Ryuichi; Takasato, Minoru

2017-06-15

From March 27-29 2017, the RIKEN Center for Developmental Biology held a symposium entitled 'Towards Understanding Human Development, Heredity, and Evolution' in Kobe, Japan. Recent advances in technologies including stem cell culture, live imaging, single-cell approaches, next-generation sequencing and genome editing have led to an expansion in our knowledge of human development. Organized by Yoshiya Kawaguchi, Mitinori Saitou, Mototsugu Eiraku, Tomoya Kitajima, Fumio Matsuzaki, Takashi Tsuji and Edith Heard, the symposium covered a broad range of topics including human germline development, epigenetics, organogenesis and evolution. This Meeting Review provides a summary of this timely and exciting symposium, which has convinced us that we are moving into the era of science targeted on humans. © 2017. Published by The Company of Biologists Ltd.

The degenerative cervical spine.

PubMed

Llopis, E; Belloch, E; León, J P; Higueras, V; Piquer, J

2016-04-01

Imaging techniques provide excellent anatomical images of the cervical spine. The choice to use one technique or another will depend on the clinical scenario and on the treatment options. Plain-film X-rays continue to be fundamental, because they make it possible to evaluate the alignment and bone changes; they are also useful for follow-up after treatment. The better contrast resolution provided by magnetic resonance imaging makes it possible to evaluate the soft tissues, including the intervertebral discs, ligaments, bone marrow, and spinal cord. The role of computed tomography in the study of degenerative disease has changed in recent years owing to its great spatial resolution and its capacity to depict osseous components. In this article, we will review the anatomy and biomechanical characteristics of the cervical spine, and then we provide a more detailed discussion of the degenerative diseases that can affect the cervical spine and their clinical management. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Histopathological changes in rat pancreas after fasting and cassava feeding.

PubMed

Geldof, A A; Becking, J L; de Vries, C D; van der Veen, E A

1992-01-01

Histopathological changes in rat pancreas were induced by cyclic periods of experimental malnutrition or by cassava (manioc) feeding for 11 weeks. Decline of body weight was correlated with decrease in testicular fat pad weight as a measure of body fat stores. A marked decrease in pancreatic weight in the cassava-fed group was correlated with shrinkage of acinar structures and degenerative features in exocrine pancreas. In the malnutrition group vacuolisation and loss of tissue architecture were observed in some parts of the organ. No signs of ductal obstruction as a tentative cause of pancreatic pathology after malnutrition could be detected. Loss of islets tissue was occasionally seen in degenerative areas. It is concluded that histopathological changes in exocrine pancreas result from malnutrition and cassava feeding differentially and precede ultimate degenerative processes of pancreas endocrine tissue. Tropical malnutrition type diabetes and low protein related diabetes may in their etiology be different entities, but may coincide in practice and aggravate each other to yield severe and irreversible morbidity.

Natural History of Rotator Cuff Disease and Implications on Management

PubMed Central

Hsu, Jason

2015-01-01

Degenerative rotator cuff disease is commonly associated with ageing and is often asymptomatic. The factors related to tear progression and pain development are just now being defined through longitudinal natural history studies. The majority of studies that follow conservatively treated painful cuff tears or asymptomatic tears that are monitored at regular intervals show slow progression of tear enlargement and muscle degeneration over time. These studies have highlighted greater risks for disease progression for certain variables, such as the presence of a full-thickness tear and involvement of the anterior aspect supraspinatus tendon. Coupling the knowledge of the natural history of degenerative cuff tear progression with variables associated with greater likelihood of successful tendon healing following surgery will allow better refinement of surgical indications for rotator cuff disease. In addition, natural history studies may better define the risks of nonoperative treatment over time. This article will review pertinent literature regarding degenerative rotator cuff disease with emphasis on variables important to defining appropriate initial treatments and refining surgical indications. PMID:26726288

Thermo-sensitive injectable glycol chitosan-based hydrogel for treatment of degenerative disc disease.

PubMed

Li, Zhengzheng; Shim, Hyeeun; Cho, Myeong Ok; Cho, Ik Sung; Lee, Jin Hyun; Kang, Sun-Woong; Kwon, Bosun; Huh, Kang Moo

2018-03-15

The use of injectable hydrogel formulations have been suggested as a promising strategy for the treatment of degenerative disc disease to both restore the biomechanical function and reduce low back pain. In this work, a new thermo-sensitive injectable hydrogels with tunable thermo-sensitivity and enhanced stability were developed with N-hexanoylation of glycol chitosan (GC) for treatment of degenerative disc disease, and their physico-chemical and biological properties were evaluated. The sol-gel transition temperature of the hydrogels was controlled in a range of 23-56 °С, depending on the degree of hexanoylation and the polymer concentration. In vitro and in vivo tests showed no cytotoxicity and no adverse effects in a rat model. The hydrogel filling of the defective IVD site in an ex vivo porcine model maintained its stability for longer than 28 days. These results suggest that the hydrogel can be used as an alternative material for treatment of disc herniation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Human Evolution in Science Textbooks from Twelve Different Countries

ERIC Educational Resources Information Center

Quessada, Marie-Pierre; Clement, Pierre; Oerke, Britta; Valente, Adriana

2008-01-01

What kinds of images of human beings illustrate human evolution in school textbooks? A comparison between the textbooks of eighteen different countries (twelve European countries and six non-European countries) was attempted. In six countries (Algeria, Malta, Morocco, Mozambique, Portugal, and Tunisia), we did not find any chapter on the topic of…

Human Development, Human Evolution.

ERIC Educational Resources Information Center

Smillie, David

One of the truly remarkable events in human evolution is the unprecedented increase in the size of the brain of "Homo" over a brief span of 2 million years. It would appear that some significant selective pressure or opportunity presented itself to this branch of the hominid line and caused a rapid increase in the brain, introducing a…

Climatic Change and Human Evolution.

ERIC Educational Resources Information Center

Garratt, John R.

1995-01-01

Traces the history of the Earth over four billion years, and shows how climate has had an important role to play in the evolution of humans. Posits that the world's rapidly growing human population and its increasing use of energy is the cause of present-day changes in the concentrations of greenhouse gases in the atmosphere. (Author/JRH)

Laser biomodulation on stem cells

NASA Astrophysics Data System (ADS)

Liu, Timon C.; Duan, Rui; Li, Yan; Li, Xue-Feng; Tan, Li-Ling; Liu, Songhao

2001-08-01

Stem cells are views from the perspectives of their function, evolution, development, and cause. Counterintuitively, most stem cells may arise late in development, to act principally in tissue renewal, thus ensuring an organisms long-term survival. Surprisingly, recent reports suggest that tissue-specific adult stem cells have the potential to contribute to replenishment of multiple adult tissues. Stem cells are currently in the news for two reasons: the successful cultivation of human embryonic stem cell lines and reports that adult stem cells can differentiate into developmentally unrelated cell types, such as nerve cells into blood cells. The spotlight on stem cells has revealed gaps in our knowledge that must be filled if we are to take advantage of their full potential for treating devastating degenerative diseases such as Parkinsons's disease and muscular dystrophy. We need to know more about the intrinsic controls that keep stem cells as stem cells or direct them along particular differentiation pathways. Such intrinsic regulators are, in turn, sensitive to the influences of the microenvironment, or niche, where stem cells normally reside. Both intrinsic and extrinsic signals regular stem cell fate and some of these signals have now been identified. Vacek et al and Wang et al have studied the effect of low intensity laser on the haemopoietic stem cells in vitro. There experiments show there is indeed the effect of low intensity laser on the haemopoietic stem cells in vitro, and the present effect is the promotion of haemopoietic stem cells proliferation. In other words, low intensity laser irradiation can act as an extrinsic signal regulating stem cell fate. In this paper, we study how low intensity laser can be used to regulate stem cell fate from the viewpoint of collective phototransduction.

It May Seem Inflammatory, but Some T Cells Are Innately Healing to the Bone.

PubMed

Kalyan, Shirin

2016-11-01

Among the most significant developments to have taken place in osteology over the last few decades is an evolution from treating and viewing bone disorders primarily through an endocrine lens to instead seeing them as metabolic disorders that interface at the molecular and cellular level with the immune system. Osteoimmunology was officially born in response to accumulating evidence that the immune system is integrally involved in bone remodeling, but much of the early work focused on the role of conventional αβ T cells in driving bone loss. There is, however, emerging data indicating that innate lymphocytes, in particular γδ T cells, may in fact be important for bone regeneration. We first observed that bisphosphonate-associated osteonecrosis of the jaw (ONJ), a rare but serious adverse drug effect characterized by nonhealing necrotic bone tissue of the mandible or maxilla, was linked to a deficiency in a subset of γδ T cells found in human peripheral blood. Patients who developed ONJ while on bisphosphonate therapy not only lacked the main subset of circulating γδ T cells, but they also all had underlying conditions that compromised their immune integrity. A number of recent studies have unraveled the role of γδ T cells (and lymphocytes sharing their characteristics) in bone regeneration-particularly for fracture healing. These findings seem to contradict the prevailing view of such "inflammatory" T cells as being bone degenerative rather than restorative. This viewpoint melds together the emerging evidence of these so-called inflammatory T cells in bone remodeling and healing-showing that they are not in fact "all bad to the bone." © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Nonsurgically managed patients with degenerative spondylolisthesis: a 10- to 18-year follow-up study.

PubMed

Matsunaga, S; Ijiri, K; Hayashi, K

2000-10-01

Controversy exists concerning the indications for surgery and choice of surgical procedure for patients with degenerative spondylolisthesis. The goals of this study were to determine the clinical course of nonsurgically managed patients with degenerative spondylolisthesis as well as the indications for surgery. A total of 145 nonsurgically managed patients with degenerative spondylolisthesis were examined annually for a minimum of 10 years follow-up evaluation. Radiographic changes, changes in clinical symptoms, and functional prognosis were surveyed. Progressive spondylolisthesis was observed in 49 patients (34%). There was no correlation between changes in clinical symptoms and progression of spondylolisthesis. The intervertebral spaces of the slipped segments were decreased significantly in size during follow-up examination in patients in whom no progression was found. Low-back pain improved following a decrease in the total intervertebral space size. A total of 84 (76%) of 110 patients who had no neurological deficits at initial examination remained without neurological deficit after 10 years of follow up. Twenty-nine (83%) of the 35 patients who had neurological symptoms, such as intermittent claudication or vesicorectal disorder, at initial examination and refused surgery experienced neurological deterioration. The final prognosis for these patients was very poor. Low-back pain was improved by restabilization. Conservative treatment is useful for patients who have low-back pain with or without pain in the lower extremities. Surgical intervention is indicated for patients with neurological symptoms including intermittent claudication or vesicorectal disorder, provided that a good functional outcome can be achieved.

Multimedia psychoeducational interventions to support patient self-care in degenerative conditions: A realist review.

PubMed

O'Halloran, Peter; Scott, David; Reid, Joanne; Porter, Sam

2015-10-01

Multimedia interventions are increasingly used to deliver information in order to promote self-care among patients with degenerative conditions. We carried out a realist review of the literature to investigate how the characteristics of multimedia psychoeducational interventions combine with the contexts in which they are introduced to help or hinder their effectiveness in supporting self-care for patients with degenerative conditions. Electronic databases (Medline, Science Direct, PSYCHinfo, EBSCO, and Embase) were searched in order to identify papers containing information on multimedia psychoeducational interventions. Using a realist review approach, we reviewed all relevant studies to identify theories that explained how the interventions work. Ten papers were included in the review. All interventions sought to promote self-care behaviors among participants. We examined the development and content of the multimedia interventions and the impact of patient motivation and of the organizational context of implementation. We judged seven studies to be methodologically weak. All completed studies showed small effects in favor of the intervention. Multimedia interventions may provide high-quality information in an accessible format, with the potential to promote self-care among patients with degenerative conditions, if the patient perceives the information as important and develops confidence about self-care. The evidence base is weak, so that research is needed to investigate effective modes of delivery at different resource levels. We recommend that developers consider how an intervention will reduce uncertainty and increase confidence in self-care, as well as the impact of the context in which it will be employed.

Ultrasound-guided interventional procedures around the shoulder.

PubMed

Messina, Carmelo; Banfi, Giuseppe; Orlandi, Davide; Lacelli, Francesca; Serafini, Giovanni; Mauri, Giovanni; Secchi, Francesco; Silvestri, Enzo; Sconfienza, Luca Maria

2016-01-01

Ultrasound is an established modality for shoulder evaluation, being accurate, low cost and radiation free. Different pathological conditions can be diagnosed using ultrasound and can be treated using ultrasound guidance, such as degenerative, traumatic or inflammatory diseases. Subacromial-subdeltoid bursitis is the most common finding on ultrasound evaluation for painful shoulder. Therapeutic injections of corticosteroids are helpful to reduce inflammation and pain. Calcific tendinopathy of rotator cuff affects up to 20% of painful shoulders. Ultrasound-guided treatment may be performed with both single- and double-needle approach. Calcific enthesopathy, a peculiar form of degenerative tendinopathy, is a common and mostly asymptomatic ultrasound finding; dry needling has been proposed in symptomatic patients. An alternative is represented by autologous platelet-rich plasma injections. Intra-articular injections of the shoulder can be performed in the treatment of a variety of inflammatory and degenerative diseases with corticosteroids or hyaluronic acid respectively. Steroid injections around the long head of the biceps brachii tendon are indicated in patients with biceps tendinopathy, reducing pain and humeral tenderness. The most common indication for acromion-clavicular joint injection is degenerative osteoarthritis, with ultrasound representing a useful tool in localizing the joint space and properly injecting various types of drugs (steroids, lidocaine or hyaluronic acid). Suprascapular nerve block is an approved treatment for chronic shoulder pain non-responsive to conventional treatments as well as candidate patients for shoulder arthroscopy. This review provides an overview of these different ultrasonography-guided procedures that can be performed around the shoulder.

Proximal sacral deformity: a common element in lytic isthmic spondylolisthesis at L5 and in degenerative spondylolisthesis at L4-L5 segment. Two apparently very different etiopathogenic entities.

PubMed

Gallego-Goyanes, A; Barahona-Lorenzo, D; Díez-Ulloa, M A

A radiographic study was carried out to investigate the relationship between proximal sacral sagittal anatomy (either kyphosis or lordosis) and either isthmic or degenerative spondylolisthesis. In addition, we studied whether there is a relationship between proximal sacral kyphosis and the degree of such listhesis in the case of L5 isthmic spondylolisthesis. Lateral standing x-rays were used from 173 patients, ninety of whom had degenerative spondylolisthesis L4-L5, and eighty-three an isthmic spondylolisthesis of L5 (67 low-grade and 16 high-grade) and compared with a control group of 100 patients adjusted by age and gender, without any type of spondylolisthesis. Listhesis was graded using Meyerding's classification and the proximal sacral kyphosis angle (CSP) was measured between S1 and S2 posterior walls, according to Harrison's method. In our series, there was a proximal sacral kyphosis in both types of spondylolisthesis, greater in the lytic type. By contrast, the control group had a proximal sacral lordosis. The differences were statistically significant. Therefore, we concluded that there was a proximal sacral kyphosis in patients with both degenerative and isthmic lytic spondylolisthesis, but with our results, we were not able to ascertain whether it is a cause or a consequence of this listhesis. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Surgical results of dynamic nonfusion stabilization with the Segmental Spinal Correction System for degenerative lumbar spinal diseases with instability: Minimum 2-year follow-up

PubMed Central

Ohta, Hideki; Matsumoto, Yoshiyuki; Morishita, Yuichirou; Sakai, Tsubasa; Huang, George; Kida, Hirotaka; Takemitsu, Yoshiharu

2011-01-01

Background When spinal fusion is applied to degenerative lumbar spinal disease with instability, adjacent segment disorder will be an issue in the future. However, decompression alone could cause recurrence of spinal canal stenosis because of increased instability on operated segments and lead to revision surgery. Covering the disadvantages of both procedures, we applied nonfusion stabilization with the Segmental Spinal Correction System (Ulrich Medical, Ulm, Germany) and decompression. Methods The surgical results of 52 patients (35 men and 17 women) with a minimum 2-year follow-up were analyzed: 10 patients with lumbar spinal canal stenosis, 15 with lumbar canal stenosis with disc herniation, 20 with degenerative spondylolisthesis, 6 with disc herniation, and 1 with lumbar discopathy. Results The Japanese Orthopaedic Association score was improved, from 14.4 ± 5.3 to 25.5 ± 2.8. The improvement rate was 76%. Range of motion of the operated segments was significantly decreased, from 9.6° ± 4.2° to 2.0° ± 1.8°. Only 1 patient had adjacent segment disease that required revision surgery. There was only 1 screw breakage, but the patient was asymptomatic. Conclusions Over a minimum 2-year follow-up, the results of nonfusion stabilization with the Segmental Spinal Correction System for unstable degenerative lumbar disease were good. It is necessary to follow up the cases with a focus on adjacent segment disorders in the future. PMID:25802671

Effect of proprioceptive training on foot posture, lower limb alignment, and knee adduction moment in patients with degenerative knee osteoarthritis: a randomized controlled trial

PubMed Central

Cho, Yumi; Kim, Minkyu; Lee, Wanhee

2015-01-01

[Purpose] The purpose of this study was to determine the effect of proprioceptive training on foot progression angle, weight-bearing ratio, and knee adduction moment in patients with degenerative osteoarthritis of the knee. [Subjects] The subjects were 37 patients diagnosed with Kellgren-Lawrence grade 2 or 3 degenerative knee osteoarthritis. They were randomly allocated to three groups: a proprioceptive training group (PT group), quadriceps strengthening group (QS group), and control group. [Methods] The study parameters of the three groups were compared before and after a 12-week training period. Therapeutic exercises were performed twice per week for 12 weeks. Outcomes included the foot progression angle, weight-bearing ratio, and knee adduction moment. [Results] First, a significant difference in the foot progression angle was observed among the groups, significantly increasing in the PTG compared with the CG. Second, a significant difference in the weight-bearing ratio was observed among the groups, significantly increasing in the PTG compared with the CG. Third, a significant difference in the first peak knee adduction moment was observed among the groups, significantly decreasing in the PTG compared with the CG. [Conclusion] The results of the present study indicate that proprioceptive training increased the foot progression angle and weight-bearing ratio and decreased the first peak knee adduction moment. Moreover, incorporating proprioceptive training into a physical therapy exercise program could improve functional ability and delay the progression of degenerative osteoarthritis. PMID:25729170

Retrospective, Demographic, and Clinical Investigation of the Causes of Postoperative Infection in Patients With Lumbar Spinal Stenosis Who Underwent Posterior Stabilization.

PubMed

Yaldiz, Can; Yaldiz, Mahizer; Ceylan, Nehir; Kacira, Ozlem Kitiki; Ceylan, Davut; Kacira, Tibet; Kizilcay, Gokhan; Tanriverdi, Taner

2015-07-01

Owing to the increasing population of elderly patients, a large number of patients with degenerative spondylosis are currently being surgically treated. Although basic measures for decreasing postoperative surgical infections (PSIs) are considered, it still remains among the leading causes of morbidity and mortality. The aim of this retrospective analysis is to present possible causes leading to PSI in patients who underwent surgery for lumbar degenerative spondylosis and highlight how it can be avoided to decrease morbidity and mortality. The study included 540 patients who underwent posterior stabilization due to degenerative lumbar stenosis between January 2013 and January 2014. The data before and after surgery was retrieved from the hospital charts. Patients with degenerative lumbar stenosis who were operated upon in this study had >2 levels of laminectomy and facetectomy. For this reason, posterior stabilization was performed for all the patients included in this study. Determining the causes of postoperative infection (PI) following spinal surgeries performed with instrumentation is a struggle. Seventeen different parameters that may be related to PI were evaluated in this study. The presence of systemic diseases, unknown glove perforations, and perioperative blood transfusions were among the parameters that increased the prevalence of PI. Alternatively, prolene sutures, double-layered gloves, and the use of rifampicin Sv (RIS) decreased the incidence of PI. Although the presence of systemic diseases, unnoticed glove perforations, and perioperative blood transfusions increased PIs, prolene suture material, double-layered gloves, and the use of RIS decreased PIs.

Agreement between computed tomography, magnetic resonance imaging, and surgical findings in dogs with degenerative lumbosacral stenosis.

PubMed

Suwankong, Niyada; Voorhout, George; Hazewinkel, Herman A W; Meij, Björn P

2006-12-15

To assess the extent of agreement between computed tomography (CT), magnetic resonance imaging (MRI), and surgical findings in dogs with degenerative lumbosacral stenosis. Observational study. 35 dogs with degenerative lumbosacral stenosis. Results of preoperative CT and MRI were compared with surgical findings with respect to degree and location of disk protrusion, position of the dural sac, amount of epidural fat, and swelling of spinal nerve roots. A lumbosacral step was seen on radiographic images from 22 of 32 (69%) dogs, on CT images from 23 of 35 (66%) dogs, and on MR images from 21 of 35 (60%) dogs. Most dogs had slight or moderate disk protrusion that was centrally located. There was substantial or near perfect agreement between CT and MRI findings in regard to degree of disk protrusion (kappa, 0.88), location of disk protrusion (0.63), position of the dural sac (0.89), amount of epidural fat (0.72), and swelling of spinal nerve roots (0.60). The degree of agreement between CT and surgical findings and between MRI and surgical findings was moderate in regard to degree and location of disk protrusion (kappa, 0.44 to 0.56) and swelling of spinal nerve roots (0.40 and 0.50). Results indicate that there is a high degree of agreement between CT and MRI findings in dogs with degenerative lumbosacral stenosis but that the degree of agreement between diagnostic imaging findings and surgical findings is lower.

Local Stability of the Trunk in Patients with Degenerative Cerebellar Ataxia During Walking.

PubMed

Chini, Giorgia; Ranavolo, Alberto; Draicchio, Francesco; Casali, Carlo; Conte, Carmela; Martino, Giovanni; Leonardi, Luca; Padua, Luca; Coppola, Gianluca; Pierelli, Francesco; Serrao, Mariano

2017-02-01

This study aims to evaluate trunk local stability in a group of patients with degenerative primary cerebellar ataxia and to correlate it with spatio-temporal parameters, clinical variables, and history of falls. Sixteen patients affected by degenerative cerebellar ataxia and 16 gender- and age-matched healthy adults were studied by means of an inertial sensor to measure trunk kinematics and spatio-temporal parameters during over-ground walking. Trunk local dynamic stability was quantified by the maximum Lyapunov exponent with short data series of the acceleration data. According to this index, low values indicate more stable trunk dynamics, while high values denote less stable trunk dynamics. Disease severity was assessed by means of International Cooperative Ataxia Rating Scale (ICARS) according to which higher values correspond to more severe disease, while lower values correspond to less severe disease.Patients displayed a higher short-term maximum Lyapunov exponent than controls in all three spatial planes, which was correlated with the age, onset of the disease, and history of falls. Furthermore, the maximum Lyapunov exponent was negatively correlated with ICARS balance, ICARS posture, and ICARS total scores.These findings indicate that trunk local stability during gait is lower in patients with cerebellar degenerative ataxia than that in healthy controls and that this may increase the risk of falls. Local dynamic stability of the trunk seems to be an important aspect in patients with ataxia and could be a useful tool in the evaluation of rehabilitative and pharmacological treatment outcomes.

Analysis of Reasons for Failure of Surgery for Degenerative Disease of Lumbar Spine.

PubMed

Baranowska, Alicja; Baranowska, Joanna; Baranowski, Paweł

2016-03-23

In the aging society, there is a growing number of patients with advanced degenerative disease of the spine. These patients frequently require surgical treatment. This paper aims to analyse the reasons for failure of surgery for degenerative disease of the lumbar spine. Histories of patients operated on by one group of surgeons in the Neuroorthopaedic Department of "STOCER" in 2014 and 2015 due to degenerative disease of the lumbar spine were analysed retrospectively. Out of the cohort, patients who had undergone a revision surgery were selected for the study and divided into two groups: group A (60) of patients previously operated on in another centre and group B (47) of patients previously operated on in "STOCER". The reasons for failure of the surgery were analysed in detail based on history, physical examination, imaging studies and surgery reports. Surgery was performed in 601 patients, of whom 107 patients had been previously operated on. The most frequent reasons for revision surgery of the same motor segment were recurrent disc herniation, inadequate decompression and inappropriate surgical technique. In the group of patients who had implants inserted to stabilise the spine, the revision surgery in most cases was due to adjacent segment disease. Use of implants and spinal fusion is always associated with a risk of complications and is frequently independent of the surgeon. 2. In order to reduce the rate of revision surgeries, it is important to perform complete decompression and select an adequate surgical technique.

Survival of the Friendliest: Homo sapiens Evolved via Selection for Prosociality.

PubMed

Hare, Brian

2017-01-03

The challenge of studying human cognitive evolution is identifying unique features of our intelligence while explaining the processes by which they arose. Comparisons with nonhuman apes point to our early-emerging cooperative-communicative abilities as crucial to the evolution of all forms of human cultural cognition, including language. The human self-domestication hypothesis proposes that these early-emerging social skills evolved when natural selection favored increased in-group prosociality over aggression in late human evolution. As a by-product of this selection, humans are predicted to show traits of the domestication syndrome observed in other domestic animals. In reviewing comparative, developmental, neurobiological, and paleoanthropological research, compelling evidence emerges for the predicted relationship between unique human mentalizing abilities, tolerance, and the domestication syndrome in humans. This synthesis includes a review of the first a priori test of the self-domestication hypothesis as well as predictions for future tests.

BEND3 is involved in the human-specific repression of calreticulin: Implication for the evolution of higher brain functions in human.

PubMed

Aghajanirefah, A; Nguyen, L N; Ohadi, M

2016-01-15

Recent emerging evidence indicates that changes in gene expression levels are linked to human evolution. We have previously reported a human-specific nucleotide in the promoter sequence of the calreticulin (CALR) gene at position -220C, which is the site of action of valproic acid. Reversion of this nucleotide to the ancestral A-allele has been detected in patients with degrees of deficit in higher brain cognitive functions. This mutation has since been reported in the 1000 genomes database at an approximate frequency of <0.0004 in humans (rs138452745). In the study reported here, we present update on the status of rs138452745 across evolution, based on the Ensembl and NCBI databases. The DNA pulldown assay was also used to identify the proteins binding to the C- and A-alleles, using two cell lines, SK-N-BE and HeLa. Consistent with our previous findings, the C-allele is human-specific, and the A-allele is the rule across all other species (N=38). This nucleotide resides in a block of 12-nucleotides that is strictly conserved across evolution. The DNA pulldown experiments revealed that in both SK-N-BE and HeLa cells, the transcription repressor BEN domain containing 3 (BEND3) binds to the human-specific C-allele, whereas the nuclear factor I (NFI) family members, NF1A, B, C, and X, specifically bind to the ancestral A-allele. This binding pattern is consistent with a previously reported decreased promoter activity of the C-allele vs. the A-allele. We propose that there is a link between binding of BEND3 to the CALR rs138452745 C-allele and removal of NFI binding site from this nucleotide, and the evolution of human-specific higher brain functions. To our knowledge, CALR rs138452745 is the first instance of enormous nucleotide conservation across evolution, except in the human species. Copyright © 2015 Elsevier B.V. All rights reserved.

Body composition in Pan paniscus compared with Homo sapiens has implications for changes during human evolution.

PubMed

Zihlman, Adrienne L; Bolter, Debra R

2015-06-16

The human body has been shaped by natural selection during the past 4-5 million years. Fossils preserve bones and teeth but lack muscle, skin, fat, and organs. To understand the evolution of the human form, information about both soft and hard tissues of our ancestors is needed. Our closest living relatives of the genus Pan provide the best comparative model to those ancestors. Here, we present data on the body composition of 13 bonobos (Pan paniscus) measured during anatomical dissections and compare the data with Homo sapiens. These comparative data suggest that both females and males (i) increased body fat, (ii) decreased relative muscle mass, (iii) redistributed muscle mass to lower limbs, and (iv) decreased relative mass of skin during human evolution. Comparison of soft tissues between Pan and Homo provides new insights into the function and evolution of body composition.

Dynamically correlated mutations drive human Influenza A evolution.

PubMed

Tria, F; Pompei, S; Loreto, V

2013-01-01

Human Influenza A virus undergoes recurrent changes in the hemagglutinin (HA) surface protein, primarily involved in the human antibody recognition. Relevant antigenic changes, enabling the virus to evade host immune response, have been recognized to occur in parallel to multiple mutations at antigenic sites in HA. Yet, the role of correlated mutations (epistasis) in driving the molecular evolution of the virus still represents a challenging puzzle. Further, though circulation at a global geographic level is key for the survival of Influenza A, its role in shaping the viral phylodynamics remains largely unexplored. Here we show, through a sequence based epidemiological model, that epistatic effects between amino acids substitutions, coupled with a reservoir that mimics worldwide circulating viruses, are key determinants that drive human Influenza A evolution. Our approach explains all the up-to-date observations characterizing the evolution of H3N2 subtype, including phylogenetic properties, nucleotide fixation patterns, and composition of antigenic clusters.

Body composition in Pan paniscus compared with Homo sapiens has implications for changes during human evolution

PubMed Central

Zihlman, Adrienne L.; Bolter, Debra R.

2015-01-01

The human body has been shaped by natural selection during the past 4–5 million years. Fossils preserve bones and teeth but lack muscle, skin, fat, and organs. To understand the evolution of the human form, information about both soft and hard tissues of our ancestors is needed. Our closest living relatives of the genus Pan provide the best comparative model to those ancestors. Here, we present data on the body composition of 13 bonobos (Pan paniscus) measured during anatomical dissections and compare the data with Homo sapiens. These comparative data suggest that both females and males (i) increased body fat, (ii) decreased relative muscle mass, (iii) redistributed muscle mass to lower limbs, and (iv) decreased relative mass of skin during human evolution. Comparison of soft tissues between Pan and Homo provides new insights into the function and evolution of body composition. PMID:26034269

Multi-level human evolution: ecological patterns in hominin phylogeny.

PubMed

Parravicini, Andrea; Pievani, Telmo

2016-06-20

Evolution is a process that occurs at many different levels, from genes to ecosystems. Genetic variations and ecological pressures are hence two sides of the same coin; but due both to fragmentary evidence and to the influence of a gene-centered and gradualistic approach to evolutionary phenomena, the field of paleoanthropology has been slow to take the role of macro-evolutionary patterns (i.e. ecological and biogeographical at large scale) seriously. However, several very recent findings in paleoanthropology stress both climate instability and ecological disturbance as key factors affecting the highly branching hominin phylogeny, from the earliest hominins to the appearance of cognitively modern humans. Allopatric speciation due to geographic displacement, turnover-pulses of species, adaptive radiation, mosaic evolution of traits in several coeval species, bursts of behavioral innovation, serial dispersals out of Africa, are just some of the macro-evolutionary patterns emerging from the field. The multilevel approach to evolution proposed by paleontologist Niles Eldredge is adopted here as interpretative tool, and has yielded a larger picture of human evolution that integrates different levels of evolutionary change, from local adaptations in limited ecological niches to dispersal phenotypes able to colonize an unprecedented range of ecosystems. Changes in global climate and Earth's surface most greatly affected human evolution. Precisely because it is cognitively hard for us to appreciate the long-term common destiny we share with the whole biosphere, it is particularly valuable to highlight the accumulating evidence that human evolution has been deeply affected by global ecological changes that transformed our African continent of origin.

Measure, Then Show: Grasping Human Evolution Through an Inquiry-Based, Data-driven Hominin Skulls Lab.

PubMed

Bayer, Chris N; Luberda, Michael

2016-01-01

Incomprehension and denial of the theory of evolution among high school students has been observed to also occur when teachers are not equipped to deliver a compelling case also for human evolution based on fossil evidence. This paper assesses the outcomes of a novel inquiry-based paleoanthropology lab teaching human evolution to high-school students. The inquiry-based Be a Paleoanthropologist for a Day lab placed a dozen hominin skulls into the hands of high-school students. Upon measuring three variables of human evolution, students explain what they have observed and discuss findings. In the 2013/14 school year, 11 biology classes in 7 schools in the Greater New Orleans area participated in this lab. The interviewed teacher cohort unanimously agreed that the lab featuring hominin skull replicas and stimulating student inquiry was a pedagogically excellent method of delivering the subject of human evolution. First, the lab's learning path of transforming facts to data, information to knowledge, and knowledge to acceptance empowered students to themselves execute part of the science that underpins our understanding of deep time hominin evolution. Second, although challenging, the hands-on format of the lab was accessible to high-school students, most of whom were readily able to engage the lab's scientific process. Third, the lab's exciting and compelling pedagogy unlocked higher order thinking skills, effectively activating the cognitive, psychomotor and affected learning domains as defined in Bloom's taxonomy. Lastly, the lab afforded students a formative experience with a high degree of retention and epistemic depth. Further study is warranted to gauge the degree of these effects.

Darwinian perspectives on the evolution of human languages.

PubMed

Pagel, Mark

2017-02-01

Human languages evolve by a process of descent with modification in which parent languages give rise to daughter languages over time and in a manner that mimics the evolution of biological species. Descent with modification is just one of many parallels between biological and linguistic evolution that, taken together, offer up a Darwinian perspective on how languages evolve. Combined with statistical methods borrowed from evolutionary biology, this Darwinian perspective has brought new opportunities to the study of the evolution of human languages. These include the statistical inference of phylogenetic trees of languages, the study of how linguistic traits evolve over thousands of years of language change, the reconstruction of ancestral or proto-languages, and using language change to date historical events.

Rules of co-occurring mutations characterize the antigenic evolution of human influenza A/H3N2, A/H1N1 and B viruses.

PubMed

Chen, Haifen; Zhou, Xinrui; Zheng, Jie; Kwoh, Chee-Keong

2016-12-05

The human influenza viruses undergo rapid evolution (especially in hemagglutinin (HA), a glycoprotein on the surface of the virus), which enables the virus population to constantly evade the human immune system. Therefore, the vaccine has to be updated every year to stay effective. There is a need to characterize the evolution of influenza viruses for better selection of vaccine candidates and the prediction of pandemic strains. Studies have shown that the influenza hemagglutinin evolution is driven by the simultaneous mutations at antigenic sites. Here, we analyze simultaneous or co-occurring mutations in the HA protein of human influenza A/H3N2, A/H1N1 and B viruses to predict potential mutations, characterizing the antigenic evolution. We obtain the rules of mutation co-occurrence using association rule mining after extracting HA1 sequences and detect co-mutation sites under strong selective pressure. Then we predict the potential drifts with specific mutations of the viruses based on the rules and compare the results with the "observed" mutations in different years. The sites under frequent mutations are in antigenic regions (epitopes) or receptor binding sites. Our study demonstrates the co-occurring site mutations obtained by rule mining can capture the evolution of influenza viruses, and confirms that cooperative interactions among sites of HA1 protein drive the influenza antigenic evolution.

Surgical Management of Degenerative Meniscus Lesions: The 2016 ESSKA Meniscus Consensus

PubMed Central

Beaufils, P.; Becker, R.; Kopf, S.; Englund, M.; Verdonk, R.; Ollivier, M.; Seil, R.

2017-01-01

Purpose  A degenerative meniscus lesion is a slowly developing process typically involving a horizontal cleavage in a middle-aged or older person. When the knee is symptomatic, arthroscopic partial meniscectomy has been practised for a long time with many case series reporting improved patient outcomes. Since 2002, several randomised clinical trials demonstrated no additional benefit of arthroscopic partial meniscectomy compared to non-operative treatment, sham surgery or sham arthroscopic partial meniscectomy. These results introduced controversy in the medical community and made clinical decision-making challenging in the daily clinical practice. To facilitate the clinical decision-making process, a consensus was developed. This initiative was endorsed by ESSKA. Methods  A degenerative meniscus lesion was defined as a lesion occurring without any history of significant acute trauma in a patient older than 35 years. Congenital lesions, traumatic meniscus tears and degenerative lesions occurring in young patients, especially in athletes, were excluded. The project followed the so-called formal consensus process, involving a steering group, a rating group and a peer-review group. A total of 84 surgeons and scientists from 22 European countries were included in the process. Twenty questions, their associated answers and an algorithm based on extensive literature review and clinical expertise, were proposed. Each question and answer set was graded according to the scientific level of the corresponding literature. Results  The main finding was that arthroscopic partial meniscectomy should not be proposed as a first line of treatment for degenerative meniscus lesions. Arthroscopic partial meniscectomy should only be considered after a proper standardised clinical and radiological evaluation and when the response to non-operative management has not been satisfactory. Magnetic resonance imaging of the knee is typically not indicated in the first-line work-up, but knee radiography should be used as an imaging tool to support a diagnosis of osteoarthritis or to detect certain rare pathologies, such as tumours or fractures of the knee. Discussion  The present work offers a clear framework for the management of degenerative meniscus lesions, with the aim to balance information extracted from the scientific evidence and clinical expertise. Because of biases and weaknesses of the current literature and lack of definition of important criteria such as mechanical symptoms, it cannot be considered as an exact treatment algorithm. It summarises the results of the “ESSKA Meniscus Consensus Project” ( http://www.esska.org/education/projects ) and is the first official European consensus on this topic. The consensus may be updated and refined as more high-quality evidence emerges. Level of Evidence  I. PMID:29114633

[Disturbed sleep, anxiety and stress are possible risk indicators for temporomandibular disorders with myofascialpain].

PubMed

Lei, J; Liu, M Q; Fu, K Y

2016-02-18

To explore the relationship betweensleep/psychological distress and temporomandibular disorders (TMD) and to discuss the possibility of disturbed sleep and psychological distress as risk indicators in relation to TMD in a Chinese population. The standardized and validated self-reported Chinese version questionnaires including Pittsburgh sleep quality index (PSQI) and depression, anxietyandstress scales-21 (DASS-21) were used to measure sleep quality and psychological distress. A total of 755 TMD patients (172 males and 583 females)with a mean age (29.99 ± 13.60) years were included in the study. The patients were divided into 7 diagnostic groups based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD), including Group I(exclusively myofascial pain), Group II(exclusively disc displacement), Group III (exclusively arthralgia or degenerative joint disease), Group IV (myofascial pain plus disc displacement), Group V (myofascial pain plus arthralgia or degenerative joint disease), Group VI (disc displacement plus arthralgia or degenerative joint disease) and Group VII (myofascial pain plus disc displacement plus arthralgia or degenerative joint disease). For statistical analysis, the patients were subsequently grouped into those with (181 patients) and without (574 patients) myofascial pain. Chi-square tests, independent-samples t test, partial correlation as well as stepwise Logistic regression analysis were used to analyze the data, using software SPSS 20.0 and P<0.05 was of significance. The prevalence of moderate to (extremely) severe disturbed sleep and psychological distress was significantly higher in the myofascial pain group (27.1%, 28.7%, 60.8% and 32.0%) than in the non-myofascial pain group (disc displacement and arthralgia or degenerative joint disease, 11.1%, 10.1%, 27.4% and 11.0%, P<0.05).The comorbidity of self-reported disturbed sleep and psychological distress was significantly higher in the myofascial pain patients than those without myofascial pain (P<0.05). Stepwise logistic regression analysis demonstrated that disturbed sleep (OR=1.74), more specifically, subjective sleep quality (OR=1.69) and sleep disturbance (OR=1.63) respectively, anxiety (OR=3.14) and stress (OR=2.15) were possible risk indicators for myofascial pain, and the results were still significant even after controlling for age, sex, educational level, disease duration, sleep quality, depression, anxiety and stress respectively (P<0.05). Disturbed sleep and psychological distress symptoms are common in TMD patients. Disturbed sleep, anxiety and stress are possible risk indicators for myofascial pain, compared with disc displacement and arthralgia or degenerative joint diseases.

[Disturbed sleep, anxiety and stress are possible risk indicators for temporomandibular disorders with myofascialpain].

PubMed

Lei, J; Liu, M Q; Fu, K Y

2016-08-18

To explore the relationship betweensleep/psychological distress and temporomandibular disorders (TMD) and to discuss the possibility of disturbed sleep and psychological distress as risk indicators in relation to TMD in a Chinese population. The standardized and validated self-reported Chinese version questionnaires including Pittsburgh sleep quality index (PSQI) and depression, anxietyandstress scales-21 (DASS-21) were used to measure sleep quality and psychological distress. A total of 755 TMD patients (172 males and 583 females)with a mean age (29.99 ± 13.60) years were included in the study. The patients were divided into 7 diagnostic groups based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD), including Group I(exclusively myofascial pain), Group II(exclusively disc displacement), Group III (exclusively arthralgia or degenerative joint disease), Group IV (myofascial pain plus disc displacement), Group V (myofascial pain plus arthralgia or degenerative joint disease), Group VI (disc displacement plus arthralgia or degenerative joint disease) and Group VII (myofascial pain plus disc displacement plus arthralgia or degenerative joint disease). For statistical analysis, the patients were subsequently grouped into those with (181 patients) and without (574 patients) myofascial pain. Chi-square tests, independent-samples t test, partial correlation as well as stepwise Logistic regression analysis were used to analyze the data, using software SPSS 20.0 and P<0.05 was of significance. The prevalence of moderate to (extremely) severe disturbed sleep and psychological distress was significantly higher in the myofascial pain group (27.1%, 28.7%, 60.8% and 32.0%) than in the non-myofascial pain group (disc displacement and arthralgia or degenerative joint disease, 11.1%, 10.1%, 27.4% and 11.0%, P<0.05).The comorbidity of self-reported disturbed sleep and psychological distress was significantly higher in the myofascial pain patients than those without myofascial pain (P<0.05). Stepwise logistic regression analysis demonstrated that disturbed sleep (OR=1.74), more specifically, subjective sleep quality (OR=1.69) and sleep disturbance (OR=1.63) respectively, anxiety (OR=3.14) and stress (OR=2.15) were possible risk indicators for myofascial pain, and the results were still significant even after controlling for age, sex, educational level, disease duration, sleep quality, depression, anxiety and stress respectively (P<0.05). Disturbed sleep and psychological distress symptoms are common in TMD patients. Disturbed sleep, anxiety and stress are possible risk indicators for myofascial pain, compared with disc displacement and arthralgia or degenerative joint diseases.

[Evaluation of the arterial blood flow parameters in the eye of myopic patients].

PubMed

Mrugacz, Małgorzata; Bryl, Anna

2013-04-01

Myopia is a common refractive defect. Has a good vision from near and deterioration of vision with increasing distance. The main reason for its occurrence is too long axis of the eyeball. The consequence of elongation of the eyeball is the development of degenerative changes in the retina. Despite much research has failed to clearly identify the causes of degenerative changes in those short-sighted. The aim of the study was to evaluate the maximum and minimum speed in arterial blood vessels of the eye in people with myopia. The study included 70 patients (138 eyes), 53 women and 17 men, aged from 18 to 79 years, with myopia of -0.25 to -18.0 Dsph and length of the eyeball from 22.61 to 33.36 mm. Depending on the kind and the degree of the progress of degenerative changes, patients were divided in 4 groups: I - without degenerative changes on the fundus (n=32; K-23, M-9); II- with the short-sighted sickle (n=20; K-14, M-6); Ill - with the structure thinned down of the retina, accompanying the short-sighted sickle (n = 8; K-6, M-2); IV - with extensive choroidal-retina disappearances in the fundus (n = 10; K-7, M-3). In all individuals enrolled underwent Color Doppler ultrasound with apparatus SSA 770A Toshiba Aplio with linear probe frequency 12 MHz, judging maximum (Vmax) and minimum (Vmin) speed in the arteries of the eye: ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary arteries (SPCA) located on the nasal and temporal side of the optic disc. The results were statistically analyzed. No statistically significant relationship between the nature of degenerative changes of the eye, and blood velocity in the OA. There was a increase in Vmax and Vmin blood in OA in Group IV, but these changes were not statistically significant. Statistically significant correlation was observed while in the CRA. With a decrease in Vmax and Vmin of blood flowing through a vessel exacerbation of retinal degeneration. Vmax and Vmin changes in the blood did not correlate significantly SPCA with retinal degeneration, although the results were much worse in the temporal vessels. With the deterioration of blood flow parameters of the central retinal artery and short posterior ciliary arteries comes to the severity of the retinal degeneration in myopic patients. More severe impairment of blood circulation in the temporal ciliary explain higher incidence of degenerative changes in the temporal side of the optic disc.

High-content screening of small compounds on human embryonic stem cells.

PubMed

Barbaric, Ivana; Gokhale, Paul J; Andrews, Peter W

2010-08-01

Human ES (embryonic stem) cells and iPS (induced pluripotent stem) cells have been heralded as a source of differentiated cells that could be used in the treatment of degenerative diseases, such as Parkinson's disease or diabetes. Despite the great potential for their use in regenerative therapy, the challenge remains to understand the basic biology of these remarkable cells, in order to differentiate them into any functional cell type. Given the scale of the task, high-throughput screening of agents and culture conditions offers one way to accelerate these studies. The screening of small-compound libraries is particularly amenable to such high-throughput methods. Coupled with high-content screening technology that enables simultaneous assessment of multiple cellular features in an automated and quantitative way, this approach is proving powerful in identifying both small molecules as tools for manipulating stem cell fates and novel mechanisms of differentiation not previously associated with stem cell biology. Such screens performed on human ES cells also demonstrate the usefulness of human ES/iPS cells as cellular models for pharmacological testing of drug efficacy and toxicity, possibly a more imminent use of these cells than in regenerative medicine.

Space Radiation and Risks to Human Health

NASA Technical Reports Server (NTRS)

Huff, Janice L.

2014-01-01

The radiation environment in space poses significant challenges to human health and is a major concern for long duration manned space missions. Outside the Earth's protective magnetosphere, astronauts are exposed to higher levels of galactic cosmic rays, whose physical characteristics are distinct from terrestrial sources of radiation such as x-rays and gamma-rays. Galactic cosmic rays consist of high energy and high mass nuclei as well as high energy protons; they impart unique biological damage as they traverse through tissue with impacts on human health that are largely unknown. The major health issues of concern are the risks of radiation carcinogenesis, acute and late decrements to the central nervous system, degenerative tissue effects such as cardiovascular disease, as well as possible acute radiation syndromes due to an unshielded exposure to a large solar particle event. The NASA Human Research Program's Space Radiation Program Element is focused on characterization and mitigation of these space radiation health risks along with understanding these risks in context of the other biological stressors found in the space environment. In this overview, we will provide a description of these health risks and the Element's research strategies to understand and mitigate these risks.

Mechanism of mast cell adhesion to human tenocytes in vitro.

PubMed

Behzad, Hayedeh; Tsai, Shu-Huei; Nassab, Paulina; Mousavizadeh, Rouhollah; McCormack, Robert G; Scott, Alex

2015-01-01

Mast cells and fibroblasts are two key players involved in many fibrotic and degenerative disorders. In the present study we examined the nature of binding interactions between human mast cells and tendon fibroblasts (tenocytes). In the mast cell-fibroblast co-culture model, mast cells were shown to spontaneously bind to tenocytes, in a process that was partially mediated by α5β1 integrin receptors. The same receptors on mast cells significantly mediated binding of these cells to tissue culture plates in the presence of tenocyte-conditioned media; the tenocyte-derived fibronectin in the media was shown to also play a major role in these binding activities. Upon binding to tenocytes or tissue culture plates, mast cells acquired an elongated phenotype, which was dependent on α5β1 integrin and tenocyte fibronectin. Additionally, tenocyte-derived fibronectin significantly enhanced mRNA expression of the adhesion molecule, THY1, by mast cells. Our data suggests that α5β1 integrin mediates binding of mast cells to human tenocyte and to tenocyte-derived ECM proteins, in particular fibronectin. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats.

PubMed

Lund, Raymond D; Wang, Shaomei; Klimanskaya, Irina; Holmes, Toby; Ramos-Kelsey, Rebeca; Lu, Bin; Girman, Sergej; Bischoff, N; Sauvé, Yves; Lanza, Robert

2006-01-01

Embryonic stem cells promise to provide a well-characterized and reproducible source of replacement tissue for human clinical studies. An early potential application of this technology is the use of retinal pigment epithelium (RPE) for the treatment of retinal degenerative diseases such as macular degeneration. Here we show the reproducible generation of RPE (67 passageable cultures established from 18 different hES cell lines); batches of RPE derived from NIH-approved hES cells (H9) were tested and shown capable of extensive photoreceptor rescue in an animal model of retinal disease, the Royal College of Surgeons (RCS) rat, in which photoreceptor loss is caused by a defect in the adjacent retinal pigment epithelium. Improvement in visual performance was 100% over untreated controls (spatial acuity was approximately 70% that of normal nondystrophic rats) without evidence of untoward pathology. The use of somatic cell nuclear transfer (SCNT) and/or the creation of banks of reduced complexity human leucocyte antigen (HLA) hES-RPE lines could minimize or eliminate the need for immunosuppressive drugs and/or immunomodulatory protocols.

Inter- and Intraspecies Phylogenetic Analyses Reveal Extensive X–Y Gene Conversion in the Evolution of Gametologous Sequences of Human Sex Chromosomes

PubMed Central

Trombetta, Beniamino; Sellitto, Daniele; Scozzari, Rosaria; Cruciani, Fulvio

2014-01-01

It has long been believed that the male-specific region of the human Y chromosome (MSY) is genetically independent from the X chromosome. This idea has been recently dismissed due to the discovery that X–Y gametologous gene conversion may occur. However, the pervasiveness of this molecular process in the evolution of sex chromosomes has yet to be exhaustively analyzed. In this study, we explored how pervasive X–Y gene conversion has been during the evolution of the youngest stratum of the human sex chromosomes. By comparing about 0.5 Mb of human–chimpanzee gametologous sequences, we identified 19 regions in which extensive gene conversion has occurred. From our analysis, two major features of these emerged: 1) Several of them are evolutionarily conserved between the two species and 2) almost all of the 19 hotspots overlap with regions where X–Y crossing-over has been previously reported to be involved in sex reversal. Furthermore, in order to explore the dynamics of X–Y gametologous conversion in recent human evolution, we resequenced these 19 hotspots in 68 widely divergent Y haplogroups and used publicly available single nucleotide polymorphism data for the X chromosome. We found that at least ten hotspots are still active in humans. Hence, the results of the interspecific analysis are consistent with the hypothesis of widespread reticulate evolution within gametologous sequences in the differentiation of hominini sex chromosomes. In turn, intraspecific analysis demonstrates that X–Y gene conversion may modulate human sex-chromosome-sequence evolution to a greater extent than previously thought. PMID:24817545

Socio-hydrologic Perspectives of the Co-evolution of Humans and Water in the Tarim River Basin, Western China

NASA Astrophysics Data System (ADS)

Liu, Ye; Tian, Fuqiang; Hu, Heping; Liu, Dengfeng; Sivapalan, Murugesu

2013-04-01

Socio-hydrology studies the co-evolution of coupled human-water systems, which is of great importance for long-term sustainable water resource management in basins suffering from serious eco-environmental degradation. Process socio-hydrology can benefit from the exploring the patterns of historical co-evolution of coupled human-water systems as a way to discovering the organizing principles that may underpin their co-evolution. As a self-organized entity, the human-water system in a river basin would evolve into certain steady states over a sufficiently long time but then could also experience sudden shifts due to internal or external disturbances that exceed system thresholds. In this study, we discuss three steady states (also called stages in the social sciences, including natural, human exploitation and recovery stages) and transitions between these during the past 1500 years in the Tarim River Basin of Western China, which a rich history of civilization including its place in the famous Silk Road that connected China to Europe. Specifically, during the natural stage with a sound environment that existed before the 19th century, shifts in the ecohydrological regime were mainly caused by environmental changes such river channel migration and climate change. During the human exploitation stages in the 5th and again in the 19th-20th centuries, however, humans gradually became the main drivers for system evolution, during which the basin experienced rapid population growth, fast socio-economic development and intense human activities. By the 1970s, after 200 years of colonization, the Tarim River Basin evolved into a new regime with vulnerable ecosystem and water system, and suffered from serious water shortages and desertification. Human society then began to take a critical look into the effects of their activities and reappraise the impact of human development on the ecohydrological system, which eventually led the basin into a treatment and recovery stage. Since then, the basin has shown a reverse trend of regime shift towards healing of the environmental damage that was inflicted in the previous stage of human development. In this paper we analyze the recasting effect of human activities on the water system and provide explanations on how human activities influence the co-evolution of human-water system from a broader perspective.

[The evolution of human cultural behavior: notes on Darwinism and complexity].

PubMed

Peric, Mikael; Murrieta, Rui Sérgio Sereni

2015-12-01

The article analyzes three schools that can be understood as central in studies of the evolution of human behavior within the paradigm of evolution by natural selection: human behavioral ecology (HBE), evolutionary psychology, and dual inheritance. These three streams of thought are used to depict the Darwinist landscape and pinpoint its strong suits and limitations. Theoretical gaps were identified that seem to reduce these schools' ability to account for the diversity of human evolutionary behavior. Their weak points include issues related to the concept of reproductive success, types of adaptation, and targets of selection. An interdisciplinary approach is proposed as the solution to this dilemma, where complex adaptive systems would serve as a source.

Evolution of the Concept of "Human Capital" in Economic Science

ERIC Educational Resources Information Center

Perepelkin, Vyacheslav A.; Perepelkina, Elena V.; Morozova, Elena S.

2016-01-01

The relevance of the researched problem is determined by transformation of the human capital into the key economic resource of development of the postindustrial society. The purpose of the article is to disclose the content of evolution of the human capital as a scientific concept and phenomenon of the economic life. The leading approach to the…

Sibling rivalry among paralogs promotes evolution of the human brain.

PubMed

Tyler-Smith, Chris; Xue, Yali

2012-05-11

Geneticists have long sought to identify the genetic changes that made us human, but pinpointing the functionally relevant changes has been challenging. Two papers in this issue suggest that partial duplication of SRGAP2, producing an incomplete protein that antagonizes the original, contributed to human brain evolution. Copyright © 2012 Elsevier Inc. All rights reserved.

Effectiveness of a Rapid Lumbar Spine MRI Protocol Using 3D T2-Weighted SPACE Imaging Versus a Standard Protocol for Evaluation of Degenerative Changes of the Lumbar Spine.

PubMed

Sayah, Anousheh; Jay, Ann K; Toaff, Jacob S; Makariou, Erini V; Berkowitz, Frank

2016-09-01

Reducing lumbar spine MRI scanning time while retaining diagnostic accuracy can benefit patients and reduce health care costs. This study compares the effectiveness of a rapid lumbar MRI protocol using 3D T2-weighted sampling perfection with application-optimized contrast with different flip-angle evolutions (SPACE) sequences with a standard MRI protocol for evaluation of lumbar spondylosis. Two hundred fifty consecutive unenhanced lumbar MRI examinations performed at 1.5 T were retrospectively reviewed. Full, rapid, and complete versions of each examination were interpreted for spondylotic changes at each lumbar level, including herniations and neural compromise. The full examination consisted of sagittal T1-weighted, T2-weighted turbo spin-echo (TSE), and STIR sequences; and axial T1- and T2-weighted TSE sequences (time, 18 minutes 40 seconds). The rapid examination consisted of sagittal T1- and T2-weighted SPACE sequences, with axial SPACE reformations (time, 8 minutes 46 seconds). The complete examination consisted of the full examination plus the T2-weighted SPACE sequence. Sensitivities and specificities of the full and rapid examinations were calculated using the complete study as the reference standard. The rapid and full studies had sensitivities of 76.0% and 69.3%, with specificities of 97.2% and 97.9%, respectively, for all degenerative processes. Rapid and full sensitivities were 68.7% and 66.3% for disk herniation, 85.2% and 81.5% for canal compromise, 82.9% and 69.1% for lateral recess compromise, and 76.9% and 69.7% for foraminal compromise, respectively. Isotropic SPACE T2-weighted imaging provides high-quality imaging of lumbar spondylosis, with multiplanar reformatting capability. Our SPACE-based rapid protocol had sensitivities and specificities for herniations and neural compromise comparable to those of the protocol without SPACE. This protocol fits within a 15-minute slot, potentially reducing costs and discomfort for a large subgroup of patients.

Transcatheter aortic valve-in-valve treatment of degenerative stentless supra-annular Freedom Solo valves: A single centre experience.

PubMed

Cockburn, James; Dooley, Maureen; Parker, Jessica; Hill, Andrew; Hutchinson, Nevil; de Belder, Adam; Trivedi, Uday; Hildick-Smith, David

2017-02-15

Redo surgery for degenerative bioprosthetic aortic valves is associated with significant morbidity and mortality. Report results of valve-in-valve therapy (ViV-TAVI) in failed supra-annular stentless Freedom Solo (FS) bioprostheses, which are the highest risk for coronary occlusion. Six patients with FS valves (mean age 78.5 years, 50% males). Five had valvular restenosis (peak gradient 87.2 mm Hg, valve area 0.63 cm 2 ), one had severe regurgitation (AR). Median time to failure was 7 years. Patients were high risk (mean STS/Logistic EuroScore 10.6 15.8, respectively). FS valves ranged from 21 to 25 mm. Successful ViV-TAVI was achieved in 4/6 patients (67%). Of the unsuccessful cases, (patient 1 and 2 of series) patient 1 underwent BAV with simultaneous aortography which revealed left main stem occlusion. The procedure was stopped and the patient went forward for repeat surgery. Patient 2 underwent successful ViV-TAVI with a 26-mm CoreValve with a guide catheter in the left main, but on removal coronary obstruction occurred, necessitating valve snaring into the aorta. Among the successful cases, (patients 3, 4, 5, 6) the TAVIs used were CoreValve Evolut R 23 mm (n = 3), and Lotus 23 mm (n = 1). In the successful cases the peak gradient fell from 83.0 to 38.3 mm Hg. No patient was left with >1+ AR. One patient had a stroke on Day 2, with full neurological recovery. Two patients underwent semi-elective pacing for LBBB and PR >280 ms. ViV-TAVI in stentless Freedom Solo valves is high risk. The risk of coronary occlusion is high. The smallest possible prosthesis (1:1 sizing) should be used, and strategies to protect the coronary vessels must be considered. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The transition to foraging for dense and predictable resources and its impact on the evolution of modern humans.

PubMed

Marean, Curtis W

2016-07-05

Scientists have identified a series of milestones in the evolution of the human food quest that are anticipated to have had far-reaching impacts on biological, behavioural and cultural evolution: the inclusion of substantial portions of meat, the broad spectrum revolution and the transition to food production. The foraging shift to dense and predictable resources is another key milestone that had consequential impacts on the later part of human evolution. The theory of economic defendability predicts that this shift had an important consequence-elevated levels of intergroup territoriality and conflict. In this paper, this theory is integrated with a well-established general theory of hunter-gatherer adaptations and is used to make predictions for the sequence of appearance of several evolved traits of modern humans. The distribution of dense and predictable resources in Africa is reviewed and found to occur only in aquatic contexts (coasts, rivers and lakes). The palaeoanthropological empirical record contains recurrent evidence for a shift to the exploitation of dense and predictable resources by 110 000 years ago, and the first known occurrence is in a marine coastal context in South Africa. Some theory predicts that this elevated conflict would have provided the conditions for selection for the hyperprosocial behaviours unique to modern humans.This article is part of the themed issue 'Major transitions in human evolution'. © 2016 The Author(s).

Inhibitory interneurons of the human prefrontal cortex display conserved evolution of the phenotype and related genes.

PubMed

Sherwood, Chet C; Raghanti, Mary Ann; Stimpson, Cheryl D; Spocter, Muhammad A; Uddin, Monica; Boddy, Amy M; Wildman, Derek E; Bonar, Christopher J; Lewandowski, Albert H; Phillips, Kimberley A; Erwin, Joseph M; Hof, Patrick R

2010-04-07

Inhibitory interneurons participate in local processing circuits, playing a central role in executive cognitive functions of the prefrontal cortex. Although humans differ from other primates in a number of cognitive domains, it is not currently known whether the interneuron system has changed in the course of primate evolution leading to our species. In this study, we examined the distribution of different interneuron subtypes in the prefrontal cortex of anthropoid primates as revealed by immunohistochemistry against the calcium-binding proteins calbindin, calretinin and parvalbumin. In addition, we tested whether genes involved in the specification, differentiation and migration of interneurons show evidence of positive selection in the evolution of humans. Our findings demonstrate that cellular distributions of interneuron subtypes in human prefrontal cortex are similar to other anthropoid primates and can be explained by general scaling rules. Furthermore, genes underlying interneuron development are highly conserved at the amino acid level in primate evolution. Taken together, these results suggest that the prefrontal cortex in humans retains a similar inhibitory circuitry to that in closely related primates, even though it performs functional operations that are unique to our species. Thus, it is likely that other significant modifications to the connectivity and molecular biology of the prefrontal cortex were overlaid on this conserved interneuron architecture in the course of human evolution.

The pathology of americium 241.

PubMed

Nilsson, A; Broomé-Karlsson, A

1976-02-01

Male CBA-mice were injected intraperitoneally with different doses of 241Am-citrate (16, 8, 0.4, 0.2, 0.04 muCi/kg). The two highest doses were highly destructive of the haematopoietic tissues, testes and bone tissue. The highest frequency of induced tumours of the skeleton and haematopoietic tissue was found in the 8 muCi group. In the liver, adrenal glands, kidney and heart degenerative lesions were found mainly in the higher dose groups. In the lower dose groups degenerative lesions seemed to appear earlier and at a higher frequency than in the control group.

Can a few non‐coding mutations make a human brain?

PubMed Central

Franchini, Lucía F.

2015-01-01

The recent finding that the human version of a neurodevelopmental enhancer of the Wnt receptor Frizzled 8 (FZD8) gene alters neural progenitor cell cycle timing and brain size is a step forward to understanding human brain evolution. The human brain is distinctive in terms of its cognitive abilities as well as its susceptibility to neurological disease. Identifying which of the millions of genomic changes that occurred during human evolution led to these and other uniquely human traits is extremely challenging. Recent studies have demonstrated that many of the fastest evolving regions of the human genome function as gene regulatory enhancers during embryonic development and that the human‐specific mutations in them might alter expression patterns. However, elucidating molecular and cellular effects of sequence or expression pattern changes is a major obstacle to discovering the genetic bases of the evolution of our species. There is much work to do before human‐specific genetic and genomic changes are linked to complex human traits. Also watch the Video Abstract. PMID:26350501

The Coverage of Human Evolution in High School Biology Textbooks in the 20th Century and in Current State Science Standards

ERIC Educational Resources Information Center

Skoog, Gerald

2005-01-01

Efforts to eliminate or neutralize the coverage of evolution in high school biology textbooks in the United States have persisted with varying degrees of intensity and success since the 1920s. In particular, the coverage of human evolution has been impacted by these efforts. Evidence of the success of these efforts can be chronicled by the…

Phonation takes precedence over articulation in development as well as evolution of language.

PubMed

Oller, D Kimbrough

2014-12-01

Early human vocal development is characterized first by emerging control of phonation and later by prosodic and supraglottal articulation. The target article has missed the opportunity to use these facts in the characterization of evolution in language-specific brain mechanisms. Phonation appears to be the initial human-specific brain change for language, and it was presumably a key target of selection in early hominin evolution.

An animal model to study human muscular diseases involving mitochondrial oxidative phosphorylation.

PubMed

Lemieux, Hélène; Warren, Blair E

2012-08-01

Mitochondria are producing most of the energy needed for many cellular functions by a process named oxidative phosphorylation (OXPHOS). It is now well recognized that mitochondrial dysfunctions are involved in several pathologies or degenerative processes, including cardiovascular diseases, diabetes, and aging. Animal models are currently used to try to understand the role of mitochondria in human diseases but a major problem is that mitochondria from different species and tissues are variable in terms of regulation. Analysis of mitochondrial function in three species of planarian flatworms (Tricladia, Platyhelminthes) shows that they share a very rare characteristic with human mitochondria: a strong control of oxidative phosphorylation by the phosphorylation system. The ratio of coupled OXPHOS over maximal electron transport capacity after uncoupling (electron transport system; ETS) well below 1.0 indicates that the phosphorylation system is limiting the rate of OXPHOS. The OXPHOS/ETS ratios are 0.62 ± 0.06 in Dugesia tigrina, 0.63 ± 0.05 in D. dorotocephala and 0.62 ± 0.05 in Procotyla fluviatilis, comparable to the value measured in human muscles. To our knowledge, no other animal model displays this peculiarity. This new model offers a venue in which to test the phosphorylation system as a potential therapeutic control point within humans.

Adjustments to de Leva-anthropometric regression data for the changes in body proportions in elderly humans.

PubMed

Ho Hoang, Khai-Long; Mombaur, Katja

2015-10-15

Dynamic modeling of the human body is an important tool to investigate the fundamentals of the biomechanics of human movement. To model the human body in terms of a multi-body system, it is necessary to know the anthropometric parameters of the body segments. For young healthy subjects, several data sets exist that are widely used in the research community, e.g. the tables provided by de Leva. None such comprehensive anthropometric parameter sets exist for elderly people. It is, however, well known that body proportions change significantly during aging, e.g. due to degenerative effects in the spine, such that parameters for young people cannot be used for realistically simulating the dynamics of elderly people. In this study, regression equations are derived from the inertial parameters, center of mass positions, and body segment lengths provided by de Leva to be adjustable to the changes in proportion of the body parts of male and female humans due to aging. Additional adjustments are made to the reference points of the parameters for the upper body segments as they are chosen in a more practicable way in the context of creating a multi-body model in a chain structure with the pelvis representing the most proximal segment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Raman detection of carotenoid pigments in the human retina

NASA Astrophysics Data System (ADS)

Gellermann, Werner; Ermakov, Igor V.; McClane, Robert W.; Bernstein, Paul S.

2000-04-01

We have used resonance Raman scattering as a novel, non- invasive, in-vivo optical technique to measure the concentration of carotenoid pigment in the human retina. Using argon laser excitation we are able to measure two strong carotenoid resonance Raman signals at 1159 and 1525 wave numbers, respectively. The required laser power levels are within the limits given by safety standards for ocular exposure. Of the approximately ten carotenoid pigment found in normal human serum, the species lutein and zeaxanthin are concentrated in high amounts in the cells of the human macula, which is an approximately 5 mm diameter area of the retina in which the visual acuity is highest. These carotenoids give the macula a characteristic yellow coloration, and it is speculated that these molecules function as filter to attenuate photochemical damage and/or image degradation under bright UV/blue light exposures. In addition, they are thought to act as free-radical scavenging antioxidants. Studies have shown that there may be a link between macular degenerative diseases, the leading cause of blindness in the elderly in the US, and the presence or absence of the carotenoids. We describe an instrument capable of measuring the macular carotenoids in human subjects in a non-invasive, rapid and quantitative way.

Design of an efficient framework for fast prototyping of customized human-computer interfaces and virtual environments for rehabilitation.

PubMed

Avola, Danilo; Spezialetti, Matteo; Placidi, Giuseppe

2013-06-01

Rehabilitation is often required after stroke, surgery, or degenerative diseases. It has to be specific for each patient and can be easily calibrated if assisted by human-computer interfaces and virtual reality. Recognition and tracking of different human body landmarks represent the basic features for the design of the next generation of human-computer interfaces. The most advanced systems for capturing human gestures are focused on vision-based techniques which, on the one hand, may require compromises from real-time and spatial precision and, on the other hand, ensure natural interaction experience. The integration of vision-based interfaces with thematic virtual environments encourages the development of novel applications and services regarding rehabilitation activities. The algorithmic processes involved during gesture recognition activity, as well as the characteristics of the virtual environments, can be developed with different levels of accuracy. This paper describes the architectural aspects of a framework supporting real-time vision-based gesture recognition and virtual environments for fast prototyping of customized exercises for rehabilitation purposes. The goal is to provide the therapist with a tool for fast implementation and modification of specific rehabilitation exercises for specific patients, during functional recovery. Pilot examples of designed applications and preliminary system evaluation are reported and discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Cultural evolutionary theory: How culture evolves and why it matters

PubMed Central

Creanza, Nicole; Kolodny, Oren; Feldman, Marcus W.

2017-01-01

Human cultural traits—behaviors, ideas, and technologies that can be learned from other individuals—can exhibit complex patterns of transmission and evolution, and researchers have developed theoretical models, both verbal and mathematical, to facilitate our understanding of these patterns. Many of the first quantitative models of cultural evolution were modified from existing concepts in theoretical population genetics because cultural evolution has many parallels with, as well as clear differences from, genetic evolution. Furthermore, cultural and genetic evolution can interact with one another and influence both transmission and selection. This interaction requires theoretical treatments of gene–culture coevolution and dual inheritance, in addition to purely cultural evolution. In addition, cultural evolutionary theory is a natural component of studies in demography, human ecology, and many other disciplines. Here, we review the core concepts in cultural evolutionary theory as they pertain to the extension of biology through culture, focusing on cultural evolutionary applications in population genetics, ecology, and demography. For each of these disciplines, we review the theoretical literature and highlight relevant empirical studies. We also discuss the societal implications of the study of cultural evolution and of the interactions of humans with one another and with their environment. PMID:28739941

The Pace of Cultural Evolution

PubMed Central

Perreault, Charles

2012-01-01

Today, humans inhabit most of the world’s terrestrial habitats. This observation has been explained by the fact that we possess a secondary inheritance mechanism, culture, in addition to a genetic system. Because it is assumed that cultural evolution occurs faster than biological evolution, humans can adapt to new ecosystems more rapidly than other animals. This assumption, however, has never been tested empirically. Here, I compare rates of change in human technologies to rates of change in animal morphologies. I find that rates of cultural evolution are inversely correlated with the time interval over which they are measured, which is similar to what is known for biological rates. This correlation explains why the pace of cultural evolution appears faster when measured over recent time periods, where time intervals are often shorter. Controlling for the correlation between rates and time intervals, I show that (1) cultural evolution is faster than biological evolution; (2) this effect holds true even when the generation time of species is controlled for; and (3) culture allows us to evolve over short time scales, which are normally accessible only to short-lived species, while at the same time allowing for us to enjoy the benefits of having a long life history. PMID:23024804

Cultural evolutionary theory: How culture evolves and why it matters.

PubMed

Creanza, Nicole; Kolodny, Oren; Feldman, Marcus W

2017-07-24

Human cultural traits-behaviors, ideas, and technologies that can be learned from other individuals-can exhibit complex patterns of transmission and evolution, and researchers have developed theoretical models, both verbal and mathematical, to facilitate our understanding of these patterns. Many of the first quantitative models of cultural evolution were modified from existing concepts in theoretical population genetics because cultural evolution has many parallels with, as well as clear differences from, genetic evolution. Furthermore, cultural and genetic evolution can interact with one another and influence both transmission and selection. This interaction requires theoretical treatments of gene-culture coevolution and dual inheritance, in addition to purely cultural evolution. In addition, cultural evolutionary theory is a natural component of studies in demography, human ecology, and many other disciplines. Here, we review the core concepts in cultural evolutionary theory as they pertain to the extension of biology through culture, focusing on cultural evolutionary applications in population genetics, ecology, and demography. For each of these disciplines, we review the theoretical literature and highlight relevant empirical studies. We also discuss the societal implications of the study of cultural evolution and of the interactions of humans with one another and with their environment.

Top 10 Lines of Evidence for Human Evolution.

ERIC Educational Resources Information Center

Nickels, Martin

2001-01-01

Provides 10 lines of evidence that support the theory of human evolution. The evidence relates to hierarchical taxonomic classification, comparative anatomy, comparative embryology and development, comparative biochemistry, adaptive compromises, vestigial structures, biogeography, the fossil sequence, ecological coherence of fossil assemblages,…

The Evolution of the Brain, the Human Nature of Cortical Circuits, and Intellectual Creativity

PubMed Central

DeFelipe, Javier

2011-01-01

The tremendous expansion and the differentiation of the neocortex constitute two major events in the evolution of the mammalian brain. The increase in size and complexity of our brains opened the way to a spectacular development of cognitive and mental skills. This expansion during evolution facilitated the addition of microcircuits with a similar basic structure, which increased the complexity of the human brain and contributed to its uniqueness. However, fundamental differences even exist between distinct mammalian species. Here, we shall discuss the issue of our humanity from a neurobiological and historical perspective. PMID:21647212

Delegation to automaticity: the driving force for cognitive evolution?

PubMed

Shine, J M; Shine, R

2014-01-01

The ability to delegate control over repetitive tasks from higher to lower neural centers may be a fundamental innovation in human cognition. Plausibly, the massive neurocomputational challenges associated with the mastery of balance during the evolution of bipedality in proto-humans provided a strong selective advantage to individuals with brains capable of efficiently transferring tasks in this way. Thus, the shift from quadrupedal to bipedal locomotion may have driven the rapid evolution of distinctive features of human neuronal functioning. We review recent studies of functional neuroanatomy that bear upon this hypothesis, and identify ways to test our ideas.

Cultural macroevolution matters

PubMed Central

Gray, Russell D.

2017-01-01

Evolutionary thinking can be applied to both cultural microevolution and macroevolution. However, much of the current literature focuses on cultural microevolution. In this article, we argue that the growing availability of large cross-cultural datasets facilitates the use of computational methods derived from evolutionary biology to answer broad-scale questions about the major transitions in human social organization. Biological methods can be extended to human cultural evolution. We illustrate this argument with examples drawn from our recent work on the roles of Big Gods and ritual human sacrifice in the evolution of large, stratified societies. These analyses show that, although the presence of Big Gods is correlated with the evolution of political complexity, in Austronesian cultures at least, they do not play a causal role in ratcheting up political complexity. In contrast, ritual human sacrifice does play a causal role in promoting and sustaining the evolution of stratified societies by maintaining and legitimizing the power of elites. We briefly discuss some common objections to the application of phylogenetic modeling to cultural evolution and argue that the use of these methods does not require a commitment to either gene-like cultural inheritance or to the view that cultures are like vertebrate species. We conclude that the careful application of these methods can substantially enhance the prospects of an evolutionary science of human history. PMID:28739960

Insights into hominid evolution from the gorilla genome sequence

PubMed Central

Scally, Aylwyn; Dutheil, Julien Y.; Hillier, LaDeana W.; Jordan, Greg E.; Goodhead, Ian; Herrero, Javier; Hobolth, Asger; Lappalainen, Tuuli; Mailund, Thomas; Marques-Bonet, Tomas; McCarthy, Shane; Montgomery, Stephen H.; Schwalie, Petra C.; Tang, Y. Amy; Ward, Michelle C.; Xue, Yali; Yngvadottir, Bryndis; Alkan, Can; Andersen, Lars N.; Ayub, Qasim; Ball, Edward V.; Beal, Kathryn; Bradley, Brenda J.; Chen, Yuan; Clee, Chris M.; Fitzgerald, Stephen; Graves, Tina A.; Gu, Yong; Heath, Paul; Heger, Andreas; Karakoc, Emre; Kolb-Kokocinski, Anja; Laird, Gavin K.; Lunter, Gerton; Meader, Stephen; Mort, Matthew; Mullikin, James C.; Munch, Kasper; O’Connor, Timothy D.; Phillips, Andrew D.; Prado-Martinez, Javier; Rogers, Anthony S.; Sajjadian, Saba; Schmidt, Dominic; Shaw, Katy; Simpson, Jared T.; Stenson, Peter D.; Turner, Daniel J.; Vigilant, Linda; Vilella, Albert J.; Whitener, Weldon; Zhu, Baoli; Cooper, David N.; de Jong, Pieter; Dermitzakis, Emmanouil T.; Eichler, Evan E.; Flicek, Paul; Goldman, Nick; Mundy, Nicholas I.; Ning, Zemin; Odom, Duncan T.; Ponting, Chris P.; Quail, Michael A.; Ryder, Oliver A.; Searle, Stephen M.; Warren, Wesley C.; Wilson, Richard K.; Schierup, Mikkel H.; Rogers, Jane; Tyler-Smith, Chris; Durbin, Richard

2012-01-01

Summary Gorillas are humans’ closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago (Mya). In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution. PMID:22398555

PHONATION TAKES PRECEDENCE IN DEVELOPMENT AS WELL AS EVOLUTION OF LANGUAGE

PubMed Central

Oller, D. Kimbrough

2014-01-01

Early development of vocalization in humans is characterized by emerging control of phonation, rather than of prosody or supraglottal articulation. This fact offers an opportunity to the authors of the target article to enrich their characterization of the evolution of differential brain mechanisms in human and non-human primates. Phonation, I suggest, is the initial target of human-specific brain changes in sound-making capability upon which language is founded. PMID:25514957

Exceptional Evolutionary Divergence of Human Muscle and Brain Metabolomes Parallels Human Cognitive and Physical Uniqueness

PubMed Central

Bozek, Katarzyna; Wei, Yuning; Yan, Zheng; Liu, Xiling; Xiong, Jieyi; Sugimoto, Masahiro; Tomita, Masaru; Pääbo, Svante; Pieszek, Raik; Sherwood, Chet C.; Hof, Patrick R.; Ely, John J.; Steinhauser, Dirk; Willmitzer, Lothar; Bangsbo, Jens; Hansson, Ola; Call, Josep; Giavalisco, Patrick; Khaitovich, Philipp

2014-01-01

Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys. PMID:24866127

Evolution of social learning does not explain the origin of human cumulative culture.

PubMed

Enquist, Magnus; Ghirlanda, Stefano

2007-05-07

Because culture requires transmission of information between individuals, thinking about the origin of culture has mainly focused on the genetic evolution of abilities for social learning. Current theory considers how social learning affects the adaptiveness of a single cultural trait, yet human culture consists of the accumulation of very many traits. Here we introduce a new modeling strategy that tracks the adaptive value of many cultural traits, showing that genetic evolution favors only limited social learning owing to the accumulation of maladaptive as well as adaptive culture. We further show that culture can be adaptive, and refined social learning can evolve, if individuals can identify and discard maladaptive culture. This suggests that the evolution of such "adaptive filtering" mechanisms may have been crucial for the birth of human culture.

Evolution of Local Mutation Rate and Its Determinants.

PubMed

Terekhanova, Nadezhda V; Seplyarskiy, Vladimir B; Soldatov, Ruslan A; Bazykin, Georgii A

2017-05-01

Mutation rate varies along the human genome, and part of this variation is explainable by measurable local properties of the DNA molecule. Moreover, mutation rates differ between orthologous genomic regions of different species, but the drivers of this change are unclear. Here, we use data on human divergence from chimpanzee, human rare polymorphism, and human de novo mutations to predict the substitution rate at orthologous regions of non-human mammals. We show that the local mutation rates are very similar between human and apes, implying that their variation has a strong underlying cryptic component not explainable by the known genomic features. Mutation rates become progressively less similar in more distant species, and these changes are partially explainable by changes in the local genomic features of orthologous regions, most importantly, in the recombination rate. However, they are much more rapid, implying that the cryptic component underlying the mutation rate is more ephemeral than the known genomic features. These findings shed light on the determinants of mutation rate evolution. local mutation rate, molecular evolution, recombination rate. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Measure, Then Show: Grasping Human Evolution Through an Inquiry-Based, Data-driven Hominin Skulls Lab

PubMed Central

Luberda, Michael

2016-01-01

Incomprehension and denial of the theory of evolution among high school students has been observed to also occur when teachers are not equipped to deliver a compelling case also for human evolution based on fossil evidence. This paper assesses the outcomes of a novel inquiry-based paleoanthropology lab teaching human evolution to high-school students. The inquiry-based Be a Paleoanthropologist for a Day lab placed a dozen hominin skulls into the hands of high-school students. Upon measuring three variables of human evolution, students explain what they have observed and discuss findings. In the 2013/14 school year, 11 biology classes in 7 schools in the Greater New Orleans area participated in this lab. The interviewed teacher cohort unanimously agreed that the lab featuring hominin skull replicas and stimulating student inquiry was a pedagogically excellent method of delivering the subject of human evolution. First, the lab’s learning path of transforming facts to data, information to knowledge, and knowledge to acceptance empowered students to themselves execute part of the science that underpins our understanding of deep time hominin evolution. Second, although challenging, the hands-on format of the lab was accessible to high-school students, most of whom were readily able to engage the lab’s scientific process. Third, the lab’s exciting and compelling pedagogy unlocked higher order thinking skills, effectively activating the cognitive, psychomotor and affected learning domains as defined in Bloom’s taxonomy. Lastly, the lab afforded students a formative experience with a high degree of retention and epistemic depth. Further study is warranted to gauge the degree of these effects. PMID:27513927

Antigenic Patterns and Evolution of the Human Influenza A (H1N1) Virus

PubMed Central

Liu, Mi; Zhao, Xiang; Hua, Sha; Du, Xiangjun; Peng, Yousong; Li, Xiyan; Lan, Yu; Wang, Dayan; Wu, Aiping; Shu, Yuelong; Jiang, Taijiao

2015-01-01

The influenza A (H1N1) virus causes seasonal epidemics that result in severe illnesses and deaths almost every year. A deep understanding of the antigenic patterns and evolution of human influenza A (H1N1) virus is extremely important for its effective surveillance and prevention. Through development of antigenicity inference method for human influenza A (H1N1), named PREDAC-H1, we systematically mapped the antigenic patterns and evolution of the human influenza A (H1N1) virus. Eight dominant antigenic clusters have been inferred for seasonal H1N1 viruses since 1977, which demonstrated sequential replacements over time with a similar pattern in Asia, Europe and North America. Among them, six clusters emerged first in Asia. As for China, three of the eight antigenic clusters were detected in South China earlier than in North China, indicating the leading role of South China in H1N1 transmission. The comprehensive view of the antigenic evolution of human influenza A (H1N1) virus can help formulate better strategy for its prevention and control. PMID:26412348

Antigenic Patterns and Evolution of the Human Influenza A (H1N1) Virus.

PubMed

Liu, Mi; Zhao, Xiang; Hua, Sha; Du, Xiangjun; Peng, Yousong; Li, Xiyan; Lan, Yu; Wang, Dayan; Wu, Aiping; Shu, Yuelong; Jiang, Taijiao

2015-09-28

The influenza A (H1N1) virus causes seasonal epidemics that result in severe illnesses and deaths almost every year. A deep understanding of the antigenic patterns and evolution of human influenza A (H1N1) virus is extremely important for its effective surveillance and prevention. Through development of antigenicity inference method for human influenza A (H1N1), named PREDAC-H1, we systematically mapped the antigenic patterns and evolution of the human influenza A (H1N1) virus. Eight dominant antigenic clusters have been inferred for seasonal H1N1 viruses since 1977, which demonstrated sequential replacements over time with a similar pattern in Asia, Europe and North America. Among them, six clusters emerged first in Asia. As for China, three of the eight antigenic clusters were detected in South China earlier than in North China, indicating the leading role of South China in H1N1 transmission. The comprehensive view of the antigenic evolution of human influenza A (H1N1) virus can help formulate better strategy for its prevention and control.

The Evolution of Human Handedness

PubMed Central

Smaers, Jeroen B; Steele, James; Case, Charleen R; Amunts, Katrin

2013-01-01

There is extensive evidence for an early vertebrate origin of lateralized motor behavior and of related asymmetries in underlying brain systems. We investigate human lateralized motor functioning in a broad comparative context of evolutionary neural reorganization. We quantify evolutionary trends in the fronto-cerebellar system (involved in motor learning) across 46 million years of divergent primate evolution by comparing rates of evolution of prefrontal cortex, frontal motor cortex, and posterior cerebellar hemispheres along individual branches of the primate tree of life. We provide a detailed evolutionary model of the neuroanatomical changes leading to modern human lateralized motor functioning, demonstrating an increased role for the fronto-cerebellar system in the apes dating to their evolutionary divergence from the monkeys (∼30 million years ago (Mya)), and a subsequent shift toward an increased role for prefrontal cortex over frontal motor cortex in the fronto-cerebellar system in the Homo-Pan ancestral lineage (∼10 Mya) and in the human ancestral lineage (∼6 Mya). We discuss these results in the context of cortico-cerebellar functions and their likely role in the evolution of human tool use and speech. PMID:23647442

Evaluation of intervertebral disc regeneration with implantation of bone marrow mesenchymal stem cells (BMSCs) using quantitative T2 mapping: a study in rabbits.

PubMed

Cai, Feng; Wu, Xiao-Tao; Xie, Xin-Hui; Wang, Feng; Hong, Xin; Zhuang, Su-Yang; Zhu, Lei; Rui, Yun-Feng; Shi, Rui

2015-01-01

The aim of the study was to investigate the curative effects of transplantation of bone marrow mesenchymal stem cells (BMSCs) on intervertebral disc regeneration and to investigate the feasibility of the quantitative T2 mapping method for evaluating repair of the nucleus pulposus after implantation of BMSCs. Forty-eight New Zealand white rabbits were used to establish the lumber disc degenerative model by stabbing the annulus fibrosus and then randomly divided into four groups, i.e. two weeks afterwards, BMSCs or phosphate-buffered saline (PBS) were transplanted into degenerative discs (BMSCs group and PBS group), while the operated rabbits without implantation of BMSCs or PBS served as the sham group and the rabbits without operation were used as the control group. At weeks two, six and ten after operation, the T2 values and disc height indices (DHI) were calculated by magnetic resonance imaging (MRI 3.0 T), and the gene expressions of type II collagen (COL2) and aggrecan (ACAN) in degenerative discs were evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR). T2 values for the nucleus pulposus were correlated with ACAN or COL2 expression by regression analysis. Cell clusters, disorganised fibres, interlamellar glycosaminoglycan (GAG) matrix and vascularisation were observed in lumber degenerative discs. BMSCs could be found to survive in intervertebral discs and differentiate into nucleus pulposus-like cells expressing COL2 and ACAN. The gene expression of COL2 and ACAN increased during ten weeks after transplantation as well as the T2 signal intensity and T2 value. The DHI in the BMSCs group decreased more slowly than that in PBS and sham groups. The T2 value correlated significantly with the gene expression of ACAN and COL2 in the nucleus pulposus. Transplantation of BMSCs was able to promote the regeneration of degenerative discs. Quantitative and non-invasive T2 mapping could be used to evaluate the regeneration of the nucleus pulposus with good sensitivity.

Middle-aged patients with an MRI-verified medial meniscal tear report symptoms commonly associated with knee osteoarthritis.

PubMed

Hare, Kristoffer B; Stefan Lohmander, L; Kise, Nina Jullum; Risberg, May Arna; Roos, Ewa M

2017-12-01

Background and purpose - No consensus exists on when to perform arthroscopic partial meniscectomy in patients with a degenerative meniscal tear. Since MRI and clinical tests are not accurate in detecting a symptomatic meniscal lesion, the patient's symptoms often play a large role when deciding when to perform surgery. We determined the prevalence and severity of self-reported knee symptoms in patients eligible for arthroscopic partial meniscectomy due to a degenerative meniscal tear. We investigated whether symptoms commonly considered to be related to meniscus injury were associated with early radiographic signs of knee osteoarthritis. Patients and methods - We included individual baseline items from the Knee injury and Osteoarthritis Outcome Score collected in 2 randomized controlled trials evaluating treatment for an MRI-verified degenerative medial meniscal tears in 199 patients aged 35-65 years. Each item was scored as no, mild, moderate, severe, extreme, and at least "mild" considering the symptoms present. Early radiographic signs of osteoarthritis, defined as a Kellgren and Lawrence grade of at least 1, were seen in 70 patients. Results - At least monthly knee pain, pain during stair walking and when twisting on the knee, and lack of confidence in knee was present in at least 80% of the patients. Median severity was at least moderate for knee pain, pain when twisting on the knee, pain walking on stairs, lack of confidence in knee, and clicking. Mechanical symptoms such as catching were rare. Early radiographic signs of osteoarthritis were associated with an increased risk of self-reported swelling, catching, and stiffness later in the day; the odds ratio was 2.4 (95% CI 1.2-4.9), 2.3 (1.2-4.3), and 2.3 (1.1-5.0), respectively. Interpretation - Middle-aged patients with a degenerative medial meniscus tear reported symptoms commonly associated with knee osteoarthritis. Frequent knee pain, presence of lack of confidence in the knee, and clicking did not distinguish those with a meniscal tear alone from those with early radiographic knee OA. Our findings support the notion that symptoms reported by those with a degenerative meniscal tear represent early signs of knee osteoarthritis.

Vertebral rotatory subluxation in degenerative scoliosis: facet joint tropism is related.

PubMed

Bao, Hongda; Zhu, Feng; Liu, Zhen; Bentley, Mark; Mao, Saihu; Zhu, Zezhang; Ding, Yitao; Qiu, Yong

2014-12-15

A cross-sectional study. To identify facet tropism as one of the possible risk factors leading to vertebral rotatory subluxation (VRS). VRS has been considered as one of the prognostic factors for degenerative scoliosis. Although several risk factors of VRS, including age and Cobb angle, have been investigated, few studies exist that have evaluated the correlation between VRS and anatomical structures of the vertebral column. This retrospective study recruited 23 patients diagnosed with degenerative lumbar scoliosis with VRS and 20 patients with degenerative scoliosis without VRS. The lateral translation on coronal radiographs was measured and 5 mm was used as the cutoff value to define rotatory subluxation. Computed tomographic scans for facet joints were made for all lumbar levels. The difference between right and left facet angles was recorded as ΔFA. Facet tropism was defined as a difference between the bilateral facet angles of more than 10°. In this study, VRS was most commonly found at the L3-L4 level (49%) and, with decreasing frequency at L2-L3 (24%), L4-L5 (20%), and L1-L2 (7%). On the convex side of the main curve, face joints at levels with VRS were more coronally oriented compared with those at levels without VRS (41.64° ± 11.65° vs. 36.30° ± 10.99°, P = 0.034). ΔFA was also significantly different between levels with and without VRS (P = 0.005). A strong correlation was found between ΔFA and lateral translation, with a coefficient of 0.33 (P < 0.001). In addition, ΔFA and a larger Cobb angle were found to be significantly associated with VRS based on binary regression analysis, with an odds ratio of 4.68 and 2.14, respectively. Facet tropism was more significantly observed at levels with VRS. On the convex side of the main curve, facet joints at levels with VRS were more coronally oriented. A larger Cobb angle and severe facet tropism in degenerative scoliosis should be considered to be related to VRS.

Back pain was less explained than leg pain: a cross-sectional study using magnetic resonance imaging in low back pain patients with and without radiculopathy.

PubMed

Jensen, Ole Kudsk; Nielsen, Claus Vinther; Sørensen, Joan Solgaard; Stengaard-Pedersen, Kristian

2015-12-03

Cross-sectional studies have shown associations between lumbar degenerative manifestations on magnetic resonance imaging (MRI) and low back pain (LBP). Disc herniations and other degenerative manifestations, however, frequently occur in asymptomatic individuals. The purpose of this cross-sectional study was to analyze for associations between pain intensity and degenerative manifestations and other pain variables in patients for whom prognostic factors have been published previously. Included were 141 consecutive patients with and without radiculopathy, all sick-listed 1-4 months due to low back pain and subsequently examined by MRI of the lumbar spine. Using different methods of grouping the degenerative manifestations, linear regression analyses were performed with the intensity of back + leg pain, back pain and leg pain as dependent variables covering actual pain and pain the preceding 2 weeks. The clinical classification into +/- radiculopathy was established before and independently of the standardised description of MRI findings. Radiculopathy was present in 43 % of the patients. Pain was best explained using rank-ordered degenerative manifestations on MRI. Back pain and leg pain were differently associated, and back pain was less explained than leg pain in the multivariate analyses (15 % vs. 31 % of the variation). Back pain intensity was higher in patients with type 1 Modic changes and in some patients with nerve root touch, but was not associated with disc herniations. Leg pain intensity was well explained by disc herniations causing MRI nerve root compromise and radiculopathy. In patients with radiculopathy, nerve root touch caused as much leg pain as nerve root displacement or compression. High intensity zones and osteophytes were not associated with back pain, but only associated with leg pain in patients with radiculopathy. Tender points explained some of the back pain, and widespread pain explained leg pain in some of the patients without radiculopathy. Back pain was associated with type 1 Modic changes, nerve root touch and tender points, whereas leg pain was associated with osteophytes, HIZ, disc herniation, all sorts of MRI nerve root compromise, radiculopathy and widespread pain.

Expression of immune response genes in the stifle joint of dogs with oligoarthritis and degenerative cranial cruciate ligament rupture.

PubMed

Muir, P; Schaefer, S L; Manley, P A; Svaren, J P; Oldenhoff, W E; Hao, Z

2007-10-15

Dysregulation of immune responses within joints plays an important role in development of inflammatory arthritis. We determined expression of a panel of immune response and matrix turnover genes in synovial fluid collected from a group of dogs with stifle oligoarthritis and associated degenerative cranial cruciate ligament (CCL) rupture (n=27). We also studied synovial fluid gene expression in dogs affected with other forms of degenerative arthritis (n=9) and in the stifle joint of healthy dogs with intact CCL (n=14). After collection, synovial cells were pelleted and RNA was isolated. Relative expression of cathepsin K, cathepsin S, tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinase-9 (MMP-9), invariant chain (li), toll-like receptor-2 (TLR-2), and TLR-9 was determined using real-time quantitative RT-PCR. Data were normalized to peripheral blood mononuclear cells (PBMC) as an internal control. Relative expression of cathepsin K, MMP-9, TRAP, and li was increased in the stifle synovial fluid of dogs with oligoarthritis, when compared with the stifles of healthy dogs (P<0.05). In contrast, relative expression of all of the genes-of-interest in synovial fluid from joints affected with other forms of arthritis was not significantly different from the stifles of healthy dogs. TRAP expression was also significantly increased in the stifle joints of dogs with oligoarthritis, when compared to joint expression of TRAP in dogs with other forms of degenerative arthritis (P<0.05). In the dogs with stifle oligoarthritis, expression of both matrix turnover and immune response genes was increased in stifle synovial fluid, when compared with the internal PBMC control, whereas in healthy dogs and dogs with other forms of arthritis, only expression of matrix turnover genes was increased in synovial fluid, when compared with the internal PBMC control (P<0.05). Taken together, these findings suggest that antigen-specific immune responses within the stifle joint may be involved in the pathogenesis of persistent synovitis and associated joint degradation in dogs with oligoarthritis and degenerative CCL rupture.

Clinical and radiological outcome of conservative vs. surgical treatment of atraumatic degenerative rotator cuff rupture: design of a randomized controlled trial.

PubMed

Lambers Heerspink, Frederik O; Hoogeslag, Roy Ag; Diercks, Ron L; van Eerden, Pepijn Jm; van den Akker-Scheek, Inge; van Raay, Jos Jam

2011-01-26

Subacromial impingement syndrome is a frequently observed disorder in orthopedic practice. Lasting symptoms and impairment may occur when a subsequent atraumatic rotator cuff rupture is also present. However, degenerative ruptures of the rotator cuff can also be observed in asymptomatic elderly individuals. Treatment of these symptomatic degenerative ruptures may be conservative or surgical. Acceptable results are reported for both treatment modalities. No evidence-based level-1 studies have been conducted so far to compare these treatment modalities. The objective of this study is to determine whether there is a difference in outcome between surgical reconstruction and conservative treatment of a degenerative atraumatic rotator cuff tendon rupture. A randomized controlled trial will be conducted. Patients aged between 45 and 75 with a symptomatic atraumatic rotator cuff rupture as diagnosed by MRI will be included. Exclusion criteria are traumatic rotator cuff rupture, frozen shoulder and diabetes mellitus. Patients will be randomized into two groups. Conservative treatment includes physical therapy according to a standardized protocol, NSAIDs and, if indicated, subacromial infiltration with a local anesthetic and corticosteroids. Surgical reconstruction is performed under general anesthesia in combination with an interscalenus plexus block. An acromioplasty with reconstruction of the rotator cuff tendon is performed, as described by Rockwood et al. Measurements take place preoperatively and 6 weeks, 3 months, 6 months and 1 year postoperatively. The primary outcome measure is the Constant score. Secondary measures include both disease-specific and generic outcome measures, and an economic evaluation. Additionally, one year after inclusion a second MRI will be taken of all patients in order to determine whether extent and localization of the rupture as well as the amount of fatty degeneration are prognostic factors. Both surgical as conservative treatment of a symptomatic atraumatic rotator cuff tendon rupture is used in current practice. There is a lack of level-1 studies comparing surgical vs. conservative treatment. This randomized controlled trial has been designed to determine whether the surgical treatment of a degenerative atraumatic rotator cuff tendon rupture may lead to a better functional and radiological outcome than conservative treatment after one year of follow-up. Netherlands Trial Register (NTR): NTRTC2343.

Comparative Analysis of Gene Expression for Convergent Evolution of Camera Eye Between Octopus and Human

PubMed Central

Ogura, Atsushi; Ikeo, Kazuho; Gojobori, Takashi

2004-01-01

Although the camera eye of the octopus is very similar to that of humans, phylogenetic and embryological analyses have suggested that their camera eyes have been acquired independently. It has been known as a typical example of convergent evolution. To study the molecular basis of convergent evolution of camera eyes, we conducted a comparative analysis of gene expression in octopus and human camera eyes. We sequenced 16,432 ESTs of the octopus eye, leading to 1052 nonredundant genes that have matches in the protein database. Comparing these 1052 genes with 13,303 already-known ESTs of the human eye, 729 (69.3%) genes were commonly expressed between the human and octopus eyes. On the contrary, when we compared octopus eye ESTs with human connective tissue ESTs, the expression similarity was quite low. To trace the evolutionary changes that are potentially responsible for camera eye formation, we also compared octopus-eye ESTs with the completed genome sequences of other organisms. We found that 1019 out of the 1052 genes had already existed at the common ancestor of bilateria, and 875 genes were conserved between humans and octopuses. It suggests that a larger number of conserved genes and their similar gene expression may be responsible for the convergent evolution of the camera eye. PMID:15289475

Human Evolution: The Real Cause for Birth Palsy

PubMed Central

Sreekanth, R; Thomas, BP

2015-01-01

ABSTRACT Objective: Birth palsy, otherwise known as obstetric brachial plexus paralysis (OBPP), is a closed stretch injury to the brachial plexus of nerves during the birth process resulting in varying degree of paralysis and contractures of the upper limb. The study aimed to find out the susceptibility of humans and small-bodied primates to birth palsy. Method: A comparative study on parturition in modern humans, hominoids, hominids, small-bodied primates and great apes was done to determine if changes in the female pelvis and neonatal head and shoulder during human evolution is the real cause for OBPP. Results: During evolution, the morphology of the female pelvis and birth canal changed into a narrow and twisted one and also the size of the fetal head increased. Thus, the narrow and twisted pelvis of the mother, and the relatively large head and broad shoulders of the newborn has made the birthing process of modern human and small bodied primates a precarious fine-tuned act with a very narrow margin for error. This has necessitated proper obstetric care to reduce or even at times obviate the incidence of birth injuries like OBPP. Conclusion: Human evolution has made human babies susceptible to birth palsy and thus is the real cause of birth palsy. PMID:26624599

Socio-hydrologic perspectives of the co-evolution of humans and water in the Tarim River basin, Western China: the Taiji-Tire model

NASA Astrophysics Data System (ADS)

Liu, Y.; Tian, F.; Hu, H.; Sivapalan, M.

2014-04-01

This paper presents a historical socio-hydrological analysis of the Tarim River basin (TRB), Xinjiang Uyghur Autonomous Region, in Western China, from the time of the opening of the Silk Road to the present. The analysis is aimed at exploring the historical co-evolution of coupled human-water systems and at identifying common patterns or organizing principles underpinning socio-hydrological systems (SHS). As a self-organized entity, the evolution of the human-water system in the Tarim Basin reached stable states for long periods of time, but then was punctuated by sudden shifts due to internal or external disturbances. In this study, we discuss three stable periods (i.e., natural, human exploitation, and degradation and recovery) and the transitions in between during the past 2000 years. During the "natural" stage that existed pre-18th century, with small-scale human society and sound environment, evolution of the SHS was mainly driven by natural environmental changes such as river channel migration and climate change. During the human exploitation stage, especially in the 19th and 20th centuries, it experienced rapid population growth, massive land reclamation and fast socio-economic development, and humans became the principal players of system evolution. By the 1970s, the Tarim Basin had evolved into a new regime with a vulnerable eco-hydrological system seemingly populated beyond its carrying capacity, and a human society that began to suffer from serious water shortages, land salinization and desertification. With intensified deterioration of river health and increased recognition of unsustainability of traditional development patterns, human intervention and recovery measures have since been adopted. As a result, the basin has shown a reverse regime shift towards some healing of the environmental damage. Based on our analysis within TRB and a common theory of social development, four general types of SHSs are defined according to their characteristic spatio-temporal variations of historical co-evolution, including primitive agricultural, traditional agricultural, industrial agricultural, and urban SHSs. These co-evolutionary changes have been explained in the paper in terms of the Taiji-Tire model, a refinement of a special concept in Chinese philosophy, relating to the co-evolution of a system because of interactions among its components.

Evolution of camel CYP2E1 and its associated power of binding toxic industrial chemicals and drugs.

PubMed

Kandeel, Mahmoud; Altaher, Abdullah; Kitade, Yukio; Abdelaziz, Magdi; Alnazawi, Mohamed; Elshazli, Kamal

2016-10-01

Camels are raised in harsh desert environment for hundreds of years ago. By modernization of live and the growing industrial revolution in camels rearing areas, camels are exposed to considerable amount of chemicals, industrial waste, environmental pollutions and drugs. Furthermore, camels have unique gene evolution of some genes to withstand living in harsh environments. In this work, the camel cytochrome P450 2E1 (CYP2E1) is compromised to detect its evolution rate and its power to bind with various chemicals, protoxins, procarcinogens, industrial toxins and drugs. In comparison with human CYP2E1, camel CYP2E1 more efficiently binds to small toxins as aniline, benzene, catechol, amides, butadiene, toluene and acrylamide. Larger compounds were more preferentially bound to the human CYP2E1 in comparison with camel CYP2E1. The binding of inhalant anesthetics was almost similar in both camel and human CYP2E1 coinciding with similar anesthetic effect as well as toxicity profiles. Furthermore, evolutionary analysis indicated the high evolution rate of camel CYP2E1 in comparison with human, farm and companion animals. The evolution rate of camel CYP2E1 was among the highest evolution rate in a subset of 57 different organisms. These results indicate rapid evolution and potent toxin binding power of camel CYP2E1. Copyright © 2016. Published by Elsevier Ltd.

Dental Calculus and the Evolution of the Human Oral Microbiome.

PubMed

Warinner, Christina

2016-07-01

Characterizing the evolution of the oral microbiome is a challenging, but increasingly feasible, task. Recently, dental calculus has been shown to preserve ancient biomolecules from the oral microbiota, host tissues and diet for tens of thousands of years. As such, it provides a unique window into the ancestral oral microbiome. This article reviews recent advancements in ancient dental calculus research and emerging insights into the evolution and ecology of the human oral microbiome.

Thinking outside the cortex: social motivation in the evolution and development of language.

PubMed

Syal, Supriya; Finlay, Barbara L

2011-03-01

Alteration of the organization of social and motivational neuroanatomical circuitry must have been an essential step in the evolution of human language. Development of vocal communication across species, particularly birdsong, and new research on the neural organization and evolution of social and motivational circuitry, together suggest that human language is the result of an obligatory link of a powerful cortico-striatal learning system, and subcortical socio-motivational circuitry.

Culture, Urbanism and Changing Human Biology.

PubMed

Schell, L M

2014-04-03

Anthropologists have long known that human activity driven by culture changes the environment. This is apparent in the archaeological record and through the study of the modern environment. Perhaps the largest change since the paleolithic era is the organization of human populations in cities. New environments can reshape human biology through evolution as shown by the evolution of the hominid lineage. Evolution is not the only process capable of reshaping our biology. Some changes in our human biology are adaptive and evolutionary while others are pathological. What changes in human biology may be wrought by the modern urban environment? One significant new change in the environment is the introduction of pollutants largely through urbanization. Pollutants can affect human biology in myriad ways. Evidence shows that human growth, reproduction, and cognitive functioning can be altered by some pollutants, and altered in different ways depending on the pollutant. Thus, pollutants have significance for human biologists and anthropologists generally. Further, they illustrate the bio-cultural interaction characterizing human change. Humans adapt by changing the environment, a cultural process, and then change biologically to adjust to that new environment. This ongoing, interactive process is a fundamental characteristic of human change over the millennia.

Culture, Urbanism and Changing Human Biology

PubMed Central

Schell, L.M.

2014-01-01

Anthropologists have long known that human activity driven by culture changes the environment. This is apparent in the archaeological record and through the study of the modern environment. Perhaps the largest change since the paleolithic era is the organization of human populations in cities. New environments can reshape human biology through evolution as shown by the evolution of the hominid lineage. Evolution is not the only process capable of reshaping our biology. Some changes in our human biology are adaptive and evolutionary while others are pathological. What changes in human biology may be wrought by the modern urban environment? One significant new change in the environment is the introduction of pollutants largely through urbanization. Pollutants can affect human biology in myriad ways. Evidence shows that human growth, reproduction, and cognitive functioning can be altered by some pollutants, and altered in different ways depending on the pollutant. Thus, pollutants have significance for human biologists and anthropologists generally. Further, they illustrate the bio-cultural interaction characterizing human change. Humans adapt by changing the environment, a cultural process, and then change biologically to adjust to that new environment. This ongoing, interactive process is a fundamental characteristic of human change over the millennia. PMID:25598655

Surgical apgar score in patients undergoing lumbar fusion for degenerative spine diseases.

PubMed

Ou, Chien-Yu; Hsu, Shih-Yuan; Huang, Jian-Hao; Huang, Yu-Hua

2017-01-01

Lumbar fusion is a procedure broadly performed for degenerative diseases of spines, but it is not without significant morbidities. Surgical Apgar Score (SAS), based on intraoperative blood loss, blood pressure, and heart rate, was developed for prognostic prediction in general and vascular operations. We aimed to examine whether the application of SAS in patients undergoing fusion procedures for degeneration of lumbar spines predicts in-hospital major complications. One hundred and ninety-nine patients that underwent lumbar fusion operation for spine degeneration were enrolled in this retrospective study. Based on whether major complications were present (N=16) or not (N=183), the patients were subdivided. We identified the intergroup differences in SAS and clinical parameters. The incidence of in-hospital major complications was 8%. The duration of hospital stay for the morbid patents was significantly prolonged (p=0.04). In the analysis of multivariable logistic regression, SAS was an independent predicting factor of the complications after lumbar fusion for degenerative spine diseases [p=0.001; odds ratio (95% confidence interval)=0.35 (0.19-0.64)]. Lower scores were accompanied with higher rates of major complications, and the area was 0.872 under the receiver operating characteristic curve. SAS is an independent predicting factor of major complications in patients after fusion surgery for degenerative diseases of lumbar spines, and provides good risk discrimination. Since the scoring system is relatively simple, objective, and practical, we suggest that SAS be included as an indicator in the guidance for level of care after lumbar fusion surgery. Copyright © 2016 Elsevier B.V. All rights reserved.