scholarly journals How repair-or-dispose decisions under stress can initiate disease progression

2019 ◽  
Author(s):  
Andreas Nold ◽  
Danylo Batulin ◽  
Katharina Birkner ◽  
Stefan Bittner ◽  
Tatjana Tchumatchenko

AbstractGlia, the helper cells of the brain, are essential in maintaining neural resilience across time and varying challenges: By reacting to changes in neuronal health glia carefully balance repair or disposal of injured neurons to prevent further tissue damage. Malfunction of these interactions is implicated in many neurodegenerative diseases. Reductionist models with a minimal number of parameters provide the opportunity to gain insight into biological functions and inform experimental designs. We introduce such a model that mimics long-term implications of repair-or-dispose decisions. Depending on the functionality of the decision-making process, the model assumes four distinct tissue states: healthy, challenged, primed tissue at risk of acute damage propagation, and chronic neurodegeneration. These states of the model correspond to the progression stages observed in the most common neurodegenerative conditions. The underlying mechanisms are in agreement with experimental observations of glia-neuron crosstalk and reproduce a homeostatic balance between repairing and damage-inducing reactions. The model suggests that the onset of neurodegeneration results from a tug-of-war between two conflicting goals: short-term resilience to stressors vs long-term prevention of tissue damage.

2008 ◽  
Vol 294 (3) ◽  
pp. R905-R914 ◽  
Author(s):  
Guadalupe Perfume ◽  
Sabrina L. Nabhen ◽  
Karla Riquelme Barrera ◽  
María G. Otero ◽  
Liliana G. Bianciotti ◽  
...  

Brain catecholamines are involved in the regulation of biological functions, including cardiovascular activity. The hypothalamus presents areas with high density of catecholaminergic neurons and the endothelin system. Two hypothalamic regions intimately related with the cardiovascular control are distinguished: the anterior (AHR) and posterior (PHR) hypothalamus, considered to be sympathoinhibitory and sympathoexcitatory regions, respectively. We previously reported that endothelins (ETs) are involved in the short-term tyrosine hydroxylase (TH) regulation in both the AHR and PHR. TH is crucial for catecholaminergic transmission and is tightly regulated by well-characterized mechanisms. In the present study, we sought to establish the effects and underlying mechanisms of ET-1 and ET-3 on TH long-term modulation. Results showed that in the AHR, ETs decreased TH activity through ETB receptor activation coupled to the nitric oxide, phosphoinositide, and CaMK-II pathways. They also reduced total TH level and TH phosphorylated forms (Ser 19 and 40). Conversely, in the PHR, ETs increased TH activity through a G protein-coupled receptor, likely an atypical ET receptor or the ETC receptor, which stimulated the phosphoinositide and adenylyl cyclase pathways, as well as CaMK-II. ETs also increased total TH level and the Ser 19, 31, and 40 phosphorylated sites of the enzyme. These findings support that ETs are involved in the long-term regulation of TH activity, leading to reduced sympathoinhibition in the AHR and increased sympathoexcitation in the PHR. Present and previous studies may partially explain the cardiovascular effects produced by ETs when applied to the brain.


2020 ◽  
Vol 29 (5) ◽  
pp. 640-649 ◽  
Author(s):  
Amy Barrette ◽  
Katherine Harman

Context: Pain in sport has been normalized to the point where athletes are expected to ignore pain and remain in the game despite the possible detrimental consequences associated with playing through pain. While rehabilitation specialists may not have an influence on an athlete’s competitive nature or the culture of risk they operate in, understanding the consequences of those factors on an athlete’s physical well-being is definitely in their area of responsibility. Objective: To explore the factors associated with the experiences of subelite athletes who play through pain in gymnastics, rowing, and speed skating. Design: The authors conducted semistructured interviews with subelite athletes, coaches, and rehabilitation specialists. They recruited coach participants through their provincial sport organization. Athletes of the recruited coaches who were recovering from a musculoskeletal injury and training for a major competition were then recruited. They also recruited rehabilitation specialists who were known to treat subelite athletes independently by e-mail. Setting: An observation session was conducted at the athlete’s training facility. Interviews were then conducted either in a room at the university or at a preferred sound-attenuated location suggested by the participant. Participants: The authors studied 5 coaches, 4 subelite athletes, and 3 rehabilitation specialists. Interventions: The authors photographed athletes during a practice shortly before an important competition, and we interviewed all the participants after that competition. Our photographs were used during the interview to stimulate discussion. Results: The participant interviews revealed 3 main themes related to playing through pain. They are: Listening to your body, Decision making, and Who decides. Conclusion: When subelite athletes, striving to be the best in their sport continue to train with the pain of an injury, performance is affected in the short-term and long-term consequences are also possible. Our study provides some insight into the contrasting forces that athletes balance as they decide to continue or to stop.


Author(s):  
Valentina Tocchioni ◽  
Alessandra Petrucci ◽  
Alessandra Minello

In the last years, there has been a large increase in high-educated and high-skilled people’s mobility as a consequence of the internationalization and globalization, the weakening of research and university systems of sending countries (the “brain drain” process), the increase in skilled demand and improvements in higher education of host countries (the “brain gain” process). At the micro-level, academic mobility has positive consequences on occupational prospects and careers of researchers, both in the short- and long- run. Nevertheless, numerous research studies have demonstrated the challenges of engaging in international academic mobility for people with caring responsibilities, particularly women. Using Italian data on occupational conditions of PhDs collected in 2018 by Istat and modelling multinomial logistic regression analyses, we intend to verify if female researchers are associated with a lower international mobility irrespective their field of study, and the extent to which gender interacts differently in the various fields of study in affecting the probability of moving abroad after PhD qualification. Also, the distinction between long-term and short-term mobility, which has been mainly neglected in the literature concentrating on longer stays, has taken into account. In this respect, short-term mobility is a potentially high-value investment that may be pursued also by those researchers and scientists who cannot move for longer periods, such as women with caring responsibilities. In the literature, it is acknowledged that an experience abroad during early career may have positive effects on future occupational prospects. With our work, we intend to shed light on potential disparities on moving abroad that may exist among researchers in their early career by gender, and which could contribute to leave behind women in academia.


Meditation refers to a state of mind of relaxation and concentration, where generally the mind and body is at rest. The process of meditation reflects the state of the brain which is distinct from sleep or typical wakeful states of consciousness. Meditative practices usually involve regulation of emotions and monitoring of attention. Over the past decade there has been a tremendous increase in an interest to study the neural mechanisms involved in meditative practices. It could also be beneficial to explore if the effect of meditation is altered by the number of years of meditation practice. Functional Magnetic Resonance Imaging (fMRI) is a very useful imaging technique which can be used to perform this analysis due to its inherent benefits, mainly it being a non-invasive technique. Functional activation and connectivity analysis can be performed on the fMRI data to find the active regions and the connectivity in the brain regions. Functional connectivity is defined as a simple temporal correlation between anatomically separate, active neural regions. Functional connectivity gives the statistical dependencies between regional time series. It is a statistical concept and is quantified using metrics like Correlation. In this study, a comparison is made between functional connectivity in the brain regions of long term meditation practitioners (LTP) and short-term meditation practitioners (STP) to see the differences and similarities in the connectivity patterns. From the analysis, it is evident that in fact there is a difference in connectivity between long term and short term practitioners and hence continuous practice of meditation can have long term effects.


2018 ◽  
Vol 159 (32) ◽  
pp. 1295-1302
Author(s):  
Erika Rozália Kovács ◽  
Sára Tóth ◽  
Dániel János Erdélyi

Abstract: Etoposide is a topoisomerase II inhibitor antitumor agent which is widely used in the treatment of several hematologic malignancies and solid tumors. The therapeutic index of etoposide is quite high, thus its application causes several short-term and long-term side effects which can decrease the chance to cure patients. Drug dosing is based on body surface area calculation; recommendations for individual dosing do not exist yet. The biotransformation and transportation of etoposide are carried out by enzymes and transporters as reported in pharmacogenomic studies published in this area. Nowadays pharmacoepigenetics research has come to the fore. The authors wish to give an insight into the research of the epigenetical changes of the etoposide pathways, especially focusing on published findings on enzymes and transporters with pharmacokinetic relevance. In the future, epigenetical changes of the etoposide pathway might have a great role in diagnostics, prognostics and personalized medicine. Orv Hetil. 2018; 159(32): 1295–1302.


2019 ◽  
Vol 11 (12) ◽  
pp. 1266-1272 ◽  
Author(s):  
Krishnan Ravindran ◽  
Lauren A Dalvin ◽  
Jose S Pulido ◽  
Waleed Brinjikji

Background and purposeIntra-arterial chemotherapy for retinoblastoma has been adopted as a first-line treatment option by numerous tertiary centers. The effect of intra-arterial chemotherapy on future rates of metastatic disease as well as on globe salvage in advanced eyes remains relatively unknown.MethodsA search of PubMED, MEDLINE, EMBASE, and Web of Science electronic databases was conducted from inception until January 2019 for studies with a minimum of 10 patients reporting outcomes and complications following intra-arterial chemotherapy for retinoblastoma.ResultsA total of 20 studies met the inclusion criteria for analysis, comprising 873 patients and 1467 eyes. Only one study was comparative; there was substantial heterogeneity in reported outcomes and several overlapping patient cohorts that were published. Across all studies, 174 of 1467 eyes were enucleated (11.8%). Metastatic disease occurred in 8 of 513 patients (1.6%). Globe salvage was achieved in 318 of 906 (35.6%) cases of advanced retinoblastoma. The most common ocular complication was retinal detachment, occurring in 23% of eyes, and the most common systemic complications were transient fever and nausea/vomiting.ConclusionsThere is a paucity of higher-level evidence with adequate follow-up surrounding the long-term safety of intra-arterial chemotherapy and effect on metastasis in retinoblastoma. Studies to date have been limited by short-term follow-up. Longitudinal prospective studies could provide greater insight into the ability of intra-arterial chemotherapy to reduce the risk of retinoblastoma metastasis.


2004 ◽  
Vol 287 (2) ◽  
pp. R465-R471 ◽  
Author(s):  
Richard A. Galbraith ◽  
Ilean Hodgdon ◽  
Michele S. Grimm ◽  
Margaret A. Vizzard

The anorectic cobalt protoporphyrin (CoPP) is known to elicit short-term hypophagia and long-term weight loss through unknown mechanisms in the brains of experimental animals. The goal of this work was to determine 1) if the prolonged duration of action of CoPP is related to its prolonged retention within the brain; and 2) with the use of immunohistochemical detection of Fos, the product of the early-immediate gene c-fos, which cells are activated after exposure to CoPP. These studies were carried out in male rats after intracerebroventricular administration of CoPP, 0.4 μmol/kg body wt, given under light halothane anesthesia. Residence of CoPP in the brain was determined by residual counts in dissected brains of 57CoPP-injected rats. Fos immunoreactivity was mapped in coronal sections of rat brains 4–6 h after injection with CoPP. The results showed that 57CoPP was retained in the hypothalamus preferentially compared with the cortex of the brain and could be detected in the hypothalamus for in excess of 5 wk. Fos activation was increased by CoPP, detected predominantly in neuronal rather than glial cells, and was markedly more robust in the hypothalamus than in other brain areas. Thus CoPP remains in the hypothalamus for prolonged periods and activates Fos expression in the hypothalamus.


1997 ◽  
Vol 24 ◽  
pp. 331-337 ◽  
Author(s):  
Luke Copland ◽  
Jon Harbor ◽  
Marie Minner ◽  
Martin Sharp

A series of boreholes were drilled with high-pressure hot water across a section of Haut Glacier d’Arolla, Switzerland, in summer 1995. Twenty-three of the boreholes were profiled with a digital inclinometer soon aller drilling, and 14 were re-profiled up to 6 weeks later to determine changes in the longitudinal shape of boreholes with time. In addition to the main surveys, three boreholes were surveyed 14 times each to assess the accuracy and reproducibility of inclinometry measurements. These repeat surveys suggest that caution is needed in the interpretation of short-term borehole displacement measurements, and that the reoccupation of boreholes from one year to the next may be a better way to determine patterns of internal deformation and basal sliding. The annual scale may also have advantages in providing more long-term insight into glaciological processes than short term (single season) measurements.


SIMULATION ◽  
1964 ◽  
Vol 3 (6) ◽  
pp. 46-51
Author(s):  
W. Ross Adey ◽  
N.V. Findler

It is attempted in this paper to give a mathematical description of the short-term memory. Instead of using the microscopic properties of individual neu rons, such as the number of interconnections, neuron density, threshold value, etc., the cerebral cortex is regarded as a "neuron gas" that is a vast conglomer ate of neurons with statistically distributed charac teristics. Stimuli from the environment cause the receptor neurons to emit virtual electromagnetic waves into the brain. A self-optimizing process of the brain tis sue is here described by which the useful, informa tion-carrying energy reaching the long-term memory tends to maximum. It is emphasized that in the following a brain model is described and the physical processes in volved may have no direct equivalent in reality.


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