[Death on the operating table and death in the early post-operative period : recommendations of forensic pathologists].

PubMed

Wolff-Maras, R; Klintschar, M

2012-07-01

Death during an operation represents a severe event for physicians and family of the deceased. A further difficulty arises when certifying the cause and manner of death because medical staff are often afraid that they will incriminate themselves when declaring an unnatural death or an unclear manner of death but are also afraid to issue a false statement by declaring a natural death. In such cases of mors in tabula it is recommended to declare an unclear manner of death because this leads to police investigations and in the majority of the cases to exoneration of the medical staff.

Belgian modified classification of Maastricht for donors after circulatory death.

PubMed

Evrard, P

2014-11-01

"Non-heart-beating donors," or, in a more recent and international definition, "donors after circulatory death," are a potential and additional group of deceased persons who are able to add organs to the pool. A new classification is proposed on the basis of the result of a consensus of experts issued from all Belgian transplant centers. The first level of definition is simple and based on whether the situation is uncontrolled (categories I and II) or controlled (categories III, IV, and V). In category I, the patient is declared "dead on arrival" and, in category II, there is an "unsuccessful resuscitation" whether it occurred out or in the hospital for both situations. Category III is the most usual situation in which the treating physician and family are "awaiting cardiac arrest" to declare the death of the patient. Category IV is always characterized by "cardiac arrest during brain death." The special situation of the Belgian law allowing the euthanasia is elaborated in category V, "euthanasia," and includes patients who grant access to medically assisted circulatory death. Organ donation after euthanasia is allowed under the scope of donation after circulatory death. This classification conserves the skeleton of the Maastricht one, as it is simple and clear, but classifies easily the different donors after circulatory death types by processes for ethical issues and for the non-medical or non-specialized reader interested in the field. This is also an argument for public consideration and trust in the difficult field of organ donation.

Attitude Toward Death, Fear of Being Declared Dead Too Soon, and Donation of Organs After Death.

ERIC Educational Resources Information Center

Hessing, Dick J.; Elffers, Henk

1987-01-01

Describes a study of willingness to donate organs for transplantation after death based on Weyant's cost-benefit model for altruistic behavior. Two death anxieties (the attitude toward death and the fear of being declared dead too soon) were introduced to help explain the discrepancy between attitudes and behavior in the matter of organ donation.…

Declarative and nondeclarative memory: multiple brain systems supporting learning and memory.

PubMed

Squire, L R

1992-01-01

Abstract The topic of multiple forms of memory is considered from a biological point of view. Fact-and-event (declarative, explicit) memory is contrasted with a collection of non conscious (non-declarative, implicit) memory abilities including skills and habits, priming, and simple conditioning. Recent evidence is reviewed indicating that declarative and non declarative forms of memory have different operating characteristics and depend on separate brain systems. A brain-systems framework for understanding memory phenomena is developed in light of lesion studies involving rats, monkeys, and humans, as well as recent studies with normal humans using the divided visual field technique, event-related potentials, and positron emission tomography (PET).

Contributions of Memory Circuits to Language: The Declarative/Procedural Model

ERIC Educational Resources Information Center

Ullman, Michael T.

2004-01-01

The structure of the brain and the nature of evolution suggest that, despite its uniqueness, language likely depends on brain systems that also subserve other functions. The declarative/procedural (DP) model claims that the mental lexicon of memorized word-specific knowledge depends on the largely temporal-lobe substrates of declarative memory,…

Pneumothorax as a Complication of Apnea Testing for Brain Death.

PubMed

Gorton, Lauren Elizabeth; Dhar, Rajat; Woodworth, Lindsey; Anand, Nitin J; Hayes, Benjamin; Ramiro, Joanna Isabelle; Kumar, Abhay

2016-10-01

Pneumothorax is an under-recognized complication of apnea testing performed as part of the neurological determination of death. It may result in hemodynamic instability or even cardiac arrest, compromising ability to declare brain death (BD) and viability of organs for transplantation. We report three cases of pneumothorax with apnea testing (PAT) and review the available literature of this phenomenon. Series of three cases supplemented with a systematic review of literature (including discussion of apnea testing in major brain death guidelines). Two patients were diagnosed with PAT due to immediate hemodynamic compromise, while the third was diagnosed many hours after BD. An additional nine cases of PAT were found in the literature. Information regarding oxygen cannula diameter was available for nine patients (range 2.3-5.3 mm), and flow rate was available for ten patients (mean 11 L/min). Pneumothorax was treated to resolution in the majority of patients (n = 8), although only six completed apnea testing following diagnosis/treatment of pneumothorax and only three patients became organ donors afterward. Review of major BD guidelines showed that although use of low oxygen flow rate (usually ≤ 6 L/min) during apnea testing is suggested, the risk of PAT was explicitly mentioned in just one. Development of PAT may adversely affect the process of BD determination and could limit the opportunity for organ donation. Each institution should have preventive measures in place.

Ethical Issues in the Use of Extracorporeal Membrane Oxygenation in Controlled Donation After Circulatory Determination of Death.

PubMed

Dalle Ave, A L; Shaw, D M; Bernat, J L

2016-08-01

The use of donor extracorporeal membrane oxygenation (ECMO) to improve graft outcomes by some controlled donation after circulatory determination of death (cDCDD) programs raises ethical issues. We reviewed cDCDD protocols using ECMO and the relevant ethics literature to analyze these issues. It is not obvious that ECMO in cDCDD improves graft outcomes. In our opinion, ECMO implemented before death can interfere with end-of-life care and damage bodily integrity. By restoring systemic circulation, ECMO risks invalidating the preceding declaration of death if brain and cardiac perfusion is not adequately excluded because of malfunction or misplacement of the supradiaphragmatic aortic occlusion balloon. The use of ECMO is not compatible with the acronym DCDD because circulation is restored after the determination of death. Because of these deficiencies, we concluded that other techniques are preferable, such as rapid recovery or in situ cold infusion. If ECMO is performed, it requires a specific informed consent and transparency. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Giving Your Last Gift: A Study of the Knowledge, Attitude and Information of Greek Students Regarding Organ Donation.

PubMed

Katsari, Vasiliki; Domeyer, Philip J; Sarafis, Pavlos; Souliotis, Kyriakos

2015-07-02

Organ donation rates in Greece are the lowest in the European Union. Studying and improving young students' awareness may increase organ donation rates. This study aimed to investigate young students' knowledge, attitude and information regarding organ donation and whether they are modified by putative predictors. A 62-item electronic questionnaire was sent to 1451 eligible students aged 18-30 years in 16 Greek public technical schools. Two composite scales (knowledge and attitude) were created. The multivariate statistical analysis included ordinal logistic and linear regression, as appropriate. Only 37.9% of the students knew the correct definition of organ donation, 40.3% knew which organs can be donated, 27.4% were informed about the new Greek legislation, and 83.1% acknowledged the need for better information. Although 60.5% would donate an organ after death, only 16.1% would become living donors. Although 83.1% of the students declared knowing what brain death means, 18.6% believe that a brain-dead person could fully recover and 32.3% are unsure about it. Being a health professional or a blood donor, the parent's educational level, the wish to donate all organs after death, the information from announcements or posters, the fear of organ removal after death without prior consent, the consent for autopsy, the wish for better information, and the misbelief that a brain-dead person could fully recover emerged as important predictors of the knowledge and attitude, regarding organ donation. An important lack of knowledge and misperceptions were noted regarding organ donation. Significant predictors were identified.

Organ Donor Recovery Performed at an Organ Procurement Organization-Based Facility Is an Effective Way to Minimize Organ Recovery Costs and Increase Organ Yield.

PubMed

Doyle, Majella; Subramanian, Vijay; Vachharajani, Neeta; Collins, Kelly; Wellen, Jason R; Stahlschmidt, Emily; Brockmeier, Diane; Coleman, Jason; Kappel, Dean; Chapman, William C

2016-04-01

A new era in organ donation with national redistricting is being proposed. With these proposals, costs of organ acquisition are estimated to more than double. Traditionally, organ recoveries occur in the donor hospital setting, incurring premium hospital expenses. The aim of the study was to determine organ recovery costs and organ yield for donor recoveries performed at an organ procurement organization (OPO) facility. In 2001, we established an OPO facility and in 2008 began transferring the donor expeditiously when brain death was declared. The OPO donor and hospital costs on a per donor basis were calculated. Donation after cardiac death donors cannot be transferred and were included in the hospital cost analysis. From January 2009 to December 2014, nine hundred and sixty-three donors originating in our OPO had organs recovered and transplanted. Seven hundred and sixty-six (79.5%) donors were transferred to the OPO facility 8.6 hours (range 0.6 to 23.6 hours) after declaration of brain death. Donor recovery cost was 51% less when donors were transferred to the OPO facility ($16,153 OPO recovery vs $33,161 hospital recovery; p < 0.0001). Organ yield was 27.5% better (3.43 organs) from OPO-recovered donors vs an organ yield of 2.69 from hospital-recovered donors (p < 0.0001). Standard criteria donor organ yield from our OPO was 6% higher than the national average (3.92 vs 3.7 nationally; p = 0.012) and expanded criteria donor organ yield was 18% higher (2.2 vs 1.87 nationally; p = 0.03). An OPO facility for donor organ recovery increases efficiency and organ yield, reduces costs, and minimizes organ acquisition charge. As we face new considerations with broader sharing, increased efficiencies, cost. and organ use should be considered. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

When organ donation from living donors serves as the main source of organ procurement: a critical examination of the ethical and legal challenges to Turkey's recent efforts to overcome organ shortage.

PubMed

Sert, G; Guven, T; Gorkey, S

2013-01-01

Despite the fact that Turkey has implemented a number of legislative and regulatory efforts to increase cadaveric donations, live donors still serve as the main source of organ procurement in this country. To address this problem, Turkey's regulatory authorities have sought to increase the number of brain death declarations. A new regulation issued in 2012 repeats the criteria for brain death that were first issued in 1993. This paper argues that these efforts are far from adequate owing to a number of complicated, ethical, and legal challenges that must be addressed to increase cadaveric organ donations. After examining these factors, which are completely neglected in current policies, we conclude that Turkey needs a realistic ethically justifiable organ procurement policy that must be supported by a framework of patient rights to implement the concept of patient autonomy and respect for human dignity in health care services as the primary goal. Copyright © 2013 Elsevier Inc. All rights reserved.

Patterns of Brain-Electrical Activity during Declarative Memory Performance in 10-Month-Old Infants

ERIC Educational Resources Information Center

Morasch, Katherine C.; Bell, Martha Ann

2009-01-01

This study of infant declarative memory concurrently examined brain-electrical activity and deferred imitation performance in 10-month-old infants. Continuous electroencephalogram (EEG) measures were collected throughout the activity-matched baseline, encoding (modeling) and retrieval (delayed test) phases of a within-subjects deferred imitation…

Ethical controversies in organ donation after circulatory death.

PubMed

2013-05-01

The persistent mismatch between the supply of and need for transplantable organs has led to efforts to increase the supply, including controlled donation after circulatory death (DCD). Controlled DCD involves organ recovery after the planned withdrawal of life-sustaining treatment and the declaration of death according to the cardiorespiratory criteria. Two central ethical issues in DCD are when organ recovery can begin and how to manage conflicts of interests. The "dead donor rule" should be maintained, and donors in cases of DCD should only be declared dead after the permanent cessation of circulatory function. Permanence is generally established by a 2- to 5-minute waiting period. Given ongoing controversy over whether the cessation must also be irreversible, physicians should not be required to participate in DCD. Because the preparation for organ recovery in DCD begins before the declaration of death, there are potential conflicts between the donor's and recipient's interests. These conflicts can be managed in a variety of ways, including informed consent and separating the various participants' roles. For example, informed consent should be sought for premortem interventions to improve organ viability, and organ procurement organization personnel and members of the transplant team should not be involved in the discontinuation of life-sustaining treatment or the declaration of death. It is also important to emphasize that potential donors in cases of DCD should receive integrated interdisciplinary palliative care, including sedation and analgesia.

29 CFR 18.804 - Hearsay exceptions; declarant unavailable.

Code of Federal Regulations, 2014 CFR

2014-07-01

... present or to testify at the hearing because of death or then existing physical or mental illness or... concerning the declarant's own birth, adoption, marriage, divorce, legitimacy, relationship by blood...

29 CFR 18.804 - Hearsay exceptions; declarant unavailable.

Code of Federal Regulations, 2012 CFR

2012-07-01

... present or to testify at the hearing because of death or then existing physical or mental illness or... concerning the declarant's own birth, adoption, marriage, divorce, legitimacy, relationship by blood...

29 CFR 18.804 - Hearsay exceptions; declarant unavailable.

Code of Federal Regulations, 2011 CFR

2011-07-01

... present or to testify at the hearing because of death or then existing physical or mental illness or... concerning the declarant's own birth, adoption, marriage, divorce, legitimacy, relationship by blood...

29 CFR 18.804 - Hearsay exceptions; declarant unavailable.

Code of Federal Regulations, 2013 CFR

2013-07-01

... present or to testify at the hearing because of death or then existing physical or mental illness or... concerning the declarant's own birth, adoption, marriage, divorce, legitimacy, relationship by blood...

Early metabolic/cellular-level resuscitation following terminal brain stem herniation: implications for organ transplantation.

PubMed

Arbour, Richard B

2013-01-01

Patients with terminal brain stem herniation experience global physiological consequences and represent a challenging population in critical care practice as a result of multiple factors. The first factor is severe depression of consciousness, with resulting compromise in airway stability and lung ventilation. Second, with increasing severity of brain trauma, progressive brain edema, mass effect, herniation syndromes, and subsequent distortion/displacement of the brain stem follow. Third, with progression of intracranial pathophysiology to terminal brain stem herniation, multisystem consequences occur, including dysfunction of the hypothalamic-pituitary axis, depletion of stress hormones, and decreased thyroid hormone bioavailability as well as biphasic cardiovascular state. Cardiovascular dysfunction in phase 1 is a hyperdynamic and hypertensive state characterized by elevated systemic vascular resistance and cardiac contractility. Cardiovascular dysfunction in phase 2 is a hypotensive state characterized by decreased systemic vascular resistance and tissue perfusion. Rapid changes along the continuum of hyperperfusion versus hypoperfusion increase risk of end-organ damage, specifically pulmonary dysfunction from hemodynamic stress and high-flow states as well as ischemic changes consequent to low-flow states. A pronounced inflammatory state occurs, affecting pulmonary function and gas exchange and contributing to hemodynamic instability as a result of additional vasodilatation. Coagulopathy also occurs as a result of consumption of clotting factors as well as dilution of clotting factors and platelets consequent to aggressive crystalloid administration. Each consequence of terminal brain stem injury complicates clinical management within this patient demographic. In general, these multisystem consequences are managed with mechanism-based interventions within the context of caring for the donor's organs (liver, kidneys, heart, etc.) after death by neurological criteria. These processes begin far earlier in the continuum of injury, at the moment of terminal brain stem herniation. As such, aggressive, mechanism-based care, including hormonal replacement therapy, becomes clinically appropriate before formal brain death declaration to support cardiopulmonary stability following terminal brain stem herniation.

Knowledge and Attitudes Toward Organ Donation in Health Care Undergraduate Students in Italy.

PubMed

Fontana, F; Massari, M; Giovannini, L; Alfano, G; Cappelli, G

2017-11-01

The number of organ donors in Italy is increasing, but with still disappointing living donation activity and relatively frequent objection by potential deceased donors' relatives to organ recovery. Few studies have assessed health care students' knowledge and attitude on donation. We administered a questionnaire to medical (MS) and nursing students (NS) at University of Modena and Reggio Emilia, Italy, and 749 students (406 MS and 343 NS) completed the questionnaire. Although 95% of students were in favor of donation, only 21.9% of NS and 24.9% of MS were registered as donors. One quarter of students reported family disagreement. MS appeared more confident with personnel involved in donation. Overall, 60% of students knew the term donation after brain death but only 40% were aware of the criteria used to define it. Barely 27.1% of NS and 15.3% of MS believed they had received sufficient information in lessons. Backward logistic regression demonstrated that students whose families agree with them and who knew the definition of donation after brain death were more likely to express the disposition of registering, and those who showed distrust in the declaration of brain death were half as likely to register as donors. Students expressed a lack of knowledge, controversial attitudes on donation, and strong need for education; increased awareness may help increase donation rates. The majority of educational institutions in Italy do not directly address training on organ donation and transplantation for health care students; an integrated curriculum favoring interpersonal discussion including practical aspects is urgently required. Copyright © 2017 Elsevier Inc. All rights reserved.

Death and consciousness--an overview of the mental and cognitive experience of death.

PubMed

Parnia, Sam

2014-11-01

Advances in resuscitation science have indicated that, contrary to perception, death by cardiorespiratory criteria can no longer be considered a specific moment but rather a potentially reversible process that occurs after any severe illness or accident causes the heart, lungs, and brain to stop functioning. The resultant loss of vital signs of life (and life processes) is used to declare a specific time of death by physicians globally. When medical attempts are made to reverse this process, it is commonly referred to as cardiac arrest; however, when these attempts do not succeed or when attempts are not made, it is called death by cardiorespiratory criteria. Thus, biologically speaking, cardiac arrest and death by cardiorespiratory criteria are synonymous. While resuscitation science has provided novel opportunities to reverse death by cardiorespiratory criteria and treat the potentially devastating consequences of the resultant postresuscitation syndrome, it has also inadvertently provided intriguing insights into the likely mental and cognitive experience of death. Recollections reported by millions of people in relation to death, so-called out-of-body experiences (OBEs) or near-death experiences (NDEs), are often-discussed phenomena that are frequently considered hallucinatory or illusory in nature; however, objective studies on these experiences are limited. To date, many consistent themes corresponding to the likely experience of death have emerged, and studies have indicated that the scientifically imprecise terms of NDE and OBE may not be sufficient to describe the actual experience of death. While much remains to be discovered, the recalled experience surrounding death merits a genuine scientific investigation without prejudice. © 2014 New York Academy of Sciences.

Palliative care consultation in the process of organ donation after cardiac death.

PubMed

Kelso, Catherine McVearry; Lyckholm, Laurie J; Coyne, Patrick J; Smith, Thomas J

2007-02-01

Palliative care consultation has been demonstrated to be useful in many situations in which expert symptom management, communication around sensitive issues, and family support may serve to enhance or improve care. The process of organ donation is an example of this concept, specifically the process of donation after cardiac death (DCD). DCD allows patients with severe, irreversible brain injuries that do not meet standard criteria for brain death to donate organs when death is declared by cardiopulmonary criteria. The DCD method of donation has been deemed an ethically appropriate means of organ donation and is supported by the organ procurement and medical communities, as well as the public. The palliative care (PC) team can make a significant contribution to the care of the patient and family in the organ donation process. In this paper we describe the controlled DCD process at one institution that utilizes the PC team to provide expert end-of-life care, including comprehensive medical management and family support. PC skills and principles applicable to the DCD process include communication, coordination of care, and skillful ventilator withdrawal. If death occurs within 90 minutes of withdrawal of life support, organs may be successfully recovered for transplantation. If the patient survives longer than 90 minutes, his or her care continues to be provided by the PC team. Palliative care can contribute to standardizing quality end-of-life care practices in the DCD process and provide education for involved personnel. Further experience, research and national discussions will be helpful in refining these practices, to make this difficult and challenging experience as gentle and supportive as possible for the courageous families who participate in this process.

Are the neural substrates of memory the final common pathway in posttraumatic stress disorder (PTSD)?

PubMed

Elzinga, B M; Bremner, J D

2002-06-01

A model for the posttraumatic stress disorder (PTSD) as a disorder of memory is presented drawing both on psychological and neurobiological data. Evidence on intrusive memories and deficits in declarative memory function in PTSD-patients is reviewed in relation to three brain areas that are involved in memory functioning and the stress response: the hippocampus, amygdala, and the prefrontal cortex. Neurobiological studies have shown that the noradrenergic stress-system is involved in enhanced encoding of emotional memories, sensitization, and fear conditioning, by way of its effects on the amygdala. Chronic stress also affects the hippocampus, a brain area involved in declarative memories, suggesting that hippocampal dysfunction may partly account for the deficits in declarative memory in PTSD-patients. Deficits in the medial prefrontal cortex, a structure that normally inhibits the amygdala, may further enhance the effects of the amygdala, thereby increasing the frequency and intensity of the traumatic memories. Thus, by way of its influence on these brain structures, exposure to severe stress may simultaneously result in strong emotional reactions and in difficulties to recall the emotional event. This model is also relevant for understanding the distinction between declarative and non-declarative memory-functions in processing trauma-related information in PTSD. Implications of our model are reviewed.

Are the neural substrates of memory the final common pathway in posttraumatic stress disorder (PTSD)?

PubMed Central

Elzinga, B.M.; Bremner, J.D.

2017-01-01

A model for the posttraumatic stress disorder (PTSD) as a disorder of memory is presented drawing both on psychological and neurobiological data. Evidence on intrusive memories and deficits in declarative memory function in PTSD-patients is reviewed in relation to three brain areas that are involved in memory functioning and the stress response: the hippocampus, amygdala, and the prefrontal cortex. Neurobiological studies have shown that the noradrenergic stress-system is involved in enhanced encoding of emotional memories, sensitization, and fear conditioning, by way of its effects on the amygdala. Chronic stress also affects the hippocampus, a brain area involved in declarative memories, suggesting that hippocampal dysfunction may partly account for the deficits in declarative memory in PTSD-patients. Deficits in the medial prefrontal cortex, a structure that normally inhibits the amygdala, may further enhance the effects of the amygdala, thereby increasing the frequency and intensity of the traumatic memories. Thus, by way of its influence on these brain structures, exposure to severe stress may simultaneously result in strong emotional reactions and in difficulties to recall the emotional event. This model is also relevant for understanding the distinction between declarative and non-declarative memory-functions in processing trauma-related information in PTSD. Implications of our model are reviewed. PMID:12113915

The role of sleep in human declarative memory consolidation.

PubMed

Alger, Sara E; Chambers, Alexis M; Cunningham, Tony; Payne, Jessica D

2015-01-01

Through a variety of methods, researchers have begun unraveling the mystery of why humans spend one-third of their lives asleep. Though sleep likely serves multiple functions, it has become clear that the sleeping brain offers an ideal environment for solidifying newly learned information in the brain. Sleep , which comprises a complex collection of brain states, supports the consolidation of many different types of information. It not only promotes learning and memory stabilization, but also memory reorganization that can lead to various forms of insightful behavior. As this chapter will describe, research provides ample support for these crucial cognitive functions of sleep . Focusing on the declarative memory system in humans, we review the literature regarding the benefits of sleep for both neutral and emotionally salient declarative memory. Finally, we discuss the literature regarding the impact of sleep on emotion regulation.

Pope John Paul II and the neurological standard for the determination of death: A critical analysis of his address to the Transplantation Society

PubMed Central

2017-01-01

The introduction of the “brain death” criterion constitutes a significant paradigm shift in the determination of death. The perception of the public at large is that the Catholic Church has formally endorsed this neurological standard. However, a critical reading of the only magisterial document on this subject, Pope John Paul II’s 2000 address, shows that the pope’s acceptance of the neurological criterion is conditional in that it entails a twofold requirement. It requires that certain medical presuppositions of the neurological standard are fulfilled, and that its philosophical premise coheres with the Church’s teaching on the body-soul union. This article demonstrates that the medical presuppositions are not fulfilled, and that the doctrine of the brain as the central somatic integrator of the body does not cohere either with the current holistic understanding of the human organism or with the Church’s Thomistic doctrine of the soul as the form of the body. Summary The concept of “brain death” (the neurological basis for legally declaring a person dead) has caused much controversy since its inception. In this regard, it has been generally perceived that the Catholic Church has officially affirmed the “brain death” criterion. The address of Pope John Paul II in 2000 shows, however, that he only gave it a conditional acceptance, one which requires that several medical and philosophical presuppositions of the “brain death” standard be fulfilled. This article demonstrates, taking into consideration both the empirical evidence and the Church’s Thomistic anthropology, that the presuppositions have not been fulfilled. PMID:28698708

Declarative and Non-declarative Memory Consolidation in Children with Sleep Disorder.

PubMed

Csábi, Eszter; Benedek, Pálma; Janacsek, Karolina; Zavecz, Zsófia; Katona, Gábor; Nemeth, Dezso

2015-01-01

Healthy sleep is essential in children's cognitive, behavioral, and emotional development. However, remarkably little is known about the influence of sleep disorders on different memory processes in childhood. Such data could give us a deeper insight into the effect of sleep on the developing brain and memory functions and how the relationship between sleep and memory changes from childhood to adulthood. In the present study we examined the effect of sleep disorder on declarative and non-declarative memory consolidation by testing children with sleep-disordered breathing (SDB) which is characterized by disrupted sleep structure. We used a story recall task to measure declarative memory and Alternating Serial Reaction time (ASRT) task to assess non-declarative memory. This task enables us to measure two aspects of non-declarative memory, namely general motor skill learning and sequence-specific learning. There were two sessions: a learning phase and a testing phase, separated by a 12 h offline period with sleep. Our data showed that children with SDB exhibited a generally lower declarative memory performance both in the learning and testing phase; however, both the SDB and control groups exhibited retention of the previously recalled items after the offline period. Here we showed intact non-declarative consolidation in SDB group in both sequence-specific and general motor skill. These findings suggest that sleep disorders in childhood have a differential effect on different memory processes (online vs. offline) and give us insight into how sleep disturbances affects developing brain.

Declarative and Non-declarative Memory Consolidation in Children with Sleep Disorder

PubMed Central

Csábi, Eszter; Benedek, Pálma; Janacsek, Karolina; Zavecz, Zsófia; Katona, Gábor; Nemeth, Dezso

2016-01-01

Healthy sleep is essential in children’s cognitive, behavioral, and emotional development. However, remarkably little is known about the influence of sleep disorders on different memory processes in childhood. Such data could give us a deeper insight into the effect of sleep on the developing brain and memory functions and how the relationship between sleep and memory changes from childhood to adulthood. In the present study we examined the effect of sleep disorder on declarative and non-declarative memory consolidation by testing children with sleep-disordered breathing (SDB) which is characterized by disrupted sleep structure. We used a story recall task to measure declarative memory and Alternating Serial Reaction time (ASRT) task to assess non-declarative memory. This task enables us to measure two aspects of non-declarative memory, namely general motor skill learning and sequence-specific learning. There were two sessions: a learning phase and a testing phase, separated by a 12 h offline period with sleep. Our data showed that children with SDB exhibited a generally lower declarative memory performance both in the learning and testing phase; however, both the SDB and control groups exhibited retention of the previously recalled items after the offline period. Here we showed intact non-declarative consolidation in SDB group in both sequence-specific and general motor skill. These findings suggest that sleep disorders in childhood have a differential effect on different memory processes (online vs. offline) and give us insight into how sleep disturbances affects developing brain. PMID:26793090

Organ donation, awareness, attitudes and beliefs among post graduate medical students.

PubMed

Bapat, Usha; Kedlaya, Prashanth G

2010-01-01

Organ transplantation is the most preferred treatment modality for patients with end-stage organ disease. There is an inadequate supply of cadaver organs commensurate with need. Health-care professionals are the critical link in augmenting public awareness about organ donation. Their attitudes and beliefs can influence the public opinion. This study aims at understanding the awareness, attitudes, and beliefs among the medical postgraduate students. A total of 123 post-graduates of a medical college hospital in South India participated in the study. A specially de-signed questionnaire was used in assessment. Data were statistically analyzed using SPSS Windows version 10.0. The mean age of the postgraduate students was 28.32 + or - 3.5 years, 54% were males, 62% belonged to Christian religion, 69% were single, 77% were from nuclear families, 87% had urban background, and 54% were from upper socioeconomic strata. About 97% said they were aware of organ donation through media, 23 understood the concept of "cadaver" as "brain-death" and 93% were able to distinguish between brain-death and persistent vegetative state. Eighty-nine percent wished to donate their organs, 77% did not believe in body disfigurement and 87% did not believe in rebirth without the donated organs, if they pledged their organs. Sixty-nine percent were willing to donate the organs of their family members. Eighty percent were willing to receive organs from family and cadaver, 40% were willing to donate a child's organs, 95% did not believe that organ donation is against their religion, 87% disagreed with the notion that doctors would not impart adequate care if they were pledged organ donors and 79% agreed that doctors would not declare death prematurely, if they had pledged their organs during life. There was a statistically significant correlation between attitudes, beliefs and demographics. In conclusion, the concept of brain-death was clearly understood by only a small number of medical postgraduate students. They however, had positive attitudes and beliefs towards organ donation.

Implications of the Declarative/Procedural Model for Improving Second Language Learning: The Role of Memory Enhancement Techniques

ERIC Educational Resources Information Center

Ullman, Michael T.; Lovelett, Jarrett T.

2018-01-01

The declarative/procedural (DP) model posits that the learning, storage, and use of language critically depend on two learning and memory systems in the brain: declarative memory and procedural memory. Thus, on the basis of independent research on the memory systems, the model can generate specific and often novel predictions for language. Till…

A network approach for modulating memory processes via direct and indirect brain stimulation: Toward a causal approach for the neural basis of memory.

PubMed

Kim, Kamin; Ekstrom, Arne D; Tandon, Nitin

2016-10-01

Electrical stimulation of the brain is a unique tool to perturb endogenous neural signals, allowing us to evaluate the necessity of given neural processes to cognitive processing. An important issue, gaining increasing interest in the literature, is whether and how stimulation can be employed to selectively improve or disrupt declarative memory processes. Here, we provide a comprehensive review of both invasive and non-invasive stimulation studies aimed at modulating memory performance. The majority of past studies suggest that invasive stimulation of the hippocampus impairs memory performance; similarly, most non-invasive studies show that disrupting frontal or parietal regions also impairs memory performance, suggesting that these regions also play necessary roles in declarative memory. On the other hand, a handful of both invasive and non-invasive studies have also suggested modest improvements in memory performance following stimulation. These studies typically target brain regions connected to the hippocampus or other memory "hubs," which may affect endogenous activity in connected areas like the hippocampus, suggesting that to augment declarative memory, altering the broader endogenous memory network activity is critical. Together, studies reporting memory improvements/impairments are consistent with the idea that a network of distinct brain "hubs" may be crucial for successful memory encoding and retrieval rather than a single primary hub such as the hippocampus. Thus, it is important to consider neurostimulation from the network perspective, rather than from a purely localizationalist viewpoint. We conclude by proposing a novel approach to neurostimulation for declarative memory modulation that aims to facilitate interactions between multiple brain "nodes" underlying memory rather than considering individual brain regions in isolation. Copyright © 2016. Published by Elsevier Inc.

New European initiatives in colorectal cancer screening: Budapest Declaration. Official appeal during the Hungarian Presidency of the Council of the European Union under the Auspices of the United European Gastroenterology Federation, the European Association for Gastroenterology and Endoscopy and the Hungarian Society of Gastroenterology.

PubMed

Wittmann, Tibor; Stockbrugger, Reinhold; Herszényi, László; Jonkers, Daisy; Molnár, Béla; Saurin, Jean-Christophe; Regula, Jaroslaw; Malesci, Alberto; Laghi, Luigi; Pintér, Tamás; Teleky, Béla; Dítě, Petr; Tulassay, Zsolt

2012-01-01

Colorectal cancer (CRC) is the second most common newly diagnosed cancer and the second most common cause of death in the European Union (EU). CRC is an enormous health and economic burden. Early detection and prevention have the possibility of reducing this burden significantly. Many cancer-associated deaths can be avoided through early detection by high-quality colorectal screening programs followed by appropriate treatment. Under the auspices of the United European Gastroenterology Federation (UEGF), the European Association for Gastroenterology and Endoscopy, the Hungarian Society of Gastroenterology and the Hungarian College of Gastroenterology, the 'Budapest Declaration' (2011) was an accepted official scientific program during the Hungarian Presidency of the Council of the European Union. The Budapest Declaration follows the Munich Declaration (2001), the Brussels Declaration (2007), the Transatlantic Declaration (2009), the Barcelona Declaration (2010), the written declaration of CRC screening, a joint initiative with European Parliamentarians coordinated by the UEGF, and finally, the 'European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis'. The 'Budapest Declaration' together with previous declarations aims to urge the national and supranational healthcare decision makers to launch new Europe-wide initiatives to establish high-quality CRC programs to achieve optimal efficiency in CRC screening. In case of implementation of the proposals, actions and conditions recommended, we can achieve that one of the basic principles of the EU - the chance of equal access - be realized in member states with respect to the prevention of CRC and reduction of cancer-related mortality. To better achieve this goal, we propose to establish an UEGF joint committee, with one participant representing each EU member state to coordinate and supervise the implementation of CRC screening. Copyright © 2012 S. Karger AG, Basel.

Subthalamic stimulation differentially modulates declarative and nondeclarative memory.

PubMed

Hälbig, Thomas D; Gruber, Doreen; Kopp, Ute A; Scherer, Peter; Schneider, Gerd-Helge; Trottenberg, Thomas; Arnold, Guy; Kupsch, Andreas

2004-03-01

Declarative memory has been reported to rely on the medial temporal lobe system, whereas non-declarative memory depends on basal ganglia structures. We investigated the functional role of the subthalamic nucleus (STN), a structure closely connected with the basal ganglia for both types of memory. Via deep brain high frequency stimulation (DBS) we manipulated neural activity of the STN in humans. We found that DBS-STN differentially modulated memory performance: declarative memory was impaired, whereas non-declarative memory was improved in the presence of STN-DBS indicating a specific role of the STN in the activation of memory systems. Copyright 2004 Lippincott Williams & Wilkins

[Anterograde declarative memory and its models].

PubMed

Barbeau, E-J; Puel, M; Pariente, J

2010-01-01

Patient H.M.'s recent death provides the opportunity to highlight the importance of his contribution to a better understanding of the anterograde amnesic syndrome. The thorough study of this patient over five decades largely contributed to shape the unitary model of declarative memory. This model holds that declarative memory is a single system that cannot be fractionated into subcomponents. As a system, it depends mainly on medial temporal lobes structures. The objective of this review is to present the main characteristics of different modular models that have been proposed as alternatives to the unitary model. It is also an opportunity to present different patients, who, although less famous than H.M., helped make signification contribution to the field of memory. The characteristics of the five main modular models are presented, including the most recent one (the perceptual-mnemonic model). The differences as well as how these models converge are highlighted. Different possibilities that could help reconcile unitary and modular approaches are considered. Although modular models differ significantly in many aspects, all converge to the notion that memory for single items and semantic memory could be dissociated from memory for complex material and context-rich episodes. In addition, these models converge concerning the involvement of critical brain structures for these stages: Item and semantic memory, as well as familiarity, are thought to largely depend on anterior subhippocampal areas, while relational, context-rich memory and recollective experiences are thought to largely depend on the hippocampal formation. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Neonatal and Pediatric Organ Donation: Ethical Perspectives and Implications for Policy.

PubMed

Sarnaik, Ajit A

2015-01-01

The lifesaving processes of organ donation and transplantation in neonatology and pediatrics carry important ethical considerations. The medical community must balance the principles of autonomy, non-maleficence, beneficence, and justice to ensure the best interest of the potential donor and to provide equitable benefit to society. Accordingly, the US Organ Procurement and Transplantation Network (OPTN) has established procedures for the ethical allocation of organs depending on several donor-specific and recipient-specific factors. To maximize the availability of transplantable organs and opportunities for dying patients and families to donate, the US government has mandated that hospitals refer potential donors in a timely manner. Expedient investigation and diagnosis of brain death where applicable are also crucial, especially in neonates. Empowering trained individuals from organ procurement organizations to discuss organ donation with families has also increased rates of consent. Other efforts to increase organ supply include recovery from donors who die by circulatory criteria (DCDD) in addition to donation after brain death (DBD), and from neonates born with immediately lethal conditions such as anencephaly. Ethical considerations in DCDD compared to DBD include a potential conflict of interest between the dying patient and others who may benefit from the organs, and the precision of the declaration of death of the donor. Most clinicians and ethicists believe in the appropriateness of the Dead Donor Rule, which states that vital organs should only be recovered from people who have died. The medical community can maximize the interests of organ donors and recipients by observing the Dead Donor Rule and acknowledging the ethical considerations in organ donation.

Neonatal and Pediatric Organ Donation: Ethical Perspectives and Implications for Policy

PubMed Central

Sarnaik, Ajit A.

2015-01-01

The lifesaving processes of organ donation and transplantation in neonatology and pediatrics carry important ethical considerations. The medical community must balance the principles of autonomy, non-maleficence, beneficence, and justice to ensure the best interest of the potential donor and to provide equitable benefit to society. Accordingly, the US Organ Procurement and Transplantation Network (OPTN) has established procedures for the ethical allocation of organs depending on several donor-specific and recipient-specific factors. To maximize the availability of transplantable organs and opportunities for dying patients and families to donate, the US government has mandated that hospitals refer potential donors in a timely manner. Expedient investigation and diagnosis of brain death where applicable are also crucial, especially in neonates. Empowering trained individuals from organ procurement organizations to discuss organ donation with families has also increased rates of consent. Other efforts to increase organ supply include recovery from donors who die by circulatory criteria (DCDD) in addition to donation after brain death (DBD), and from neonates born with immediately lethal conditions such as anencephaly. Ethical considerations in DCDD compared to DBD include a potential conflict of interest between the dying patient and others who may benefit from the organs, and the precision of the declaration of death of the donor. Most clinicians and ethicists believe in the appropriateness of the Dead Donor Rule, which states that vital organs should only be recovered from people who have died. The medical community can maximize the interests of organ donors and recipients by observing the Dead Donor Rule and acknowledging the ethical considerations in organ donation. PMID:26636051

Improving donation outcomes: hospital development and the Rapid Assessment of Hospital Procurement Barriers in Donation.

PubMed

Siminoff, Laura A; Traino, Heather M

2009-06-01

Deficiencies in the donation process continue to contribute to the shortage of organs available for transplant. Continuous quality improvement of hospitals' donation processes is needed to identify and correct the problems. To test the Rapid Assessment of Hospital Procurement Barriers in Donation (RAPiD), a direct observation technique with a focused ethnographic strategy, for assessing hospitals' donation processes and identifying areas in need of continuous quality improvement interventions. A pre-post assessment of hospitals' barriers to patient identification and referral, and family consent to donation. Seventeen hospitals within the catchment area of a Northeastern organ procurement organization were assessed by using the RAPiD method. Hospital administrators, health care providers, and staff (N = 537) were interviewed as part of the assessments. Interventions, including on-site training and education, and the use of in-house coordinators, were specifically tailored to each hospital's unique set of barriers to donation. The interventions were delivered to the hospitals in the form of recommendations. The participating organ procurement organization was responsible for implementation of the interventions. The RAPiD hospital evaluations revealed gaps in respondents' knowledge of organ donation, brain death, and referral criteria; a reluctance to declare brain death; and a rocky relationship between the hospitals and the organ procurement organization. As a result of the interventions, 9 hospitals' environments for organ donation improved, 7 showed no change, and 1 was worse.

Brain-Based Learning. Research Brief

ERIC Educational Resources Information Center

Walker, Karen

2005-01-01

What does brain-based research say about how adolescents learn? The 1990s was declared as the Decade of the Brain by President Bush and Congress. With the advancement of MRIs (Magnetic Resonance Imagining) and PET (positron emission tomography) scans, it has become much easier to study live healthy brains. As a result, the concept of…

28 CFR Appendix A to Part 74 - Declarations of Eligibility by Persons Identified by the Office of Redress Administration and...

Code of Federal Regulations, 2014 CFR

2014-07-01

... penalty of perjury that the foregoing is true and correct. Signature Date Privacy Act Statement: The... 1001). I declare under penalty of perjury that the foregoing is true and correct. Signature Date.... DOCUMENTATION: I. One Document as Evidence of the Deceased Eligible Individual's Death 1. A certified copy or...

28 CFR Appendix A to Part 74 - Declarations of Eligibility by Persons Identified by the Office of Redress Administration and...

Code of Federal Regulations, 2013 CFR

2013-07-01

... penalty of perjury that the foregoing is true and correct. Signature Date Privacy Act Statement: The... 1001). I declare under penalty of perjury that the foregoing is true and correct. Signature Date.... DOCUMENTATION: I. One Document as Evidence of the Deceased Eligible Individual's Death 1. A certified copy or...

28 CFR Appendix A to Part 74 - Declarations of Eligibility by Persons Identified by the Office of Redress Administration and...

Code of Federal Regulations, 2011 CFR

2011-07-01

... penalty of perjury that the foregoing is true and correct. Signature Date Privacy Act Statement: The... 1001). I declare under penalty of perjury that the foregoing is true and correct. Signature Date.... DOCUMENTATION: I. One Document as Evidence of the Deceased Eligible Individual's Death 1. A certified copy or...

28 CFR Appendix A to Part 74 - Declarations of Eligibility by Persons Identified by the Office of Redress Administration and...

Code of Federal Regulations, 2012 CFR

2012-07-01

... penalty of perjury that the foregoing is true and correct. Signature Date Privacy Act Statement: The... 1001). I declare under penalty of perjury that the foregoing is true and correct. Signature Date.... DOCUMENTATION: I. One Document as Evidence of the Deceased Eligible Individual's Death 1. A certified copy or...

Working, declarative and procedural memory in specific language impairment

PubMed Central

Lum, Jarrad A.G.; Conti-Ramsden, Gina; Page, Debra; Ullman, Michael T.

2012-01-01

According to the Procedural Deficit Hypothesis (PDH), abnormalities of brain structures underlying procedural memory largely explain the language deficits in children with specific language impairment (SLI). These abnormalities are posited to result in core deficits of procedural memory, which in turn explain the grammar problems in the disorder. The abnormalities are also likely to lead to problems with other, non-procedural functions, such as working memory, that rely at least partly on the affected brain structures. In contrast, declarative memory is expected to remain largely intact, and should play an important compensatory role for grammar. These claims were tested by examining measures of working, declarative and procedural memory in 51 children with SLI and 51 matched typically-developing (TD) children (mean age 10). Working memory was assessed with the Working Memory Test Battery for Children, declarative memory with the Children’s Memory Scale, and procedural memory with a visuo-spatial Serial Reaction Time task. As compared to the TD children, the children with SLI were impaired at procedural memory, even when holding working memory constant. In contrast, they were spared at declarative memory for visual information, and at declarative memory in the verbal domain after controlling for working memory and language. Visuo-spatial short-term memory was intact, whereas verbal working memory was impaired, even when language deficits were held constant. Correlation analyses showed neither visuo-spatial nor verbal working memory was associated with either lexical or grammatical abilities in either the SLI or TD children. Declarative memory correlated with lexical abilities in both groups of children. Finally, grammatical abilities were associated with procedural memory in the TD children, but with declarative memory in the children with SLI. These findings replicate and extend previous studies of working, declarative and procedural memory in SLI. Overall, we suggest that the evidence largely supports the predictions of the PDH. PMID:21774923

A Response to the Legitimacy of Brain Death in Islam.

PubMed

Rady, Mohamed Y; Verheijde, Joseph L

2016-08-01

Brain death is a novel construct of death for the procurement of transplantable organs. Many authoritative Islamic organizations and governments have endorsed brain death as true death for organ donation. Many commentators have reiterated the misconception that the Quranic text does not define death. We respond by clarifying: (1) the Quran does define death as biologic disintegration and clearly distinguishes it from the dying process, (2) brain death belongs scientifically within the spectrum of neurologic disorders of consciousness and should not be confused with death, and (3) religious and legal discord about brain death has grown in jurisdictions worldwide. We urge for public transparency and truthfulness about brain death and the accommodation and respect of religious objection to the determination of death by neurologic criteria.

Knowledge acquisition is governed by striatal prediction errors.

PubMed

Pine, Alex; Sadeh, Noa; Ben-Yakov, Aya; Dudai, Yadin; Mendelsohn, Avi

2018-04-26

Discrepancies between expectations and outcomes, or prediction errors, are central to trial-and-error learning based on reward and punishment, and their neurobiological basis is well characterized. It is not known, however, whether the same principles apply to declarative memory systems, such as those supporting semantic learning. Here, we demonstrate with fMRI that the brain parametrically encodes the degree to which new factual information violates expectations based on prior knowledge and beliefs-most prominently in the ventral striatum, and cortical regions supporting declarative memory encoding. These semantic prediction errors determine the extent to which information is incorporated into long-term memory, such that learning is superior when incoming information counters strong incorrect recollections, thereby eliciting large prediction errors. Paradoxically, by the same account, strong accurate recollections are more amenable to being supplanted by misinformation, engendering false memories. These findings highlight a commonality in brain mechanisms and computational rules that govern declarative and nondeclarative learning, traditionally deemed dissociable.

Presumed consent for organ preservation in uncontrolled donation after cardiac death in the United States: a public policy with serious consequences

PubMed Central

Verheijde, Joseph L; Rady, Mohamed Y; McGregor, Joan

2009-01-01

Organ donation after cessation of circulation and respiration, both controlled and uncontrolled, has been proposed by the Institute of Medicine as a way to increase opportunities for organ procurement. Despite claims to the contrary, both forms of controlled and uncontrolled donation after cardiac death raise significant ethical and legal issues. Identified causes for concern include absence of agreement on criteria for the declaration of death, nonexistence of universal guidelines for duration before stopping resuscitation efforts and techniques, and assumption of presumed intent to donate for the purpose of initiating temporary organ-preservation interventions when no expressed consent to donate is present. From a legal point of view, not having scientifically valid criteria of cessation of circulation and respiration for declaring death could lead to a conclusion that organ procurement itself is the proximate cause of death. Although the revised Uniform Anatomical Gift Act of 2006 provides broad immunity to those involved in organ-procurement activities, courts have yet to provide an opinion on whether persons can be held liable for injuries arising from the determination of death itself. Preserving organs in uncontrolled donation after cardiac death requires the administration of life-support systems such as extracorporeal membrane oxygenation. These life-support systems can lead to return of signs of life that, in turn, have to be deliberately suppressed by the administration of pharmacological agents. Finally, allowing temporary organ-preservation interventions without expressed consent is inherently a violation of the principle of respect for a person's autonomy. Proponents of organ donation from uncontrolled donation after cardiac death, on the other hand, claim that these nonconsensual interventions enhance respect for autonomy by allowing people, through surrogate decision making, to execute their right to donate organs. However, the lack of transparency and the absence of protection of individual autonomy, for the sake of maximizing procurement opportunities, have placed the current organ-donation system of opting-in in great jeopardy. Equally as important, current policies enabling and enhancing organ procurement practices, pose challenges to the constitutional rights of individuals in a pluralistic society as these policies are founded on flawed medical standards for declaring death. PMID:19772617

Presumed consent for organ preservation in uncontrolled donation after cardiac death in the United States: a public policy with serious consequences.

PubMed

Verheijde, Joseph L; Rady, Mohamed Y; McGregor, Joan

2009-09-22

Organ donation after cessation of circulation and respiration, both controlled and uncontrolled, has been proposed by the Institute of Medicine as a way to increase opportunities for organ procurement. Despite claims to the contrary, both forms of controlled and uncontrolled donation after cardiac death raise significant ethical and legal issues. Identified causes for concern include absence of agreement on criteria for the declaration of death, nonexistence of universal guidelines for duration before stopping resuscitation efforts and techniques, and assumption of presumed intent to donate for the purpose of initiating temporary organ-preservation interventions when no expressed consent to donate is present. From a legal point of view, not having scientifically valid criteria of cessation of circulation and respiration for declaring death could lead to a conclusion that organ procurement itself is the proximate cause of death. Although the revised Uniform Anatomical Gift Act of 2006 provides broad immunity to those involved in organ-procurement activities, courts have yet to provide an opinion on whether persons can be held liable for injuries arising from the determination of death itself. Preserving organs in uncontrolled donation after cardiac death requires the administration of life-support systems such as extracorporeal membrane oxygenation. These life-support systems can lead to return of signs of life that, in turn, have to be deliberately suppressed by the administration of pharmacological agents. Finally, allowing temporary organ-preservation interventions without expressed consent is inherently a violation of the principle of respect for a person's autonomy. Proponents of organ donation from uncontrolled donation after cardiac death, on the other hand, claim that these nonconsensual interventions enhance respect for autonomy by allowing people, through surrogate decision making, to execute their right to donate organs. However, the lack of transparency and the absence of protection of individual autonomy, for the sake of maximizing procurement opportunities, have placed the current organ-donation system of opting-in in great jeopardy. Equally as important, current policies enabling and enhancing organ procurement practices, pose challenges to the constitutional rights of individuals in a pluralistic society as these policies are founded on flawed medical standards for declaring death.

An educational initiative to improve medical student awareness about brain death.

PubMed

Lewis, Ariane; Howard, Jonathan; Watsula-Morley, Amanda; Gillespie, Colleen

2018-04-01

Medical student knowledge about brain death determination is limited. We describe an educational initiative to improve medical student awareness about brain death and assess the impact of this initiative. Beginning in July 2016, students at our medical school were required to attend a 90-min brain death didactic and simulation session during their neurology clerkship. Students completed a test immediately before and after participating in the initiative. Of the 145 students who participated in this educational initiative between July 2016 and June 2017, 124 (86%) consented to have their data used for research purposes as part of a medical education registry. Students correctly answered a median of 53% of questions (IQR 47-58%) on the pretest and 86% of questions (IQR 78-89%) on the posttest (p < .001). Comfort with both performing a brain death evaluation and talking to a family about brain death improved significantly after this initiative (18% of students were comfortable performing a brain death evaluation before the initiative and 86% were comfortable doing so after the initiative, p < .001; 18% were comfortable talking to a family about brain death before the initiative and 76% were comfortable doing so after the initiative, p < .001). Incorporation of simulation in undergraduate medical education is high-yield. At our medical school, knowledge about brain death and comfort performing a brain death exam or talking to a family about brain death was limited prior to development of this initiative, but awareness and comfort dealing with brain death improved significantly after this initiative. Copyright © 2018 Elsevier B.V. All rights reserved.

NOAA declares string of seal deaths in New England an unusual mortality

Science.gov Websites

Alerts NOAA Organizations Working With NOAA Media & Constituents NOAA In Your State Emergency string of seal deaths in New England an unusual mortality event Public reminded to maintain safe distance the Working Group on Marine Mammal Unusual Mortality Events, a panel of international experts

Renaissance of criticism on the concept of brain death--the role of legal medicine in the context of the interdisciplinary discussion.

PubMed

Markert, L; Bockholdt, B; Verhoff, M A; Heinze, S; Parzeller, M

2016-03-01

In the practice of legal medicine in Germany, the assessment of brain death is of minor importance and attracts little attention. However, since several years, international criticism on the concept of brain death has culminated. By reviewing literature and the results of a questionnaire distributed among the participants of the 93rd Annual Congress of the Germany Society of Legal Medicine, the state of knowledge and the current views on brain death were evaluated. Literature search of recent publications regarding brain death was performed (PubMed database, references of legal medicine, Report of the President's Council on Bioethics, USA 2008). A questionnaire was developed and distributed among the participants of the Congress. The assumption that individual and brain death are synonymous is criticized. Internationally, there are trends to harmonize the very different clinical criteria to assess brain death. The diagnostic advantage of novel techniques such as CT angiography is controversially discussed. It becomes apparent that procedures which record the blood flow and perfusion of the brain will be applied more in the future. Regrettably, these developments are not described in the literature of legal medicine. Moreover, among German forensic scientists, different views concerning brain death exist. The majority favors its equivalent treatment with individual death. The thanatological background can be improved concerning certain aspects of brain death as well as its legal implications. Teaching and research in legal medicine should include the subject brain death. Expertise in forensic science may contribute to the interdisciplinary discussion on brain death. The transfer of actual knowledge, also on disputed ethical aspects of thanatology, to physicians of all disciplines is of great importance.

Neuroscience and Brain Death Controversies: The Elephant in the Room.

PubMed

Verheijde, Joseph L; Rady, Mohamed Y; Potts, Michael

2018-06-21

The conception and the determination of brain death continue to raise scientific, legal, philosophical, and religious controversies. While both the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research in 1981 and the President's Council on Bioethics in 2008 committed to a biological definition of death as the basis for the whole-brain death criteria, contemporary neuroscientific findings augment the concerns about the validity of this biological definition. Neuroscientific evidentiary findings, however, have not yet permeated discussions about brain death. These findings have critical relevance (scientifically, medically, legally, morally, and religiously) because they indicate that some core assumptions about brain death are demonstrably incorrect, while others lack sufficient evidential support. If behavioral unresponsiveness does not equate to unconsciousness, then the philosophical underpinning of the definition based on loss of capacity for consciousness as well as the criteria, and tests in brain death determination are incongruent with empirical evidence. Thus, the primary claim that brain death equates to biological death has then been de facto falsified. This conclusion has profound philosophical, religious, and legal implications that should compel respective authorities to (1) reassess the philosophical rationale for the definition of death, (2) initiate a critical reappraisal of the presumed alignment of brain death with the theological definition of death in Abrahamic faith traditions, and (3) enact new legislation ratifying religious exemption to death determination by neurologic criteria.

Impact of a quality improvement project on deceased organ donor management

PubMed Central

Olmos, Andrea; Feiner, John; Hirose, Ryutaro; Swain, Sharon; Blasi, Annabel; Roberts, John P.; Niemann, Claus U.

2017-01-01

Context Donors showed poor glucose control in the period between declaration of brain death and organ recovery. The level of hyperglycemia in the donors was associated with a decline in terminal renal function. Objective To determine whether implementation of a quality improvement project improved glucose control and preserved renal function in deceased organ donors. Methods Data collected retrospectively included demographics, medical history, mechanism of death, laboratory values, and data from the United Network for Organ Sharing. Results After implementation of the quality improvement project, deceased donors had significantly lower mean glucose concentrations (mean [SD], 162 [44] vs 212 [42] mg/dL; P < .001) and prerecovery glucose concentration (143 [66] vs 241 [69] mg/dL; P < .001). When the donor cohorts from before and after the quality improvement project were analyzed together, mean glucose concentration remained a significant predictor of terminal creatinine level (P < .001). Multivariate analysis of delayed graft function in kidney recipients matched to donors indicated that higher terminal creatinine level was associated with delayed graft function in recipients (P < .001). Conclusion The quality improvement project improved donor glucose homeostasis, and the data confirm that poor glucose homeostasis is associated with worsening terminal renal function. PMID:26645930

Total Brain Death and the Integration of the Body Required of a Human Being

PubMed Central

Lee, Patrick

2016-01-01

I develop and refine an argument for the total brain death criterion of death previously advanced by Germain Grisez and me: A human being is essentially a rational animal, and so must have a radical capacity for rational operations. For rational animals, conscious sensation is a pre-requisite for rational operation. But total brain death results in the loss of the radical capacity for conscious sensation, and so also for rational operations. Hence, total brain death constitutes a substantial change—the ceasing to be of the human being. Objections are considered, including the objection that total brain death need not result in the loss of capacity for sensation, and that damage to the brain less than total brain death can result in loss of capacity for rational operations. PMID:27097647

Sleeping brain, learning brain. The role of sleep for memory systems.

PubMed

Peigneux, P; Laureys, S; Delbeuck, X; Maquet, P

2001-12-21

The hypothesis that sleep participates in the consolidation of recent memory traces has been investigated using four main paradigms: (1) effects of post-training sleep deprivation on memory consolidation, (2) effects of learning on post-training sleep, (3) effects of within sleep stimulation on the sleep pattern and on overnight memories, and (4) re-expression of behavior-specific neural patterns during post-training sleep. These studies convincingly support the idea that sleep is deeply involved in memory functions in humans and animals. However, the available data still remain too scarce to confirm or reject unequivocally the recently upheld hypothesis that consolidations of non-declarative and declarative memories are respectively dependent upon REM and NREM sleep processes.

East-West differences in perception of brain death. Review of history, current understandings, and directions for future research.

PubMed

Yang, Qing; Miller, Geoffrey

2015-06-01

The concept of brain death as equivalent to cardiopulmonary death was initially conceived following developments in neuroscience, critical care, and transplant technology. It is now a routine part of medicine in Western countries, including the United States. In contrast, Eastern countries have been reluctant to incorporate brain death into legislation and medical practice. Several countries, most notably China, still lack laws recognizing brain death and national medical standards for making the diagnosis. The perception is that Asians are less likely to approve of brain death or organ transplant from brain dead donors. Cultural and religious traditions have been referenced to explain this apparent difference. In the West, the status of the brain as home to the soul in Enlightenment philosophy, combined with pragmatism and utilitarianism, supports the concept of brain death. In the East, the integration of body with spirit and nature in Buddhist and folk beliefs, along with the Confucian social structure that builds upon interpersonal relationships, argues against brain death. However, it is unclear whether these reasoning strategies are explicitly used when families and medical providers are faced with acknowledging brain death. Their decisions are more likely to involve a prioritization of values and a rationalization of intuitive responses. Why and whether there might be differences between East and West in the acceptance of the brain death concept requires further empirical testing, which would help inform policy-making and facilitate communication between providers and patients from different cultural and ethnic backgrounds.

Did the Moral Education Establishment Kill Character? An Autopsy of "The Death of Character."

ERIC Educational Resources Information Center

Glanzer, Perry L.

2003-01-01

Examines James Davison Hunter's claim that the moral education establishment is responsible for the death of character. Declares that moral education must grapple with Hunter's finding that effective moral education requires coherent moral culture with a clear conception of public and private good. Compares post-Soviet and current U.S. moral…

32 CFR Appendix A to Part 270 - Application for Compensation of Vietnamese Commandos

Code of Federal Regulations, 2014 CFR

2014-07-01

... operative is the basis for applying for payment: (1) Current legal name or legal name at death: (a) Aliases: (b) Former, or other legal names used: (2) Current address or last address prior to death: (3... 1958 through 1975. I declare under penalty of perjury under the laws of the United States of America...

32 CFR Appendix A to Part 270 - Application for Compensation of Vietnamese Commandos

Code of Federal Regulations, 2013 CFR

2013-07-01

... operative is the basis for applying for payment: (1) Current legal name or legal name at death: (a) Aliases: (b) Former, or other legal names used: (2) Current address or last address prior to death: (3... 1958 through 1975. I declare under penalty of perjury under the laws of the United States of America...

32 CFR Appendix A to Part 270 - Application for Compensation of Vietnamese Commandos

Code of Federal Regulations, 2012 CFR

2012-07-01

... operative is the basis for applying for payment: (1) Current legal name or legal name at death: (a) Aliases: (b) Former, or other legal names used: (2) Current address or last address prior to death: (3... 1958 through 1975. I declare under penalty of perjury under the laws of the United States of America...

32 CFR Appendix A to Part 270 - Application for Compensation of Vietnamese Commandos

Code of Federal Regulations, 2011 CFR

2011-07-01

... operative is the basis for applying for payment: (1) Current legal name or legal name at death: (a) Aliases: (b) Former, or other legal names used: (2) Current address or last address prior to death: (3... 1958 through 1975. I declare under penalty of perjury under the laws of the United States of America...

Mechanisms for widespread hippocampal involvement in cognition

PubMed Central

Shohamy, Daphna; Turk-Browne, Nicholas B.

2014-01-01

The quintessential memory system in the human brain — the hippocampus and surrounding medial temporal lobe (MTL) — is often treated as a module for the formation of conscious, or declarative memories. However, growing evidence suggests that the hippocampus plays a broader role in memory and cognition and that theories organizing memory into strictly dedicated systems may need to be updated. We first consider the historical evidence for the specialized role of the hippocampus in declarative memory. Then, we describe the serendipitous encounter that motivated this special section, based on parallel research from our labs that suggested a more pervasive contribution of the hippocampus to cognition beyond declarative memory. Finally, we develop a theoretical framework that describes two general mechanisms for how the hippocampus interacts with other brain systems and cognitive processes: the Memory Modulation Hypothesis, in which mnemonic representations in the hippocampus modulate the operation of other systems, and the Adaptive Function Hypothesis, in which specialized computations in the hippocampus are recruited as a component of both mnemonic and non-mnemonic functions. This framework is consistent with an emerging view that the most fertile ground for discovery in cognitive psychology and neuroscience lies at the interface between parts of the mind and brain that have traditionally been studied in isolation. PMID:24246058

The Learning Hippocampus: Education and Experience-Dependent Plasticity

ERIC Educational Resources Information Center

Wenger, Elisabeth; Lövdén, Martin

2016-01-01

The hippocampal formation of the brain plays a crucial role in declarative learning and memory while at the same time being particularly susceptible to environmental influences. Education requires a well-functioning hippocampus, but may also influence the development of this brain structure. Understanding these bidirectional influences may have…

A change of heart and a change of mind? Technology and the redefinition of death in 1968.

PubMed

Giacomini, M

1997-05-01

In 1968, an ad hoc committee of Harvard faculty publicly redefined death as "brain death". What interests and issues compelled the redefinition of death, and formed the "spirit" of this precedent-setting policy? This paper reports on an historical study of the files of the Harvard ad hoc committee, the proceedings of an international conference on ethical issues in organ transplantation, and a review of the medical literature and media in the decades preceding the redefinition of death. This analysis of the technological and professional forces involved in the redefinition of death in 1968 questions two common theses: that technological "progress", primarily in the areas of life support and electroencephalography, literally created brain-dead bodies and dictated their defining features (respectively), and that Harvard's definition of brain death by committee constituted a net loss of autonomy for medicine. In fact, medical researchers through the 1960s disputed and negotiated many features of the brain death syndrome, and transplantation interests-perhaps more kidney than heart-played a particularly influential role in tailoring the final criteria put forth by Harvard in 1968. It is also doubtful whether Harvard's definition of brain death by multidisciplinary committee undermined medical privilege and autonomy. The Harvard Ad Hoc Committee may not have succeeded in establishing definitive, indisputable brain death criteria and ensuring their consistent application to all clinical cases of brain death. However, it did gain significant ground for transplant and other medical interests by (1) establishing brain death as a technical "fact" and the definition of brain death as an exercise for medical theorists, (2) involving non-medical ethics and humanities experts in supporting the technical redefinition of death, and, (3) successfully involving transplant surgeons in the redefinition of death and attempting (albeit unsuccessfully) not to exclude them from the actual diagnosis of death in individual cases.

Deconstructing the Brain Disconnection–Brain Death Analogy and Clarifying the Rationale for the Neurological Criterion of Death

PubMed Central

Moschella, Melissa

2016-01-01

This article explains the problems with Alan Shewmon’s critique of brain death as a valid sign of human death, beginning with a critical examination of his analogy between brain death and severe spinal cord injury. The article then goes on to assess his broader argument against the necessity of the brain for adult human organismal integration, arguing that he fails to translate correctly from biological to metaphysical claims. Finally, on the basis of a deeper metaphysical analysis, I offer a revised rationale for the validity of the neurological criterion of human death. PMID:27095749

Total brain death: a reply to Alan Shewmon.

PubMed

Lee, Patrick; GriseZ, Germain

2012-06-01

D. Alan Shewmon has advanced a well-documented challenge to the widely accepted total brain death criterion for death of the human being. We show that Shewmon’s argument against this criterion is unsound, though he does refute the standard argument for that criterion. We advance a distinct argument for the total brain death criterion and answer likely objections. Since human beings are rational animals--sentient organisms of a specific type--the loss of the radical capacity for sentience (the capacity to sense or to develop the capacity to sense) involves a substantial change, the passing away of the human organism. In human beings total brain death involves the complete loss of the radical capacity for sentience, and so in human beings total brain death is death.

Donation after cardio-circulatory death liver transplantation

PubMed Central

Le Dinh, Hieu; de Roover, Arnaud; Kaba, Abdour; Lauwick, Séverine; Joris, Jean; Delwaide, Jean; Honoré, Pierre; Meurisse, Michel; Detry, Olivier

2012-01-01

The renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ supply and following the request of potential DCD families. Since then, DCD organ procurement and transplantation activities have rapidly expanded, particularly for non-vital organs, like kidneys. In liver transplantation (LT), DCD donors are a valuable organ source that helps to decrease the mortality rate on the waiting lists and to increase the availability of organs for transplantation despite a higher risk of early graft dysfunction, more frequent vascular and ischemia-type biliary lesions, higher rates of re-listing and re-transplantation and lower graft survival, which are obviously due to the inevitable warm ischemia occurring during the declaration of death and organ retrieval process. Experimental strategies intervening in both donors and recipients at different phases of the transplantation process have focused on the attenuation of ischemia-reperfusion injury and already gained encouraging results, and some of them have found their way from pre-clinical success into clinical reality. The future of DCD-LT is promising. Concerted efforts should concentrate on the identification of suitable donors (probably Maastricht category III DCD donors), better donor and recipient matching (high risk donors to low risk recipients), use of advanced organ preservation techniques (oxygenated hypothermic machine perfusion, normothermic machine perfusion, venous systemic oxygen persufflation), and pharmacological modulation (probably a multi-factorial biologic modulation strategy) so that DCD liver allografts could be safely utilized and attain equivalent results as DBD-LT. PMID:22969222

Total Brain Death and the Integration of the Body Required of a Human Being.

PubMed

Lee, Patrick

2016-06-01

I develop and refine an argument for the total brain death criterion of death previously advanced by Germain Grisez and me: A human being is essentially a rational animal, and so must have a radical capacity for rational operations. For rational animals, conscious sensation is a pre-requisite for rational operation. But total brain death results in the loss of the radical capacity for conscious sensation, and so also for rational operations. Hence, total brain death constitutes a substantial change-the ceasing to be of the human being. Objections are considered, including the objection that total brain death need not result in the loss of capacity for sensation, and that damage to the brain less than total brain death can result in loss of capacity for rational operations. © The Author 2016. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Confounding factors in diagnosing brain death: a case report.

PubMed

Burns, Jeffrey M; Login, Ivan S

2002-06-26

Brain death is strictly defined medically and legally. This diagnosis depends on three cardinal neurological features: coma, absent brainstem reflexes, and apnea. The diagnosis can only be made, however, in the absence of intoxication, hypothermia, or certain medical illnesses. A patient with severe hypoxic-ischemic brain injury met the three cardinal neurological features of brain death but concurrent profound hypothyroidism precluded the diagnosis. Our clinical and ethical decisions were further challenged by another facet of this complex case. Although her brain damage indicated a hopeless prognosis, we could not discontinue care based on futility because the only known surrogate was mentally retarded and unable to participate in medical planning. The presence of certain medical conditions prohibits a diagnosis of brain death, which is a medicolegal diagnosis of death, not a prediction or forecast of future outcome. While prognostication is important in deciding to withdraw care, it is not a component in diagnosing brain death.

Diagnosing Autism Spectrum Disorder through Brain Functional Magnetic Resonance Imaging

DTIC Science & Technology

2016-03-01

Diagnosing Autism Spectrum Disorder through Brain Functional Magnetic Resonance Imaging THESIS MARCH 2016 Kyle A. Palko, Second Lieutenant, USAF AFIT...declared a work of the U.S. Government and is not subject to copyright protection in the United States. AFIT-ENC-MS-16-M-123 DIAGNOSING AUTISM SPECTRUM...PUBLIC RELEASE; DISTRIBUTION UNLIMITED. AFIT-ENC-MS-16-M-123 DIAGNOSING AUTISM SPECTRUM DISORDER THROUGH BRAIN FUNCTIONAL MAGNETIC RESONANCE IMAGING Kyle

Brain death: the challenges of translating medical science into Islamic bioethical discourse.

PubMed

Padela, Aasim I; Basser, Taha A

2012-09-01

Islamic ethico-legal assessments of brain death are varied and controversial. Some Islamic ethico-legal bodies have concluded that brain death is equivalent to cardiopulmonary death; others regard it as an intermediate state between life and death, and a few opine that it does not meet the standards for legal death according to Islamic law. Yet this translation of the concept of brain death into the Islamic ethico-legal domain has generated multiple ethical complexities that receive insufficient attention within the extant medical and fiqh literature. How do Islamic legists understand brain death as a clinical phenomenon? How does the Islamic ethico-legal system treat medical uncertainty? What Islamic ethico-legal principles should apply to bioethical questions about life and death? In this paper, we analyze the arguments for, and against, the acceptance of brain death within the context of the deliberation of a representative juridical council. In our discussion we focus on areas in which the legists' ethico-legal reasoning hinges upon clinical conceptions of the state of the individual when diagnosed as brain dead. As Islamic ethics continues to engage scientific and technological advancements in these areas, such exploration of internal workings is necessary if we wish to better understand how Islamic ethical principles can contribute to bioethical deliberation.

A Needs Assessment of Brain Death Education in Pediatric Critical Care Medicine Fellowships.

PubMed

Ausmus, Andrew M; Simpson, Pippa M; Zhang, Liyun; Petersen, Tara L

2018-04-12

To assess the current training in brain death examination provided during pediatric critical care medicine fellowship. Internet-based survey. United States pediatric critical care medicine fellowship programs. Sixty-four pediatric critical care medicine fellowship program directors and 230 current pediatric critical care medicine fellows/recent graduates were invited to participate. Participants were asked demographic questions related to their fellowship programs, training currently provided at their fellowship programs, previous experience with brain death examinations (fellows/graduates), and perceptions regarding the adequacy of current training. Twenty-nine program directors (45%) and 91 current fellows/graduates (40%) responded. Third-year fellows reported having performed a median of five examinations (interquartile range, 3-6). On a five-point Likert scale, 93% of program directors responded they "agree" or "strongly agree" that their fellows receive enough instruction on performing brain death examinations compared with 67% of fellows and graduates (p = 0.007). The responses were similar when asked about opportunity to practice brain death examinations (90% vs 54%; p < 0.001). In a regression tree analysis, number of brain death examinations performed was the strongest predictor of trainee satisfaction. Both fellows and program directors preferred bedside demonstration or simulation as educational modalities to add to the fellowship curriculum. Pediatric critical care medicine fellows overall perform relatively few brain death examinations during their training. Pediatric critical care medicine fellows and program directors disagree in their perceptions of the current training in brain death examination, with fellows perceiving a need for increased training. Both program directors and fellows prefer additional training using bedside demonstration or simulation. Since clinical exposure to brain death examinations is variable, adding simulated brain death examinations to the pediatric critical care medicine fellowship curriculum could help standardize the experience.

Brain death in Islamic ethico-legal deliberation: challenges for applied Islamic bioethics.

PubMed

Padela, Aasim I; Arozullah, Ahsan; Moosa, Ebrahim

2013-03-01

Since the 1980s, Islamic scholars and medical experts have used the tools of Islamic law to formulate ethico-legal opinions on brain death. These assessments have varied in their determinations and remain controversial. Some juridical councils such as the Organization of Islamic Conferences' Islamic Fiqh Academy (OIC-IFA) equate brain death with cardiopulmonary death, while others such as the Islamic Organization of Medical Sciences (IOMS) analogize brain death to an intermediate state between life and death. Still other councils have repudiated the notion entirely. Similarly, the ethico-legal assessments are not uniform in their acceptance of brain-stem or whole-brain criteria for death, and consequently their conceptualizations of, brain death. Within the medical literature, and in the statements of Muslim medical professional societies, brain death has been viewed as sanctioned by Islamic law with experts citing the aforementioned rulings. Furthermore, health policies around organ transplantation and end-of-life care within the Muslim world have been crafted with consideration of these representative religious determinations made by transnational, legally-inclusive, and multidisciplinary councils. The determinations of these councils also have bearing upon Muslim clinicians and patients who encounter the challenges of brain death at the bedside. For those searching for 'Islamically-sanctioned' responses that can inform their practice, both the OIC-IFA and IOMS verdicts have palpable gaps in their assessments and remain clinically ambiguous. In this paper we analyze these verdicts from the perspective of applied Islamic bioethics and raise several questions that, if answered by future juridical councils, will better meet the needs of clinicians and bioethicists. © 2011 Blackwell Publishing Ltd.

Cranial nerve clock. Part II: functional MR imaging of brain activation during a declarative memory task.

PubMed

Weiss, K L; Welsh, R C; Eldevik, P; Bieliauskas, L A; Steinberg, B A

2001-12-01

The authors performed this study to assess brain activation during encoding and successful recall with a declarative memory paradigm that has previously been demonstrated to be effective for teaching students about the cranial nerves. Twenty-four students underwent functional magnetic resonance (MR) imaging during encoding and recall of the name, number, and function of the 12 cranial nerves. The students viewed mnemonic graphic and text slides related to individual nerves, as well as their respective control slides. For the recall paradigm, students were prompted with the numbers 1-12 (test condition) intermixed with the number 14 (control condition). Subjects were tested about their knowledge of cranial nerves outside the MR unit before and after functional MR imaging. Students learned about the cranial nerves while undergoing functional MR imaging (mean post- vs preparadigm score, 8.1 +/- 3.4 [of a possible 12] vs 0.75 +/- 0.94, bilateral prefrontal cortex, left greater than right; P < 2.0 x 10(-12)) and maintained this knowledge at I week. The encoding and recall paradigms elicited distributed networks of brain activation. Encoding revealed statistically significant activation in the bilateral prefrontal cortex, left greater than right [corrected]; bilateral occipital and parietal associative cortices, parahippocampus region, fusiform gyri, and cerebellum. Successful recall activated the left much more than the right prefrontal, parietal associative, and anterior cingulate cortices; bilateral precuneus and cerebellum; and right more than the left posterior cingulate. A predictable pattern of brain activation at functional MR imaging accompanies the encoding and successful recall of the cranial nerves with this declarative memory paradigm.

[Selective alteration of the declarative memory systems in patients treated with a high number of electroconvulsive therapy sessions].

PubMed

Rami-González, L; Boget-Llucià, T; Bernardo, M; Marcos, T; Cañizares-Alejos, S; Penadés, R; Portella, M J; Castelví, M; Raspall, T; Salamero, M

The reversible electrochemical effects of electroconvulsive therapy (ECT) on specific areas of the brain enable the neuroanatomical bases of some cognitive functions to be studied. In research carried out on memory systems, a selective alteration of the declarative ones has been observed after treatment with ECT. Little work has been done to explore the differential alteration of the memory subsystems in patients with a high number of ECT sessions. AIM. To study the declarative and non declarative memory system in psychiatric patients submitted to maintenance ECT treatment, with a high number of previous ECT sessions. 20 patients submitted to treatment with ECT (10 diagnosed as having depression and 10 with schizophrenia) and 20 controls, who were paired by age, sex and psychopathological diagnosis. For the evaluation of the declarative memory system, the Wechsler Memory Scale (WMS) logical memory test was used. The Hanoi Tower procedural test was employed to evaluate the non declarative system. Patients treated with ECT performed worse in the WMS logical memory test, but this was only significant in patients diagnosed as suffering from depression. No significant differences were observed in the Hanoi Tower test. A selective alteration of the declarative systems was observed in patients who had been treated with a high number of ECT sessions, while the non declarative memory systems remain unaffected.

27 CFR 31.116 - Execution of registration form.

Code of Federal Regulations, 2013 CFR

2013-04-01

... representative who continues the business of a dealer by reason of death, insolvency, or other circumstance must... written declaration that it has been executed under the penalties of perjury. (26 U.S.C. 6061, 6065) ...

27 CFR 31.116 - Execution of registration form.

Code of Federal Regulations, 2014 CFR

2014-04-01

... representative who continues the business of a dealer by reason of death, insolvency, or other circumstance must... written declaration that it has been executed under the penalties of perjury. (26 U.S.C. 6061, 6065) ...

27 CFR 31.116 - Execution of registration form.

Code of Federal Regulations, 2010 CFR

2010-04-01

... representative who continues the business of a dealer by reason of death, insolvency, or other circumstance must... written declaration that it has been executed under the penalties of perjury. (26 U.S.C. 6061, 6065) ...

27 CFR 31.116 - Execution of registration form.

Code of Federal Regulations, 2011 CFR

2011-04-01

... representative who continues the business of a dealer by reason of death, insolvency, or other circumstance must... written declaration that it has been executed under the penalties of perjury. (26 U.S.C. 6061, 6065) ...

27 CFR 31.116 - Execution of registration form.

Code of Federal Regulations, 2012 CFR

2012-04-01

... representative who continues the business of a dealer by reason of death, insolvency, or other circumstance must... written declaration that it has been executed under the penalties of perjury. (26 U.S.C. 6061, 6065) ...

Which experimental model can sensitively indicate brain death by functional near-infrared spectroscopy?

NASA Astrophysics Data System (ADS)

Pan, Boan; Liu, Weichao; Fang, Xiang; Huang, Xiaobo; Li, Ting

2018-02-01

Brain death is defined as permanent loss of the brain functions. The evaluation of it has many meanings, such as the relief of organ transplantation stress and family burden. However, it is hard to be judged precisely. The standard clinical tests are expensive, time consuming and even dangerous, and some auxiliary methods have limitations. Functional near infrared spectroscopy (fNIRS), monitoring cerebral hemodynamic responses noninvasively, evaluate brain death in some papers published, but there is no discussion about which experimental mode can monitor brain death patient more sensitively. Here, we attempt to use our fNIRS to evaluate brain death and find which experimental mode is effective. In order to discuss the problem, we detected eleven brain death patients and twenty normal patients under natural state. They were provided different fraction of inspiration O2 (FIO2) in different phase. We found that the ratio of Δ[HbO2] (the concentration changes in oxyhemoglobin) to Δ[Hb] (the concentration changes in deoxyhemoglobin) in brain death patients is significantly higher than normal patients in FIO2 experiment. Combined with the data analysis result, restore oxygen change process and low-high-low paradigm is more sensitively.

Evaluation and diagnosis of brain death by functional near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Pan, Boan; Zhong, Fulin; Huang, Xiaobo; Pan, Lingai; Lu, Sen; Li, Ting

2017-02-01

Brain death, the irreversible and permanent loss of the brain and brainstem functions, is hard to be judged precisely for some clinical reasons. The traditional diagnostic methods are time consuming, expensive and some are even dangerous. Functional near infrared spectroscopy (FNIRS), using the good scattering properties of major component of blood to NIR, is capable of noninvasive monitoring cerebral hemodynamic responses. Here, we attempt to use portable FNIRS under patients' natural state for brain death diagnosis. Ten brain death patients and seven normal subjects participated in FNIRS measurements. All of them were provided different fractional concentration of inspired oxygen (FIO2) in different time periods. We found that the concentration variation of deoxyhemoglobin concentration (Δ[Hb]) presents the trend of decrease in the both brain death patients and normal subjects with the raise of the FIO2, however, the data in the normal subjects is more significant. And the concentration variation of oxyhemoglobins concentration (Δ[HbO2]) emerges the opposite trends. Thus Δ[HbO2]/Δ[Hb] in brain death patients is significantly higher than normal subjects, and emerges the rising trend as time went on. The findings indicated the potential of FNIRS-measured hemodynamic index in diagnosing brain death.

Serum S100B protein concentration in brain-dead organ donors: a pilot study.

PubMed

Krzych, Łukasz J; Czempik, Piotr Filip; Saucha, Wojciech; Kokocińska, Danuta; Knapik, Piotr

2015-01-01

Protein S100B is considered to be a marker of brain damage, but there is a paucity of data regarding the utility of its assessment in brain-dead organ donors. The aim of the study was to compare serum protein S100B concentrations between brain-dead organ donors and patients with a confirmed permanent neurological deficit but without signs of brain death. The concentration of serum S100B protein was measured in 12 brain-dead organ donors (including 7 males with a median age of 40 years). All measurements were taken when brain death was confirmed by the commission. Twenty-nine patients (including 13 males with a median age of 63 years) who died in the medical ICU with confirmed permanent brain injury without signs of brain death acted as controls. In these patients, S-100B protein measurements were performed upon ICU admission. In brain-dead organ donors, the median values of serum S100B protein were much higher in comparison to the control group (median and IQR, respectively: 5.04 μg L⁻¹; 1.775-6.765 vs 0.897 μg L⁻¹; 0.324-1.880, P < 0.001). S100B serum values > 1.81 μg L⁻¹ predicted brain death with the highest accuracy (AUROC = 0.83; 95% CI 0.68-0.93; P < 0.001). Concentrations of serum S100B protein in brain-dead organ donors are extremely high and may support the diagnosis of brain death. This fact may be of value when the presence of reflex movements (frequently reported despite brain death) might delay determination of brain death and result in the failure of organ donation.

Scientific, legal, and ethical challenges of end-of-life organ procurement in emergency medicine.

PubMed

Rady, Mohamed Y; Verheijde, Joseph L; McGregor, Joan L

2010-09-01

We review (1) scientific evidence questioning the validity of declaring death and procuring organs in heart-beating (i.e., neurological standard of death) and non-heart-beating (i.e., circulatory-respiratory standard of death) donation; (2) consequences of collaborative programs realigning hospital policies to maximize access of procurement coordinators to critically and terminally ill patients as potential donors on arrival in emergency departments; and (3) ethical and legal ramifications of current practices of organ procurement on patients and their families. Relevant publications in peer-reviewed journals and government websites. Scientific evidence undermines the biological criteria of death that underpin the definition of death in heart-beating (i.e., neurological standard) and non-heart-beating (i.e., circulatory-respiratory standard) donation. Philosophical reinterpretation of the neurological and circulatory-respiratory standards in the death statute, to avoid the appearance of organ procurement as an active life-ending intervention, lacks public and medical consensus. Collaborative programs bundle procurement coordinators together with hospital staff for a team-huddle and implement a quality improvement tool for a Rapid Assessment of Hospital Procurement Barriers in Donation. Procurement coordinators have access to critically ill patients during the course of medical treatment with no donation consent and with family or surrogates unaware of their roles. How these programs affect the medical care of these patients has not been studied. Policies enforcing end-of-life organ procurement can have unintended consequences: (1) erosion of care in the patient's best interests, (2) lack of transparency, and (3) ethical and legal ramifications of flawed standards of declaring death. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

A compensatory role for declarative memory in neurodevelopmental disorders.

PubMed

Ullman, Michael T; Pullman, Mariel Y

2015-04-01

Most research on neurodevelopmental disorders has focused on their abnormalities. However, what remains intact may also be important. Increasing evidence suggests that declarative memory, a critical learning and memory system in the brain, remains largely functional in a number of neurodevelopmental disorders. Because declarative memory remains functional in these disorders, and because it can learn and retain numerous types of information, functions, and tasks, this system should be able to play compensatory roles for multiple types of impairments across the disorders. Here, we examine this hypothesis for specific language impairment, dyslexia, autism spectrum disorder, Tourette syndrome, and obsessive-compulsive disorder. We lay out specific predictions for the hypothesis and review existing behavioral, electrophysiological, and neuroimaging evidence. Overall, the evidence suggests that declarative memory indeed plays compensatory roles for a range of impairments across all five disorders. Finally, we discuss diagnostic, therapeutic and other implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

A compensatory role for declarative memory in neurodevelopmental disorders

PubMed Central

Ullman, Michael T.; Pullman, Mariel Y.

2015-01-01

Most research on neurodevelopmental disorders has focused on their abnormalities. However, what remains intact may also be important. Increasing evidence suggests that declarative memory, a critical learning and memory system in the brain, remains largely functional in a number of neurodevelopmental disorders. Because declarative memory remains functional, and because this system can learn and retain numerous types of information, functions, and tasks, it should be able to play compensatory roles for multiple types of impairments across the disorders. Here, we examine this hypothesis for specific language impairment, dyslexia, autism spectrum disorder, Tourette syndrome, and obsessive-compulsive disorder. We lay out specific predictions for the hypothesis and review existing behavioral, electrophysiological, and neuroimaging evidence. Overall, the evidence suggests that declarative memory indeed plays compensatory roles for a range of impairments across all five disorders. Finally, we discuss diagnostic, therapeutic and other implications. PMID:25597655

Confounding factors in diagnosing brain death: a case report

PubMed Central

Burns, Jeffrey M; Login, Ivan S

2002-01-01

Background Brain death is strictly defined medically and legally. This diagnosis depends on three cardinal neurological features: coma, absent brainstem reflexes, and apnea. The diagnosis can only be made, however, in the absence of intoxication, hypothermia, or certain medical illnesses. Case presentation A patient with severe hypoxic-ischemic brain injury met the three cardinal neurological features of brain death but concurrent profound hypothyroidism precluded the diagnosis. Our clinical and ethical decisions were further challenged by another facet of this complex case. Although her brain damage indicated a hopeless prognosis, we could not discontinue care based on futility because the only known surrogate was mentally retarded and unable to participate in medical planning. Conclusion The presence of certain medical conditions prohibits a diagnosis of brain death, which is a medicolegal diagnosis of death, not a prediction or forecast of future outcome. While prognostication is important in deciding to withdraw care, it is not a component in diagnosing brain death. PMID:12097152

"Brain Death" and dead donor rule. Discussion and proposals on the thesis of Truog.

PubMed

Bruzzone, Paolo

2015-01-01

The introduction in 1968 by the "ad hoc" Harvard committee of the concept of "Brain Death" gave birth to the worldwide diffusion of organ transplantation. Recently "Total Brain Failure" has been proposed as preferred term, instead of "Brain Death", by the President's Council on Bioethics. The concepts of "brain death" and of "dead donor rule" remain the ethical and moral support of organ transplantation. However both criteria has been questioned , either separately or all together , by many authors and particularly by Dr. Robert D. Truog.

Predictors of neurologic and nonneurologic death in patients with brain metastasis initially treated with upfront stereotactic radiosurgery without whole-brain radiation therapy

PubMed Central

Johnson, Adam G.; Ruiz, Jimmy; Isom, Scott; Lucas, John T.; Hinson, William H.; Watabe, Kounosuke; Laxton, Adrian W.; Tatter, Stephen B.; Chan, Michael D.

2017-01-01

Abstract Background. In this study we attempted to discern the factors predictive of neurologic death in patients with brain metastasis treated with upfront stereotactic radiosurgery (SRS) without whole brain radiation therapy (WBRT) while accounting for the competing risk of nonneurologic death. Methods. We performed a retrospective single-institution analysis of patients with brain metastasis treated with upfront SRS without WBRT. Competing risks analysis was performed to estimate the subdistribution hazard ratios (HRs) for neurologic and nonneurologic death for predictor variables of interest. Results. Of 738 patients treated with upfront SRS alone, neurologic death occurred in 226 (30.6%), while nonneurologic death occurred in 309 (41.9%). Multivariate competing risks analysis identified an increased hazard of neurologic death associated with diagnosis-specific graded prognostic assessment (DS-GPA) ≤ 2 (P = .005), melanoma histology (P = .009), and increased number of brain metastases (P<.001), while there was a decreased hazard associated with higher SRS dose (P = .004). Targeted agents were associated with a decreased HR of neurologic death in the first 1.5 years (P = .04) but not afterwards. An increased hazard of nonneurologic death was seen with increasing age (P =.03), nonmelanoma histology (P<.001), presence of extracranial disease (P<.001), and progressive systemic disease (P =.004). Conclusions. Melanoma, DS-GPA, number of brain metastases, and SRS dose are predictive of neurologic death, while age, nonmelanoma histology, and more advanced systemic disease are predictive of nonneurologic death. Targeted agents appear to delay neurologic death. PMID:27571883

Deconstructing the Brain Disconnection-Brain Death Analogy and Clarifying the Rationale for the Neurological Criterion of Death.

PubMed

Moschella, Melissa

2016-06-01

This article explains the problems with Alan Shewmon's critique of brain death as a valid sign of human death, beginning with a critical examination of his analogy between brain death and severe spinal cord injury. The article then goes on to assess his broader argument against the necessity of the brain for adult human organismal integration, arguing that he fails to translate correctly from biological to metaphysical claims. Finally, on the basis of a deeper metaphysical analysis, I offer a revised rationale for the validity of the neurological criterion of human death. © The Author 2016. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Spanish experience as a leading country: what kind of measures were taken?

PubMed

Matesanz, Rafael; Domínguez-Gil, Beatriz; Coll, Elisabeth; de la Rosa, Gloria; Marazuela, Rosario

2011-04-01

A recent call for self-sufficiency in transplantation issued by the WHO faces variable worldwide activity, in which Spain occupies a privileged position, with deceased donation rates of 33-35per million population (pmp) and 85 transplants pmp. An evaluation of current challenges, including a decrease in deaths because of traffic accidents and cerebrovascular diseases, and a diversity of cultures in Spain, has been followed by a comprehensive strategy to increase organ availability. Actions include an earlier referral of possible donors to the transplant coordination teams, a benchmarking project to identify critical success factors in donation after brain death, new family approach and care methods, and the development of additional training courses aimed at specific groups of professionals, supported by their corresponding societies. Consensus documents to improve knowledge about safety limits for organ donation have been developed to minimize inappropriate discarding of organs. Use of organs from expanded criteria donors under an 'old for old' allocation policy has resulted from adaptation to the progressive decline of optimal organs. National strategic plans to deal better with organ shortage, while respecting solid ethical standards, are essential, as reflected in the WHO Guiding Principles and the Istanbul Declaration on Organ Trafficking and Transplant tourism. © 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.

Ebola and Its Control in Liberia, 2014–2015

PubMed Central

Nyenswah, Tolbert G.; Kateh, Francis; Bawo, Luke; Massaquoi, Moses; Gbanyan, Miatta; Fallah, Mosoka; Nagbe, Thomas K.; Karsor, Kollie K.; Wesseh, C. Sanford; Sieh, Sonpon; Gasasira, Alex; Graaff, Peter; Hensley, Lisa; Rosling, Hans; Lo, Terrence; Pillai, Satish K.; Gupta, Neil; Montgomery, Joel M.; Ransom, Ray L.; Williams, Desmond; Laney, A. Scott; Lindblade, Kim A.; Slutsker, Laurence; Telfer, Jana L.; Christie, Athalia; Mahoney, Frank

2016-01-01

The severe epidemic of Ebola virus disease in Liberia started in March 2014. On May 9, 2015, the World Health Organization declared Liberia free of Ebola, 42 days after safe burial of the last known case-patient. However, another 6 cases occurred during June–July; on September 3, 2015, the country was again declared free of Ebola. Liberia had by then reported 10,672 cases of Ebola and 4,808 deaths, 37.0% and 42.6%, respectively, of the 28,103 cases and 11,290 deaths reported from the 3 countries that were heavily affected at that time. Essential components of the response included government leadership and sense of urgency, coordinated international assistance, sound technical work, flexibility guided by epidemiologic data, transparency and effective communication, and efforts by communities themselves. Priorities after the epidemic include surveillance in case of resurgence, restoration of health services, infection control in healthcare settings, and strengthening of basic public health systems. PMID:26811980

Ebola and Its Control in Liberia, 2014-2015.

PubMed

Nyenswah, Tolbert G; Kateh, Francis; Bawo, Luke; Massaquoi, Moses; Gbanyan, Miatta; Fallah, Mosoka; Nagbe, Thomas K; Karsor, Kollie K; Wesseh, C Sanford; Sieh, Sonpon; Gasasira, Alex; Graaff, Peter; Hensley, Lisa; Rosling, Hans; Lo, Terrence; Pillai, Satish K; Gupta, Neil; Montgomery, Joel M; Ransom, Ray L; Williams, Desmond; Laney, A Scott; Lindblade, Kim A; Slutsker, Laurence; Telfer, Jana L; Christie, Athalia; Mahoney, Frank; De Cock, Kevin M

2016-02-01

The severe epidemic of Ebola virus disease in Liberia started in March 2014. On May 9, 2015, the World Health Organization declared Liberia free of Ebola, 42 days after safe burial of the last known case-patient. However, another 6 cases occurred during June-July; on September 3, 2015, the country was again declared free of Ebola. Liberia had by then reported 10,672 cases of Ebola and 4,808 deaths, 37.0% and 42.6%, respectively, of the 28,103 cases and 11,290 deaths reported from the 3 countries that were heavily affected at that time. Essential components of the response included government leadership and sense of urgency, coordinated international assistance, sound technical work, flexibility guided by epidemiologic data, transparency and effective communication, and efforts by communities themselves. Priorities after the epidemic include surveillance in case of resurgence, restoration of health services, infection control in healthcare settings, and strengthening of basic public health systems.

Of wholes and parts: A Thomistic refutation of "Brain Death".

PubMed

Accad, Michel

2015-08-01

I propose a refutation of the two major arguments that support the concept of "brain death" as an ontological equivalent to death of the human organism. I begin with a critique of the notion that a body part, such as the brain, could act as "integrator" of a whole body. I then proceed with a rebuttal of the argument that destruction of a body part essential for rational operations-such as the brain-necessarily entails that the remaining whole is indisposed to accrue a rational soul. Next, I point to the equivocal use of the terms "alive" or "living" as being at the root of conceptual errors about brain death. I appeal to the Thomistic definition of life and to the hylomorphic concept of "virtual presence" to clarify this confusion. Finally, I show how the Thomistic definition of life supports the traditional criterion for the determination of death. Lay summary: By the mid-1960s, medical technology became available that could keep "alive" the bodies of patients who had sustained complete and irreversible brain injury. The concept of "brain death" emerged to describe such states. Physicians, philosophers, and ethicists then proposed that the state of brain death is equivalent to the state of death traditionally identified by the absence of spontaneous pulse and respiration. This article challenges the major philosophical arguments that have been advanced to draw this equivalence.

Lived Experiences of Iranian Nurses Caring for Brain Death Organ Donor Patients: Caring as “Halo of Ambiguity and Doubt”

PubMed Central

Keshtkaran, Zahra; Sharif, Farkhondeh; Navab, Elham; Gholamzadeh, Sakineh

2016-01-01

Background: Brain death is a concept in which its criteria have been expressed as documentations in Harvard Committee of Brain Death. The various perceptions of caregiver nurses for brain death patients may have effect on the chance of converting potential donors into actual organ donors. Objective: The present study has been conducted in order to perceive the experiences of nurses in care-giving to the brain death of organ donor patients. Methods: This qualitative study was carried out by means of Heidegger’s hermeneutic phenomenology. Eight nurses who have been working in ICU were interviewed. The semi-structured interviews were recorded by a tape-recorder and the given texts were transcribed and the analyses were done by Van-Mannen methodology and (thematic) analysis. Results: One of the foremost themes extracted from this study included ‘Halo of ambiguity and doubt’ that comprised of two sub-themes of ‘having unreasonable hope’ and ‘Conservative acceptance of brain death’. The unreasonable hope included lack of trust (uncertainty) in diagnosis and verification of brain death, passing through denial wall, and avoidance from explicit and direct disclosure of brain death in patients’ family. In this investigation, the nurses were involved in a type of ambiguity and doubt in care-giving to the potentially brain death of organ donor patients, which were also evident in their interaction with patients’ family and for this reason, they did not definitely announce the brain death and so far they hoped for treatment of the given patient. Such confusion and hesitance both caused annoyance of nurses and strengthening the denial of patients’ family to be exposed to death. Conclusion: The results of this study reveal the fundamental perceived care-giving of brain death in organ donor patients and led to developing some strategies to improve care-giving and achievement in donation of the given organ and necessity for presentation of educational and supportive services for nurses might become more evident than ever. PMID:26925919

Knowledge of the Brain Death Concept Among the Population of Havana, Cuba.

PubMed

Ríos, A; López-Navas, A I; Sánchez, Á; Martinez-Alarcon, L; Ayala, M A; Garrido, G; Sebastián, M J; Ramis, G; Abdo-Cuza, A; Hernández, A; Ramírez, P; Parrilla, P

2018-03-01

One of the main reasons against organ donation is the fear of apparent death due to ignorance of the brain death concept. Our aim was to assess knowledge about and acceptance of the brain death concept among the population of Havana, Cuba. The population screened, stratified by gender and age, included those >15 years old and living in Havana, Cuba. The appraisal tool utilized was a questionnaire on attitude toward organ donation ("PCID-DTO Ríos"). A random selection of individuals were surveyed according to the stratification. Cuba's census data were used. The participation was anonymized and self-administered. The verbal consent of participants was provided. There were 920 respondents: 31% (n = 282) knew the concept of brain death and accepted it; 57% (n = 529) did not; and 12% (n = 109) had a misperception, or did not accept brain death as a person's death. Those who knew and accepted the concept had a more favorable attitude toward their own organ donation after death (85% vs 61%; P < .001). The psychosocial factors related to the knowledge of brain death concept were: the gender (P = .002), to make up for speaking at a family level about the organ transplant (P < .001), the couple's opinion about the organ donation (P < .001) and the religion (P < .001). The brain death concept is not well understood in the population of Havana, Cuba. Copyright © 2017 Elsevier Inc. All rights reserved.

Case 252: Acute Hyperammonemic Encephalopathy Resulting from Late-Onset Ornithine Transcarbamylase Deficiency.

PubMed

Hershman, Michelle; Carmody, Raymond; Udayasankar, Unni K

2018-04-01

History A 19-year-old woman with no pertinent medical history was brought to the emergency department after being found unconscious on her bathroom floor by her roommate. In the preceding weeks, she had reported intractable nausea and vomiting, for which she had been taking ondansetron. No other medications had been prescribed. The day prior to presentation, she had contacted her mother and described increasing confusion. Glasgow coma scale score on arrival in the emergency department was 4. Intravenous naloxone was administered, without immediate response. Initial blood glucose level was 232 mg/dL (12.8 mmol/L) (normal range, 79-140 mg/dL [4.4- 7.7 mmol/L]), and other routine laboratory test results were normal. Urine toxicology results were negative. Cerebrospinal fluid evaluation revealed levels were within normal limits. Neurologic examination revealed dilated pupils, which showed a sluggish response to light, and left lower extremity rigidity with intermittent tremors. Initial unenhanced cranial computed tomographic (CT) findings were negative. Magnetic resonance (MR) imaging of the brain was performed. The patient's condition deteriorated, with increasing cerebral edema over the next week, and she was declared brain dead. Her liver was transplanted into an adult recipient, who subsequently developed cerebral edema and elevated plasma ammonia levels, resulting in death in the immediate postoperative period.

Predictors of neurologic and nonneurologic death in patients with brain metastasis initially treated with upfront stereotactic radiosurgery without whole-brain radiation therapy.

PubMed

McTyre, Emory R; Johnson, Adam G; Ruiz, Jimmy; Isom, Scott; Lucas, John T; Hinson, William H; Watabe, Kounosuke; Laxton, Adrian W; Tatter, Stephen B; Chan, Michael D

2017-04-01

In this study we attempted to discern the factors predictive of neurologic death in patients with brain metastasis treated with upfront stereotactic radiosurgery (SRS) without whole brain radiation therapy (WBRT) while accounting for the competing risk of nonneurologic death. We performed a retrospective single-institution analysis of patients with brain metastasis treated with upfront SRS without WBRT. Competing risks analysis was performed to estimate the subdistribution hazard ratios (HRs) for neurologic and nonneurologic death for predictor variables of interest. Of 738 patients treated with upfront SRS alone, neurologic death occurred in 226 (30.6%), while nonneurologic death occurred in 309 (41.9%). Multivariate competing risks analysis identified an increased hazard of neurologic death associated with diagnosis-specific graded prognostic assessment (DS-GPA) ≤ 2 (P = .005), melanoma histology (P = .009), and increased number of brain metastases (P<.001), while there was a decreased hazard associated with higher SRS dose (P = .004). Targeted agents were associated with a decreased HR of neurologic death in the first 1.5 years (P = .04) but not afterwards. An increased hazard of nonneurologic death was seen with increasing age (P =.03), nonmelanoma histology (P<.001), presence of extracranial disease (P<.001), and progressive systemic disease (P =.004). Melanoma, DS-GPA, number of brain metastases, and SRS dose are predictive of neurologic death, while age, nonmelanoma histology, and more advanced systemic disease are predictive of nonneurologic death. Targeted agents appear to delay neurologic death. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Legislative Enforcement of Nonconsensual Determination of Neurological (Brain) Death in Muslim Patients: A Violation of Religious Rights.

PubMed

Rady, Mohamed Y; Verheijde, Joseph L

2018-04-01

Death is defined in the Quran with a single criterion of irreversible separation of the ruh (soul) from the body. The Quran is a revelation from God to man, and the primary source of Islamic knowledge. The secular concept of death by neurological criteria, or brain death, is at odds with the Quranic definition of death. The validity of this secular concept has been contested scientifically and philosophically. To legitimize brain death for the purpose of organ donation and transplantation in Muslim communities, Chamsi-Pasha and Albar (concurring with the US President's Council on Bioethics) have argued that irreversible loss of capacity for consciousness and breathing (apneic coma) in brain death defines true death in accordance with Islamic sources. They have postulated that the absence of nafs (personhood) and nafas (breath) in apneic coma constitutes true death because of departure of the soul (ruh) from the body. They have also asserted that general anesthesia is routine in brain death before surgical procurement. Their argument is open to criticism because: (1) the ruh is described as the essence of life, whereas the nafs and nafas are merely human attributes; (2) unlike true death, the ruh is still present even with absent nafs and nafas in apneic coma; and (3) the routine use of general anesthesia indicates the potential harm to brain-dead donors from surgical procurement. Postmortem general anesthesia is not required for autopsy. Therefore, the conclusion must be that legislative enforcement of nonconsensual determination of neurological (brain) death and termination of life-support and medical treatment violates the religious rights of observant Muslims.

Informed consent for the diagnosis of brain death: a conceptual argument.

PubMed

Muramoto, Osamu

2016-10-13

This essay provides an ethical and conceptual argument for the use of informed consent prior to the diagnosis of brain death. It is meant to enable the family to make critical end-of-life decisions, particularly withdrawal of life support system and organ donation, before brain death is diagnosed, as opposed to the current practice of making such decisions after the diagnosis of death. The recent tragic case of a 13-year-old brain-dead patient in California who was maintained on a ventilator for over 2 years illustrates how such a consent would have made a crucial difference. Conceptual, philosophical, and ethical analysis. I first consider a conceptual justification for the use of consent for certain non-beneficial and unwanted medical diagnoses. I suggest that the diagnosis of brain death falls into this category for some patients. Because the diagnostic process of brain death lacks the transparency of traditional death determination, has a unique epistemic structure and a complex risk-benefit profile which differs markedly from case to case, and presents conflicts of interest for physicians and society, I argue that pre-diagnostic counseling and informed consent should be part of the diagnostic process. This approach can be termed as "allow cardiac death", whose parallel logic with "allow natural death" is discussed. I also discuss potential negative impacts on organ donation and health care cost from this proposal and offer possible mitigation. I show that the pre-diagnostic counseling can improve the possibility for well-thought-out decisions regarding organ donation and terminating life-support system in cases of hopeless prognosis. This approach differs conceptually from the pluralism of the definition of death, such as those in New Jersey and Japan, and it upholds the Uniform Determination of Death Act. My intention is not to provide an instant panacea for the ongoing impasse of the brain death debate, but to point to a novel conceptual ground for a more pragmatic, and more patient- and family-centered approach. By enabling the family to consent to or decline the diagnostic process of brain death, but not to choose the definition of death, it upholds the current legal definition of death.

Numbers of Brain Deaths and Deceased Donors in Hospitals in Istanbul Region That Have Transplantation Units: A Retrospective Analysis Between the Years 2005 and 2015.

PubMed

Harmanci Seren, A K; Yavuz, H

2017-04-01

Turkey is one of the countries facing a serious organ shortage problem, with thousands of patients with end-stage organ failure. The Social Security Institution started to increase the reimbursement for transplantation operations in 2007 to solve this problem, and this policy has continued since then. Although the number of transplantation centers and operations in Turkey increased in this term, according to organ donation and transplantation statistics from the Ministry of Health, the rate of organ retrieval from deceased organ donors has decreased. This study was performed with the purpose of retrospectively analyzing (between the years 2005 and 2015) the number of brain deaths and donors after brain death in hospitals that are affiliated with the Istanbul Regional Coordination Office and have transplantation units. Data were collected via the website of the Ministry of Health. Hospitals were categorized as those directly affiliated with the Ministry of Health, university hospitals, and private hospitals. This study found that the number of transplantation centers has increased >3 times since 2005, and the number of private transplantation centers has increased 9 times for the same period. We also found that the number of brain deaths, donors after brain death in hospitals, and number of brain deaths and donors after brain death per hospital had varied throughout the study years. Although the number of transplantation centers has increased since 2005, the number of brain deaths and donors after brain death has not increased to the same extent for this period in these hospitals that have transplantation units. Copyright © 2017 Elsevier Inc. All rights reserved.

Ethical and medical management of a pregnant woman with brain stem death resulting in delivery of a healthy child and organ donation.

PubMed

Gopčević, A; Rode, B; Vučić, M; Horvat, A; Širanović, M; Gavranović, Ž; Košec, V; Košec, A

2017-11-01

Maternal brain death during pregnancy remains an exceedingly complex situation that requires not only a well-considered medical management plan, but also careful decision-making in a legally and ethically delicate situation. Management of brain dead pregnant patients needs to adhere to special strategies that support the mother in a way that she can deliver a viable and healthy child. Brain death in pregnant women is very rare, with only a few published cases. We present a case of a pregnant woman with previously diagnosed multiple brain cavernomas that led to intracranial hemorrhage and brain stem death during the 21st week of pregnancy. The condition that can be proven unequivocally, using tests that do not endanger viability of the fetus, is brain stem death, diagnosed through absence of cranial reflexes. The patient was successfully treated until delivery of a healthy female child at 29weeks of gestation. The patient received continuous hormone substitution therapy, fetal monitoring and extrinsic regulation of maternal homeostasis over 64days. After delivery, the final diagnosis of brain death was established through multi-slice computerized tomography pan-angiography. This challenging case discusses ethical and medical circumstances arising from a diagnosis of maternal brain death, while showing that prolongation of somatic life support in a multidisciplinary setting can result in a successful pregnancy outcome. Copyright © 2017 Elsevier Ltd. All rights reserved.

Brain death revisited: it is not 'complete death' according to Islamic sources.

PubMed

Bedir, Ahmet; Aksoy, Sahin

2011-05-01

Concepts, such as death, life and spirit cannot be known in their quintessential nature, but can be defined in accordance with their effects. In fact, those who think within the mode of pragmatism and Cartesian logic have ignored the metaphysical aspects of these terms. According to Islam, the entity that moves the body is named the soul. And the aliment of the soul is air. Cessation of breathing means leaving of the soul from the body. Those who agree on the diagnosis of brain death may not able to agree unanimously on the rules that lay down such diagnosis. That is to say, there are a heap of suspicions regarding the diagnosis of brain death, and these suspicions are on the increase. In fact, Islamic jurisprudence does not put provisions, decisions on suspicious grounds. By virtue of these facts, it can be asserted that brain death is not absolute death according to Islamic sources; for in the patients diagnosed with brain death the soul still has not abandoned the body. Therefore, these patients suffer in every operation performed on them.

38 CFR 3.901 - Fraud.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., Compensation, and Dependency and Indemnity Compensation Forfeiture § 3.901 Fraud. (a) Definition. An act... death benefit payable. (2) Amount of compensation payable but for the forfeiture. No benefits are... affidavit, declaration, certificate, statement, voucher, or paper, concerning any claim for benefits under...

Brain dead or not? CT angiogram yielding false-negative result on brain death confirmation.

PubMed

Johnston, Robyn; Kaliaperumal, Chandrasekaran; Wyse, Gerald; Kaar, George

2013-01-08

We describe a case of severe traumatic brain injury with multiple facial and skull fractures where CT angiogram (CTA) failed to yield a definite result of brain death as an ancillary test. A 28-year-old man was admitted following a road traffic accident with a Glasgow Coma Score (GCS) of 3/15 and fixed pupils. CT brain revealed uncal herniation and diffuse cerebral oedema with associated multiple facial and skull fractures. 72 h later, his clinical condition remained the same with high intracranial pressure refractory to medical management. Clinical confirmation on brain death was not feasible owing to facial injuries. A CTA, performed to determine brain perfusion, yielded a 'false-negative' result. Skull fractures have possibly led to venous prominence in the cortical and deep venous drainage system. This point needs to be borne in mind while considering CTA as an ancillary test to confirm brain death.

Brain dead or not? CT angiogram yielding false-negative result on brain death confirmation

PubMed Central

Johnston, Robyn; Kaliaperumal, Chandrasekaran; Wyse, Gerald; Kaar, George

2013-01-01

We describe a case of severe traumatic brain injury with multiple facial and skull fractures where CT angiogram (CTA) failed to yield a definite result of brain death as an ancillary test. A 28-year-old man was admitted following a road traffic accident with a Glasgow Coma Score (GCS) of 3/15 and fixed pupils. CT brain revealed uncal herniation and diffuse cerebral oedema with associated multiple facial and skull fractures. 72 h later, his clinical condition remained the same with high intracranial pressure refractory to medical management. Clinical confirmation on brain death was not feasible owing to facial injuries. A CTA, performed to determine brain perfusion, yielded a ‘false-negative’ result. Skull fractures have possibly led to venous prominence in the cortical and deep venous drainage system. This point needs to be borne in mind while considering CTA as an ancillary test to confirm brain death. PMID:23302550

Portrayal of Brain Death in Film and Television.

PubMed

Lewis, A; Weaver, J; Caplan, A

2017-03-01

We sought to evaluate whether television and cinematic coverage of brain death is educational or misleading. We identified 24 accessible productions that addressed brain death using the archives of the Paley Center for Media (160 000 titles) and the Internet Movie Database (3.7 million titles). Productions were reviewed by two board-certified neurologists. Although 19 characters were pronounced brain dead, no productions demonstrated a complete examination to assess for brain death (6 included an assessment for coma, 9 included an evaluation of at least 1 brainstem reflex, but none included an assessment of every brainstem reflex, and 2 included an apnea test). Subjectively, both authors believed only a small fraction of productions (13% A.L., 13% J.W.) provided the public a complete and accurate understanding of brain death. Organ donation was addressed in 17 productions (71%), but both reviewers felt that the discussions about organ donation were professional in a paucity of productions (9% for A.L., 27% for J.W.). Because television and movies serve as a key source for public education, the quality of productions that feature brain death must be improved. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Rationale for Activity Based Alternatives in Lieu of Lectures. Research Brief

ERIC Educational Resources Information Center

Walker, Karen

2005-01-01

Since the 1990s was declared to be the decade of the brain, technology has advanced enough through MRIs, CAT Scans and PET Scans, that live brains have been able to be studied. Although this is still a relatively new field of study, what has been discovered thus far, has wide reaching implications for educators in the area of pedagogy and how to…

Is donation after cardiac death reducing the brain-dead donor pool in Australia?

PubMed

Sampson, Brett G; O'Callaghan, Gerry P; Russ, Graeme R

2013-03-01

Donation after cardiac death (DCD) has increased faster than donation after brain death (DBD) in Australia. However, DBD is the preferred pathway because it provides more organs per donor, the donation process is simpler and transplant outcomes are optimised. To determine if the increase in DCD has reduced the brain-dead donor pool in Australia. Retrospective analysis of records of organ donors (intended and actual) with brain injury as the cause of death from 2001 to 2011 in Australian intensive care units. Change in median ventilation period, over time, before brain-death determination in DBD donors (as DCD increased); a decreased median ventilation period in DBD donors being consistent with the conversion of DBD to DCD. As DCD (n = 311) increased, the median ventilation period in DBD donors (n = 2218) did not fall overall (P = 0.83), in all jurisdictions (P > 0.25) and for all causes of death (P > 0.3). The proportion of patients ventilated for less than 2 days was unchanged over time in both DBD (P = 1) and DCD (P = 0.99). The overall ventilation period in DCD donors (3.8 days; interquartile range [IQR], 2.1-6.3 days), exceeded the ventilation period in DBD donors (1.3 days; IQR, 1.0-2.4 days; P < 0.0001). DCD ventilation period was significantly longer in all jurisdictions, for all causes of death and annually (P < 0.05). In Australia, brain-injured donors appear to be ventilated long enough to allow progression to brain death before proceeding to DCD. Therefore, DCD is unlikely to have reduced the brain-dead donor pool.

Multicolor Fluorescence Imaging of Traumatic Brain Injury in a Cryolesion Mouse Model

PubMed Central

2012-01-01

Traumatic brain injury is characterized by initial tissue damage, which then can lead to secondary processes such as cell death and blood-brain-barrier disruption. Clinical and preclinical studies of traumatic brain injury typically employ anatomical imaging techniques and there is a need for new molecular imaging methods that provide complementary biochemical information. Here, we assess the ability of a targeted, near-infrared fluorescent probe, named PSS-794, to detect cell death in a brain cryolesion mouse model that replicates certain features of traumatic brain injury. In short, the model involves brief contact of a cold rod to the head of a living, anesthetized mouse. Using noninvasive whole-body fluorescence imaging, PSS-794 permitted visualization of the cryolesion in the living animal. Ex vivo imaging and histological analysis confirmed PSS-794 localization to site of brain cell death. The nontargeted, deep-red Tracer-653 was validated as a tracer dye for monitoring blood-brain-barrier disruption, and a binary mixture of PSS-794 and Tracer-653 was employed for multicolor imaging of cell death and blood-brain-barrier permeability in a single animal. The imaging data indicates that at 3 days after brain cryoinjury the amount of cell death had decreased significantly, but the integrity of the blood-brain-barrier was still impaired; at 7 days, the blood-brain-barrier was still three times more permeable than before cryoinjury. PMID:22860222

Non-declarative memory in the rehabilitation of amnesia.

PubMed

Cavaco, S; Malec, J F; Bergquist, T

2005-09-01

The ability of amnesic patients to learn and retain non-declarative information has been consistently demonstrated in the literature. This knowledge provided by basic cognitive neuroscience studies has been widely neglected in neuropsychological rehabilitation of memory impaired patients. This study reports the case of a 43 year old man with severe amnesia following an anterior communicating artery (ACoA) aneurysm rupture. The patient integrated a comprehensive (holistic) day treatment programme for rehabilitation of brain injury. The programme explored the advantages of using preserved non-declarative memory capacities, in the context of commonly used rehabilitation approaches (i.e. compensation for lost function and domain-specific learning). The patient's ability to learn and retain new cognitive and perceptual-motor skills was found to be critical for the patient's improved independence and successful return to work.

Gray Matter-White Matter De-Differentiation on Brain Computed Tomography Predicts Brain Death Occurrence.

PubMed

Vigneron, C; Labeye, V; Cour, M; Hannoun, S; Grember, A; Rampon, F; Cotton, F

2016-01-01

Previous studies have shown that a loss of distinction between gray matter (GM) and white matter (WM) on unenhanced CT scans was predictive of poor outcome after cardiac arrest. The aim of this study was to identify a marker/predictor of imminent brain death. In this retrospective study, 15 brain-dead patients after anoxia and cardiac arrest were included. Patients were paired (1:1) with normal control subjects. Only patients' unenhanced CT scans performed before brain death and during the 24 hours after initial signs were analyzed. WM and GM densities were measured in predefined regions of interest (basal ganglia level, centrum semi-ovale level, high convexity level, brainstem level). At each level, GM and WM density and GM/WM ratio for brain-dead patients and normal control subjects were compared using the Wilcoxon signed-rank test. At each level, a lower GM/WM ratio and decreased GM and WM densities were observed in brain-dead patients' CT scans when compared with normal control subject CT scans. A cut-off value of 1.21 at the basal ganglia level was identified, below which brain death systematically occurred. GM/WM dedifferentiation on unenhanced CT scan is measurable before the occurrence of brain death, highlighting its importance in brain death prediction. The mechanism of GM/WM differentiation loss could be explained by the lack of oxygen caused by ischemia initially affecting the mitochondrial system. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain death and marginal grafts in liver transplantation.

PubMed

Jiménez-Castro, M B; Gracia-Sancho, J; Peralta, C

2015-06-04

It is well known that most organs for transplantation are currently procured from brain-dead donors; however, the presence of brain death is an important risk factor in liver transplantation. In addition, one of the mechanisms to avoid the shortage of liver grafts for transplant is the use of marginal livers, which may show higher risk of primary non-function or initial poor function. To our knowledge, very few reviews have focused in the field of liver transplantation using brain-dead donors; moreover, reviews that focused on both brain death and marginal grafts in liver transplantation, both being key risk factors in clinical practice, have not been published elsewhere. The present review aims to describe the recent findings and the state-of-the-art knowledge regarding the pathophysiological changes occurring during brain death, their effects on marginal liver grafts and summarize the more controversial topics of this pathology. We also review the therapeutic strategies designed to date to reduce the detrimental effects of brain death in both marginal and optimal livers, attempting to explain why such strategies have not solved the clinical problem of liver transplantation.

[Revised act on organ transplantation: a pediatrician's viewpoint].

PubMed

Mizuguchi, Masashi

2010-06-01

In Japan, from July 2010, an infant or a child with brain death will be legally regarded as a candidate of donor for organ transplantation under the consent of his or her family members. Official diagnostic criteria of brain death in children are currently under compilation. The causes and incidence of brain death remarkably differ among individuals belonging to different age groups. Secondary brain damages resulting from asphyxia, drowning, hypoxemia, and cardiopulmonary arrest more commonly occur in childhood than in adulthood. Child abuse or neglect is suspected to be involved in many of the cases of brain death. The current Japanese diagnostic criteria hitherto used for adults require several modifications before these can be applied to infants and children. According to the requirements of the new act, abused or neglected infants and children must be excluded from the category of donor candidates. Neonates and young infants below 12 weeks of corrected age will also be excluded, because neurological diagnosis of brain death is difficult in these individuals.

A Double-Edged Sword Role for Ubiquitin-Proteasome System in Brain Stem Cardiovascular Regulation During Experimental Brain Death

PubMed Central

Wu, Carol H. Y.; Chan, Julie Y. H.; Chan, Samuel H. H.; Chang, Alice Y. W.

2011-01-01

Background Brain stem cardiovascular regulatory dysfunction during brain death is underpinned by an upregulation of nitric oxide synthase II (NOS II) in rostral ventrolateral medulla (RVLM), the origin of a life-and-death signal detected from blood pressure of comatose patients that disappears before brain death ensues. Furthermore, the ubiquitin-proteasome system (UPS) may be involved in the synthesis and degradation of NOS II. We assessed the hypothesis that the UPS participates in brain stem cardiovascular regulation during brain death by engaging in both synthesis and degradation of NOS II in RVLM. Methodology/Principal Findings In a clinically relevant experimental model of brain death using Sprague-Dawley rats, pretreatment by microinjection into the bilateral RVLM of proteasome inhibitors (lactacystin or proteasome inhibitor II) antagonized the hypotension and reduction in the life-and-death signal elicited by intravenous administration of Escherichia coli lipopolysaccharide (LPS). On the other hand, pretreatment with an inhibitor of ubiquitin-recycling (ubiquitin aldehyde) or ubiquitin C-terminal hydrolase isozyme L1 (UCH-L1) potentiated the elicited hypotension and blunted the prevalence of the life-and-death signal. Real-time polymerase chain reaction, Western blot, electrophoresis mobility shift assay, chromatin immunoprecipitation and co-immunoprecipitation experiments further showed that the proteasome inhibitors antagonized the augmented nuclear presence of NF-κB or binding between NF-κB and nos II promoter and blunted the reduced cytosolic presence of phosphorylated IκB. The already impeded NOS II protein expression by proteasome inhibitor II was further reduced after gene-knockdown of NF-κB in RVLM. In animals pretreated with UCH-L1 inhibitor and died before significant increase in nos II mRNA occurred, NOS II protein expression in RVLM was considerably elevated. Conclusions/Significance We conclude that UPS participates in the defunct and maintained brain stem cardiovascular regulation during experimental brain death by engaging in both synthesis and degradation of NOS II at RVLM. Our results provide information on new therapeutic initiatives against this fatal eventuality. PMID:22110641

Brain Death and Islam

PubMed Central

Ziad-Miller, Amna; Elamin, Elamin M.

2014-01-01

How one defines death may vary. It is important for clinicians to recognize those aspects of a patient’s religious beliefs that may directly influence medical care and how such practices may interface with local laws governing the determination of death. Debate continues about the validity and certainty of brain death criteria within Islamic traditions. A search of PubMed, Scopus, EMBASE, Web of Science, PsycNet, Sociological Abstracts, DIALOGUE ProQuest, Lexus Nexus, Google, and applicable religious texts was conducted to address the question of whether brain death is accepted as true death among Islamic scholars and clinicians and to discuss how divergent opinions may affect clinical care. The results of the literature review inform this discussion. Brain death has been acknowledged as representing true death by many Muslim scholars and medical organizations, including the Islamic Fiqh Academies of the Organization of the Islamic Conference and the Muslim World League, the Islamic Medical Association of North America, and other faith-based medical organizations as well as legal rulings by multiple Islamic nations. However, consensus in the Muslim world is not unanimous, and a sizable minority accepts death by cardiopulmonary criteria only. PMID:25287999

Pupillometry in brain death: differences in pupillary diameter between paediatric and adult subjects.

PubMed

Olgun, Gokhan; Newey, Christopher R; Ardelt, Agnieszka

2015-11-01

The determination of brain death in neonates, infants, children and adults relies on a clinical diagnosis based on the absence of neurological function with a known irreversible cause of brain injury. Evaluation of pupil size and non-reactivity is a requisite for determination of brain death. There are no studies in the literature that quantitatively assess pupil size in brain dead children and adults. Infants, children and adults diagnosed with brain death were included in the study. Pupils were measured with a quantitative pupillometer (Forsite; Neuroptics, Irvine, CA, USA). Median, minimum and maximum pupil sizes were documented and the results were adjudicated for age, vasopressor use and temperature. Median right and left pupil sizes were 5.01 ± 0.85 mm and 5.12 ± 0.87 mm, respectively, with a range between 3.69 and 7.34 mm. Paediatric pupils were larger than adult pupils (right pupil 5.53 vs 4.73 mm p: 0.018; left pupil 5.87 vs 4.77 mm P: 0.03), and there was no correlation of pupil size with temperature or increasing number of vasopressors. This is the first study in the literature objectively evaluating pupil sizes in infants, children and adults diagnosed with brain death. We observed variation between observed pupil size and that expected based on brain death determination guidelines.

[Prolonged clinical pattern of brain death in patients under barbiturate sedation: usefulness of transcranial Doppler].

PubMed

Segura, T; Jiménez, P; Jerez, P; García, F; Córcoles, V

2002-04-01

Throughout the world, is fully accepted that a person is dead when brain death exists. In most situations, neurological criteria permit the diagnosis of brain death, but in some instances, as when high-dose barbiturate therapy has been used, confirmatory testing are required by law. We report the case of a 17 year-old women who suffered high-dose barbiturate therapy due to post traumatic intracranial hypertension. During the period of the barbiturate infusion and until six days after the suppression of this therapy, neurological exploration and EEG findings seem to confirm brain death, while transcranial Doppler (TCD) study remained normal. TCD is a fast, simple and accurate confirmatory testing in the determination of brain death and its findings are not affected by high-dose barbiturate therapy. We think that TCD must be present in all hospitals where mechanical ventilation and support of patients are carried out.

Use of Ancillary Tests When Determining Brain Death in Pediatric Patients in the United States.

PubMed

Lewis, Ariane; Adams, Nellie; Chopra, Arun; Kirschen, Matthew P

2017-10-01

Although pediatric brain death guidelines stipulate when ancillary testing should be used during brain death determination, little is known about the way these recommendations are implemented in clinical practice. We conducted a survey of pediatric intensivists and neurologists in the United States on the use of ancillary testing. Although most respondents noted they only performed an ancillary test if the clinical examination and apnea test could not be completed, 20% of 195 respondents performed an ancillary test for other reasons, including (1) to convince a family that objected to the brain death determination that a patient is truly dead (n = 21), (2) personal preference (n = 14), and (3) institutional requirement (n = 5). Our findings suggest that pediatricians use ancillary tests for a variety of reasons during brain death determination. Medical societies and governmental regulatory bodies must reinforce the need for homogeneity in practice.

How many deaths will it take? A death from asthma associated with work-related environmental tobacco smoke.

PubMed

Stanbury, Martha; Chester, Debra; Hanna, Elizabeth A; Rosenman, Kenneth D

2008-02-01

Despite epidemiologic, experimental and observational data on the association of environmental tobacco smoke (ETS) and adverse health effects, bar and restaurant workers remain exposed to ETS in the majority of states and countries. Three public health surveillance systems were used to identify and conduct a follow-up investigation of a reported acute asthma death of a young waitress in a bar. The waitress collapsed at the bar where she worked and was declared dead shortly thereafter. Evaluation of the circumstances of her death and her medical history concluded that her death was from acute asthma due to environmental tobacco smoke at work. This is the first reported acute asthma death associated with work-related ETS. Recent studies of asthma among bar and restaurant workers before and after smoking bans support this association. This death dramatizes the need to enact legal protections for workers in the hospitality industry from secondhand smoke.

[Determination of irreversibility of clinical brain death. Electroencephalography and evoked potentials].

PubMed

Buchner, H; Ferbert, A

2016-02-01

Principally, in the fourth update of the rules for the procedure to finally determine the irreversible cessation of function of the cerebrum, the cerebellum and the brainstem, the importance of an electroencephalogram (EEG), somatosensory evoked potentials (SEP) and brainstem auditory evoked potentials (BAEP) are confirmed. This paper presents the reliability and validity of the electrophysiological diagnosis, discusses the amendments in the fourth version of the guidelines and introduces the practical application, problems and sources of error.An EEG is the best established supplementary diagnostic method for determining the irreversibility of clinical brain death syndrome. It should be noted that residual brain activity can often persist for many hours after the onset of brain death syndrome, particularly in patients with primary brainstem lesions. The derivation and analysis of an EEG requires a high level of expertise to be able to safely distinguish artefacts from primary brain activity. The registration of EEGs to demonstrate the irreversibility of clinical brain death syndrome is extremely time consuming.The BAEPs can only be used to confirm the irreversibility of brain death syndrome in serial examinations or in the rare cases of a sustained wave I or sustained waves I and II. Very often, an investigation cannot be reliably performed because of existing sound conduction disturbances or failure of all potentials even before the onset of clinical brain death syndrome. This explains why BAEPs are only used in exceptional cases.The SEPs of the median nerve can be very reliably derived, are technically simple and with few sources of error. A serial investigation is not required and the time needed for examination is short. For these reasons SEPs are given preference over EEGs and BAEPs for establishing the irreversibility of clinical brain death syndrome.

Arguments against promoting organ transplants from brain-dead donors, and views of contemporary Japanese on life and death.

PubMed

Asai, Atsushi; Kadooka, Yasuhiro; Aizawa, Kuniko

2012-05-01

As of 2009, the number of donors in Japan is the lowest among developed countries. On July 13, 2009, Japan's Organ Transplant Law was revised for the first time in 12 years. The revised and old laws differ greatly on four primary points: the definition of death, age requirements for donors, requirements for brain-death determination and organ extraction, and the appropriateness of priority transplants for relatives. In the four months of deliberations in the National Diet before the new law was established, various arguments regarding brain death and organ transplantation were offered. An amazing variety of opinions continue to be offered, even after more than 40 years have elapsed since the first heart organ transplant in Japan. Some are of the opinion that with the passage of the revised law, Japan will finally become capable of performing transplants according to global standards. Contrarily, there are assertions that organ transplants from brain-dead donors are unacceptable because they result in organs being taken from living human beings. Considering the current conditions, we will organize and introduce the arguments for and against organ transplants from brain-dead donors in contemporary Japan. Subsequently, we will discuss the primary arguments against organ transplants from brain-dead donors from the perspective of contemporary Japanese views on life and death. After introducing the recent view that brain death should not be regarded as equivalent to the death of a human being, we would like to probe the deeply-rooted views on life and death upon which it is based. © 2010 Blackwell Publishing Ltd.

Ethical controversies surrounding the management of potential organ donors in the emergency department.

PubMed

Venkat, Arvind; Baker, Eileen F; Schears, Raquel M

2014-08-01

On a daily basis, emergency physicians are confronted by patients with devastating neurological injuries and insults. Some of these patients, despite our best efforts, will not survive. However, from these tragedies, there may be benefit given to others who are awaiting organ transplantation. Steps taken in the emergency department (ED) can be critical to preserving the option of organ donation in patients whose neurologic insult places them on a potential path to declaration of brain death. Much of the literature on this subject has focused on the utilitarian value of clinical interventions in the potential organ donor to optimize the likelihood of effective organ procurement. In this article, we present an actual case that reveals additional ethical perspectives to consider in how emergency physicians manage patients in the ED who can be confidently predicted to progress to death, as attested by neurologic criteria, and become organ donors. The case involves a patient with a devastating, nonsurvivable intracerebral hemorrhage who rapidly progressed to hemodynamic instability. This case reveals how the current organ donor referral and maintenance system raises ethical tensions for emergency physicians and ED personnel. This process imposes limitations on communication with patient surrogate decision-makers while calling for interventions with the primary purpose of benefiting off-site patients awaiting transplantation. Copyright © 2014 Elsevier Inc. All rights reserved.

Brain stem death and organ donation.

PubMed

Davies, C

1996-01-01

Our understanding of the concept and definition of death has changed over time. The British contribution to the body of knowledge on the diagnosis of brain steam death was the publication by the medical royal colleges (1976) of diagnostic criteria. Most literature and research which explores the knowledge and attitudes of nurses towards the concept of brain stem death is from the USA. Several issues which arise from the literature are discussed in relation to organ donation. Further UK-based research is required.

Factors Affecting the Occurrence of Spinal Reflexes in Brain Dead Cases.

PubMed

Hosseini, Mahsa Sadat; Ghorbani, Fariba; Ghobadi, Omid; Najafizadeh, Katayoun

2015-08-01

Brain death is defined as the permanent absence of all cortical and brain stem reflexes. A wide range of spontaneous or reflex movements that are considered medullary reflexes are observed in heart beating cases that appear brain dead, which may create uncertainty about the diagnosis of brain death and cause delays in deceased-donor organ donation process. We determined the frequency and type of medullary reflexes and factors affecting their occurrence in brain dead cases. During 1 year, 122 cases who fulfilled the criteria for brain death were admitted to the special intensive care unit for organ procurement of Masih Daneshvari Hospital. Presence of spinal reflexes was evaluated by trained coordinators and was recorded in a form in addition to other information including demographic characteristics, cause of brain death, time from detection of brain death, history of craniotomy, vital signs, serum electrolyte levels, and parameters of arterial blood gas determination. Most cases (63%) included in this study were male, and mean age was 33 ± 15 y. There was > 1 spinal reflex observed in 40 cases (33%). The most frequent reflex was plantar response (17%) following by myoclonus (10%), triple flexion reflex (9%), pronator extension reflex (8%), and undulating toe reflex (7%). Mean systolic blood pressure was significantly higher in cases who exhibited medullary reflexes than other cases (126 ± 19 mm Hg vs 116 ± 17 mm Hg; P = .007). Spinal reflexes occur frequently in brain dead cases, especially when they become hemodynamically stable after treatment in the organ procurement unit. Observing these movements by caregivers and family members has a negative effect on obtaining family consent and organ donation. Increasing awareness about spinal reflexes is necessary to avoid suspicion about the brain death diagnosis and delays in organ donation.

Determination of Death and the Dead Donor Rule: A Survey of the Current Law on Brain Death

PubMed Central

Nikas, Nikolas T.; Bordlee, Dorinda C.; Moreira, Madeline

2016-01-01

Despite seeming uniformity in the law, end-of-life controversies have highlighted variations among state brain death laws and their interpretation by courts. This article provides a survey of the current legal landscape regarding brain death in the United States, for the purpose of assisting professionals who seek to formulate or assess proposals for changes in current law and hospital policy. As we note, the public is increasingly wary of the role of organ transplantation in determinations of death, and of the variability of brain death diagnosing criteria. We urge that any attempt to alter current state statutes or to adopt a national standard must balance the need for medical accuracy with sound ethical principles which reject the utilitarian use of human beings and are consistent with the dignity of the human person. Only in this way can public trust be rebuilt. PMID:27097648

The neural basis of novelty and appropriateness in processing of creative chunk decomposition.

PubMed

Huang, Furong; Fan, Jin; Luo, Jing

2015-06-01

Novelty and appropriateness have been recognized as the fundamental features of creative thinking. However, the brain mechanisms underlying these features remain largely unknown. In this study, we used event-related functional magnetic resonance imaging (fMRI) to dissociate these mechanisms in a revised creative chunk decomposition task in which participants were required to perform different types of chunk decomposition that systematically varied in novelty and appropriateness. We found that novelty processing involved functional areas for procedural memory (caudate), mental rewarding (substantia nigra, SN), and visual-spatial processing, whereas appropriateness processing was mediated by areas for declarative memory (hippocampus), emotional arousal (amygdala), and orthography recognition. These results indicate that non-declarative and declarative memory systems may jointly contribute to the two fundamental features of creative thinking. Copyright © 2015 Elsevier Inc. All rights reserved.

Causes of organ donation failure in Brazil.

PubMed

Dell Agnolo, C M; de Freitas, R A; Toffolo, V J O; de Oliveira, M L F; de Almeida, D F; Carvalho, M D B; Pelloso, S M

2012-10-01

There has been a great improvement in transplantation medicine in Brazil in the last 2 decades. However, there remain several barriers regarding notification of brain and cardiac death as well as completion of the donation process. This retrospective study was performed between January 2008 and December 2010. We reviewed all deaths in a University Hospital, observing the causes of non-notification to the State Transplantation Authority and non-donations. There were 41 notifications of brain death resulting in donation in only 19.5% of those cases. Cardiac death was diagnosed in 21 patients, resulting in 52.4% donations. The main cause for non-donation were family refusal (37.2%), infectious diseases (30.2%), and clinical contraindications (32.6%). Most of the missed possible donors occurred during the night (54.8%) and in the emergency room (80.9%). There is an urgent need for better education of the Brazilian population about organ donation and brain death definitions. Other identified problems include lack of uniformity in brain death determinations among hospitals, rigid contraindications to donation in the State of Parana, physician unawareness or disbelief about brain death diagnostic criteria, and lack of structure of our Hospital. Copyright © 2012. Published by Elsevier Inc.

Ethical issues in critical care and cardiac arrest: clinical research, brain death, and organ donation.

PubMed

Donatelli, Luke A; Geocadin, Romergryko G; Williams, Michael A

2006-09-01

Cardiac arrest results in global hypoxic-ischemic brain injury from which there is a range of possible neurological outcomes. In most cases, patients may require a surrogate to make decisions regarding end-of-life care, including the withdrawal of life-sustaining therapies. This article reviews ethical considerations that arise in the clinical care of patients following cardiac arrest, including decisions to continue or withdraw life-sustaining therapies; brain death determination; and organ donation in the context of brain death and cardiac death (so-called non-heart-beating donation). This article also discusses ethical concerns pertaining to the design and conduct of resuscitation research that is necessary for the development of effective therapies to prevent anoxic brain injury or promote neurological recovery.

Upregulated miR-29b promotes neuronal cell death by inhibiting Bcl2L2 after ischemic brain injury.

PubMed

Shi, Guodong; Liu, Yang; Liu, Tielong; Yan, Wangjun; Liu, Xiaowei; Wang, Yuan; Shi, Jiangang; Jia, Lianshun

2012-01-01

It is increasingly clear that microRNAs (miRNAs) play an important role in controlling cell survival. However, the functional significance of miRNAs in ischemic brain injury remains poorly understood. In the present study, we assayed the expression levels of miR-29b after ischemic brain injury, and defined the target genes and biological functions of miR-29b. We found that the miR-29b levels were significantly increased in rat brain after transient middle cerebral artery occlusion and neurons after oxygen-glucose deprivation. Moreover, ectopic expression of miR-29b promoted neuronal cell death, whereas its repression decreased cell death. Furthermore, we verified that miR-29b directly targeted and inhibited Bcl2L2 gene expression, and then increased neuronal cell death. Importantly, Bcl2L2 overexpression rescued neuronal cell death induced by miR-29b. These results suggest an important role of miR-29b in regulating neuronal cell death, thus offering a new target for the development of therapeutic agents against ischemic brain injury.

A Thomistic defense of whole-brain death

PubMed Central

Eberl, Jason T.

2015-01-01

Michel Accad critiques the currently accepted whole-brain criterion for determining the death of a human being from a Thomistic metaphysical perspective and, in so doing, raises objections to a particular argument defending the whole-brain criterion by Patrick Lee and Germain Grisez. In this paper, I will respond to Accad's critique of the whole-brain criterion and defend its continued validity as a criterion for determining when a human being's death has occurred in accord with Thomistic metaphysical principles. I will, however, join Accad in criticizing Lee and Grisez's proposed defense of the whole-brain criterion as potentially leading to erroneous conclusions regarding the determination of human death. Lay summary: Catholic physicians and bioethicists currently debate the legally accepted clinical standard for determining when a human being has died—known as the “wholebrain criterion”—which has also been morally affirmed by the Magisterium. This paper responds to physician Michel Accad’s critique of the whole-brain criterion based upon St. Thomas Aquinas’s metaphysical account of human nature as a union of a rational soul and a material body. I defend the whole-brain criterion from the same Thomistic philosophical perspective, while agreeing with Accad’s objection to an alternative Thomistic defense of whole-brain death by philosophers Patrick Lee and Germain Grisez. PMID:26912933

A Thomistic defense of whole-brain death.

PubMed

Eberl, Jason T

2015-08-01

Michel Accad critiques the currently accepted whole-brain criterion for determining the death of a human being from a Thomistic metaphysical perspective and, in so doing, raises objections to a particular argument defending the whole-brain criterion by Patrick Lee and Germain Grisez. In this paper, I will respond to Accad's critique of the whole-brain criterion and defend its continued validity as a criterion for determining when a human being's death has occurred in accord with Thomistic metaphysical principles. I will, however, join Accad in criticizing Lee and Grisez's proposed defense of the whole-brain criterion as potentially leading to erroneous conclusions regarding the determination of human death. Lay summary: Catholic physicians and bioethicists currently debate the legally accepted clinical standard for determining when a human being has died-known as the "wholebrain criterion"-which has also been morally affirmed by the Magisterium. This paper responds to physician Michel Accad's critique of the whole-brain criterion based upon St. Thomas Aquinas's metaphysical account of human nature as a union of a rational soul and a material body. I defend the whole-brain criterion from the same Thomistic philosophical perspective, while agreeing with Accad's objection to an alternative Thomistic defense of whole-brain death by philosophers Patrick Lee and Germain Grisez.

[Ludwig II of Bavaria - the "fairy tale king": his last years from a psychiatric point of view].

PubMed

V Zerssen, D

2010-11-01

Ludwig II of Bavaria (Germany) entered the political stage at the age of 18, following the premature death of his father Maximilian II in 1864. At that time, Ludwig was a very handsome, slender young man; he was enthusiastic and had a pronounced taste for fine arts and music, and was admired by the people as a "fairy tale king". However, already during the first years of his reign, he displayed traits that fulfilled the ICD-10 criteria for schizotypal disorder together with a combined cluster B personality disorder. They became even more pronounced over time. Towards the end of his life, Ludwig developed "imperial madness", a typical pattern of behavioural excesses including craving for power, splendour, construction, unrestrained spending, excessive eating and sexual exploitation, revenge with a tendency for cruelty, and an inclination for theatrical and sometimes irrational acts. This complex syndrome is usually manifested in excessively egocentric rulers who have almost unlimited power or, in the case of Ludwig II, an overwhelming desire to possess it. His imperial madness was possibly contributed to by an orbitofrontal brain syndrome. One conjecture is that this condition reflected a neurodegenerative process; another is that a primary deficit, initiated by brain damage following a severe bout of meningitis during Ludwig's babyhood, played a role. In this case, functional compensation by other brain areas may have eventually been counteracted by chronic substance abuse in his thirties. The monarch's life ended tragically when he was 40 by which time he had become adipose and had lost most of his teeth; meanwhile, he was placed under tutelage, dismissed and detained. Before his death by drowning in Lake Starnberg (suicide? attempted escape??), Ludwig apparently killed his psychiatrist, Bernhard von Gudden, who carelessly served as his sole attendant. Yet Ludwig's image as the beautiful fairy tale king is still alive in the hearts of successive generations of Bavarians and in the fascination demonstrated by the masses of tourists from throughout the world who visit (against his formerly declared wishes) his "dream castles".

Brain death and true patient care

PubMed Central

2016-01-01

The “brain death” standard as a criterion of death is closely associated with the need for transplantable organs from heart-beating donors. Are all of these potential donors really dead, or does the documented evidence of patients destined for organ harvesting who improve, or even recover to live normal lives, call into question the premise underlying “brain death”? The aim of this paper is to re-examine the notion of “brain death,” especially its clinical test-criteria, in light of a broad framework, including medical knowledge in the field of neuro-intensive care and the traditional ethics of the medical profession. I will argue that both the empirical medical evidence and the ethics of the doctor–patient relationship point to an alternative approach toward the severely comatose patient (potential brain-dead donor). Lay Summary: Though legally accepted and widely practiced, the “brain death” standard for the determination of death has remained a controversial issue, especially in view of the occurrence of “chronic brain death” survivors. This paper critically re-evaluates the clinical test-criteria for “brain death,” taking into account what is known about the neuro-critical care of severe brain injury. The medical evidence, together with the understanding of the moral role of the physician toward the patient present before him or her, indicate that an alternative approach should be offered to the deeply comatose patient. PMID:27833207

Brain death and Islam: the interface of religion, culture, history, law, and modern medicine.

PubMed

Miller, Andrew C; Ziad-Miller, Amna; Elamin, Elamin M

2014-10-01

How one defines death may vary. It is important for clinicians to recognize those aspects of a patient's religious beliefs that may directly influence medical care and how such practices may interface with local laws governing the determination of death. Debate continues about the validity and certainty of brain death criteria within Islamic traditions. A search of PubMed, Scopus, EMBASE, Web of Science, PsycNet, Sociological Abstracts, DIALOGUE ProQuest, Lexus Nexus, Google, and applicable religious texts was conducted to address the question of whether brain death is accepted as true death among Islamic scholars and clinicians and to discuss how divergent opinions may affect clinical care. The results of the literature review inform this discussion. Brain death has been acknowledged as representing true death by many Muslim scholars and medical organizations, including the Islamic Fiqh Academies of the Organization of the Islamic Conference and the Muslim World League, the Islamic Medical Association of North America, and other faith-based medical organizations as well as legal rulings by multiple Islamic nations. However, consensus in the Muslim world is not unanimous, and a sizable minority accepts death by cardiopulmonary criteria only.

QuickStats: Brain Cancer Death Rates Among Children and Teens Aged 1-19 Years,* by Sex† and Age Group - United States, 2013-2015.

PubMed

2017-05-05

The death rate for brain cancer, the most common cancer cause of death for children and teens aged 1-19 years, was 24% higher in males (0.73 per 100,000) than females (0.59) aged 1-19 years during 2013-2015. Death rates were higher for males than females for all age groups, but the difference did not reach statistical significance for the age group 5-9 years. Death rates caused by brain cancer were highest at ages 5-9 years (0.98 for males and 0.85 for females).

28 CFR 301.319 - Exclusiveness of remedy.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Exclusiveness of remedy. 301.319 Section... COMPENSATION Compensation for Work-Related Physical Impairment or Death § 301.319 Exclusiveness of remedy... Accident Compensation procedure was declared by the U.S. Supreme Court to be the exclusive remedy in the...

Attitudes toward death criteria and organ donation among healthcare personnel and the general public.

PubMed

DuBois, James M; Anderson, Emily E

2006-03-01

To examine attitudes toward death criteria and their relation to attitudes and behaviors regarding organ donation. This article reviews empirical studies on the attitudes of healthcare personnel and the general public regarding death criteria and organ donation. The review was restricted to studies that had as a primary focus attitudes toward 1 or more of the following 3 specific criteria for determining death: (1) brain death, the irreversible loss of all functions of the entire brain; (2) higher brain death, the loss of cerebral cortex function alone; and (3) the circulatory-respiratory criteria commonly used in donation after cardiac death. Studies consistently show that the general public and some medical personnel are inadequately familiar with the legal and medical status of brain death; attitudes toward the dead donor rule are strong predictors of willingness to donate organs using controversial criteria; concerns about donation after cardiac death surround the withdrawal of life support more than the actual death criteria used; and concerns about death criteria correlate with less favorable attitudes toward organ donation. Both general and ethical education may serve to guide policy and facilitate family member requests and informed consent dialogues. Furthermore, helping families to understand and accept not only medical and legal criteria for determining death, but also ethical criteria for withdrawing life support may help them be more comfortable with their decisions.

Culture, brain death, and transplantation.

PubMed

Bowman, Kerry W; Richard, Shawn A

2003-09-01

From the social sciences, we know the space between life and death is historically and culturally constructed, fluid and open to dispute. The definition of death has cultural, legal, and political dimensions. As healthcare becomes more culturally diverse, the interface between culture and the delivery of healthcare will increase. In our increasingly pluralistic, interdependent society, there is a growing demand to integrate healthcare, including transplantation, into a broader context that respects both individual and cultural diversity. It is important that we first consider and explore what elements of Western healthcare practices including definitions and advances, such as brain death and organ donation, are culturally influenced. This article highlights some of the cultural influences on brain death by focusing on Western and Japanese perspectives on the permissibility of organ procurement from brain-dead persons. It also offers 4 recommendations for healthcare workers working cross-culturally.

Brain Death and Transplant in Islamic Countries.

PubMed

Altınörs, Nur; Haberal, Mehmet

2016-11-01

The aim of this study was to investigate the present status regarding brain death, its consequences, and transplant activities in Islamic countries. A thorough literature survey was conducted about transplant activities in Islamic countries, and the Turkish Ministry of Health Web site was analyzed. Expert opinions about the issue were obtained. The present status of brain death and transplant activities has shown a heterogeneous appearance in the Islamic world. Our literature survey clearly revealed that transplant is still in its early stages in many Islamic states. The legislative framework, infrastructure, and related education needs radical improvements in these states. The concept of death has to be redefined and a consensus should be reached about brain death. The pioneer countries like Turkey, Iran, and Saudi Arabia. which already have considerable experience in transplant, should share their expertise and knowledge with the countries that need guidance.

Where's Waldo? The 'decapitation gambit' and the definition of death.

PubMed

Lizza, John P

2011-12-01

The 'decapitation gambit' holds that, if physical decapitation normally entails the death of the human being, then physiological decapitation, evident in cases of total brain failure, entails the death of the human being. This argument has been challenged by Franklin Miller and Robert Truog, who argue that physical decapitation does not necessarily entail the death of human beings and that therefore, by analogy, artificially sustained human bodies with total brain failure are living human beings. They thus challenge the current neurological criterion for determining death and argue for a return to the traditional criterion of the irreversible loss of circulation and respiration. In this paper, I defend the decapitation gambit and total brain failure as a criterion for determining death against Miller and Truog's criticism.

Role of ischemic modified albumin in the early diagnosis of increased intracranial pressure and brain death.

PubMed

Kara, I; Pampal, H K; Yildirim, F; Dilekoz, E; Emmez, G; U, F P; Kocabiyik, M; Demirel, C B

Increased intracranial pressure following trauma and subsequent possible development of brain death are important factors for morbidity and mortality due to ischemic changes. We aimed to establish the role of ischemic modified albumin (IMA) in the early diagnosis of the process, starting with increased intracranial pressure and ending with brain death. Eighteen Wistar-Albino rats were divided into three groups; control (CG, n = 6), increased intracranial pressure (ICPG, n = 6), and brain death (BDG, n = 6). Intracranial pressure elevation and brain death were constituted with the inflation of a balloon of a Fogarty catheter in the epidural space. In all three groups, blood samples were drawn before the procedure, and at minutes 150 and 240 for IMA and malondialdehyde (MDA) analysis. Serum IMA levels at 150 and 240 minutes were higher in ICPG than in CG (p < 0.05). IMA levels were similar in ICPG and BDG. Serum MDA levels at 150 and 240 minutes increased in ICPG and BDG groups compared to CG (p < 0.05). MDA levels were similar in ICP and BD groups. IMA should be considered as a biochemical parameter in the process starting from increased intracranial pressure elevation and ending at brain death (Tab. 3, Fig. 5, Ref. 31).

Practical Considerations in Donation After Circulatory Determination of Death in Switzerland.

PubMed

Dalle Ave, Anne L; Shaw, David M; Elger, Bernice

2017-09-01

Faced with similar issues of organ scarcity to its neighbors, Switzerland has developed donation after circulatory determination of death (DCDD) as a way to expand the organ pool since 1985. Here, we analyze the history, practical considerations, and ethical issues relating to the Swiss donation after circulatory death programs. In Switzerland, determination of death for DCDD requires a stand-off period of 10 minutes. This time between cardiac arrest and the declaration of death is mandated in the guidelines of the Swiss Academy of Medical Sciences. As in other DCDD programs, safeguards are put to avoid physicians denying lifesaving treatment to savable patients because of being influenced by receivers' interest. An additional recommendation could be made: Recipients should be transparently informed of the worse graft outcomes with DCDD programs and given the possibility to refuse such organs.

The degree of certainty in brain death: probability in clinical and Islamic legal discourse.

PubMed

Qazi, Faisal; Ewell, Joshua C; Munawar, Ayla; Asrar, Usman; Khan, Nadir

2013-04-01

The University of Michigan conference "Where Religion, Policy, and Bioethics Meet: An Interdisciplinary Conference on Islamic Bioethics and End-of-Life Care" in April 2011 addressed the issue of brain death as the prototype for a discourse that would reflect the emergence of Islamic bioethics as a formal field of study. In considering the issue of brain death, various Muslim legal experts have raised concerns over the lack of certainty in the scientific criteria as applied to the definition and diagnosis of brain death by the medical community. In contrast, the medical community at large has not required absolute certainty in its process, but has sought to eliminate doubt through cumulative diagnostic modalities and supportive scientific evidence. This has recently become a principal model, with increased interest in data analysis and evidence-based medicine with the intent to analyze and ultimately improve outcomes. Islamic law has also long employed a systematic methodology with the goal of eliminating doubt from rulings regarding the question of certainty. While ample criticism of the scientific criteria of brain death (Harvard criteria) by traditional legal sources now exists, an analysis of the legal process in assessing brain death, geared toward informing the clinician's perspective on the issue, is lacking. In this article, we explore the role of certainty in the diagnostic modalities used to establish diagnoses of brain death in current medical practice. We further examine the Islamic jurisprudential approach vis-à-vis the concept of certainty (yaqīn). Finally, we contrast the two at times divergent philosophies and consider what each perspective may contribute to the global discourse on brain death, understanding that the interdependence that exists between the theological, juridical, ethical, and medical/scientific fields necessitates an open discussion and active collaboration between all parties. We hope that this article serves to continue the discourse that was successfully begun by this initial interdisciplinary endeavor at the University of Michigan.

Do not resuscitate, brain death, and organ transplantation: Islamic perspective

PubMed Central

Chamsi-Pasha, Hassan; Albar, Mohammed Ali

2017-01-01

Muslim patients and families are often reluctant to discuss and accept fatal diagnoses and prognoses. In many instances, aggressive therapy is requested by a patient's family, prolonging the life of the patient at all costs. Islamic law permits the withdrawal of futile treatment, including life support, from terminally ill patients allowing death to take its natural course. “Do not resuscitate” is permitted in Islamic law in certain situations. Debate continues about the certainty of brain death criteria within Islamic scholars. Although brain death is accepted as true death by the majority of Muslim scholars and medical organizations, the consensus in the Muslim world is not unanimous, and some scholars still accept death only by cardiopulmonary criteria. Organ transplantation has been accepted in Islamic countries (with some resistance from some jurists). Many fatwas (decrees) of Islamic Jurisprudence Councils have been issued and allowed organs to be donated from living competent adult donor; and from deceased (cadavers), provided that they have agreed to donate or their families have agreed to donate after their death (usually these are brain-dead cases). A clear and well-defined policy from the ministry of health regarding do not resuscitate, brain death, and other end-of-life issues is urgently needed for all hospitals and health providers in most (if not all) Muslim and Arab countries. PMID:28469984

The dead donor rule: can it withstand critical scrutiny?

PubMed

Miller, Franklin G; Truog, Robert D; Brock, Dan W

2010-06-01

Transplantation of vital organs has been premised ethically and legally on "the dead donor rule" (DDR)-the requirement that donors are determined to be dead before these organs are procured. Nevertheless, scholars have argued cogently that donors of vital organs, including those diagnosed as "brain dead" and those declared dead according to cardiopulmonary criteria, are not in fact dead at the time that vital organs are being procured. In this article, we challenge the normative rationale for the DDR by rejecting the underlying premise that it is necessarily wrong for physicians to cause the death of patients and the claim that abandoning this rule would exploit vulnerable patients. We contend that it is ethical to procure vital organs from living patients sustained on life support prior to treatment withdrawal, provided that there is valid consent for both withdrawing treatment and organ donation. However, the conservatism of medical ethics and practical concerns make it doubtful that the DDR will be abandoned in the near future. This leaves the current practice of organ transplantation based on the "moral fiction" that donors are dead when vital organs are procured.

Conscious and Unconscious Memory Systems

PubMed Central

Squire, Larry R.; Dede, Adam J.O.

2015-01-01

The idea that memory is not a single mental faculty has a long and interesting history but became a topic of experimental and biologic inquiry only in the mid-20th century. It is now clear that there are different kinds of memory, which are supported by different brain systems. One major distinction can be drawn between working memory and long-term memory. Long-term memory can be separated into declarative (explicit) memory and a collection of nondeclarative (implicit) forms of memory that include habits, skills, priming, and simple forms of conditioning. These memory systems depend variously on the hippocampus and related structures in the parahippocampal gyrus, as well as on the amygdala, the striatum, cerebellum, and the neocortex. This work recounts the discovery of declarative and nondeclarative memory and then describes the nature of declarative memory, working memory, nondeclarative memory, and the relationship between memory systems. PMID:25731765

Direct Peritoneal Resuscitation Reduces Leukocyte Infiltration in the Kidney after Acute Brain Death.

PubMed

Weaver, Jessica Lee; Matheson, Paul J; Matheson, Amy; Graham, Victoria S; Downard, Cynthia; Garrison, Richard Neal; Smith, Jason W

2018-04-18

Brain death is associated with significant inflammation within the kidneys, which may contribute to reduced graft survival. Direct peritoneal resuscitation (DPR) has been shown to reduce systemic inflammation after brain death. To determine its effects, brain dead rats were resuscitated with normal saline (targeted intravenous fluid, TIVF) to maintain a mean arterial pressure of 80 mmHg and DPR animals also received 30cc of intraperitoneal peritoneal dialysis solution. Rats were euthanized at zero, two, four, and six hours after brain death. Pro-inflammatory cytokines were measured using ELISA. Levels of IL-1β, TNF-α, and IL-6 in the kidney were significantly increased as early as two hours after brain death and significantly decreased with DPR. Levels of leukocyte adhesion molecules ICAM and VCAM increased after brain death and were decreased with DPR (ICAM 2.33{plus minus}0.14 v 0.42{plus minus}0.04 p=0.002, VCAM 82.6{plus minus}5.8 v 37.3{plus minus}1.9 p=0.002 at four hours) as were E-selectin and P-selectin (E-selectin 25605 v 16144 p=0.005, P-selectin 82.5{plus minus}3.3 v 71.0{plus minus}2.3 p=0.009 at four hours). Use of DPR reduces inflammation and adhesion molecule expression in the kidneys, and is associated with reduced macrophages and neutrophils on immunohistochemistry. Using DPR in brain dead donors has the potential to reduce the immunologic activity of transplanted kidneys and could improve graft survival.

Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology.

PubMed

Wijdicks, Eelco F M; Varelas, Panayiotis N; Gronseth, Gary S; Greer, David M

2010-06-08

To provide an update of the 1995 American Academy of Neurology guideline with regard to the following questions: Are there patients who fulfill the clinical criteria of brain death who recover neurologic function? What is an adequate observation period to ensure that cessation of neurologic function is permanent? Are complex motor movements that falsely suggest retained brain function sometimes observed in brain death? What is the comparative safety of techniques for determining apnea? Are there new ancillary tests that accurately identify patients with brain death? A systematic literature search was conducted and included a review of MEDLINE and EMBASE from January 1996 to May 2009. Studies were limited to adults. In adults, there are no published reports of recovery of neurologic function after a diagnosis of brain death using the criteria reviewed in the 1995 American Academy of Neurology practice parameter. Complex-spontaneous motor movements and false-positive triggering of the ventilator may occur in patients who are brain dead. There is insufficient evidence to determine the minimally acceptable observation period to ensure that neurologic functions have ceased irreversibly. Apneic oxygenation diffusion to determine apnea is safe, but there is insufficient evidence to determine the comparative safety of techniques used for apnea testing. There is insufficient evidence to determine if newer ancillary tests accurately confirm the cessation of function of the entire brain.

Liver transplant using donors after cardiac death: a single-center approach providing outcomes comparable to donation after brain death.

PubMed

Vanatta, Jason M; Dean, Amanda G; Hathaway, Donna K; Nair, Satheesh; Modanlou, Kian A; Campos, Luis; Nezakatgoo, Nosratollah; Satapathy, Sanjaya K; Eason, James D

2013-04-01

Organ donation after cardiac death remains an available resource to meet the demand for transplant. However, concern persists that outcomes associated with donation after cardiac death liver allografts are not equivalent to those obtained with organ donation after brain death. The aim of this matched case control study was to determine if outcomes of liver transplants with donation after cardiac death donors is equivalent to outcomes with donation after brain death donors by controlling for careful donor and recipient selection, surgical technique, and preservation solution. A retrospective, matched case control study of adult liver transplant recipients at the University of Tennessee/Methodist University Hospital Transplant Institute, Memphis, Tennessee was performed. Thirty-eight donation after cardiac death recipients were matched 1:2, with 76 donation after brain death recipients by recipient age, recipient laboratory Model for End Stage Liver Disease score, and donor age to form the 2 groups. A comprehensive approach that controlled for careful donor and recipient matching, surgical technique, and preservation solution was used to minimize warm ischemia time, cold ischemia time, and ischemia-reperfusion injury. Patient and graft survival rates were similar in both groups at 1 and 3 years (P = .444 and P = .295). There was no statistically significant difference in primary nonfunction, vascular complications, or biliary complications. In particular, there was no statistically significant difference in ischemic-type diffuse intrahepatic strictures (P = .107). These findings provide further evidence that excellent patient and graft survival rates expected with liver transplants using organ donation after brain death donors can be achieved with organ donation after cardiac death donors without statistically higher rates of morbidity or mortality when a comprehensive approach that controls for careful donor and recipient matching, surgical technique, and preservation solution is used.

Brain structure-function associations in multi-generational families genetically enriched for bipolar disorder.

PubMed

Fears, Scott C; Schür, Remmelt; Sjouwerman, Rachel; Service, Susan K; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Knowles, Emma; Gomez-Makhinson, Juliana; Lopez, Maria C; Aldana, Ileana; Teshiba, Terri M; Abaryan, Zvart; Al-Sharif, Noor B; Navarro, Linda; Tishler, Todd A; Altshuler, Lori; Bartzokis, George; Escobar, Javier I; Glahn, David C; Thompson, Paul M; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I; Sabatti, Chiara; Cantor, Rita M; Freimer, Nelson B; Bearden, Carrie E

2015-07-01

Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain-behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18-87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain-behaviour associations and test whether brain-behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain-behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family members. Additionally, while age had a relatively strong impact on all neurocognitive traits, the effects of age on cognition did not differ between diagnostic groups. Most brain-behaviour associations were also similar across the age range, with the exception of cortical and ventricular volume and lingual gyrus thickness, which showed weak correlations with verbal fluency and inhibitory control at younger ages that increased in magnitude in older subjects, regardless of diagnosis. Findings indicate that neuroanatomical traits potentially impacted by bipolar disorder are significantly associated with multiple neurobehavioural domains. Structure-function relationships are generally preserved across diagnostic groups, with the notable exception of ventrolateral prefrontal and parietal association cortex, volumetric increases in which may be associated with cognitive resilience specifically in individuals with bipolar disorder. Although age impacted all neurobehavioural traits, we did not find any evidence of accelerated cognitive decline specific to bipolar disorder subjects. Regardless of diagnosis, greater global brain volume may represent a protective factor for the effects of ageing on executive functioning. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Police Officers' Knowledge and Attitudes Toward Brain Death and Organ Donation in Korea.

PubMed

Kim, H S; Yoo, Y S; Cho, O-H; Lee, C E; Choi, Y-H; Kim, H J; Park, J Y; Park, H S; Kwon, Y J

2018-05-01

Administrative processing by the police may affect the process involved in organ donation in the event of an accidental brain injury. The purpose of this study was to evaluate the knowledge and attitude of police toward brain-dead donors and organ donation. This was a descriptive research study using a 41-item questionnaire. As of July 19, 2017, 11 police stations in Seoul had collected questionnaires completed by 115 police officers. Data were analyzed using SAS (version 9.4) software. There were statistically significant differences in the scores on knowledge about brain death/donation according to religion (P = .022). Attitude was significantly positively correlated with the knowledge about brain-death organ donation (P = .029). It is necessary to understand and cooperate with the police when processing brain death organs from accidents. Education about organ donation can enhance the information and knowledge of the police and can also help to establish a positive attitude about organ donation. Copyright © 2018 Elsevier Inc. All rights reserved.

Nitrates in drinking water and the risk of death from brain cancer: does hardness in drinking water matter?

PubMed

Ho, Chi-Kung; Yang, Ya-Hui; Yang, Chun-Yuh

2011-01-01

The objectives of this study were to (1) examine the relationship between nitrate levels in public water supplies and risk of death from brain cancer and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the influence of nitrates on development of brain cancer. A matched cancer case-control study was used to investigate the relationship between the risk of death from brain cancer and exposure to nitrates in drinking water in Taiwan. All brain cancer deaths of Taiwan residents from 2003 through 2008 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to cancer cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen (NO₃-N), Ca, and Mg in drinking water was obtained from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was presumed to be the source of the subject's NO₃-N, Ca, and Mg exposure via drinking water. Relative to individuals whose NO₃-N exposure level was <0.38 ppm, the adjusted OR (95% CI) for brain cancer occurrence was 1.04 (0.85-1.27) for individuals who resided in municipalities served by drinking water with a NO₃-N exposure ≥ 0.38 ppm. No marked effect modification was observed due to Ca and Mg intake via drinking water on brain cancer occurrence.

[Rigor mortis -- a definite sign of death?].

PubMed

Heller, A R; Müller, M P; Frank, M D; Dressler, J

2005-04-01

In the past years an ongoing controversial debate exists in Germany, regarding quality of the coroner's inquest and declaration of death by physicians. We report the case of a 90-year old female, who was found after an unknown time following a suicide attempt with benzodiazepine. The examination of the patient showed livores (mortis?) on the left forearm and left lower leg. Moreover, rigor (mortis?) of the left arm was apparent which prevented arm flexion and extension. The hypothermic patient with insufficient respiration was intubated and mechanically ventilated. Chest compressions were not performed, because central pulses were (hardly) palpable and a sinus bradycardia 45/min (AV-block 2 degrees and sole premature ventricular complexes) was present. After placement of an intravenous line (17 G, external jugular vein) the hemodynamic situation was stabilized with intermittent boli of epinephrine and with sodium bicarbonate. With improved circulation livores and rigor disappeared. In the present case a minimal central circulation was noted, which could be stabilized, despite the presence of certain signs of death ( livores and rigor mortis). Considering the finding of an abrogated peripheral perfusion (livores), we postulate a centripetal collapse of glycogen and ATP supply in the patients left arm (rigor), which was restored after resuscitation and reperfusion. Thus, it appears that livores and rigor are not sensitive enough to exclude a vita minima, in particular in hypothermic patients with intoxications. Consequently a careful ABC-check should be performed even in the presence of apparently certain signs of death, to avoid underdiagnosing a vita minima. Additional ECG- monitoring is required to reduce the rate of false positive declarations of death. To what extent basic life support by paramedics should commence when rigor and livores are present until physician DNR order, deserves further discussion.

Somatic survival and organ donation among brain-dead patients in the state of Qatar.

PubMed

George, Saibu; Thomas, Merlin; Ibrahim, Wanis H; Abdussalam, Ahmed; Chandra, Prem; Ali, Husain Shabbir; Raza, Tasleem

2016-10-31

The Qatari law, as in many other countries, uses brain death as the main criteria for organ donation and cessation of medical support. By contrast, most of the public in Qatar do not agree with the limitation or withdrawal of medical care until the time of cardiac death. The current study aims to examine the duration of somatic survival after brain death, organ donation rate in brain-dead patients as well as review the underlying etiologies and level of support provided in the state of Qatar. This is a retrospective study of all patients diagnosed with brain death over a 10-year period conducted at the largest tertiary center in Qatar (Hamad General Hospital). Among the 53 patients who were diagnosed with brain death during the study period, the median and mean somatic survivals of brain-dead patients in the current study were 3 and 4.5 days respectively. The most common etiology was intracranial hemorrhage (45.3 %) followed by ischemic stroke (17 %). Ischemic stroke patients had a median survival of 11 days. Organ donation was accepted by only two families (6.6 %) of the 30 brain dead patients deemed suitable for organ donation. The average somatic survival of brain-dead patients is less than one week irrespective of supportive measures provided. Organ donation rate was extremely low among brain-dead patients in Qatar. Improved public education may lead to significant improvement in resource utilization as well as organ transplant donors and should be a major target area of future health care policies.

Medical and ethical dilemma in brain death.

PubMed

Streba, Irina; Damian, Simona; Ioan, Beatrice

2012-01-01

For centuries, death has been defined, medically speaking, as the irreversible cessation of breathing and of nervous and cardiac activity. What radically changed this definition was the introduction of the concept "brain death" in 1968, by the "Ad Hoc Committee of the Harvard Medical School". According to it, the irreversible coma was associated with brain death and considered to be a criterion for the diagnosis of the deceased individual. The evergrowing need for transplant organs (provided this respects the dead honor rule, stipulating that organs can't be harvested unless someone is deceased) lead to making arbitrary decisions regarding the establishment of the exact time of death during the process of "losing life". What actually triggers the controversy related to the concept of brain death is the dilemma of associating this concept with that of biologic death or death of the person, the difference between the two being made by whether the mental characteristics are accepted or not in defining and individualizing the death of the human being. Given these circumstances, a dilemma appears--that of defining the death of the individual: we define death, as it has been for centuries, as the moment when the cardio-respiratory function no longer exists, which leads to the loss of tens of thousands of lives that might have been saved through transplant. Yet, this may lead to manipulating the border between life and death, with the risk of trespassing each individual's right to life.

Learning To Remember: Building Memory Cues into a Geology Lesson.

ERIC Educational Resources Information Center

King-Friedrichs, Jeanne; Browne, Daniel

2001-01-01

Presents five guidelines for helping students retrieve declarative memories in the context of geology activities. Based on research findings on brain function from the fields of neuroscience and psychology, the activities provide opportunities for students to practice using cues to enhance memory. (DLH)

Cognitive correlates of pragmatic language comprehension in adult traumatic brain injury: A systematic review and meta-analyses.

PubMed

Rowley, Dane A; Rogish, Miles; Alexander, Timothy; Riggs, Kevin J

2017-01-01

Effective pragmatic comprehension of language is critical for successful communication and interaction, but this ability is routinely impaired following Traumatic Brain Injury (TBI) (1,2). Individual studies have investigated the cognitive domains associated with impaired pragmatic comprehension, but there remains little understanding of the relative importance of these domains in contributing to pragmatic comprehension impairment following TBI. This paper presents a systematic meta-analytic review of the observed correlations between pragmatic comprehension and cognitive processes following TBI. Five meta-analyses were computed, which quantified the relationship between pragmatic comprehension and five key cognitive constructs (declarative memory; working memory; attention; executive functions; social cognition). Significant moderate-to-strong correlations were found between all cognitive measures and pragmatic comprehension, where declarative memory was the strongest correlate. Thus, our findings indicate that pragmatic comprehension in TBI is associated with an array of domain general cognitive processes, and as such deficits in these cognitive domains may underlie pragmatic comprehension difficulties following TBI. The clinical implications of these findings are discussed.

Agmatine Attenuates Brain Edema and Apoptotic Cell Death after Traumatic Brain Injury.

PubMed

Kim, Jae Young; Lee, Yong Woo; Kim, Jae Hwan; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun

2015-07-01

Traumatic brain injury (TBI) is associated with poor neurological outcome, including necrosis and brain edema. In this study, we investigated whether agmatine treatment reduces edema and apoptotic cell death after TBI. TBI was produced by cold injury to the cerebral primary motor cortex of rats. Agmatine was administered 30 min after injury and once daily until the end of the experiment. Animals were sacrificed for analysis at 1, 2, or 7 days after the injury. Various neurological analyses were performed to investigate disruption of the blood-brain barrier (BBB) and neurological dysfunction after TBI. To examine the extent of brain edema after TBI, the expression of aquaporins (AQPs), phosphorylation of mitogen-activated protein kinases (MAPKs), and nuclear translocation of nuclear factor-κB (NF-κB) were investigated. Our findings demonstrated that agmatine treatment significantly reduces brain edema after TBI by suppressing the expression of AQP1, 4, and 9. In addition, agmatine treatment significantly reduced apoptotic cell death by suppressing the phosphorylation of MAPKs and by increasing the nuclear translocation of NF-κB after TBI. These results suggest that agmatine treatment may have therapeutic potential for brain edema and neural cell death in various central nervous system diseases.

Apolipoprotein ɛ4 breaks the association between declarative long-term memory and memory-based orienting of spatial attention in middle-aged individuals.

PubMed

Salvato, Gerardo; Patai, Eva Z; McCloud, Tayla; Nobre, Anna C

2016-09-01

Apolipoprotein (APOE) ɛ4 genotype has been identified as a risk factor for late-onset Alzheimer disease (AD). The memory system is mostly involved in AD, and memory deficits represent its key feature. A growing body of studies has focused on the earlier identification of cognitive dysfunctions in younger and older APOE ɛ4 carriers, but investigation on middle-aged individuals remains rare. Here we sought to investigate if the APOE ɛ4 genotype modulates declarative memory and its influences on perception in the middle of the life span. We tested 60 middle-aged individuals recruited according to their APOE allele variants (ɛ3/ɛ3, ɛ3/ɛ4, ɛ4/ɛ4) on a long-term memory-based orienting of attention task. Results showed that the APOE ɛ4 genotype impaired neither explicit memory nor memory-based orienting of spatial attention. Interestingly, however, we found that the possession of the ɛ4 allele broke the relationship between declarative long-term memory and memory-guided orienting of visuo-spatial attention, suggesting an earlier modulation exerted by pure genetic characteristics on cognition. These findings are discussed in light of possible accelerated brain ageing in middle-aged ɛ4-carriers, and earlier structural changes in the brain occurring at this stage of the lifespan. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mortality among Workers Exposed to Polychlorinated Biphenyls (PCBs) in an Electrical Capacitor Manufacturing Plant in Indiana: An Update

PubMed Central

Ruder, Avima M.; Hein, Misty J.; Nilsen, Nancy; Waters, Martha A.; Laber, Patricia; Davis-King, Karen; Prince, Mary M.; Whelan, Elizabeth

2006-01-01

An Indiana capacitor-manufacturing cohort (n = 3,569) was exposed to polychlorinated biphenyls (PCBs) from 1957 to 1977. The original study of mortality through 1984 found excess melanoma and brain cancer; other studies of PCB-exposed individuals have found excess non-Hodgkin lymphoma and rectal, liver, biliary tract, and gallbladder cancer. Mortality was updated through 1998. Analyses have included standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) using rates for Indiana and the United States, standardized rate ratios (SRRs), and Poisson regression rate ratios (RRs). Estimated cumulative exposure calculations used a new job–exposure matrix. Mortality overall was reduced (547 deaths; SMR, 0.81; 95% CI, 0.7–0.9). Non-Hodgkin lymphoma mortality was elevated (9 deaths; SMR, 1.23; 95% CI, 0.6–2.3). Melanoma remained in excess (9 deaths; SMR, 2.43; 95% CI, 1.1–4.6), especially in the lowest tertile of estimated cumulative exposure (5 deaths; SMR, 3.72; 95% CI, 1.2–8.7). Seven of the 12 brain cancer deaths (SMR, 1.91; 95% CI, 1.0–3.3) occurred after the original study. Brain cancer mortality increased with exposure (in the highest tertile, 5 deaths; SMR, 2.71; 95% CI, 0.9–6.3); the SRR dose–response trend was significant (p = 0.016). Among those working ≥90 days, both melanoma (8 deaths; SMR, 2.66; 95% CI, 1.1–5.2) and brain cancer (11 deaths; SMR, 2.12; 95% CI, 1.1–3.8) were elevated, especially for women: melanoma, 3 deaths (SMR, 5.99; 95% CI, 1.2–17.5); brain cancer, 3 deaths (SMR, 2.87; 95% CI, 0.6–8.4). These findings of excess melanoma and brain cancer mortality confirm results of the original study. Melanoma mortality was not associated with estimated cumulative exposure. Brain cancer mortality did not demonstrate a clear dose–response relationship with estimated cumulative exposure. PMID:16393652

The expression of '150-kDa oxygen regulated protein (ORP-150)' in human brain and its relationship with duration time until death.

PubMed

Ikematsu, Kazuya; Tsuda, Ryouichi; Kondo, Toshikazu; Kondo, Hisayoshi; Ozawa, Kentaro; Ogawa, Satoshi; Nakasono, Ichiro

2004-04-01

The expression of oxygen regulated protein 150-kDa (ORP-150) was strongly induced in human brain under the hypoxic conditions. We examined the expression of ORP-150 in the brain samples, and discussed its significance in forensic practice. The cerebral cortexes of 31 cases (asphyxia: 9 cases, hypothermia: 4, exsanguinations: 5, CO intoxication (CO): 6, sudden cardiac death (SCD): 7) were used for this study. Each tissue section was incubated with anti-ORP-150 polyclonal antibody and the number of ORP-150 positive cells were counted. In the multiple linear regression method, the estimated regression coefficient of ORP-150 on age was significant (P=0.039) thus, we could find that the ORP-150 expression level depended on age. Using analysis of covariance, we compared the means of ORP-150, LSMEAN, which means hypothetic average value excluding influence of age, for each cause of death. The LSMEAN+/-SE was 84.74+/-9.03 in hypothermia, 57.52+/-6.34 in asphyxia, 46.68+/-6.70 in CO, 24.84+/-8.05 in exsanguinations, and 16.24+/-7.35 in SCD. As a result of the analysis, the LSMEAN of the ORP-150 expression level was related to the cause of death. There might be differences in the duration of brain ischemia before death. For example, SCD is presumed to be instant death, while brain ischemia continues for several minutes in asphyxia, CO and exsanguinations, and for several hours in hypothermia cases. Therefore, the immunohistochemical and morphometrical analysis of ORP-150 in the brain may be very useful to determine the duration of brain ischemia before death in forensic autopsy cases.

Suicide by fentanyl.

PubMed

Sutlović, Davorka; Definis-Gojanović, Marija

2007-09-01

Fentanyl is a potent, short-acting narcotic analgesic widely used as surgical anaesthetic. This article presents a case in which fentanyl was self-injected by a 41-year old nurse, an employee at the hospital emergency department, who was found dead at home. She had no known history of drug and alcohol abuse. Two syringes, one empty and one filled with a clear liquid, were found near the body, while a needle was stuck into her hand. Toxicological analysis showed fentanyl poisoning. Fentanyl overdose was declared the cause of death and the manner of death was classified as suicide. To our knowledge, death due to the intravenous injection of fentanyl has not previously been reported in Croatia.

Transplanting hearts after death measured by cardiac criteria: the challenge to the dead donor rule.

PubMed

Veatch, Robert M

2010-06-01

The current definition of death used for donation after cardiac death relies on a determination of the irreversible cessation of the cardiac function. Although this criterion can be compatible with transplantation of most organs, it is not compatible with heart transplantation since heart transplants by definition involve the resuscitation of the supposedly "irreversibly" stopped heart. Subsequently, the definition of "irreversible" has been altered so as to permit heart transplantation in some circumstances, but this is unsatisfactory. There are three available strategies for solving this "irreversibility problem": altering the definition of death so as to rely on circulatory irreversibility, rather than cardiac; defining death strictly on the basis of brain death (either whole-brain or more pragmatically some higher brain criteria); or redefining death in traditional terms and simultaneously legalizing some limited instances of medical killing to procure viable hearts. The first two strategies are the most ethically justifiable and practical.

Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury

PubMed Central

Xie, Cuicui; Ginet, Vanessa; Sun, Yanyan; Koike, Masato; Zhou, Kai; Li, Tao; Li, Hongfu; Li, Qian; Wang, Xiaoyang; Uchiyama, Yasuo; Truttmann, Anita C.; Kroemer, Guido; Puyal, Julien; Blomgren, Klas; Zhu, Changlian

2016-01-01

ABSTRACT Perinatal asphyxia induces neuronal cell death and brain injury, and is often associated with irreversible neurological deficits in children. There is an urgent need to elucidate the neuronal death mechanisms occurring after neonatal hypoxia-ischemia (HI). We here investigated the selective neuronal deletion of the Atg7 (autophagy related 7) gene on neuronal cell death and brain injury in a mouse model of severe neonatal hypoxia-ischemia. Neuronal deletion of Atg7 prevented HI-induced autophagy, resulted in 42% decrease of tissue loss compared to wild-type mice after the insult, and reduced cell death in multiple brain regions, including apoptosis, as shown by decreased caspase-dependent and -independent cell death. Moreover, we investigated the lentiform nucleus of human newborns who died after severe perinatal asphyxia and found increased neuronal autophagy after severe hypoxic-ischemic encephalopathy compared to control uninjured brains, as indicated by the numbers of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3)-, LAMP1 (lysosomal-associated membrane protein 1)-, and CTSD (cathepsin D)-positive cells. These findings reveal that selective neuronal deletion of Atg7 is strongly protective against neuronal death and overall brain injury occurring after HI and suggest that inhibition of HI-enhanced autophagy should be considered as a potential therapeutic target for the treatment of human newborns developing severe hypoxic-ischemic encephalopathy. PMID:26727396

26 CFR 1.6012-3 - Returns by fiduciaries.

Code of Federal Regulations, 2010 CFR

2010-04-01

...), accompanied by a written declaration of the fiduciary under the penalties of perjury that it is a true and... of the fiduciary under the penalties of perjury that it is a true and complete copy, shall be... such decedent. For the decedent's taxable year which ends with the date of his death, the return shall...

Extending the boundaries of the Declaration of Helsinki: a case study of an unethical experiment in a non-medical setting

PubMed Central

Richter, E.; Barach, P.; Berman, T.; Ben-David, G; Weinberger, Z.

2001-01-01

To examine the ethical issues involved in governmental decisions with potential health risks, we review the history of the decision to raise the interurban speed limit in Israel in light of its impact on road death and injury. In 1993, the Israeli Ministry of Transportation initiated an "experiment" to raise the interurban speed limit from 90 to 100 kph. The "experiment" did not include a protocol and did not specify cut-off points for early termination in the case of adverse results. After the raise in the speed limit, the death toll on interurban roads rose as a result of a sudden increase in speeds and case fatality rates. The committee's decision is a case study in unfettered human experimentation and public health risks when the setting is non-medical and lacks a defined ethical framework. The case study states the case for extending Helsinki type safeguards to experimentation in non-medical settings. Key Words: Declaration of Helsinki • human experimentation • speed limit PMID:11314157

[Structural Equation Modeling on Living and Brain Death Organ Donation Intention in Nursing Students].

PubMed

Kim, Eun A; Choi, So Eun

2015-12-01

The purpose of this study was to test and validate a model to predict living and brain death organ donation intention in nursing students. The conceptual model was based on the theory planned behavior. Quota sampling methodology was used to recruit 921 nursing students from all over the country and data collection was done from October 1 to December 20, 2013. The model fit indices for the hypothetical model were suitable for the recommended level. Knowledge, attitude, subjective norm and perceived behavioral control explained 40.2% and 40.1% respectively for both living and brain death organ donation intention. Subjective norm was the most direct influential factor for organ donation intention. Knowledge had significant direct effect on attitude and indirect effect on subjective norm and perceived behavioral control. These effects were higher in brain death organ donation intention than in living donation intention. The overall findings of this study suggest the need to develop systematic education programs to increases knowledge about brain death organ donation. The development, application, and evaluation of intervention programs are required to improve subjective norm.

First experience of liver transplantation with type 2 donation after cardiac death in France.

PubMed

Savier, Eric; Dondero, Federica; Vibert, Eric; Eyraud, Daniel; Brisson, Hélène; Riou, Bruno; Fieux, Fabienne; Naili-Kortaia, Salima; Castaing, Denis; Rouby, Jean-Jacques; Langeron, Olivier; Dokmak, Safi; Hannoun, Laurent; Vaillant, Jean-Christophe

2015-05-01

Organ donation after unexpected cardiac death [type 2 donation after cardiac death (DCD)] is currently authorized in France and has been since 2006. Following the Spanish experience, a national protocol was established to perform liver transplantation (LT) with type 2 DCD donors. After the declaration of death, abdominal normothermic oxygenated recirculation was used to perfuse and oxygenate the abdominal organs until harvesting and cold storage. Such grafts were proposed to consenting patients < 65 years old with liver cancer and without any hepatic insufficiency. Between 2010 and 2013, 13 LTs were performed in 3 French centers. Six patients had a rapid and uneventful postoperative recovery. However, primary nonfunction occurred in 3 patients, with each requiring urgent retransplantation, and 4 early allograft dysfunctions were observed. One patient developed a nonanastomotic biliary stricture after 3 months, whereas 8 patients showed no sign of ischemic cholangiopathy at their 1-year follow-up. In comparison with a control group of patients receiving grafts from brain-dead donors (n = 41), donor age and cold ischemia time were significantly lower in the type 2 DCD group. Time spent on the national organ wait list tended to be shorter in the type 2 DCD group: 7.5 months [interquartile range (IQR), 4.0-11.0 months] versus 12.0 months (IQR, 6.8-16.7 months; P = 0.08. The 1-year patient survival rates were similar (85% in the type 2 DCD group versus 93% in the control group), but the 1-year graft survival rate was significantly lower in the type 2 DCD group (69% versus 93%; P = 0.03). In conclusion, to treat borderline hepatocellular carcinoma, LT with type 2 DCD donors is possible as long as strict donor selection is observed. © 2015 American Association for the Study of Liver Diseases.

End-of-life practices in patients with devastating brain injury in Spain: implications for organ donation.

PubMed

Domínguez-Gil, B; Coll, E; Pont, T; Lebrón, M; Miñambres, E; Coronil, A; Quindós, B; Herrero, J E; Liébanas, C; Marcelo, B; Sanmartín, A M; Matesanz, R

2017-04-01

To describe end-of-life care practices relevant to organ donation in patients with devastating brain injury in Spain. A multicenter prospective study of a retrospective cohort. 1 November 2014 to 30 April 2015. Sixty-eight hospitals authorized for organ procurement. Patients dying from devastating brain injury (possible donors). Age: 1 month-85 years. Type of care, donation after brain death, donation after circulatory death, intubation/ventilation, referral to the donor coordinator. A total of 1,970 possible donors were identified, of which half received active treatment in an Intensive Care Unit (ICU) until brain death (27%), cardiac arrest (5%) or the withdrawal of life-sustaining therapy (19%). Of the rest, 10% were admitted to the ICU to facilitate organ donation, while 39% were not admitted to the ICU. Of those patients who evolved to a brain death condition (n=695), most transitioned to actual donation (n=446; 64%). Of those who died following the withdrawal of life-sustaining therapy (n=537), 45 (8%) were converted into actual donation after circulatory death donors. The lack of a dedicated donation after circulatory death program was the main reason for non-donation. Thirty-seven percent of the possible donors were not intubated/ventilated at death, mainly because the professional in charge did not consider donation alter discarding therapeutic intubation. Thirty-six percent of the possible donors were never referred to the donor coordinator. Although deceased donation is optimized in Spain, there are still opportunities for improvement in the identification of possible donors outside the ICU and in the consideration of donation after circulatory death in patients who die following the withdrawal of life-sustaining therapy. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

A study on knowledge and attitude toward brain death and organ retrieval among health care professionals in Korea.

PubMed

Jeon, K O; Kim, B N; Kim, H S; Byeon, N-I; Hong, J J; Bae, S H; Son, S Y

2012-05-01

The practice of retrieving vital organs from brain-dead donors is legally and medically accepted in Korea, but health care professionals' beliefs and opinions regarding these matters have not been sufficiently explored. The purpose of this study was to evaluate the knowledge and attitudes of health care professionals to the concepts of brain death and organ retrieval. Data were collected using a 41-item questionnaire during a week in June 2011. Sixty-one doctors and 109 nurses from five hospitals with more than 2000 beds in Seoul, Korea, participated in the survey. The data was analyzed using SPSS version 17.0 (SPSS Inc. Chicago, Illinois, USA). There were statistically significant differences in the scores on knowledge according to marital status (P = .001) education level (P = .019), whether the participants were informed about organ donation from a brain-dead donor (P = .002), and the participant's experience managing potential brain-dead patients (P = .037). There were statistically significant differences in the scores on the attitude according to gender (P < .001), age (P < .001), marital status (P < .001), education level (P = .003), job position (P < .001), and the participant's experience referring brain-dead patients to the hospital-based organ procurement organization (P = .001). Significantly, attitude's positively correlated with knowledge about brain-dead organ donation (P < .001). Compared with previous studies, the knowledge and attitudes of health care professionals' regarding brain death and organ retrieval were not improved. There are passive attitudes to brain death and organ retrieval. More research must be performed to promote knowledge and understanding toward brain death and organ retrieval among health care professionals. Copyright © 2012 Elsevier Inc. All rights reserved.

Determination of Death and the Dead Donor Rule: A Survey of the Current Law on Brain Death.

PubMed

Nikas, Nikolas T; Bordlee, Dorinda C; Moreira, Madeline

2016-06-01

Despite seeming uniformity in the law, end-of-life controversies have highlighted variations among state brain death laws and their interpretation by courts. This article provides a survey of the current legal landscape regarding brain death in the United States, for the purpose of assisting professionals who seek to formulate or assess proposals for changes in current law and hospital policy. As we note, the public is increasingly wary of the role of organ transplantation in determinations of death, and of the variability of brain death diagnosing criteria. We urge that any attempt to alter current state statutes or to adopt a national standard must balance the need for medical accuracy with sound ethical principles which reject the utilitarian use of human beings and are consistent with the dignity of the human person. Only in this way can public trust be rebuilt. © The Author 2016. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Hippocampal declarative memory supports gesture production: Evidence from amnesia

PubMed Central

Hilliard, Caitlin; Cook, Susan Wagner; Duff, Melissa C.

2016-01-01

Spontaneous co-speech hand gestures provide a visuospatial representation of what is being communicated in spoken language. Although it is clear that gestures emerge from representations in memory for what is being communicated (De Ruiter, 1998; Wesp, Hesse, Keutmann, & Wheaton, 2001), the mechanism supporting the relationship between gesture and memory is unknown. Current theories of gesture production posit that action – supported by motor areas of the brain – is key in determining whether gestures are produced. We propose that when and how gestures are produced is determined in part by hippocampally-mediated declarative memory. We examined the speech and gesture of healthy older adults and of memory-impaired patients with hippocampal amnesia during four discourse tasks that required accessing episodes and information from the remote past. Consistent with previous reports of impoverished spoken language in patients with hippocampal amnesia, we predicted that these patients, who have difficulty generating multifaceted declarative memory representations, may in turn have impoverished gesture production. We found that patients gestured less overall relative to healthy comparison participants, and that this was particularly evident in tasks that may rely more heavily on declarative memory. Thus, gestures do not just emerge from the motor representation activated for speaking, but are also sensitive to the representation available in hippocampal declarative memory, suggesting a direct link between memory and gesture production. PMID:27810497

Altered declarative memory in introverted middle-aged adults carrying the BDNF val66met allele.

PubMed

De Beaumont, Louis; Fiocco, Alexandra J; Quesnel, Geneviève; Lupien, Sonia; Poirier, Judes

2013-09-15

The val66met polymorphism of the brain-derived neurotrophic factor gene (BDNFMet) is associated with impaired learning/memory function, affective dysregulation and maladaptive personality traits. Here, we examine the potential relationship between the BDNFMet allele, introversion and declarative memory in middle-age adults. A total of 132 middle-aged healthy adults took part in this study that included taking a blood sample for genetic profiling, a short battery of neuropsychological tests and the NEO-Five Factor Inventory (NEO-FFI), widely used to assess the Big Five personality. Controlling for age, level of education and sex, a multiple analysis of covariance (MANCOVA) computing the effect of BDNF polymorphism on extraversion and declarative memory revealed a significant association (D1,128=4.79; p=0.03; ηp(2)=0.053). Using the Sobel Goodman Mediation Test, it was found that 25.61% of the relationship between genotype and declarative memory performance was mediated by introversion. Subsequent correlational analyses yielded a strong and significant correlation (β=0.53; p<0.001) between introversion and declarative memory specific to BDNFMet individuals. this study highlights the pertinence of further investigating gene×personality×environment interactions to account for the significant variability that is observed in cognitive function in late life. Copyright © 2013 Elsevier B.V. All rights reserved.

Optical imaging of cell death in traumatic brain injury using a heat shock protein-90 alkylator

PubMed Central

Xie, B-W; Park, D; Van Beek, E R; Blankevoort, V; Orabi, Y; Que, I; Kaijzel, E L; Chan, A; Hogg, P J; Löwik, C W G M

2013-01-01

Traumatic brain injury is a major public health concern and is characterised by both apoptotic and necrotic cell death in the lesion. Anatomical imaging is usually used to assess traumatic brain injuries and there is a need for imaging modalities that provide complementary cellular information. We sought to non-invasively image cell death in a mouse model of traumatic brain injury using a near-infrared fluorescent conjugate of a synthetic heat shock protein-90 alkylator, 4-(N-(S-glutathionylacetyl) amino) phenylarsonous acid (GSAO). GSAO labels both apoptotic and necrotic cells coincident with loss of plasma membrane integrity. The optical GSAO specifically labelled apoptotic and necrotic cells in culture and did not accumulate in healthy organs or tissues in the living mouse body. The conjugate is a very effective imager of cell death in brain lesions. The optical GSAO was detected by fluorescence intensity and GSAO bound to dying/dead cells was detected from prolongation of the fluorescence lifetime. An optimal signal-to-background ratio was achieved as early as 3 h after injection of the probe and the signal intensity positively correlated with both lesion size and probe concentration. This optical GSAO offers a convenient and robust means to non-invasively image apoptotic and necrotic cell death in brain and other lesions. PMID:23348587

Diagnosis of brain death by transcranial Doppler sonography.

PubMed

Bode, H; Sauer, M; Pringsheim, W

1988-12-01

The blood flow velocities in the basal cerebral arteries can be recorded at any age by transcranial Doppler sonography. We examined nine children with either initial or developing clinical signs of brain death. Soon after successful resuscitation increased diastolic flow velocities indicated a probable decrease in cerebrovascular resistance; this was of no particular prognostic importance. As soon as there was a clinical deterioration, there was a reduction in flow velocities with retrograde flow during early diastole, probably due to an increase in cerebrovascular resistance; this indicated a doubtful prognosis. In eight of the nine children with clinical signs of brain death a typical reverberating flow pattern was found, which was characterised by a counterbalancing short forward flow in systole and a short retrograde flow in early diastole. This indicated arrest of cerebral blood flow. One newborn showed normal systolic and end diastolic flow velocities in the basal cerebral arteries for two days despite clinical and electroencephalographic signs of brain death. Shunting of blood through the circle of Willis without effective cerebral perfusion may explain this phenomenon. No patient had the typical reverberating flow pattern without being clinically brain dead. Transcranial Doppler sonography is a reliable technique, which can be used at the bedside for the confirmation or the exclusion of brain death in children in addition to the clinical examination.

Diagnosis of brain death by transcranial Doppler sonography.

PubMed Central

Bode, H; Sauer, M; Pringsheim, W

1988-01-01

The blood flow velocities in the basal cerebral arteries can be recorded at any age by transcranial Doppler sonography. We examined nine children with either initial or developing clinical signs of brain death. Soon after successful resuscitation increased diastolic flow velocities indicated a probable decrease in cerebrovascular resistance; this was of no particular prognostic importance. As soon as there was a clinical deterioration, there was a reduction in flow velocities with retrograde flow during early diastole, probably due to an increase in cerebrovascular resistance; this indicated a doubtful prognosis. In eight of the nine children with clinical signs of brain death a typical reverberating flow pattern was found, which was characterised by a counterbalancing short forward flow in systole and a short retrograde flow in early diastole. This indicated arrest of cerebral blood flow. One newborn showed normal systolic and end diastolic flow velocities in the basal cerebral arteries for two days despite clinical and electroencephalographic signs of brain death. Shunting of blood through the circle of Willis without effective cerebral perfusion may explain this phenomenon. No patient had the typical reverberating flow pattern without being clinically brain dead. Transcranial Doppler sonography is a reliable technique, which can be used at the bedside for the confirmation or the exclusion of brain death in children in addition to the clinical examination. PMID:3069052

Central diabetes insipidus in pediatric severe traumatic brain injury.

PubMed

Alharfi, Ibrahim M; Stewart, Tanya Charyk; Foster, Jennifer; Morrison, Gavin C; Fraser, Douglas D

2013-02-01

To determine the occurrence rate of central diabetes insipidus in pediatric patients with severe traumatic brain injury and to describe the clinical, injury, biochemical, imaging, and intervention variables associated with mortality. Retrospective chart and imaging review. Children's Hospital, level 1 trauma center. Severely injured (Injury Severity Score ≥ 12) pediatric trauma patients (>1 month and <18 yr) with severe traumatic brain injury (presedation Glasgow Coma Scale ≤ 8 and head Maximum Abbreviated Injury Scale ≥ 4) that developed acute central diabetes insipidus between January 2000 and December 2011. Of 818 severely injured trauma patients, 180 had severe traumatic brain injury with an overall mortality rate of 27.2%. Thirty-two of the severe traumatic brain injury patients developed acute central diabetes insipidus that responded to desamino-8-D-arginine vasopressin and/or vasopressin infusion, providing an occurrence rate of 18%. At the time of central diabetes insipidus diagnosis, median urine output and serum sodium were 6.8 ml/kg/hr (interquartile range = 5-11) and 154 mmol/L (interquartile range = 149-159), respectively. The mortality rate of central diabetes insipidus patients was 87.5%, with 71.4% declared brain dead after central diabetes insipidus diagnosis. Early central diabetes insipidus onset, within the first 2 days of severe traumatic brain injury, was strongly associated with mortality (p < 0.001), as were a lower presedation Glasgow Coma Scale (p = 0.03), a lower motor Glasgow Coma Scale (p = 0.01), an occurrence of fixed pupils (p = 0.04), and a prolonged partial thromboplastin time (p = 0.04). Cerebral edema on the initial computed tomography, obtained in the first 24 hrs after injury, was the only imaging finding associated with death (p = 0.002). Survivors of central diabetes insipidus were more likely to have intracranial pressure monitoring (p = 0.03), have thiopental administered to induce coma (p = 0.04) and have received a decompressive craniectomy for elevated intracranial pressure (p = 0.04). The incidence of central diabetes insipidus in pediatric patients with severe traumatic brain injury is 18%. Mortality was associated with early central diabetes insipidus onset and cerebral edema on head computed tomography. Central diabetes insipidus nonsurvivors were less likely to have received intracranial pressure monitoring, thiopental coma and decompressive craniectomy.

Transcranial oscillatory direct current stimulation during sleep improves declarative memory consolidation in children with attention-deficit/hyperactivity disorder to a level comparable to healthy controls.

PubMed

Prehn-Kristensen, Alexander; Munz, Manuel; Göder, Robert; Wilhelm, Ines; Korr, Katharina; Vahl, Wiebke; Wiesner, Christian D; Baving, Lioba

2014-01-01

Slow oscillations (<1 Hz) during slow wave sleep (SWS) promote the consolidation of declarative memory. Children with attention-deficit/hyperactivity disorder (ADHD) have been shown to display deficits in sleep-dependent consolidation of declarative memory supposedly due to dysfunctional slow brain rhythms during SWS. Using transcranial oscillating direct current stimulation (toDCS) at 0.75 Hz, we investigated whether an externally triggered increase in slow oscillations during early SWS elevates memory performance in children with ADHD. 12 children with ADHD underwent a toDCS and a sham condition in a double-blind crossover study design conducted in a sleep laboratory. Memory was tested using a 2D object-location task. In addition, 12 healthy children performed the same memory task in their home environment. Stimulation enhanced slow oscillation power in children with ADHD and boosted memory performance to the same level as in healthy children. These data indicate that increasing slow oscillation power during sleep by toDCS can alleviate declarative memory deficits in children with ADHD. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

The Effect of Early Detection of Occult Brain Metastases in HER2-Positive Breast Cancer Patients on Survival and Cause of Death

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

Niwinska, Anna, E-mail: alphaonetau@poczta.onet.p; Tacikowska, Malgorzata; Murawska, Magdalena

2010-07-15

Purpose: The aim of the study is to evaluate disease-free survival, survival from the detection of brain metastases, overall survival, and cause of death in patients with occult brain metastases (Group I) vs. patients with symptomatic brain metastases (Group II). Methods and Materials: In 80 HER2-positive breast cancer patients, treated with trastuzumab and cytostatic agents for metastatic disease, magnetic resonance imaging screening of the brain was performed, and in 29 patients (36%) occult brain metastasis was detected (Group I). Whole-brain radiotherapy was delivered to Group I. This first group was compared with 52 patients who had symptomatic brain metastases (Groupmore » II) and was treated the same way, at the same clinic, during the same time period. Results: Median disease-free survival was 17 months in Group I and 19.9 months in Group II (p = 0.58). The median time interval between the dissemination of the disease and the detection of occult or symptomatic brain metastases was 9 and 15 months, respectively (p = 0.11). When the brain metastases were detected, the median survival was 9 and 8.78 months, respectively (p = 0.80). The median overall survival was 53 and 51 months, respectively (p = 0.94). In the group with occult brain metastases (Group I) 16% of patients died because of progression within the brain. In the group with symptomatic brain metastases (Group II) the rate of cerebral death was 48% (p = 0.009). Conclusions: Whole-brain radiotherapy of occult brain metastases in HER2-positive breast cancer patients with visceral dissemination produces a three-fold decrease in cerebral deaths but does not prolong survival.« less

Brain death in the pediatric patient: historical, sociological, medical, religious, cultural, legal, and ethical considerations.

PubMed

Farrell, M M; Levin, D L

1993-12-01

To detail the origins of the definition of death, the development of the criterion of whole brain death as fulfilling the definition of death, and the tests used to fulfill that criterion. A review of the literature was performed. No Institutional Review Board approval was necessary. In 1959, patients were described as being in "coma dépassé" or beyond coma. In 1967, the first successful heart transplantation took place, with the organ coming from a brain-dead, beating-heart donor. However, anxiety over the definitions of death did not begin with the modern, technological era, and death itself has never been definable in objective terms. It has always been a subjective and value-based construct. During ancient times, most people agreed that death occurred when a person's heartbeat and breathing stopped. For the Greeks, the heart was the center of life; for the ancient Hebrews and Christians, the breath was the center of life. In the 12th century, Maimonides pointed toward the head, and the loss thereof, as the reason for lack of central guidance of the soul. Physicians neither diagnosed nor certified death. During the Enlightenment, the necessity of heartbeat, breath, and consciousness for the definition of life was questioned, leading to questioning regarding the definition of death. Tests to fulfill the criteria of death, and tests to determine the absence of integration between functions of respiration, circulation, and neurology were introduced. Sensorimotor potential was becoming recognized as defining life, rather than heartbeat and respiration. As new tests were devised to fulfill criteria of death, the physician developed a professional monopoly on meeting the criteria of brain death. In the modern era, the boundary between life and death has been blurred, but the intensive care unit straddles this boundary. We may have situations where the patient is alive but in a coma, without functioning heart, lungs, kidneys, or gastrointestinal tract, with a transplanted liver, a reversed coagulation system, a blocked immune system, and a paralyzed musculoskeletal system. A human being is a man, woman, or child who is a composite of two intricately related but conceptually distinguishable components: the biological entity and the person. Therefore, human beings can suffer more than one death: a biological death and decay, and another death. Biological death is a cessation of processes of biological synthesis and replication, and is an irreversible loss of integration of the biological units. The reasons for having criteria for death are to diagnose death and pronounce a person dead. Society can then begin to engage in grief, religious rites, funerals, and burials, and accept biological death. Wills can be read, property distributed, insurance claimed, individuals can remarry, succession can take place, and legal proceedings can begin. Also, organ donation can take place, which entails difficult ethical decisions. The Harvard criteria of 1968 were devised to set forth brain-death criteria with whole brain death in mind. Currently, there are several controversies regarding these criteria: a) whether they apply to infants and children; b) whether ancillary tests are necessary; c) what the intervals of observation and testing are; and d) are there exceptions to the whole brain death criteria. Concerning the use of the adult criteria for infants and children, most researchers now agree that the adult criteria apply to infants and children who are full term and > 7 days of age. Concerning ancillary tests, there has been, in our machine- and technology-oriented profession, a great deal of emphasis on the different tests and their ability to fulfill the criteria of whole brain death. However, clinical examination and the apnea test are usually sufficient to fulfill the criteria. Ancillary tests may be desired in some cases, and a variety of these tests is available. (ABSTRACT TR

HIV and Tuberculosis (TB)

MedlinePlus

... or brain. If not treated, TB disease can cause death. HIV weakens the immune system , increasing the risk ... spine, or brain. If not treated, TB can cause death. How does TB spread from person to person? ...

Care pathways for organ donation after brain death: guidance from available literature?

PubMed

Hoste, Pieter; Vanhaecht, Kris; Ferdinande, Patrick; Rogiers, Xavier; Eeckloo, Kristof; Blot, Stijn; Hoste, Eric; Vogelaers, Dirk; Vandewoude, Koenraad

2016-10-01

A discussion of the literature concerning the impact of care pathways in the complex and by definition multidisciplinary process of organ donation following brain death. Enhancing the quality and safety of organs for transplantation has become a central concern for governmental and professional organizations. At the local hospital level, a donor coordinator can use a range of interventions to improve the donation and procurement process. Care pathways have been proven to represent an effective intervention in several settings for optimizing processes and outcomes. A discussion paper. A systematic review of the Medline, CINAHL, EMBASE and The Cochrane Library databases was conducted for articles published until June 2015, using the keywords donation after brain death and care pathways. Each paper was reviewed to investigate the effects of existing care pathways for donation after brain death. An additional search for unpublished information was conducted. Although literature supports care pathways as an effective intervention in several settings, few studies have explored its use and effectiveness for complex care processes such as donation after brain death. Nurses should be aware of their role in the donation process. Care pathways have the potential to support them, but their effectiveness has been insufficiently explored. Further research should focus on the development and standardization of the clinical content of a care pathway for donation after brain death and the identification of quality indicators. These should be used in a prospective effectiveness assessment of the proposed pathway. © 2016 John Wiley & Sons Ltd.

Time trends in organ donation after neurologic determination of death: a cohort study

PubMed Central

Kramer, Andreas H.; Baht, Ryan; Doig, Christopher J.

2017-01-01

Background: The cause of brain injury may influence the number of organs that can be procured and transplanted with donation following neurologic determination of death. We investigated whether the distribution of causes responsible for neurologic death has changed over time and, if so, whether this has had an impact on organ quality, transplantation rates and recipient outcomes. Methods: We performed a cohort study involving consecutive brain-dead organ donors in southern Alberta between 2003 and 2014. For each donor, we determined last available measures of organ injury and number of organs transplanted, and compared these variables for various causes of neurologic death. We compared trends to national Canadian data for 2000-2013 (2000-2011 for Quebec). Results: There were 226 brain-dead organ donors over the study period, of whom 100 (44.2%) had anoxic brain injury, 63 (27.9%) had stroke, and 51 (22.6%) had traumatic brain injury. The relative proportion of donors with traumatic brain injury decreased over time (> 30% in 2003-2005 v. 6%-23% in 2012-2014) (p = 0.004), whereas that with anoxic brain injury increased (14%-37% v. 46%-80%, respectively) (p < 0.001). Nationally, the annual number of brain-dead donors with traumatic brain injury decreased from 4.4 to less than 3 per million population between 2000 and 2013, and that with anoxic brain injury increased from 1.1 to 3.1 per million. Donors with anoxic brain injury had higher concentrations of creatinine, alanine aminotransferase and troponin T, and lower PaO2/FIO2 and urine output than donors with other diagnoses. The average number of organs transplanted per donor was 3.6 with anoxic brain injury versus 4.5 with traumatic brain injury or stroke (p = 0.002). Interpretation: Anoxic brain injury has become a leading cause of organ donation after neurologic determination of death in Canada. Organs from donors with anoxic brain injury have a greater degree of injury, and fewer are transplanted. These findings have implications for availability of organs for transplantation in patients with end-stage organ failure. PMID:28401114

28 CFR Appendix A to Part 74 - Declarations of Eligibility by Persons Identified by the Office of Redress Administration and...

Code of Federal Regulations, 2010 CFR

2010-07-01

... representative. Complete the following information: (1) Current Legal Name: (2) Current Address: Street: City.... app. 1989b. Complete the following information: (1) Current Legal Name: (2) Current Address: Street... to ORA such as the signed statements of two or more people with personal knowledge of the death...

The Zika virus and pregnancy: evidence, management, and prevention.

PubMed

Citil Dogan, Ayse; Wayne, Sandra; Bauer, Samuel; Ogunyemi, Dotun; Kulkharni, Santosh K; Maulik, Devika; Carpenter, Christopher F; Bahado-Singh, Ray O

2017-02-01

To comprehensively review the available evidence and existing consensus reports and guidelines regarding the pregnancy and reproductive implications of the mosquito-transmitted Zika virus (ZIKV) infection. A primary focus was to provide pertinent information to aid clinicians in the management of pregnancies at risk for, exposed to, or with confirmed ZIKV infection. An extensive literature review was performed using Pubmed. Practice guidelines and consensus reports were accessed from international, national, and professional organizations' websites. The clinical articles for ZIKV infection testing varied from case reports to small epidemiologic studies. A ZIKV epidemic has been declared in several countries in the Americas. Fifty-two travel-associated ZIKV infection cases have been reported throughout the USA (as of February 10, 2016). The consequences of congenital fetal/newborn ZIKV infection could potentially have devastating consequences including miscarriage, fetal death, and major anomalies such as microcephaly, brain and brain-stem defects, and long-term neurologic sequelae. While not definitive, current evidence suggests the existence of nonvector-borne transmission through sexual activity with an infected male partner. For women at risk for sexual transmission, condom use is advised, especially during pregnancy. While ZIKV infection appears to be a mild disease in the general population the potential consequences to the fetus and newborn could be profound. Management guidelines are currently evolving and will be significantly impacted as new evidence develops. It is therefore imperative that obstetric health-care providers keep abreast of this rapidly evolving information landscape that has so far characterized this outbreak.

Brain death and the historical understanding of bioethics.

PubMed

Belkin, Gary S

2003-07-01

In a 1968 Report, the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death promulgated influential criteria for the idea and practice known as "brain death." Before and since the Committee met, brain death has been a focal point of visions and nightmares of medical progress, purpose, and moral authority. Critics of the Committee felt it was deaf to apparently central moral considerations and focused on the self-serving purpose of expanding transplantation. Historical characterizations of the uses and meanings of brain death and the work of the Committee have tended to echo these themes, which means also generally repeating a widely held bioethical self-understanding of how the field appeared-that is, as a necessary antidote of moral expertise. This paper looks at the Committee and finds that historical depictions of it have been skewed by such a bioethical agenda. Entertaining different possibilities as to the motives and historical circumstances behind the Report it famously produced may point to not only different histories of the Committee, but also different perspectives on the historical legacy and role of bioethics as a discourse for addressing anxieties about medicine.

Preventable and Potentially Preventable Traumatic Death Rates in Neurosurgery Department: A Single Center Experience.

PubMed

Ha, Mahnjeong; Kim, Byung Chul; Choi, Seonuoo; Cho, Won Ho; Choi, Hyuk Jin

2016-10-01

Preventable and potentially preventable traumatic death rates is a method to evaluate the preventability of the traumatic deaths in emergency medical department. To evaluate the preventability of the traumatic deaths in patients who were admitted to neurosurgery department, we performed this study. A retrospective review identified 52 patients who admitted to neurosurgery department with severe traumatic brain injuries between 2013 and 2014. Based on radiologic and clinical state at emergency room, each preventability of death was estimated by professional panel discussion. And the final death rates were calculated. The preventable and potentially preventable traumatic death rates was 19.2% in this study. This result is lower than that of the research of 2012, Korean preventable and potentially preventable traumatic death rates. The rate of preventable and potentially preventable traumatic death of operation group is lower than that of conservative treatment group. Also, we confirmed that direct transfer and the time to operation are important to reduce the preventability. We report the preventable and potentially preventable traumatic death rates of our institute for evaluation of preventability in severe traumatic brain injuries during the last 2 years. For decrease of preventable death, we suggest that continuous survey of the death rate of traumatic brain injury patients is required.

Preventable and Potentially Preventable Traumatic Death Rates in Neurosurgery Department: A Single Center Experience

PubMed Central

Ha, Mahnjeong; Kim, Byung Chul; Choi, Seonuoo; Cho, Won Ho

2016-01-01

Objective Preventable and potentially preventable traumatic death rates is a method to evaluate the preventability of the traumatic deaths in emergency medical department. To evaluate the preventability of the traumatic deaths in patients who were admitted to neurosurgery department, we performed this study. Methods A retrospective review identified 52 patients who admitted to neurosurgery department with severe traumatic brain injuries between 2013 and 2014. Based on radiologic and clinical state at emergency room, each preventability of death was estimated by professional panel discussion. And the final death rates were calculated. Results The preventable and potentially preventable traumatic death rates was 19.2% in this study. This result is lower than that of the research of 2012, Korean preventable and potentially preventable traumatic death rates. The rate of preventable and potentially preventable traumatic death of operation group is lower than that of conservative treatment group. Also, we confirmed that direct transfer and the time to operation are important to reduce the preventability. Conclusion We report the preventable and potentially preventable traumatic death rates of our institute for evaluation of preventability in severe traumatic brain injuries during the last 2 years. For decrease of preventable death, we suggest that continuous survey of the death rate of traumatic brain injury patients is required. PMID:27857910

Near-death experience: arising from the borderlands of consciousness in crisis.

PubMed

Nelson, Kevin R

2014-11-01

Brain activity explains the essential features of near-death experience, including the perceptions of envelopment by light, out-of-body, and meeting deceased loved ones or spiritual beings. To achieve their fullest expression, such near-death experiences require a confluence of events and draw upon more than a single physiological or biochemical system, or one anatomical structure. During impaired cerebral blood flow from syncope or cardiac arrest that commonly precedes near-death, the boundary between consciousness and unconsciousness is often indistinct and a person may enter a borderland and be far more aware than is appreciated by others. Consciousness can also come and go if blood flow rises and falls across a crucial threshold. During crisis the brain's prime biologic purpose to keep itself alive lies at the heart of many spiritual experiences and inextricably binds them to the primal brain. Brain ischemia can disrupt the physiological balance between conscious states by leading the brainstem to blend rapid eye movement (REM) and waking into another borderland of consciousness during near-death. Evidence converges from many points to support this notion, including the observation that the majority of people with a near-death experience possess brains predisposed to fusing REM and waking consciousness into an unfamiliar reality, and are as likely to have out-of-body experience while blending REM and waking consciousness as they are to have out-of-body experience during near-death. © 2014 New York Academy of Sciences.

Getting comfortable with near death experiences. Out of one's mind or beyond the brain? The challenge of interpreting near-death experiences.

PubMed

Radin, Dean

2014-01-01

With one exception, near-death experiences (NDEs) may be interpreted as unusual forms of hallucinations associated with the injured or dying brain. The exception involves perceptions described from vantage points outside the body that are later confirmed to be correct and could not have been inferred. Over a century of laboratory studies have investigated whether it is possible in principle for the mind to transcend the physical boundaries of the brain. The cumulative experimental database strongly indicates that it can. It is not clear that this implies the mind is separate from the brain, but it does suggest that a comprehensive explanation for NDEs will require revisions to present scientific assumptions about the brain-mind relationship.

Molecular pathology of brain edema after severe burns in forensic autopsy cases with special regard to the importance of reference gene selection.

PubMed

Wang, Qi; Ishikawa, Takaki; Michiue, Tomomi; Zhu, Bao-Li; Guan, Da-Wei; Maeda, Hitoshi

2013-09-01

Brain edema is believed to be linked to high mortality incidence after severe burns. The present study investigated the molecular pathology of brain damage and responses involving brain edema in forensic autopsy cases of fire fatality (n = 55) compared with sudden cardiac death (n = 11), mechanical asphyxia (n = 13), and non-brain injury cases (n = 22). Postmortem mRNA and immunohistochemical expressions of aquaporins (AQPs), claudin5 (CLDN5), and matrix metalloproteinases (MMPs) were examined. Prolonged deaths due to severe burns showed an increase in brain water content, but relative mRNA quantification, using different normalization methods, showed inconsistent results: in prolonged deaths due to severe burns, higher expression levels were detected for all markers when three previously validated reference genes, PES1, POLR2A, and IPO8, were used for normalization, higher for AQP1 and MMP9 when GAPDH alone was used for normalization and higher for MMP9, but lower for MMP2 when B2M alone was used for normalization. Additionally, when B2M alone was used for normalization, higher expression of AQP4 was detected in acute fire deaths. Furthermore, the expression stability values of these five reference genes calculated by geNorm demonstrated that B2M was the least stable one, followed by GAPDH. In immunostaining, only AQP1 and MMP9 showed differences among the causes of death: they were evident in most prolonged deaths due to severe burns. These findings suggest that systematic analysis of gene expressions using real-time PCR might be a useful procedure in forensic death investigation, and validation of reference genes is crucial.

Acute brain herniation from lead toxicity.

PubMed

Berkowitz, Sheldon; Tarrago, Rod

2006-12-01

A 4-year-old black boy was admitted to the hospital with vomiting, low-grade fever, and dehydration that were thought to be caused by viral gastroenteritis. He proceeded over the next 12 hours to rapidly deteriorate with brain herniation leading to brain death. The ultimate cause of death was found to be acute lead intoxication from a swallowed foreign body.

Hemodynamic resuscitation with arginine vasopressin reduces lung injury after brain death in the transplant donor.

PubMed

Rostron, Anthony J; Avlonitis, Vassilios S; Cork, David M W; Grenade, Danielle S; Kirby, John A; Dark, John H

2008-02-27

The autonomic storm accompanying brain death leads to neurogenic pulmonary edema and triggers development of systemic and pulmonary inflammatory responses. Neurogenic vasoplegia exacerbates the pulmonary injury caused by brain death and primes the lung for ischemia reperfusion injury and primary graft dysfunction in the recipient. Donor resuscitation with norepinephrine ameliorates the inflammatory response to brain death, however norepinephrine has deleterious effects, particularly on the heart. We tested the hypothesis that arginine vasopressin is a suitable alternative to norepinephrine in managing the hypotensive brain dead donor. Brain death was induced in Wistar rats by intracranial balloon inflation. Pulmonary capillary leak was estimated using radioiodinated albumin. Development of pulmonary edema was assessed by measurement of wet and dry lung weights. Cell surface expression of CD11b/CD18 by neutrophils was determined using flow cytometry. Enzyme-linked immunosorbent assays were used to measure the levels of TNFalpha, IL-1beta, CINC-1, and CINC-3 in serum and bronchoalveolar lavage. Quantitative reverse-transcription polymerase chain reaction was used to determine the expression of cytokine mRNA (IL-1beta, CINC-1 and CINC-3) in lung tissue. There was a significant increase in pulmonary capillary permeability, wet/dry lung weight ratios, neutrophil integrin expression and pro-inflammatory cytokines in serum (TNFalpha, IL-1beta, CINC-1 and CINC-3), bronchoalveolar lavage (TNFalpha and IL-1beta) and lung tissue (IL-1beta and CINC-1) in braindead animals compared to controls. Correction of neurogenic hypotension with either arginine vasopressin or norepinephrine limits edema, reduces pulmonary capillary leak, and modulates systemic and pulmonary inflammatory responses to brain death. Arginine vasopressin and norepinephrine are equally effective in treating the hypotensive pulmonary donor in this rodent model.

Of wholes and parts: A Thomistic refutation of “Brain Death”

PubMed Central

Accad, Michel

2015-01-01

I propose a refutation of the two major arguments that support the concept of “brain death” as an ontological equivalent to death of the human organism. I begin with a critique of the notion that a body part, such as the brain, could act as “integrator” of a whole body. I then proceed with a rebuttal of the argument that destruction of a body part essential for rational operations—such as the brain—necessarily entails that the remaining whole is indisposed to accrue a rational soul. Next, I point to the equivocal use of the terms “alive” or “living” as being at the root of conceptual errors about brain death. I appeal to the Thomistic definition of life and to the hylomorphic concept of “virtual presence” to clarify this confusion. Finally, I show how the Thomistic definition of life supports the traditional criterion for the determination of death. Lay summary: By the mid-1960s, medical technology became available that could keep “alive” the bodies of patients who had sustained complete and irreversible brain injury. The concept of “brain death” emerged to describe such states. Physicians, philosophers, and ethicists then proposed that the state of brain death is equivalent to the state of death traditionally identified by the absence of spontaneous pulse and respiration. This article challenges the major philosophical arguments that have been advanced to draw this equivalence. PMID:26912932

Genetic and epigenetic transgenerational implications related to omega-3 fatty acids. Part II: maternal FADS2 rs174575 genotype and DNA methylation predict toddler cognitive performance.

PubMed

Cheatham, Carol L; Lupu, Daniel S; Niculescu, Mihai D

2015-11-01

Maternal transfer of fatty acids is important to fetal brain development. The prenatal environment may differentially affect the substrates supporting declarative memory abilities, as the level of fatty acids transferred across the placenta may be affected by the maternal fatty acid desaturase 2 (FADS2) rs174575 single nucleotide polymorphism. In this study, we hypothesized that toddler and maternal rs174575 genotype and FADS2 promoter methylation would be related to the toddlers' declarative memory performance. Seventy-one 16-month-old toddlers participated in an imitation paradigm designed to test immediate and long-term declarative memory abilities. FADS2 rs174575 genotype was determined and FADS2 promoter methylation was quantified from blood by bisulfite pyrosequencing for the toddlers and their natural mothers. Toddlers of GG mothers at the FADS2 rs174575 single nucleotide polymorphism did not perform as well on memory assessments as toddlers of CC or CG mothers when controlling for plasma α-linolenic acid and child genotype. Toddler methylation status was related to immediate memory performance, whereas maternal methylation status was related to delayed memory performance. Thus, prenatal experience and maternal FADS2 status have a pervasive, long-lasting influence on the brain development of the offspring, but as the postnatal environment becomes more primary, the offsprings' own biology begins to have an effect. Copyright © 2015 Elsevier Inc. All rights reserved.

D. Alan Shewmon and the PCBE's White Paper on Brain Death: are brain-dead patients dead?

PubMed

Brugger, E Christian

2013-04-01

The December 2008 White Paper (WP) on "Brain Death" published by the President's Council on Bioethics (PCBE) reaffirmed its support for the traditional neurological criteria for human death. It spends considerable time explaining and critiquing what it takes to be the most challenging recent argument opposing the neurological criteria formulated by D. Alan Shewmon, a leading critic of the "whole brain death" standard. The purpose of this essay is to evaluate and critique the PCBE's argument. The essay begins with a brief background on the history of the neurological criteria in the United States and on the preparation of the 2008 WP. After introducing the WP's contents, the essay sets forth Shewmon's challenge to the traditional neurological criteria and the PCBE's reply to Shewmon. The essay concludes by critiquing the WP's novel justification for reaffirming the traditional conclusion, a justification the essay finds wanting.

Death receptors DR6 and TROY regulate brain vascular development.

PubMed

Tam, Stephen J; Richmond, David L; Kaminker, Joshua S; Modrusan, Zora; Martin-McNulty, Baby; Cao, Tim C; Weimer, Robby M; Carano, Richard A D; van Bruggen, Nick; Watts, Ryan J

2012-02-14

Signaling events that regulate central nervous system (CNS) angiogenesis and blood-brain barrier (BBB) formation are only beginning to be elucidated. By evaluating the gene expression profile of mouse vasculature, we identified DR6/TNFRSF21 and TROY/TNFRSF19 as regulators of CNS-specific angiogenesis in both zebrafish and mice. Furthermore, these two death receptors interact both genetically and physically and are required for vascular endothelial growth factor (VEGF)-mediated JNK activation and subsequent human brain endothelial sprouting in vitro. Increasing beta-catenin levels in brain endothelium upregulate DR6 and TROY, indicating that these death receptors are downstream target genes of Wnt/beta-catenin signaling, which has been shown to be required for BBB development. These findings define a role for death receptors DR6 and TROY in CNS-specific vascular development. Copyright © 2012 Elsevier Inc. All rights reserved.

Bigger is better! Hippocampal volume and declarative memory performance in healthy young men.

PubMed

Pohlack, Sebastian T; Meyer, Patric; Cacciaglia, Raffaele; Liebscher, Claudia; Ridder, Stephanie; Flor, Herta

2014-01-01

The importance of the hippocampus for declarative memory processes is firmly established. Nevertheless, the issue of a correlation between declarative memory performance and hippocampal volume in healthy subjects still remains controversial. The aim of the present study was to investigate this relationship in more detail. For this purpose, 50 healthy young male participants performed the California Verbal Learning Test. Hippocampal volume was assessed by manual segmentation of high-resolution 3D magnetic resonance images. We found a significant positive correlation between putatively hippocampus-dependent memory measures like short-delay retention, long-delay retention and discriminability and percent hippocampal volume. No significant correlation with measures related to executive processes was found. In addition, percent amygdala volume was not related to any of these measures. Our data advance previous findings reported in studies of brain-damaged individuals in a large and homogeneous young healthy sample and are important for theories on the neural basis of episodic memory.

Comparison of outcomes of kidney transplantation from donation after brain death, donation after circulatory death, and donation after brain death followed by circulatory death donors.

PubMed

Chen, Guodong; Wang, Chang; Ko, Dicken Shiu-Chung; Qiu, Jiang; Yuan, Xiaopeng; Han, Ming; Wang, Changxi; He, Xiaoshun; Chen, Lizhong

2017-11-01

There are three categories of deceased donors of kidney transplantation in China, donation after brain death (DBD), donation after circulatory death (DCD), and donation after brain death followed by circulatory death (DBCD) donors. The aim of this study was to compare the outcomes of kidney transplantation from these three categories of deceased donors. We retrospectively reviewed 469 recipients who received deceased kidney transplantation in our hospital from February 2007 to June 2015. The recipients were divided into three groups according to the source of their donor kidneys: DBD, DCD, or DBCD. The primary endpoints were delayed graft function (DGF), graft loss, and patient death. The warm ischemia time was much longer in DCD group compared to DBCD group (18.4 minutes vs 12.9 minutes, P < .001). DGF rate was higher in DCD group than in DBD and DBCD groups (22.5% vs 10.2% and 13.8%, respectively, P = .021). Urinary leakage was much higher in DCD group (P = .049). Kaplan-Meier analysis showed that 1-, 2-, and 3-year patient survivals were all comparable among the three groups. DBCD kidney transplantation has lower incidences of DGF and urinary leakage than DCD kidney transplant. However, the overall patient and graft survival were comparable among DBD, DCD, and DBCD kidney transplantation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings

PubMed Central

Michalak, Zuzanna; Wright, Gabriella; Dawson, Timothy; Hilton, David; Joshi, Abhijit; Diehl, Beate; Koepp, Matthias; Lhatoo, Samden; Sander, Josemir W.; Sisodiya, Sanjay M.

2015-01-01

Aims Sudden unexpected death in epilepsy (SUDEP) is one of the leading causes of death in people with epilepsy. For classification of definite SUDEP, a post mortem (PM), including anatomical and toxicological examination, is mandatory to exclude other causes of death. We audited PM practice as well as the value of brain examination in SUDEP. Methods We reviewed 145 PM reports in SUDEP cases from four UK neuropathology centres. Data were extracted for clinical epilepsy details, circumstances of death and neuropathological findings. Results Macroscopic brain abnormalities were identified in 52% of cases. Mild brain swelling was present in 28%, and microscopic pathologies relevant to cause or effect of seizures were seen in 89%. Examination based on whole fixed brains (76.6% of all PMs), and systematic regional sampling was associated with higher detection rates of underlying pathology (P < 0.01). Information was more frequently recorded regarding circumstances of death and body position/location than clinical epilepsy history and investigations. Conclusion Our findings support the contribution of examination of the whole fixed brain in SUDEP, with high rates of detection of relevant pathology. Availability of full clinical epilepsy‐related information at the time of PM could potentially further improve detection through targeted tissue sampling. Apart from confirmation of SUDEP, complete neuropathological examination contributes to evaluation of risk factors as well as helping to direct future research into underlying causes. PMID:26300477

Control of adult neurogenesis by programmed cell death in the mammalian brain.

PubMed

Ryu, Jae Ryun; Hong, Caroline Jeeyeon; Kim, Joo Yeon; Kim, Eun-Kyoung; Sun, Woong; Yu, Seong-Woon

2016-04-21

The presence of neural stem cells (NSCs) and the production of new neurons in the adult brain have received great attention from scientists and the public because of implications to brain plasticity and their potential use for treating currently incurable brain diseases. Adult neurogenesis is controlled at multiple levels, including proliferation, differentiation, migration, and programmed cell death (PCD). Among these, PCD is the last and most prominent process for regulating the final number of mature neurons integrated into neural circuits. PCD can be classified into apoptosis, necrosis, and autophagic cell death and emerging evidence suggests that all three may be important modes of cell death in neural stem/progenitor cells. However, the molecular mechanisms that regulate PCD and thereby impact the intricate balance between self-renewal, proliferation, and differentiation during adult neurogenesis are not well understood. In this comprehensive review, we focus on the extent, mechanism, and biological significance of PCD for the control of adult neurogenesis in the mammalian brain. The role of intrinsic and extrinsic factors in the regulation of PCD at the molecular and systems levels is also discussed. Adult neurogenesis is a dynamic process, and the signals for differentiation, proliferation, and death of neural progenitor/stem cells are closely interrelated. A better understanding of how adult neurogenesis is influenced by PCD will help lead to important insights relevant to brain health and diseases.

Impact of brain death on ischemia/reperfusion injury in liver transplantation.

PubMed

Dziodzio, Tomasz; Biebl, Matthias; Pratschke, Johann

2014-04-01

In liver transplantation, the ischemia/reperfusion injury (IRI) is influenced by factors related to graft quality, organ procurement and the transplant procedure itself. However, in brain-dead donors, the process of death itself also thoroughly affects organ damage through breakdown of the autonomous nervous system and subsequent massive cytokine release. This review highlights the actual knowledge on these proinflammatory effects of brain death on IRI in liver transplantation. Brain death affects IRI either through hemodynamical or molecular effects with proinflammatory activation. Immunological effects are mainly mediated through Kupffer cell activation, leading to TNF-α and TLR4 amplification. Proinflammatory cytokines such as interleukin (IL)-6, IL-10, TNF-β and MIP-1α are released, together with activation of the innate immune system via natural killer cells and natural killer T cells, which promote organ damage and activation of fibrosis. Preprocurement treatment regimens attempt to hamper inflammatory response by the application of methylprednisolone or thymoglobulin to the donor. Selective P-selectin antagonism resulted in improved function in marginal liver grafts. Inhaled nitric oxide was found to reduce apoptosis in liver grafts. Other medications like the immunosuppressant tacrolimus produced conflicting results regarding organ protection. Furthermore, improved organ storage after procurement - such as machine perfusion - can diminish effects of IRI in a clinical setting. Brain death plays a fundamental role in the regulation of molecular markers triggering inflammation and IRI-related tissue damage in liver transplants. Although several treatment options have reached clinical application, to date, the effects of brain death during donor conditioning and organ procurement remain relevant for organ function and survival.

Implementation and clinical characteristics of a posttraumatic stress disorder brain collection.

PubMed

Mighdoll, Michelle I; Deep-Soboslay, Amy; Bharadwaj, Rahul A; Cotoia, John A; Benedek, David M; Hyde, Thomas M; Kleinman, Joel E

2018-01-01

A postmortem human brain collection to study posttraumatic stress disorder (PTSD) is critical for uncovering the molecular mechanisms that contribute to this psychiatric disorder. We describe here the PTSD brain collection at the Lieber Institute for Brain Development in Baltimore, Maryland, consisting of postmortem brain donations acquired between 2012 and 2017. Thus far, 87 brains from individuals meeting DSM-5 criteria for PTSD were collected after consent was obtained from legal next-of-kin, and subsequently clinically characterized for molecular studies. PTSD brain donors had high rates of comorbid diagnoses, including depression (62.1%), substance abuse (74.7%), drug-related death (69.0%), and suicide completion (17.2%). PTSD cases were subdivided into two categories: combat-related PTSD (n = 24) and noncombat/domestic PTSD (n = 63). The major differences between the combat-related and domestic PTSD cohorts were sex, drug-related death, and the prevalence of bipolar disorder (BPD) comorbidity. The combat-related group was entirely male, with only one BPD subject (4.2%), and had significantly fewer drug-related deaths (45.8%) in contrast to the domestic group (31.8% male, 36.5% bipolar, and 77.8% drug-related deaths). Medical examiners' offices, particularly in areas with higher military populations, are an excellent source for PTSD brain donations of both combat-related and domestic PTSD. © 2017 Wiley Periodicals, Inc.

Brain Arterial Diameters as a Risk Factor for Vascular Events.

PubMed

Gutierrez, Jose; Cheung, Ken; Bagci, Ahmet; Rundek, Tatjana; Alperin, Noam; Sacco, Ralph L; Wright, Clinton B; Elkind, Mitchell S V

2015-08-06

Arterial luminal diameters are routinely used to assess for vascular disease. Although small diameters are typically considered pathological, arterial dilatation has also been associated with disease. We hypothesize that extreme arterial diameters are biomarkers of the risk of vascular events. Participants in the Northern Manhattan Study who had a time-of-flight magnetic resonance angiography were included in this analysis (N=1034). A global arterial Z-score, called the brain arterial remodeling (BAR) score, was obtained by averaging the measured diameters within each individual. Individuals with a BAR score <-2 SDs were considered to have the smallest diameters, individuals with a BAR score >-2 and <2 SDs had average diameters, and individuals with a BAR score >2 SDs had the largest diameters. All vascular events were recorded prospectively after the brain magnetic resonance imaging. Spline curves and incidence rates were used to test our hypothesis. The association of the BAR score with death (P=0.001), vascular death (P=0.02), any vascular event (P=0.05), and myocardial infarction (P=0.10) was U-shaped except for ischemic stroke (P=0.74). Consequently, incidence rates for death, vascular death, myocardial infarction, and any vascular event were higher in individuals with the largest diameters, whereas individuals with the smallest diameters had a higher incidence of death, vascular death, any vascular event, and ischemic stroke compared with individuals with average diameters. The risk of death, vascular death, and any vascular event increased at both extremes of brain arterial diameters. The pathophysiology linking brain arterial remodeling to systemic vascular events needs further research. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Up-regulation of K{sub ir}2.1 by ER stress facilitates cell death of brain capillary endothelial cells

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

Kito, Hiroaki; Yamazaki, Daiju; Department of Biological Chemistry, Kyoto University, Graduate School of Pharmaceutical Sciences, Kyoto

Highlights: {yields} We found that application of endoplasmic reticulum (ER) stress with tunicamycin to brain capillary endothelial cells (BCECs) induced cell death. {yields} The ER stress facilitated the expression of inward rectifier K{sup +} channel (K{sub ir}2.1) and induced sustained membrane hyperpolarization. {yields} The membrane hyperpolarization induced sustained Ca{sup 2+} entry through voltage-independent nonspecific cation channels and consequently facilitated cell death. {yields} The K{sub ir}2.1 up-regulation by ER stress is, at least in part, responsible for cell death of BCECs under pathological conditions. -- Abstract: Brain capillary endothelial cells (BCECs) form blood brain barrier (BBB) to maintain brain homeostasis. Cellmore » turnover of BCECs by the balance of cell proliferation and cell death is critical for maintaining the integrity of BBB. Here we found that stimuli with tunicamycin, endoplasmic reticulum (ER) stress inducer, up-regulated inward rectifier K{sup +} channel (K{sub ir}2.1) and facilitated cell death in t-BBEC117, a cell line derived from bovine BCECs. The activation of K{sub ir} channels contributed to the establishment of deeply negative resting membrane potential in t-BBEC117. The deep resting membrane potential increased the resting intracellular Ca{sup 2+} concentration due to Ca{sup 2+} influx through non-selective cation channels and thereby partly but significantly regulated cell death in t-BBEC117. The present results suggest that the up-regulation of K{sub ir}2.1 is, at least in part, responsible for cell death/cell turnover of BCECs induced by a variety of cellular stresses, particularly ER stress, under pathological conditions.« less

Islam, brain death, and transplantation: culture, faith, and jurisprudence.

PubMed

Arbour, Richard; AlGhamdi, Hanan Mesfer Saad; Peters, Linda

2012-01-01

A significant gap exists between availability of organs for transplant and patients with end-stage organ failure for whom organ transplantation is the last treatment option. Reasons for this mismatch include inadequate approach to potential donor families and donor loss as a result of refractory cardiopulmonary instability during and after brainstem herniation. Other reasons include inadequate cultural competence and sensitivity when communicating with potential donor families. Clinicians may not have an understanding of the cultural and religious perspectives of Muslim families of critically ill patients who may be approached about brain death and organ donation. This review analyzes Islamic cultural and religious perspectives on organ donation, transplantation, and brain death, including faith-based directives from Islamic religious authorities, definitions of death in Islam, and communication strategies when discussing brain death and organ donation with Muslim families. Optimal family care and communication are highlighted using case studies and backgrounds illustrating barriers and approaches with Muslim families in the United States and in the Kingdom of Saudi Arabia that can improve cultural competence and family care as well as increase organ availability within the Muslim population and beyond.

Letter: Can Islamic Jurisprudence Justify Procurement of Transplantable Vital Organs in Brain Death?

PubMed

Rady, Mohamed Y

2018-01-01

In their article, "An International Legal Review of the Relationship between Brain Death and Organ Transplantation," in The Journal of Clinical Ethics 29, no. 1, Aramesh, Arima, Gardiner, and Shah reported on diverse international legislative approaches for justifying procurement of transplantable vital organs in brain death. They stated, "In Islamic traditions in particular, the notion of unstable life is a way to justify organ donation from brain-dead patients that we believe has not been fully described previously in the literature." This commentary queries the extent to which this concept is valid in accordance with the primary source of Islamic law, that is, the Quran. Copyright 2018 The Journal of Clinical Ethics. All rights reserved.

[Deceased organ donors, legal regulations governing diagnosis of brain death, overview of donors and liver transplants in the Czech Republic].

PubMed

Pokorná, E

2013-08-01

The key restriction of transplantation medicine globally, as well as in the Czech Republic, concerns the lack of organs. The number of deceased donors, and thus the availability of organ transplants, has been stagnating in our country. The paper describes current legal regulations governing the dia-gnosis of brain death and primary legal and medical criteria for the contraindication of the deceased for organ explantation, gives an overview of the number of liver transplants, age structure, and diagnosis resulting in brain death of the deceased liver donors in the Czech Republic.

Transplantation of donor hearts after circulatory or brain death in a rat model.

PubMed

Li, Shiliang; Loganathan, Sivakkanan; Korkmaz, Sevil; Radovits, Tamás; Hegedűs, Peter; Zhou, Yan; Karck, Matthias; Szabó, Gábor

2015-05-01

Heart transplantation represents the only curative treatment for end-stage heart failure. Presently, the donor pool is restricted to brain-dead donors. Based on the lack of suitable donors and the increasing number of patients, we investigated some molecular pathomechanisms of the potential use of hearts after circulatory determination of death (DCDD) in transplantation. Rats were either maintained brain death for 5 h by inflation of a subdurally placed balloon catheter (n = 6) or subjected to cardiac arrest by exsanguinations (n = 6). Additionally, a control group was used (n = 9). Then the hearts were perfused with a cold preservation solution (Custodiol), explanted, stored at 4°C in Custodiol, and heterotopically transplanted. Brain death was associated with decreased left-ventricular contractility (dP/dtmax: 4895 ± 505 versus 8037 ± 565 mm Hg/s; ejection fraction: 27 ± 5 versus 44 ± 5%; Emax: 2.2 ± 0.3 versus 4.2 ± 0.3 mm Hg/μL; preload recruitable stroke work: 59 ± 5 versus 96 ± 6 mm Hg; 5 h after brain death versus before brain death; P < 0.05) and impaired cardiac relaxation (dP/dtmin: -4734 ± 575 versus -9404 ± 550 mm Hg/s and prolonged Tau, P < 0.05) compared with controls. After transplantation, significantly decreased systolic function and prolonged Tau were observed in brain-dead and DCDD groups compared with those in controls. Tumor necrosis factor-alpha, cyclooxygenase-2, nuclear factor-κB, inducible-NOS, and caspase-3 messenger RNA and protein-levels were significantly increased in the brain-dead compared with both control and DCDD groups. Additionally, marked myocardial inflammatory cell infiltration, edema, necrosis, and DNA-strand breaks were observed in the brain-dead group. Our results show that despite the similar functional outcome in DCDD and brain-dead groups, brain-dead hearts showed marked myocardial inflammatory cell infiltration, edema, necrosis, DNA-strand breaks, and increased transcriptional and posttranscriptional expression for markers of apoptosis and inflammatory signaling pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

The Dead Donor Rule: Can It Withstand Critical Scrutiny?

PubMed Central

Miller, Franklin G.; Truog, Robert D.; Brock, Dan W.

2010-01-01

Transplantation of vital organs has been premised ethically and legally on “the dead donor rule” (DDR)—the requirement that donors are determined to be dead before these organs are procured. Nevertheless, scholars have argued cogently that donors of vital organs, including those diagnosed as “brain dead” and those declared dead according to cardiopulmonary criteria, are not in fact dead at the time that vital organs are being procured. In this article, we challenge the normative rationale for the DDR by rejecting the underlying premise that it is necessarily wrong for physicians to cause the death of patients and the claim that abandoning this rule would exploit vulnerable patients. We contend that it is ethical to procure vital organs from living patients sustained on life support prior to treatment withdrawal, provided that there is valid consent for both withdrawing treatment and organ donation. However, the conservatism of medical ethics and practical concerns make it doubtful that the DDR will be abandoned in the near future. This leaves the current practice of organ transplantation based on the “moral fiction” that donors are dead when vital organs are procured. PMID:20439355

5-HTTLPR moderates the association between interdependence and brain responses to mortality threats.

PubMed

Luo, Siyang; Yu, Dian; Han, Shihui

2017-12-01

While behavioral research suggests an association between cultural worldview and decreased anxiety of death, the underlying neurobiological mechanisms remain unclear. Using functional MRI, we investigated whether and how the serotonin transporter promoter polymorphism (5-HTTLPR), which has been associated with mental disorders such as anxiety and depression, moderates the associations between a cultural trait (i.e., interdependence) and self-report of death anxiety/depression and between interdependence and brain responses to mortality threats. Long/long and short/short allele carriers of the 5-HTTLPR were scanned using fMRI while they performed a one-back task on death-related, death-unrelated negative, and neutral words. Participants' interdependence and death anxiety/depression were assessed using questionnaires after scanning. We found that participants who assessed themselves with greater interdependence reported lower death anxiety/depression and showed decreased neural response to death-related words in emotion-related brain regions including the anterior cingulate, putamen, and thalamus. However, these results were evident in long/long allele carriers of the 5-HTTLPR but not in short/short allele carriers who even showed positive associations between interdependence and neural activities in the anterior cingulate, putamen and thalamus in response to death-related words. Our findings suggest candidate mechanisms for explaining the complex relationship between genotype, cultural traits, and mental/neural responses to mortality threats. Hum Brain Mapp 38:6157-6171, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Whole brain analysis of postmortem density changes of grey and white matter on computed tomography by statistical parametric mapping.

PubMed

Nishiyama, Yuichi; Kanayama, Hidekazu; Mori, Hiroshi; Tada, Keiji; Yamamoto, Yasushi; Katsube, Takashi; Takeshita, Haruo; Kawakami, Kazunori; Kitagaki, Hajime

2017-06-01

This study examined the usefulness of statistical parametric mapping (SPM) for investigating postmortem changes on brain computed tomography (CT). This retrospective study included 128 patients (23 - 100 years old) without cerebral abnormalities who underwent unenhanced brain CT before and after death. The antemortem CT (AMCT) scans and postmortem CT (PMCT) scans were spatially normalized using our original brain CT template, and postmortem changes of CT values (in Hounsfield units; HU) were analysed by the SPM technique. Compared with AMCT scans, 58.6 % and 98.4 % of PMCT scans showed loss of the cerebral sulci and an unclear grey matter (GM)-white matter (WM) interface, respectively. SPM analysis revealed a significant decrease in cortical GM density within 70 min after death on PMCT scans, suggesting cytotoxic brain oedema. Furthermore, there was a significant increase in the density of the WM, lenticular nucleus and thalamus more than 120 min after death. The SPM technique demonstrated typical postmortem changes on brain CT scans, and revealed that the unclear GM-WM interface on early PMCT scans is caused by a rapid decrease in cortical GM density combined with a delayed increase in WM density. SPM may be useful for assessment of whole brain postmortem changes. • The original brain CT template achieved successful normalization of brain morphology. • Postmortem changes in the brain were independent of sex. • Cortical GM density decreased rapidly after death. • WM and deep GM densities increased following cortical GM density change. • SPM could be useful for assessment of whole brain postmortem changes.

A matter of respect: a defense of the dead donor rule and of a "whole-brain" criterion for determination of death.

PubMed

Khushf, George

2010-06-01

Many accounts of the historical development of neurological criteria for determination of death insufficiently distinguish between two strands of interpretation advanced by advocates of a "whole-brain" criterion. One strand focuses on the brain as the organ of integration. Another provides a far more complex and nuanced account, both of death and of a policy on the determination of death. Current criticisms of the whole-brain criterion are effective in refuting the first interpretation, but not the second, which is advanced in the 2008 President's Council report on the determination of death. In this essay, I seek to further develop this second strand of interpretation. I argue that policy on determination of death aligns moral, biological, and ontological death concepts. Morally, death marks the stage when respect is no longer owed. Biologically, death concerns integrated functioning of an organism as a whole. But the biological concepts are underdetermined. The moral concerns lead to selection of strong individuality concepts rather than weak ones. They also push criteria to the "far side" of the dying process. There is a countervailing consideration associated with optimizing the number of available organs, and this pushes to the "near side" of death. Policy is governed by a conviction that it is possible to align these moral and biological death concepts, but this conviction simply lays out an agenda. There is also a prescription-integral to the dead donor rule-that lexically prioritizes the deontic concerns and that seeks to balance the countervailing tendencies by using science-based refinements to make the line between life and death more precise. After showing how these concerns have been effectively aligned in the current policy, I present a modified variant of a "division" scenario and show how an "inverse decapitation problem" leads to a conclusive refutation of the nonbrain account of death.

Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings.

PubMed

Thom, Maria; Michalak, Zuzanna; Wright, Gabriella; Dawson, Timothy; Hilton, David; Joshi, Abhijit; Diehl, Beate; Koepp, Matthias; Lhatoo, Samden; Sander, Josemir W; Sisodiya, Sanjay M

2016-08-01

Sudden unexpected death in epilepsy (SUDEP) is one of the leading causes of death in people with epilepsy. For classification of definite SUDEP, a post mortem (PM), including anatomical and toxicological examination, is mandatory to exclude other causes of death. We audited PM practice as well as the value of brain examination in SUDEP. We reviewed 145 PM reports in SUDEP cases from four UK neuropathology centres. Data were extracted for clinical epilepsy details, circumstances of death and neuropathological findings. Macroscopic brain abnormalities were identified in 52% of cases. Mild brain swelling was present in 28%, and microscopic pathologies relevant to cause or effect of seizures were seen in 89%. Examination based on whole fixed brains (76.6% of all PMs), and systematic regional sampling was associated with higher detection rates of underlying pathology (P < 0.01). Information was more frequently recorded regarding circumstances of death and body position/location than clinical epilepsy history and investigations. Our findings support the contribution of examination of the whole fixed brain in SUDEP, with high rates of detection of relevant pathology. Availability of full clinical epilepsy-related information at the time of PM could potentially further improve detection through targeted tissue sampling. Apart from confirmation of SUDEP, complete neuropathological examination contributes to evaluation of risk factors as well as helping to direct future research into underlying causes. © 2015 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

Traumatic Brain and Spinal Cord Fatalities Among High School and College Football Players - United States, 2005-2014.

PubMed

Kucera, Kristen L; Yau, Rebecca K; Register-Mihalik, Johna; Marshall, Stephen W; Thomas, Leah C; Wolf, Susanne; Cantu, Robert C; Mueller, Frederick O; Guskiewicz, Kevin M

2017-01-06

An estimated 1.1 million high school and 75,000 college athletes participate in tackle football annually in the United States. Football is a collision sport; traumatic injuries are frequent (1,2), and can be fatal (3). This report updates the incidence and characteristics of deaths caused by traumatic brain injury and spinal cord injury (4) in high school and college football and presents illustrative case descriptions. Information was analyzed from the National Center for Catastrophic Sport Injury Research (NCCSIR). During 2005-2014, a total of 28 deaths (2.8 deaths per year) from traumatic brain and spinal cord injuries occurred among high school (24 deaths) and college football players (four deaths) combined. Most deaths occurred during competitions and resulted from tackling or being tackled. All four of the college deaths and 14 (58%) of the 24 high school deaths occurred during the last 5 years (2010-2014) of the 10-year study period. These findings support the need for continued surveillance and safety efforts (particularly during competition) to ensure proper tackling techniques, emergency planning for severe injuries, availability of medical care onsite during competitions, and assessment that it is safe to return to play following a concussion.

A consideration of the ethics of brain death--what are the ethical guidelines for physician, family and society in dealing with brain death?

PubMed

Brooks, C M

1985-06-01

There is at present considerable confusion with respect to ethical guidelines that should govern the behavior of society and the physician confronted by problems resulting from recent attainments of medicine and science. The use of life supporting devices raises the problem of determining when death has occurred and what is proper ethical procedure in dealing with the deficient half life caused by "Brain Death." Some guidance is obtained from a consideration of the nature of life, the nature of death, the nature of man, and the essence lost in death of man. A parallel consideration of the nature of ethics, the bases of ethics and of ethical decision can be helpful. An individual may have ideals which control behavior, even elevate ethical standards; others entertain concepts that destroy social ethics. Ethics control and direct social interactions; ethics determine the quality of social behavior--ethics are established by societies not by individuals. Numerous commissions have endeavored to define the requirements of physicians for diagnosing brain death and for appropriate subsequent actions. The rationales presented, however, are not invariably accepted by lay society. The problem is created by numerous trends. Among them are the "rightest" movement which, though possessing many virtues, has its excesses such as expressed in the "right to life movement." These have not been beneficial and have necessitated "right to death movements." Opposition is also due to the fact that society's concepts of the medical profession have changed. The practice of organ transplantation has created problems. Finally, the concept of death as other than evil is no longer generally accepted. As more biological manipulations are possible ever more difficult ethical problems will arise. It is a certainty, however, that when brain death has occurred life of man and that of the individual has ended. Although others might not agree, our ethic requires us to use life assist techniques to preserve the vegetative man, the individual who can still breathe spontaneously though lacking consciousness and behavioral ability. All the codes of medical ethics state that a physician shall not kill--this does not mean he cannot permit the terminal phases of death when the essence of human life is lost. A major question is the ethical responsibility of one society toward another. Can an affluent society squander its resources in the preservation of ineffectual life in the body after "brain death" when others are without the medical assistance which would permit total living?

"Rigor mortis" in a live patient.

PubMed

Chakravarthy, Murali

2010-03-01

Rigor mortis is conventionally a postmortem change. Its occurrence suggests that death has occurred at least a few hours ago. The authors report a case of "Rigor Mortis" in a live patient after cardiac surgery. The likely factors that may have predisposed such premortem muscle stiffening in the reported patient are, intense low cardiac output status, use of unusually high dose of inotropic and vasopressor agents and likely sepsis. Such an event may be of importance while determining the time of death in individuals such as described in the report. It may also suggest requirement of careful examination of patients with muscle stiffening prior to declaration of death. This report is being published to point out the likely controversies that might arise out of muscle stiffening, which should not always be termed rigor mortis and/ or postmortem.

Effectiveness of a nonpenetrating captive bolt for euthanasia of 3 kg to 9 kg pigs.

PubMed

Casey-Trott, T M; Millman, S T; Turner, P V; Nykamp, S G; Lawlis, P C; Widowski, T M

2014-11-01

The objective of this study was to determine the effectiveness of a nonpenetrating captive bolt, Zephyr-E, for euthanasia of suckling and weaned pigs from 3 to 9 kg (5-49 d of age) using signs of insensibility and death as well as postmortem assessment of traumatic brain injury (TBI). The Zephyr-E was used by 15 stock people to euthanize 150 compromised pigs from 4 farrowing and nursery units from commercial farms and 2 research stations. Brainstem reflexes, convulsions, and heartbeat were used to assess insensibility, time of brain death, and cardiac arrest following Zephyr-E application. Skull fracture displacement (FD) was quantified from computed tomography (CT) scans (n = 24), macroscopic scoring was used to assess brain hemorrhage and skull fracture severity (n = 150), and microscopic scoring was used to assess subdural hemorrhage (SDH) and parenchymal hemorrhage within specific brain regions that are responsible for consciousness and vital function (n = 32). The Zephyr-E caused immediate, sustained insensibility until death in 98.6% of pigs. On average, clonic convulsions (CC) ceased in 82.2 s (± 3.4 SE), brain death was achieved in 144.9 s (± 5.4 SE), and cardiac arrest occurred in 226.5 s (± 8.7 SE). Time of brain death and cardiac arrest differed significantly among stock people (P = 0.0225 and P = 0.0369). Age was positively related to the duration of CC (P = 0.0092), time of brain death (P = 0.0025), and cardiac arrest (P = 0.0068) with shorter durations seen in younger pigs. Average FD was 8.3 mm (± 1.0 SE). Macroscopic scores were significantly different among weight classes for subcutaneous (P = 0.0402) and subdural-ventral (P = 0.0037) hemorrhage with the lowest severity hemorrhage found in the 9-kg weight category. Microscopic scores differed among brain sections (P = 0.0070) for SDH with lower scores found in the brainstem compared to the cerebral cortex and midbrain. Parenchymal hemorrhage differed among brain sections (P = 0.0052) and weight categories (P = 0.0128) with the lowest scores in the midbrain and brainstem and the 7- and 9-kg weight categories. The Zephyr-E was highly effective for the euthanasia of pigs up to 9 kg (49 d) based on immediate insensibility sustained until death. Postmortem results confirmed that severe skull fracture and widespread brain hemorrhage were caused by the Zephyr-E nonpenetrating captive bolt.

Attitudes to brain death and organ procurement among university students and critical care physicians in poland.

PubMed

Kubler, A; Lipinska-Gediga, M; Kedziora, J; Kubler, M

2009-06-01

The practice of retrieving vital organs from brain-dead heart-beating donors is legally and medically accepted in Poland, but public beliefs and opinions regarding these matters have not been sufficiently explored. The purpose of this study was to evaluate the attitude of university students to the concepts of brain death and organ retrieval, compared with the attitude of critical care physicians. The cohorts of 989 students and 139 physicians completed a questionnaire based on a survey instrument developed in an earlier reported study on Ohio residents. Participants assessed 3 scenarios: (1) brain death, (2) coma, and (3) vegetative state. More than 48% of students classified the patient from the brain death scenario as alive, and 51% of them were willing to donate organs of this patient. Ninety percent of students classified the patients in coma and in a vegetative state as alive, but still 34% of them would donate organs of those patients. The group of physicians properly determined the patients' diagnoses, but 10% of them accepted organ procurement from patients in coma and in a vegetative state. Our results supported the earlier observations of low public knowledge and inadequate understanding of brain death criteria and organ procurement processes. The majority of students were willing to accept organ procurement from severely ill but alive patients, in contrast with physicians. A considerable increase in public educational activity in this field is urgently recommended.

Simulation-based training in brain death determination.

PubMed

MacDougall, Benjamin J; Robinson, Jennifer D; Kappus, Liana; Sudikoff, Stephanie N; Greer, David M

2014-12-01

Despite straightforward guidelines on brain death determination by the American Academy of Neurology (AAN), substantial practice variability exists internationally, between states, and among institutions. We created a simulation-based training course on proper determination based on the AAN practice parameters to address and assess knowledge and practice gaps at our institution. Our intervention consisted of a didactic course and a simulation exercise, and was bookended by before and after multiple-choice tests. The 40-min didactic course, including a video demonstration, covered all aspects of the brain death examination. Simulation sessions utilized a SimMan 3G manikin and involved a complete examination, including an apnea test. Possible confounders and signs incompatible with brain death were embedded throughout. Facilitators evaluated performance with a 26-point checklist based on the most recent AAN guidelines. A senior neurologist conducted all aspects of the course, including the didactic session, simulation, and debriefing session. Ninety physicians from multiple specialties have participated in the didactic session, 38 of whom have completed the simulation. Pre-test scores were poor (41.4 %), with attendings scoring higher than residents (46.6 vs. 40.4 %, p = 0.07), and neurologists and neurosurgeons significantly outperforming other specialists (53.9 vs. 38.9 %, p = 0.003). Post-test scores (73.3 %) were notably higher than pre-test scores (45.4 %). Participant feedback has been uniformly positive. Baseline knowledge of brain death determination among providers was low but improved greatly after the course. Our intervention represents an effective model that can be replicated at other institutions to train clinicians in the determination of brain death according to evidence-based guidelines.

Mechanical versus humoral determinants of brain death-induced lung injury

PubMed Central

Dewachter, Laurence; Rorive, Sandrine; Remmelink, Myriam; Weynand, Birgit; Melot, Christian; Hupkens, Emeline; Dewachter, Céline; Creteur, Jacques; Mc Entee, Kathleen; Naeije, Robert; Rondelet, Benoît

2017-01-01

Background The mechanisms of brain death (BD)-induced lung injury remain incompletely understood, as uncertainties persist about time-course and relative importance of mechanical and humoral perturbations. Methods Brain death was induced by slow intracranial blood infusion in anesthetized pigs after randomization to placebo (n = 11) or to methylprednisolone (n = 8) to inhibit the expression of pro-inflammatory mediators. Pulmonary artery pressure (PAP), wedged PAP (PAWP), pulmonary vascular resistance (PVR) and effective pulmonary capillary pressure (PCP) were measured 1 and 5 hours after Cushing reflex. Lung tissue was sampled to determine gene expressions of cytokines and oxidative stress molecules, and pathologically score lung injury. Results Intracranial hypertension caused a transient increase in blood pressure followed, after brain death was diagnosed, by persistent increases in PAP, PCP and the venous component of PVR, while PAWP did not change. Arterial PO2/fraction of inspired O2 (PaO2/FiO2) decreased. Brain death was associated with an accumulation of neutrophils and an increased apoptotic rate in lung tissue together with increased pro-inflammatory interleukin (IL)-6/IL-10 ratio and increased heme oxygenase(HO)-1 and hypoxia inducible factor(HIF)-1 alpha expression. Blood expressions of IL-6 and IL-1β were also increased. Methylprednisolone pre-treatment was associated with a blunting of increased PCP and PVR venous component, which returned to baseline 5 hours after BD, and partially corrected lung tissue biological perturbations. PaO2/FiO2 was inversely correlated to PCP and lung injury score. Conclusions Brain death-induced lung injury may be best explained by an initial excessive increase in pulmonary capillary pressure with increased pulmonary venous resistance, and was associated with lung activation of inflammatory apoptotic processes which were partially prevented by methylprednisolone. PMID:28753621

Frequency and Type of Situational Awareness Errors Contributing to Death and Brain Damage: A Closed Claims Analysis.

PubMed

Schulz, Christian M; Burden, Amanda; Posner, Karen L; Mincer, Shawn L; Steadman, Randolph; Wagner, Klaus J; Domino, Karen B

2017-08-01

Situational awareness errors may play an important role in the genesis of patient harm. The authors examined closed anesthesia malpractice claims for death or brain damage to determine the frequency and type of situational awareness errors. Surgical and procedural anesthesia death and brain damage claims in the Anesthesia Closed Claims Project database were analyzed. Situational awareness error was defined as failure to perceive relevant clinical information, failure to comprehend the meaning of available information, or failure to project, anticipate, or plan. Patient and case characteristics, primary damaging events, and anesthesia payments in claims with situational awareness errors were compared to other death and brain damage claims from 2002 to 2013. Anesthesiologist situational awareness errors contributed to death or brain damage in 198 of 266 claims (74%). Respiratory system damaging events were more common in claims with situational awareness errors (56%) than other claims (21%, P < 0.001). The most common specific respiratory events in error claims were inadequate oxygenation or ventilation (24%), difficult intubation (11%), and aspiration (10%). Payments were made in 85% of situational awareness error claims compared to 46% in other claims (P = 0.001), with no significant difference in payment size. Among 198 claims with anesthesia situational awareness error, perception errors were most common (42%), whereas comprehension errors (29%) and projection errors (29%) were relatively less common. Situational awareness error definitions were operationalized for reliable application to real-world anesthesia cases. Situational awareness errors may have contributed to catastrophic outcomes in three quarters of recent anesthesia malpractice claims.Situational awareness errors resulting in death or brain damage remain prevalent causes of malpractice claims in the 21st century.

Cognitive Consilience: Primate Non-Primary Neuroanatomical Circuits Underlying Cognition

PubMed Central

Solari, Soren Van Hout; Stoner, Rich

2011-01-01

Interactions between the cerebral cortex, thalamus, and basal ganglia form the basis of cognitive information processing in the mammalian brain. Understanding the principles of neuroanatomical organization in these structures is critical to understanding the functions they perform and ultimately how the human brain works. We have manually distilled and synthesized hundreds of primate neuroanatomy facts into a single interactive visualization. The resulting picture represents the fundamental neuroanatomical blueprint upon which cognitive functions must be implemented. Within this framework we hypothesize and detail 7 functional circuits corresponding to psychological perspectives on the brain: consolidated long-term declarative memory, short-term declarative memory, working memory/information processing, behavioral memory selection, behavioral memory output, cognitive control, and cortical information flow regulation. Each circuit is described in terms of distinguishable neuronal groups including the cerebral isocortex (9 pyramidal neuronal groups), parahippocampal gyrus and hippocampus, thalamus (4 neuronal groups), basal ganglia (7 neuronal groups), metencephalon, basal forebrain, and other subcortical nuclei. We focus on neuroanatomy related to primate non-primary cortical systems to elucidate the basis underlying the distinct homotypical cognitive architecture. To display the breadth of this review, we introduce a novel method of integrating and presenting data in multiple independent visualizations: an interactive website (http://www.frontiersin.org/files/cognitiveconsilience/index.html) and standalone iPhone and iPad applications. With these tools we present a unique, annotated view of neuroanatomical consilience (integration of knowledge). PMID:22194717

The nucleus accumbens and learning and memory.

PubMed

Setlow, B

1997-09-01

Recent research on the nucleus accumbens (NA) indicates that this brain region is involved in learning and memory processes in a way that is separable from its other well-known roles in behavior, such as motivation, reward, and locomotor activity. These findings have suggested that 1) the NA may be involved in declarative, or hippocampal formation-dependent learning and memory, and not in several other non-declarative forms of learning and memory, and 2) the NA may be selectively involved in certain stages of learning and memory. These characteristics suggest that the NA may be part of a larger striatal system which subserves acquisition and consolidation, but is not a site of long-term storage, of different forms of learning and memory.

A Case Report of Successful Kidney Donation After Brain Death Following Nicotine Intoxication.

PubMed

Räsänen, M; Helanterä, I; Kalliomäki, J; Savikko, J; Parry, M; Lempinen, M

Nicotine intoxication is a rare cause of death and can lead to brain death after respiratory arrest and hypoxic-ischemic encephalopathy. To our knowledge, no previous reports regarding organ donation after nicotine intoxication have been described. We present a successful case of kidney donation after brain death caused by subcutaneous nicotine overdose from liquid nicotine from an e-cigarette cartridge in an attempted suicide. Both kidneys were transplanted successfully with immediate graft function, and both recipients were discharged at postoperative day 9 with normal plasma creatinine levels. Graft function has remained excellent in follow-up. This case suggests that kidneys from a donor with fatal nicotine intoxication may be successfully used for kidney transplantation in the absence of other contraindications for donation. Copyright © 2016 Elsevier Inc. All rights reserved.

Proteomic analysis of differentially expressed proteins in kidneys of brain dead rabbits

PubMed Central

Li, Ling; Li, Ning; He, Chongxiang; Huang, Wei; Fan, Xiaoli; Zhong, Zibiao; Wang, Yanfeng; Ye, Qifa

2017-01-01

A large number of previous clinical studies have reported a delayed graft function for brain dead donors, when compared with living relatives or cadaveric organ transplantations. However, there is no accurate method for the quality evaluation of kidneys from brain-dead donors. In the present study, two-dimensional gel electrophoresis and MALDI-TOF MS-based comparative proteomic analysis were conducted to profile the differentially-expressed proteins between brain death and the control group renal tissues. A total of 40 age- and sex-matched rabbits were randomly divided into donation following brain death (DBD) and control groups. Following the induction of brain death via intracranial progressive pressure, the renal function and the morphological alterations were measured 2, 6 and 8 h afterwards. The differentially expressed proteins were detected from renal histological evidence at 6 h following brain death. Although 904±19 protein spots in control groups and 916±25 in DBD groups were identified in the two-dimensional gel electrophoresis, >2-fold alterations were identified by MALDI-TOF MS and searched by NCBI database. The authors successfully acquired five downregulated proteins, these were: Prohibitin (isoform CRA_b), beta-1,3-N-acetylgalactosaminyltransferase 1, Annexin A5, superoxide dismutase (mitochondrial) and cytochrome b-c1 complex subunit 1 (mitochondrial precursor). Conversely, the other five upregulated proteins were: PRP38 pre-mRNA processing factor 38 (yeast) domain containing A, calcineurin subunit B type 1, V-type proton ATPase subunit G 1, NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 and peroxiredoxin-3 (mitochondrial). Immunohistochemical results revealed that the expressions of prohibitin (PHB) were gradually increased in a time-dependent manner. The results indicated that there were alterations in levels of several proteins in the kidneys of those with brain death, even if the primary function and the morphological changes were not obvious. PHB may therefore be a novel biomarker for primary quality evaluation of kidneys from brain-dead donors. PMID:28534953

Roles of inflammation and apoptosis in experimental brain death-induced right ventricular failure.

PubMed

Belhaj, Asmae; Dewachter, Laurence; Rorive, Sandrine; Remmelink, Myriam; Weynand, Birgit; Melot, Christian; Galanti, Laurence; Hupkens, Emeline; Sprockeels, Thomas; Dewachter, Céline; Creteur, Jacques; McEntee, Kathleen; Naeije, Robert; Rondelet, Benoît

2016-12-01

Right ventricular (RV) dysfunction remains the leading cause of early death after cardiac transplantation. Methylprednisolone is used to improve graft quality; however, evidence for that remains empirical. We sought to determine whether methylprednisolone, acting on inflammation and apoptosis, might prevent brain death-induced RV dysfunction. After randomization to placebo (n = 11) or to methylprednisolone (n = 8; 15 mg/kg), 19 pigs were assigned to a brain-death procedure. The animals underwent hemodynamic evaluation at 1 and 5 hours after Cushing reflex (i.e., hypertension and bradycardia). The animals euthanized, and myocardial tissue was sampled. This was repeated in a control group (n = 8). At 5 hours after the Cushing reflex, brain death resulted in increased pulmonary artery pressure (27 ± 2 vs 18 ± 1 mm Hg) and in a 30% decreased ratio of end-systolic to pulmonary arterial elastances (Ees/Ea). Cardiac output and right atrial pressure did not change. This was prevented by methylprednisolone. Brain death-induced RV dysfunction was associated with increased RV expression of heme oxygenase-1, interleukin (IL)-6, IL-10, IL-1β, tumor necrosis factor (TNF)-α, IL-1 receptor-like (ST)-2, signal transducer and activator of transcription-3, intercellular adhesion molecules-1 and -2, vascular cell adhesion molecule-1, and neutrophil infiltration, whereas IL-33 expression decreased. RV apoptosis was confirmed by terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling staining. Methylprednisolone pre-treatment prevented RV-arterial uncoupling and decreased RV expression of TNF-α, IL-1 receptor-like-2, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and neutrophil infiltration. RV Ees/Ea was inversely correlated to RV TNF-α and IL-6 expression. Brain death-induced RV dysfunction is associated with RV activation of inflammation and apoptosis and is partly limited by methylprednisolone. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Law & psychiatry: mental retardation and the death penalty: after Atkins.

PubMed

Appelbaum, Paul S

2009-10-01

In Atkins v. Virginia the U.S. Supreme Court declared execution of persons with mental retardation to constitute cruel and unusual punishment, and thus to be unconstitutional under the Eighth Amendment. However, the Court left all considerations regarding how to implement the decision explicitly to the states. Since Atkins was decided in 2002, legislatures, courts, and mental health experts have struggled with its implementation, highlighting the complexities that can arise when the courts base legal rules on clinical findings. This column reviews the Atkins case and considers the challenges associated with a clinical determination that can have life-or-death consequences for capital defendants.

Integrated But Not Whole? Applying an Ontological Account of Human Organismal Unity to the Brain Death Debate.

PubMed

Moschella, Melissa

2016-10-01

As is clear in the 2008 report of the President's Council on Bioethics, the brain death debate is plagued by ambiguity in the use of such key terms as 'integration' and 'wholeness'. Addressing this problem, I offer a plausible ontological account of organismal unity drawing on the work of Hoffman and Rosenkrantz, and then apply that account to the case of brain death, concluding that a brain dead body lacks the unity proper to a human organism, and has therefore undergone a substantial change. I also show how my view can explain hard cases better than one in which biological integration (as understood by Alan Shewmon and the President's Council) is taken to imply ontological wholeness or unity. © 2016 John Wiley & Sons Ltd.

Brain protection by methylprednisolone in rats with spinal cord injury.

PubMed

Chang, Chia-Mao; Lee, Ming-Hsueh; Wang, Ting-Chung; Weng, Hsu-Huei; Chung, Chiu-Yen; Yang, Jen-Tsung

2009-07-01

Traumatic spinal cord injury is clinically treated by high doses of methylprednisolone. However, the effect of methylprednisolone on the brain in spinal cord injury patients has been little investigated. This experimental study examined Bcl-2 and Bax protein expression and Nissl staining to evaluate an apoptosis-related intracellular signaling event and final neuron death, respectively. Spinal cord injury produced a significant apoptotic change and cell death not only in the spinal cord but also in the supraventricular cortex and hippocampal cornu ammonis 1 region in the rat brains. The treatment of methylprednisolone increased the Bcl-2/Bax ratio and prevented neuron death for 1-7 days after spinal cord injury. These findings suggest that rats with spinal cord injury show ascending brain injury that could be restricted through methylprednisolone management.

Individual choice in the definition of death.

PubMed

Bagheri, A

2007-03-01

While there are numerous doubts, controversies and lack of consensus on alternative definitions of human death, it is argued that it is more ethical to allow people to choose either cessation of cardio-respiratory function or loss of entire brain function as the definition of death based on their own views. This paper presents the law of organ transplantation in Japan, which allows people to decide whether brain death can be used to determine their death in agreement with their family. Arguably, Japan could become a unique example of individual choice in the definition of death if the law is revised to allow individuals choose definition of death independently of their family. It suggests that such an approach is one of the reasonable policy options a country can adopt for legislation on issues related to the definition of death.

Abandoning the dead donor rule? A national survey of public views on death and organ donation

PubMed Central

Nair-Collins, Michael; Green, Sydney R; Sutin, Angelina R

2015-01-01

Brain dead organ donors are the principal source of transplantable organs. However, it is controversial whether brain death is the same as biological death. Therefore, it is unclear whether organ removal in brain death is consistent with the ‘dead donor rule’, which states that organ removal must not cause death. Our aim was to evaluate the public's opinion about organ removal if explicitly described as causing the death of a donor in irreversible apneic coma. We conducted a cross-sectional internet survey of the American public (n=1096). Questionnaire domains included opinions about a hypothetical scenario of organ removal described as causing the death of a patient in irreversible coma, and items measuring willingness to donate organs after death. Some 71% of the sample agreed that it should be legal for patients to donate organs in the scenario described and 67% agreed that they would want to donate organs in a similar situation. Of the 85% of the sample who agreed that they were willing to donate organs after death, 76% agreed that they would donate in the scenario of irreversible coma with organ removal causing death. There appears to be public support for organ donation in a scenario explicitly described as violating the dead donor rule. Further, most but not all people who would agree to donate when organ removal is described as occurring after death would also agree to donate when organ removal is described as causing death in irreversible coma. PMID:25260779

Serum levels of S100B from jugular bulb as a biomarker of poor prognosis in patients with severe acute brain injury.

PubMed

Ballesteros, María A; Rubio-Lopez, María I; San Martín, María; Padilla, Ana; López-Hoyos, Marcos; Llorca, Javier; Miñambres, Eduardo

2018-02-15

To evaluate the correlation between protein S100B concentrations measured in the jugular bulb as well as at peripheral level and the prognostic usefulness of this marker. A prospective study of all patients admitted to the intensive care unit with acute brain damage was carried out. Peripheral and jugular bulb blood samples were collected upon admission and every 24h for three days. The endpoints were brain death diagnosis and the Glasgow Outcome Scale score after 6months. A total of 83 patients were included. Jugular protein S100B levels were greater than systemic levels upon admission and also after 24 and 72h (mean difference>0). Jugular protein S100B levels showed acceptable precision in predicting brain death both upon admission [AUC 0.67 (95% CI 0.53-0.80)] and after 48h [AUC 0.73 (95% CI 0.57-0.89)]. Similar results were obtained regarding the capacity of jugular protein S100B levels upon admission to predict an unfavourable outcome (AUC 0.69 (95% CI 0.56-0.79)). The gradient upon admission (jugular-peripheral levels) showed its capacity to predict the development of brain death [AUC 0.74 (95% CI 0.62-0.86)] and together with the Glasgow Coma Scale constituted the independent factors associated with the development of brain death. Regional protein S100B determinations are higher than systemic determinations, thus confirming the cerebral origin of protein S100B. The transcranial protein S100B gradient is correlated to the development of brain death. Copyright © 2017. Published by Elsevier B.V.

Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models

PubMed Central

Karuppagounder, Saravanan S.; Alim, Ishraq; Khim, Soah J.; Bourassa, Megan W.; Sleiman, Sama F.; John, Roseleen; Thinnes, Cyrille C.; Yeh, Tzu-Lan; Demetriades, Marina; Neitemeier, Sandra; Cruz, Dana; Gazaryan, Irina; Killilea, David W.; Morgenstern, Lewis; Xi, Guohua; Keep, Richard F.; Schallert, Timothy; Tappero, Ryan V.; Zhong, Jian; Cho, Sunghee; Maxfield, Frederick R.; Holman, Theodore R.; Culmsee, Carsten; Fong, Guo-Hua; Su, Yijing; Ming, Guo-li; Song, Hongjun; Cave, John W.; Schofield, Christopher J.; Colbourne, Frederick; Coppola, Giovanni; Ratan, Rajiv R.

2017-01-01

Disability or death due to intracerebral hemorrhage (ICH) is attributed to blood lysis, liberation of iron, and consequent oxidative stress. Iron chelators bind to free iron and prevent neuronal death induced by oxidative stress and disability due to ICH, but the mechanisms for this effect remain unclear. We show that the hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD) family of iron-dependent, oxygen-sensing enzymes are effectors of iron chelation. Molecular reduction of the three HIF-PHD enzyme isoforms in the mouse striatum improved functional recovery after ICH. A low-molecular-weight hydroxyquinoline inhibitor of the HIF-PHD enzymes, adaptaquin, reduced neuronal death and behavioral deficits after ICH in several rodent models without affecting total iron or zinc distribution in the brain. Unexpectedly, protection from oxidative death in vitro or from ICH in vivo by adaptaquin was associated with suppression of activity of the prodeath factor ATF4 rather than activation of an HIF-dependent prosurvival pathway. Together, these findings demonstrate that brain-specific inactivation of the HIF-PHD metalloenzymes with the blood-brain barrier-permeable inhibitor adaptaquin can improve functional outcomes after ICH in several rodent models. PMID:26936506

Do Spanish Medical Students Understand the Concept of Brain Death?

PubMed

Ríos, Antonio; López-Navas, A; López-López, A; Gómez, F J; Iriarte, J; Herruzo, R; Blanco, G; Llorca, F J; Asunsolo, A; Sánchez, P; Gutiérrez, P R; Fernández, A; de Jesús, M T; Alarcón, L Martínez; Del Olivo, M; Fuentes, L; Hernández, J R; Virseda, J; Yelamos, J; Bondía, J A; Hernández, A M; Ayala, M A; Ramírez, P; Parrilla, P

2018-03-01

To analyze the level of understanding of the brain death concept among medical students in universities in Spain. This cross-sectional sociological, interdisciplinary, and multicenter study was performed on 9598 medical students in Spain. The sample was stratified by geographical area and academic year. A previously validated self-reported measure of brain death knowledge (questionnaire Proyecto Colaborativo Internacional Donante sobre la Donación y Transplante de Organos) was completed anonymously by students. Respondents completed 9275 surveys for a completion rate of 95.7%. Of those, 67% (n = 6190) of the respondents understood the brain death concept. Of the rest, 28% (n = 2652) did not know what it meant, and the remaining 5% (n = 433) believed that it did not mean that the patient was dead. The variables related to a correct understanding of the concept were: (1) being older ( P < .001), (2) studying at a public university ( P < .001), (3) year of medical school ( P < .001), (4) studying at one of the universities in the south of Spain ( P = .003), (5) having discussed donation and transplantation with the family ( P < .001), (6) having spoken to friends about the matter ( P < .001), (7) a partner's favorable attitude toward donation and transplantation ( P < .001), and (8) religious beliefs ( P < .001). Sixty-seven percent of medical students know the concept of brain death, and knowledge improved as they advanced in their degree.

Early stages of Alzheimer's disease are alarming signs in injury deaths caused by traffic accidents in elderly people (≥60 years of age): A neuropathological study.

PubMed

Wijesinghe, Printha; Gorrie, Catherine; Shankar, S K; Chickabasaviah, Yasha T; Amaratunga, Dhammika; Hulathduwa, Sanjayah; Kumara, K Sunil; Samarasinghe, Kamani; Suh, Yoo-Hun; Steinbusch, H W M; De Silva, K Ranil D

2017-01-01

There is little information available in the literature concerning the contribution of dementia in injury deaths in elderly people (≥60 years). This study was intended to investigate the extent of dementia-related pathologies in the brains of elderly people who died in traffic accidents or by suicide and to compare our findings with age- and sex-matched natural deaths in an elderly population. Autopsy-derived human brain samples from nine injury death victims (5 suicide and 4 traffic accidents) and nine age- and sex-matched natural death victims were screened for neurodegenerative and cerebrovascular pathologies using histopathological and immunohistochemical techniques. For the analysis, Statistical Package for the Social Sciences (SPSS) version 16.0 was used. There was a greater likelihood for Alzheimer's disease (AD)-related changes in the elders who succumbed to traffic accidents (1 out of 4) compared to age- and sex-matched suicides (0 out of 5) or natural deaths (0 out of 9) as assessed by the National Institute on Aging - Alzheimer's Association guidelines. Actual burden of both neurofibrillary tangles (NFTs) and (SPs) was comparatively higher in the brains of traffic accidents, and the mean NFT counts were significantly higher in the region of entorhinal cortex ( P < 0.05). However, associations obtained for other dementia-related pathologies were not statistically important. Our findings suggest that early Alzheimer stages may be a contributing factor to injury deaths caused by traffic accidents in elderly people whereas suicidal brain neuropathologies resembled natural deaths.

The declarative/procedural model of lexicon and grammar.

PubMed

Ullman, M T

2001-01-01

Our use of language depends upon two capacities: a mental lexicon of memorized words and a mental grammar of rules that underlie the sequential and hierarchical composition of lexical forms into predictably structured larger words, phrases, and sentences. The declarative/procedural model posits that the lexicon/grammar distinction in language is tied to the distinction between two well-studied brain memory systems. On this view, the memorization and use of at least simple words (those with noncompositional, that is, arbitrary form-meaning pairings) depends upon an associative memory of distributed representations that is subserved by temporal-lobe circuits previously implicated in the learning and use of fact and event knowledge. This "declarative memory" system appears to be specialized for learning arbitrarily related information (i.e., for associative binding). In contrast, the acquisition and use of grammatical rules that underlie symbol manipulation is subserved by frontal/basal-ganglia circuits previously implicated in the implicit (nonconscious) learning and expression of motor and cognitive "skills" and "habits" (e.g., from simple motor acts to skilled game playing). This "procedural" system may be specialized for computing sequences. This novel view of lexicon and grammar offers an alternative to the two main competing theoretical frameworks. It shares the perspective of traditional dual-mechanism theories in positing that the mental lexicon and a symbol-manipulating mental grammar are subserved by distinct computational components that may be linked to distinct brain structures. However, it diverges from these theories where they assume components dedicated to each of the two language capacities (that is, domain-specific) and in their common assumption that lexical memory is a rote list of items. Conversely, while it shares with single-mechanism theories the perspective that the two capacities are subserved by domain-independent computational mechanisms, it diverges from them where they link both capacities to a single associative memory system with broad anatomic distribution. The declarative/procedural model, but neither traditional dual- nor single-mechanism models, predicts double dissociations between lexicon and grammar, with associations among associative memory properties, memorized words and facts, and temporal-lobe structures, and among symbol-manipulation properties, grammatical rule products, motor skills, and frontal/basal-ganglia structures. In order to contrast lexicon and grammar while holding other factors constant, we have focused our investigations of the declarative/procedural model on morphologically complex word forms. Morphological transformations that are (largely) unproductive (e.g., in go-went, solemn-solemnity) are hypothesized to depend upon declarative memory. These have been contrasted with morphological transformations that are fully productive (e.g., in walk-walked, happy-happiness), whose computation is posited to be solely dependent upon grammatical rules subserved by the procedural system. Here evidence is presented from studies that use a range of psycholinguistic and neurolinguistic approaches with children and adults. It is argued that converging evidence from these studies supports the declarative/procedural model of lexicon and grammar.

Ten Leading Causes of Death and Injury

MedlinePlus

... Brain Injury Violence Prevention Ten Leading Causes of Death and Injury Recommend on Facebook Tweet Share Compartir ... Emergency Departments, United States – 2014 Leading Causes of Death Charts Causes of Death by Age Group 2016 [ ...

The profile of head injuries and traumatic brain injury deaths in Kashmir.

PubMed

Yattoo, Gh; Tabish, Amin

2008-06-21

This study was conducted on patients of head injury admitted through Accident & Emergency Department of Sher-i-Kashmir Institute of Medical Sciences during the year 2004 to determine the number of head injury patients, nature of head injuries, condition at presentation, treatment given in hospital and the outcome of intervention. Traumatic brain injury (TBI) deaths were also studied retrospectively for a period of eight years (1996 to 2003).The traumatic brain injury deaths showed a steady increase in number from year 1996 to 2003 except for 1999 that showed decline in TBI deaths. TBI deaths were highest in age group of 21-30 years (18.8%), followed by 11-20 years age group (17.8%) and 31-40 years (14.3%). The TBI death was more common in males. Maximum number of traumatic brain injury deaths was from rural areas as compared to urban areas.To minimize the morbidity and mortality resulting from head injury there is a need for better maintenance of roads, improvement of road visibility and lighting, proper mechanical maintenance of automobile and other vehicles, rigid enforcement of traffic rules, compulsory wearing of crash helmets by motor cyclist and scooterists and shoulder belt in cars and imparting compulsory road safety education to school children from primary education level. Moreover, appropriate medical care facilities (including trauma centres) need to be established at district level, sub-divisional and block levels to provide prompt and quality care to head injury patients.

Posttraumatic Propofol Neurotoxicity Is Mediated via the Pro-Brain-Derived Neurotrophic Factor-p75 Neurotrophin Receptor Pathway in Adult Mice.

PubMed

Sebastiani, Anne; Granold, Matthias; Ditter, Anja; Sebastiani, Philipp; Gölz, Christina; Pöttker, Bruno; Luh, Clara; Schaible, Eva-Verena; Radyushkin, Konstantin; Timaru-Kast, Ralph; Werner, Christian; Schäfer, Michael K; Engelhard, Kristin; Moosmann, Bernd; Thal, Serge C

2016-02-01

The gamma-aminobutyric acid modulator propofol induces neuronal cell death in healthy immature brains by unbalancing neurotrophin homeostasis via p75 neurotrophin receptor signaling. In adulthood, p75 neurotrophin receptor becomes down-regulated and propofol loses its neurotoxic effect. However, acute brain lesions, such as traumatic brain injury, reactivate developmental-like programs and increase p75 neurotrophin receptor expression, probably to foster reparative processes, which in turn could render the brain sensitive to propofol-mediated neurotoxicity. This study investigates the influence of delayed single-bolus propofol applications at the peak of p75 neurotrophin receptor expression after experimental traumatic brain injury in adult mice. Randomized laboratory animal study. University research laboratory. Adult C57BL/6N and nerve growth factor receptor-deficient mice. Sedation by IV propofol bolus application delayed after controlled cortical impact injury. Propofol sedation at 24 hours after traumatic brain injury increased lesion volume, enhanced calpain-induced αII-spectrin cleavage, and increased cell death in perilesional tissue. Thirty-day postinjury motor function determined by CatWalk (Noldus Information Technology, Wageningen, The Netherlands) gait analysis was significantly impaired in propofol-sedated animals. Propofol enhanced pro-brain-derived neurotrophic factor/brain-derived neurotrophic factor ratio, which aggravates p75 neurotrophin receptor-mediated cell death. Propofol toxicity was abolished both by pharmacologic inhibition of the cell death domain of the p75 neurotrophin receptor (TAT-Pep5) and in mice lacking the extracellular neurotrophin binding site of p75 neurotrophin receptor. This study provides first evidence that propofol sedation after acute brain lesions can have a deleterious impact and implicates a role for the pro-brain-derived neurotrophic factor-p75 neurotrophin receptor pathway. This observation is important as sedation with propofol and other compounds with GABA receptor activity are frequently used in patients with acute brain pathologies to facilitate sedation or surgical and interventional procedures.

Binge drinking and declarative memory in university students.

PubMed

Parada, María; Corral, Montserrat; Caamaño-Isorna, Francisco; Mota, Nayara; Crego, Alberto; Holguín, Socorro Rodríguez; Cadaveira, Fernando

2011-08-01

Binge drinking (BD), which is characterized by sporadic consumption of large quantities of alcohol in short periods, is prevalent among university students. Animal studies have shown that BD is associated with damage to the hippocampus, a region of the brain that plays a key role in learning and memory. The temporal cortex undergoes structural and functional changes during adolescence. The aim of the present study was to examine the association between BD and declarative memory in male and female university students. The participants were 122 students (between 18 and 20 years of age): 62 BD (30 women) and 60 non-BD (29 women). The neuropsychological assessment included the Rey Auditory Verbal Learning Test (RAVLT) and Weschler Memory Scale-3rd ed. (WMS-III) Logical Memory subtest, to evaluate verbal declarative memory, and the WMS-III Family Pictures subtest, to measure visual declarative memory. The BD students remembered fewer words in the interference list and displayed greater proactive interference in the RAVLT; they performed worse in the Logical Memory subtest, both on immediate and delayed recall. There were no differences between the groups in performance of the Family Pictures subtest. No significant interactions were observed between BD and sex. Binge drinking is associated with poorer verbal declarative memory, regardless of sex. The findings are consistent with the vulnerability of the adolescent hippocampus to the neurotoxic effects of alcohol. Longitudinal studies will help determine the nature of this relationship, the neurodevelopmental trajectories for each sex, and the repercussions on academic performance. Copyright © 2011 by the Research Society on Alcoholism.

Declarative Consciousness for Reconstruction

NASA Astrophysics Data System (ADS)

Seymour, Leslie G.

2013-12-01

Existing information technology tools are harnessed and integrated to provide digital specification of human consciousness of individual persons. An incremental compilation technology is proposed as a transformation of LifeLog derived persona specifications into a Canonical representation of the neocortex architecture of the human brain. The primary purpose is to gain an understanding of the semantical allocation of the neocortex capacity. Novel neocortex content allocation simulators with browsers are proposed to experiment with various approaches of relieving the brain from overload conditions. An IT model of the neocortex is maintained, which is then updated each time new stimuli are received from the LifeLog data stream; new information is gained from brain signal measurements; and new functional dependencies are discovered between live persona consumed/produced signals

Brain injury following trial of hypothermia for neonatal hypoxic–ischaemic encephalopathy

PubMed Central

Shankaran, Seetha; Barnes, Patrick D; Hintz, Susan R; Laptook, Abbott R; Zaterka-Baxter, Kristin M; McDonald, Scott A; Ehrenkranz, Richard A; Walsh, Michele C; Tyson, Jon E; Donovan, Edward F; Goldberg, Ronald N; Bara, Rebecca; Das, Abhik; Finer, Neil N; Sanchez, Pablo J; Poindexter, Brenda B; Van Meurs, Krisa P; Carlo, Waldemar A; Stoll, Barbara J; Duara, Shahnaz; Guillet, Ronnie; Higgins, Rosemary D

2013-01-01

Objective The objective of our study was to examine the relationship between brain injury and outcome following neonatal hypoxic–ischaemic encephalopathy treated with hypothermia. Design and patients Neonatal MRI scans were evaluated in the National Institute of Child Health and Human Development (NICHD) randomised controlled trial of whole-body hypothermia and each infant was categorised based upon the pattern of brain injury on the MRI findings. Brain injury patterns were assessed as a marker of death or disability at 18–22 months of age. Results Scans were obtained on 136 of 208 trial participants (65%); 73 in the hypothermia and 63 in the control group. Normal scans were noted in 38 of 73 infants (52%) in the hypothermia group and 22 of 63 infants (35%) in the control group. Infants in the hypothermia group had fewer areas of infarction (12%) compared to infants in the control group (22%). Fifty-one of the 136 infants died or had moderate or severe disability at 18 months. The brain injury pattern correlated with outcome of death or disability and with disability among survivors. Each point increase in the severity of the pattern of brain injury was independently associated with a twofold increase in the odds of death or disability. Conclusions Fewer areas of infarction and a trend towards more normal scans were noted in brain MRI following whole-body hypothermia. Presence of the NICHD pattern of brain injury is a marker of death or moderate or severe disability at 18–22 months following hypothermia for neonatal encephalopathy. PMID:23080477

Brain Death and Human Organismal Integration: A Symposium on the Definition of Death

PubMed Central

Moschella, Melissa

2016-01-01

Does the ability of some brain dead bodies to maintain homeostasis with the help of artificial life support actually imply that those bodies are living human organisms? Or might it be possible that a brain dead body on life support is a mere collection of still-living cells, organs and tissues which can coordinate with one another, but which lack the genuine integration that is the hallmark of a unified human organism as a whole? To foster further study of these difficult and timely questions, a Symposium on the Definition of Death was held at The Catholic University of America in June 2014. The Symposium brought together scholars from a variety of disciplines—law, medicine, biology, philosophy and theology—who all share a commitment to the dead donor rule and to a biological definition of death, but who have differing opinions regarding the validity of neurological criteria for human death. The papers found in this special issue are among the fruits of this Symposium. PMID:27107428

Transcranial Doppler ultrasound in the diagnosis of brain death. Is it useful or does it delay the diagnosis?

PubMed

Escudero, D; Otero, J; Quindós, B; Viña, L

2015-05-01

Transcranial Doppler ultrasound is able to demonstrate cerebral circulatory arrest associated to brain death, being especially useful in sedated patients, or in those in which complete neurological exploration is not possible. Transcranial Doppler ulstrasound is a portable, noninvasive and high-availability technique. Among its limitations, mention must be made of the absence of acoustic windows and false-negative cases. In patients clinically diagnosed with brain death, with open skulls or with anoxia as the cause of death, cerebral blood flow can be observed by ultrasound, since cerebral circulatory arrest is not always synchronized to the clinical diagnosis. The diagnostic rate is therefore time-dependent, and this fact that must be recognized in order to avoid delays in death certification. Despite its limitations, transcranial Doppler ulstrasound helps solve common diagnostic problems, avoids the unnecessary consumption of resources, and can optimize organ harvesting for transplantation. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

Growth of melanoma brain tumors monitored by photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Staley, Jacob; Grogan, Patrick; Samadi, Abbas K.; Cui, Huizhong; Cohen, Mark S.; Yang, Xinmai

2010-07-01

Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.

Copper brain protein protection against free radical-induced neuronal death: Survival ratio in SH-SY5Y neuroblastoma cell cultures.

PubMed

Deloncle, Roger; Fauconneau, Bernard; Guillard, Olivier; Delaval, José; Lesage, Gérard; Pineau, Alain

2017-01-01

In Creutzfeldt Jakob, Alzheimer and Parkinson diseases, copper metalloproteins such as prion, amyloid protein precursor and α-synuclein are able to protect against free radicals by reduction from cupric Cu +2 to cupreous Cu + . In these pathologies, a regional copper (Cu) brain decrease correlated with an iron, zinc or manganese (Mn) increase has previously been observed, leading to local neuronal death and abnormal deposition of these metalloproteins in β-sheet structures. In this study we demonstrate the protective effect of Cu metalloproteins against deleterious free-radical effects. With neuroblastoma SH-SY5Y cell cultures, we show that bovine brain prion protein in Cu but not Mn form prevents free radical-induced neuronal death. The survival ratio of SH-SY5Y cells has been measured after UV irradiation (free radical production), when the incubating medium is supplemented with bovine brain homogenate in native, Cu or Mn forms. This ratio, about 28% without any addition or with bovine brain protein added in Mn form, increases by as much as 54.73% with addition to the culture medium of native bovine brain protein and by as much as 95.95% if the addition is carried out in cupric form. This protective effect of brain copper protein against free radical-induced neuronal death has been confirmed with Inductively Coupled Plasma Mass Spectrometry Mn and Cu measurement in bovine brain homogenates: respectively lower than detection limit and 9.01μg/g dry weight for native form; lower than detection limit and 825.85μg/g dry weight for Cu-supplemented form and 1.75 and 68.1μg/g dry weight in Mn-supplemented brain homogenate. Copyright © 2016 Elsevier GmbH. All rights reserved.

Neuroprotective effect of p-coumaric acid in mice with cerebral ischemia reperfusion injuries.

PubMed

Sakamula, Romgase; Thong-Asa, Wachiryah

2018-06-01

Cerebral ischemia reperfusion (IR) is associated with neuronal death, which leads to disability and cognitive decline. The pathomechanism occurs because ischemia is exacerbated during the reperfusion period. Neuronal damage susceptibility depends on the affected brain areas and the duration of ischemia. Prevention and supplementation to neurons may help them endure during IR and further benefit them in rehabilitation. We investigated the protective effect of p-coumaric acid (PC) on cerebral IR injuries in mice. We randomly divided 30 male ICR mice into 3 groups of Sham (received vehicle and not induced IR), Control-IR (received vehicle and induced IR) and PC-IR (received 100 mg/kg PC and induced IR). We orally administered vehicle or 100 mg/kg of p-coumaric acid for 2 weeks before inducing the cerebral IR injuries by using 30 min of a bilateral common carotid artery occlusion followed by a 45-min reperfusion. We induced the IR condition in the Control-IR and PC-IR groups but not the Sham group, and only the PC-IR group received p-coumaric acid. After IR induction, we sacrificed all the mice and collected their brain tissues to evaluate their oxidative statuses, whole brain infarctions and vulnerable neuronal deaths. We studied the whole-brain infarction volume by 2, 3, 5-triethyltetrazoliumchloride staining of sections. We performed a histological investigation of the vulnerable neuronal population in the dorsal hippocampus by staining brain sections with 0.1% cresyl violet. The results indicated that IR caused significant increases in calcium and malondialdehyde (MDA) levels, whole brain infarction volume and hippocampal neuronal death. Pretreatment with p-coumaric acid significantly reduced MDA levels, whole-brain infarction volume and hippocampal neuronal death together and increased catalase and superoxide dismutase activities. We conclude here that pretreating animals with p-coumaric acid can prevent IR-induced brain oxidative stress, infarction size and neuronal vulnerability to death in cerebral IR injuries.

Accelerated death rate in population-based cohort of persons with traumatic brain injury.

PubMed

Selassie, Anbesaw W; Cao, Yue; Church, Elizabeth C; Saunders, Lee L; Krause, James

2014-01-01

To determine the influence of preexisting heart, liver, kidney, cancer, stroke, and mental health problems and examine the influence of low socioeconomic status on mortality after discharge from acute care facilities for individuals with traumatic brain injury. Population-based retrospective cohort study of 33695 persons discharged from acute care hospital with traumatic brain injury in South Carolina, 1999-2010. Days elapsing from the dates of injury to death established the survival time (T). Data were censored at the 145th month. Multivariable Cox regression was used to examine the independent effect of the variables on death. Age-adjusted cumulative probability of death for each chronic disease of interest was plotted. By the 70th month of follow-up, rate of death was accelerated from 10-fold for heart diseases to 2.5-fold for mental health problems. Adjusted hazard ratios for diseases of the heart (2.13), liver-renal (3.25), cancer (2.64), neurological diseases and stroke (2.07), diabetes (1.89), hypertension (1.43), and mental health problems (1.59) were highly significant (each with P < .001). Compared with persons with private insurance, the hazard ratio was significantly elevated with Medicaid (1.67), Medicare (1.54), and uninsured (1.27) (each with P < .001). Specific chronic diseases strongly influenced postdischarge mortality after traumatic brain injury. Low socioeconomic status as measured by the type of insurance elevated the risk of death.

Two Strikes: American Intervention in Haiti

DTIC Science & Technology

2002-04-12

Richard Millet , “A Multiplicity of Threats, A Paucity of Options: The Global Security Environment at the End of the Twentieth Century” in Beyond Declaring...execute their campaign of pacification.27 Toussaint and his principle generals, including a rising and brutal leader Jean -Jacques Dessalines, reacted by...French and consigned to exile where he died.28 The death of Toussaint signaled the beginning of a new war, Jean -Jacques Dessalines succeeded Toussaint, as

Involvement of Programmed Cell Death in Neurotoxicity of Metallic Nanoparticles: Recent Advances and Future Perspectives

NASA Astrophysics Data System (ADS)

Song, Bin; Zhou, Ting; Liu, Jia; Shao, LongQuan

2016-11-01

The widespread application of metallic nanoparticles (NPs) or NP-based products has increased the risk of exposure to NPs in humans. The brain is an important organ that is more susceptible to exogenous stimuli. Moreover, any impairment to the brain is irreversible. Recently, several in vivo studies have found that metallic NPs can be absorbed into the animal body and then translocated into the brain, mainly through the blood-brain barrier and olfactory pathway after systemic administration. Furthermore, metallic NPs can cross the placental barrier to accumulate in the fetal brain, causing developmental neurotoxicity on exposure during pregnancy. Therefore, metallic NPs become a big threat to the brain. However, the mechanisms underlying the neurotoxicity of metallic NPs remain unclear. Programmed cell death (PCD), which is different from necrosis, is defined as active cell death and is regulated by certain genes. PCD can be mainly classified into apoptosis, autophagy, necroptosis, and pyroptosis. It is involved in brain development, neurodegenerative disorders, psychiatric disorders, and brain injury. Given the pivotal role of PCD in neurological functions, we reviewed relevant articles and tried to summarize the recent advances and future perspectives of PCD involvement in the neurotoxicity of metallic NPs, with the purpose of comprehensively understanding the neurotoxic mechanisms of NPs.

A model to predict progression in brain-injured patients.

PubMed

Tommasino, N; Forteza, D; Godino, M; Mizraji, R; Alvarez, I

2014-11-01

The study of brain death (BD) epidemiology and the acute brain injury (ABI) progression profile is important to improve public health programs, organ procurement strategies, and intensive care unit (ICU) protocols. The purpose of this study was to analyze the ABI progression profile among patients admitted to ICUs with a Glasgow Coma Score (GCS) ≤8, as well as establishing a prediction model of probability of death and BD. This was a retrospective analysis of prospective data that included all brain-injured patients with GCS ≤8 admitted to a total of four public and private ICUs in Uruguay (N = 1447). The independent predictor factors of death and BD were studied using logistic regression analysis. A hierarchical model consisting of 2 nested logit regression models was then created. With these models, the probabilities of death, BD, and death by cardiorespiratory arrest were analyzed. In the first regression, we observed that as the GCS decreased and age increased, the probability of death rose. Each additional year of age increased the probability of death by 0.014. In the second model, however, BD risk decreased with each year of age. The presence of swelling, mass effect, and/or space-occupying lesion increased BD risk for the same given GCS. In the presence of injuries compatible with intracranial hypertension, age behaved as a protective factor that reduced the probability of BD. Based on the analysis of the local epidemiology, a model to predict the probability of death and BD can be developed. The organ potential donation of a country, region, or hospital can be predicted on the basis of this model, customizing it to each specific situation.

Early stages of Alzheimer's disease are alarming signs in injury deaths caused by traffic accidents in elderly people (≥60 years of age): A neuropathological study

PubMed Central

Wijesinghe, Printha; Gorrie, Catherine; Shankar, S. K.; Chickabasaviah, Yasha T.; Amaratunga, Dhammika; Hulathduwa, Sanjayah; Kumara, K. Sunil; Samarasinghe, Kamani; Suh, Yoo-Hun; Steinbusch, H. W. M.; De Silva, K. Ranil D.

2017-01-01

Background: There is little information available in the literature concerning the contribution of dementia in injury deaths in elderly people (≥60 years). Aim: This study was intended to investigate the extent of dementia-related pathologies in the brains of elderly people who died in traffic accidents or by suicide and to compare our findings with age- and sex-matched natural deaths in an elderly population. Materials and Methods: Autopsy-derived human brain samples from nine injury death victims (5 suicide and 4 traffic accidents) and nine age- and sex-matched natural death victims were screened for neurodegenerative and cerebrovascular pathologies using histopathological and immunohistochemical techniques. For the analysis, Statistical Package for the Social Sciences (SPSS) version 16.0 was used. Results: There was a greater likelihood for Alzheimer's disease (AD)-related changes in the elders who succumbed to traffic accidents (1 out of 4) compared to age- and sex-matched suicides (0 out of 5) or natural deaths (0 out of 9) as assessed by the National Institute on Aging – Alzheimer's Association guidelines. Actual burden of both neurofibrillary tangles (NFTs) and (SPs) was comparatively higher in the brains of traffic accidents, and the mean NFT counts were significantly higher in the region of entorhinal cortex (P < 0.05). However, associations obtained for other dementia-related pathologies were not statistically important. Conclusion: Our findings suggest that early Alzheimer stages may be a contributing factor to injury deaths caused by traffic accidents in elderly people whereas suicidal brain neuropathologies resembled natural deaths. PMID:29497190

Organ donation in adults: a critical care perspective.

PubMed

Citerio, Giuseppe; Cypel, Marcelo; Dobb, Geoff J; Dominguez-Gil, Beatriz; Frontera, Jennifer A; Greer, David M; Manara, Alex R; Shemie, Sam D; Smith, Martin; Valenza, Franco; Wijdicks, Eelco F M

2016-03-01

The shortage of organs for transplantation is an important medical and societal problem because transplantation is often the best therapeutic option for end-stage organ failure. We review the potential deceased organ donation pathways in adult ICU practice, i.e. donation after brain death (DBD) and controlled donation after circulatory death (cDCD), which follows the planned withdrawal of life-sustaining treatments (WLST) and subsequent confirmation of death using cardiorespiratory criteria. Strategies in the ICU to increase the number of organs available for transplantation are discussed. These include timely identification of the potential organ donor, optimization of the brain-dead donor by aggressive management of the physiological consequence of brain death, implementation of cDCD protocols, and the potential for ex vivo perfusion techniques. Organ donation should be offered as a routine component of the end-of-life care plan of every patient dying in the ICU where appropriate, and intensivists are the key professional in this process.

Characteristics of memories for near-death experiences.

PubMed

Moore, Lauren E; Greyson, Bruce

2017-05-01

Near-death experiences are vivid, life-changing experiences occurring to people who come close to death. Because some of their features, such as enhanced cognition despite compromised brain function, challenge our understanding of the mind-brain relationship, the question arises whether near-death experiences are imagined rather than real events. We administered the Memory Characteristics Questionnaire to 122 survivors of a close brush with death who reported near-death experiences. Participants completed Memory Characteristics Questionnaires for three different memories: that of their near-death experience, that of a real event around the same time, and that of an event they had imagined around the same time. The Memory Characteristics Questionnaire score was higher for the memory of the near-death experience than for that of the real event, which in turn was higher than that of the imagined event. These data suggest that memories of near-death experiences are recalled as "realer" than real events or imagined events. Copyright © 2017 Elsevier Inc. All rights reserved.

Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models

DOE PAGES

Karuppagounder, Saravanan S.; Alim, Ishraq; Khim, Soah J.; ...

2016-03-02

Disability or death due to intracerebral hemorrhage (ICH) is attributed to blood lysis, liberation of iron and consequent oxidative stress. Iron chelators bind to free iron and prevent neuronal death induced by oxidative stress and disability due to ICH, but the mechanisms for this effect remain unclear. Here we show that the hypoxia-inducible factor prolyl-hydroxylase (HIF- PHD) family of iron-dependent oxygen sensing enzymes are effectors of iron chelation. Molecular reduction of the three HIF-PHD enzyme isoforms in mouse striatum improved functional recovery following ICH. A low molecular weight hydroxyquinoline inhibitor of the HIF-PHDs, adaptaquin, reduced neuronal death and behavioral deficitsmore » following ICH in several rodent models without affecting total iron or zinc distribution in the brain. Unexpectedly, protection from oxidative death in vitro or from ICH in vivo by adaptaquin was associated with suppression of expression of the prodeath factor ATF4 rather than activation of a HIF-dependent prosurvival pathway. In conclusion, together these findings demonstrate that brain-specific inactivation of the HIF-PHD metalloenzymes with the blood-brain barrier permeable inhibitor adaptaquin can improve functional outcomes following ICH in multiple rodent species.« less

Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models

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

Karuppagounder, Saravanan S.; Alim, Ishraq; Khim, Soah J.

Disability or death due to intracerebral hemorrhage (ICH) is attributed to blood lysis, liberation of iron and consequent oxidative stress. Iron chelators bind to free iron and prevent neuronal death induced by oxidative stress and disability due to ICH, but the mechanisms for this effect remain unclear. Here we show that the hypoxia-inducible factor prolyl-hydroxylase (HIF- PHD) family of iron-dependent oxygen sensing enzymes are effectors of iron chelation. Molecular reduction of the three HIF-PHD enzyme isoforms in mouse striatum improved functional recovery following ICH. A low molecular weight hydroxyquinoline inhibitor of the HIF-PHDs, adaptaquin, reduced neuronal death and behavioral deficitsmore » following ICH in several rodent models without affecting total iron or zinc distribution in the brain. Unexpectedly, protection from oxidative death in vitro or from ICH in vivo by adaptaquin was associated with suppression of expression of the prodeath factor ATF4 rather than activation of a HIF-dependent prosurvival pathway. In conclusion, together these findings demonstrate that brain-specific inactivation of the HIF-PHD metalloenzymes with the blood-brain barrier permeable inhibitor adaptaquin can improve functional outcomes following ICH in multiple rodent species.« less

Recovery from a possible cytomegalovirus meningoencephalitis-induced apparent brain stem death in an immunocompetent man: a case report.

PubMed

Rahardjo, Theresia Monica; Maskoen, Tinni Trihartini; Redjeki, Ike Sri

2016-08-26

Recovery from cytomegalovirus meningoencephalitis with brain stem death in an immunocompetent patient is almost impossible. We present a remarkable recovery from a possible cytomegalovirus infection in an immunocompetent man who had severe neurological syndromes, suggesting brain stem death complicated by pneumonia and pleural effusion. A 19-year-old Asian man presented at our hospital's emergency department with reduced consciousness and seizures following high fever, headache, confusion, and vomitus within a week before arrival. He was intubated and sent to our intensive care unit. He had nuchal rigidity and tetraparesis with accentuated tendon reflexes. Electroencephalography findings suggested an acute structural lesion at his right temporal area or an epileptic state. A cerebral spinal fluid examination suggested viral infection. A computed tomography scan was normal at the early stage of disease. Immunoglobulin M, immunoglobulin G anti-herpes simplex virus, and immunoglobulin M anti-cytomegalovirus were negative. However, immunoglobulin G anti-cytomegalovirus was positive, which supported a diagnosis of cytomegalovirus meningoencephalitis. His clinical condition deteriorated, spontaneous respiration disappeared, cranial reflexes became negative, and brain stem death was suspected. Therapy included antivirals, corticosteroids, antibiotics, anticonvulsant, antipyretics, antifungal agents, and a vasopressor to maintain hemodynamic stability. After 1 month, he showed a vague response to painful stimuli at his supraorbital nerve and respiration started to appear the following week. After pneumonia and pleural effusion were resolved, he was weaned from the ventilator and moved from the intensive care unit on day 90. This case highlights several important issues that should be considered. First, the diagnosis of brain stem death must be confirmed with caution even if there are negative results of brain stem death test for a long period. Second, cytomegalovirus meningoencephalitis should be considered in the differential diagnosis even for an immunocompetent adult. Third, accurate therapy and simultaneous intensive care have very important roles in the recovery process of patients with cytomegalovirus meningoencephalitis.

Usefulness of venous oxygen saturation in the jugular bulb for the diagnosis of brain death: report of 118 patients.

PubMed

Díaz-Regañón, Genaro; Miñambres, Eduardo; Holanda, Marisol; González-Herrera, Segundo; López-Espadas, Francisco; Garrido-Díaz, Carlos

2002-12-01

To assess the usefulness of venous oxygen saturation in the jugular bulb (SjO(2)) as a complementary test for the diagnosis of brain death. Prospective observational study. Polytrauma intensive care unit (ICU) of an acute-care teaching hospital in Santander, Spain. We studied 118 (44%) out of 270 patients with severe head injury and intracranial hemorrhage meeting criteria of brain death (lack of cardiac response to atropine, unresponsive apnea, and iso-electric EEG in the absence of shock, hypotension and treatment with muscle relaxants and/or central nervous system (CNS) depressant drugs). At the moment at which clinical diagnosis of brain death was made and an iso-electric EEG was obtained, simultaneous oxygen saturation in central venous blood (right atrium) (SvO(2)) and jugular venous bulb (SjO(2)) samples was measured. The ratio between SvO(2) and SjO(2), expressed as CvjO(2) (the so-called central venous-jugular bulb oxygen saturation rate; CvjO(2) = SvO(2)/SjO(2)) was calculated. CvjO(2) less than 1 was obtained in 114 patients [mean (SD): 0.89 (0.02)], whereas CvjO(2) greater than 1 was obtained in only 4 (3.38%). In the group of 152 survivors, a single patient was discharged from the ICU in a vegetative state in which CvjO(2) was below 1. CvjO(2)as a complementary test for the diagnosis of brain death showed 96.6% sensitivity, 99.3% specificity, and 99.1% and 97.4% positive and negative predictive values, respectively. Central venous-jugular bulb oxygen saturation rate below 1 together with accepted clinical criteria (unresponsive coma with brainstem areflexia) provides non-invasive assessment of cerebral circulatory arrest that can help to suspect brain death.

Brain endothelial TAK1 and NEMO safeguard the neurovascular unit

PubMed Central

Ridder, Dirk A.; Wenzel, Jan; Müller, Kristin; Töllner, Kathrin; Tong, Xin-Kang; Assmann, Julian C.; Stroobants, Stijn; Weber, Tobias; Niturad, Cristina; Fischer, Lisanne; Lembrich, Beate; Wolburg, Hartwig; Grand’Maison, Marilyn; Papadopoulos, Panayiota; Korpos, Eva; Truchetet, Francois; Rades, Dirk; Sorokin, Lydia M.; Schmidt-Supprian, Marc; Bedell, Barry J.; Pasparakis, Manolis; Balschun, Detlef; D’Hooge, Rudi; Löscher, Wolfgang; Hamel, Edith

2015-01-01

Inactivating mutations of the NF-κB essential modulator (NEMO), a key component of NF-κB signaling, cause the genetic disease incontinentia pigmenti (IP). This leads to severe neurological symptoms, but the mechanisms underlying brain involvement were unclear. Here, we show that selectively deleting Nemo or the upstream kinase Tak1 in brain endothelial cells resulted in death of endothelial cells, a rarefaction of brain microvessels, cerebral hypoperfusion, a disrupted blood–brain barrier (BBB), and epileptic seizures. TAK1 and NEMO protected the BBB by activating the transcription factor NF-κB and stabilizing the tight junction protein occludin. They also prevented brain endothelial cell death in a NF-κB–independent manner by reducing oxidative damage. Our data identify crucial functions of inflammatory TAK1–NEMO signaling in protecting the brain endothelium and maintaining normal brain function, thus explaining the neurological symptoms associated with IP. PMID:26347470

Serpins Promote Cancer Cell Survival and Vascular Cooption in Brain Metastasis

PubMed Central

Valiente, Manuel; Obenauf, Anna C.; Jin, Xin; Chen, Qing; Zhang, Xiang H.-F.; Lee, Derek J.; Chaft, Jamie E.; Kris, Mark G.; Huse, Jason T.; Brogi, Edi; Massagué, Joan

2014-01-01

Brain metastasis is an ominous complication of cancer, yet most cancer cells that infiltrate the brain die of unknown causes. Here we identify plasmin from the reactive brain stroma as a defense against metastatic invasion, and plasminogen activator (PA) inhibitory serpins in cancer cells as a shield against this defense. Plasmin suppresses brain metastasis in two ways: by converting membrane-bound astrocytic FasL into a paracrine death signal for cancer cells, and by inactivating the axon pathfinding molecule L1CAM that metastatic cells express for spreading along brain capillaries and for metastatic outgrowth. Brain metastatic cells from lung cancer and breast cancer express high levels of anti-PA serpins, including neuroserpin and serpin B2, to prevent plasmin generation and its deleterious consequences. By protecting cancer cells from death signals and fostering vascular cooption, anti-PA serpins provide a unifying mechanism for the initiation of brain metastasis in lung and breast cancers. PMID:24581498

The distribution of apolipoprotein E alleles in Scottish perinatal deaths

PubMed Central

Becher, J‐C; Keeling, J W; McIntosh, N; Wyatt, B; Bell, J

2006-01-01

Background The apolipoprotein E (ApoE) polymorphism has been well studied in the adult human population, in part because the e4 allele is a known risk factor for Alzheimer's disease. Little is known of the distribution of ApoE alleles in newborns, and their association with perinatal brain damage has not been investigated. Methods ApoE genotyping was undertaken in a Scottish cohort of perinatal deaths (n = 261), some of whom had prenatal brain damage. The distribution of ApoE alleles in perinatal deaths was compared with that in healthy liveborn infants and in adults in Scotland. Results ApoE e2 was over‐represented in 251 perinatal deaths (13% v 8% in healthy newborns, odds ratio (OR) = 1.63, 95% confidence interval (CI) 1.13 to 2.36 and 13% v 8% in adults, OR = 1.67, 95% CI 1.16 to 2.41), both in liveborn and stillborn perinatal deaths. In contrast, the prevalence of ApoE e4 was raised in healthy liveborn infants (19%) compared with stillbirths (13%, OR = 1.59, 95% CI 1.11 to 2.26) and with adults (15%, OR = 1.35, 95% CI 1.04 to 1.76). However, no correlation was found between ApoE genotype and the presence or absence of perinatal brain damage. Conclusions This study shows a shift in ApoE allelic distribution in early life compared with adults. The raised prevalence of ApoE e2 associated with perinatal death suggests that this allele is detrimental to pregnancy outcome, whereas ApoE e4 may be less so. However, ApoE genotype did not appear to influence the vulnerability for perinatal hypoxic/ischaemic brain damage, in agreement with findings in adult brains and in animal models. PMID:16183800

Cardiovascular disease 2005--the global picture.

PubMed

Callow, Allan D

2006-11-01

Although the past twenty years have seen a remarkable decline in the death rates of heart disease and stroke in the United States and several countries of western Europe, a reverse trend is occurring in other parts of the world. This is especially true in sub-Saharan Africa, India, China and Russia. World-wide, deaths from cardiovascular disease exceed those caused by cancer, infectious disease and trauma, constituting a deadly epidemic. Yet, in 1996 the Victoria Declaration stated that the world has the knowledge to eliminate cardiovascular disease as a major illness. Defeating such an initiative are other priorities such as education, housing, transportation, defense, as well as ignorance. The Earth Institute has labeled the needed effort, "A Race Against Time".

[Digital electroencephalography in brain death diagnostics : Technical requirements and results of a survey on the compatibility with medical guidelines of digital EEG systems from providers in Germany].

PubMed

Walter, U; Noachtar, S; Hinrichs, H

2018-02-01

The guidelines of the German Medical Association and the German Society for Clinical Neurophysiology and Functional Imaging (DGKN) require a high procedural and technical standard for electroencephalography (EEG) as an ancillary method for diagnosing the irreversible cessation of brain function (brain death). Nowadays, digital EEG systems are increasingly being applied in hospitals. So far it is unclear to what extent the digital EEG systems currently marketed in Germany meet the guidelines for diagnosing brain death. In the present article, the technical und safety-related requirements for digital EEG systems and the EEG documentation for diagnosing brain death are described in detail. On behalf of the DGKN, the authors sent out a questionnaire to all identified distributors of digital EEG systems in Germany with respect to the following technical demands: repeated recording of the calibration signals during an ongoing EEG recording, repeated recording of all electrode impedances during an ongoing EEG recording, assessability of intrasystem noise and galvanic isolation of measurement earthing from earthing conductor (floating input). For 15 of the identified 20 different digital EEG systems the specifications were provided by the distributors (among them all distributors based in Germany). All of these EEG systems are provided with a galvanic isolation (floating input). The internal noise can be tested with all systems; however, some systems do not allow repeated recording of the calibration signals and/or the electrode impedances during an ongoing EEG recording. The majority but not all of the currently available digital EEG systems offered for clinical use are eligible for use in brain death diagnostics as per German guidelines.

A Prototype Symbolic Model of Canonical Functional Neuroanatomy of the Motor System

PubMed Central

Rubin, Daniel L.; Halle, Michael; Musen, Mark; Kikinis, Ron

2008-01-01

Recent advances in bioinformatics have opened entire new avenues for organizing, integrating and retrieving neuroscientific data, in a digital, machine-processable format, which can be at the same time understood by humans, using ontological, symbolic data representations. Declarative information stored in ontological format can be perused and maintained by domain experts, interpreted by machines, and serve as basis for a multitude of decision-support, computerized simulation, data mining, and teaching applications. We have developed a prototype symbolic model of canonical neuroanatomy of the motor system. Our symbolic model is intended to support symbolic lookup, logical inference and mathematical modeling by integrating descriptive, qualitative and quantitative functional neuroanatomical knowledge. Furthermore, we show how our approach can be extended to modeling impaired brain connectivity in disease states, such as common movement disorders. In developing our ontology, we adopted a disciplined modeling approach, relying on a set of declared principles, a high-level schema, Aristotelian definitions, and a frame-based authoring system. These features, along with the use of the Unified Medical Language System (UMLS) vocabulary, enable the alignment of our functional ontology with an existing comprehensive ontology of human anatomy, and thus allow for combining the structural and functional views of neuroanatomy for clinical decision support and neuroanatomy teaching applications. Although the scope of our current prototype ontology is limited to a particular functional system in the brain, it may be possible to adapt this approach for modeling other brain functional systems as well. PMID:18164666

Intrapulmonary aquaporin-5 expression as a possible biomarker for discriminating smothering and choking from sudden cardiac death: a pilot study.

PubMed

Wang, Qi; Ishikawa, Takaki; Michiue, Tomomi; Zhu, Bao-Li; Guan, Da-Wei; Maeda, Hitoshi

2012-07-10

The diagnosis of mechanical asphyxia as a cause of death, especially smothering and choking lacking evident injury, is one of the most difficult tasks in forensic pathology. The present study investigated the intrapulmonary expressions of aquaporins (AQPs; AQP-1 and AQP-5), as markers of water homeostasis, in forensic autopsy cases (total n=64, within 48 h postmortem) of mechanical asphyxiation due to neck compression (strangulation, n=24), including manual/ligature strangulation (n=12) and atypical hanging (n=12), smothering (n=7) and choking (n=8), compared with sudden cardiac death (n=14) and acute brain injury (n=11). Quantification of mRNA using a Taqman real-time PCR assay system demonstrated suppressed expression of AQP-5, but not AQP-1, in smothering and choking, compared with that in strangulation as well as sudden cardiac death and acute brain injury death. Immunostaining of AQP-5 was weakly detected in a linear pattern in the type I alveolar epithelial cells in smothering and choking cases, while cardiac and brain injury death showed marked positivity, and most strangulation cases had AQP-5-positive granular aggregates and fragments in intra-alveolar spaces. These observations indicate a partial difference in pulmonary molecular pathology among these causes of death, suggesting a procedure for possible discrimination of smothering and choking from sudden cardiac death. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain.

PubMed

Cauli, Omar; González-Usano, Alba; Cabrera-Pastor, Andrea; Gimenez-Garzó, Carla; López-Larrubia, Pilar; Ruiz-Sauri, Amparo; Hernández-Rabaza, Vicente; Duszczyk, Malgorzata; Malek, Michal; Lazarewicz, Jerzy W; Carratalá, Arturo; Urios, Amparo; Miguel, Alfonso; Torregrosa, Isidro; Carda, Carmen; Montoliu, Carmina; Felipo, Vicente

2014-06-01

Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration.

COBI (COntinuous hyperosmolar therapy for traumatic Brain-Injured patients) trial protocol: a multicentre randomised open-label trial with blinded adjudication of primary outcome.

PubMed

Roquilly, Antoine; Lasocki, Sigismond; Moyer, Jean Denis; Huet, Olivier; Perrigault, Pierre François; Dahyot-Fizelier, Claire; Seguin, Philippe; Sharshar, Tarek; Geeraerts, Thomas; Remerand, Francis; Feuillet, Fanny; Asehnoune, Karim

2017-09-24

Traumatic brain injury (TBI) is a major cause of death and severe prolonged disability. Intracranial hypertension (ICH) is a critical risk factor of bad outcomes after TBI. Continuous infusion of hyperosmolar therapy has been proposed for the prevention and the treatment of ICH. Whether an early administration of continuous hyperosmolar therapy improves long-term outcomes of patients with TBI is uncertain. The aim of the COBI study (number clinicaltrial.gov 03143751, pre-results stage) is to assess the efficiency and the safety of continuous hyperosmolar therapy in patients with TBI. The COBI (COntinuous hyperosmolar therapy in traumatic Brain-Injured patients) trial is a multicentre, randomised, controlled, open-label, two-arms study with blinded adjudication of primary outcome. Three hundred and seventy patients hospitalised in intensive care unit with a TBI (Glasgow Coma Scale ≤12 and abnormal brain CT scan) are randomised in the first 24 hours following trauma to standard care or continuous hyperosmolar therapy (20% NaCl) plus standard care. Continuous hyperosmolar therapy is maintained for at least 48 hours in the treatment group and continued for as long as is necessary to prevent ICH. The primary outcome is the score on the Extended Glasgow Outcome Scale at 6 months. The treatment effect is estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common OR. The COBI trial protocol has been approved by the ethics committee of Paris Ile de France VIII and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. The COBI trial is the first randomised controlled trial powered to investigate whether continuous hyperosmolar therapy in patients with TBI improve long-term recovery. Trial registration number is NCT03143751. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Abandoning the dead donor rule? A national survey of public views on death and organ donation.

PubMed

Nair-Collins, Michael; Green, Sydney R; Sutin, Angelina R

2015-04-01

Brain dead organ donors are the principal source of transplantable organs. However, it is controversial whether brain death is the same as biological death. Therefore, it is unclear whether organ removal in brain death is consistent with the 'dead donor rule', which states that organ removal must not cause death. Our aim was to evaluate the public's opinion about organ removal if explicitly described as causing the death of a donor in irreversible apneic coma. We conducted a cross-sectional internet survey of the American public (n=1096). Questionnaire domains included opinions about a hypothetical scenario of organ removal described as causing the death of a patient in irreversible coma, and items measuring willingness to donate organs after death. Some 71% of the sample agreed that it should be legal for patients to donate organs in the scenario described and 67% agreed that they would want to donate organs in a similar situation. Of the 85% of the sample who agreed that they were willing to donate organs after death, 76% agreed that they would donate in the scenario of irreversible coma with organ removal causing death. There appears to be public support for organ donation in a scenario explicitly described as violating the dead donor rule. Further, most but not all people who would agree to donate when organ removal is described as occurring after death would also agree to donate when organ removal is described as causing death in irreversible coma. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Traumatic Brain Injury (TBI) Data and Statistics

MedlinePlus

... data.cdc.gov . Emergency Department Visits, Hospitalizations, and Deaths Rates of TBI-related Emergency Department Visits, Hospitalizations, ... related Hospitalizations by Age Group and Injury Mechanism Deaths Rates of TBI-related Deaths by Sex Rates ...

Proteomic analysis of differentially expressed proteins in kidneys of brain dead rabbits.

PubMed

Li, Ling; Li, Ning; He, Chongxiang; Huang, Wei; Fan, Xiaoli; Zhong, Zibiao; Wang, Yanfeng; Ye, Qifa

2017-07-01

A large number of previous clinical studies have reported a delayed graft function for brain dead donors, when compared with living relatives or cadaveric organ transplantations. However, there is no accurate method for the quality evaluation of kidneys from brain‑dead donors. In the present study, two‑dimensional gel electrophoresis and MALDI‑TOF MS‑based comparative proteomic analysis were conducted to profile the differentially‑expressed proteins between brain death and the control group renal tissues. A total of 40 age‑ and sex‑matched rabbits were randomly divided into donation following brain death (DBD) and control groups. Following the induction of brain death via intracranial progressive pressure, the renal function and the morphological alterations were measured 2, 6 and 8 h afterwards. The differentially expressed proteins were detected from renal histological evidence at 6 h following brain death. Although 904±19 protein spots in control groups and 916±25 in DBD groups were identified in the two‑dimensional gel electrophoresis, >2‑fold alterations were identified by MALDI‑TOF MS and searched by NCBI database. The authors successfully acquired five downregulated proteins, these were: Prohibitin (isoform CRA_b), beta-1,3‑N-acetylgalactosaminyltransferase 1, Annexin A5, superoxide dismutase (mitochondrial) and cytochrome b‑c1 complex subunit 1 (mitochondrial precursor). Conversely, the other five upregulated proteins were: PRP38 pre‑mRNA processing factor 38 (yeast) domain containing A, calcineurin subunit B type 1, V‑type proton ATPase subunit G 1, NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 and peroxiredoxin‑3 (mitochondrial). Immunohistochemical results revealed that the expressions of prohibitin (PHB) were gradually increased in a time‑dependent manner. The results indicated that there were alterations in levels of several proteins in the kidneys of those with brain death, even if the primary function and the morphological changes were not obvious. PHB may therefore be a novel biomarker for primary quality evaluation of kidneys from brain‑dead donors.

Will the European Union reach the United Nations Millennium declaration target of a 50% reduction of tuberculosis mortality between 1990 and 2015?

PubMed

van der Werf, Marieke J; Bonfigli, Sandro; Hruba, Frantiska

2017-07-06

The Millennium Development Goals (MDG) provide targets for 2015. MDG 6 includes a target to reduce the tuberculosis (TB) death rate by 50% compared with 1990. We aimed to assess whether this target was reached by the European Union (EU) and European Economic Area countries. We used Eurostat causes of death data to assess whether the target was reached in the EU. We calculated the reduction in reported and adjusted death rates and the annual average percentage decline based on the available data. Between 1999 and 2014, the TB death rate decreased by 50%, the adjusted death rate by 56% and the annual average percentage decline was 5.43% (95% confidence interval 4.94-6.74) for the EU. Twenty of 26 countries reporting >5 TB deaths in the first reporting year reached the target of 50% reduction in adjusted death rate. The EU reached the MDG target of a 50% reduction of the TB death rate and also the annual average percentage decline was larger than the 2.73% needed to reach the target. The World Health Organization 'End TB Strategy' requires a further reduction of the number of TB deaths of 35% by 2020 compared to 2015, which will challenge TB prevention and care services in the EU.

The efficiency of utilization of potential donors for organ transplantation in Saudi Arabia: a pilot study.

PubMed

Al Sebayel, M I M; Khalaf, H A

2004-09-01

Organ shortage has been the main obstacle in the progress of organ transplantation in Saudi Arabia. The aim of this pilot study was to determine the percentage of potential donors among all deaths in Riyadh hospital intensive care units (ICUs). Mortality data were collected by a medical professional in each ICU and analyzed on weekly basis for 1 year (June 2001 through May 2002): The final analysis at the end of the year showed the number of brain death cases in all hospitals to be 114 out of 542 deaths. Fifty-four percent occurred in one hospital. Thirty-eight cases were reported to the Saudi Center for Organ Transplantation (33%). Documentation was completed in only 23 cases (60%). Only four cases became actual donors. In conclusion, there is underreporting of brain death cases. Dealing with the reported cases is inefficient since only four cases became actual donors out of 38. Improving the efficiency of ICUs in dealing with brain death cases (reporting, documentation, maintenance and consent) will require solving several problems at the medical, administrative, religious, and mass media levels.

miR-Let7A Controls the Cell Death and Tight Junction Density of Brain Endothelial Cells under High Glucose Condition

PubMed Central

Song, Juhyun; Yoon, So Ra

2017-01-01

Hyperglycemia-induced stress in the brain of patients with diabetes triggers the disruption of blood-brain barrier (BBB), leading to diverse neurological diseases including stroke and dementia. Recently, the role of microRNA becomes an interest in the research for deciphering the mechanism of brain endothelial cell damage under hyperglycemia. Therefore, we investigated whether mircoRNA Let7A (miR-Let7A) controls the damage of brain endothelial (bEnd.3) cells against high glucose condition. Cell viability, cell death marker expressions (p-53, Bax, and cleaved poly ADP-ribose polymerase), the loss of tight junction proteins (ZO-1 and claudin-5), proinflammatory response (interleukin-6, tumor necrosis factor-α), inducible nitric oxide synthase, and nitrite production were confirmed using MTT, reverse transcription-PCR, quantitative-PCR, Western blotting, immunofluorescence, and Griess reagent assay. miR-Let7A overexpression significantly prevented cell death and loss of tight junction proteins and attenuated proinflammatory response and nitrite production in the bEnd.3 cells under high glucose condition. Taken together, we suggest that miR-Let7A may attenuate brain endothelial cell damage by controlling cell death signaling, loss of tight junction proteins, and proinflammatory response against high glucose stress. In the future, the manipulation of miR-Let7A may be a novel solution in controlling BBB disruption which leads to the central nervous system diseases. PMID:28680530

miR-Let7A Controls the Cell Death and Tight Junction Density of Brain Endothelial Cells under High Glucose Condition.

PubMed

Song, Juhyun; Yoon, So Ra; Kim, Oh Yoen

2017-01-01

Hyperglycemia-induced stress in the brain of patients with diabetes triggers the disruption of blood-brain barrier (BBB), leading to diverse neurological diseases including stroke and dementia. Recently, the role of microRNA becomes an interest in the research for deciphering the mechanism of brain endothelial cell damage under hyperglycemia. Therefore, we investigated whether mircoRNA Let7A (miR-Let7A) controls the damage of brain endothelial (bEnd.3) cells against high glucose condition. Cell viability, cell death marker expressions (p-53, Bax, and cleaved poly ADP-ribose polymerase), the loss of tight junction proteins (ZO-1 and claudin-5), proinflammatory response (interleukin-6, tumor necrosis factor- α ), inducible nitric oxide synthase, and nitrite production were confirmed using MTT, reverse transcription-PCR, quantitative-PCR, Western blotting, immunofluorescence, and Griess reagent assay. miR-Let7A overexpression significantly prevented cell death and loss of tight junction proteins and attenuated proinflammatory response and nitrite production in the bEnd.3 cells under high glucose condition. Taken together, we suggest that miR-Let7A may attenuate brain endothelial cell damage by controlling cell death signaling, loss of tight junction proteins, and proinflammatory response against high glucose stress. In the future, the manipulation of miR-Let7A may be a novel solution in controlling BBB disruption which leads to the central nervous system diseases.

Transcriptional up-regulation of nitric oxide synthase II by nuclear factor-kappaB at rostral ventrolateral medulla in a rat mevinphos intoxication model of brain stem death.

PubMed

Chan, Julie Y H; Wu, Carol H Y; Tsai, Ching-Yi; Cheng, Hsiao-Lei; Dai, Kuang-Yu; Chan, Samuel H H; Chang, Alice Y W

2007-06-15

As the origin of a 'life-and-death' signal that reflects central cardiovascular regulatory failure during brain stem death, the rostral ventrolateral medulla (RVLM) is a suitable neural substrate for mechanistic delineation of this vital phenomenon. Using a clinically relevant animal model that employed the organophosphate pesticide mevinphos (Mev) as the experimental insult, we evaluated the hypothesis that transcriptional up-regulation of nitric oxide synthase I or II (NOS I or II) gene expression by nuclear factor-kappaB (NF-kappaB) on activation of muscarinic receptors in the RVLM underlies brain stem death. In Sprague-Dawley rats maintained under propofol anaesthesia, co-microinjection of muscarinic M2R (methoctramine) or M4R (tropicamide), but not M1R (pirenzepine) or M3R (4-diphenylacetoxy-N-dimethylpiperidinium) antagonist significantly reduced the enhanced NOS I-protein kinase G signalling ('pro-life' phase) or augmented NOS II-peroxynitrite cascade ('pro-death' phase) in ventrolateral medulla, blunted the biphasic increase and decrease in baroreceptor reflex-mediated sympathetic vasomotor tone that reflect the transition from life to death, and diminished the elevated DNA binding activity or nucleus-bound translocation of NF-kappaB in RVLM neurons induced by microinjection of Mev into the bilateral RVLM. However, NF-kappaB inhibitors (diethyldithiocarbamate or pyrrolidine dithiocarbamate) or double-stranded kappaB decoy DNA preferentially antagonized the augmented NOS II-peroxynitrite cascade and the associated cardiovascular depression exhibited during the 'pro-death' phase. We conclude that transcriptional up-regulation of NOS II gene expression by activation of NF-kappaB on selective stimulation of muscarinic M2 or M4 subtype receptors in the RVLM underlies the elicited cardiovascular depression during the 'pro-death' phase in our Mev intoxication model of brain stem death.

MicroRNA profiling reveals new aspects of HIV neurodegeneration: caspase-6 regulates astrocyte survival.

PubMed

Noorbakhsh, Farshid; Ramachandran, Rithwik; Barsby, Nicola; Ellestad, Kristofor K; LeBlanc, Andrea; Dickie, Peter; Baker, Glen; Hollenberg, Morley D; Cohen, Eric A; Power, Christopher

2010-06-01

MicroRNAs (miRNAs) are small noncoding RNA molecules, which are known to regulate gene expression in physiological and pathological conditions. miRNA profiling was performed using brain tissue from patients with HIV encephalitis (HIVE), a neuroinflammatory/degenerative disorder caused by HIV infection of the brain. Microarray analysis showed differential expression of multiple miRNAs in HIVE compared to control brains. Target prediction and gene ontology enrichment analysis disclosed targeting of several gene families/biological processes by differentially expressed miRNAs (DEMs), with cell death-related genes, including caspase-6, showing a bias toward down-regulated DEMs. Consistent with the miRNA data, HIVE brains exhibited higher levels of caspase-6 transcripts compared with control patients. Immunohistochemical analysis showed localization of the cleaved form of caspase-6 in astrocytes in HIVE brain sections. Exposure of cultured human primary astrocytes to HIV viral protein R (Vpr) induced p53 up-regulation, loss of mitochondrial membrane potential, and caspase-6 activation followed by cell injury. Transgenic mice, expressing Vpr in microglial cells, demonstrated astrocyte apoptosis in brain, which was associated with caspase-6 activation and neurobehavioral abnormalities. Overall, these data point to previously unrecognized alterations in miRNA profile in the brain during HIV infection, which contribute to cell death through dysregulation of cell death machinery.

Necrostatin-1 attenuates early brain injury after subarachnoid hemorrhage in rats by inhibiting necroptosis.

PubMed

Chen, Fuxiang; Su, Xingfen; Lin, Zhangya; Lin, Yuanxiang; Yu, Lianghong; Cai, Jiawei; Kang, Dezhi; Hu, Liwen

2017-01-01

Necroptosis is programmed cell death that has been recently proposed and reported to be involved in several neurologic diseases. However, the role of necroptosis in early brain injury after subarachnoid hemorrhage (SAH) is still unknown. The purpose of this study was to investigate whether necroptosis was involved in SAH-induced early brain injury, and to assess the possible neuroprotective effect of necrostatin-1 using an endovascular perforation rat model of SAH. Our results showed that the expression levels of necroptosis-related proteins including RIP1, RIP3 and MLKL in the basal cortex all increased at 3 hours after SAH ( P <0.05) and peaked at 48 hours after SAH ( P <0.05). However, they were greatly reduced after treatment with necrostatin-1 ( P <0.05). Concurrently, neurologic outcomes were significantly improved after necrostatin-1 treatment ( P <0.05). Furthermore, brain edema, blood-brain barrier disruption, necrotic cell death and neuroinflammation were also greatly inhibited after necrostatin-1 treatment. These results indicate that necroptosis is an important mechanism of cell death involved in the early brain injury after experimental SAH. Necrostatin-1 perhaps can serve as a promising neuroprotective agent for SAH treatment.

Postmortem Brain and Blood Reference Concentrations of Alprazolam, Bromazepam, Chlordiazepoxide, Diazepam, and their Metabolites and a Review of the Literature.

PubMed

Skov, Louise; Holm, Karen Marie Dollerup; Johansen, Sys Stybe; Linnet, Kristian

2016-09-01

To interpret postmortem toxicology results, reference concentrations for non-toxic and toxic levels are needed. Usually, measurements are performed in blood, but because of postmortem redistribution phenomena this may not be optimal. Rather, measurement in the target organ of psychoactive drugs, the brain, might be considered. Here we present reference concentrations of femoral blood and brain tissue of selected benzodiazepines (BZDs). Using LC-MS/MS, we quantified alprazolam, bromazepam, chlordiazepoxide, diazepam, and the metabolites desmethyldiazepam, oxazepam and temazepam in postmortem femoral blood and brain tissue in 104 cases. BZDs were judged to be unrelated to the cause of death in 88 cases and contributing to death in 16 cases. No cases were found with cause of death solely attributed to BZD poisoning. All BZDs investigated tended to have higher concentrations in brain than in blood with median brain-blood ratios ranging from 1.1 to 2.3. A positive correlation between brain and blood concentrations was found with R(2) values from 0.51 to 0.95. Our reported femoral blood concentrations concur with literature values, but sparse information on brain concentration was available. Drug-metabolite ratios were similar in brain and blood for most compounds. Duplicate measurements of brain samples showed that the pre-analytical variation in brain (5.9%) was relatively low, supporting the notion that brain tissue is a suitable postmortem specimen. The reported concentrations in both brain and blood can be used as reference values when evaluating postmortem cases. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mechanisms of Neurodegeneration and Regeneration in Alcoholism

PubMed Central

Crews, Fulton T.; Nixon, Kim

2009-01-01

Aims: This is a review of preclinical studies covering alcohol-induced brain neuronal death and loss of neurogenesis as well as abstinence-induced brain cell genesis, e.g. brain regeneration. Efforts are made to relate preclinical studies to human studies. Methods: The studies described are preclinical rat experiments using a 4-day binge ethanol treatment known to induce physical dependence to ethanol. Neurodegeneration and cognitive deficits following binge treatment mimic the mild degeneration and cognitive deficits found in humans. Various histological methods are used to follow brain regional degeneration and regeneration. Results: Alcohol-induced degeneration occurs due to neuronal death during alcohol intoxication. Neuronal death is related to increases in oxidative stress in brain that coincide with the induction of proinflammatory cytokines and oxidative enzymes that insult brain. Degeneration is associated with increased NF-κB proinflammatory transcription and decreased CREB transcription. Corticolimbic brain regions are most sensitive to binge-induced degeneration and induce relearning deficits. Drugs that block oxidative stress and NF-κB transcription or increase CREB transcription block binge-induced neurodegeneration, inhibition of neurogenesis and proinflammatory enzyme induction. Regeneration of brain occurs during abstinence following binge ethanol treatment. Bursts of proliferating cells occur across multiple brain regions, with many new microglia across brain after months of abstinence and many new neurons in neurogenic hippocampal dentate gyrus. Brain regeneration may be important to sustain abstinence in humans. Conclusions: Alcohol-induced neurodegeneration occurs primarily during intoxication and is related to increased oxidative stress and proinflammatory proteins that are neurotoxic. Abstinence after binge ethanol intoxication results in brain cell genesis that could contribute to the return of brain function and structure found in abstinent humans. PMID:18940959

Pietro Manni (1778-1839) and the care of the apparently dead in the Age of Positivism.

PubMed

Cascella, Marco

2016-08-01

When can a man be declared 'really dead'? Being able to determine whether an individual's life has ended or not implies two important considerations, whether we can resuscitate him and avoid premature burial, the fear of which is termed 'taphophobia'. By the end of the 18th century, several scientists were involved in the study of apparent death and resuscitation. Pietro Manni was an obstetrician who, affected by his brother's death and his inability to help him, devoted himself to the study of apparent death, which became his aim in life. His Practical handbook for the care of the apparently dead is a detailed essay on resuscitation with a precise arrangement of topics - ventilation, tracheostomy, electricity and asphyxia in newborns - organised into chapters and paragraphs that resemble current texts on resuscitation. © The Author(s) 2016.

Rabies: risk, prognosis and prevention.

PubMed

Driver, Carolyn

While the UK was declared free from rabies over 100 years ago, the disease remains a significant cause of death in many other countries around the world. It is hoped that eradication programmes in affected countries will succeed in the long term but, until then, prompt and thorough treatment can prevent people who have potentially been in contact with the rabies virus from developing this infection. This article provides a review of the disease and its prevention.

Floods of August and September 2004 in Eastern Ohio: FEMA Disaster Declaration 1556

USGS Publications Warehouse

Ebner, Andrew D.; Straub, David E.; Lageman, Jonathan D.

2008-01-01

A band of severe thunderstorms at the end of August 2004 and the passage of the remnants of Hurricanes Frances and Ivan during September 2004 caused severe flooding in eastern Ohio during August and September 2004. Record peak streamflow occurred at 12 U.S. Geological Survey (USGS) streamgages. Damages caused by the flooding produced by these storms were severe enough for 21 counties in eastern Ohio to be declared Federal disaster areas. In all, there were 4 storm- or flood-related deaths, 2,563 private structures damaged or destroyed, and an estimated $81 million in damages. This report describes the meteorological factors that resulted in severe flooding in eastern Ohio during August 27-September 27, 2004, and examines the damages caused by the storms and flooding. Peak-stage, peak-streamflow, and recurrence-interval data are reported for selected USGS streamgages. Flood profiles determined by the USGS are presented for selected streams.

The Troubling Trichotomy 10 Years Later: Where Are We Now?

PubMed

Barrocas, Albert

2016-06-01

A decade ago, "Nutrition Support and The Troubling Trichotomy: A Call To Action" was published in this journal, identifying existing conflicts among technological, ethical, and legal aspects of nutrition support therapy, particularly in terminal or end-of-life situations. Over the past 10 years, the American Society for Parenteral and Enteral Nutrition and others have responded to the action call. A "state of the trichotomy" reveals that while much has been achieved, differences in all 3 aspects will continue to exist due to their dynamic and ever-changing states. The technology arena has made it possible to increase the delivery of nutrition support in alternative settings with the use of telemedicine and social media. Critical/crucial conversations and earlier declarations of individual wishes for care and treatment while having decision-making capacity have been enhanced with the focus on patient-centered and family-centered care. The definition of death as brain death has been challenged in at least one instance. Conflicts between the state's interests and the individual's interests have added to recent legal controversies. Notwithstanding the progress made over the past 10 years, several challenges remain. The future challenges presented by the Troubling Trichotomy can be best confronted if we ACT-Accountability, Communication, and Teamwork. The focus of teamwork should move from multidisciplinary and interdisciplinary teams to transdisciplinary teams, reflecting the shift to function rather than form presented by the new healthcare environment. The transdisciplinary team will be able address the opportunities of the Troubling Trichotomy in the next decade by incorporating the 12 Cs, as detailed in the article. © 2016 American Society for Parenteral and Enteral Nutrition.

Evaluation of the law of presumed consent after brain death by Spanish journalism students.

PubMed

Martínez-Alarcón, L; Ríos, A; Sánchez, J; Ramis, G; López-Navas, A; Ramírez, P; Parrilla, P

2010-10-01

Information provided by journalists is crucial to create a climate of social opinion. This is important in organ donation and transplantation (ODT), wherein the participation of the general public is essential to obtain organs. The objective of this study was to determine the knowledge of students taking a degree in journalism about the concept of brain death and the law of presumed consent. The study involved 129 journalism degree students in the 2005-2006 academic year from a university in the south-east of Spain. Attitudes on the psychosocial aspects of ODT were evaluated using a validated questionnaire. The self-administered survey was completed anonymously in classes and compulsory practical sessions. The questionnaire completion rate was 98% (n=126). Of the students surveyed, 43% (n=54) understood the concept of brain death, 44% (n=56) stated that they had doubts, whereas 13% (n=16) believed that a person with brain death can recover and lead a normal life. Their knowledge was more accurate in the final than in the first year (54% vs 47%; P=.016). Most students 66% (n=83) believed that it would be interesting to receive an informative talk about ODT. Concerning legislation, 75% of students were against the law of presumed consent, whereas 25% were in favor. More than 50% of journalism students do not understand the concept of brain death. Furthermore, up to 75% do not accept the law of presumed consent that donation must be made. Copyright © 2010 Elsevier Inc. All rights reserved.

Do the 'brain dead' merely appear to be alive?

PubMed

Nair-Collins, Michael; Miller, Franklin G

2017-11-01

The established view regarding 'brain death' in medicine and medical ethics is that patients determined to be dead by neurological criteria are dead in terms of a biological conception of death, not a philosophical conception of personhood, a social construction or a legal fiction. Although such individuals show apparent signs of being alive, in reality they are (biologically) dead, though this reality is masked by the intervention of medical technology. In this article, we argue that an appeal to the distinction between appearance and reality fails in defending the view that the 'brain dead' are dead. Specifically, this view relies on an inaccurate and overly simplistic account of the role of medical technology in the physiology of a 'brain dead' patient. We conclude by offering an explanation of why the conventional view on 'brain death', though mistaken, continues to be endorsed in light of its connection to organ transplantation and the dead donor rule. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Sudden unexpected death from oligodendroglioma: a case report and review of the literature.

PubMed

Manousaki, Maria; Papadaki, Helen; Papavdi, Asteria; Kranioti, Elena F; Mylonakis, Panagiotis; Varakis, John; Michalodimitrakis, Manolis

2011-12-01

Sudden and unexpected deaths due to asymptomatic 5 primary brain tumors are extremely rare, with an incidence that ranges from 0.16 to 3.2%. Usually, such tumors are glioblastomas or, less commonly, astrocytomas. Asymptomatic oligodendrogliomas causing sudden death are hardly ever reported among medico-legal investigated cases.We report a rare case of sudden and unexpected death from a previously asymptomatic and undiagnosed, well-differentiated, grade II oligodendrogloioma (WHO classification). According to the autopsy and the microscopic findings brain edema as a result of obstruction of the cerebrospinal fluid flow due to hemorrhagic leakage of the oligodendroglioma is incriminated as the most probable physiopathological mechanism for the sudden death. Diagnosis is mainly based on the special microscopic features of the tumor cells (typical "fried-egg" appearance), interrupted by a dense network of branching capillaries. We discuss further the pathophysiological mechanisms of death and present a short review of literature.

No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults.

PubMed

Lippelt, D P; van der Kint, S; van Herk, K; Naber, M

2016-01-01

Choline is a dietary component and precursor of acetylcholine, a crucial neurotransmitter for memory-related brain functions. In two double-blind, placebo-controlled cross-over experiments, we investigated whether the food supplement choline bitartrate improved declarative memory and working memory in healthy, young students one to two hours after supplementation. In experiment 1, 28 participants performed a visuospatial working memory task. In experiment 2, 26 participants performed a declarative picture memorization task. In experiment 3, 40 participants performed a verbal working memory task in addition to the visuospatial working memory and declarative picture task. All tasks were conducted approximately 60 minutes after the ingestion of 2.0-2.5g of either choline bitartrate or placebo. We found that choline did not significantly enhance memory performance during any of the tasks. The null hypothesis that choline does not improve memory performance as compared to placebo was strongly supported by Bayesian statistics. These results are in contrast with animal studies suggesting that choline supplementation boosts memory performance and learning. We conclude that choline likely has no acute effects on cholinergic memory functions in healthy human participants.

No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults

PubMed Central

Lippelt, D. P.; van der Kint, S.; van Herk, K.; Naber, M.

2016-01-01

Choline is a dietary component and precursor of acetylcholine, a crucial neurotransmitter for memory-related brain functions. In two double-blind, placebo-controlled cross-over experiments, we investigated whether the food supplement choline bitartrate improved declarative memory and working memory in healthy, young students one to two hours after supplementation. In experiment 1, 28 participants performed a visuospatial working memory task. In experiment 2, 26 participants performed a declarative picture memorization task. In experiment 3, 40 participants performed a verbal working memory task in addition to the visuospatial working memory and declarative picture task. All tasks were conducted approximately 60 minutes after the ingestion of 2.0–2.5g of either choline bitartrate or placebo. We found that choline did not significantly enhance memory performance during any of the tasks. The null hypothesis that choline does not improve memory performance as compared to placebo was strongly supported by Bayesian statistics. These results are in contrast with animal studies suggesting that choline supplementation boosts memory performance and learning. We conclude that choline likely has no acute effects on cholinergic memory functions in healthy human participants. PMID:27341028

Ammonium Accumulation and Cell Death in a Rat 3D Brain Cell Model of Glutaric Aciduria Type I

PubMed Central

Jafari, Paris; Braissant, Olivier; Zavadakova, Petra; Henry, Hugues; Bonafé, Luisa; Ballhausen, Diana

2013-01-01

Glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency) is an inborn error of metabolism that usually manifests in infancy by an acute encephalopathic crisis and often results in permanent motor handicap. Biochemical hallmarks of this disease are elevated levels of glutarate and 3-hydroxyglutarate in blood and urine. The neuropathology of this disease is still poorly understood, as low lysine diet and carnitine supplementation do not always prevent brain damage, even in early-treated patients. We used a 3D in vitro model of rat organotypic brain cell cultures in aggregates to mimic glutaric aciduria type I by repeated administration of 1 mM glutarate or 3-hydroxyglutarate at two time points representing different developmental stages. Both metabolites were deleterious for the developing brain cells, with 3-hydroxyglutarate being the most toxic metabolite in our model. Astrocytes were the cells most strongly affected by metabolite exposure. In culture medium, we observed an up to 11-fold increase of ammonium in the culture medium with a concomitant decrease of glutamine. We further observed an increase in lactate and a concomitant decrease in glucose. Exposure to 3-hydroxyglutarate led to a significantly increased cell death rate. Thus, we propose a three step model for brain damage in glutaric aciduria type I: (i) 3-OHGA causes the death of astrocytes, (ii) deficiency of the astrocytic enzyme glutamine synthetase leads to intracerebral ammonium accumulation, and (iii) high ammonium triggers secondary death of other brain cells. These unexpected findings need to be further investigated and verified in vivo. They suggest that intracerebral ammonium accumulation might be an important target for the development of more effective treatment strategies to prevent brain damage in patients with glutaric aciduria type I. PMID:23326493

Ammonium accumulation and cell death in a rat 3D brain cell model of glutaric aciduria type I.

PubMed

Jafari, Paris; Braissant, Olivier; Zavadakova, Petra; Henry, Hugues; Bonafé, Luisa; Ballhausen, Diana

2013-01-01

Glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency) is an inborn error of metabolism that usually manifests in infancy by an acute encephalopathic crisis and often results in permanent motor handicap. Biochemical hallmarks of this disease are elevated levels of glutarate and 3-hydroxyglutarate in blood and urine. The neuropathology of this disease is still poorly understood, as low lysine diet and carnitine supplementation do not always prevent brain damage, even in early-treated patients. We used a 3D in vitro model of rat organotypic brain cell cultures in aggregates to mimic glutaric aciduria type I by repeated administration of 1 mM glutarate or 3-hydroxyglutarate at two time points representing different developmental stages. Both metabolites were deleterious for the developing brain cells, with 3-hydroxyglutarate being the most toxic metabolite in our model. Astrocytes were the cells most strongly affected by metabolite exposure. In culture medium, we observed an up to 11-fold increase of ammonium in the culture medium with a concomitant decrease of glutamine. We further observed an increase in lactate and a concomitant decrease in glucose. Exposure to 3-hydroxyglutarate led to a significantly increased cell death rate. Thus, we propose a three step model for brain damage in glutaric aciduria type I: (i) 3-OHGA causes the death of astrocytes, (ii) deficiency of the astrocytic enzyme glutamine synthetase leads to intracerebral ammonium accumulation, and (iii) high ammonium triggers secondary death of other brain cells. These unexpected findings need to be further investigated and verified in vivo. They suggest that intracerebral ammonium accumulation might be an important target for the development of more effective treatment strategies to prevent brain damage in patients with glutaric aciduria type I.

Declarative long-term memory and the mesial temporal lobe: Insights from a 5-year postsurgery follow-up study on refractory temporal lobe epilepsy.

PubMed

Salvato, Gerardo; Scarpa, Pina; Francione, Stefano; Mai, Roberto; Tassi, Laura; Scarano, Elisa; Lo Russo, Giorgio; Bottini, Gabriella

2016-11-01

It is largely recognized that the mesial temporal lobe and its substructure support declarative long-term memory (LTM). So far, different theories have been suggested, and the organization of declarative verbal LTM in the brain is still a matter of debate. In the current study, we retrospectively selected 151 right-handed patients with temporal lobe epilepsy with and without hippocampal sclerosis, with a homogeneous (seizure-free) clinical outcome. We analyzed verbal memory performance within a normalized scores context, by means of prose recall and word paired-associate learning tasks. Patients were tested at presurgical baseline, 6months, 2 and 5years after anteromesial temporal lobe surgery, using parallel versions of the neuropsychological tests. Our main finding revealed a key involvement of the left temporal lobe and, in particular, of the left hippocampus in prose recall rather than word paired-associate task. We also confirmed that shorter duration of epilepsy, younger age, and withdrawal of antiepileptic drugs would predict a better memory outcome. When individual memory performance was taken into account, data showed that females affected by left temporal lobe epilepsy for longer duration were more at risk of presenting a clinically pathologic LTM at 5years after surgery. Taken together, these findings shed new light on verbal declarative memory in the mesial temporal lobe and on the behavioral signature of the functional reorganization after the surgical treatment of temporal lobe epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

The neural basis of implicit learning and memory: a review of neuropsychological and neuroimaging research.

PubMed

Reber, Paul J

2013-08-01

Memory systems research has typically described the different types of long-term memory in the brain as either declarative versus non-declarative or implicit versus explicit. These descriptions reflect the difference between declarative, conscious, and explicit memory that is dependent on the medial temporal lobe (MTL) memory system, and all other expressions of learning and memory. The other type of memory is generally defined by an absence: either the lack of dependence on the MTL memory system (nondeclarative) or the lack of conscious awareness of the information acquired (implicit). However, definition by absence is inherently underspecified and leaves open questions of how this type of memory operates, its neural basis, and how it differs from explicit, declarative memory. Drawing on a variety of studies of implicit learning that have attempted to identify the neural correlates of implicit learning using functional neuroimaging and neuropsychology, a theory of implicit memory is presented that describes it as a form of general plasticity within processing networks that adaptively improve function via experience. Under this model, implicit memory will not appear as a single, coherent, alternative memory system but will instead be manifested as a principle of improvement from experience based on widespread mechanisms of cortical plasticity. The implications of this characterization for understanding the role of implicit learning in complex cognitive processes and the effects of interactions between types of memory will be discussed for examples within and outside the psychology laboratory. Copyright © 2013 Elsevier Ltd. All rights reserved.

Empathy in Hippocampal Amnesia

PubMed Central

Beadle, J. N.; Tranel, D.; Cohen, N. J.; Duff, M. C.

2013-01-01

Empathy is critical to the quality of our relationships with others and plays an important role in life satisfaction and well-being. The scientific investigation of empathy has focused on characterizing its cognitive and neural substrates, and has pointed to the importance of a network of brain regions involved in emotional experience and perspective taking (e.g., ventromedial prefrontal cortex, amygdala, anterior insula, cingulate). While the hippocampus has rarely been the focus of empathy research, the hallmark properties of the hippocampal declarative memory system (e.g., representational flexibility, relational binding, on-line processing capacity) make it well-suited to meet some of the crucial demands of empathy, and a careful investigation of this possibility could make a significant contribution to the neuroscientific understanding of empathy. The present study is a preliminary investigation of the role of the hippocampal declarative memory system in empathy. Participants were three patients (1 female) with focal, bilateral hippocampal (HC) damage and severe declarative memory impairments and three healthy demographically matched comparison participants. Empathy was measured as a trait through a battery of gold standard questionnaires and through on-line ratings and prosocial behavior in response to a series of empathy inductions. Patients with hippocampal amnesia reported lower cognitive and emotional trait empathy than healthy comparison participants. Unlike healthy comparison participants, in response to the empathy inductions hippocampal patients reported no increase in empathy ratings or prosocial behavior. The results provide preliminary evidence for a role for hippocampal declarative memory in empathy. PMID:23526601

Serpins promote cancer cell survival and vascular co-option in brain metastasis.

PubMed

Valiente, Manuel; Obenauf, Anna C; Jin, Xin; Chen, Qing; Zhang, Xiang H-F; Lee, Derek J; Chaft, Jamie E; Kris, Mark G; Huse, Jason T; Brogi, Edi; Massagué, Joan

2014-02-27

Brain metastasis is an ominous complication of cancer, yet most cancer cells that infiltrate the brain die of unknown causes. Here, we identify plasmin from the reactive brain stroma as a defense against metastatic invasion, and plasminogen activator (PA) inhibitory serpins in cancer cells as a shield against this defense. Plasmin suppresses brain metastasis in two ways: by converting membrane-bound astrocytic FasL into a paracrine death signal for cancer cells, and by inactivating the axon pathfinding molecule L1CAM, which metastatic cells express for spreading along brain capillaries and for metastatic outgrowth. Brain metastatic cells from lung cancer and breast cancer express high levels of anti-PA serpins, including neuroserpin and serpin B2, to prevent plasmin generation and its metastasis-suppressive effects. By protecting cancer cells from death signals and fostering vascular co-option, anti-PA serpins provide a unifying mechanism for the initiation of brain metastasis in lung and breast cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

[Prognosis in pediatric traumatic brain injury. A dynamic cohort study].

PubMed

Vázquez-Solís, María G; Villa-Manzano, Alberto I; Sánchez-Mosco, Dalia I; Vargas-Lares, José de Jesús; Plascencia-Fernández, Irma

2013-01-01

traumatic brain injury is a main cause of hospital admission and death in children. Our objective was to identify prognostic factors of pediatric traumatic brain injury. this was a dynamic cohort study of traumatic brain injury with 6 months follow-up. The exposition was: mild or moderate/severe traumatic brain injury, searching for prognosis (morbidity-mortality and decreased Glasgow scale). Relative risk and logistic regression was estimated for prognostic factors. we evaluated 440 patients with mild traumatic brain injury and 98 with moderate/severe traumatic brain injury. Morbidity for mild traumatic brain injury was 1 %; for moderate/severe traumatic brain injury, 5 %. There were no deaths. Prognostic factors for moderate/severe traumatic brain injury were associated injuries (RR = 133), fractures (RR = 60), street accidents (RR = 17), night time accidents (RR = 2.3) and weekend accidents (RR = 2). Decreased Glasgow scale was found in 9 %, having as prognostic factors: visible injuries (RR = 3), grown-up supervision (RR = 2.5) and time of progress (RR = 1.6). there should be a prognosis established based on kinetic energy of the injury and not only with Glasgow Scale.

[The epidemiology of suicide in bipolar disorder in the manic episode--preliminary reports].

PubMed

Wierzbiński, Piotr; Zdanowicz, Anna; Klekowska, Justyna; Broniarczyk-Czarniak, Marta; Zboralski, Krzysztof

2014-04-01

Suicide is among ten leading causes of death in each country and the third most common cause of death in the age group 16-35. The presence of mental illness is the most important risk factor for suicide. Affective disorders contribute to 15-25% of deaths due to suicide attempts. Depression is the most likely cause of the patients attempt on his life. Contrary to popular opinion, manic episode can also increase the risk of suicide, especially if the patient dominates by productive symptoms in the form of delusions. The aim of study was to determine the frequency of suicide attempts and their determinants in an episode of mania in bipolar disorder. The study included 16 people with a diagnosed bipolar disorder, hospitalized with manic episode at the age of 28-76. Patients hospitalized in the Department of Adult Psychiatry were selected randomly. The number of suicide attempts, comorbid conditions, and basic epidemiological data were estimated. Five patients declared suicide attempt, one of which wanted to make more than one attempt at suicide. 3 people took it during an episode of depression, two in an episode of mania. The methods of suicide were associated with an overdose of medication and this was accompanied by a greater amount of alcohol intake. 11 persons did not declare any willingness to attempt suicide. A mania episode did not increase the risk of suicide in bipolar disorder compared to an episode of depression in the study conducted. The importance of somatic illness in patients with bipolar disorder is increased if the suicide attempt occurs in an episode of depression. Alcohol abuse showed no negative effects on suicidal behavior of patients. During abuse was the most common way of commit suicide.

Head Trauma with or without Mild Brain Injury Increases the Risk of Future Traumatic Death: A Controlled Prospective 15-Year Follow-Up Study.

PubMed

Vaaramo, Kalle; Puljula, Jussi; Tetri, Sami; Juvela, Seppo; Hillbom, Matti

2015-10-15

Patients who have recovered from traumatic brain injury (TBI) show an increased risk of premature death. To investigate long-term mortality rates in a population admitted to the hospital for head injury (HI), we conducted a population-based prospective case-control, record-linkage study, All subjects who were living in Northern Ostrobothnia, and who were admitted to Oulu University Hospital in 1999 because of HI (n=737), and 2196 controls matched by age, gender, and residence randomly drawn from the population of Northern Ostrobothnia were included. Death rate and causes of death in HI subjects during 15 years of follow-up was compared with the general population controls. The crude mortality rates were 56.9, 18.6, and 23.8% for subjects having moderate-to-severe traumatic brain injury (TBI), mild TBI, and head injury without TBI, respectively. The corresponding approximate annual mortality rates were 6.7%, 1.4%, and 1.9%. All types of index HI predicted a significant risk of traumatic death in the future. Subjects who had HI without TBI had an increased risk of both death from all causes (hazard ratio 2.00; 95% confidence interval 1.57-2.55) and intentional or unintentional traumatic death (4.01, 2.20-7.30), compared with controls. The main founding was that even HI without TBI carries an increased risk of future traumatic death. The reason for this remains unknown and further studies are needed. To prevent such premature deaths, post-traumatic therapy should include an interview focusing on lifestyle factors.

Active Donor Management During the Hospital Phase of Care Is Associated with More Organs Transplanted per Donor.

PubMed

Patel, Madhukar S; De La Cruz, Salvador; Sally, Mitchell B; Groat, Tahnee; Malinoski, Darren J

2017-10-01

Meeting donor management goals when caring for potential organ donors has been associated with more organs transplanted per donor (OTPD). Concern persists, however, as to whether this indicates that younger/healthier donors are more likely to meet donor management goals or whether active management affects outcomes. A prospective observational study of all standard criteria donors was conducted by 10 organ procurement organizations across United Network for Organ Sharing Regions 4, 5, and 6. Donor management goals representing normal critical care end points were measured at 2 time points: when a catastrophic brain injury was recognized and a referral was made to the organ procurement organization by the DH; and after brain death was declared and authorization for organ donation was obtained. Donor management goals Bundle "met" was defined as achieving any 7 of 9 end points. A positive Bundle status change was defined as not meeting the Bundle at referral and subsequently achieving it at authorization. The primary outcomes measure was having ≥4 OTPD. Data were collected for 1,398 standard criteria donors. Of the 1,166 (83%) who did not meet the Bundle at referral, only 254 (22%) had a positive Bundle status change. On adjusted analysis, positive Bundle status change increased the odds of achieving ≥4 OTPD significantly (odds ratio 2.04; 95% CI 1.49 to 2.81; p < 0.001). A positive donor management goal Bundle status change during donor hospital management is associated with a 2-fold increase in achieving ≥4 OTPD. Active critical care management of the potential organ donor, as evidenced by improvement in routinely measured critical care end points can be a means by which to substantially increase the number of organs available for transplantation. Published by Elsevier Inc.

Increased reduction in exsanguination rates leaves brain injury as the only major cause of death in blunt trauma.

PubMed

Jochems, D; Leenen, L P H; Hietbrink, F; Houwert, R M; van Wessem, K J P

2018-05-23

Central nervous system (CNS) related injuries and exsanguination have been the most common causes of death in trauma for decades. Despite improvements in haemorrhage control in recent years exsanguination is still a major cause of death. We conducted a prospective database study to investigate the current incidence of haemorrhage related mortality. A prospective database study of all trauma patients admitted to an urban major trauma centre between January 2007 and December 2016 was conducted. All in-hospital trauma deaths were included. Cause of death was reviewed by a panel of trauma surgeons. Patients who were dead on arrival were excluded. Trends in demographics and outcome were analysed per year. Further, 2 time periods (2007-2012 and 2013-2016) were selected representing periods before and after implementation of haemostatic resuscitation and damage control procedures in our hospital to analyse cause of death into detail. 11,553 trauma patients were admitted, 596 patients (5.2%) died. Mean age of deceased patients was 61 years and 61% were male. Mechanism of injury (MOI) was blunt in 98% of cases. Mean ISS was 28 with head injury the most predominant injury (mean AIS head 3.4). There was no statistically significant difference in sex and MOI over time. Even though deceased patients were older in 2016 compared to 2007 (67 vs. 46 years, p < 0.001), mortality was lower in later years (p = 0.02). CNS related injury was the main cause of death in the whole decade; 58% of patients died of CNS in 2007-2012 compared to 76% of patients in 2013-2016 (p = 0.001). In 2007-2012 9% died of exsanguination compared to 3% in 2013-2016 (p = 0.001). In this cohort in a major trauma centre death by exsanguination has decreased to 3% of trauma deaths. The proportion of traumatic brain injury has increased over time and has become the most common cause of death in blunt trauma. Besides on-going prevention of brain injury future studies should focus on treatment strategies preventing secondary damage of the brain once the injury has occurred. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pathological characteristics of liver allografts from donation after brain death followed by cardiac death in pigs.

PubMed

Ye, Hui; Wang, Dong-Ping; Zhang, Chuan-Zhao; Zhang, Long-Juan; Wang, Hao-Chen; Li, Zhuo-Hui; Chen, Zhen; Zhang, Tao; Cai, Chang-Jie; Ju, Wei-Qiang; Ma, Yi; Guo, Zhi-Yong; He, Xiao-Shun

2014-10-01

Donation after brain death followed by circulatory death (DBCD) is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs (25-30 kg) were allocated randomly into donation after brain death (DBD), donation after circulatory death (DCD) and DBCD groups. Brain death was induced by augmenting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were collected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [(0.56±0.30)%] and DBCD [(0.50 ± 0.11)%] groups was much lower than that in DCD group [(3.78±0.33)%] (P<0.05). And there was no significant difference between DBD group and DBCD group (P>0.05)). The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.

The role of the basal ganglia in learning and memory: Insight from Parkinson's disease

PubMed Central

2013-01-01

It has long been known that memory is not a single process. Rather, there are different kinds of memory that are supported by distinct neural systems. This idea stemmed from early findings of dissociable patterns of memory impairments in patients with selective damage to different brain regions. These studies highlighted the role of the basal ganglia in non-declarative memory, such as procedural or habit learning, contrasting it with the known role of the medial temporal lobes in declarative memory. In recent years, major advances across multiple areas of neuroscience have revealed an important role for the basal ganglia in motivation and decision making. These findings have led to new discoveries about the role of the basal ganglia in learning and highlighted the essential role of dopamine in specific forms of learning. Here we review these recent advances with an emphasis on novel discoveries from studies of learning in patients with Parkinson's disease. We discuss how these findings promote the development of current theories away from accounts that emphasize the verbalizability of the contents of memory and towards a focus on the specific computations carried out by distinct brain regions. Finally, we discuss new challenges that arise in the face of accumulating evidence for dynamic and interconnected memory systems that jointly contribute to learning. PMID:21945835

Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest

PubMed Central

Tian, Fangyun; Liu, Tiecheng; Xu, Gang; Li, Duan; Ghazi, Talha; Shick, Trevor; Sajjad, Azeem; Wang, Michael M.; Farrehi, Peter; Borjigin, Jimo

2018-01-01

Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO2-mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG) and electroencephalogram (EEG) signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients. PMID:29487541

The effect of brain death in rat steatotic and non-steatotic liver transplantation with previous ischemic preconditioning.

PubMed

Jiménez-Castro, Mónica B; Meroño, Noelia; Mendes-Braz, Mariana; Gracia-Sancho, Jordi; Martínez-Carreres, Laia; Cornide-Petronio, Maria Eugenia; Casillas-Ramirez, Araní; Rodés, Juan; Peralta, Carmen

2015-01-01

Most liver grafts undergoing transplantation derive from brain dead donors, which may also show hepatic steatosis, being both characteristic risk factors in liver transplantation. Ischemic preconditioning shows benefits when applied in non-brain dead clinical situations like hepatectomies, whereas it has been less promising in the transplantation from brain dead patients. This study examined how brain death affects preconditioned steatotic and non-steatotic liver grafts undergoing transplantation. Steatotic and non-steatotic grafts from non-brain dead and brain dead-donors were cold stored for 6h and then transplanted. After 2, 4, and 16 h of reperfusion, hepatic damage was analysed. In addition, two therapeutic strategies, ischemic preconditioning and/or acetylcholine pre-treatment, and their underlying mechanisms were characterized. Preconditioning benefits in non-brain dead donors were associated with nitric oxide and acetylcholine generation. In brain dead donors, preconditioning generated nitric oxide but did not promote acetylcholine upregulation, and this resulted in inflammation and damage. Acetylcholine treatment in brain dead donors, through PKC, increased antioxidants and reduced lipid peroxidation, nitrotyrosines and neutrophil accumulation, altogether protecting against damage. The combination of acetylcholine and preconditioning conferred stronger protection against damage, oxidative stress and neutrophil accumulation than acetylcholine treatment alone. These superior beneficial effects were due to a selective preconditioning-mediated generation of nitric oxide and regulation of PPAR and TLR4 pathways, which were not observed when acetylcholine was administered alone. Our findings propose the combination of acetylcholine+preconditioning as a feasible and highly protective strategy to reduce the adverse effects of brain death and to ultimately improve liver graft quality. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest.

PubMed

Tian, Fangyun; Liu, Tiecheng; Xu, Gang; Li, Duan; Ghazi, Talha; Shick, Trevor; Sajjad, Azeem; Wang, Michael M; Farrehi, Peter; Borjigin, Jimo

2018-01-01

Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO 2 -mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG) and electroencephalogram (EEG) signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients.

Latin American Consensus on the use of transcranial Doppler in the diagnosis of brain death

PubMed Central

2014-01-01

Transcranial Doppler evaluates cerebral hemodynamics in patients with brain injury and is a useful technical tool in diagnosing cerebral circulatory arrest, usually present in the brain-dead patient. This Latin American Consensus was formed by a group of 26 physicians experienced in the use of transcranial Doppler in the context of brain death. The purpose of this agreement was to make recommendations regarding the indications, technique, and interpretation of the study of transcranial ultrasonography in patients with a clinical diagnosis of brain death or in the patient whose clinical diagnosis presents difficulties; a working group was formed to enable further knowledge and to strengthen ties between Latin American physicians working on the same topic. A review of the literature, concepts, and experiences were exchanged in two meetings and via the Internet. Questions about pathophysiology, equipment, techniques, findings, common problems, and the interpretation of transcranial Doppler in the context of brain death were answered. The basic consensus statements are the following: cerebral circulatory arrest is the final stage in the evolution of progressive intracranial hypertension, which is visualized with transcranial Doppler as a "pattern of cerebral circulatory arrest". The following are accepted as the standard of cerebral circulatory arrest: reverberant pattern, systolic spikes, and absence of previously demonstrated flow. Ultrasonography should be used - in acceptable hemodynamic conditions - in the anterior circulation bilaterally (middle cerebral artery) and in the posterior (basilar artery) territory. If no ultrasonographic images are found in any or all of these vessels, their proximal arteries are acceptable to be studied to look for a a pattern of cerebral circulatory arrest. PMID:25295818

Endotoxin-activated microglia injure brain derived endothelial cells via NF-κB, JAK-STAT and JNK stress kinase pathways

PubMed Central

2011-01-01

Background We previously showed that microglia damage blood brain barrier (BBB) components following ischemic brain insults, but the underlying mechanism(s) is/are not well known. Recent work has established the contribution of toll-like receptor 4 (TLR4) activation to several brain pathologies including ischemia, neurodegeneration and sepsis. The present study established the requirement of microglia for lipopolysaccharide (LPS) mediated endothelial cell death, and explored pathways involved in this toxicity. LPS is a classic TLR4 agonist, and is used here to model aspects of brain conditions where TLR4 stimulation occurs. Methods/Results In monocultures, LPS induced death in microglia, but not brain derived endothelial cells (EC). However, LPS increased EC death when cocultured with microglia. LPS led to nitric oxide (NO) and inducible NO synthase (iNOS) induction in microglia, but not in EC. Inhibiting microglial activation by blocking iNOS and other generators of NO or blocking reactive oxygen species (ROS) also prevented injury in these cocultures. To assess the signaling pathway(s) involved, inhibitors of several downstream TLR-4 activated pathways were studied. Inhibitors of NF-κB, JAK-STAT and JNK/SAPK decreased microglial activation and prevented cell death, although the effect of blocking JNK/SAPK was rather modest. Inhibitors of PI3K, ERK, and p38 MAPK had no effect. Conclusions We show that LPS-activated microglia promote BBB disruption through injury to endothelial cells, and the specific blockade of JAK-STAT, NF-κB may prove to be especially useful anti-inflammatory strategies to confer cerebrovascular protection. PMID:21385378

Human Traumatic Brain Injury Results in Oligodendrocyte Death and Increases the Number of Oligodendrocyte Progenitor Cells.

PubMed

Flygt, Johanna; Gumucio, Astrid; Ingelsson, Martin; Skoglund, Karin; Holm, Jonatan; Alafuzoff, Irina; Marklund, Niklas

2016-06-01

Oligodendrocyte (OL) death may contribute to white matter pathology, a common cause of network dysfunction and persistent cognitive problems in patients with traumatic brain injury (TBI). Oligodendrocyte progenitor cells (OPCs) persist throughout the adult CNS and may replace dead OLs. OL death and OPCs were analyzed by immunohistochemistry of human brain tissue samples, surgically removed due to life-threatening contusions and/or focal brain swelling at 60.6 ± 75 hours (range 4-192 hours) postinjury in 10 severe TBI patients (age 51.7 ± 18.5 years). Control brain tissue was obtained postmortem from 5 age-matched patients without CNS disorders. TUNEL and CC1 co-labeling was used to analyze apoptotic OLs, which were increased in injured brain tissue (p < 0.05), without correlation with time from injury until surgery. The OPC markers Olig2, A2B5, NG2, and PDGFR-α were used. In contrast to the number of single-labeled Olig2, A2B5, NG2, and PDGFR-α-positive cells, numbers of Olig2 and A2B5 co-labeled cells were increased in TBI samples (p < 0.05); this was inversely correlated with time from injury to surgery (r = -0.8, p < 0.05). These results indicate that severe focal human TBI results in OL death and increases in OPCs postinjury, which may influence white matter function following TBI. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

The Nepalese Army in Internal Peace and Security

DTIC Science & Technology

2013-06-14

instead of milk leading to the death of the buffalo and cow ” (Baral 2012, 13). 43 Nepali is not the first language of the majority of the Nepalese...religious places. Baral states, “People in the villages would not even give milk to the Dalits because of the belief that [thereafter] blood would come...GoN itself is reluctant to promote diverse cultures and languages as it continues to declare Nepal a Hindu country. The cow , simrik (vermilion

Pro-life role for c-Jun N-terminal kinase and p38 mitogen-activated protein kinase at rostral ventrolateral medulla in experimental brain stem death.

PubMed

Chang, Alice Y W

2012-11-17

Based on an experimental brain stem death model, we demonstrated previously that activation of the mitogen-activated protein kinase kinase 1/2 (MEK1/2)/extracellular signal-regulated kinase 1/2 (ERK1/2)/ mitogen-activated protein kinase signal-interacting kinase 1/2 (MNK1/2) cascade plays a pro-life role in the rostral ventrolateral medulla (RVLM), the origin of a life-and-death signal detected from systemic arterial pressure, which sequentially increases (pro-life) and decreases (pro-death) to reflect progressive dysfunction of central cardiovascular regulation during the advancement towards brain stem death in critically ill patients. The present study assessed the hypothesis that, in addition to ERK1/2, c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK), the other two mammalian members of MAPKs that are originally identified as stress-activated protein kinases, are activated specifically by MAPK kinase 4 (MAP2K4) or MAP2K6 and play a pro-life role in RVLM during experimental brain stem death. We further delineated the participation of phosphorylating activating transcriptional factor-2 (ATF-2) and c-Jun, the classical transcription factor activated by JNK or p38MAPK, in this process. An experimental model of brain stem death that employed microinjection of the organophosphate insecticide mevinphos (Mev; 10 nmol) bilaterally into RVLM of Sprague-Dawley rats was used, alongside cardiovascular, pharmacological and biochemical evaluations. Results from ELISA showed that whereas the total JNK, p38MAPK, MAP2K4 and MAP2K6 were not affected, augmented phosphorylation of JNK at Thr183 and Tyr185 and p38MAPK at Thr180 and Tyr182, accompanied by phosphorylation of their upstream activators MAP2K4 at Ser257 and Thr261 and MAP2K6 at Ser207 and Thr211 in RVLM occurred preferentially during the pro-life phase of experimental brain stem death. Moreover, the activity of transcription factors ATF-2 at Thr71 and c-Jun at Ser73, rather than Elk-1 at Ser383 in RVLM were also augmented during the pro-life phase. Furthermore, pretreatment by microinjection into the bilateral RVLM of specific JNK inhibitors, JNK inhibitor I (100 pmol) or SP600125 (5 pmol), or specific p38MAPK inhibitors, p38MAPK inhibitor III (500 pmol) or SB203580 (2 nmol), exacerbated the depressor effect and blunted the augmented life-and-death signal exhibited during the pro-life phase. On the other hand, pretreatment with the negative control for JNK or p38MAPK inhibitor, JNK inhibitor I negative control (100 pmol) or SB202474 (2 nmol), was ineffective in the vehicle-controls and Mev-treatment groups. Our results demonstrated that activation of JNK or p38MAPK in RVLM by their upstream activators MAP2K4 or MAP2K6 plays a preferential pro-life role by sustaining the central cardiovascular regulatory machinery during experimental brain stem death via phosphorylation and activation of nuclear transcription factor ATF-2 or c-Jun.

Public Perception of the Risks Associated with Infectious Diseases in Poland: Ebola and Influenza and Their Impact on the Attitude to Vaccination.

PubMed

Kuchar, Ernest; Ludwikowska, Kamila; Marciniak, Dominik; Szenborn, Leszek; Nitsch-Osuch, Aneta

2017-01-01

While the Ebola outbreak in 2014 was strongly highlighted in mainstream media and perceived as a threat to public health in Poland, influenza was regarded as a triviality and the vaccination coverage was low. In the present study, by analyzing feedback from an on-line questionnaire (from November 2014 to January 2015) we assessed the knowledge concerning Ebola and influenza together with attitudes to immunization of 544 respondents (45% medical staff). The findings were that 92.6% of respondents declared readiness to vaccination before traveling to endemic regions if a vaccine against Ebola would have existed, but adverse reactions, high costs, and low effectiveness would adversely affect that decision. While 84.2% of respondents declared awareness of influenza attributing significantly to the cause of death, only 65.4% considered influenza as an actual danger for people in Poland and 46.7% thought that Poland was not an endemic region for influenza. Nearly 23% declared that they were already vaccinated against influenza. The majority of respondents (67.5%) were not going to be vaccinated. We conclude that awareness of risk related to infectious diseases is an important determinant when deciding whether to vaccinate. However, negative information about the vaccine has some bearing on the decision to get vaccinated.

Donor brain death predisposes human kidney grafts to a proinflammatory reaction after transplantation.

PubMed

de Vries, D K; Lindeman, J H N; Ringers, J; Reinders, M E J; Rabelink, T J; Schaapherder, A F M

2011-05-01

Donor brain death has profound effects on post-transplantation graft function and survival. We hypothesized that changes initiated in the donor influence the graft's response to ischemia and reperfusion. In this study, human brain dead donor kidney grafts were compared to living and cardiac dead donor kidney grafts. Pretransplant biopsies of brain dead donor kidneys contained notably more infiltrating T lymphocytes and macrophages. To assess whether the different donor conditions result in a different response to reperfusion, local cytokine release from the reperfused kidney was studied by measurement of paired arterial and renal venous blood samples. Reperfusion of kidneys from brain dead donors was associated with the instantaneous release of inflammatory cytokines, such as G-CSF, IL-6, IL-9, IL-16 and MCP-1. In contrast, kidneys from living and cardiac dead donors showed a more modest cytokine response with release of IL-6 and small amounts of MCP-1. In conclusion, this study shows that donor brain death initiates an inflammatory state of the graft with T lymphocyte and macrophage infiltration and massive inflammatory cytokine release upon reperfusion. These observations suggest that brain dead donors require a novel approach for donor pretreatment aimed at preventing this inflammatory response to increase graft survival. ©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

Intravascular Inflammation Triggers Intracerebral Activated Microglia and Contributes to Secondary Brain Injury After Experimental Subarachnoid Hemorrhage (eSAH).

PubMed

Atangana, Etienne; Schneider, Ulf C; Blecharz, Kinga; Magrini, Salima; Wagner, Josephin; Nieminen-Kelhä, Melina; Kremenetskaia, Irina; Heppner, Frank L; Engelhardt, Britta; Vajkoczy, Peter

2017-04-01

Activation of innate immunity contributes to secondary brain injury after experimental subarachnoid hemorrhage (eSAH). Microglia accumulation and activation within the brain has recently been shown to induce neuronal cell death after eSAH. In isolated mouse brain capillaries after eSAH, we show a significantly increased gene expression for intercellular adhesion molecule-1 (ICAM-1) and P-selectin. Hence, we hypothesized that extracerebral intravascular inflammatory processes might initiate the previously reported microglia accumulation within the brain tissue. We therefore induced eSAH in knockout mice for ICAM-1 (ICAM-1 -/- ) and P-selectin glycoprotein ligand-1 (PSGL-1 -/- ) to find a significant decrease in neutrophil-endothelial interaction within the first 7 days after the bleeding in a chronic cranial window model. This inhibition of neutrophil recruitment to the endothelium results in significantly ameliorated microglia accumulation and neuronal cell death in knockout animals in comparison to controls. Our results suggest an outside-in activation of the CNS innate immune system at the vessel/brain interface following eSAH. Microglia cells, as part of the brain's innate immune system, are triggered by an inflammatory reaction in the microvasculature after eSAH, thus contributing to neuronal cell death. This finding offers a whole range of new research targets, as well as possible therapy options for patients suffering from eSAH.

Brain Oscillations, Hypnosis, and Hypnotizability.

PubMed

Jensen, Mark P; Adachi, Tomonori; Hakimian, Shahin

2015-01-01

This article summarizes the state-of-science knowledge regarding the associations between hypnosis and brain oscillations. Brain oscillations represent the combined electrical activity of neuronal assemblies, usually measured as specific frequencies representing slower (delta, theta, alpha) and faster (beta, gamma) oscillations. Hypnosis has been most closely linked to power in the theta band and changes in gamma activity. These oscillations are thought to play a critical role in both the recording and recall of declarative memory and emotional limbic circuits. The authors propose that this role may be the mechanistic link between theta (and perhaps gamma) oscillations and hypnosis, specifically, that the increases in theta oscillations and changes in gamma activity observed with hypnosis may underlie some hypnotic responses. If these hypotheses are supported, they have important implications for both understanding the effects of hypnosis and for enhancing response to hypnotic treatments.

Process and barriers to organ donation and causes of brain death in northeast of Iran.

PubMed

Bahrami, Abdollah; Khaleghi, Ebrahim; Vakilzadeh, Ali Khorsand; Afzalaghaee, Monavar

2017-02-01

Organ transplantation is the treatment of choice for some diseases. However, the need for cadaveric organ donation has either plateaued or is on a decreasing trend in some countries, especially in developed ones. In this study, we aimed to identify the barriers to organ donation in brain dead patients, who were referred to the organ procurement organizations (OPO) in northeast Iran. In this cross-sectional study during 2006 to 2013, data were collected from medical records of brain dead patients. Demographic information, cause of brain death, the process of obtaining informed consent, and the reasons for declining organ donation were obtained from the OPO records. The data were analyzed using chi-square test by SPSS 13 software. Of 1034 brain dead patients, 751 cases (72.6%) were eligible for organ donation, and, ultimately, 344 cases underwent organ donation. The rate of organ donation increased during the course of the study; medical and legal reasons as well as family refusal to authorize donation were the main barriers to the process. Based on the pattern of mortality, the need for living donors in developing countries, such as Iran and other countries in the Mediterranean region, can be reduced by improving the quality of healthcare, efficient identification of brain death, and obtaining consent with appropriate strategies.

Brain Death and Human Organismal Integration: A Symposium on the Definition of Death.

PubMed

Moschella, Melissa

2016-06-01

Does the ability of some brain dead bodies to maintain homeostasis with the help of artificial life support actually imply that those bodies are living human organisms? Or might it be possible that a brain dead body on life support is a mere collection of still-living cells, organs and tissues which can coordinate with one another, but which lack the genuine integration that is the hallmark of a unified human organism as a whole? To foster further study of these difficult and timely questions, a Symposium on the Definition of Death was held at The Catholic University of America in June 2014. The Symposium brought together scholars from a variety of disciplines-law, medicine, biology, philosophy and theology-who all share a commitment to the dead donor rule and to a biological definition of death, but who have differing opinions regarding the validity of neurological criteria for human death. The papers found in this special issue are among the fruits of this Symposium. © The Author 2016. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Anesthesia Management of Organ Donors.

PubMed

Xia, Victor W; Braunfeld, Michelle

2017-09-01

The shortage of suitable organs is the biggest obstacle for transplants. At present, most organs for transplant in the United States are from donation after neurologic determination of death (brain death). Potential organs for transplant need to maintain their viability during a series of insults, including the original disease, physiologic derangements during the dying process, ischemia, and reperfusion. Proper donor management before, during, and after procurement has potential to increase the number and quality of organs from donors. Anesthesiologists need to understand the physiologic derangements associated with brain death and the updated donor management during the periprocurement period. Copyright © 2017 Elsevier Inc. All rights reserved.

Legal Standards for Brain Death and Undue Influence in Euthanasia Laws.

PubMed

Pope, Thaddeus Mason; Okninski, Michaela E

2016-06-01

A major appellate court decision from the United States seriously questions the legal sufficiency of prevailing medical criteria for the determination of death by neurological criteria. There may be a mismatch between legal and medical standards for brain death, requiring the amendment of either or both. In South Australia, a Bill seeks to establish a legal right for a defined category of persons suffering unbearably to request voluntary euthanasia. However, an essential criterion of a voluntary decision is that it is not tainted by undue influence, and this Bill falls short of providing adequate guidance to assess for undue influence.

Alcohol-induced apoptosis of oligodendrocytes in the fetal macaque brain.

PubMed

Creeley, Catherine E; Dikranian, Krikor T; Johnson, Stephen A; Farber, Nuri B; Olney, John W

2013-06-12

In utero exposure of the fetal non-human primate (NHP) brain to alcohol on a single occasion during early or late third-trimester gestation triggers widespread acute apoptotic death of cells in both gray and white matter (WM) regions of the fetal brain. In a prior publication, we documented that the dying gray matter cells are neurons, and described the regional distribution and magnitude of this cell death response. Here, we present new findings regarding the magnitude, identity and maturational status of the dying WM cells in these alcohol-exposed fetal NHP brains. Our findings document that the dying WM cells belong to the oligodendrocyte (OL) lineage. OLs become vulnerable when they are just beginning to generate myelin basic protein in preparation for myelinating axons, and they remain vulnerable throughout later stages of myelination. We found no evidence linking astrocytes, microglia or OL progenitors to this WM cell death response. The mean density (profiles per mm3) of dying WM cells in alcohol-exposed brains was 12.7 times higher than the mean density of WM cells dying by natural apoptosis in drug-naive control brains. In utero exposure of the fetal NHP brain to alcohol on a single occasion triggers widespread acute apoptotic death of neurons (previous study) and of OLs (present study) throughout WM regions of the developing brain. The rate of OL apoptosis in alcohol-exposed brains was 12.7 times higher than the natural OL apoptosis rate. OLs become sensitive to the apoptogenic action of alcohol when they are just beginning to generate constituents of myelin in their cytoplasm, and they remain vulnerable throughout later stages of myelination. There is growing evidence for a similar apoptotic response of both neurons and OLs following exposure of the developing brain to anesthetic and anticonvulsant drugs. Collectively, this body of evidence raises important questions regarding the role that neuro and oligo apoptosis may play in the human condition known as fetal alcohol spectrum disorder (FASD), and also poses a question whether other apoptogenic drugs, although long considered safe for pediatric/obstetric use, may have the potential to cause iatrogenic FASD-like developmental disability syndromes.

Death, democracy and public ethical choice.

PubMed

Cushman, Reid; Holm, Soren

1990-07-01

The Danish Council of Ethics...believed that the brain-death criterion should not be accepted without public education and debate. Following the introduction of a spectrum of educational and related activites, a Gallup poll found that 98% of the survey population was aware of the debate over brain-vs-heart criteria and that 80% favoured the adoption of a supplemental brain-death standard... This raises the fundamental question of decisionmaking in pluralist democratic societies, of the limits of democratic involvement in such choices, and of the role of bodies like the Danish Council of Ethics... It must be part of the mission of a governmental bioethical body to use its peculiar expertise to teach and to lead -- to build a popular consensus out of confusion. But in doing so, such a Commission will be steering a dangerous course....

Global Burden of Childhood Tuberculosis.

PubMed

Jenkins, Helen E

2016-01-01

In 2015, the World Health Organization (WHO) declared tuberculosis (TB) to be responsible for more deaths than any other single infectious disease. The burden of TB among children has frequently been dismissed as relatively low with resulting deaths contributing very little to global under-five all-cause mortality, although without rigorous estimates of these statistics, the burden of childhood TB was, in reality, unknown. Recent work in the area has resulted in a WHO estimate of 1 million new cases of childhood TB in 2014 resulting in 136,000 deaths. Around 3% of these cases likely have multidrug-resistant TB and at least 40,000 are in HIV-infected children. TB is now thought to be a major or contributory cause of many deaths in children under five years old, despite not being recorded as such, and is likely in the top ten causes of global mortality in this age group. In particular, recent work has shown that TB is an under-lying cause of a substantial proportion of pneumonia deaths in TB-endemic countries. Childhood TB should be given higher priority: we need to identify children at greatest risk of TB disease and death and make more use of tools such as active case-finding and preventive therapy. TB is a preventable and treatable disease from which no child should die.

Experimental methods for testing the effects of neurotrophic peptide, ADNF-9, against alcohol-induced apoptosis during pregnancy in c57bl/6 mice.

PubMed

Sari, Youssef

2013-04-24

Experimental designs for investigating the effects of prenatal alcohol exposure during early embryonic stages in fetal brain growth are challenging. This is mostly due to the difficulty of microdissection of fetal brains and their sectioning for determination of apoptotic cells caused by prenatal exposure to alcohol. The experiments described here provide visualized techniques from mice breeding to the identification of cell death in fetal brain tissue. This study used C57BL/6 mice as the animal model for studying fetal alcohol exposure and the role of trophic peptide against alcohol-induced apoptosis. The breeding consists of a 2-hr matting window to determine the exact stage of embryonic age. An established fetal alcohol exposure model has been used in this study to determine the effects of prenatal alcohol exposure in fetal brains. This involves free access to alcohol or pair-fed liquid diets as the sole source of nutrients for the pregnant mice. The techniques involving dissection of fetuses and microdissection of fetal brains are described carefully, since the latter can be challenging. Microdissection requires a stereomicroscope and ultra-fine forceps. Step-by-step procedures for dissecting the fetal brains are provided visually. The fetal brains are dissected from the base of the primordium olfactory bulb to the base of the metencephalon. For investigating apoptosis, fetal brains are first embedded in gelatin using a peel-away mold to facilitate their sectioning with a vibratome apparatus. Fetal brains embedded and fixed in paraformaldehyde are easily sectioned, and the free floating sections can be mounted in superfrost plus slides for determination of apoptosis or cell death. TUNEL (TdT-mediated dUTP Nick End Labeling; TdT: terminal deoxynucleotidyl transferase) assay has been used to identify cell death or apoptotic cells. It is noteworthy that apoptosis and cell-mediated cytotoxicity are characterized by DNA fragmentation. Thus, the visualized TUNEL-positive cells are indicative of cell death or apoptotic cells. The experimental designs here provide information about the use of an established liquid diet for studying the effects of alcohol and the role of neurotrophic peptides during pregnancy in fetal brains. This involves breeding and feeding pregnant mice, microdissecting fetal brains, and determining apoptosis. Together, these visual and textual techniques might be a source for investigating prenatal exposure of harmful agents in fetal brains.

Apoptosis and brain ischaemia.

PubMed

Love, Seth

2003-04-01

There is increasing evidence that some neuronal death after brain ischaemia is mediated by the action of cysteine-requiring aspartate-directed proteases (caspases), the proteases responsible for apoptosis in mammals, although this form of neuronal death is not always accompanied by the morphological changes that are typical of apoptosis in other tissues. Caspase-mediated neuronal death is more extensive after transient than permanent focal brain ischaemia and may contribute to delayed loss of neurons from the penumbral region of infarcts. The activation of caspases after brain ischaemia is largely consequent on the translocation of Bax, Bak, and other BH3-only members of the Bcl-2 family to the mitochondrial outer membrane and the release of cytochrome c, procaspase-9, and apoptosis activating factor-1 (Apaf-1) from the mitochondrial intermembrane space. How exactly ischaemia induces this translocation is still poorly understood. NF-kappaB, the c-jun N-terminal kinase-c-Jun pathway, p53, E2F1, and other transcription factors are probably all involved in regulating the expression of BH3-only proteins after brain ischaemia, and mitochondrial translocation of Bad from sequestering cytosolic proteins is promoted by inactivation of the serine-threonine kinase, Akt. Other processes that are probably involved in the activation of caspases after brain ischaemia include the mitochondrial release of the second mitochondrial activator of caspases (Smac) or direct inhibitor-of-apoptosis-binding protein with low pI (DIABLO), the accumulation of products of lipid peroxidation, a marked reduction in protein synthesis, and the aberrant reentry of neurons into the cell cycle. Non-caspase-mediated neuronal apoptosis may also occur, but there is little evidence to date that this makes a significant contribution to brain damage after ischaemia. The intracellular processes that contribute to caspase-mediated neuronal death after ischaemia are all potential targets for therapy. However, anti-apoptotic interventions in stroke patients will require detailed evaluation using a range of outcome measures, as some such interventions seem simply to delay neuronal death and others to preserve neurons but not neuronal function.

Factors associated with resistance to dementia despite high Alzheimer disease pathology.

PubMed

Erten-Lyons, D; Woltjer, R L; Dodge, H; Nixon, R; Vorobik, R; Calvert, J F; Leahy, M; Montine, T; Kaye, J

2009-01-27

Autopsy series have shown that some elderly people remain with normal cognitive function during life despite having high burdens of pathologic lesions associated with Alzheimer disease (AD) at death. Understanding why these individuals show no cognitive decline, despite high AD pathologic burdens, may be key to discovery of neuroprotective mechanisms. A total of 36 subjects who on autopsy had Braak stage V or VI and moderate or frequent neuritic plaque scores based on Consortium to Establish a Registry for Alzheimer's Disease (CERAD) standards were included. Twelve had normal cognitive function and 24 a diagnosis of AD before death. Demographic characteristics, clinical and pathologic data, as well as antemortem brain volumes were compared between the groups. In multiple regression analysis, antemortem hippocampal and total brain volumes were significantly larger in the group with normal cognitive function after adjusting for gender, age at MRI, time from MRI to death, Braak stage, CERAD neuritic plaque score, and overall presence of vascular disease. Larger brain and hippocampal volumes were associated with preserved cognitive function during life despite a high burden of Alzheimer disease (AD) pathologic lesions at death. A better understanding of processes that lead to preservation of brain volume may provide important clues for the discovery of mechanisms that protect the elderly from AD.

Brain Swelling and Loss of Gray and White Matter Differentiation in Human Postmortem Cases by Computed Tomography.

PubMed

Shirota, Go; Gonoi, Wataru; Ishida, Masanori; Okuma, Hidemi; Shintani, Yukako; Abe, Hiroyuki; Takazawa, Yutaka; Ikemura, Masako; Fukayama, Masashi; Ohtomo, Kuni

2015-01-01

The purpose of this study was to evaluate the brain by postmortem computed tomography (PMCT) versus antemortem computed tomography (AMCT) using brains from the same patients. We studied 36 nontraumatic subjects who underwent AMCT, PMCT, and pathological autopsy in our hospital between April 2009 and December 2013. PMCT was performed within 20 h after death, followed by pathological autopsy including the brain. Autopsy confirmed the absence of intracranial disorders that might be related to the cause of death or might affect measurements in our study. Width of the third ventricle, width of the central sulcus, and attenuation in gray matter (GM) and white matter (WM) from the same area of the basal ganglia, centrum semiovale, and high convexity were statistically compared between AMCT and PMCT. Both the width of the third ventricle and the central sulcus were significantly shorter in PMCT than in AMCT (P < 0.0001). GM attenuation increased after death at the level of the centrum semiovale and high convexity, but the differences were not statistically significant considering the differences in attenuation among the different computed tomography scanners. WM attenuation significantly increased after death at all levels (P<0.0001). The differences were larger than the differences in scanners. GM/WM ratio of attenuation was significantly lower by PMCT than by AMCT at all levels (P<0.0001). PMCT showed an increase in WM attenuation, loss of GM-WM differentiation, and brain swelling, evidenced by a decrease in the size of ventricles and sulci.

[Post-ischemic innate immunity and its application for novel therapeutic strategy targeting brain inflammation].

PubMed

Ito, Minako; Kondo, Taisuke; Shichita, Takashi; Yoshimura, Akihiko

2013-07-01

Stroke or brain ischemia is one of the major causes of death and disability worldwide. Post-ischemic inflammation is an essential step in the progression of brain ischemia-reperfusion injury. In a mouse stroke model, we have reported that IL-23 produced from infiltrating macrophages induces IL-17 producing T cells. IL-17 is mainly produced from gammadeltaT cells and promotes delayed (day 3-4) ischemic brain damage. We also demonstrated that peroxiredoxin (Prx) family proteins released extracellularly from necrotic brain cells induce expression of inflammatory cytokines including IL-23 in macrophages through activation of Toll-like receptor 2(TLR2) and TLR4, thereby promoting neural cell death. We thus propose that regulation of the IL-23-IL-17 axis including gammadeltaT cells, macrophages, and extracellular Prxs could be a potent neuroprotective tool.

Brain-dead patients are not cadavers: the need to revise the definition of death in Muslim communities.

PubMed

Rady, Mohamed Y; Verheijde, Joseph L

2013-03-01

The utilitarian construct of two alternative criteria of human death increases the supply of transplantable organs at the end of life. Neither the neurological criterion (heart-beating donation) nor the circulatory criterion (non-heart-beating donation) is grounded in scientific evidence but based on philosophical reasoning. A utilitarian death definition can have unintended consequences for dying Muslim patients: (1) the expedited process of determining death for retrieval of transplantable organs can lead to diagnostic errors, (2) the equivalence of brain death with human death may be incorrect, and (3) end-of-life religious values and traditional rituals may be sacrificed. Therefore, it is imperative to reevaluate the two different types and criteria of death introduced by the Resolution (Fatwa) of the Council of Islamic Jurisprudence on Resuscitation Apparatus in 1986. Although we recognize that this Fatwa was based on best scientific evidence available at that time, more recent evidence shows that it rests on outdated knowledge and understanding of the phenomenon of human death. We recommend redefining death in Islam to reaffirm the singularity of this biological phenomenon as revealed in the Quran 14 centuries ago.

Organismal death, the dead-donor rule and the ethics of vital organ procurement.

PubMed

Symons, Xavier; Chua, Reginald Mary

2018-06-19

Several bioethicists have recently discussed the complexity of defining human death, and considered in particular how our definition of death affects our understanding of the ethics of vital organ procurement. In this brief paper, we challenge the mainstream medical definition of human death-namely, that death is equivalent to total brain failure-and argue with Nair-Collins and Miller that integrated biological functions can continue even after total brain failure has occurred. We discuss the implications of Nair-Collins and Miller's argument and suggest that it may be necessary to look for alternative biological markers that reliably indicate the death of a human being. We reject the suggestion that we should abandon the dead-donor criteria for organ donation. Rather than weaken the ethical standards for vital organ procurement, it may be necessary to make them more demanding. The aim of this paper is not to justify the dead donor rule. Rather, we aim to explore the perspective of those who agree with critiques of the whole brain and cardiopulmonary definitions of death but yet disagree with the proposal that we should abandon the dead-donor rule. We will consider what those who want to retain the dead-donor rule must argue in light of Nair-Collins and Miller's critique. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Deaths among adult patients with hypopituitarism: hypocortisolism during acute stress, and de novo malignant brain tumors contribute to an increased mortality.

PubMed

Burman, P; Mattsson, A F; Johannsson, G; Höybye, C; Holmer, H; Dahlqvist, P; Berinder, K; Engström, B E; Ekman, B; Erfurth, E M; Svensson, J; Wahlberg, J; Karlsson, F A

2013-04-01

Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified. To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up. All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed. Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up. An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy. Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease.

Knowledge of the Concept of Encephalic Death: Is This an Obstacle in the Acceptance of Donation and Transplantation of Organs Among Students of Nursing at the Medical University of Warsaw in Poland?

PubMed

Mikla, M; Rios, A; Lopez-Navas, A; Gotlib, J; Kilanska, D; Martinez-Alarcón, L; Ramis, G; Ramirez, P; Lopez Montesinos, M J

2016-09-01

The knowledge and acceptance of the concept of brain death among future health professionals is essential. The objective of this study was to analyze the knowledge of the concept of brain death among nursing students at the Medical University of Warsaw and determine the factors that affect it. Academic year 2011-2012, nursing students of the University of Poland. Sampling points in 5 compulsory-attendance nursing courses with a completion rate >80%. Validated questionnaire (PCID-DTO Rios), anonymous and self-administered. The completion rate was 96% (793/828); 71% (n = 561) knew the concept of brain death, 22% (n = 178) did not know it, and 7% (n = 54) did not know that it implies the death of the patient. Variables related to the correct knowledge: 1) to be studying in 4th year compared with 1st year (85% vs 60%; P ≤ .001); 2) discuss the subject with family (76% vs 61%; P ≤ .001); 3) discuss with friends (73% vs 63%; P = .009); and 4) having a favorable attitude toward organ donation (74% vs 65%; P = .011). In the multivariate analysis, the variables that remained independent were studying in 4th year (odds ratio [OR], 3.809; 95% confidence interval [CI], 2.006-5.823; P ≤ .001) and discussed with family concerning donation and transplantation (OR, 1.718; 95% CI, 1.241-2.381; P ≤ .001). One-third of the nursing students were unfamiliar with the concept of brain death. Copyright © 2016 Elsevier Inc. All rights reserved.

Mitochondrial mechanisms of neuronal rescue by F-68, a hydrophilic Pluronic block co-polymer, following acute substrate deprivation.

PubMed

Wang, Janice C; Bindokas, Vytautas P; Skinner, Matthew; Emrick, Todd; Marks, Jeremy D

2017-10-01

Global brain ischemia can lead to widespread neuronal death and poor neurologic outcomes in patients. Despite detailed understanding of the cellular and molecular mechanisms mediating neuronal death following focal and global brain hypoxia-ischemia, treatments to reduce ischemia-induced brain injury remain elusive. One pathway central to neuronal death following global brain ischemia is mitochondrial dysfunction, one consequence of which is the cascade of intracellular events leading to mitochondrial outer membrane permeabilization. A novel approach to rescuing injured neurons from death involves targeting cellular membranes using a class of synthetic molecules called Pluronics. Pluronics are triblock copolymers of hydrophilic poly[ethylene oxide] (PEO) and hydrophobic poly[propylene oxide] (PPO). Evidence is accumulating to suggest that hydrophilic Pluronics rescue injured neurons from death following substrate deprivation by preventing mitochondrial dysfunction. Here, we will review current understanding of the nature of interaction of Pluronic molecules with biological membranes and the efficacy of F-68, an 80% hydrophilic Pluronic, in rescuing neurons from injury. We will review data indicating that F-68 reduces mitochondrial dysfunction and mitochondria-dependent death pathways in a model of neuronal injury in vitro, and present new evidence that F-68 acts directly on mitochondria to inhibit mitochondrial outer membrane permeabilization. Finally, we will present results of a pilot, proof-of-principle study suggesting that F-68 is effective in reducing hippocampal injury induced by transient global ischemia in vivo. By targeting mitochondrial dysfunction, F-68 and other Pluronic molecules constitute an exciting new approach to rescuing neurons from acute injury. Copyright © 2017 Elsevier Ltd. All rights reserved.

The “Visual Shock” of Francis Bacon: an essay in neuroesthetics

PubMed Central

Zeki, Semir; Ishizu, Tomohiro

2013-01-01

In this paper we discuss the work of Francis Bacon in the context of his declared aim of giving a “visual shock.”We explore what this means in terms of brain activity and what insights into the brain's visual perceptive system his work gives. We do so especially with reference to the representation of faces and bodies in the human visual brain. We discuss the evidence that shows that both these categories of stimuli have a very privileged status in visual perception, compared to the perception of other stimuli, including man-made artifacts such as houses, chairs, and cars. We show that viewing stimuli that depart significantly from a normal representation of faces and bodies entails a significant difference in the pattern of brain activation. We argue that Bacon succeeded in delivering his “visual shock” because he subverted the normal neural representation of faces and bodies, without at the same time subverting the representation of man-made artifacts. PMID:24339812

The "Visual Shock" of Francis Bacon: an essay in neuroesthetics.

PubMed

Zeki, Semir; Ishizu, Tomohiro

2013-01-01

In this paper we discuss the work of Francis Bacon in the context of his declared aim of giving a "visual shock."We explore what this means in terms of brain activity and what insights into the brain's visual perceptive system his work gives. We do so especially with reference to the representation of faces and bodies in the human visual brain. We discuss the evidence that shows that both these categories of stimuli have a very privileged status in visual perception, compared to the perception of other stimuli, including man-made artifacts such as houses, chairs, and cars. We show that viewing stimuli that depart significantly from a normal representation of faces and bodies entails a significant difference in the pattern of brain activation. We argue that Bacon succeeded in delivering his "visual shock" because he subverted the normal neural representation of faces and bodies, without at the same time subverting the representation of man-made artifacts.

A small frog that makes a big difference: brain wave testing of TV advertisements.

PubMed

Ohme, Rafal; Matukin, Michal

2012-01-01

It is important for the marketing industry to better understand the role of the unconscious and emotions in advertising communication and shopping behavior. Yet, traditional consumer research is not enough for such a purpose. Conventional paper-and-pencil or verbal declarations favor conscious pragmatism and functionality as the principles underlying consumer decisions and motives. These approaches should be combined with an emerging discipline (consumer neuroscience or neuromarketing) to examine the brain and its functioning in the context of consumer choices. It has been widely acknowledged that patterns of brain activity are closely related to consumers cognition and behavior. Thus, the analysis of consumers neurophysiology may increase the understanding of how consumers process incoming information and how they use their memory and react emotionally (See "Three Types of Brain Wave Research on TV Advertisements"): Moreover, as the majority of consumer mental processes occur below the level of conscious awareness, observations of the brain reactions enable researchers to reach the very core (which is consciously inaccessible) foundations of consumer decisions, emotions, motivations, and preferences.

Annual report to the nation on the status of cancer, 1975-2007, featuring tumors of the brain and other nervous system.

PubMed

Kohler, Betsy A; Ward, Elizabeth; McCarthy, Bridget J; Schymura, Maria J; Ries, Lynn A G; Eheman, Christie; Jemal, Ahmedin; Anderson, Robert N; Ajani, Umed A; Edwards, Brenda K

2011-05-04

The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute, and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information on cancer occurrence and trends in the United States. This year's report highlights brain and other nervous system (ONS) tumors, including nonmalignant brain tumors, which became reportable on a national level in 2004. Cancer incidence data were obtained from the National Cancer Institute, CDC, and NAACCR, and information on deaths was obtained from the CDC's National Center for Health Statistics. The annual percentage changes in age-standardized incidence and death rates (2000 US population standard) for all cancers combined and for the top 15 cancers for men and for women were estimated by joinpoint analysis of long-term (1992-2007 for incidence; 1975-2007 for mortality) trends and short-term fixed interval (1998-2007) trends. Analyses of malignant neuroepithelial brain and ONS tumors were based on data from 1980-2007; data on nonmalignant tumors were available for 2004-2007. All statistical tests were two-sided. Overall cancer incidence rates decreased by approximately 1% per year; the decrease was statistically significant (P < .05) in women, but not in men, because of a recent increase in prostate cancer incidence. The death rates continued to decrease for both sexes. Childhood cancer incidence rates continued to increase, whereas death rates continued to decrease. Lung cancer death rates decreased in women for the first time during 2003-2007, more than a decade after decreasing in men. During 2004-2007, more than 213 500 primary brain and ONS tumors were diagnosed, and 35.8% were malignant. From 1987-2007, the incidence of neuroepithelial malignant brain and ONS tumors decreased by 0.4% per year in men and women combined. The decrease in cancer incidence and mortality reflects progress in cancer prevention, early detection, and treatment. However, major challenges remain, including increasing incidence rates and continued low survival for some cancers. Malignant and nonmalignant brain tumors demonstrate differing patterns of occurrence by sex, age, and race, and exhibit considerable biologic diversity. Inclusion of nonmalignant brain tumors in cancer registries provides a fuller assessment of disease burden and medical resource needs associated with these unique tumors.

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

PubMed

Murray, Christopher J L; Ortblad, Katrina F; Guinovart, Caterina; Lim, Stephen S; Wolock, Timothy M; Roberts, D Allen; Dansereau, Emily A; Graetz, Nicholas; Barber, Ryan M; Brown, Jonathan C; Wang, Haidong; Duber, Herbert C; Naghavi, Mohsen; Dicker, Daniel; Dandona, Lalit; Salomon, Joshua A; Heuton, Kyle R; Foreman, Kyle; Phillips, David E; Fleming, Thomas D; Flaxman, Abraham D; Phillips, Bryan K; Johnson, Elizabeth K; Coggeshall, Megan S; Abd-Allah, Foad; Abera, Semaw Ferede; Abraham, Jerry P; Abubakar, Ibrahim; Abu-Raddad, Laith J; Abu-Rmeileh, Niveen Me; Achoki, Tom; Adeyemo, Austine Olufemi; Adou, Arsène Kouablan; Adsuar, José C; Agardh, Emilie Elisabet; Akena, Dickens; Al Kahbouri, Mazin J; Alasfoor, Deena; Albittar, Mohammed I; Alcalá-Cerra, Gabriel; Alegretti, Miguel Angel; Alemu, Zewdie Aderaw; Alfonso-Cristancho, Rafael; Alhabib, Samia; Ali, Raghib; Alla, Francois; Allen, Peter J; Alsharif, Ubai; Alvarez, Elena; Alvis-Guzman, Nelson; Amankwaa, Adansi A; Amare, Azmeraw T; Amini, Hassan; Ammar, Walid; Anderson, Benjamin O; Antonio, Carl Abelardo T; Anwari, Palwasha; Arnlöv, Johan; Arsenijevic, Valentina S Arsic; Artaman, Ali; Asghar, Rana J; Assadi, Reza; Atkins, Lydia S; Badawi, Alaa; Balakrishnan, Kalpana; Banerjee, Amitava; Basu, Sanjay; Beardsley, Justin; Bekele, Tolesa; Bell, Michelle L; Bernabe, Eduardo; Beyene, Tariku Jibat; Bhala, Neeraj; Bhalla, Ashish; Bhutta, Zulfiqar A; Abdulhak, Aref Bin; Binagwaho, Agnes; Blore, Jed D; Basara, Berrak Bora; Bose, Dipan; Brainin, Michael; Breitborde, Nicholas; Castañeda-Orjuela, Carlos A; Catalá-López, Ferrán; Chadha, Vineet K; Chang, Jung-Chen; Chiang, Peggy Pei-Chia; Chuang, Ting-Wu; Colomar, Mercedes; Cooper, Leslie Trumbull; Cooper, Cyrus; Courville, Karen J; Cowie, Benjamin C; Criqui, Michael H; Dandona, Rakhi; Dayama, Anand; De Leo, Diego; Degenhardt, Louisa; Del Pozo-Cruz, Borja; Deribe, Kebede; Des Jarlais, Don C; Dessalegn, Muluken; Dharmaratne, Samath D; Dilmen, Uğur; Ding, Eric L; Driscoll, Tim R; Durrani, Adnan M; Ellenbogen, Richard G; Ermakov, Sergey Petrovich; Esteghamati, Alireza; Faraon, Emerito Jose A; Farzadfar, Farshad; Fereshtehnejad, Seyed-Mohammad; Fijabi, Daniel Obadare; Forouzanfar, Mohammad H; Fra Paleo, Urbano; Gaffikin, Lynne; Gamkrelidze, Amiran; Gankpé, Fortuné Gbètoho; Geleijnse, Johanna M; Gessner, Bradford D; Gibney, Katherine B; Ginawi, Ibrahim Abdelmageem Mohamed; Glaser, Elizabeth L; Gona, Philimon; Goto, Atsushi; Gouda, Hebe N; Gugnani, Harish Chander; Gupta, Rajeev; Gupta, Rahul; Hafezi-Nejad, Nima; Hamadeh, Randah Ribhi; Hammami, Mouhanad; Hankey, Graeme J; Harb, Hilda L; Haro, Josep Maria; Havmoeller, Rasmus; Hay, Simon I; Hedayati, Mohammad T; Pi, Ileana B Heredia; Hoek, Hans W; Hornberger, John C; Hosgood, H Dean; Hotez, Peter J; Hoy, Damian G; Huang, John J; Iburg, Kim M; Idrisov, Bulat T; Innos, Kaire; Jacobsen, Kathryn H; Jeemon, Panniyammakal; Jensen, Paul N; Jha, Vivekanand; Jiang, Guohong; Jonas, Jost B; Juel, Knud; Kan, Haidong; Kankindi, Ida; Karam, Nadim E; Karch, André; Karema, Corine Kakizi; Kaul, Anil; Kawakami, Norito; Kazi, Dhruv S; Kemp, Andrew H; Kengne, Andre Pascal; Keren, Andre; Kereselidze, Maia; Khader, Yousef Saleh; Khalifa, Shams Eldin Ali Hassan; Khan, Ejaz Ahmed; Khang, Young-Ho; Khonelidze, Irma; Kinfu, Yohannes; Kinge, Jonas M; Knibbs, Luke; Kokubo, Yoshihiro; Kosen, S; Defo, Barthelemy Kuate; Kulkarni, Veena S; Kulkarni, Chanda; Kumar, Kaushalendra; Kumar, Ravi B; Kumar, G Anil; Kwan, Gene F; Lai, Taavi; Balaji, Arjun Lakshmana; Lam, Hilton; Lan, Qing; Lansingh, Van C; Larson, Heidi J; Larsson, Anders; Lee, Jong-Tae; Leigh, James; Leinsalu, Mall; Leung, Ricky; Li, Yichong; Li, Yongmei; De Lima, Graça Maria Ferreira; Lin, Hsien-Ho; Lipshultz, Steven E; Liu, Shiwei; Liu, Yang; Lloyd, Belinda K; Lotufo, Paulo A; Machado, Vasco Manuel Pedro; Maclachlan, Jennifer H; Magis-Rodriguez, Carlos; Majdan, Marek; Mapoma, Christopher Chabila; Marcenes, Wagner; Marzan, Melvin Barrientos; Masci, Joseph R; Mashal, Mohammad Taufiq; Mason-Jones, Amanda J; Mayosi, Bongani M; Mazorodze, Tasara T; Mckay, Abigail Cecilia; Meaney, Peter A; Mehndiratta, Man Mohan; Mejia-Rodriguez, Fabiola; Melaku, Yohannes Adama; Memish, Ziad A; Mendoza, Walter; Miller, Ted R; Mills, Edward J; Mohammad, Karzan Abdulmuhsin; Mokdad, Ali H; Mola, Glen Liddell; Monasta, Lorenzo; Montico, Marcella; Moore, Ami R; Mori, Rintaro; Moturi, Wilkister Nyaora; Mukaigawara, Mitsuru; Murthy, Kinnari S; Naheed, Aliya; Naidoo, Kovin S; Naldi, Luigi; Nangia, Vinay; Narayan, K M Venkat; Nash, Denis; Nejjari, Chakib; Nelson, Robert G; Neupane, Sudan Prasad; Newton, Charles R; Ng, Marie; Nisar, Muhammad Imran; Nolte, Sandra; Norheim, Ole F; Nowaseb, Vincent; Nyakarahuka, Luke; Oh, In-Hwan; Ohkubo, Takayoshi; Olusanya, Bolajoko O; Omer, Saad B; Opio, John Nelson; Orisakwe, Orish Ebere; Pandian, Jeyaraj D; Papachristou, Christina; Caicedo, Angel J Paternina; Patten, Scott B; Paul, Vinod K; Pavlin, Boris Igor; Pearce, Neil; Pereira, David M; Pervaiz, Aslam; Pesudovs, Konrad; Petzold, Max; Pourmalek, Farshad; Qato, Dima; Quezada, Amado D; Quistberg, D Alex; Rafay, Anwar; Rahimi, Kazem; Rahimi-Movaghar, Vafa; Ur Rahman, Sajjad; Raju, Murugesan; Rana, Saleem M; Razavi, Homie; Reilly, Robert Quentin; Remuzzi, Giuseppe; Richardus, Jan Hendrik; Ronfani, Luca; Roy, Nobhojit; Sabin, Nsanzimana; Saeedi, Mohammad Yahya; Sahraian, Mohammad Ali; Samonte, Genesis May J; Sawhney, Monika; Schneider, Ione J C; Schwebel, David C; Seedat, Soraya; Sepanlou, Sadaf G; Servan-Mori, Edson E; Sheikhbahaei, Sara; Shibuya, Kenji; Shin, Hwashin Hyun; Shiue, Ivy; Shivakoti, Rupak; Sigfusdottir, Inga Dora; Silberberg, Donald H; Silva, Andrea P; Simard, Edgar P; Singh, Jasvinder A; Skirbekk, Vegard; Sliwa, Karen; Soneji, Samir; Soshnikov, Sergey S; Sreeramareddy, Chandrashekhar T; Stathopoulou, Vasiliki Kalliopi; Stroumpoulis, Konstantinos; Swaminathan, Soumya; Sykes, Bryan L; Tabb, Karen M; Talongwa, Roberto Tchio; Tenkorang, Eric Yeboah; Terkawi, Abdullah Sulieman; Thomson, Alan J; Thorne-Lyman, Andrew L; Towbin, Jeffrey A; Traebert, Jefferson; Tran, Bach X; Dimbuene, Zacharie Tsala; Tsilimbaris, Miltiadis; Uchendu, Uche S; Ukwaja, Kingsley N; Uzun, Selen Begüm; Vallely, Andrew J; Vasankari, Tommi J; Venketasubramanian, N; Violante, Francesco S; Vlassov, Vasiliy Victorovich; Vollset, Stein Emil; Waller, Stephen; Wallin, Mitchell T; Wang, Linhong; Wang, XiaoRong; Wang, Yanping; Weichenthal, Scott; Weiderpass, Elisabete; Weintraub, Robert G; Westerman, Ronny; White, Richard A; Wilkinson, James D; Williams, Thomas Neil; Woldeyohannes, Solomon Meseret; Wong, John Q; Xu, Gelin; Yang, Yang C; Yano, Yuichiro; Yentur, Gokalp Kadri; Yip, Paul; Yonemoto, Naohiro; Yoon, Seok-Jun; Younis, Mustafa; Yu, Chuanhua; Jin, Kim Yun; El Sayed Zaki, Maysaa; Zhao, Yong; Zheng, Yingfeng; Zhou, Maigeng; Zhu, Jun; Zou, Xiao Nong; Lopez, Alan D; Vos, Theo

2014-09-13

The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. Bill & Melinda Gates Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

PubMed Central

Ortblad, Katrina F; Guinovart, Caterina; Lim, Stephen S; Wolock, Timothy M; Roberts, D Allen; Dansereau, Emily A; Graetz, Nicholas; Barber, Ryan M; Brown, Jonathan C; Wang, Haidong; Duber, Herbert C; Naghavi, Mohsen; Dicker, Daniel; Dandona, Lalit; Salomon, Joshua A; Heuton, Kyle R; Foreman, Kyle; Phillips, David E; Fleming, Thomas D; Flaxman, Abraham D; Phillips, Bryan K; Johnson, Elizabeth K; Coggeshall, Megan S; Abd-Allah, Foad; Ferede, Semaw; Abraham, Jerry P; Abubakar, Ibrahim; Abu-Raddad, Laith J; Abu-Rmeileh, Niveen Me; Achoki, Tom; Adeyemo, Austine Olufemi; Adou, Arsène Kouablan; Adsuar, José C; Agardh, Emilie Elisabet; Akena, Dickens; Al Kahbouri, Mazin J; Alasfoor, Deena; Albittar, Mohammed I; Alcalá-Cerra, Gabriel; Alegretti, Miguel Angel; Alemu, Zewdie Aderaw; Alfonso-Cristancho, Rafael; Alhabib, Samia; Ali, Raghib; Alla, Francois; Allen, Peter J; Alsharif, Ubai; Alvarez, Elena; Alvis-Guzman, Nelson; Amankwaa, Adansi A; Amare, Azmeraw T; Amini, Hassan; Ammar, Walid; Anderson, Benjamin O; Antonio, Carl Abelardo T; Anwari, Palwasha; Ärnlöv, Johan; Arsenijevic, Valentina S Arsic; Artaman, Ali; Asghar, Rana J; Assadi, Reza; Atkins, Lydia S; Badawi, Alaa; Balakrishnan, Kalpana; Banerjee, Amitava; Basu, Sanjay; Beardsley, Justin; Bekele, Tolesa; Bell, Michelle L; Bernabe, Eduardo; Beyene, Tariku Jibat; Bhala, Neeraj; Bhalla, Ashish; Bhutta, Zulfiqar A; Abdulhak, Aref Bin; Binagwaho, Agnes; Blore, Jed D; Basara, Berrak Bora; Bose, Dipan; Brainin, Michael; Breitborde, Nicholas; Castañeda-Orjuela, Carlos A; Catalá-López, Ferrán; Chadha, Vineet K; Chang, Jung-Chen; Chiang, Peggy Pei-Chia; Chuang, Ting-Wu; Colomar, Mercedes; Cooper, Leslie Trumbull; Cooper, Cyrus; Courville, Karen J; Cowie, Benjamin C; Criqui, Michael H; Dandona, Rakhi; Dayama, Anand; De Leo, Diego; Degenhardt, Louisa; Del Pozo-Cruz, Borja; Deribe, Kebede; Jarlais, Don C Des; Dessalegn, Muluken; Dharmaratne, Samath D; Dilmen, Uğur; Ding, Eric L; Driscoll, Tim R; Durrani, Adnan M; Ellenbogen, Richard G; Ermakov, Sergey Petrovich; Esteghamati, Alireza; Faraon, Emerito Jose A; Farzadfar, Farshad; Fereshtehnejad, Seyed-Mohammad; Fijabi, Daniel Obadare; Forouzanfar, Mohammad H; Paleo, Urbano Fra.; Gaffikin, Lynne; Gamkrelidze, Amiran; Gankpé, Fortuné Gbètoho; Geleijnse, Johanna M; Gessner, Bradford D; Gibney, Katherine B; Ginawi, Ibrahim Abdelmageem Mohamed; Glaser, Elizabeth L; Gona, Philimon; Goto, Atsushi; Gouda, Hebe N; Gugnani, Harish Chander; Gupta, Rajeev; Gupta, Rahul; Hafezi-Nejad, Nima; Hamadeh, Randah Ribhi; Hammami, Mouhanad; Hankey, Graeme J; Harb, Hilda L; Haro, Josep Maria; Havmoeller, Rasmus; Hay, Simon I; Hedayati, Mohammad T; Pi, Ileana B Heredia; Hoek, Hans W; Hornberger, John C; Hosgood, H Dean; Hotez, Peter J; Hoy, Damian G; Huang, John J; Iburg, Kim M; Idrisov, Bulat T; Innos, Kaire; Jacobsen, Kathryn H; Jeemon, Panniyammakal; Jensen, Paul N; Jha, Vivekanand; Jiang, Guohong; Jonas, Jost B; Juel, Knud; Kan, Haidong; Kankindi, Ida; Karam, Nadim E; Karch, André; Karema, Corine Kakizi; Kaul, Anil; Kawakami, Norito; Kazi, Dhruv S; Kemp, Andrew H; Kengne, Andre Pascal; Keren, Andre; Kereselidze, Maia; Khader, Yousef Saleh; Khalifa, Shams Eldin Ali Hassan; Khan, Ejaz Ahmed; Khang, Young-Ho; Khonelidze, Irma; Kinfu, Yohannes; Kinge, Jonas M; Knibbs, Luke; Kokubo, Yoshihiro; Kosen, S; Defo, Barthelemy Kuate; Kulkarni, Veena S; Kulkarni, Chanda; Kumar, Kaushalendra; Kumar, Ravi B; Kumar, G Anil; Kwan, Gene F; Lai, Taavi; Balaji, Arjun Lakshmana; Lam, Hilton; Lan, Qing; Lansingh, Van C; Larson, Heidi J; Larsson, Anders; Lee, Jong-Tae; Leigh, James; Leinsalu, Mall; Leung, Ricky; Li, Yichong; Li, Yongmei; De Lima, Graça Maria Ferreira; Lin, Hsien-Ho; Lipshultz, Steven E; Liu, Shiwei; Liu, Yang; Lloyd, Belinda K; Lotufo, Paulo A; Machado, Vasco Manuel Pedro; Maclachlan, Jennifer H; Magis-Rodriguez, Carlos; Majdan, Marek; Mapoma, Christopher Chabila; Marcenes, Wagner; Marzan, Melvin Barrientos; Masci, Joseph R; Mashal, Mohammad Taufiq; Mason-Jones, Amanda J; Mayosi, Bongani M; Mazorodze, Tasara T; Mckay, Abigail Cecilia; Meaney, Peter A; Mehndiratta, Man Mohan; Mejia-Rodriguez, Fabiola; Melaku, Yohannes Adama; Memish, Ziad A; Mendoza, Walter; Miller, Ted R; Mills, Edward J; Mohammad, Karzan Abdulmuhsin; Mokdad, Ali H; Mola, Glen Liddell; Monasta, Lorenzo; Montico, Marcella; Moore, Ami R; Mori, Rintaro; Moturi, Wilkister Nyaora; Mukaigawara, Mitsuru; Murthy, Kinnari S; Naheed, Aliya; Naidoo, Kovin S; Naldi, Luigi; Nangia, Vinay; Narayan, K M Venkat; Nash, Denis; Nejjari, Chakib; Nelson, Robert G; Neupane, Sudan Prasad; Newton, Charles R; Ng, Marie; Nisar, Muhammad Imran; Nolte, Sandra; Norheim, Ole F; Nowaseb, Vincent; Nyakarahuka, Luke; Oh, In-Hwan; Ohkubo, Takayoshi; Olusanya, Bolajoko O; Omer, Saad B; Opio, John Nelson; Orisakwe, Orish Ebere; Pandian, Jeyaraj D; Papachristou, Christina; Caicedo, Angel J Paternina; Patten, Scott B; Paul, Vinod K; Pavlin, Boris Igor; Pearce, Neil; Pereira, David M; Pervaiz, Aslam; Pesudovs, Konrad; Petzold, Max; Pourmalek, Farshad; Qato, Dima; Quezada, Amado D; Quistberg, D Alex; Rafay, Anwar; Rahimi, Kazem; Rahimi-Movaghar, Vafa; Rahman, Sajjad Ur; Raju, Murugesan; Rana, Saleem M; Razavi, Homie; Reilly, Robert Quentin; Remuzzi, Giuseppe; Richardus, Jan Hendrik; Ronfani, Luca; Roy, Nobhojit; Sabin, Nsanzimana; Saeedi, Mohammad Yahya; Sahraian, Mohammad Ali; Samonte, Genesis May J; Sawhney, Monika; Schneider, Ione J C; Schwebel, David C; Seedat, Soraya; Sepanlou, Sadaf G; Servan-Mori, Edson E; Sheikhbahaei, Sara; Shibuya, Kenji; Shin, Hwashin Hyun; Shiue, Ivy; Shivakoti, Rupak; Sigfusdottir, Inga Dora; Silberberg, Donald H; Silva, Andrea P; Simard, Edgar P; Singh, Jasvinder A; Skirbekk, Vegard; Sliwa, Karen; Soneji, Samir; Soshnikov, Sergey S; Sreeramareddy, Chandrashekhar T; Stathopoulou, Vasiliki Kalliopi; Stroumpoulis, Konstantinos; Swaminathan, Soumya; Sykes, Bryan L; Tabb, Karen M; Talongwa, Roberto Tchio; Tenkorang, Eric Yeboah; Terkawi, Abdullah Sulieman; Thomson, Alan J; Thorne-Lyman, Andrew L; Towbin, Jeffrey A; Traebert, Jefferson; Tran, Bach X; Dimbuene, Zacharie Tsala; Tsilimbaris, Miltiadis; Uchendu, Uche S; Ukwaja, Kingsley N; Uzun, Selen Begüm; Vallely, Andrew J; Vasankari, Tommi J; Venketasubramanian, N; Violante, Francesco S; Vlassov, Vasiliy Victorovich; Vollset, Stein Emil; Waller, Stephen; Wallin, Mitchell T; Wang, Linhong; Wang, XiaoRong; Wang, Yanping; Weichenthal, Scott; Weiderpass, Elisabete; Weintraub, Robert G; Westerman, Ronny; White, Richard A; Wilkinson, James D; Williams, Thomas Neil; Woldeyohannes, Solomon Meseret; Wong, John Q; Xu, Gelin; Yang, Yang C; Yano, Yuichiro; Yentur, Gokalp Kadri; Yip, Paul; Yonemoto, Naohiro; Yoon, Seok-Jun; Younis, Mustafa; Yu, Chuanhua; Jin, Kim Yun; El Sayed Zaki, Maysaa; Zhao, Yong; Zheng, Yingfeng; Zhou, Maigeng; Zhu, Jun; Zou, Xiao Nong; Lopez, Alan D; Vos, Theo

2014-01-01

Summary Background The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occurred since the Millennium Declaration. Methods To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010–13) of incidence, drug resistance, and coverage of insecticide-treated bednets. Findings Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. Interpretation Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS’s estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. Funding Bill & Melinda Gates Foundation. PMID:25059949

Characterization of Death in Neonatal Encephalopathy in the Hypothermia Era.

PubMed

Lemmon, Monica E; Boss, Renee D; Bonifacio, Sonia L; Foster-Barber, Audrey; Barkovich, A James; Glass, Hannah C

2017-03-01

This study aimed to characterize the circumstances of death in encephalopathic neonates treated with therapeutic hypothermia. Patients who died after or during treatment with therapeutic hypothermia between 2007-2014 were identified. Patient circumstance of death was characterized using an established paradigm. Thirty-one of 229 patients died (14%) at a median of 3 days of life. Most who died were severely encephalopathic on examination (90%) and had severely abnormal electroencephalographic (EEG) findings (87%). All those who had magnetic resonance images (n = 13) had evidence of moderate-severe brain injury; 6 had near-total brain injury. Cooling was discontinued prematurely in 61% of patients. Most patients (90%) were physiologically stable at the time of death; 81% died following elective extubation for quality of life considerations. Three patients (10%) died following withholding or removal of artificial hydration and nutrition. Characterization of death in additional cohorts is needed to identify differences in decision making practices over time and between centers.

Life and death of neurons in the aging brain

NASA Technical Reports Server (NTRS)

Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)

1997-01-01

Neurodegenerative disorders are characterized by extensive neuron death that leads to functional decline, but the neurobiological correlates of functional decline in normal aging are less well defined. For decades, it has been a commonly held notion that widespread neuron death in the neocortex and hippocampus is an inevitable concomitant of brain aging, but recent quantitative studies suggest that neuron death is restricted in normal aging and unlikely to account for age-related impairment of neocortical and hippocampal functions. In this article, the qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored. When these data are viewed comprehensively, it appears that the primary neurobiological substrates for functional impairment in aging differ in important ways from those in neurodegenerative disorders such as Alzheimer's disease.

[Causes of the people death from drunkenness and alcoholism].

PubMed

Erokhin, Iu A; Paukov, V S; Kirillov, Iu A

2012-01-01

We analyzed causes of 1008 people death, who abused by alcohol. Among them 2 groups were separated out: people died due to drunkenness and due to alcoholism. The structure of the death was similar in the both groups, however depended on alcoholism stages. The major cause of the death in group of drunkenness people was acute heart insufficiency, less commonly--lung pathology, and very rarely--brain vessels pathology and liver cirrhosis. In group of people, who died due to alcoholism, lung pathology was the major cause of these deaths, acute heart insufficiency was occurred less commonly, and very rare brain pathology because of delirium tremens or alcohol withdrawal syndrome, as so liver cirrhosis with complications. Hemorrhagic pancreonecrosis after alcoholic excess was found out in both groups, but it was more often in people, who died due to drunkenness. Obtained results show importance of chronic alcoholism identification as a disease with several stages including drunkenness and alcoholism.

Cylindromatosis mediates neuronal cell death in vitro and in vivo.

PubMed

Ganjam, Goutham K; Terpolilli, Nicole Angela; Diemert, Sebastian; Eisenbach, Ina; Hoffmann, Lena; Reuther, Christina; Herden, Christiane; Roth, Joachim; Plesnila, Nikolaus; Culmsee, Carsten

2018-01-19

The tumor-suppressor cylindromatosis (CYLD) is a deubiquitinating enzyme and key regulator of cell proliferation and inflammation. A genome-wide siRNA screen linked CYLD to receptor interacting protein-1 (RIP1) kinase-mediated necroptosis; however, the exact mechanisms of CYLD-mediated cell death remain unknown. Therefore, we investigated the precise role of CYLD in models of neuronal cell death in vitro and evaluated whether CYLD deletion affects brain injury in vivo. In vitro, downregulation of CYLD increased RIP1 ubiquitination, prevented RIP1/RIP3 complex formation, and protected neuronal cells from oxidative death. Similar protective effects were achieved by siRNA silencing of RIP1 or RIP3 or by pharmacological inhibition of RIP1 with necrostatin-1. In vivo, CYLD knockout mice were protected from trauma-induced brain damage compared to wild-type littermate controls. These findings unravel the mechanisms of CYLD-mediated cell death signaling in damaged neurons in vitro and suggest a cell death-mediating role of CYLD in vivo.

A Study on Nursing Students' Knowledge, Attitude, and Educational Needs for Brain-Death Organ Transplantation and Donation and Intent to Donate Organs.

PubMed

Ju, M K; Sim, M K; Son, S Y

2018-05-01

The purpose of this study was to identify the knowledge, attitude, educational needs, and will of nursing students on organ donation from brain-dead donors. Data were collected by using a 40-item questionnaire to measure knowledge, attitude, educational needs, and will for organ donation of 215 nursing college students in one university in Dangjin city from May 11 to May 31, 2017. The data were analyzed using SPSS 22 program (Data Solution Inc, Seoul). In the general characteristics, 85.1% of the subjects did not receive education on donation, and 99.5% of the subjects responded that education is needed. The desired methods of education were special lecture in school (55.3%), "webtoons" on the Internet (19.5%), formal curriculum (15.8%). Points to improve to increase brain-death organ transplantation and donation included "active publicity through pan-national campaign activities" (56.3%), "respecting prior consent from brain-dead donors" (21.9%), and "encouragement and increased support for organ donors" (12.1%). There was a significant difference in knowledge according to will for organ donation (t = 3.29, P = .001) and consent to brain-death organ donation in family members (t = 3.29, P = .001). There was a statistically significant positive correlation between attitude and knowledge of the subjects regarding brain-death organ donation. The knowledge, attitude, educational need, and will for organ donation of nursing students revealed in this study will be used as basic data to provide systematic transplant education including contents about organ transplantation in the regular nursing curriculum in the future. It will contribute to the activation of organ donation. Copyright © 2018 Elsevier Inc. All rights reserved.

Inhibition of activated NR2B gene- and caspase-3 protein-expression by glutathione following traumatic brain injury in a rat model

PubMed Central

Arifin, Muhammad Zafrullah; Faried, Ahmad; Shahib, Muhammad Nurhalim; Wiriadisastra, Kahdar; Bisri, Tatang

2011-01-01

Background. Traumatic brain injury (TBI) remains a major cause of death and disability. Oxidative stress is an important element of the injury cascade following TBI. Progressive compromise of antioxidant defenses and free radical-mediated lipid peroxidation are one of the major mechanisms of secondary TBI. NR2B is a glutamate receptor and its activation is caused by TBI increasing a brain cell death, along with caspase-3 as a hall mark of apoptosis. Glutathione is a potent free radical scavenger that might prevent secondary TBI damage and inhibited apoptosis. Materials and Methods. In the present study, it aims to demonstrate the effect of glutathione on inhibition of brain oxidative damage in a TBI rat model. Results. In this study, the expressions of mRNA NR2B in placebo group and groups with glutathione administration at 0, 3, and 6 hours after TBI were 328.14, 229.90, 178.50, and 136.14, respectively (P<0.001). The highest caspase-3 expression was shown in placebo group with 66.7% showing strong positive results (>80%); as expected, glutathione administered in 0, 3, and 6 hours groups had lower strong positive results of 50%, 16.7%, and 16.7%, respectively, (P=0.025). Conclusion. In conclusion, this study showed that glutathione administration in a TBI rat model decreased NR2B gene- and caspase-3 protein-expression that lead to the inhibition of brain cell death. Our results suggest that glutathione, as a potent free radical scavenger, has a brain cell protective effect against oxidative damage and cell death induced by TBI in rat model. PMID:22347327

Pro-life role for c-Jun N-terminal kinase and p38 mitogen-activated protein kinase at rostral ventrolateral medulla in experimental brain stem death

PubMed Central

2012-01-01

Background Based on an experimental brain stem death model, we demonstrated previously that activation of the mitogen-activated protein kinase kinase 1/2 (MEK1/2)/extracellular signal-regulated kinase 1/2 (ERK1/2)/ mitogen-activated protein kinase signal-interacting kinase 1/2 (MNK1/2) cascade plays a pro-life role in the rostral ventrolateral medulla (RVLM), the origin of a life-and-death signal detected from systemic arterial pressure, which sequentially increases (pro-life) and decreases (pro-death) to reflect progressive dysfunction of central cardiovascular regulation during the advancement towards brain stem death in critically ill patients. The present study assessed the hypothesis that, in addition to ERK1/2, c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK), the other two mammalian members of MAPKs that are originally identified as stress-activated protein kinases, are activated specifically by MAPK kinase 4 (MAP2K4) or MAP2K6 and play a pro-life role in RVLM during experimental brain stem death. We further delineated the participation of phosphorylating activating transcriptional factor-2 (ATF-2) and c-Jun, the classical transcription factor activated by JNK or p38MAPK, in this process. Results An experimental model of brain stem death that employed microinjection of the organophosphate insecticide mevinphos (Mev; 10 nmol) bilaterally into RVLM of Sprague–Dawley rats was used, alongside cardiovascular, pharmacological and biochemical evaluations. Results from ELISA showed that whereas the total JNK, p38MAPK, MAP2K4 and MAP2K6 were not affected, augmented phosphorylation of JNK at Thr183 and Tyr185 and p38MAPK at Thr180 and Tyr182, accompanied by phosphorylation of their upstream activators MAP2K4 at Ser257 and Thr261 and MAP2K6 at Ser207 and Thr211 in RVLM occurred preferentially during the pro-life phase of experimental brain stem death. Moreover, the activity of transcription factors ATF-2 at Thr71 and c-Jun at Ser73, rather than Elk-1 at Ser383 in RVLM were also augmented during the pro-life phase. Furthermore, pretreatment by microinjection into the bilateral RVLM of specific JNK inhibitors, JNK inhibitor I (100 pmol) or SP600125 (5 pmol), or specific p38MAPK inhibitors, p38MAPK inhibitor III (500 pmol) or SB203580 (2 nmol), exacerbated the depressor effect and blunted the augmented life-and-death signal exhibited during the pro-life phase. On the other hand, pretreatment with the negative control for JNK or p38MAPK inhibitor, JNK inhibitor I negative control (100 pmol) or SB202474 (2 nmol), was ineffective in the vehicle-controls and Mev-treatment groups. Conclusions Our results demonstrated that activation of JNK or p38MAPK in RVLM by their upstream activators MAP2K4 or MAP2K6 plays a preferential pro-life role by sustaining the central cardiovascular regulatory machinery during experimental brain stem death via phosphorylation and activation of nuclear transcription factor ATF-2 or c-Jun. PMID:23157661

The relationships between memory systems and sleep stages.

PubMed

Rauchs, Géraldine; Desgranges, Béatrice; Foret, Jean; Eustache, Francis

2005-06-01

Sleep function remains elusive despite our rapidly increasing comprehension of the processes generating and maintaining the different sleep stages. Several lines of evidence support the hypothesis that sleep is involved in the off-line reprocessing of recently-acquired memories. In this review, we summarize the main results obtained in the field of sleep and memory consolidation in both animals and humans, and try to connect sleep stages with the different memory systems. To this end, we have collated data obtained using several methodological approaches, including electrophysiological recordings of neuronal ensembles, post-training modifications of sleep architecture, sleep deprivation and functional neuroimaging studies. Broadly speaking, all the various studies emphasize the fact that the four long-term memory systems (procedural memory, perceptual representation system, semantic and episodic memory, according to Tulving's SPI model; Tulving, 1995) benefit either from non-rapid eye movement (NREM) (not just SWS) or rapid eye movement (REM) sleep, or from both sleep stages. Tulving's classification of memory systems appears more pertinent than the declarative/non-declarative dichotomy when it comes to understanding the role of sleep in memory. Indeed, this model allows us to resolve several contradictions, notably the fact that episodic and semantic memory (the two memory systems encompassed in declarative memory) appear to rely on different sleep stages. Likewise, this model provides an explanation for why the acquisition of various types of skills (perceptual-motor, sensory-perceptual and cognitive skills) and priming effects, subserved by different brain structures but all designated by the generic term of implicit or non-declarative memory, may not benefit from the same sleep stages.

Knowledge and attitudes of nurses on a regional neurological intensive therapy unit towards brain stem death and organ donation.

PubMed

Davies, C

1997-01-01

The study aimed to explore nurses knowledge and attitudes towards brain stem death and organ donation. An ex post facto research design was used to determine relationships between variables. A 16 item questionnaire was used to collect data. Statistical analysis revealed one significant result. The limitations of the sample size is acknowledged and the conclusion suggests a larger study is required.

Apoptotic cell death correlates with ROS overproduction and early cytokine expression after hypoxia-ischemia in fetal lambs.

PubMed

Alonso-Alconada, Daniel; Hilario, Enrique; Álvarez, Francisco José; Álvarez, Antonia

2012-07-01

Despite advances in neonatology, the hypoxic-ischemic injury in the perinatal period remains the single most important cause of brain injury in the newborn, leading to death or lifelong sequelae. Using a sheep model of intrauterine asphyxia, we evaluated the correlation between reactive oxygen species (ROS) overproduction, cytokine expression, and apoptotic cell death. Fetal lambs were assigned to sham group, nonasphyctic animals; and hypoxia-ischemia (HI) group, lambs subjected to 60 minutes of HI) by partial cord occlusion and sacrificed 3 hours later. Different brain regions were separated to quantify the number of apoptotic cells and the same territories were dissociated for flow cytometry studies. Our results suggest that the overproduction of ROS and the early increase in cytokine production after HI in fetal lambs correlate in a significant manner with the apoptotic index, as well as with each brain region evaluated.

Brain Volume as an Integrated Marker for the Risk of Death in a Community-Based Sample: Age Gene/Environment Susceptibility--Reykjavik Study.

PubMed

Van Elderen, Saskia S G C; Zhang, Qian; Sigurdsson, Sigudur; Haight, Thaddeus J; Lopez, Oscar; Eiriksdottir, Gudny; Jonsson, Palmi; de Jong, Laura; Harris, Tamara B; Garcia, Melissa; Gudnason, Vilmundar; van Buchem, Mark A; Launer, Lenore J

2016-01-01

Total brain volume is an integrated measure of health and may be an independent indicator of mortality risk independent of any one clinical or subclinical disease state. We investigate the association of brain volume to total and cause-specific mortality in a large nondemented stroke-free community-based cohort. The analysis includes 3,543 men and women (born 1907-1935) participating in the Age, Gene, Environment Susceptibility-Reykjavik Study. Participants with a known brain-related high risk for mortality (cognitive impairment or stroke) were excluded from these analyses. Quantitative estimates of total brain volume, white matter, white matter lesions, total gray matter (GM; cortical GM and subcortical GM separately), and focal cerebral vascular disease were generated from brain magnetic resonance imaging. Brain atrophy was expressed as brain tissue volume divided by total intracranial volume, yielding a percentage. Mean follow-up duration was 7.2 (0-10) years, with 647 deaths. Cox regression was used to analyze the association of mortality to brain atrophy, adjusting for demographics, cardiovascular risk factors, and cerebral vascular disease. Reduced risk of mortality was significantly associated with higher total brain volume (hazard ratio, 95% confidence interval = 0.71, 0.65-0.78), white matter (0.85, 0.78-0.93), total GM (0.74, 0.68-0.81), and cortical GM (0.78, 0.70-0.87). Overall, the associations were similar for cardiovascular and noncardiovascular-related deaths. Independent of multiple risk factors and cerebral vascular damage, global brain volume predicts mortality in a large nondemented stroke-free community-dwelling older cohort. Total brain volume may be an integrated measure reflecting a range of health and with further investigation could be a useful clinical tool when assessing risk for mortality. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.

Cerebral Oximetry as an Auxiliary Diagnostic Tool in the Diagnosis of Brain Death.

PubMed

Tatli, O; Bekar, O; Imamoglu, M; Gonenc Cekic, O; Aygun, A; Eryigit, U; Karaca, Y; Sahin, A; Turkmen, S; Turedi, S

2017-10-01

To investigate the efficacy of cerebral oximetry (CO) as an auxiliary diagnostic tool in brain death (BD). This observational case-control study was performed on patients with suspected BD. Patients with diagnosis of BD confirmed by the brain death committee were enrolled as the BD group and other patients as the non-BD group. CO monitoring was performed at least 6 h, and cerebral tissue oxygen saturation (ScO 2 ) parameters were compared. Mean ScO 2 level in the BD group was lower than non-brain-dead patients: mean difference for right lobe = 6.48 (95% confidence interval [CI] 0.08-12.88) and for left lobe = 6.09 (95% CI -0.22-12.41). Maximum ScO 2 values in the BD group were significantly lower than the non-BD group: mean difference for right lobe = 8.20 (95% CI 1.64-14.77) and for left lobe = 9.54 (95% CI 3.06-16.03). The area under the curve for right lobe maximum ScO 2 was 0.69 (95% CI 0.55-0.81) and for left lobe was 0.72 (95% CI 0.58-0.84). Maximum ScO 2 in brain-dead patients at CO monitoring is significantly low. However, this cannot be used to differentiate brain-dead and non-brain-dead patients. CO monitoring is therefore not an appropriate auxiliary diagnostic tool for confirming BD. Copyright © 2017 Elsevier Inc. All rights reserved.

The profile of potential organ and tissue donors.

PubMed

Moraes, Edvaldo Leal de; Silva, Leonardo Borges de Barros E; Moraes, Tatiana Cristine de; Paixão, Nair Cordeiro dos Santos da; Izumi, Nelly Miyuki Shinohara; Guarino, Aparecida de Jesus

2009-01-01

This study aimed to characterize donors according to gender, age group, cause of brain death; quantify donors with hypernatremia, hyperpotassemia and hypopotassemia; and get to know which organs were the most used in transplantations. This quantitative, descriptive, exploratory and retrospective study was performed at the Organ Procurement Organization of the University of São Paulo Medical School Hospital das Clínicas. Data from the medical records of 187 potential donors were analyzed. Cerebrovascular accidents represented 53.48% of all brain death causes, sodium and potassium disorders occurred in 82.36% of cases and 45.46% of the potential donors were between 41 and 60 years old. The results evidenced that natural death causes exceeded traumatic deaths, and that most donors presented sodium and potassium alterations, likely associated to inappropriate maintenance.

Effects of mechanical ventilation on gene expression profiles in renal allografts from brain dead rats.

PubMed

Hottenrott, Maximilia C; Krebs, Joerg; Pelosi, Paolo; Luecke, Thomas; Rocco, Patricia R M; Sticht, Carsten; Breedijk, Annette; Yard, Benito; Tsagogiorgas, Charalambos

2017-12-01

Pathophysiological changes of brain death (BD) are impairing distal organ function and harming potential renal allografts. Whether ventilation strategies influence the quality of renal allografts from BD donors has not been thoroughly studied. 28 adult male Wistar rats were randomly assigned to four groups: 1) no brain death (NBD) with low tidal volume/low positive endexpiratory pressure (PEEP) titrated to minimal static elastance of the respiratory system (LVT/OLPEEP); 2) NBD with high tidal volume/low PEEP (HVT/LPEEP); 3) brain death (BD) with LVT/OLPEEP; and 4) BD with HVT/LPEEP. We hypothesized that HVT/LPEEP in BD leads to increased interleukin 6 (IL-6) gene expression and impairs potential renal allografts after six hours of mechanical ventilation. We assessed inflammatory cytokines in serum, genome wide gene expression profiles and quantitative PCR (qPCR) in kidney tissue. The influence of BD on renal gene-expression profiles was greater than the influence of the ventilation strategy. In BD, LVT ventilation did not influence the inflammatory parameters or kidney function in our experimental model. Copyright © 2017. Published by Elsevier B.V.

Brain Oscillations, Hypnosis, and Hypnotizability

PubMed Central

Jensen, Mark P.; Adachi, Tomonori; Hakimian, Shahin

2014-01-01

In this article, we summarize the state-of-science knowledge regarding the associations between hypnosis and brain oscillations. Brain oscillations represent the combined electrical activity of neuronal assemblies, and are usually measured as specific frequencies representing slower (delta, theta, alpha) and faster (beta, gamma) oscillations. Hypnosis has been most closely linked to power in the theta band and changes in gamma activity. These oscillations are thought to play a critical role in both the recording and recall of declarative memory and emotional limbic circuits. Here we propose that it is this role that may be the mechanistic link between theta (and perhaps gamma) oscillations and hypnosis; specifically that theta oscillations may facilitate, and that changes in gamma activity observed with hypnosis may underlie, some hypnotic responses. If these hypotheses are supported, they have important implications for both understanding the effects of hypnosis, and for enhancing response to hypnotic treatments. PMID:25792761

The Biological Effects of Kambo: Is There a Relationship Between its Administration and Sudden Death?

PubMed

Aquila, Isabella; Gratteri, Santo; Sacco, Matteo A; Fineschi, Vittorio; Magi, Simona; Castaldo, Pasqualina; Viscomi, Graziella; Amoroso, Salvatore; Ricci, Pietrantonio

2018-05-01

Kambo is a substance obtained from the skin secretions of a frog, Phyllomedusa bicolor, popular in the Amazon region, which is administered via the transdermal route. We report a case of 42-year-old man found dead in his house. Near the corpse, a plastic box labeled as "Kambo sticks" was found. The man was a chronic consumer of Kambo and no previous pathology or genetic disease emerged in clinical history from the declaration of his general practitioner. Autopsy investigations and toxicological analysis were performed. The histopathological examination showed left ventricular hypertrophy. Toxicological screening was negative for ethanol and other drugs. Phyllocaerulein, phyllokinin, and deltorphin A were isolated from the Kambo sticks but, only deltorphin A was detected in blood sample. We describe the first forensic case of death associated with Kambo administration. We attempt to explain how its use could be related to the cause of sudden death in this case. © 2017 American Academy of Forensic Sciences.

Disentangling the roles of arousal and amygdala activation in emotional declarative memory

PubMed Central

Fernández, Guillén; Hermans, Erno J.

2016-01-01

A large body of evidence in animals and humans implicates the amygdala in promoting memory for arousing experiences. Although the amygdala can trigger threat-related noradrenergic-sympathetic arousal, in humans amygdala activation and noradrenergic-sympathetic arousal do not always concur. This raises the question how these two processes play a role in enhancing emotional declarative memory. This study was designed to disentangle these processes in a combined subsequent-memory/fear-conditioning paradigm with neutral items belonging to two conceptual categories as conditioned stimuli. Functional MRI, skin conductance (index of sympathetic activity), and pupil dilation (indirect index of central noradrenergic activity) were acquired throughout procedures. Recognition memory for individual items was tested 24 h later. We found that pupil dilation and skin conductance responses were higher on CS+ (associated with a shock) compared with CS− trials, irrespective of later memory for those items. By contrast, amygdala activity was only higher for CS+ items that were later confidently remembered compared with CS+ items that were later forgotten. Thus, amygdala activity and not noradrenergic-sympathetic arousal, predicted enhanced declarative item memory. This dissociation is in line with animal models stating that the amygdala integrates arousal-related neuromodulatory changes to alter mnemonic processes elsewhere in the brain. PMID:27217115

A Role for Central Nervous Growth Hormone-Releasing Hormone Signaling in the Consolidation of Declarative Memories

PubMed Central

Michel, Christian; Perras, Boris; Born, Jan

2011-01-01

Contributions of somatotropic hormonal activity to memory functions in humans, which are suggested by clinical observations, have not been systematically examined. With previous experiments precluding a direct effect of systemic growth hormone (GH) on acute memory formation, we assessed the role of central nervous somatotropic signaling in declarative memory consolidation. We examined the effect of intranasally administered growth hormone releasing-hormone (GHRH; 600 µg) that has direct access to the brain and suppresses endogenous GHRH via an ultra-short negative feedback loop. Twelve healthy young men learned word-pair associates at 2030 h and were administered GHRH and placebo, respectively, at 2100 h. Retrieval was tested after 11 hours of wakefulness. Compared to placebo, intranasal GHRH blunted GH release within 3 hours after substance administration and reduced the number of correctly recalled word-pairs by ∼12% (both P<0.05). The impairment of declarative memory consolidation was directly correlated to diminished GH concentrations (P<0.05). Procedural memory consolidation as examined by the parallel assessment of finger sequence tapping performance was not affected by GHRH administration. Our findings indicate that intranasal GHRH, by counteracting endogenous GHRH release, impairs hippocampal memory processing. They provide first evidence for a critical contribution of central nervous somatotropic activity to hippocampus-dependent memory consolidation. PMID:21850272

Motor skill learning and offline-changes in TGA patients with acute hippocampal CA1 lesions.

PubMed

Döhring, Juliane; Stoldt, Anne; Witt, Karsten; Schönfeld, Robby; Deuschl, Günther; Born, Jan; Bartsch, Thorsten

2017-04-01

Learning and the formation of memory are reflected in various memory systems in the human brain such as the hippocampus based declarative memory system and the striatum-cortex based system involved in motor sequence learning. It is a matter of debate how both memory systems interact in humans during learning and consolidation and how this interaction is influenced by sleep. We studied the effect of an acute dysfunction of hippocampal CA1 neurons on the acquisition (on-line condition) and off-line changes of a motor skill in patients with a transient global amnesia (TGA). Sixteen patients (68 ± 4.4 yrs) were studied in the acute phase and during follow-up using a declarative and procedural test, and were compared to controls. Acute TGA patients displayed profound deficits in all declarative memory functions. During the acute amnestic phase, patients were able to acquire the motor skill task reflected by increasing finger tapping speed across the on-line condition, albeit to a lesser degree than during follow-up or compared to controls. Retrieval two days later indicated a greater off-line gain in motor speed in patients than controls. Moreover, this gain in motor skill performance was negatively correlated to the declarative learning deficit. Our results suggest a differential interaction between procedural and declarative memory systems during acquisition and consolidation of motor sequences in older humans. During acquisition, hippocampal dysfunction attenuates fast learning and thus unmasks the slow and rigid learning curve of striatum-based procedural learning. The stronger gains in the post-consolidation condition in motor skill in CA1 lesioned patients indicate a facilitated consolidation process probably occurring during sleep, and suggest a competitive interaction between the memory systems. These findings might be a reflection of network reorganization and plasticity in older humans and in the presence of CA1 hippocampal pathology. Copyright © 2016 Elsevier Ltd. All rights reserved.

Floods of May and June 2004 in Central and Eastern Ohio: FEMA Disaster Declaration 1519

USGS Publications Warehouse

Ebner, Andrew D.; Straub, David E.; Lageman, Jonathan D.

2008-01-01

Several severe thunderstorms that passed through Ohio between May 17 and June 17, 2004, produced large amounts of rain in an already wet central and eastern Ohio, resulting in flooding in this region from May 18 to June 21, 2004. Record peak streamflow occurred at three U.S. Geological Survey (USGS) streamgages. Damages caused by the flooding resulting from these storms were severe enough that 25 counties in central and eastern Ohio were declared Federal disaster areas. In all, there were two storm- or flood-related deaths, 3,529 private structures damaged or destroyed, and an estimated $43 million in damages. This report describes the meteorological factors that resulted in severe flooding in central and eastern Ohio between May 18 and June 21, 2004, and addresses the damages caused by the storms and flooding. Peak-stage, peak-streamflow, and recurrence-interval data are reported for selected USGS streamgages. Flood profiles determined by the USGS are presented for selected streams.

Using the endocannabinoid system as a neuroprotective strategy in perinatal hypoxic-ischemic brain injury

PubMed Central

Lara-Celador, I.; Goñi-de-Cerio, F.; Alvarez, Antonia; Hilario, Enrique

2013-01-01

One of the most important causes of brain injury in the neonatal period is a perinatal hypoxic-ischemic event. This devastating condition can lead to long-term neurological deficits or even death. After hypoxic-ischemic brain injury, a variety of specific cellular mechanisms are set in motion, triggering cell damage and finally producing cell death. Effective therapeutic treatments against this phenomenon are still unavailable because of complex molecular mechanisms underlying hypoxic-ischemic brain injury. After a thorough understanding of the mechanism underlying neural plasticity following hypoxic-ischemic brain injury, various neuroprotective therapies have been developed for alleviating brain injury and improving long-term outcomes. Among them, the endocannabinoid system emerges as a natural system of neuroprotection. The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury, acting as a natural neuroprotectant. The aim of this review is to study the use of different therapies to induce long-term therapeutic effects after hypoxic-ischemic brain injury, and analyze the important role of the endocannabinoid system as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury. PMID:25206720

Role of Caspase-8 and Fas in Cell Death After Spinal Cord Injury

PubMed Central

Sobrido-Cameán, Daniel; Barreiro-Iglesias, Antón

2018-01-01

Spinal cord injury (SCI) causes the death of neurons and glial cells due to the initial mechanical forces (i.e., primary injury) and through a cascade of secondary molecular events (e.g., inflammation or excitotoxicity) that exacerbate cell death. The loss of neurons and glial cells that are not replaced after the injury is one of the main causes of disability after SCI. Evidence accumulated in last decades has shown that the activation of apoptotic mechanisms is one of the factors causing the death of intrinsic spinal cord (SC) cells following SCI. Although this is not as clear for brain descending neurons, some studies have also shown that apoptosis can be activated in the brain following SCI. There are two main apoptotic pathways, the extrinsic and the intrinsic pathways. Activation of caspase-8 is an important step in the initiation of the extrinsic pathway. Studies in rodents have shown that caspase-8 is activated in SC glial cells and neurons and that the Fas receptor plays a key role in its activation following a traumatic SCI. Recent work in the lamprey model of SCI has also shown the retrograde activation of caspase-8 in brain descending neurons following SCI. Here, we review our current knowledge on the role of caspase-8 and the Fas pathway in cell death following SCI. We also provide a perspective for future work on this process, like the importance of studying the possible contribution of Fas/caspase-8 signaling in the degeneration of brain neurons after SCI in mammals. PMID:29666570

Cerebral and brainstem electrophysiologic activity during euthanasia with pentobarbital sodium in horses.

PubMed

Aleman, M; Williams, D C; Guedes, A; Madigan, J E

2015-01-01

An overdose of pentobarbital sodium administered i.v. is the most commonly used method of euthanasia in veterinary medicine. Determining death after the infusion relies on the observation of physical variables. However, it is unknown when cortical electrical activity and brainstem function are lost in a sequence of events before death. To examine changes in the electrical activity of the cerebral cortex and brainstem during an overdose of pentobarbital sodium solution for euthanasia. Our testing hypothesis is that isoelectric pattern of the brain in support of brain death occurs before absence of electrocardiogram (ECG) activity. Fifteen horses requiring euthanasia. Prospective observational study. Horses with neurologic, orthopedic, and cardiac illnesses were selected and instrumented for recording of electroencephalogram, electrooculogram, brainstem auditory evoked response (BAER), and ECG. Physical and neurologic (brainstem reflexes) variables were monitored. Loss of cortical electrical activity occurred during or within 52 seconds after the infusion of euthanasia solution. Cessation of brainstem function as evidenced by a lack of brainstem reflexes and disappearance of the BAER happened subsequently. Despite undetectable heart sounds, palpable arterial pulse, and mean arterial pressure, recordable ECG was the last variable to be lost after the infusion (5.5-16 minutes after end of the infusion). Overdose of pentobarbital sodium solution administered i.v. is an effective, fast, and humane method of euthanasia. Brain death occurs within 73-261 seconds of the infusion. Although absence of ECG activity takes longer to occur, brain death has already occurred. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Deletion of a single allele of the Pex11β gene is sufficient to cause oxidative stress, delayed differentiation and neuronal death in mouse brain

PubMed Central

Ahlemeyer, Barbara; Gottwald, Magdalena; Baumgart-Vogt, Eveline

2012-01-01

SUMMARY Impaired neuronal migration and cell death are commonly observed in patients with peroxisomal biogenesis disorders (PBDs), and in mouse models of this diseases. In Pex11β-deficient mice, we observed that the deletion of a single allele of the Pex11β gene (Pex11β+/− heterozygous mice) caused cell death in primary neuronal cultures prepared from the neocortex and cerebellum, although to a lesser extent as compared with the homozygous-null animals (Pex11β−/− mice). In corresponding brain sections, cell death was rare, but differences between the genotypes were similar to those found in vitro. Because PEX11β has been implicated in peroxisomal proliferation, we searched for alterations in peroxisomal abundance in the brain of heterozygous and homozygous Pex11β-null mice compared with wild-type animals. Deletion of one allele of the Pex11β gene slightly increased the abundance of peroxisomes, whereas the deletion of both alleles caused a 30% reduction in peroxisome number. The size of the peroxisomal compartment did not correlate with neuronal death. Similar to cell death, neuronal development was delayed in Pex11β+/− mice, and to a further extent in Pex11β−/− mice, as measured by a reduced mRNA and protein level of synaptophysin and a reduced protein level of the mature isoform of MAP2. Moreover, a gradual increase in oxidative stress was found in brain sections and primary neuronal cultures from wild-type to heterozygous to homozygous Pex11β-deficient mice. SOD2 was upregulated in neurons from Pex11β+/− mice, but not from Pex11β−/− animals, whereas the level of catalase remained unchanged in neurons from Pex11β+/− mice and was reduced in those from Pex11β−/− mice, suggesting a partial compensation of oxidative stress in the heterozygotes, but a failure thereof in the homozygous Pex11β−/− brain. In conclusion, we report the alterations in the brain caused by the deletion of a single allele of the Pex11β gene. Our data might lead to the reconsideration of the clinical treatment of PBDs and the common way of using knockout mouse models for studying autosomal recessive diseases. PMID:21954064

Resveratrol and pinostilbene confer neuroprotection against aging-related deficits through an ERK1/2 dependent-mechanism

USDA-ARS?s Scientific Manuscript database

Age-related declines in motor function may be due, in part, to an increase in oxidative stress in the aging brain leading to death of brain cells that transmit dopamine (DA), one of the brain chemicals responsible for transmitting signals between brain nerve cells. We examined the neuroprotective ef...

Mechanisms of gender-linked ischemic brain injury

PubMed Central

Liu, Mingyue; Dziennis, Suzan; Hurn, Patricia D.; Alkayed, Nabil J.

2010-01-01

Biological sex is an important determinant of stroke risk and outcome. Women are protected from cerebrovascular disease relative to men, an observation commonly attributed to the protective effect of female sex hormones, estrogen and progesterone. However, sex differences in brain injury persist well beyond the menopause and can be found in the pediatric population, suggesting that the effects of reproductive steroids may not completely explain sexual dimorphism in stroke. We review recent advances in our understanding of sex steroids (estradiol, progesterone and testosterone) in the context of ischemic cell death and neuroprotection. Understanding the molecular and cell-based mechanisms underlying sex differences in ischemic brain injury will lead to a better understanding of basic mechanisms of brain cell death and is an important step toward designing more effective therapeutic interventions in stroke. PMID:19531872

One thousand consecutive in-hospital deaths following severe injury: Has the etiology of traumatic inpatient death changed in Canada?

PubMed Central

Roberts, Derek J.; Harzan, Christina; Kirkpatrick, Andrew W.; Dixon, Elijah; Grondin, Sean C.; McBeth, Paul B.; Kaplan, Gilaad G.

2018-01-01

Summary A wide range of factors have traditionally led to early in-hospital death following severe injury. The primary goal of this commentary was to evaluate the causes of early posttraumatic inpatient deaths over an extended period. Although early posttraumatic in-hospital death remains multifactorial, severe traumatic brain injuries are the dominant cause and have increased in proportion over time. Other traditional causes of death have also decreased owing to improved clinical care. PMID:29806810

Determination of death: Metaphysical and biomedical discourse.

PubMed

Jakušovaitė, Irayda; Luneckaitė, Žydrunė; Peičius, Eimantas; Bagdonaitė, Živilė; Riklikienė, Olga; Stankevičius, Edgaras

2016-01-01

The prominence of biomedical criteria relying on brain death reduces the impact of metaphysical, anthropological, psychosocial, cultural, religious, and legal aspects disclosing the real value and essence of human life. The aim of this literature review is to discuss metaphysical and biomedical approaches toward death and their complimentary relationship in the determination of death. A critical appraisal of theoretical and scientific evidence and legal documents supported analytical discourse. In the metaphysical discourse of death, two main questions about what human death is and how to determine the fact of death clearly separate the ontological and epistemological aspects of death. During the 20th century, various understandings of human death distinguished two different approaches toward the human: the human is a subject of activities or a subject of the human being. Extinction of the difference between the entities and the being, emphasized as rational-logical instrumentation, is not sufficient to understand death thoroughly. Biological criteria of death are associated with biological features and irreversible loss of certain cognitive capabilities. Debating on the question "Does a brain death mean death of a human being?" two approaches are considering: the body-centrist and the mind-centrist. By bridging those two alternatives human death appears not only as biomedical, but also as metaphysical phenomenon. It was summarized that a predominance of clinical criteria for determination of death in practice leads to medicalization of death and limits the holistic perspective toward individual's death. Therefore, the balance of metaphysical and biomedical approaches toward death and its determination would decrease the medicalization of the concept of death. Copyright © 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Moderate zinc deficiency increases cell death after brain injury in the rat.

PubMed

Yeiser, E Carden; Vanlandingham, Jacob W; Levenson, Cathy W

2002-10-01

Zinc supplementation has been used clinically to reduce Zn losses and protein turnover in patients suffering from traumatic brain injury. Despite the known role of zinc in cell survival and integrity, the influence of zinc status on central nervous system wound healing in the weeks and months after brain injury has not been addressed. In this investigation, we examined cell death after unilateral cortical stab wounds in adult rats (n = 5 per group) that were provided diets containing adequate zinc (30 mg Zn/kg diet), supplemental zinc (180 mg/kg), or moderately deficient zinc (5 mg/kg). Four weeks following the brain injury there was a 1.82-2.65-fold increase in terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick-end labeling (TUNEL)-positive cells with DNA fragmentation at the site of injury in animals receiving a moderately zinc deficient diet compared to animals receiving a zinc-adequate or supplemented diet (p0.05). Examination of the nuclear morphology of these cells suggested the presence of both apoptosis and necrosis. Immunohistochemistry showed that the TUNEL-positive cells expressed both ED-1 and OX-42, identifying them as microglia/macrophages. Thus it appears that adequate zinc status may be necessary to minimize the amount of neuroimmune cell death after brain injury.

Achieving enlightenment: what do we know about the implicit learning system and its interaction with explicit knowledge?

PubMed

Vidoni, Eric D; Boyd, Lara A

2007-09-01

Two major memory and learning systems operate in the brain: one for facts and ideas (ie, the declarative or explicit system), one for habits and behaviors (ie, the procedural or implicit system). Broadly speaking these two memory systems can operate either in concert or entirely independently of one another during the performance and learning of skilled motor behaviors. This Special Issue article has two parts. In the first, we present a review of implicit motor skill learning that is largely centered on the interactions between declarative and procedural learning and memory. Because distinct neuroanatomical substrates support unique aspects of learning and memory and thus focal injury can cause impairments that are dependent on lesion location, we also broadly consider which brain regions mediate implicit and explicit learning and memory. In the second part of this article, the interactive nature of these two memory systems is illustrated by the presentation of new data that reveal that both learning implicitly and acquiring explicit knowledge through physical practice lead to motor sequence learning. In our new data, we discovered that for healthy individuals use of the implicit versus explicit memory system differently affected variability of performance during acquisition practice; variability was higher early in practice for the implicit group and later in practice for the acquired explicit group. Despite the difference in performance variability, by retention both groups demonstrated comparable change in tracking accuracy and thus, motor sequence learning. Clinicians should be aware of the potential effects of implicit and explicit interactions when designing rehabilitation interventions, particularly when delivering explicit instructions before task practice, working with individuals with focal brain damage, and/or adjusting therapeutic parameters based on acquisition performance variability.

A biased competition account of attention and memory in Alzheimer's disease

PubMed Central

Finke, Kathrin; Myers, Nicholas; Bublak, Peter; Sorg, Christian

2013-01-01

The common view of Alzheimer's disease (AD) is that of an age-related memory disorder, i.e. declarative memory deficits are the first signs of the disease and associated with progressive brain changes in the medial temporal lobes and the default mode network. However, two findings challenge this view. First, new model-based tools of attention research have revealed that impaired selective attention accompanies memory deficits from early pre-dementia AD stages on. Second, very early distributed lesions of lateral parietal networks may cause these attention deficits by disrupting brain mechanisms underlying attentional biased competition. We suggest that memory and attention impairments might indicate disturbances of a common underlying neurocognitive mechanism. We propose a unifying account of impaired neural interactions within and across brain networks involved in attention and memory inspired by the biased competition principle. We specify this account at two levels of analysis: at the computational level, the selective competition of representations during both perception and memory is biased by AD-induced lesions; at the large-scale brain level, integration within and across intrinsic brain networks, which overlap in parietal and temporal lobes, is disrupted. This account integrates a large amount of previously unrelated findings of changed behaviour and brain networks and favours a brain mechanism-centred view on AD. PMID:24018724

A biased competition account of attention and memory in Alzheimer's disease.

PubMed

Finke, Kathrin; Myers, Nicholas; Bublak, Peter; Sorg, Christian

2013-10-19

The common view of Alzheimer's disease (AD) is that of an age-related memory disorder, i.e. declarative memory deficits are the first signs of the disease and associated with progressive brain changes in the medial temporal lobes and the default mode network. However, two findings challenge this view. First, new model-based tools of attention research have revealed that impaired selective attention accompanies memory deficits from early pre-dementia AD stages on. Second, very early distributed lesions of lateral parietal networks may cause these attention deficits by disrupting brain mechanisms underlying attentional biased competition. We suggest that memory and attention impairments might indicate disturbances of a common underlying neurocognitive mechanism. We propose a unifying account of impaired neural interactions within and across brain networks involved in attention and memory inspired by the biased competition principle. We specify this account at two levels of analysis: at the computational level, the selective competition of representations during both perception and memory is biased by AD-induced lesions; at the large-scale brain level, integration within and across intrinsic brain networks, which overlap in parietal and temporal lobes, is disrupted. This account integrates a large amount of previously unrelated findings of changed behaviour and brain networks and favours a brain mechanism-centred view on AD.

Dose-dependent lipopolysaccharide-induced fetal brain injury in the guinea pig.

PubMed

Harnett, Erica L; Dickinson, Michelle A; Smith, Graeme N

2007-08-01

This study determined whether a lipopolysaccharide (LPS) dose-dependent increase in fetal brain injury occurs to further characterize the relationship between maternal inflammation and fetal brain injury. Pregnant guinea pigs (n = 59) at 70% gestation were injected intraperitoneally with 1, 5, 25, 50, 100, 200, or 300 microg LPS per kilogram of maternal body weight or an equivalent volume of vehicle. Animals were killed 7 days later. Maternal serum and amniotic fluid samples were assayed for proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 using enzyme-linked immunosorbent assay kits. Fetal brains (n = 72) were stained for evidence of cell death with NeuroTACS stain. Seven days after LPS injections, cytokine concentrations in maternal serum and amniotic fluid were not different (P > .05) from controls. Levels of cell death in all brain regions examined were highest following the maternal administration of 300 mug/kg LPS (P < .05). The dose effect was brain region-dependent (P < .05). A threshold of maternal infection/inflammation exists, beyond which demonstrable fetal brain injury may result.

Federal and Provincial Responsibilities to Implement Physician-Assisted Suicide.

PubMed

Baker, David; Sharpe, Gilbert; Lauks, Rebeka

2016-02-01

In the most significant constitutional decision of the last generation, Carter v. Canada, the Supreme Court of Canada reversed itself and decided that it was possible for Parliament to enact safeguards that would be adequate to protect persons who are vulnerable in times of weakness, then proceeded to declare that Canadians were entitled to a s. 7 Charter right to physician-assisted death. David Baker and Gilbert Sharpe accepted the challenge issued by the Court and drafted a Bill to amend the Criminal Code in a manner they believed would strike a constitutional balance between providing access to the right declared by the Court and protecting the vulnerable. This article represents their attempt, along with co-author Rebeka Lauks, to explain many of the key provisions in their draft. Amongst the most noteworthy are their attempts to ensure that those choosing PAD are informed about quality of life, as well as treatment choices; to define vulnerability and to install safeguards adequate to protect persons while vulnerable; and finally a prior review process that would ensure both ready access to the Charter right declared by the Court and consistent and transparent application of the law. The authors have attempted to establish an alternative model to that currently in effect in the Benelux countries, which they regard as having been ineffective in achieving any of these objectives.

Advances in memory research: single-neuron recordings from the human medial temporal lobe aid our understanding of declarative memory.

PubMed

Viskontas, Indre V

2008-12-01

To gain a complete understanding of how the brain functions, both in illness and good health, data from multiple levels of analysis must be integrated. Technical advances have made direct recordings of neuronal activity deep inside the human brain tractable, providing a rare glimpse into cellular processes during long-term memory formation. Recent findings using intracranial recordings in the medial temporal lobe inform current neural network models of memory, and may lead to a more comprehensive understanding of the neural basis of memory-related processes. These recordings have shown that cells in the hippocampus appear to support declarative learning by distinguishing novel and familiar stimuli via changes in firing patterns. Some cells with highly selective and invariant responses have also been described, and these responses seem to represent abstract concepts such as identity, rather than superficial perceptual features of items. Importantly, however, both selective and globally responsive cells are capable of changing their preferred stimulus depending on the conscious demands of the task. Firing patterns of human medial temporal lobe neurons indicate that cells can be both plastic and stable in terms of the information that they code; although some cells show highly selective and reproducible excitatory responses when presented with a familiar object, other cells change their receptive fields in line with changes in experience and the cognitive environment.

The role of the basal ganglia in learning and memory: insight from Parkinson's disease.

PubMed

Foerde, Karin; Shohamy, Daphna

2011-11-01

It has long been known that memory is not a single process. Rather, there are different kinds of memory that are supported by distinct neural systems. This idea stemmed from early findings of dissociable patterns of memory impairments in patients with selective damage to different brain regions. These studies highlighted the role of the basal ganglia in non-declarative memory, such as procedural or habit learning, contrasting it with the known role of the medial temporal lobes in declarative memory. In recent years, major advances across multiple areas of neuroscience have revealed an important role for the basal ganglia in motivation and decision making. These findings have led to new discoveries about the role of the basal ganglia in learning and highlighted the essential role of dopamine in specific forms of learning. Here we review these recent advances with an emphasis on novel discoveries from studies of learning in patients with Parkinson's disease. We discuss how these findings promote the development of current theories away from accounts that emphasize the verbalizability of the contents of memory and towards a focus on the specific computations carried out by distinct brain regions. Finally, we discuss new challenges that arise in the face of accumulating evidence for dynamic and interconnected memory systems that jointly contribute to learning. Copyright © 2011 Elsevier Inc. All rights reserved.

Postmortem and perimortem cesarean section: historical, religious and ethical considerations.

PubMed

Fadel, Hossam E

2011-12-01

Guillimeau was the first to use the term cesarean section (CS) in 1598, but this name became universal only in the 20th century. The many theories of the origin of this name will be discussed. This surgery has been reported to be performed in all cultures dating to ancient times. In the past, it was mainly done to deliver a live baby from a dead mother, hence the name postmortem CS (PMCS). Many heroes are reported to have been delivered this way. Old Jewish sacred books have made references to abdominal delivery. It was especially encouraged and often mandated in Catholicism. There is evidence that the operation was done in Muslim countries in the middle ages. Islamic rulings support the performance of PMCS. Now that most maternal deaths occur in the hospital, perimortem CS (PRMCS) is recommended for the delivery of a fetus after 24 weeks from a pregnant woman with cardiac arrest. It is believed that emergent delivery within four minutes of initiation of cardiopulmonary resuscitation (CPR) improves the chances of success of maternal resuscitation and survival and increases the chance of delivering a neurologically intact neonate. It is agreed that physicians are not to be held legally liable for the performance of PMCS and PRMCS regardless of the outcome. The ethical aspects of these operations are also discussed including a discussion about PMCS for the delivery of women who have been declared brain dead.

Reye Syndrome

MedlinePlus

Reye syndrome is a rare illness that can affect the blood, liver, and brain of someone who has recently ... a viral illness, seek medical attention immediately. Reye syndrome can lead to a coma and brain death, ...

Improving the Outcomes of Organs Obtained From Controlled Donation After Circulatory Death Donors Using Abdominal Normothermic Regional Perfusion.

PubMed

Miñambres, E; Suberviola, B; Dominguez-Gil, B; Rodrigo, E; Ruiz-San Millan, J C; Rodríguez-San Juan, J C; Ballesteros, M A

2017-08-01

The use of donation after circulatory death (DCD) has increased significantly during the past decade. However, warm ischemia results in a greater risk for transplantation. Indeed, controlled DCD (cDCD) was associated with inferior outcomes compared with donation after brain death. The use of abdominal normothermic regional perfusion (nRP) to restore blood flow before organ recovery in cDCD has been proposed as better than rapid recovery to reverse the effect of ischemia and improve recipients' outcome. Here, the first Spanish series using abdominal nRP as an in situ conditioning method is reported. A specific methodology to avoid restoring circulation to the brain after death determination is described. Twenty-seven cDCD donors underwent abdominal nRP during at least 60 min. Thirty-seven kidneys, 11 livers, six bilateral lungs, and one pancreas were transplanted. The 1-year death-censored kidney survival was 91%, and delayed graft function rate was 27%. The 1-year liver survival rate was 90.1% with no cases of ischemic cholangiopathy. Transplanted lungs and pancreas exhibited primary function. The use of nRP may represent an advance to increase the number and quality of grafts in cDCD. Poor results in cDCD livers could be reversed with nRP. Concerns about restoring brain circulation after death are easily solved. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Crossing the Rubicon: Death in 'The Year of the Transplant'.

PubMed

MacDonald, Helen

2017-01-01

How death should be measured was a subject of intense debate during the late 1960s, and one in which transplant surgeons had a particular interest. Legislation required a doctor to first pronounce 'extinct' the patients from whom 'spare parts' were sought for grafting. But transplant surgeons increasingly argued the moment of death was less important than was the moment of establishing that a patient was beyond the point of no return in dying, at which time she or he should be passed to the transplant team. This raised concerns that people identified as being a potential source of organs might not be adequately cared for in their own right. In 1968 the World Medical Association issued an international statement on death at its meeting in Sydney, Australia following a debate between delegates about how and by whom death should be assessed prior to organ removal. Soon afterwards Australian surgeons performed two of the one hundred and five heart transplants carried out around the world that year, dubbed by the New York Times to be one during which an 'international epidemic' of such grafts were carried out. This essay examines debates about death and transplanting, then analyses the pioneering Australian heart transplants, in the context of the Declaration of Sydney and continuing international discussions about whether these operations were moral and legal.

Coding pulmonary sepsis and mortality statistics in Rio de Janeiro, RJ.

PubMed

Cardoso, Bruno Baptista; Kale, Pauline Lorena

2016-01-01

This study aimed to describe "pulmonary sepsis" reported as a cause of death, measure its association to pneumonia, and the significance of the coding rules in mortality statistics, including the diagnosis of pneumonia on death certificates (DC) with the mention of pulmonary sepsis in Rio de Janeiro, Brazil, in 2011. DC with mention of pulmonary sepsis was identified, regardless of the underlying cause of death. Medical records related to the certificates with reference to "pulmonary sepsis" were reviewed and physicians were interviewed to measure the association between pulmonary sepsis and pneumonia. A simulation was performed in the mortality data by inserting the International Classification of Diseases (ICD-10) code for pneumonia in the certificates with pulmonary sepsis. "Pulmonary sepsis" constituted 30.9% of reported sepsis and pneumonia was not reported in 51.3% of these DC. Pneumonia was registered in 82.8% of the sample of the medical records. Among physicians interviewed, 93.3% declared pneumonia as the most common cause of "pulmonary sepsis." The simulation of the coding process resulted in a different underlying cause of death for 7.8% of the deaths with sepsis reported and 2.4% of all deaths, regardless the original cause. The conclusion is that "pulmonary sepsis" is frequently associated to pneumonia and that the addition of the ICD-10 code for pneumonia in DC could affect the mortality statistics, highlighting the need to improve mortality coding rules.

Mortality pattern in otorhinolaryngology ward: A 5 years retrospective study at an urban tertiary health care center in India.

PubMed

Kumar, Vivek; Kumar, Satish; Chandra Sharma, Naresh; Kumar, Badal

2017-10-01

To recognize deaths in the otorhinolaryngology indoor wards, determine the reason behind the mortalities and recommend modifications for betterment of patient care and surgical outcomes. Data was collected from the mortality register, operation theatre registers, ward registers and case notes of patients declared dead at an urban tertiary health care center in India for a period of 5 years; from January 2012 to December 2016. The data included date of admission, age, sex, educational status, residence, and clinical diagnosis, course of hospital stay and medical cause of death. Data acquired was reviewed and statistically interpreted and presented in graphical and descriptive formats. 6157 admissions were made in otorhinolaryngology (ENT) ward in the 5 year period which included 3969 males and 2188 female patients. 58 deaths were recorded during this period which gives overall death per admission crude mortality rate of 9.42% at an average of about 12 (11.60) deaths per year. The major causes of death were malignancy and septicemia. The significance of health education, aggressive healthcare campaigns, enhancement of healthcare services and wide accessibility of healthcare services to remote areas has been emphasized. Role of structured study and protocols in the management of serious cases is highlighted along with the need for prompt referral and better interdepartmental cooperation. Copyright © 2017 Chang Gung University. Published by Elsevier B.V. All rights reserved.

Crossing the Rubicon: Death in ‘The Year of the Transplant’

PubMed Central

MacDonald, Helen

2017-01-01

How death should be measured was a subject of intense debate during the late 1960s, and one in which transplant surgeons had a particular interest. Legislation required a doctor to first pronounce ‘extinct’ the patients from whom ‘spare parts’ were sought for grafting. But transplant surgeons increasingly argued the moment of death was less important than was the moment of establishing that a patient was beyond the point of no return in dying, at which time she or he should be passed to the transplant team. This raised concerns that people identified as being a potential source of organs might not be adequately cared for in their own right. In 1968 the World Medical Association issued an international statement on death at its meeting in Sydney, Australia following a debate between delegates about how and by whom death should be assessed prior to organ removal. Soon afterwards Australian surgeons performed two of the one hundred and five heart transplants carried out around the world that year, dubbed by the New York Times to be one during which an ‘international epidemic’ of such grafts were carried out. This essay examines debates about death and transplanting, then analyses the pioneering Australian heart transplants, in the context of the Declaration of Sydney and continuing international discussions about whether these operations were moral and legal. PMID:27998333

C-type natriuretic peptide functions as an innate neuroprotectant in neonatal hypoxic-ischemic brain injury in mouse via natriuretic peptide receptor 2.

PubMed

Ma, Qingyi; Zhang, Lubo

2018-06-01

Neonatal hypoxia-ischemia (HI) is the most common cause of brain injury in neonates, which leads to high neonatal mortality and severe neurological morbidity in later life (Vannucci, 2000; Volpe, 2001). Yet the molecular mechanisms of neuronal death and brain damage induced by neonatal HI remain largely elusive. Herein, using both in vivo and in vitro models, we determine an endogenous neuroprotectant role of c-type natriuretic peptide (CNP) in preserving neuronal survival after HI brain injury in mouse pups. Postnatal day 7 (P7) mouse pups with CNP deficiency (Nppc lbab/lbab ) exhibit increased brain infarct size and worsened long-term locomotor function after neonatal HI compared with wildtype control (Nppc +/+ ). In isolated primary cortical neurons, recombinant CNP dose-dependently protects primary neurons from oxygen-glucose deprivation (OGD) insult. This neuroprotective effect appears to be mediated through its cognate natriuretic peptide receptor 2 (NPR2), in that antagonization of NPR2, but not NPR3, exacerbates neuronal death and counteracts the protective effect of CNP on primary neurons exposed to OGD insult. Immunoblot and confocal microscopy demonstrate the abundant expression of NPR2 in neurons of the neonatal brain and in isolated primary cortical neurons as well. Moreover, similar to CNP deficiency, administration of NPR2 antagonist P19 via intracerebroventricular injection prior to HI results in exacerbated neuronal death and brain injury after HI. Altogether, the present study indicates that CNP and its cognate receptor NPR2 mainly expressed in neurons represent an innate neuroprotective mechanism in neonatal HI brain injury. Copyright © 2018 Elsevier Inc. All rights reserved.

N-acetyl-L-cysteine protects against cadmium-induced neuronal apoptosis by inhibiting ROS-dependent activation of Akt/mTOR pathway in mouse brain

PubMed Central

Chen, Sujuan; Ren, Qian; Zhang, Jinfei; Ye, Yangjing; Zhang, Zhen; Xu, Yijiao; Guo, Min; Ji, Haiyan; Xu, Chong; Gu, Chenjian; Gao, Wei; Huang, Shile; Chen, Long

2014-01-01

Aims This study explores the neuroprotective effects and mechanisms of N-acetyl-L-cysteine (NAC) in mice exposed to cadmium (Cd). Methods NAC (150 mg/kg) was intraperitoneally administered to mice exposed to Cd (10-50 mg/L) in drinking water for 6 weeks. The changes of cell damage and death, reactive oxygen species (ROS), antioxidant enzymes, as well as Akt/mammalian target of rapamycin (mTOR) signaling pathway in brain neurons were assessed. To verify the role of mTOR activation in Cd-induced neurotoxicity, mice also received a subacute regimen of intraperitoneally administered Cd (1 mg/kg) with/without rapamycin (7.5 mg/kg) for 11 days. Results Chronic exposure of mice to Cd induced brain damage or neuronal cell death, due to ROS induction. Co-administration of NAC significantly reduced Cd levels in the plasma and brain of the animals. NAC prevented Cd-induced ROS and significantly attenuated Cd-induced brain damage or neuronal cell death. The protective effect of NAC was mediated, at least partially, by elevating the activities of Cu/Zn-superoxide dismutase, catalase and glutathione peroxidase, as well as the level of glutathione in the brain. Furthermore, Cd-induced activation of Akt/mTOR pathway in the brain was also inhibited by NAC. Rapamycin in vitro and in vivo protected against Cd-induced neurotoxicity. Conclusions NAC protects against Cd-induced neuronal apoptosis in mouse brain partially by inhibiting ROS-dependent activation of Akt/mTOR pathway. The findings highlight that NAC may be exploited for prevention and treatment of Cd-induced neurodegenerative diseases. PMID:24299490

Angiotensin II potentiates zinc-induced cortical neuronal death by acting on angiotensin II type 2 receptor.

PubMed

Park, Mi-Ha; Kim, Ha Na; Lim, Joon Seo; Ahn, Jae-Sung; Koh, Jae-Young

2013-12-01

The angiotensin system has several non-vascular functions in the central nervous system. For instance, inhibition of the brain angiotensin system results in a reduction in neuronal death following acute brain injury such as ischemia and intracerebral hemorrhage, even under conditions of constant blood pressure. Since endogenous zinc has been implicated as a key mediator of ischemic neuronal death, we investigated the possibility that the angiotensin system affects the outcome of zinc-triggered neuronal death in cortical cell cultures. Exposure of cortical cultures containing neurons and astrocytes to 300 μM zinc for 15 min induced submaximal death in both types of cells. Interestingly, addition of angiotensin II significantly enhanced the zinc-triggered neuronal death, while leaving astrocytic cell death relatively unchanged. Both type 1 and 2 angiotensin II receptors (AT1R and AT2R, respectively) were expressed in neurons as well as astrocytes. Zinc neurotoxicity was substantially attenuated by PD123319, a specific inhibitor of AT2R, and augmented by CGP42112, a selective activator of AT2R, indicating a critical role for this receptor subtype in the augmentation of neuronal cell death.Because zinc toxicity occurs largely through oxidative stress, the levels of superoxides in zinc-treated neurons were assessed by DCF fluorescence microscopy. Combined treatment with zinc and angiotensin II substantially increased the levels of superoxides in neurons compared to those induced by zinc alone. This increase in oxidative stress by angiotensin II was completely blocked by the addition of PD123319. Finally, since zinc-induced oxidative stress may be caused by induction and/or activation of NADPH oxidase, the activation status of Rac and the level of the NADPH oxidase subunit p67phox were measured. Angiotensin II markedly increased Rac activity and the levels of p67phox in zinc-treated neurons and astrocytes in a PD123319-dependent manner. The present study shows that the angiotensin system, especially that involving AT2R, may have an oxidative injury-potentiating effect via augmentation of the activity of NADPH oxidase. Hence, blockade of angiotensin signaling cascades in the brain may prove useful in protecting against the oxidative neuronal death that is likely to occur in acute brain injury.

78 FR 48692 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-09

... Skull as Route of Delivery for Treatment of Brain Injury and Disease Description of Technology: Traumatic Brain injury (TBI) often results from head impact and is a major cause of death and disability. Brain injuries vary in severity and can be associated with hemorrhaging, swelling, inflammation, and...

Annual Report to the Nation on the Status of Cancer, 1975–2007, Featuring Tumors of the Brain and Other Nervous System

PubMed Central

Ward, Elizabeth; McCarthy, Bridget J.; Schymura, Maria J.; Eheman, Christie; Jemal, Ahmedin; Anderson, Robert N.; Ajani, Umed A.; Edwards, Brenda K.

2011-01-01

Background The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute, and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information on cancer occurrence and trends in the United States. This year’s report highlights brain and other nervous system (ONS) tumors, including nonmalignant brain tumors, which became reportable on a national level in 2004. Methods Cancer incidence data were obtained from the National Cancer Institute, CDC, and NAACCR, and information on deaths was obtained from the CDC’s National Center for Health Statistics. The annual percentage changes in age-standardized incidence and death rates (2000 US population standard) for all cancers combined and for the top 15 cancers for men and for women were estimated by joinpoint analysis of long-term (1992–2007 for incidence; 1975–2007 for mortality) trends and short-term fixed interval (1998–2007) trends. Analyses of malignant neuroepithelial brain and ONS tumors were based on data from 1980–2007; data on nonmalignant tumors were available for 2004–2007. All statistical tests were two-sided. Results Overall cancer incidence rates decreased by approximately 1% per year; the decrease was statistically significant (P < .05) in women, but not in men, because of a recent increase in prostate cancer incidence. The death rates continued to decrease for both sexes. Childhood cancer incidence rates continued to increase, whereas death rates continued to decrease. Lung cancer death rates decreased in women for the first time during 2003–2007, more than a decade after decreasing in men. During 2004–2007, more than 213 500 primary brain and ONS tumors were diagnosed, and 35.8% were malignant. From 1987–2007, the incidence of neuroepithelial malignant brain and ONS tumors decreased by 0.4% per year in men and women combined. Conclusions The decrease in cancer incidence and mortality reflects progress in cancer prevention, early detection, and treatment. However, major challenges remain, including increasing incidence rates and continued low survival for some cancers. Malignant and nonmalignant brain tumors demonstrate differing patterns of occurrence by sex, age, and race, and exhibit considerable biologic diversity. Inclusion of nonmalignant brain tumors in cancer registries provides a fuller assessment of disease burden and medical resource needs associated with these unique tumors. PMID:21454908

Tunicamycin-induced unfolded protein response in the developing mouse brain

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

Wang, Haiping; Wang, Xin; Ke, Zun-Ji

Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress, resulting in the activation of the unfolded protein response (UPR). ER stress and UPR are associated with many neurodevelopmental and neurodegenerative disorders. The developing brain is particularly susceptible to environmental insults which may cause ER stress. We evaluated the UPR in the brain of postnatal mice. Tunicamycin, a commonly used ER stress inducer, was administered subcutaneously to mice of postnatal days (PDs) 4, 12 and 25. Tunicamycin caused UPR in the cerebral cortex, hippocampus and cerebellum of mice of PD4 and PD12, which was evident bymore » the upregulation of ATF6, XBP1s, p-eIF2α, GRP78, GRP94 and MANF, but failed to induce UPR in the brain of PD25 mice. Tunicamycin-induced UPR in the liver was observed at all stages. In PD4 mice, tunicamycin-induced caspase-3 activation was observed in layer II of the parietal and optical cortex, CA1–CA3 and the subiculum of the hippocampus, the cerebellar external germinal layer and the superior/inferior colliculus. Tunicamycin-induced caspase-3 activation was also shown on PD12 but to a much lesser degree and mainly located in the dentate gyrus of the hippocampus, deep cerebellar nuclei and pons. Tunicamycin did not activate caspase-3 in the brain of PD25 mice and the liver of all stages. Similarly, immature cerebellar neurons were sensitive to tunicamycin-induced cell death in culture, but became resistant as they matured in vitro. These results suggest that the UPR is developmentally regulated and the immature brain is more susceptible to ER stress. - Highlights: • Tunicamycin caused a development-dependent UPR in the mouse brain. • Immature brain was more susceptible to tunicamycin-induced endoplasmic reticulum stress. • Tunicamycin caused more neuronal death in immature brain than mature brain. • Tunicamycin-induced neuronal death is region-specific.« less

Rapid brain death caused by a cerebellar abscess with Fusobacterium nucleatum in a young man with drug abuse: a case report.

PubMed

Hischebeth, Gunnar T R; Keil, Vera C; Gentil, Katrin; Boström, Azize; Kuchelmeister, Klaus; Bekeredjian-Ding, Isabelle

2014-06-10

Fusobacterium nucleatum is a strict anaerobic microorganism that causes disease entities such as periodontal and soft tissue abscesses, pulmonary and intraabdominal infections and very rarely intracerebral infections. Here, we report the rare case of a previously healthy 25-year-old German man with a cerebellar abscess caused by Fusobacterium nucleatum that resulted in rapid brain death. Toxicological screening showed positivity for amphetamines and cannabis. The diagnosis was obtained by polymerase chain reaction amplification of bacterial deoxyribonucleic acid in cerebrospinal fluid. In drug users clinicians should think about rare causes of brain abscesses/meningitis. Early diagnosis is necessary and justifies the use of molecular techniques.

Combat veterans, mental health issues, and the death penalty: addressing the impact of post-traumatic stress disorder and traumatic brain injury.

PubMed

Giardino, Anthony E

2009-05-01

More than 1.5 million Americans have participated in combat operations in Iraq and Afghanistan over the past seven years. Some of these veterans have subsequently committed capital crimes and found themselves in our nation's criminal justice system. This Essay argues that combat veterans suffering from post-traumatic stress disorder or traumatic brain injury at the time of their offenses should not be subject to the death penalty.Offering mitigating evidence regarding military training, post-traumatic stress disorder, and traumatic brain injury presents one means that combat veterans may use to argue for their lives during the sentencing phase of their trials. Alternatively, Atkins v. Virginia and Roper v. Simmons offer a framework for establishing a legislatively or judicially created categorical exclusion for these offenders, exempting them from the death penalty as a matter of law. By understanding how combat service and service-related injuries affect the personal culpability of these offenders, the legal system can avoid the consequences of sentencing to death America's mentally wounded warriors, ensuring that only the worst offenders are subject to the ultimate punishment.

Two perspectives on organ donation: experiences of potential donor families and intensive care physicians of the same event.

PubMed

Sanner, Margareta A

2007-12-01

The aim was to explore how relatives and physicians understood cases where organ donation had been requested and what factors were salient for the decision on donation. Physicians of 25 deceased patients and 20 relatives were interviewed. The material was analyzed using qualitative methods. Eleven patients had declared their wishes on donation before death; in 14 cases the relatives had to decide. Half of these relatives accepted donation and half refused. The donation request was of secondary importance to the families; they were totally occupied by the death and initially tried to avoid the request by regarding "no" as a nonresponse. They needed support to relieve their immediate reactions of uneasiness, start rational thought processes, and reach well-grounded answers. The basis for requesting donation was good; relatives, with regard to circumstances, had been well prepared for the death by continuous information from the physicians and had confidence in staff, accepted that the question was raised, and understood the death criteria. However, about half the physicians experienced conflicts regarding prerequisites of procuring organs and dealing with relatives. Three different approaches were displayed: prodonation, neutral, and ambivalent. Only physicians with a prodonation approach received acceptance for donation.

Death from undiagnosed glioblastoma multiforme and toxic self-medication presenting with concurrent dysfunctional behavior.

PubMed

Carson, Henry J; Eilers, Stanley G

2008-08-01

We encountered a decedent with an unexpected glioblastoma multiforme. A 61-year-old retired African-American woman was found dead in her home, fully clothed in her bathtub, with a pillow under her head. At autopsy, the brain showed a glioblastoma multiforme. Toxicology showed elevated hydrocodone, propoxyphene, acetaminophen, and positive paroxetine. The presence of a brain tumor likely caused a severe headache. The use of her medications could have indicated a reaction to the escalating pain of the brain trauma, and overuse could be consistent with escalating pain or loss of rational thought processes. The present case is interesting in that it had evidence of behavioral dysfunction that could be related to the brain tumor, and death arising from the glioblastoma multiforme (cerebral hemorrhage and edema) with concurrent multiple drug intoxication.

Competing Risk Analysis of Neurologic versus Nonneurologic Death in Patients Undergoing Radiosurgical Salvage After Whole-Brain Radiation Therapy Failure: Who Actually Dies of Their Brain Metastases?

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

Lucas, John T., E-mail: jolucas@wakehealth.edu; Colmer, Hentry G.; White, Lance

Purpose: To estimate the hazard for neurologic (central nervous system, CNS) and nonneurologic (non-CNS) death associated with patient, treatment, and systemic disease status in patients receiving stereotactic radiosurgery after whole-brain radiation therapy (WBRT) failure, using a competing risk model. Patients and Methods: Of 757 patients, 293 experienced recurrence or new metastasis following WBRT. Univariate Cox proportional hazards regression identified covariates for consideration in the multivariate model. Competing risks multivariable regression was performed to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for both CNS and non-CNS death after adjusting for patient, disease, and treatment factors. The resultantmore » model was converted into an online calculator for ease of clinical use. Results: The cumulative incidence of CNS and non-CNS death at 6 and 12 months was 20.6% and 21.6%, and 34.4% and 35%, respectively. Patients with melanoma histology (relative to breast) (aHR 2.7, 95% CI 1.5-5.0), brainstem location (aHR 2.1, 95% CI 1.3-3.5), and number of metastases (aHR 1.09, 95% CI 1.04-1.2) had increased aHR for CNS death. Progressive systemic disease (aHR 0.55, 95% CI 0.4-0.8) and increasing lowest margin dose (aHR 0.97, 95% CI 0.9-0.99) were protective against CNS death. Patients with lung histology (aHR 1.3, 95% CI 1.1-1.9) and progressive systemic disease (aHR 2.14, 95% CI 1.5-3.0) had increased aHR for non-CNS death. Conclusion: Our nomogram provides individual estimates of neurologic death after salvage stereotactic radiosurgery for patients who have failed prior WBRT, based on histology, neuroanatomical location, age, lowest margin dose, and number of metastases after adjusting for their competing risk of death from other causes.« less

Comparison of water-based foam and carbon dioxide gas mass emergency depopulation of White Pekin ducks.

PubMed

Caputo, M P; Benson, E R; Pritchett, E M; Hougentogler, D P; Jain, P; Patil, C; Johnson, A L; Alphin, R L

2012-12-01

The mass depopulation of production birds remains an effective means of controlling fast-moving, highly infectious diseases such as avian influenza and virulent Newcastle disease. Two experiments were performed to compare the physiological responses of White Pekin commercial ducks during foam depopulation and CO(2) gas depopulation. Both experiment 1 (5 to 9 wk of age) and 2 (8 to 14 wk of age) used electroencephalogram, electrocardiogram, and accelerometer to monitor and evaluate the difference in time to unconsciousness, motion cessation, brain death, altered terminal cardiac activity, duration of bradycardia, and elapsed time from onset of bradycardia to onset of unconsciousness between foam and CO(2) gas. Experiment 2 also added a third treatment, foam + atropine injection, to evaluate the effect of suppressing bradycardia. Experiment 1 resulted in significantly shorter times for all 6 physiological points for CO(2) gas compared with foam, whereas experiment 2 found that there were no significant differences between foam and CO(2) gas for these physiological points except brain death, in which CO(2) was significantly faster than foam and duration of bradycardia, which was shorter for CO(2). Experiment 2 also determined there was a significant positive correlation between duration of bradycardia and time to unconsciousness, motion cessation, brain death, and altered terminal cardiac activity. The time to unconsciousness, motion cessation, brain death, and altered terminal cardiac activity was significantly faster for the treatment foam + atropine injection compared with foam. Both experiments showed that bradycardia can occur as a result of either submersion in foam or exposure to CO(2) gas. The duration of bradycardia has a significant impact on the time it takes White Pekin ducks to reach unconsciousness and death during depopulation.

The efficiency in the utilization of potential donors for organ transplantation in Riyadh, Saudi Arabia.

PubMed

Al-Sebayel, Mohammed I

2003-07-01

Organ transplantation programs have been successful in the Kingdom of Saudi Arabia. This success is limited by organ shortage. The aim of this study is to find out the percentage of actual donors out of all potential donors in intensive care units (ICU), and to look at problems related to the donation process, particularly from the logistical point of view. The study was conducted prospectively for a one year period, June 2001 through to May 2002, in 4 main Riyadh hospitals. Mortality data was collected by a medical professional in each ICU and analyzed on a weekly basis. Final analysis was made at the end of the year. Five hundred and forty-two deaths occurred in these ICUs. Fifty-four percent occurred in one hospital. The number of brain death cases in all hospitals was 114 cases. Thirty-eight cases were reported to the Saudi Center for Organ Transplantation (33%). Documentation was completed in only 23 cases (60%). In these, there was a significant delay in documentation (second test was carried out in 6-12 hours in 4 cases only). We have found that the reporting of brain death cases was low (33%). Dealing with the reported cases is inefficient since only 4 cases were able to become the actual donor out of 38 cases. We found also that there is a gross difference in the number of brain death cases among different hospitals. To improve the efficiency of ICUs in dealing with brain death cases (reporting, documentation, maintenance and consent) will require solving several problems at the medical, administrative, and religious and mass media levels.

Defining human death: an intersection of bioethics and metaphysics.

PubMed

Manninen, Bertha Alvarez

2009-01-01

For many years now, bioethicists, physicians, and others in the medical field have disagreed concerning how to best define human death. Different theories range from the Harvard Criteria of Brain Death, which defines death as the cessation of all brain activity, to the Cognitive Criteria, which is based on the loss of almost all core mental properties, e.g., memory, self-consciousness, moral agency, and the capacity for reason. A middle ground is the Irreversibility Standard, which defines death as occurring when the capacity for consciousness is forever lost. Given all these different theories, how can we begin to approach solving the issue of how to define death? I propose that a necessary starting point is discussing an even more fundamental question that properly belongs in the philosophical field of metaphysics: we must first address the issue of diachronic identity over time, and the persistence conditions of personal identity. In this paper, I illustrate the interdependent relationship between this metaphysical question and questions concerning the definition of death. I also illustrate how it is necessary to antecedently attend to the metaphysical issue of defining death before addressing certain issues in medical ethics, e.g., whether it is morally permissible to euthanize patients in persistent vegetative states or procure organs from anencephalic infants.

Emotional and neutral declarative memory impairments and associated white matter microstructural abnormalities in adults with type 2 diabetes.

PubMed

Yau, Po Lai; Javier, David; Tsui, Wai; Sweat, Victoria; Bruehl, Hannah; Borod, Joan C; Convit, Antonio

2009-12-30

Declarative memory impairment is frequently reported among adults with type 2 diabetes mellitus (T2DM), who also demonstrate hippocampal volume reduction. Our goals were to ascertain whether emotional memory, which is mediated by neural circuits overlapping those of declarative memory, is also affected. In addition we wanted to characterize cerebral white matter (WM) involvement in T2DM. We studied 24 middle-aged and elderly patients with T2DM who were free of obvious vascular pathology or a psychiatric disorder, and 17 age- and education-matched healthy individuals with no evidence of insulin resistance. We examined emotional and neutral memory and performed a whole-brain voxelwise WM assessment utilizing diffusion tensor imaging (DTI). We found clear evidence of impairment in declarative memory among diabetic subjects and in addition found some preliminary support to suggest a possible blunting of the memory facilitation by emotional material among female but not male diabetics. This report is also the first DTI assessment among individuals with T2DM, which after accounting for overt WM damage, revealed diffuse but predominantly frontal and temporal WM microstructural abnormalities, with extensive involvement of the temporal stem. Hierarchical regression analyses demonstrated that immediate, but not delayed, emotional memory performance was explained by temporal stem FA, independent of age, poor metabolic regulation, and systolic blood pressure. Given that the temporal lobe memory networks appear to be particularly vulnerable to the deleterious effects of T2DM, this may help explain the observed memory impairments among diabetics. Future efforts should better clarify, with a larger sample, whether emotional memory is affected in adults with T2DM and whether there are clear gender effects.

Oscillatory Reinstatement Enhances Declarative Memory.

PubMed

Javadi, Amir-Homayoun; Glen, James C; Halkiopoulos, Sara; Schulz, Mei; Spiers, Hugo J

2017-10-11

Declarative memory recall is thought to involve the reinstatement of neural activity patterns that occurred previously during encoding. Consistent with this view, greater similarity between patterns of activity recorded during encoding and retrieval has been found to predict better memory performance in a number of studies. Recent models have argued that neural oscillations may be crucial to reinstatement for successful memory retrieval. However, to date, no causal evidence has been provided to support this theory, nor has the impact of oscillatory electrical brain stimulation during encoding and retrieval been assessed. To explore this we used transcranial alternating current stimulation over the left dorsolateral prefrontal cortex of human participants [ n = 70, 45 females; age mean (SD) = 22.12 (2.16)] during a declarative memory task. Participants received either the same frequency during encoding and retrieval (60-60 or 90-90 Hz) or different frequencies (60-90 or 90-60 Hz). When frequencies matched there was a significant memory improvement (at both 60 and 90 Hz) relative to sham stimulation. No improvement occurred when frequencies mismatched. Our results provide support for the role of oscillatory reinstatement in memory retrieval. SIGNIFICANCE STATEMENT Recent neurobiological models of memory have argued that large-scale neural oscillations are reinstated to support successful memory retrieval. Here we used transcranial alternating current stimulation (tACS) to test these models. tACS has recently been shown to induce neural oscillations at the frequency stimulated. We stimulated over the left dorsolateral prefrontal cortex during a declarative memory task involving learning a set of words. We found that tACS applied at the same frequency during encoding and retrieval enhances memory. We also find no difference between the two applied frequencies. Thus our results are consistent with the proposal that reinstatement of neural oscillations during retrieval supports successful memory retrieval. Copyright © 2017 Javadi et al.

Aquaporin-4 polymorphisms and brain/body weight ratio in sudden infant death syndrome (SIDS).

PubMed

Studer, Jacqueline; Bartsch, Christine; Haas, Cordula

2014-07-01

Failure in the regulation of homeostatic water balance in the brain is associated with severe cerebral edema and increased brain weights and may also play an important role in the pathogenesis of sudden infant death syndrome (SIDS). We genotyped three single-nucleotide polymorphisms in the aquaporin-4 water channel-encoding gene (AQP4), which were previously shown to be associated with (i) SIDS in Norwegian infants (rs2075575), (ii) severe brain edema (rs9951307), and (iii) increased brain water permeability (rs3906956). We also determined whether the brain/body weight ratio is increased in SIDS infants compared with sex- and age-matched controls. Genotyping of the three AQP4 single-nucleotide polymorphisms was performed in 160 Caucasian SIDS infants and 181 healthy Swiss adults using a single-base extension method. Brain and body weights were measured during autopsy in 157 SIDS and 59 non-SIDS infants. No differences were detected in the allelic frequencies of the three AQP4 single-nucleotide polymorphisms between SIDS and adult controls. The brain/body weight ratio was similarly distributed in SIDS and non-SIDS infants. Variations in the AQP4 gene seem of limited significance as predisposing factors in Caucasian SIDS infants. Increased brain weights may only become evident in conjunction with environmental or other genetic risk factors.

Antioxidant gene therapy against neuronal cell death

PubMed Central

Navarro-Yepes, Juliana; Zavala-Flores, Laura; Annadurai, Anandhan; Wang, Fang; Skotak, Maciej; Chandra, Namas; Li, Ming; Pappa, Aglaia; Martinez-Fong, Daniel; Razo, Luz Maria Del; Quintanilla-Vega, Betzabet; Franco, Rodrigo

2014-01-01

Oxidative stress is a common hallmark of neuronal cell death associated with neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, as well as brain stroke/ischemia and traumatic brain injury. Increased accumulation of reactive species of both oxygen (ROS) and nitrogen (RNS) has been implicated in mitochondrial dysfunction, energy impairment, alterations in metal homeostasis and accumulation of aggregated proteins observed in neurodegenerative disorders, which lead to the activation/modulation of cell death mechanisms that include apoptotic, necrotic and autophagic pathways. Thus, the design of novel antioxidant strategies to selectively target oxidative stress and redox imbalance might represent important therapeutic approaches against neurological disorders. This work reviews the evidence demonstrating the ability of genetically encoded antioxidant systems to selectively counteract neuronal cell loss in neurodegenerative diseases and ischemic brain damage. Because gene therapy approaches to treat inherited and acquired disorders offer many unique advantages over conventional therapeutic approaches, we discussed basic research/clinical evidence and the potential of virus-mediated gene delivery techniques for antioxidant gene therapy. PMID:24333264

Trend of brain tumor incidence by histological subtypes in Japan: estimation from the Brain Tumor Registry of Japan, 1973-1993.

PubMed

Kaneko, Satoshi; Nomura, Kazuhiro; Yoshimura, Takesumi; Yamaguchi, Naohito

2002-10-01

In order to estimate the risk of primary brain tumor (PBT), we attempted to estimate the national incidence rates of PBT by histological subtypes using the Brain Tumor Registry of Japan (BTR). The number of deaths due to PBT in a certain year is the sum of the deaths among patients diagnosed in different years. Registered cases in the BTR represent incident cases of PBT in the whole country multiplied by a cover rate. The cover rate is defined as the proportions of PBT cases that the Registry counts in relation to all the cases in the country in a given year. If the survival experience among the registered cases represents the survival experience of all cases, then the rate of registered deaths represents all deaths due to PBT in Japan. By this logic, we estimated the cover rates and incidence rates from 1973 to 1993 using the BTR and National Vital Statistics data. Our estimates showed three patterns of time trends: (1) a gradual linear increasing trend before the 1980s followed by a plateau (total PBT, gliomas, meningioma, and hemangioblastoma), (2) a trend with a step-up increase in the 1980s followed by a plateau (germ cell tumor and pituitary tumor), and (3) a linear increasing trend throughout the observation period with no plateau (malignant lymphoma and neurinoma). Furthermore, obvious sex differences in time trends were observed in rates of meningioma, germ cell tumor, and pituitary tumor. The results of this study demonstrated several distinctive patterns in time trends, which give us insight into the possible etiologies of brain tumors. Further epidemiological study is needed to elucidate these findings.

The influence of sociocultural factors on organ donation and transplantation in Korea: findings from key informant interviews.

PubMed

Kim, Jung Ran; Elliott, Doug; Hyde, Cheryl

2004-04-01

Although brain death was formally recognized in Korea in 2000 for the purpose of organ donation, traditional Confucian-based thought still prevails. The aim of this study was to explore sociocultural perspectives that influence health professionals' attitudes and perceptions regarding organ donation. Semistructured interviews were conducted with nine key informants from three major hospitals providing transplant services in South Korea. Several themes were identified as barriers to organ donation: Confucianism, misunderstandings and myths, organs as spare for selling, lack of clarity in the definition of death in the new legislation, and limited medical insurance coverage. It remains difficult for brain death to be accepted as true death, and there is currently a poor rate of organ procurement. Findings of the study will help identify socioculturally appropriate strategies to promote acceptance and accessibility of organ transplantation among South Koreans.

Methamphetamine-induced neuronal necrosis: the role of electrographic seizure discharges

PubMed Central

Fujikawa, Denson G.; Pais, Emil S.; Aviles, Ernesto R.; Hsieh, Kung-Chiao; Bashir, Muhammad Tariq

2016-01-01

We have evidence that methamphetamine (METH)-induced neuronal death is morphologically necrotic, not apoptotic, as is currently believed, and that electrographic seizures may be responsible. We administered 40 mg/kg i.p. to 12 male C57BL/6 mice and monitored EEGs continuously and rectal temperatures every 15 min, keeping rectal temperatures <41.0 °C. Seven of the 12 mice had repetitive electrographic seizure discharges (RESDs) and 5 did not. The RESDs were often not accompanied by behavioral signs of seizures–i.e., they were often not accompanied by clonic forelimb movements. The 7 mice with RESDs had acidophilic neurons (the H&E light-microscopic equivalent of necrotic neurons by ultrastructural examination) in all of 7 brain regions (hippocampal CA1, CA2, CA3 and hilus, amygdala, piriform cortex and entorhinal cortex), the same brain regions damaged following generalized seizures, 24 h after METH administration. The 5 mice without RESDs had a few acidophilic neurons in 4 of the 7 brain regions, but those with RESDs had significantly more in 6 of the 7 brain regions. Maximum rectal temperatures were comparable in mice with and without RESDs, so that cannot explain the difference between the two groups with respect to METH-induced neuronal death. Our data show that METH-induced neuronal death is morphologically necrotic, that EEGs must be recorded to detect electrographic seizure activity in rodents without behavioral evidence of seizures, and that RESDs may be responsible for METH-induced neuronal death. PMID:26562800

[Short-term outcomes of lung transplant recipients using organs from brain death donors].

PubMed

He, W X; Jiang, C; Liu, X G; Huang, W; Chen, C; Jiang, L; Yang, B; Wu, K; Chen, Q K; Yang, Y; Yu, Y M; Jiang, G N

2016-12-01

Objective: To assess short-term outcomes after lung transplantation with organs procured following brain death. Methods: Between April 2015 and July 2016, all 17 recipients after lung transplantation using organs from brain death donors (DBD) at Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine were enrolled in this study. All patients were male, aging (60±7) years, including 11 chronic obstructive pulmonary disease, 5 idiopathic pulmonary fibrosis, 1 silicosis. Seventeen donors were 16 males and 1 female, with 10 traumatic brain injury, 5 cerebrovascular accident and 2 sudden cardiac death. Of 17 recipients receiving DBD lung transplant, 16 were single lung transplant. Data were collected including intubation duration of mechanical ventilation, hospital length of stay, incidence of pulmonary infection bronchus anastomosis complications, primary graft dysfunction (PGD), and acute rejection, bronchiolitis obliterans syndrome (BOS) as well as mortality of 90-day after lung transplantation. Results: Median duration of intubation were 2 (2) days ( M ( Q R )) in recipients after lung transplantation. The incidence of pulmonary infection and bronchus anastomosis complications were 15/17 and 5/17, respectively. Median length of stay in hospital were 56 (19) days. The ratio of readmission 1 month after discharge were 10/17. Mortality of 90-day post-transplant were 2/17. The incidence of PGD and BOS were 1/17 and 2/17, respectively. Conclusion: Recipients with DBD lung transplantation have an acceptable survival during short-term follow-up, but with higher incidences of complications related to infection post-transplantation.

[Is the brain the creator of psychic phenomena or is a paradigm shift inevitable?].

PubMed

Bonilla, Ernesto

2014-06-01

Every day new scientific information is appearing that cannot be explained using the classical Newtonian model and is calling for the emergence of a new paradigm that would include the explanation of such phenomena as telepathy, clairvoyance, presentiment, precognition, out of the body experiences, psychic healing, after-death communication, near-death experiences and reincarnation. The materialist paradigm which considers the brain as the sole cause of consciousness and psychic phenomena has been challenged by a new paradigm that seems to demonstrate that there is not a cause-effect relationship between brain activity and psychic phenomena but only a correlation between them, since these phenomena can be experienced without the body and appear to have an extra-cerebral origin (cosmic field, cosmic consciousness?). Of course, the brain is intensely involved in the manifestation of consciousness in our daily life but this is not equivalent to affirm that brain creates consciousness. Recent findings force us to consider a non-physical, spiritual and transpersonal aspect of reality.

Sulthiame but not levetiracetam exerts neurotoxic effect in the developing rat brain.

PubMed

Manthey, Daniela; Asimiadou, Stella; Stefovska, Vanya; Kaindl, Angela M; Fassbender, Jessica; Ikonomidou, Chrysanthy; Bittigau, Petra

2005-06-01

Antiepileptic drugs (AEDs) used to treat seizures in pregnant women, infants, and young children can cause cognitive impairment. One mechanism implicated in the development of neurocognitive deficits is a pathologic enhancement of physiologically occurring apoptotic neuronal death in the developing brain. We investigated whether the newer antiepileptic drug levetiracetam (LEV) and the older antiepileptic drug sulthiame (SUL) have neurotoxic properties in the developing rat brain. SUL significantly enhanced neuronal death in the brains of rat pups ages 0 to 7 days at doses of 100 mg/kg and above, whereas LEV did not show this neurotoxic effect. Dosages of both drugs used in the context of this study comply with an effective anticonvulsant dose range applied in rodent seizure models. Thus, LEV is an AED which lacks neurotoxicity in the developing rat brain and should be considered in the treatment of epilepsy in pregnant women, infants, and toddlers once general safety issues have been properly addressed.

Quantitative in vivo detection of brain cell death after hypoxia ischemia using the lipid peak at 1.3 ppm of proton magnetic resonance spectroscopy in neonatal rats.

PubMed

Ahn, So Yoon; Yoo, Hye Soo; Lee, Jang Hoon; Sung, Dong Kyung; Jung, Yu Jin; Sung, Se In; Lim, Keun Ho; Chang, Yun Sil; Lee, Jung Hee; Kim, Ki Soo; Park, Won Soon

2013-07-01

This study was performed to determine the accuracy of proton magnetic spectroscopy ((1)H-MRS) lipid peak as a noninvasive tool for quantitative in vivo detection of brain cell death. Seven day-old Sprague Dawley rats were subjected to 8% oxygen following a unilateral carotid artery ligation. For treatment, cycloheximide was given immediately after hypoxic ischemia (HI). Lipid peak was measured using (1)H-MRS at 24 hr after HI, and then brains were harvested for fluorocytometric analyses with annexin V/propidium iodide (PI) and fluorescent probe JC-1, and for adenosine-5'-triphosphate (ATP) and lactate. Increased lipid peak at 1.3 ppm measured with (1)H-MRS, apoptotic and necrotic cells, and loss of mitochondrial membrane potential (ΔΨ) at 24 hr after HI were significantly improved with cycloheximide treatment. Significantly reduced brain ATP and increased lactate levels observed at 24 hr after HI showed a tendency to improve without statistical significance with cycloheximide treatment. Lipid peak at 1.3 ppm showed significant positive correlation with both apoptotic and necrotic cells and loss of ΔΨ, and negative correlation with normal live cells. Lipid peak at 1.3 ppm measured by (1)H-MRS might be a sensitive and reliable diagnostic tool for quantitative in vivo detection of brain cell death after HI.

Differential DNA damage in response to the neonatal and adult excitotoxic hippocampal lesion in rats.

PubMed

Khaing, Z Z; Weickert, C S; Weinberger, D R; Lipska, B K

2000-12-01

We examined the developmental profile of excitotoxin-induced nuclear DNA fragmentation using the transferase dUTP nick-end labelling (TUNEL) technique, as a marker of DNA damage and cell death in rats with neonatal and adult excitotoxic lesions of the ventral hippocampus. We hypothesized that infusion of neurotoxin may result in a differential pattern of cell death in neonatally and adult lesioned rats, both in the infusion site and in remote brain regions presumably involved in mediating behavioural changes observed in these animals. Brains of rats lesioned at 7 days of age and in adulthood were collected at several survival times 1-21 days after the lesion. In the lesioned neonates 1-3 days postlesion, marked increases in TUNEL-positive cells occurred in the ventral hippocampus, the site of neurotoxin infusion, and in a wide surrounding area. Adult lesioned brains showed more positive cells than controls only at the infusion site. In the lesioned neonates, TUNEL-labelled cells were also present in the striatum and nucleus accumbens 1 day postlesion but not at later survival times. Our findings indicate that cell death in remote regions is more prominent in immature than adult brains, that it may lead to distinct alterations in development of these brain regions, and thus may be responsible for functional differences between neonatally and adult lesioned rats.

Electrical Stimulation Modulates High γ Activity and Human Memory Performance

PubMed Central

Berry, Brent M.; Miller, Laura R.; Khadjevand, Fatemeh; Ezzyat, Youssef; Wanda, Paul; Sperling, Michael R.; Lega, Bradley; Stead, S. Matt

2018-01-01

Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We found that high γ (62–118 Hz) activity induced by word presentation was modulated by electrical stimulation. This modulatory effect was greatest for trials with “poor” memory encoding. The high γ modulation correlated with the behavioral effect of stimulation in a given brain region: it was negative, i.e., the induced high γ activity was decreased, in the regions where stimulation decreased memory performance, and positive in the lateral TC where memory enhancement was observed. Our results suggest that the effect of electrical stimulation on high γ activity induced by word presentation may be a useful biomarker for mapping memory networks and guiding therapeutic brain stimulation. PMID:29404403

Memory and cognitive control circuits in mathematical cognition and learning.

PubMed

Menon, V

2016-01-01

Numerical cognition relies on interactions within and between multiple functional brain systems, including those subserving quantity processing, working memory, declarative memory, and cognitive control. This chapter describes recent advances in our understanding of memory and control circuits in mathematical cognition and learning. The working memory system involves multiple parietal-frontal circuits which create short-term representations that allow manipulation of discrete quantities over several seconds. In contrast, hippocampal-frontal circuits underlying the declarative memory system play an important role in formation of associative memories and binding of new and old information, leading to the formation of long-term memories that allow generalization beyond individual problem attributes. The flow of information across these systems is regulated by flexible cognitive control systems which facilitate the integration and manipulation of quantity and mnemonic information. The implications of recent research for formulating a more comprehensive systems neuroscience view of the neural basis of mathematical learning and knowledge acquisition in both children and adults are discussed. © 2016 Elsevier B.V. All rights reserved.

Hand gestures support word learning in patients with hippocampal amnesia.

PubMed

Hilverman, Caitlin; Cook, Susan Wagner; Duff, Melissa C

2018-06-01

Co-speech hand gesture facilitates learning and memory, yet the cognitive and neural mechanisms supporting this remain unclear. One possibility is that motor information in gesture may engage procedural memory representations. Alternatively, iconic information from gesture may contribute to declarative memory representations mediated by the hippocampus. To investigate these alternatives, we examined gesture's effects on word learning in patients with hippocampal damage and declarative memory impairment, with intact procedural memory, and in healthy and in brain-damaged comparison groups. Participants learned novel label-object pairings while producing gesture, observing gesture, or observing without gesture. After a delay, recall and object identification were assessed. Unsurprisingly, amnesic patients were unable to recall the labels at test. However, they correctly identified objects at above chance levels, but only if they produced a gesture at encoding. Comparison groups performed well above chance at both recall and object identification regardless of gesture. These findings suggest that gesture production may support word learning by engaging nondeclarative (procedural) memory. © 2018 Wiley Periodicals, Inc.

[Posttraumatic stress disorder in patients with neurogenic amnesia for the traumatic event].

PubMed

Podoll, K; Kunert, H J; Sass, H

2000-10-01

The development of symptoms of posttraumatic stress disorder (PTSD) in patients with neurogenic amnesia for the traumatic event is recorded in 2 own patients and in 19 cases from the clinical literature. With a single exception, all patients were accident victims with closed head injuries. Only about three quarters of the patients completely fulfilled DSM-III-R criteria of PTSD. Nineteen patients displayed involuntary conscious memories of aspects of the traumatic event (presenting as recurrent intrusive thoughts, images or dreams) co-existent with a complete or partial lack of voluntary conscious memories of the trauma, suggesting that different memory systems and distinct brain mechanisms subserve these phenomena. The said clinical observations are discussed against the background of current neuropsychological models of multiple memory systems. The recorded cases demonstrate that declarative episodic memory is not necessary for symptoms of PTSD to emerge, whereas preserved functions of non-declarative memory systems represent a sufficient condition for the development of PTSD symptoms.

Memory and cognitive control circuits in mathematical cognition and learning

PubMed Central

Menon, V.

2018-01-01

Numerical cognition relies on interactions within and between multiple functional brain systems, including those subserving quantity processing, working memory, declarative memory, and cognitive control. This chapter describes recent advances in our understanding of memory and control circuits in mathematical cognition and learning. The working memory system involves multiple parietal–frontal circuits which create short-term representations that allow manipulation of discrete quantities over several seconds. In contrast, hippocampal–frontal circuits underlying the declarative memory system play an important role in formation of associative memories and binding of new and old information, leading to the formation of long-term memories that allow generalization beyond individual problem attributes. The flow of information across these systems is regulated by flexible cognitive control systems which facilitate the integration and manipulation of quantity and mnemonic information. The implications of recent research for formulating a more comprehensive systems neuroscience view of the neural basis of mathematical learning and knowledge acquisition in both children and adults are discussed. PMID:27339012

Induction of specific micro RNA (miRNA) species by ROS-generating metal sulfates in primary human brain cells

PubMed Central

Lukiw, Walter J.; Pogue, Aileen I.

2007-01-01

Iron- and aluminum-sulfate together, at nanomolar concentrations, trigger the production of reactive oxygen species (ROS) in cultures of human brain cells. Previous studies have shown that following ROS induction, a family of pathogenic brain genes that promote inflammatory signalling, cellular apoptosis and brain cell death is significantly over-expressed. Notably, iron- and aluminum-sulfate induce genes in cultured human brain cells that exhibit expression patterns similar to those observed to be up-regulated in moderate- to late-stage Alzheimer's disease (AD). In this study we have extended our investigations to analyze the expression of micro RNA (miRNA) populations in iron- and aluminum-sulfate treated human neural cells in primary culture. The main finding was that these ROS-generating neurotoxic metal sulfates also up-regulate a specific set of miRNAs that includes miR-9, miR-125b and miR-128. Notably, these same miRNAs are up-regulated in AD brain. These findings further support the idea that iron- and aluminum-sulfates induce genotoxicity via a ROS-mediated up-regulation of specific regulatory elements and pathogenic genes that redirect brain cell fate towards progressive dysfunction and apoptotic cell death. PMID:17629564

Near-Death-Like Experiences without Life-Threatening Conditions or Brain Disorders: A Hypothesis from a Case Report

PubMed Central

Facco, Enrico; Agrillo, Christian

2012-01-01

Near-death experiences (NDEs) are profound psychic experiences commonly occurring in life-threatening conditions. They include feeling a sense of peace, of seeing a bright light, encountering deceased relatives or religious figures, and of transcending space and time. To explain them, it has been suggested that they stem from brain disorders and/or psychological reactions to approaching death, a sort of wishful thinking in response to the perceived threat. This is a report on a case with most of the features typical of NDEs except that it occurred entirely without any life-threatening conditions. This evidence is theoretically incompatible with either of the above hypotheses, suggesting that a broader interpretation of the phenomenon is needed. PMID:23162522

Excess cancer mortality among children and adolescents in residential districts polluted by petrochemical manufacturing plants in Taiwan

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

Bi Jen Pan; Yu Jue Hong; Gwo Chin Chang

1994-12-31

We have collected data on the cancer deaths of children and adolescents 0-19 yr old living in a residential area near 3 large petroleum and petrochemical complexes in and near Kaohsiung city (petrochemical industrial districts, PIDs) in the period of 1971-1990 and compared these with the cancer deaths of children and adolescents 0-19 yr old among the entire population of Taiwan (national reference) and among the residents of 26 administrative districts, comprising all of Kaohsiung city and Kaohsiung county (local reference), except for 8 sparsely populated, rural districts. Having scrutinized all cancer death certificates, we have identified various statistically significantmore » excess deaths, as compared with the national and local reference, due to cancers at all sites. Cancer of the bone, brain, and bladder in boys and girls 0-9 yr and 10-19 yr of age in the 1981-1990 decade that followed the establishment of petrochemical production in the PIDs was studied. However, excess cancer deaths seemed to have clustered in the 10-19 yr age group, who had been potentially exposed to the petrochemical pollutants for the longest period of time from the youngest age. Almost all bone, brain, and bladder cancer deaths registered were within 3 km of the 3 complexes. Bone and brain cancers in particular occurred in girls in the PIDs more frequently than in boys, even though these are believed to occur more in males than females elsewhere. 32 refs., 1 fig., 6 tabs.« less

Fentanyl and heroin contained in seized illicit drugs and overdose-related deaths in British Columbia, Canada: An observational analysis.

PubMed

Baldwin, Nicholas; Gray, Roger; Goel, Anirudh; Wood, Evan; Buxton, Jane A; Rieb, Launette Marie

2018-04-01

Due to the alarming rise in opioid-related overdose deaths, a public health emergency was declared in British Columbia (BC). In this study, we examined the relationship between illicit fentanyl and heroin found in seized drugs and illicit overdose deaths in BC. An observational cross-sectional survey was conducted using BC data from Health Canada's Drug Analysis Service, which analyzes drug samples seized by law enforcement agencies, and non-intentional illicit overdoses from the BC Coroner's Service, from 2000 to 2016. Initial scatter plots and subsequent multivariate regression analysis were performed to describe the potential relationship between seized illicit fentanyl samples and overdose deaths and to determine if this differed from seized heroin and overdose deaths. Fentanyl samples were analyzed for other drug content. Fentanyl is increasingly being found combined with other opioid and non-opioid illicit drugs. Strong positive relationships were found between the number of seized fentanyl samples and total overdose deaths (R2 = 0.97) as well as between seized fentanyl and fentanyl-detected overdose deaths (R2 = 0.99). A positive association was found between the number of seized heroin samples and total overdose deaths (R2 = 0.78). This research contributes to the expanding body of evidence implicating illicit fentanyl use (often combined with heroin or other substances) in overdose deaths in BC. Policy makers and healthcare providers are urged to implement drug treatment and harm reduction strategies for people at risk of overdose associated with current trends in illicit opioid use. Copyright © 2018 Elsevier B.V. All rights reserved.

Patterns of cell death in the perinatal mouse forebrain.

PubMed

Mosley, Morgan; Shah, Charisma; Morse, Kiriana A; Miloro, Stephen A; Holmes, Melissa M; Ahern, Todd H; Forger, Nancy G

2017-01-01

The importance of cell death in brain development has long been appreciated, but many basic questions remain, such as what initiates or terminates the cell death period. One obstacle has been the lack of quantitative data defining exactly when cell death occurs. We recently created a "cell death atlas," using the detection of activated caspase-3 (AC3) to quantify apoptosis in the postnatal mouse ventral forebrain and hypothalamus, and found that the highest rates of cell death were seen at the earliest postnatal ages in most regions. Here we have extended these analyses to prenatal ages and additional brain regions. We quantified cell death in 16 forebrain regions across nine perinatal ages from embryonic day (E) 17 to postnatal day (P) 11 and found that cell death peaks just after birth in most regions. We found greater cell death in several regions in offspring delivered vaginally on the day of parturition compared with those of the same postconception age but still in utero at the time of collection. We also found massive cell death in the oriens layer of the hippocampus on P1 and in regions surrounding the anterior crossing of the corpus callosum on E18 as well as the persistence of large numbers of cells in those regions in adult mice lacking the pro-death Bax gene. Together these findings suggest that birth may be an important trigger of neuronal cell death and identify transient cell groups that may undergo wholesale elimination perinatally. J. Comp. Neurol. 525:47-64, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Expressions of Mast Cell Tryptase and Brain Natriuretic Peptide in Myocardium of Sudden Death due to Hypersensitivity and Coronary Atherosclerotic Heart Disease.

PubMed

Shi, J R; Tian, C J; Zeng, Q; Guo, X J; Lu, J; Gao, C R

2016-06-01

To explore the value of mast cell tryptase and brain natriuretic peptide（BNP） in the differential diagnostic of sudden death due to hypersensitivity and coronary atherosclerotic heart disease. Totally 30 myocardial samples were collected from the autopsy cases in the Department of Forensic Pathology, Shanxi Medical University during 2010-2015. All samples were divided into three groups： death of craniocerebral injury group, sudden death of hypersensitivity group and sudden death of coronary atherosclerotic heart disease group, 10 cases in each group. Mast cell tryptase and BNP in myocardium were detected by immunofluorescence staining and Western Blotting. Immunofluorescence staining showed that the positive staining mast cell tryptase appeared in myocardium of sudden death of hypersensitivity group and coronary atherosclerotic heart disease group. Among the three groups, the expression of mast cell tryptase showed significantly differences through pairwise comparison （ P <0.05）; The expression level of BNP in sudden death of coronary atherosclerotic heart disease group were significantly higher than the sudden death of hypersensitivity group and death of craniocerebral injury group （ P <0.05）. The difference of the expression level of BNP between the sudden death of hypersensitivity group and the death of craniocerebral injury group had no statistical significance （ P >0.05）. The combined detection of the mast cell tryptase and BNP in myocardium is expected to provide help for the forensic differential diagnosis of sudden death due to hypersensitivity and coronary atherosclerotic heart disease. Copyright© by the Editorial Department of Journal of Forensic Medicine

Tissue residues of dieldrin in relation to mortality in birds and mammals

USGS Publications Warehouse

Stickel, W.H.; Stickel, L.F.; Spann, J.W.; Miller, M.W.; Berg, G.G.

1969-01-01

An experiment was performed with Coturnix to learn what residue levels were indicative of death from dieldrin poisoning. Birds were fed diets containing 250, 50, 10, and 2 ppm dieldrin for periods up to 158 days. The dieldrin was 95% pure HEOD, which is 1,2,3,4,10,10-hexachloro-6, 7.epoxy. l,4,4a,5,6,7,8,8a-octahydro-l,4-endo,exo-5,8- dimethanonaphthalene. When half of a group was dead, the other half was sacrificed for comparison of residues in dead and survivors. Dosage levels controlled time to death, but did not control residue levels in the dead. Residues in liver and carcass proved to be misleading and complicated by changes in lipid content. Brain residues correlated well with death although residues in dead and survivors overlapped. Brain residues of animals killed by dieldrin in the field and in other experiments are listed. Data agree in general for several species of birds and mammals. There is evidence, however, for species differences in average lethal brain residues. It is concluded that brain residues of 4 or 5 ppm (wet weight) or higher indicate that the animal was in the known danger zone and may have died from dieldrin. Brain residues averaged lower in wild than in experimental animals. Possible explanations include species differences, more stress and exertion in the wild, and overrepresentation in the field series of individuals that will die with low but lethal brain residues. The latter is supported by the fact that the first Coturnix to die in each sex and treatment group had the lowest brain residue of its group. Birds receiving 2 ppm dieldrin, and some receiving 10 ppm, were able to maintain low brain residues throughout the experiment. However, birds of the 10 ppm group could withstand little stress and mobilization of toxicant, for a few micrograms in the brain were lethal and bodies contained hundreds or thousands of micrograms.

Good Samaritan surgeon wrongly accused of contributing to President Lincoln's death: an experimental study of the President's fatal wound.

PubMed

Lattimer, J K; Laidlaw, A

1996-05-01

When President Abraham Lincoln was shot in the back of the head at Ford's Theater in Washington, D.C., on April 14, 1865, he was immediately rendered unconscious and apneic. Doctor Charles A. Leale, an Army surgeon, who had special training in the care of brain injuries, rushed to Lincoln's assistance. When Doctor Leale probed the wound in Lincoln's thickened scalp, feeling for the bullet, he dislodged a blood clot, and Lincoln began to breathe again. However, Lincoln progressively deteriorated and died at 7:22 AM on April 15, 1865. During the postmortem examination of Lincoln's body, numerous secondary missiles of bone and metal were found in the track of pultaceous brain tissue, extending completely through the brain to the front of the skull. In February 1995, an article in a popular magazine alleged that Doctor Leale had caused further (fatal) damage to Lincoln's brain by thrusting his finger into the brain through the bullet hole. The article alleged (wrongly) that most bullet wounds of the brain incurred in Civil War times were not fatal. The following study demonstrates that it is impossible to introduce even the tip of the little finger through a hole in the skull resulting from a .41-caliber bullet fired from a derringer. In our study, a .41-caliber derringer was used to fire bullets into numerous fresh skulls; the bullet holes all had razor-sharp edges and were much too small to accommodate a fingertip. Thus, the allegation that President Lincoln's brain was damaged further because Doctor Leale thrust his finger through the bullet hole into the brain parenchyma is not valid. In this study, experimental data are presented to demonstrate the foregoing point. The wound made by John Wilkes Booth's derringer ball in Lincoln's brain was devastating; it was clearly the cause of his death. Good Samaritan surgeon Leale has been falsely accused of contributing to Lincoln's death.

Disentangling the roles of arousal and amygdala activation in emotional declarative memory.

PubMed

de Voogd, Lycia D; Fernández, Guillén; Hermans, Erno J

2016-09-01

A large body of evidence in animals and humans implicates the amygdala in promoting memory for arousing experiences. Although the amygdala can trigger threat-related noradrenergic-sympathetic arousal, in humans amygdala activation and noradrenergic-sympathetic arousal do not always concur. This raises the question how these two processes play a role in enhancing emotional declarative memory. This study was designed to disentangle these processes in a combined subsequent-memory/fear-conditioning paradigm with neutral items belonging to two conceptual categories as conditioned stimuli. Functional MRI, skin conductance (index of sympathetic activity), and pupil dilation (indirect index of central noradrenergic activity) were acquired throughout procedures. Recognition memory for individual items was tested 24 h later. We found that pupil dilation and skin conductance responses were higher on CS+ (associated with a shock) compared with CS- trials, irrespective of later memory for those items. By contrast, amygdala activity was only higher for CS+ items that were later confidently remembered compared with CS+ items that were later forgotten. Thus, amygdala activity and not noradrenergic-sympathetic arousal, predicted enhanced declarative item memory. This dissociation is in line with animal models stating that the amygdala integrates arousal-related neuromodulatory changes to alter mnemonic processes elsewhere in the brain. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Threat of Punishment Motivates Memory Encoding via Amygdala, Not Midbrain, Interactions with the Medial Temporal Lobe

PubMed Central

Murty, Vishnu P.; LaBar, Kevin S.; Adcock, R. Alison

2012-01-01

Neural circuits associated with motivated declarative encoding and active threat avoidance have both been described, but the relative contribution of these systems to punishment-motivated encoding remains unknown. The current study used functional magnetic resonance imaging in humans to examine mechanisms of declarative memory enhancement when subjects were motivated to avoid punishments that were contingent on forgetting. A motivational cue on each trial informed participants whether they would be punished or not for forgetting an upcoming scene image. Items associated with the threat of shock were better recognized 24 h later. Punishment-motivated enhancements in subsequent memory were associated with anticipatory activation of right amygdala and increases in its functional connectivity with parahippocampal and orbitofrontal cortices. On a trial-by-trial basis, right amygdala activation during the motivational cue predicted hippocampal activation during encoding of the subsequent scene; across participants, the strength of this interaction predicted memory advantages due to motivation. Of note, punishment-motivated learning was not associated with activation of dopaminergic midbrain, as would be predicted by valence-independent models of motivation to learn. These data are consistent with the view that motivation by punishment activates the amygdala, which in turn prepares the medial temporal lobe for memory formation. The findings further suggest a brain system for declarative learning motivated by punishment that is distinct from that for learning motivated by reward. PMID:22745496

Threat of punishment motivates memory encoding via amygdala, not midbrain, interactions with the medial temporal lobe.

PubMed

Murty, Vishnu P; Labar, Kevin S; Adcock, R Alison

2012-06-27

Neural circuits associated with motivated declarative encoding and active threat avoidance have both been described, but the relative contribution of these systems to punishment-motivated encoding remains unknown. The current study used functional magnetic resonance imaging in humans to examine mechanisms of declarative memory enhancement when subjects were motivated to avoid punishments that were contingent on forgetting. A motivational cue on each trial informed participants whether they would be punished or not for forgetting an upcoming scene image. Items associated with the threat of shock were better recognized 24 h later. Punishment-motivated enhancements in subsequent memory were associated with anticipatory activation of right amygdala and increases in its functional connectivity with parahippocampal and orbitofrontal cortices. On a trial-by-trial basis, right amygdala activation during the motivational cue predicted hippocampal activation during encoding of the subsequent scene; across participants, the strength of this interaction predicted memory advantages due to motivation. Of note, punishment-motivated learning was not associated with activation of dopaminergic midbrain, as would be predicted by valence-independent models of motivation to learn. These data are consistent with the view that motivation by punishment activates the amygdala, which in turn prepares the medial temporal lobe for memory formation. The findings further suggest a brain system for declarative learning motivated by punishment that is distinct from that for learning motivated by reward.

Cognitive effects of methylphenidate and levodopa in healthy volunteers.

PubMed

Linssen, A M W; Sambeth, A; Vuurman, E F P M; Riedel, W J

2014-02-01

Our previous study showed enhanced declarative memory consolidation after acute methylphenidate (MPH) administration. The primary aim of the current study was to investigate the duration of this effect. Secondary, the dopaminergic contribution of MPH effects, the electrophysiological correlates of declarative memory, and the specificity of memory enhancing effects of MPH to declarative memory were assessed. Effects of 40 mg of MPH on memory performance were compared to 100mg of levodopa (LEV) in a placebo-controlled crossover study with 30 healthy volunteers. Memory performance testing included a word learning test, the Sternberg memory scanning task, a paired associates learning task, and a spatial working memory task. During the word learning test, event-related brain potentials (ERPs) were measured. MPH failed to enhance retention of words at a 30 min delay, but it improved 24 h delayed memory recall relative to PLA and LEV. Furthermore, during encoding, the P3b and P600 ERP latencies were prolonged and the P600 amplitude was larger after LEV compared to PLA and MPH. MPH speeded response times on the Sternberg Memory Scanning task and improved performance on the Paired Associates Learning task, relative to LEV, but not PLA. Performance on the Spatial working memory task was not affected by the treatments. These findings suggest that MPH and LEV might have opposite effects on memory. © 2013 Published by Elsevier B.V. and ECNP.

Place of death of pediatric cancer patients in a single institute during 7 years.

PubMed

Yanai, Tomoko; Hirase, Satoshi; Matsunoshita, Natsuki; Yamamoto, Nobuyuki; Ninchoji, Takeshi; Kubokawa, Ikuko; Mori, Takeshi; Hayakawa, Akira; Takeshima, Yasuhiro; Iijima, Kazumoto; Matsuo, Masafumi

2012-06-27

Place of death is an important issue at the end-of-life. It is poorly understood in pediatric cancer patients in Japan. This study aimed to clarify place of death of children with cancer as well as variables associated with place of death. Study population was pediatric cancer patients who died in the Department of Pediatrics at Kobe University Hospital during the last 7 years. The medical records were retrospectively reviewed regardless of cause of death to derive data relating to patients' characteristics and disease. 18 patients were included. Median age at death was 12.2 years old. 6 patients including 5 children in complete remission had hematological disease and 12 patients suffered from solid tumors. 4 patients (22.2%) died at home, whereas 14 patients (77.8%) died in the hospital including 6 ICU deaths. No one died in hospices. Preference of patients was unavailable due to the lack of inquiry. Factors influencing place of death (home, ICU, non-ICU) were disease (hematological disease vs. solid tumor, p=0.010, brain tumor vs. non-brain tumor, p=0.023), disease status (complete remission vs. non-complete remission, p=0.0014) and preference of families (p=0.029). Among 6 families who expressed preference, no disparity was observed between actual and preferred place of death. This is the first English publication of place of death of pediatric cancer patients in Japan. The low percentage of home death, factors influencing place of death and the lack of disparity between actual and preferred place of death were indicated. Further studies are required to better understand place of death.

Effectiveness of a nonpenetrating captive bolt for euthanasia of piglets less than 3 d of age.

PubMed

Casey-Trott, T M; Millman, S T; Turner, P V; Nykamp, S G; Widowski, T M

2013-11-01

The objective of this study was to determine the effectiveness of a nonpenetrating captive bolt (NPCB), the Zephyr-Euthanasia (Zephyr-E), for euthanasia of neonatal piglets<72 h of age using signs of insensibility and death, as well as postmortem assessment of traumatic brain injury (TBI). The Zephyr-E was used by 10 stock people to euthanize 100 low viability neonatal piglets from 3 commercial farrowing units and 1 research farm. Brainstem reflexes, convulsions, and heartbeat were used to assess insensibility, time of brain death, and cardiac arrest after Zephyr-E application. Hemorrhage severity and skull fracture displacement (FD) were quantified from computed tomography scans (n=10), macroscopic scoring was used to assess brain hemorrhage and skull fracture (SK) severity (n=100), and microscopic scoring was used to assess subdural (SDH) and parenchymal (PH) hemorrhage within specific brain regions that are responsible for consciousness and vital function (n=10). All 100 piglets were rendered immediately insensible without return to sensibility. On average, clonic convulsions (CC) ceased in 101 s (±7.4 SE), brain death was achieved in 229 s (±9.18 SE), and cardiac arrest occurred in 420 s (±13.57 SE). Time of cardiac arrest differed significantly among stock people when either body weight (BW: P=0.0053) or body mass index (BMI: P=0.0059) was used as a covariate. The BMI was inversely related to the duration of CC (P=0.0227). Moderate to severe hemorrhage severity was reported in 9 of 10 piglets. There was no relationship between FD and BW (P=0.8408) or BMI (P=0.6439). Macroscopic analyses indicated moderate to severe hemorrhage and SK in all piglets. No differences were found among brain sections for SDH (P=0.2302); PH was greater in the cerebral cortex than in the midbrain and brainstem (P=0.0328). The Zephyr-E NPCB reliably caused immediate, sustained insensibility followed by death in neonatal piglets. Postmortem assessment confirmed that application of the Zephyr-E caused widespread, irreversible brain damage.

Gender difference in the effect of progesterone on neonatal hypoxic/ischemic brain injury in mouse.

PubMed

Dong, Shuyu; Zhang, Qian; Kong, Delian; Zhou, Chao; Zhou, Jie; Han, Jingjing; Zhou, Yan; Jin, Guoliang; Hua, Xiaodong; Wang, Jun; Hua, Fang

2018-08-01

This study investigated the effects of progesterone (PROG) on neonatal hypoxic/ischemic (NHI) brain injury, the differences in effects between genders, and the underlying mechanisms. NHI brain injury was established in both male and female neonatal mice induced by occlusion of the left common carotid artery followed by hypoxia. The mice were treated with PROG or vehicle. Fluoro-Jade B staining (F-JB), long term behavior testing, and brain magnetic resonance image (MRI) were applied to evaluate neuronal death, neurological function, and brain damage. The underlying molecular mechanisms were also investigated by Western blots. The results showed that, in the male mice, administration of PROG significantly reduced neuronal death, improved the learning and memory function impaired by cerebral HI, decreased infarct size, and maintained the thickness of the cortex after cerebral HI. PROG treatment, however, did not show significant neuroprotective effects on female mice subjected to HI. In addition, the data demonstrated a gender difference in the expression of tumor necrosis factor receptor 1 (TNFR1), TNF receptor associated factor 6 (TRAF6), Fas associated protein with death domain (FADD), and TIR-domain-containing adapter-inducing interferon-β (TRIF) between males and females. Our results indicated that treatment with PROG had beneficial effects on NHI injured brain in acute stage and improved the long term cognitive function impaired by cerebral HI in male mice. In addition, the activation of TNF and TRIF mediated signaling in response to cerebral HI and the treatment of PROG varied between genders, which highly suggested that gender differences should be emphasized in evaluating neonatal HI brain injury and PROG effects, as well as the underlying mechanisms. Copyright © 2018 Elsevier Inc. All rights reserved.

Inadequate Antioxidative Responses in Kidneys of Brain-Dead Rats.

PubMed

Hoeksma, Dane; Rebolledo, Rolando A; Hottenrott, Maximilia; Bodar, Yves S; Wiersema-Buist, Janneke J; Van Goor, Harry; Leuvenink, Henri G D

2017-04-01

Brain death (BD)-related lipid peroxidation, measured as serum malondialdehyde (MDA) levels, correlates with delayed graft function in renal transplant recipients. How BD affects lipid peroxidation is not known. The extent of BD-induced organ damage is influenced by the speed at which intracranial pressure increases. To determine possible underlying causes of lipid peroxidation, we investigated the renal redox balance by assessing oxidative and antioxidative processes in kidneys of brain-dead rats after fast and slow BD induction. Brain death was induced in 64 ventilated male Fisher rats by inflating a 4.0F Fogarty catheter in the epidural space. Fast and slow inductions were achieved by an inflation speed of 0.45 and 0.015 mL/min, respectively, until BD confirmation. Healthy non-brain-dead rats served as reference values. Brain-dead rats were monitored for 0.5, 1, 2, or 4 hours, after which organs and blood were collected. Increased MDA levels became evident at 2 hours of slow BD induction at which increased superoxide levels, decreased glutathione peroxidase (GPx) activity, decreased glutathione levels, increased inducible nitric oxide synthase and heme-oxygenase 1 expression, and increased plasma creatinine levels were evident. At 4 hours after slow BD induction, superoxide, MDA, and plasma creatinine levels increased further, whereas GPx activity remained decreased. Increased MDA and plasma creatinine levels also became evident after 4 hours fast BD induction. Brain death leads to increased superoxide production, decreased GPx activity, decreased glutathione levels, increased inducible nitric oxide synthase and heme-oxygenase 1 expression, and increased MDA and plasma creatinine levels. These effects were more pronounced after slow BD induction. Modulation of these processes could lead to decreased incidence of delayed graft function.

Brain-Dead Donors on Extracorporeal Membrane Oxygenation.

PubMed

Bronchard, Régis; Durand, Louise; Legeai, Camille; Cohen, Johana; Guerrini, Patrice; Bastien, Olivier

2017-10-01

To describe donors after brain death with ongoing extracorporeal membrane oxygenation and to analyze the outcome of organs transplanted from these donors. Retrospective analysis of the national information system run by the French Biomedicine Agency (CRISTAL database). National registry data of all donors after brain death in France and their organ recipients between 2007 and 2013. Donors after brain death and their organ recipients. None. During the study period, there were 22,270 brain-dead patients diagnosed in France, of whom 161 with extracorporeal membrane oxygenation. Among these patients, 64 donors on extracorporeal membrane oxygenation and 10,805 donors without extracorporeal membrane oxygenation had at least one organ retrieved. Donors on extracorporeal membrane oxygenation were significantly younger and had more severe intensive care medical conditions (hemodynamic, biological, renal, and liver insults) than donors without extracorporeal membrane oxygenation. One hundred nine kidneys, 37 livers, seven hearts, and one lung were successfully transplanted from donors on extracorporeal membrane oxygenation. We found no significant difference in 1-year kidney graft survival (p = 0.24) and function between recipients from donors on extracorporeal membrane oxygenation (92.7% [85.9-96.3%]) and matching recipients from donors without extracorporeal membrane oxygenation (95.4% [93.0-97.0%]). We also found no significant difference in 1-year liver recipient survival (p = 0.91): 86.5% (70.5-94.1) from donors on extracorporeal membrane oxygenation versus 80.7% (79.8-81.6) from donors without extracorporeal membrane oxygenation. Brain-dead patients with ongoing extracorporeal membrane oxygenation have more severe medical conditions than those without extracorporeal membrane oxygenation. However, kidney graft survival and function were no different than usual. Brain-dead patients with ongoing extracorporeal membrane oxygenation are suitable for organ procurement.

Recollecting, recognizing, and other acts of remembering: an overview of human memory.

PubMed

LaVoie, Donna J; Cobia, Derin J

2007-09-01

The question of whether memory is important to human existence is simple to answer: life without memory would be devoid of any meaning. The question of what memory is, however, is much more difficult to answer. The main purpose of this article is to provide an overview of memory function, by drawing distinctions between different memory systems, specifically declarative (ie, conscious) versus nondeclarative (ie, nonconscious) memory systems. To distinguish between these larger systems and their various components, we include discussion of deficits in memory that occur as a consequence of brain injury and normative aging processes. Included in these descriptions is discussion of the neuroanatomical correlates of each memory component described to illustrate the importance of particular brain regions to different aspects of memory function.

Rapid brain death caused by a cerebellar abscess with Fusobacterium nucleatum in a young man with drug abuse: a case report

PubMed Central

2014-01-01

Background Fusobacterium nucleatum is a strict anaerobic microorganism that causes disease entities such as periodontal and soft tissue abscesses, pulmonary and intraabdominal infections and very rarely intracerebral infections. Case presentation Here, we report the rare case of a previously healthy 25-year-old German man with a cerebellar abscess caused by Fusobacterium nucleatum that resulted in rapid brain death. Toxicological screening showed positivity for amphetamines and cannabis. The diagnosis was obtained by polymerase chain reaction amplification of bacterial deoxyribonucleic acid in cerebrospinal fluid. Conclusions In drug users clinicians should think about rare causes of brain abscesses/meningitis. Early diagnosis is necessary and justifies the use of molecular techniques. PMID:24915846

Microscopic analysis of the different regions of three Alzheimer brains aged 93, 94, and 104 years old.

PubMed

Zhu, Yonghong; Xu, Jie; Kwong, Wing Hang; Wai, Sen Mun; Lam, Wai Ping; Yew, David T

2007-10-01

The brains of three Alzheimer patients aged 93, 94, and 104 years old were analyzed. Although cell death was apparent in different cortices, the prefrontal cortex and the Broca's appeared to be hit hardest. The different CA areas of the hippocampal formation all displayed equivalent degrees of cell death but the entorhinal areas showed the most severe degree of cell degeneration. Both apoptosis and necrosis were observed in the different cerebral regions of these very old patients, as expected.

Seeking an ethical and legal way of procuring transplantable organs from the dying without further attempts to redefine human death

PubMed Central

Evans, David Wainwright

2007-01-01

Because complex organs taken from unequivocally dead people are not suitable for transplantation, human death has been redefined so that it can be certified at some earlier stage in the dying process and thereby make viable organs available without legal problems. Redefinitions based on concepts of "brain death" have underpinned transplant practice for many years although those concepts have never found universal philosophical acceptance. Neither is there consensus about the clinical tests which have been held sufficient to diagnose the irreversible cessation of all brain function – or as much of it as is deemed relevant – while the body remains alive. For these reasons, the certification of death for transplant purposes on "brain death" grounds is increasingly questioned and there has been pressure to return to its diagnosis on the basis of cardiac arrest and the consequent cessation of blood circulation throughout the body. While superficially a welcome return to the traditional and universally accepted understanding of human death, examination of the protocols using such criteria for the diagnosis of death prior to organ removal reveals a materially different scenario in which the circulatory arrest is not certainly final and purely nominal periods of arrest are required before surgery begins. Recognizing the probably unresolvable conflict between allowing enough time to pass after truly final circulatory arrest for a safe diagnosis of death and its minimization for the sake of the wanted organs, Verheijde and colleagues follow others in calling for the abandonment of the "dead donor rule" and the enactment of legislation to permit the removal of organs from the dying, without pretence that they are dead before that surgery. While it may be doubted whether such a "paradigm change" in the ethics of organ procurement would be accepted by society, their call for its consideration as a fully and fairly informed basis for organ donation is to be applauded. PMID:17603889

Fisetin as a caloric restriction mimetic protects rat brain against aging induced oxidative stress, apoptosis and neurodegeneration.

PubMed

Singh, Sandeep; Singh, Abhishek Kumar; Garg, Geetika; Rizvi, Syed Ibrahim

2018-01-15

In the present study, attempts have been made to evaluate the potential role of fisetin, a caloric restriction mimetic (CRM), for neuroprotection in D-galactose (D-gal) induced accelerated and natural aging models of rat. Fisetin was supplemented (15mg/kg b.w., orally) to young, D-gal induced aged (D-gal 500mg/kg b.w subcutaneously) and naturally aged rats for 6weeks. Standard protocols were employed to measure pro-oxidants, antioxidants and mitochondrial membrane potential in brain tissues. Gene expression analysis with reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to assess the expression of autophagy, neuronal, aging as well as inflammatory marker genes. We have also evaluated apoptotic cell death and synaptosomal membrane-bound ion transporter activities in brain tissues. Our data demonstrated that fisetin significantly decreased the level of pro-oxidants and increased the level of antioxidants. Furthermore, fisetin also ameliorated mitochondrial membrane depolarization, apoptotic cell death and impairments in the activities of synaptosomal membrane-bound ion transporters in aging rat brain. RT-PCR data revealed that fisetin up-regulated the expression of autophagy genes (Atg-3 and Beclin-1), sirtuin-1 and neuronal markers (NSE and Ngb), and down-regulated the expression of inflammatory (IL-1β and TNF-α) and Sirt-2 genes respectively in aging brain. The present study suggests that fisetin supplementation may provide neuroprotection against aging-induced oxidative stress, apoptotic cell death, neuro-inflammation, and neurodegeneration in rat brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Parental Concussion Education Assessment: A Quality Improvement Initiative

ERIC Educational Resources Information Center

Best, Melanie

2017-01-01

Background of Problem: Brain injury is a leading cause of death and disability in children and adolescents. According to the Brain Injury Association of America (2015) ages 0-4 and 15-19 are the two age groups at greatest risk for traumatic brain injury (TBI) or concussion. Five out of ten concussions are not reported or go undetected. The…

The Least Bad Option: Unilateral Extubation after Declaration of Death by Neurological Criteria.

PubMed

Bliss, Sally E; Macauley, Robert C

2015-01-01

Typically, the determination of death by neurological criteria follows a very specific protocol. An apnea test is performed with further confirmation as necessary, and then mechanical ventilation is withdrawn with the consent of the family after they have had an opportunity to "say goodbye," and at such a time to permit organ retrieval (with authorization of the patient or consent of the next of kin). Such a process maximizes transparency and ensures generalizability. In exceptional circumstances, however, it may be necessary to deviate from this protocol in order to spare family members unnecessary suffering and to reduce moral distress felt by clinical staff. It may also be appropriate, we argue, to refrain from even inquiring about organ donation when the next-of-kin is not only certain to refuse, but lacks the decision-making capacity to potentially consent. The case described in this article calls into question generally reliable assumptions about determination of death by neurological criteria, where the best the clinical team could do for the patient and his family was "the least bad option." Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

Contesting the Equivalency of Continuous Sedation until Death and Physician-assisted Suicide/Euthanasia: A Commentary on LiPuma.

PubMed

Raho, Joseph A; Miccinesi, Guido

2015-10-01

Patients who are imminently dying sometimes experience symptoms refractory to traditional palliative interventions, and in rare cases, continuous sedation is offered. Samuel H. LiPuma, in a recent article in this Journal, argues that continuous sedation until death is equivalent to physician-assisted suicide/euthanasia based on a higher brain neocortical definition of death. We contest his position that continuous sedation involves killing and offer four objections to the equivalency thesis. First, sedation practices are proportional in a way that physician-assisted suicide/euthanasia is not. Second, continuous sedation may not entirely abolish consciousness. Third, LiPuma's particular version of higher brain neocortical death relies on an implausibly weak construal of irreversibility--a position that is especially problematic in the case of continuous sedation. Finally, we explain why continuous sedation until death is not functionally equivalent to neocortical death and, hence, physician-assisted suicide/euthanasia. Concluding remarks review the differences between these two end-of-life practices. © The Author 2015. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

What You Need to Know about Drugs: Ecstasy

MedlinePlus

... his or her body can dangerously overheat during dancing or other physical activities, which can lead to muscle breakdown, kidney, liver and heart damage, and even death. Taking the drug can cause seizures, brain swelling and permanent brain ...

Intranasal insulin improves memory in humans.

PubMed

Benedict, Christian; Hallschmid, Manfred; Hatke, Astrid; Schultes, Bernd; Fehm, Horst L; Born, Jan; Kern, Werner

2004-11-01

Previous studies have suggested an acutely improving effect of insulin on memory function. To study changes in memory associated with a prolonged increase in brain insulin activity in humans, here we used the intranasal route of insulin administration known to provide direct access of the substance to the cerebrospinal fluid compartment. Based on previous results indicating a prevalence of insulin receptors in limbic and hippocampal regions as well as improvements in memory with systemic insulin administration, we expected that intranasal administration of insulin improves primarily hippocampus dependent declaration memory function. Also, improvements in mood were expected. We investigated the effects of 8 weeks of intranasal administration of insulin (human regular insulin 4 x 40 IU/d) on declarative memory (immediate and delayed recall of word lists), attention (Stroop test), and mood in 38 healthy subjects (24 males) in a double blind, between-subject comparison. Blood glucose and plasma insulin levels did not differ between the placebo and insulin conditions. Delayed recall of words significantly improved after 8 weeks of intranasal insulin administration (words recalled, Placebo 2.92 +/- 1.00, Insulin 6.20 +/- 1.03, p < 0.05). Moreover, subjects after insulin reported signs of enhanced mood, such as reduced anger (p < 0.02) and enhanced self-confidence (p < 0.03). Results indicate a direct action of prolonged intranasal administration of insulin on brain functions, improving memory and mood in the absence of systemic side effects. These findings could be of relevance for the treatment of patients with memory disorders like in Alzheimer's disease.

[Developmental amnesia and early brain damage: neuropsychology and neuroimaging].

PubMed

Crespo-Eguilaz, N; Dominguez, P D; Vaquero, M; Narbona, J

2018-03-01

To contribute to neuropsychological profiling of developmental amnesia subsequent to bilateral damage to both hippocampi in early age. The total sample of 24 schoolchildren from both sexes is distributed in three groups: perinatal hypoxic-ischaemic encephalopathy and everyday complaints of memory in school age (n = 8); perinatal hypoxic-ischaemic encephalopathy without memory complaints (n = 7); and a group of typically developing (n = 9). All participants in every groups did have normal general intelligence and attention. Both clinical groups had, as another clinical consequence, spastic cerebral palsy (diplegia). Neuropsychological exam consisted on tests of general intelligence, attentional abilities, declarative memory and semantic knowledge. All participants had a brain magnetic resonance image and spectroscopy of hippocampi. Scheltens criteria were used for visual estimation of hippocampal atrophy. Parametric and non-parametric statistical contrasts were made. Despite preservation of semantic and procedural learning, declarative-episodic memory is impaired in the first group versus the other two groups. A significant proportion of bilateral hippocampal atrophy is only present in the first group versus the other two non-amnesic groups using Scheltens estimation on MRI. Two cases without evident atrophy did have diminished NAA/(Cho + Cr) index in both hippocampi. Taken together, these results contribute to delineate developmental amnesia as an specific impairment due to early partial bihippocampal damage, in agreement with previous studies. After diagnosis of developmental amnesia, a specific psychoeducational intervention must be made; also this impairment could be candidate for pharmacological trials in the future.

Neuronal gap junctions play a role in the secondary neuronal death following controlled cortical impact.

PubMed

Belousov, Andrei B; Wang, Yongfu; Song, Ji-Hoon; Denisova, Janna V; Berman, Nancy E; Fontes, Joseph D

2012-08-22

In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI) and epilepsy. Recent studies in mice showed a critical role for neuronal gap junctions in NMDA receptor-mediated excitotoxicity and ischemia-mediated neuronal death. Here, using controlled cortical impact (CCI) in adult mice, as a model of TBI, and Fluoro-Jade B staining for analysis of neuronal death, we set to determine whether neuronal gap junctions play a role in the CCI-mediated secondary neuronal death. We report that 24h post-CCI, substantial neuronal death is detected in a number of brain regions outside the injury core, including the striatum. The striatal neuronal death is reduced both in wild-type mice by systemic administration of mefloquine (a relatively selective blocker of neuronal gap junctions) and in knockout mice lacking connexin 36 (neuronal gap junction protein). It is also reduced by inactivation of group II metabotropic glutamate receptors (with LY341495) which, as reported previously, control the rapid increase in neuronal gap junction coupling following different types of neuronal injury. The results suggest that neuronal gap junctions play a critical role in the CCI-induced secondary neuronal death. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Associations between community-level disaster exposure and individual-level changes in disability and risk of death for older Americans

PubMed Central

Brilleman, Samuel L.; Wolfe, Rory; Moreno-Betancur, Margarita; Sales, Anne E.; Langa, Kenneth M.; Li, Yun; Daugherty Biddison, Elizabeth L.; Rubinson, Lewis; Iwashyna, Theodore J.

2016-01-01

Disasters occur frequently in the United States (US) and their impact on acute morbidity, mortality and short-term increased health needs has been well described. However, barring mental health, little is known about the medium or longer-term health impacts of disasters. This study sought to determine if there is an association between community-level disaster exposure and individual-level changes in disability and/or the risk of death for older Americans. Using the US Federal Emergency Management Agency’s database of disaster declarations, 602 disasters occurred between August 1998 and December 2010 and were characterized by their presence, intensity, duration and type. Repeated measurements of a disability score (based on activities of daily living) and dates of death were observed between January 2000 and November 2010 for 18,102 American individuals aged 50 to 89 years, who were participating in the national longitudinal Health and Retirement Study. Longitudinal (disability) and time-to-event (death) data were modelled simultaneously using a ‘joint modelling’ approach. There was no evidence of an association between community-level disaster exposure and individual-level changes in disability or the risk of death. Our results suggest that future research should focus on individual-level disaster exposures, moderate to severe disaster events, or higher-risk groups of individuals. PMID:27960126

Killing by organ procurement: brain-based death and legal fictions.

PubMed

Veatch, Robert M

2015-06-01

The dead donor rule (DDR) governs procuring life-prolonging organs. They should be taken only from deceased donors. Miller and Truog have proposed abandoning the rule when patients have decided to forgo life-sustaining treatment and have consented to procurement. Organs could then be procured from living patients, thus killing them by organ procurement. This proposal warrants careful examination. They convincingly argue that current brain or circulatory death pronouncement misidentifies the biologically dead. After arguing convincingly that physicians already cause death by withdrawing treatment, they claim no bright-line differences preclude organ removal from the living. The argument fails for those who accept the double effect doctrine or other grounds for distinguishing forgoing life support from active, intentional killing. If the goal is determining irreversible loss of somatic function, they correctly label current death pronouncement a "legal fiction." Recognizing a second, public policy meaning of the term death provides grounds for maintaining the DDR without jeopardizing procurement. © The Author 2015. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Thyroid gland and cerebella lesions: New risk factors for sudden cardiac death in schizophrenia?

PubMed

Scorza, Fulvio A; Cavalheiro, Esper A; de Albuquerque, Marly; de Albuquerque, Juliana; Cysneiros, Roberta M; Terra, Vera C; Arida, Ricardo M

2011-02-01

People with schizophrenia show a two to threefold increased risk to die prematurely than those without schizophrenia. Patients' life style, suicide, premature development of cardiovascular disease, high prevalence of metabolic syndrome and sudden cardiac death are well-known causes of the excess mortality. The exact pathophysiological cause of sudden death in schizophrenia is unknown, but it is likely that cardiac arrhythmia and respiratory abnormalities play potential role. Some antipsychotics may be associated with cardiovascular adverse events (e.g., QT interval prolongation) and lesions in specific brain regions, such as cerebella may be associated with respiratory abnormalities, suggesting that metabolic and brain dysfunction could lead to sudden cardiac death in patients with schizophrenia. However, exact knowledge regarding the association of these findings and schizophrenia is lacking. As subclinical hyperthyroidism has been linked with increased risk of cardiovascular disease and cerebella progressive atrophy has been observed in patients with schizophrenia, we propose in this paper that subclinical thyroid dysfunction and cerebella volume loss could be considered as new risk factor for sudden cardiac death in schizophrenia. Copyright © 2010 Elsevier Ltd. All rights reserved.

Activation of the endoplasmic reticulum stress response by the amyloid-beta 1-40 peptide in brain endothelial cells.

PubMed

Fonseca, Ana Catarina R G; Ferreiro, Elisabete; Oliveira, Catarina R; Cardoso, Sandra M; Pereira, Cláudia F

2013-12-01

Neurovascular dysfunction arising from endothelial cell damage is an early pathogenic event that contributes to the neurodegenerative process occurring in Alzheimer's disease (AD). Since the mechanisms underlying endothelial dysfunction are not fully elucidated, this study was aimed to explore the hypothesis that brain endothelial cell death is induced upon the sustained activation of the endoplasmic reticulum (ER) stress response by amyloid-beta (Aβ) peptide, which deposits in the cerebral vessels in many AD patients and transgenic mice. Incubation of rat brain endothelial cells (RBE4 cell line) with Aβ1-40 increased the levels of several markers of ER stress-induced unfolded protein response (UPR), in a time-dependent manner, and affected the Ca(2+) homeostasis due to the release of Ca(2+) from this intracellular store. Finally, Aβ1-40 was shown to activate both mitochondria-dependent and -independent apoptotic cell death pathways. Enhanced release of cytochrome c from mitochondria and activation of the downstream caspase-9 were observed in cells treated with Aβ1-40 concomitantly with caspase-12 activation. Furthermore, Aβ1-40 activated the apoptosis effectors' caspase-3 and promoted the translocation of apoptosis-inducing factor (AIF) to the nucleus demonstrating the involvement of caspase-dependent and -independent mechanisms during Aβ-induced endothelial cell death. In conclusion, our data demonstrate that ER stress plays a significant role in Aβ1-40-induced apoptotic cell death in brain endothelial cells suggesting that ER stress-targeted therapeutic strategies might be useful in AD to counteract vascular defects and ultimately neurodegeneration. © 2013.

A statistical model describing combined irreversible electroporation and electroporation-induced blood-brain barrier disruption.

PubMed

Sharabi, Shirley; Kos, Bor; Last, David; Guez, David; Daniels, Dianne; Harnof, Sagi; Mardor, Yael; Miklavcic, Damijan

2016-03-01

Electroporation-based therapies such as electrochemotherapy (ECT) and irreversible electroporation (IRE) are emerging as promising tools for treatment of tumors. When applied to the brain, electroporation can also induce transient blood-brain-barrier (BBB) disruption in volumes extending beyond IRE, thus enabling efficient drug penetration. The main objective of this study was to develop a statistical model predicting cell death and BBB disruption induced by electroporation. This model can be used for individual treatment planning. Cell death and BBB disruption models were developed based on the Peleg-Fermi model in combination with numerical models of the electric field. The model calculates the electric field thresholds for cell kill and BBB disruption and describes the dependence on the number of treatment pulses. The model was validated using in vivo experimental data consisting of rats brains MRIs post electroporation treatments. Linear regression analysis confirmed that the model described the IRE and BBB disruption volumes as a function of treatment pulses number (r(2) = 0.79; p < 0.008, r(2) = 0.91; p < 0.001). The results presented a strong plateau effect as the pulse number increased. The ratio between complete cell death and no cell death thresholds was relatively narrow (between 0.88-0.91) even for small numbers of pulses and depended weakly on the number of pulses. For BBB disruption, the ratio increased with the number of pulses. BBB disruption radii were on average 67% ± 11% larger than IRE volumes. The statistical model can be used to describe the dependence of treatment-effects on the number of pulses independent of the experimental setup.

Why do I stand against the movement for cardiac transplantation in Japan?

PubMed

Watanabe, Y

1994-11-01

In order to clarify the reason the author stands against the movement for cardiac transplantation in Japan, certain crucial differences between death judged by the classical criteria and so-called brain death are briefly discussed, followed by the presentation of three major arguments. First, various problems associated with postoperative care of organ recipients are delineated, particularly side effects of immunosuppressive drugs and long term prognosis with reference of life expectancy as well as quality of life. Second, it is emphasized that transplantation involves prejudice and inequality, since the number of potential organ recipients far exceeds that of donors and only a small portion of transplant candidates can actually receive the organs while others have to wait in vain. Third, once organ transplantation from brain dead patients is allowed, numerous ethical and social problems would arise including an arbitrary expansion of the criteria for brain death, selection of donors and recipients by taking non-medial factors into consideration, development of organ commerce leading to the involvement of organized crime, and the birth of a trend in transplant candidates to wish for an early death of histocompatible donors. Finally, it is pointed out that we must give serious thought to the danger of "from neck down" transplantation creating a new person from two bodies (which is a brain transplant in actuality) in the future, since the difference between such a procedure and the multiorgan transplantation presently practiced in many developed countries is only quantitative and one cannot find a logical reason to ban the former while retaining the latter.

Deaths from external causes in Cuiabá, 0 a 24 years: Profile of victims and families according to intentionality.

PubMed

Martins, Christine Baccarat de Godoy; Jorge, Maria Helena Prado de Mello

2013-06-01

In view of the importance of knowing the circumstances associated with external causes (accidents and violence), this study analyzes the profile of the victims and their families as to the intentionality of the event (intentional or accidental). Cross-sectional study, which population comprise children, adolescents, and young people (age 0 to 24) who lived in Cuiabá, MT, and died from external causes in 2009. The data, processed by the Epi-Info software, were taken from the Declarations of Death and interviews with the families of the victims. The nonparametric chi-square test showed statistically significant differences between accidental and intentional deaths by sex and the type of accident or violence, the occurrence of the previous event external cause, parental education, family type, income, responsible for supporting the house, mother's age and caregiver. Among the victims, male participation (88.7 %) stands out compared to female (11.3 %). 50.0% of the deaths of females were accidental and 50.0% intentional; 68.2% of the deaths of males were intentional, 29.1% accidental and 2.7% from undetermined intent. Among the intentional deaths, 72.5% of the victims had already suffered violence. As the degree of instruction of the parents increases, intentional deaths decrease. The proportion of reconstituted/fragmented families is higher for fatal accidents. Intentional causes increase as family income decreases and the age of the parents increases. The agglomeration of people in the homes is higher for intentional deaths. Analizing the profiles of families and victims as to the intentionality of the event allows directing local prevention and control policies.

Neuronal Deletion of Caspase 8 Protects against Brain Injury in Mouse Models of Controlled Cortical Impact and Kainic Acid-Induced Excitotoxicity

PubMed Central

Krajewska, Maryla; You, Zerong; Rong, Juan; Kress, Christina; Huang, Xianshu; Yang, Jinsheng; Kyoda, Tiffany; Leyva, Ricardo; Banares, Steven; Hu, Yue; Sze, Chia-Hung; Whalen, Michael J.; Salmena, Leonardo; Hakem, Razqallah; Head, Brian P.; Reed, John C.; Krajewski, Stan

2011-01-01

Background Acute brain injury is an important health problem. Given the critical position of caspase 8 at the crossroads of cell death pathways, we generated a new viable mouse line (Ncasp8 −/−), in which the gene encoding caspase 8 was selectively deleted in neurons by cre-lox system. Methodology/Principal Findings Caspase 8 deletion reduced rates of neuronal cell death in primary neuronal cultures and in whole brain organotypic coronal slice cultures prepared from 4 and 8 month old mice and cultivated up to 14 days in vitro. Treatments of cultures with recombinant murine TNFα (100 ng/ml) or TRAIL (250 ng/mL) plus cyclohexamide significantly protected neurons against cell death induced by these apoptosis-inducing ligands. A protective role of caspase 8 deletion in vivo was also demonstrated using a controlled cortical impact (CCI) model of traumatic brain injury (TBI) and seizure-induced brain injury caused by kainic acid (KA). Morphometric analyses were performed using digital imaging in conjunction with image analysis algorithms. By employing virtual images of hundreds of brain sections, we were able to perform quantitative morphometry of histological and immunohistochemical staining data in an unbiased manner. In the TBI model, homozygous deletion of caspase 8 resulted in reduced lesion volumes, improved post-injury motor performance, superior learning and memory retention, decreased apoptosis, diminished proteolytic processing of caspases and caspase substrates, and less neuronal degeneration, compared to wild type, homozygous cre, and caspase 8-floxed control mice. In the KA model, Ncasp8 −/− mice demonstrated superior survival, reduced seizure severity, less apoptosis, and reduced caspase 3 processing. Uninjured aged knockout mice showed improved learning and memory, implicating a possible role for caspase 8 in cognitive decline with aging. Conclusions Neuron-specific deletion of caspase 8 reduces brain damage and improves post-traumatic functional outcomes, suggesting an important role for this caspase in pathophysiology of acute brain trauma. PMID:21957448

Neuropathology of SUDEP: Role of inflammation, blood-brain barrier impairment, and hypoxia.

PubMed

Michalak, Zuzanna; Obari, Dima; Ellis, Matthew; Thom, Maria; Sisodiya, Sanjay M

2017-02-07

To seek a neuropathologic signature of sudden unexpected death in epilepsy (SUDEP) in a postmortem cohort by use of immunohistochemistry for specific markers of inflammation, gliosis, acute neuronal injury due to hypoxia, and blood-brain barrier (BBB) disruption, enabling the generation of hypotheses about potential mechanisms of death in SUDEP. Using immunohistochemistry, we investigated the expression of 6 markers (CD163, human leukocyte antigen-antigen D related, glial fibrillary acid protein, hypoxia-inducible factor-1α [HIF-1α], immunoglobulin G, and albumin) in the hippocampus, amygdala, and medulla in 58 postmortem cases: 28 SUDEP (definite and probable), 12 epilepsy controls, and 18 nonepileptic sudden death controls. A semiquantitative measure of immunoreactivity was scored for all markers used, and quantitative image analysis was carried out for selected markers. Immunoreactivity was observed for all markers used within all studied brain regions and groups. Immunoreactivity for inflammatory reaction, BBB leakage, and HIF-1α in SUDEP cases was not different from that seen in control groups. This study represents a starting point to explore by immunohistochemistry the mechanisms underlying SUDEP in human brain tissue. Our approach highlights the potential and importance of considering immunohistochemical analysis to help identify biomarkers of SUDEP. Our results suggest that with the markers used, there is no clear immunohistochemical signature of SUDEP in human brain. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Neuronal survival in the brain: neuron type-specific mechanisms.

PubMed

Pfisterer, Ulrich; Khodosevich, Konstantin

2017-03-02

Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation. Furthermore, pro-survival factors and intracellular responses depend on the type of neuron and region of the brain. Thus, in addition to some common neuronal pro-survival signaling, different types of neurons possess a variety of 'neuron type-specific' pro-survival constituents that might help them to adapt for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various types of immature neurons. Importantly, we mainly focus on in vivo data to describe neuronal survival specifically in the brain, without extrapolating data obtained in the PNS or spinal cord, and thus emphasize the influence of the complex brain environment on neuronal survival during development.

Minocycline causes widespread cell death and increases microglial labeling in the neonatal mouse brain.

PubMed

Strahan, J Alex; Walker, William H; Montgomery, Taylor R; Forger, Nancy G

2017-06-01

Minocycline, an antibiotic of the tetracycline family, inhibits microglia in many paradigms and is among the most commonly used tools for examining the role of microglia in physiological processes. Microglia may play an active role in triggering developmental neuronal cell death, although findings have been contradictory. To determine whether microglia influence developmental cell death, we treated perinatal mice with minocycline (45 mg/kg) and quantified effects on dying cells and microglial labeling using immunohistochemistry for activated caspase-3 (AC3) and ionized calcium-binding adapter molecule 1 (Iba1), respectively. Contrary to our expectations, minocycline treatment from embryonic day 18 to postnatal day (P)1 caused a > tenfold increase in cell death 8 h after the last injection in all brain regions examined, including the primary sensory cortex, septum, hippocampus and hypothalamus. Iba1 labeling was also increased in most regions. Similar effects, although of smaller magnitude, were seen when treatment was delayed to P3-P5. Minocycline treatment from P3 to P5 also decreased overall cell number in the septum at weaning, suggesting lasting effects of the neonatal exposure. When administered at lower doses (4.5 or 22.5 mg/kg), or at the same dose 1 week later (P10-P12), minocycline no longer increased microglial markers or cell death. Taken together, the most commonly used microglial "inhibitor" increases cell death and Iba1 labeling in the neonatal mouse brain. Minocycline is used clinically in infant and pediatric populations; caution is warrented when using minocycline in developing animals, or extrapolating the effects of this drug across ages. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 753-766, 2017. © 2016 Wiley Periodicals, Inc.

Minocycline Causes Widespread Cell Death and Increases Microglial Labeling in the Neonatal Mouse Brain

PubMed Central

Strahan, J. Alex; Walker, William H.; Montgomery, Taylor R.; Forger, Nancy G.

2016-01-01

Minocycline, an antibiotic of the tetracycline family, inhibits microglia in many paradigms, and is among the most commonly used tools for examining the role of microglia in physiological processes. Microglia may play an active role in triggering developmental neuronal cell death, although findings have been contradictory. To determine whether microglia influence developmental cell death, we treated perinatal mice with minocycline (45 mg/kg) and quantified effects on dying cells and microglial labeling using immunohistochemistry for activated caspase-3 (AC3) and ionized calcium-binding adapter molecule 1 (Iba1), respectively. Contrary to our expectations, minocycline treatment from embryonic day 18 to postnatal day (P)1 caused a >10-fold increase in cell death 8 h after the last injection in all brain regions examined, including the primary sensory cortex (S1), septum, hippocampus and hypothalamus. Iba1 labeling was also increased in most regions. Similar effects, although of smaller magnitude, were seen when treatment was delayed to P3-P5. Minocycline treatment from P3-P5 also decreased overall cell number in the septum at weaning, suggesting lasting effects of the neonatal exposure. When administered at lower doses (4.5 or 22.5 mg/kg), or at the same dose one week later (P10-P12), minocycline no longer increased microglial markers or cell death. Taken together, the most commonly used microglial “inhibitor” increases cell death and Iba1 labeling in the neonatal mouse brain. Minocycline is used clinically in infant and pediatric populations; caution is warrented when using minocycline in developing animals, or extrapolating the effects of this drug across ages. PMID:27706925

Differences in mushroom bodies morphogenesis in workers, queens and drones of Apis mellifera: neuroblasts proliferation and death.

PubMed

Roat, Thaisa Cristina; da Cruz Landim, Carminda

2010-06-01

Apis mellifera is an interesting model to neurobiological studies. It has a relatively small brain that commands the complex learning and memory tasks demanded by the social organization. An A. mellifera colony is made up of a queen, thousands of workers and a varying number of drones. The latter are males, whereas the former are the two female castes. These three phenotypes differ in morphology, physiology and behavior, correlated with their respective functions in the society. Such differences include the morphology and architecture of their brains. To understand the processes generating such polymorphic brains we characterized the cell division and cell death dynamics which underlie the morphogenesis of the mushroom bodies, through several methods suitable for evidence the time and place of occurrence. Cell death was detected in mushroom bodies of last larval instar and mainly in black-eyed pupae. Cell division was observed in mushroom bodies, primarily at the start of metamorphosis, exhibiting temporal differences among workers, queens and males. Copyright 2010 Elsevier Ltd. All rights reserved.

Severe neurological impairment: legal aspects of decisions to reduce care.

PubMed

Beresford, H R

1984-05-01

Decisions to reduce care for patients with severe neurological impairment may raise legal questions. The laws of most states now authorize physicians to stop care for those who have suffered irreversible cessation of all functions of the brain ("brain death"). Where state law is not explicit, it is nevertheless probably lawful to regard brain death as death for legal purposes so long as currently accepted criteria are satisfied. Several courts have ruled that it is lawful to reduce care for patients in vegetative states, but have prescribed differing standards and procedures for implementing such decisions. The issue of whether parents can authorize physicians to reduce care for neurologically impaired children is the focus of current litigation. Implicit in this litigation is the question of how severe neurological impairment must be before parents and physicians may lawfully agree to reduce care. For severely impaired but not vegetative adults, there is some legal authority to justify certain decisions to reduce care. The issue of whether withholding feeding from a severely demented patient with life-threatening medical problems constitutes criminal behavior is now being considered by a state supreme court.

Advanced Pediatric Brain Imaging Research and Training Program

DTIC Science & Technology

2014-10-01

death and disability in children. Recent advances in pediatric magnetic resonance imaging ( MRI ) techniques are revolutionizing our understanding of... MRI , brain injury. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a...principles of pediatric brain injury and recovery following injury, as well as the clinical application of sophisticated MRI techniques that are

Loss of PAFR prevents neuroinflammation and brain dysfunction after traumatic brain injury

PubMed Central

Yin, Xiang-Jie; Chen, Zhen-Yan; Zhu, Xiao-Na; Hu, Jin-Jia

2017-01-01

Traumatic brain injury (TBI) is a principal cause of death and disability worldwide, which is a major public health problem. Death caused by TBI accounts for a third of all damage related illnesses, which 75% TBI occurred in low and middle income countries. With the increasing use of motor vehicles, the incidence of TBI has been at a high level. The abnormal brain functions of TBI patients often show the acute and long-term neurological dysfunction, which mainly associated with the pathological process of malignant brain edema and neuroinflammation in the brain. Owing to the neuroinflammation lasts for months or even years after TBI, which is a pivotal causative factor that give rise to neurodegenerative disease at late stage of TBI. Studies have shown that platelet activating factor (PAF) inducing inflammatory reaction after TBI could not be ignored. The morphological and behavioral abnormalities after TBI in wild type mice are rescued by general knockout of PAFR gene that neuroinflammation responses and cognitive ability are improved. Our results thus define a key inflammatory molecule PAF that participates in the neuroinflammation and helps bring about cerebral dysfunction during the TBI acute phase. PMID:28094295

Transcranial amelioration of inflammation and cell death after brain injury

NASA Astrophysics Data System (ADS)

Roth, Theodore L.; Nayak, Debasis; Atanasijevic, Tatjana; Koretsky, Alan P.; Latour, Lawrence L.; McGavern, Dorian B.

2014-01-01

Traumatic brain injury (TBI) is increasingly appreciated to be highly prevalent and deleterious to neurological function. At present, no effective treatment options are available, and little is known about the complex cellular response to TBI during its acute phase. To gain insights into TBI pathogenesis, we developed a novel murine closed-skull brain injury model that mirrors some pathological features associated with mild TBI in humans and used long-term intravital microscopy to study the dynamics of the injury response from its inception. Here we demonstrate that acute brain injury induces vascular damage, meningeal cell death, and the generation of reactive oxygen species (ROS) that ultimately breach the glial limitans and promote spread of the injury into the parenchyma. In response, the brain elicits a neuroprotective, purinergic-receptor-dependent inflammatory response characterized by meningeal neutrophil swarming and microglial reconstitution of the damaged glial limitans. We also show that the skull bone is permeable to small-molecular-weight compounds, and use this delivery route to modulate inflammation and therapeutically ameliorate brain injury through transcranial administration of the ROS scavenger, glutathione. Our results shed light on the acute cellular response to TBI and provide a means to locally deliver therapeutic compounds to the site of injury.

Cellular mechanisms of estradiol-mediated sexual differentiation of the brain.

PubMed

Wright, Christopher L; Schwarz, Jaclyn S; Dean, Shannon L; McCarthy, Margaret M

2010-09-01

Gonadal steroids organize the developing brain during a perinatal sensitive period and have enduring consequences for adult behavior. In male rodents testicular androgens are aromatized in neurons to estrogens and initiate multiple distinct cellular processes that ultimately determine the masculine phenotype. Within specific brain regions, overall cell number and dendritic morphology are the principal targets for hormonal organization. Recent advances have been made in elucidating the cellular mechanisms by which the neurological underpinnings of sexually dimorphic physiology and behavior are determined. These include estradiol-mediated prostaglandin synthesis, presynaptic release of glutamate, postsynaptic changes in glutamate receptors and changes in cell adhesion molecules. Sex differences in cell death are mediated by hormonal modulation of survival and death factors such as TNFalpha and Bcl-2/BAX. Copyright 2010 Elsevier Ltd. All rights reserved.

Brain age predicts mortality

PubMed Central

Cole, J H; Ritchie, S J; Bastin, M E; Valdés Hernández, M C; Muñoz Maniega, S; Royle, N; Corley, J; Pattie, A; Harris, S E; Zhang, Q; Wray, N R; Redmond, P; Marioni, R E; Starr, J M; Cox, S R; Wardlaw, J M; Sharp, D J; Deary, I J

2018-01-01

Age-associated disease and disability are placing a growing burden on society. However, ageing does not affect people uniformly. Hence, markers of the underlying biological ageing process are needed to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death. Here, we present such a biomarker, ‘brain-predicted age’, derived using structural neuroimaging. Brain-predicted age was calculated using machine-learning analysis, trained on neuroimaging data from a large healthy reference sample (N=2001), then tested in the Lothian Birth Cohort 1936 (N=669), to determine relationships with age-associated functional measures and mortality. Having a brain-predicted age indicative of an older-appearing brain was associated with: weaker grip strength, poorer lung function, slower walking speed, lower fluid intelligence, higher allostatic load and increased mortality risk. Furthermore, while combining brain-predicted age with grey matter and cerebrospinal fluid volumes (themselves strong predictors) not did improve mortality risk prediction, the combination of brain-predicted age and DNA-methylation-predicted age did. This indicates that neuroimaging and epigenetics measures of ageing can provide complementary data regarding health outcomes. Our study introduces a clinically-relevant neuroimaging ageing biomarker and demonstrates that combining distinct measurements of biological ageing further helps to determine risk of age-related deterioration and death. PMID:28439103

In vivo inhibition of the mitochondrial H+-ATP synthase in neurons promotes metabolic preconditioning.

PubMed

Formentini, Laura; Pereira, Marta P; Sánchez-Cenizo, Laura; Santacatterina, Fulvio; Lucas, José J; Navarro, Carmen; Martínez-Serrano, Alberto; Cuezva, José M

2014-04-01

A key transducer in energy conservation and signaling cell death is the mitochondrial H(+)-ATP synthase. The expression of the ATPase inhibitory factor 1 (IF1) is a strategy used by cancer cells to inhibit the activity of the H(+)-ATP synthase to generate a ROS signal that switches on cellular programs of survival. We have generated a mouse model expressing a mutant of human IF1 in brain neurons to assess the role of the H(+)-ATP synthase in cell death in vivo. The expression of hIF1 inhibits the activity of oxidative phosphorylation and mediates the shift of neurons to an enhanced aerobic glycolysis. Metabolic reprogramming induces brain preconditioning affording protection against quinolinic acid-induced excitotoxicity. Mechanistically, preconditioning involves the activation of the Akt/p70S6K and PARP repair pathways and Bcl-xL protection from cell death. Overall, our findings provide the first in vivo evidence highlighting the H(+)-ATP synthase as a target to prevent neuronal cell death.

Postmortem and Perimortem Cesarean Section: Historical, Religious and Ethical Considerations

PubMed Central

Fadel, Hossam E.

2012-01-01

Guillimeau was the first to use the term cesarean section (CS) in 1598, but this name became universal only in the 20th century. The many theories of the origin of this name will be discussed. This surgery has been reported to be performed in all cultures dating to ancient times. In the past, it was mainly done to deliver a live baby from a dead mother, hence the name postmortem CS (PMCS). Many heroes are reported to have been delivered this way. Old Jewish sacred books have made references to abdominal delivery. It was especially encouraged and often mandated in Catholicism. There is evidence that the operation was done in Muslim countries in the middle ages. Islamic rulings support the performance of PMCS. Now that most maternal deaths occur in the hospital, perimortem CS (PRMCS) is recommended for the delivery of a fetus after 24 weeks from a pregnant woman with cardiac arrest. It is believed that emergent delivery within four minutes of initiation of cardiopulmonary resuscitation (CPR) improves the chances of success of maternal resuscitation and survival and increases the chance of delivering a neurologically intact neonate. It is agreed that physicians are not to be held legally liable for the performance of PMCS and PRMCS regardless of the outcome. The ethical aspects of these operations are also discussed including a discussion about PMCS for the delivery of women who have been declared brain dead. PMID:23610509

Traumatic asphyxia--fatal accident in an automatic revolving door.

PubMed

Cortis, J; Falk, J; Rothschild, M A

2015-09-01

Due to continuing modernisation, the number of automatic doors in routine use, including powered revolving doors, has increased in recent years. Automatic revolving doors are found mostly in department stores, airports, railway stations and hospitals. Although safety arrangements and guidelines concerning the installation of automatic doors are in existence, their disregard in conjunction with obsolete or incorrect installation can lead to fatal accidents. In this report, a 19-month-old boy is described whose right arm was caught between the elements of an automatic revolving door. As a direct result of rescue attempts, the child's body was drawn further into the narrow gap between elements of the door. To get the boy's body out of the 4-cm-wide gap between the fixed outer wall of the revolving door and the revolving inner, back-up batteries had to be disconnected so as to stop the electrical motor powering the door. Cardiopulmonary resuscitation was begun immediately after the rescue but was unsuccessful; the child was declared dead at the hospital he was taken to. The cause of death was a combination of compression-related skull and brain injury together with thoracic compression. This case shows an outstanding example of the preventive aspect as a special task of forensic medicine. Additionally, it serves as a warning for the correct installation and use of automatic revolving doors. Even so, small children should not use these doors on their own, but only with an alert companion, so as to prevent further fatal accidents of this sort.

Chronology of the birth and death of a health bill.

PubMed

Jacks, J C; Jacks, L

1995-01-01

A two-year attempt by the Clinton administration to develop and pass a health care reform bill was from the beginning destined for failure. The health care reform plan was developed in secret, leaving the plan open for special interest suspect. It was overly complex and difficult to understand. Congress and the general public initially supported the effort, but wavered under pressure and negative messages generated by special interest groups. After a year of intense debate, health care reform was declared dead, with very little hope of resurrection in the 1994 election year, which saw Republicans make significant gains in Congress.

A brain computer interface using electrocorticographic signals in humans

NASA Astrophysics Data System (ADS)

Leuthardt, Eric C.; Schalk, Gerwin; Wolpaw, Jonathan R.; Ojemann, Jeffrey G.; Moran, Daniel W.

2004-06-01

Brain-computer interfaces (BCIs) enable users to control devices with electroencephalographic (EEG) activity from the scalp or with single-neuron activity from within the brain. Both methods have disadvantages: EEG has limited resolution and requires extensive training, while single-neuron recording entails significant clinical risks and has limited stability. We demonstrate here for the first time that electrocorticographic (ECoG) activity recorded from the surface of the brain can enable users to control a one-dimensional computer cursor rapidly and accurately. We first identified ECoG signals that were associated with different types of motor and speech imagery. Over brief training periods of 3-24 min, four patients then used these signals to master closed-loop control and to achieve success rates of 74-100% in a one-dimensional binary task. In additional open-loop experiments, we found that ECoG signals at frequencies up to 180 Hz encoded substantial information about the direction of two-dimensional joystick movements. Our results suggest that an ECoG-based BCI could provide for people with severe motor disabilities a non-muscular communication and control option that is more powerful than EEG-based BCIs and is potentially more stable and less traumatic than BCIs that use electrodes penetrating the brain. The authors declare that they have no competing financial interests.

Use of Lung Allografts from Brain-Dead Donors after Cardiopulmonary Arrest and Resuscitation

PubMed Central

Worni, Mathias; Osho, Asishana A.; Snyder, Laurie D.; Palmer, Scott M.; Pietrobon, Ricardo; Davis, R. Duane; Hartwig, Matthew G.

2013-01-01

Rationale: Patients who progress to brain death after resuscitation from cardiac arrest have been hypothesized to represent an underused source of potential organ donors; however, there is a paucity of data regarding the viability of lung allografts after a period of cardiac arrest in the donor. Objectives: To analyze postoperative complications and survival after lung transplant from brain-dead donors resuscitated after cardiac arrest. Methods: The United Network for Organ Sharing database records donors with cardiac arrest occurring after brain death. Adult recipients of lung allografts from these arrest/resuscitation donors between 2005 and 2011 were compared with nonarrest donors. Propensity score matching was used to reduce the effect of confounding. Postoperative complications and overall survival were assessed using McNemar’s test for correlated binary proportions and Kaplan–Meier methods. Measurements and Main Results: A total of 479 lung transplant recipients from arrest/resuscitation donors were 1:1 propensity matched from a cohort of 9,076 control subjects. Baseline characteristics in the 1:1-matched cohort were balanced. There was no significant difference in perioperative mortality, airway dehiscence, dialysis requirement, postoperative length of stay (P ≥ 0.38 for all), or overall survival (P = 0.52). A subanalysis of the donor arrest group demonstrated similar survival when stratified by resuscitation time quartile (P = 0.38). Conclusions: There is no evidence of inferior outcomes after lung transplant from brain-dead donors who have had a period of cardiac arrest provided that good lung function is preserved and the donor is otherwise deemed acceptable for transplantation. Potential expansion of the donor pool to include cardiac arrest as the cause of brain death requires further study. PMID:23777361

Apoptosis and Acute Brain Ischemia in Ischemic Stroke.

PubMed

Radak, Djordje; Katsiki, Niki; Resanovic, Ivana; Jovanovic, Aleksandra; Sudar-Milovanovic, Emina; Zafirovic, Sonja; Mousad, Shaker A; Isenovic, Esma R

2017-01-01

Apoptosis may contribute to a significant proportion of neuron death following acute brain ischemia (ABI), but the underlying mechanisms are still not fully understood. Brain ischemia may lead to stroke, which is one of the main causes of long-term morbidity and mortality in both developed and developing countries. Therefore, stroke prevention and treatment is clinically important. There are two important separate areas of the brain during ABI: the ischemic core and the ischemic penumbra. The ischemic core of the brain experiences a sudden reduction of blood flow, just minutes after ischemic attack with irreversible injury and subsequent cell death. On the other hand, apoptosis within the ischemic penumbra may occur after several hours or days, while necrosis starts in the first hours after the onset of ABI in the ischemic core. ABI is characterized by key molecular events that initiate apoptosis in many cells, such as overproduction of free radicals, Ca2+ overload and excitotoxicity. These changes in cellular homeostasis may trigger either necrosis or apoptosis, which often depends on cell type, cell age, and location in the brain. Apoptosis results in DNA fragmentation, degradation of cytoskeletal and nuclear proteins, cross-linking of proteins, formation of apoptotic bodies, expression of ligands for phagocytic cell receptors and finally uptake by phagocytic cells. This review focuses on recent findings based on animal and human studies regarding the apoptotic mechanisms of neuronal death following ABI and the development of potential neuroprotective agents that reduce morbidity. The effects of statins on stroke prevention and treatment as well as on apoptotic mediators are also considered. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Treatment rationale and design of the RAMNITA study: A phase II study of the efficacy of docetaxel + ramucirumab for non-small cell lung cancer with brain metastasis.

PubMed

Tanimura, Keiko; Uchino, Junji; Tamiya, Nobuyo; Kaneko, Yoshiko; Yamada, Tadaaki; Yoshimura, Kenichi; Takayama, Koichi

2018-06-01

We described the treatment rationale and procedure for a phase II study of docetaxel plus ramucirumab for non-small cell lung cancer (NSCLC) patients with brain metastasis (RAMNITA study: University Information Network Clinical Trials Registry identification no. [UMIN]: 000024551). Combination therapy of angiogenetic inhibitor with chemotherapy improved the outcome of patients with brain metastasis in previous reports; however, the efficacy of ramucirumab, a vascular endothelial growth factor receptor-2 monoclonal antibody, for brain metastasis has not been shown. This RAMNITA study is a prospective, multicenter, open-label, single-arm phase II study designed to evaluate efficacy and safety of docetaxel and ramucirumab for advanced NSCLC patients with brain metastasis. Eligible patients will receive docetaxel (60 mg/m) and ramucirumab (10 mg/kg) every 21 days until disease progression. The primary endpoint is progression-free survival (PFS), and secondary endpoints are overall survival, intracranial PFS, response rate, and safety. Sixty-five participants will be recruited from September 2017 to December 2019 and followed up for 1 year after final registration. The results from this study may suggest a treatment option for brain metastasis in NSCLC. The protocol was approved by the institutional review board of each study center. Written informed consent will be obtained from all patients before registration, in accordance with the Declaration of Helsinki.

Causes of death in remote symptomatic epilepsy.

PubMed

Day, S M; Wu, Y W; Strauss, D J; Shavelle, R M; Reynolds, R J

2005-07-26

To determine the causes of death of individuals with developmental disabilities that occur more frequently among those with remote symptomatic epilepsy (i.e., epilepsy occurring in persons with developmental delay or identified brain lesions) than for those without. The authors compared causes of mortality in persons with (n = 10,030) and without (n = 96,163) history of epilepsy in a California population of persons with mild developmental disabilities, 1988 to 2002. Subjects had traumatic brain injury, cerebral palsy, Down syndrome, autism, or a developmental disability with other or unknown etiology. There were 721,759 person-years of data, with 2,397 deaths. Underlying causes of death were determined from the State of California's official mortality records. Cause-specific death rates and standardized mortality ratios (SMRs) were computed for those with and without epilepsy relative to subjects in the California general population. Comparisons were then made between SMRs of those with and without epilepsy, and CIs on the ratios of SMRs were determined. Death rates for persons with epilepsy were elevated for several causes. The greatest excess was due to seizures (International Classification of Diseases-9 [ICD-9] 345; SMR 53.1, 95% CI 28.0 to 101.0) and convulsions (ICD-9 780.3; SMR 25.2, 95% CI 11.7 to 54.2). Other causes occurring more frequently in those with epilepsy included brain cancer (SMR 5.2, 95% CI 2.2 to 12.1), respiratory diseases (SMR 1.7, 95% CI 1.2 to 2.5), circulatory diseases (SMR 1.3, 95% CI 1.0 to 1.7), and accidents (SMR 2.7, 95% CI 1.9 to 3.7), especially accidental drowning (SMR 12.8, 95% CI 7.0 to 23.2). Remote symptomatic epilepsy is associated with an increased risk of death. Seizures, aspiration pneumonia, and accidental drowning are among the leading contributors.

Sugar for the brain: the role of glucose in physiological and pathological brain function

PubMed Central

Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A.; Meisel, Andreas

2013-01-01

The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We aim at synthesizing these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation which lead to disease. PMID:23968694

Inhaled 45-50% argon augments hypothermic brain protection in a piglet model of perinatal asphyxia.

PubMed

Broad, Kevin D; Fierens, Igor; Fleiss, Bobbi; Rocha-Ferreira, Eridan; Ezzati, Mojgan; Hassell, Jane; Alonso-Alconada, Daniel; Bainbridge, Alan; Kawano, Go; Ma, Daqing; Tachtsidis, Ilias; Gressens, Pierre; Golay, Xavier; Sanders, Robert D; Robertson, Nicola J

2016-03-01

Cooling to 33.5°C in babies with neonatal encephalopathy significantly reduces death and disability, however additional therapies are needed to maximize brain protection. Following hypoxia-ischemia we assessed whether inhaled 45-50% Argon from 2-26h augmented hypothermia neuroprotection in a neonatal piglet model, using MRS and aEEG, which predict outcome in babies with neonatal encephalopathy, and immunohistochemistry. Following cerebral hypoxia-ischemia, 20 Newborn male Large White piglets<40h were randomized to: (i) Cooling (33°C) from 2-26h (n=10); or (ii) Cooling and inhaled 45-50% Argon (Cooling+Argon) from 2-26h (n=8). Whole-brain phosphorus-31 and regional proton MRS were acquired at baseline, 24 and 48h after hypoxia-ischemia. EEG was monitored. At 48h after hypoxia-ischemia, cell death (TUNEL) was evaluated over 7 brain regions. There were no differences in body weight, duration of hypoxia-ischemia or insult severity; throughout the study there were no differences in heart rate, arterial blood pressure, blood biochemistry and inotrope support. Two piglets in the Cooling+Argon group were excluded. Comparing Cooling+Argon with Cooling there was preservation of whole-brain MRS ATP and PCr/Pi at 48h after hypoxia-ischemia (p<0.001 for both) and lower (1)H MRS lactate/N acetyl aspartate in white (p=0.03 and 0.04) but not gray matter at 24 and 48h. EEG background recovery was faster (p<0.01) with Cooling+Argon. An overall difference between average cell-death of Cooling versus Cooling+Argon was observed (p<0.01); estimated cells per mm(2) were 23.9 points lower (95% C.I. 7.3-40.5) for the Cooling+Argon versus Cooling. Inhaled 45-50% Argon from 2-26h augmented hypothermic protection at 48h after hypoxia-ischemia shown by improved brain energy metabolism on MRS, faster EEG recovery and reduced cell death on TUNEL. Argon may provide a cheap and practical therapy to augment cooling for neonatal encephalopathy. Copyright © 2015. Published by Elsevier Inc.

Association of BDNF Val66Met Polymorphism and Brain BDNF Levels with Major Depression and Suicide.

PubMed

Youssef, Mariam M; Underwood, Mark D; Huang, Yung-Yu; Hsiung, Shu-Chi; Liu, Yan; Simpson, Norman R; Bakalian, Mihran J; Rosoklija, Gorazd B; Dwork, Andrew J; Arango, Victoria; Mann, J John

2018-06-01

Brain-derived neurotrophic factor is implicated in the pathophysiology of major depressive disorder and suicide. Both are partly caused by early life adversity, which reduces brain-derived neurotrophic factor protein levels. This study examines the association of brain-derived neurotrophic factor Val66Met polymorphism and brain brain-derived neurotrophic factor levels with depression and suicide. We hypothesized that both major depressive disorder and early life adversity would be associated with the Met allele and lower brain brain-derived neurotrophic factor levels. Such an association would be consistent with low brain-derived neurotrophic factor mediating the effect of early life adversity on adulthood suicide and major depressive disorder. Brain-derived neurotrophic factor Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 nonsuicides. Additionally, brain-derived neurotrophic factor protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9), anterior cingulate cortex (Brodmann area 24), caudal brainstem, and rostral brainstem. The relationships between these measures and major depressive disorder, death by suicide, and reported early life adversity were examined. Subjects with the Met allele had an increased risk for depression. Depressed patients also have lower brain-derived neurotrophic factor levels in anterior cingulate cortex and caudal brainstem compared with nondepressed subjects. No effect of history of suicide death or early life adversity was observed with genotype, but lower brain-derived neurotrophic factor levels in the anterior cingulate cortex were found in subjects who had been exposed to early life adversity and/or died by suicide compared with nonsuicide decedents and no reported early life adversity. This study provides further evidence implicating low brain brain-derived neurotrophic factor and the brain-derived neurotrophic factor Met allele in major depression risk. Future studies should seek to determine how altered brain-derived neurotrophic factor expression contributes to depression and suicide.

Brain Basics: Preventing Stroke

MedlinePlus

... of death or disability from stroke. With good control, the risk of stroke in most age groups can be kept below that for accidental injury ... of death or disability from stroke. With good control, the risk of stroke in most age groups can be kept below that for accidental injury ...

A mouse model for creatine transporter deficiency reveals early onset cognitive impairment and neuropathology associated with brain aging.

PubMed

Baroncelli, Laura; Molinaro, Angelo; Cacciante, Francesco; Alessandrì, Maria Grazia; Napoli, Debora; Putignano, Elena; Tola, Jonida; Leuzzi, Vincenzo; Cioni, Giovanni; Pizzorusso, Tommaso

2016-10-01

Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and autistic-like behavioural disturbances, language and speech impairment. Since no data are available about the neural and molecular underpinnings of this disease, we performed a longitudinal analysis of behavioural and pathological alterations associated with CrT deficiency in a CCDS1 mouse model. We found precocious cognitive and autistic-like defects, mimicking the early key features of human CCDS1. Moreover, mutant mice displayed a progressive impairment of short and long-term declarative memory denoting an early brain aging. Pathological examination showed a prominent loss of GABAergic synapses, marked activation of microglia, reduction of hippocampal neurogenesis and the accumulation of autofluorescent lipofuscin. Our data suggest that brain Cr depletion causes both early intellectual disability and late progressive cognitive decline, and identify novel targets to design intervention strategies aimed at overcoming brain CCDS1 alterations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Interaction between lexical and grammatical language systems in the brain

NASA Astrophysics Data System (ADS)

Ardila, Alfredo

2012-06-01

This review concentrates on two different language dimensions: lexical/semantic and grammatical. This distinction between a lexical/semantic system and a grammatical system is well known in linguistics, but in cognitive neurosciences it has been obscured by the assumption that there are several forms of language disturbances associated with focal brain damage and hence language includes a diversity of functions (phoneme discrimination, lexical memory, grammar, repetition, language initiation ability, etc.), each one associated with the activity of a specific brain area. The clinical observation of patients with cerebral pathology shows that there are indeed only two different forms of language disturbances (disturbances in the lexical/semantic system and disturbances in the grammatical system); these two language dimensions are supported by different brain areas (temporal and frontal) in the left hemisphere. Furthermore, these two aspects of the language are developed at different ages during child's language acquisition, and they probably appeared at different historical moments during human evolution. Mechanisms of learning are different for both language systems: whereas the lexical/semantic knowledge is based in a declarative memory, grammatical knowledge corresponds to a procedural type of memory. Recognizing these two language dimensions can be crucial in understanding language evolution and human cognition.

Current status of pregnancy-related maternal mortality in Japan: a report from the Maternal Death Exploratory Committee in Japan.

PubMed

Hasegawa, Junichi; Sekizawa, Akihiko; Tanaka, Hiroaki; Katsuragi, Shinji; Osato, Kazuhiro; Murakoshi, Takeshi; Nakata, Masahiko; Nakamura, Masamitsu; Yoshimatsu, Jun; Sadahiro, Tomohito; Kanayama, Naohiro; Ishiwata, Isamu; Kinoshita, Katsuyuki; Ikeda, Tomoaki

2016-03-21

To clarify the problems related to maternal deaths in Japan, including the diseases themselves, causes, treatments and the hospital or regional systems. Descriptive study. Maternal death registration system established by the Japan Association of Obstetricians and Gynecologists (JAOG). Women who died during pregnancy or within a year after delivery, from 2010 to 2014, throughout Japan (N=213). The preventability and problems in each maternal death. Maternal deaths were frequently caused by obstetric haemorrhage (23%), brain disease (16%), amniotic fluid embolism (12%), cardiovascular disease (8%) and pulmonary disease (8%). The Committee considered that it was impossible to prevent death in 51% of the cases, whereas they considered prevention in 26%, 15% and 7% of the cases to be slightly, moderately and highly possible, respectively. It was difficult to prevent maternal deaths due to amniotic fluid embolism and brain disease. In contrast, half of the deaths due to obstetric haemorrhage were considered preventable, because the peak duration between the initial symptoms and initial cardiopulmonary arrest was 1-3 h. A range of measures, including individual education and the construction of good relationships among regional hospitals, should be established in the near future, to improve primary care for patients with maternal haemorrhage and to save the lives of mothers in Japan. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Demyelination as a rational therapeutic target for ischemic or traumatic brain injury.

PubMed

Shi, Hong; Hu, Xiaoming; Leak, Rehana K; Shi, Yejie; An, Chengrui; Suenaga, Jun; Chen, Jun; Gao, Yanqin

2015-10-01

Previous research on stroke and traumatic brain injury (TBI) heavily emphasized pathological alterations in neuronal cells within gray matter. However, recent studies have highlighted the equal importance of white matter integrity in long-term recovery from these conditions. Demyelination is a major component of white matter injury and is characterized by loss of the myelin sheath and oligodendrocyte cell death. Demyelination contributes significantly to long-term sensorimotor and cognitive deficits because the adult brain only has limited capacity for oligodendrocyte regeneration and axonal remyelination. In the current review, we will provide an overview of the major causes of demyelination and oligodendrocyte cell death following acute brain injuries, and discuss the crosstalk between myelin, axons, microglia, and astrocytes during the process of demyelination. Recent discoveries of molecules that regulate the processes of remyelination may provide novel therapeutic targets to restore white matter integrity and improve long-term neurological recovery in stroke or TBI patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance.

PubMed

Schreiweis, Christiane; Bornschein, Ulrich; Burguière, Eric; Kerimoglu, Cemil; Schreiter, Sven; Dannemann, Michael; Goyal, Shubhi; Rea, Ellis; French, Catherine A; Puliyadi, Rathi; Groszer, Matthias; Fisher, Simon E; Mundry, Roger; Winter, Christine; Hevers, Wulf; Pääbo, Svante; Enard, Wolfgang; Graybiel, Ann M

2014-09-30

The acquisition of language and speech is uniquely human, but how genetic changes might have adapted the nervous system to this capacity is not well understood. Two human-specific amino acid substitutions in the transcription factor forkhead box P2 (FOXP2) are outstanding mechanistic candidates, as they could have been positively selected during human evolution and as FOXP2 is the sole gene to date firmly linked to speech and language development. When these two substitutions are introduced into the endogenous Foxp2 gene of mice (Foxp2(hum)), cortico-basal ganglia circuits are specifically affected. Here we demonstrate marked effects of this humanization of Foxp2 on learning and striatal neuroplasticity. Foxp2(hum/hum) mice learn stimulus-response associations faster than their WT littermates in situations in which declarative (i.e., place-based) and procedural (i.e., response-based) forms of learning could compete during transitions toward proceduralization of action sequences. Striatal districts known to be differently related to these two modes of learning are affected differently in the Foxp2(hum/hum) mice, as judged by measures of dopamine levels, gene expression patterns, and synaptic plasticity, including an NMDA receptor-dependent form of long-term depression. These findings raise the possibility that the humanized Foxp2 phenotype reflects a different tuning of corticostriatal systems involved in declarative and procedural learning, a capacity potentially contributing to adapting the human brain for speech and language acquisition.

Advantages of analyzing postmortem brain samples in routine forensic drug screening-Case series of three non-natural deaths tested positive for lysergic acid diethylamide (LSD).

PubMed

Mardal, Marie; Johansen, Sys Stybe; Thomsen, Ragnar; Linnet, Kristian

2017-09-01

Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma and urine when available. LSD, its main metabolite 2-oxo-3-hydroxy-LSD (oxo-HO-LSD), and iso-LSD were quantified in biological samples according to a previously published procedure involving liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). LSD was measured in the brain tissue of all presented cases at a concentration level from 0.34-10.8μg/kg. The concentration level in the target organ was higher than in peripheral blood. Additional psychoactive compounds were quantified in blood and brain tissue, though all below toxic concentration levels. The cause of death in case 1 was collision-induced brain injury, while it was drowning in case 2 and 3 and thus not drug intoxication. However, the toxicological findings could help explain the decedent's inability to cope with brain injury or drowning incidents. The presented findings could help establish reference concentrations in brain samples and assist in interpretation of results from forensic drug screening in brain tissue. This is to the author's knowledge the first report of LSD, iso-LSD, and oxo-HO-LSD measured in brain tissue samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Restoration of stressor-induced calcium dysregulation and autophagy inhibition by polyphenol-rich acai (Euterpe sps.) fruit pulp extracts in rodent brain cells in vitro

USDA-ARS?s Scientific Manuscript database

Oxidative damage to lipids, proteins and nucleic acids in brain often causes progressive neuronal degeneration and death which are the focal traits of chronic and acute pathologies in the brain, including those involving cognitive decline. It has been postulated that at least part of the loss of cog...

Increased level of apoptosis in rat brains and SH-SY5Y cells exposed to excessive fluoride--a mechanism connected with activating JNK phosphorylation.

PubMed

Liu, Yan-Jie; Guan, Zhi-Zhong; Gao, Qin; Pei, Jin-Jing

2011-07-28

In order to reveal the mechanism of the brain injury induced by chronic fluorosis, the levels of apoptosis and c-Jun N-terminal kinases (JNK) in brains of rats and SH-SY5Y cells exposed to different concentrations of sodium fluoride (NaF) were detected. The dental fluorosis and fluoride contents in blood, urine and bones of rats were measured to evaluate the exhibition of fluorosis. The apoptotic death rate was measured by flow cytometry and the expression of JNK at protein level by Western blotting. The results showed that as compared with controls, the apoptotic death rate was obviously increased in brains of the rats exposed to high-fluoride (50ppm) for 6 months with a concentration dependent manner, but no significant change for 3 months. In SH-SY5Y cells treated with high concentration (50ppm) of fluoride, the increased apoptotic death rate was obviously observed as compared to controls. In addition, the expressions of phospho-JNK at protein level were raised by 20.5% and 107.6%, respectively, in brains of the rats exposed to low-fluoride (5ppm) and high-fluoride for 6 months; while no significant changes were found between the rats exposed to fluoride and the controls for 3 months. The protein level of phospho-JNK was also increased in SH-SY5Y cells exposed to high-fluoride. There were no changes of total-JNK both in the rats and in the SH-SY5Y cells exposed to excessive fluoride as compared to controls. When SH-SY5Y cells were singly treated with SP600125, an inhibitor of phospho-JNK, the decreased expression of phospho-JNK, but no apoptosis, was detected. Interestingly, after JNK phosphorylation in the cultured cells was inhibited by SP600125, the treatment with high-fluoride did not induce the increase of apoptosis. In addition, there was a positive correlation between the expression of phospho-JNK and the apoptotic death rate in rat brains or SH-SY5Y cells treated with high-fluoride. The results indicated that exposure to excessive fluoride resulted in the increase of apoptosis in rat brains and SH-SY5Y cells, in which one of the mechanisms might be activating JNK phosphorylation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

[External post-mortem examination].

PubMed

Hartwig, S

2016-09-01

The external post-mortem examination in Germany is a non-delegable medical duty for determination of death, identity of the deceased, cause of death, manner of death, time of death and notifiable infectious diseases. Within the framework of rescue service missions the physician is limited to ascertaining that death has occurred. The determination of death must be reliable and is automatically followed by a complete external post-mortem examination of the body, if necessary by another physician. The certain signs of death are livor mortis, rigor mortis and putrefaction. Reliable features for the occurrence of death are injuries which are not compatible with life and brain death. The external post-mortem examination is the basis for the decision on whether further criminal investigations are necessary. The external post-mortem examination and the accompanying death certification must always be meticulously carried out.

Caspase Activation in Fetal Rat Brain Following Experimental Intrauterine Inflammation

PubMed Central

Sharangpani, Aditi; Takanohashi, Asako; Bell, Michael J.

2009-01-01

Intrauterine inflammation has been implicated in developmental brain injuries, including the development of periventricular leukomalacia (PVL) and cerebral palsy (CP). Previous studies in our rat model of intrauterine inflammation demonstrated apoptotic cell death in fetal brains within the first 5 days after lipopolysaccharide (LPS) administration to mothers and eventual dysmyelination. Cysteine-containing, aspartate-specific proteases, or caspases, are proteins involved with apoptosis through both intracellular (intrinsic pathway) and extracellular (extrinsic pathway) mechanisms. We hypothesized that cell death in our model would occur mainly via activation of the extrinsic pathway. We further hypothesized that Fas, a member of the tumor necrosis factor receptor (TNFR) superfamily, would be increased and the death inducing signaling complex (DISC) would be detectable. Pregnant rats were injected intracervically with LPS at E15 and immunoblotting, immunohistochemical and immunoprecipitation analyses were performed. The presence of the activated form of the effector caspase (caspase-3) was observed 24 h after LPS administration. Caspase activity assays demonstrated rapid increases in (i) caspases-9 and -10 within 1 h, (ii) caspase-8 at 2 h and (iii) caspase-3 at 4 h. At 24 h after LPS, activated caspase-3+/Fas+ cells were observed within the developing white matter. Lastly, the DISC complex (caspase-8, Fas and Fas-associated Death Domain (FADD)) was observed within 30 min by immunoprecipitation. Apoptosis in our model occurs via both extrinsic and intrinsic pathways, and activation of Fas may play a role. Understanding the mechanisms of cell death in models of intrauterine inflammation may affect development of future strategies to mitigate these injuries in children. PMID:18289516