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Apart from the deontological argument, utilitarian argu- ments have also been added to recent de- bates on euthanasia. Their argument claims that a particular action is to be considered wrong not because there is a norm prohib- iting it, but rather because the action goes against the greatest good for the great- est number of the people.

For the case in point, the utilitarian or consequentialist argument rejects the practice of euthanasia. This is a brief statement, like the rest of the statements that are mentioned in the Oath, which instructs doctors not to provide patients with any means to end their lives. However, medical tradition has always seen it as a prohibition of any lethal act on the part of the doctor. The anthropologist Margaret Mead explains that Greek medicine distin- guished the doctor from the magician, when the definitive separation between to kill and to cure was achieved [6].

As concerns the current debate on euthana- sia, this ethical rule is extremely important, for it was written in a social and philosophi- cal context that widely favoured suicide. Platonists as well as cynics and stoics were in favour of euthanasia in the event of ill- ness, and in some cases it was actually seen as an act of courage. Aristotle and Epicu- rus held a less positive outlook on suicide, though left certain space for its justification [7].

This is a significant fact,for even though it was a relatively common and socially jus- tified practice, Medical Ethics considered it important for doctors to avoid in order not to contradict their profession which is precisely to cure and not to kill the patient. Euthanasia would repre- sent the illusion of being in control of ill- ness at all times and of being able to put an end to life, when considered the best choice, without having to succumb to the domi- nance of technology that can keep people alive as long as possible.

Fundamentally, there is a feeling of mistrust towards the doctor and his medicine. What the author finds paradoxical is that in order to protect itself from this technological assault, society would so easily choose this path and happily entrust the doctor with the power of delib- erately ending a life [10]. The author is of the per- sonal view that there is no moral issue in ap- plying euthanasia to specific cases; but the European experience shows the great influ- ence the legalisation of this practice has on the doctor-patient relationship.

Another important aspect when consider- ing euthanasia that goes beyond the doctor- patient relationship is the weighty matter of critically ill patients having to make a decision, and in a certain sense justify, their desire to carry on living. Although its pro- ponents insist that the choice of euthanasia must be free from coercion, in practice this hardly ever happens.

In , Tonti-Filippini, an Australian bioethicist who recently passed away , wrote an open letter in plain and di- rect language to the then Prime Minister of his Country, Mike Rann, concerning a legislative proposal in favour of euthanasia. He pointed out that for people like himself, who found themselves in a situation eligible for euthanasia, the last thing they needed was precisely such a possibility. What they needed was human contact, support and good medical care, since their critical state of health was already dulling their will to fight…and to live [12].

It seems to me that this aspect of the matter is rarely taken into serious consideration,whereas it should give healthcare professionals food for thought. Slippery slope The debate on euthanasia has increasingly given greater weight to moral arguments based on consequences caused by actions and on healthcare policies. Experience proves, moreover, that in time the restric- tions are weakened and euthanasia ends up being applied to patients who in principle should have been excluded. Before we move on to study this issue, let us look at some data. As a matter of fact in the Netherlands it was legalised in as a result of a deci- sion of the Dutch Suprme Court.

In the de- bates previous to the ratification of the law, they talked of limit cases in which medical care, it was held, was incapable of provid- ing a satisfactory answer. Instead what has been witnessed over the years has been an annual increase in the practice of euthanasia as more and more justifications have been given for it. It is true that, in the years fol- lowing the approval of the law in favour of euthanasia in the Netherlands, there was a slight decrease in the number of cases com- pared to the previous years. In , deaths from euthanasia and assisted suicide repre- sented 2.

Nevertheless, after the numbers settled, there has been a considerable increase over the last few years. In the report of the Regional euthana- sia review committees which gives data from the first year of the promulgation of the law, cases of euthanasia and assisted sui- cide were recorded; in , they increased to and in , they reached cases. In the report, the total number of deaths by euthanasia and assisted suicides was [14]. In , the deaths from con- tinuous deep sedation amounted to 5. Although the Dutch Medical Associa- tion considers this practice distinct from as- sisted suicide, in our opinion there is hardly any difference between the two [15].

These statistics help give an idea of the situation regarding euthanasia and similar practices at the end-of-life in the country with the most experience of such issues. He distinguishes two main aspects of the argument: an empirical and a logical one. The first is a simple observation: in those places in which euthanasia was ap- proved for persons with incurable illness as- sociated with intolerable suffering and who would repeatedly request for an end to their lives, it is has been seen that, over the years, euthanasia has been performed on patients with curable illnesses, who did not have in- tolerable suffering or who had not requested to die.

The logical aspect of the argument, holds that the specific precautions, which are taken with the specific purpose of reduc- ing the practice of euthanasia to only limit cases, disappears not only because of the practical question at the moment of imple- mentation, but also because of a theoretical reason. What justifies euthanasia in certain limit cases, making reference to patient au- tonomy or to the fact that some patients would be better off dead, can also be used to justify its practice when patients voluntarily ask for it even if they do not have intoler- able suffering such as in the case for elderly people.

Similarly, non-voluntary euthanasia would be also considered justifiable in those cases in which chronically unconscious pa- tients are considered to be better off dead. Raphael Cohen-Almagor, another author who has made an in-depth study of euthanasia in the countries that have legalised it, is of the same opinion. The entire system controlling euthanasia in the Netherlands and Belgium relies on the information gleaned from questionnaires completed by doctors for each case and sent to the relevant Commission for evaluation.

This control system fails in the assessment of less clear cases or when not all the legal provisions have been followed. In a study published in the British Medical Journal in , Smets et al. The conclusion of the study was that only half of the cases of euthanasia were re- ported to the Commission. In some cases, the error was due to the fact that doctors did not consider the death as due to euthanasia; in others it was due to the feeling that com- pleting the documentation was an admin- istrative burden, or that not all the legal re- quirements had been applied.

Due to limited space, we will only mention three major points: euthanasia for the el- derly people who are not suffering from any incurable illness; euthanasia for newborns or minors and euthanasia for patients with depression. At the beginning, the law required an incurable illness, which would cause intolerable suffer- ing. The text goes as far as pointing out that this question was the issue of previ- ous debate but which has been resolved as it has been noted that intolerable suffering is not only caused by terminal illnesses but also by many geriatric conditions [21].

It is easy to understand how difficult it is for doctors to evaluate such a request. Euthanasia is also problematic when con- sidered at the opposite extreme of age. In the first years of the debate on euthanasia and during the drafting of the first legislation, the practice of euthanasia was intended for adults,who could provide a valid consent. In the Dutch situation, it only took a few years to extend euthanasia to those over 16 with- out their parents consent, and to those be- tween 12 and 16 with parental consent [22].

Neither did it take long to justify euthanasia for newborns born with serious conditions [23]. Although it may be true that these are very complex cases, in which the best inter- ests of the child are being sought, it is also true that in their justification the basic mor- al element of autonomous decision is lost.

In , Belgium abolished the age limit on euthanasia. A similar problem arises when euthanasia is granted to people with psychi- atric illnesses, and in particular those who suffer from depression. In these cases, it is very hard to ascertain that the request to die is the result of a well informed decision made with the minimum amount of interior freedom required for such a decision. We can conclude that, from both a medical and ethical point of view, it represents an inadequate solution to a real problem; a solution that, as we have seen, leads doctors and patients to get used to it and to consider it as one more therapeu- tic option.

This in turn explains the growing number of euthanasia cases every year. We believe that Medicine has much more to offer and that, today, its ability to deal with many symptoms is incomparably bet- ter than it was a few years ago. In many articles that describe the experience of eu- thanasia in the Netherlands and Belgium, pain, and generally pain caused by cancer, is one of the major reasons why people ask for euthanasia [24].

In some cases,it is true that treating this kind of pain might be very dif- ficult, but modern palliative care is capable of alleviating the majority of this type of pain. The problem is that, often, physicians do not possess the appropriate competence to do so. This figure appears to us to suggest that the solution to requests for euthanasia, which in reality are always a request for help, lies in this direction. A request for help can be answered in many different ways, but not all the answers are equally beneficial. As we said at the begin- ning, closing the door on euthanasia should represent a starting point for substantially improving professional training in the ter- minal care of patients.

Therefore, we believe that WMA should not change its policy on euthanasia. A pol- icy based on a Medical Ethic thousands of years old, which does not involve any exter- nal control of medical care but rather is a constant stimulus to better the care of pa- tients in the final moments of their lives, al- ways guaranteeing their personal autonomy. I am very grateful to Dr. Paul Kioko and Prof. John Keown for their invaluable help with the final draft of this article. Maxence van der Meersch. Bodies and Souls. David J.

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New Brun- swick: AldineTransaction, The Hippocratic Oath. Baltimore: Johns Hopkins Press, ; 3. Nigel M. New ed Chicago; London: Bioethics Press, ; William Frankena. The ethics of respect for life. Temkin, W. Frankena, S. Kadish eds. Respect for life in medicine, philosophy, and the law. This paper will outline seven arguments that will likely be pressed on the WMA; and why they all fail [2]. As the first two arguments are typically at the forefront of the case for decriminalisation, more space will be devoted to them.

Seven Arguments for Decriminalisation 1. While autonomy is an im- portant capacity, respect for autonomy has its 8. Gaylin et al. JAMA , No. Daniel Callahan. Herbert Hendin. New York: W. Norton, Published in the Herald Sun Agnes van der Heide et al. Royal Dutch Medical Association. Amsterdam: KNMG,; 34— John Keown. Cam- bridge: Cambridge University Press; Bregje D. Onwuteaka-Philipsen et al.

Lancet, , No. Euthanasia in the Netherlands: What Lessons for Elsewhere? Lan- cet , No. This study shows cases of speeding death without request in and cases in Raphael Cohen-Almagor. Tinne Smets et al. David Lamb. Rome: Pontifical University of the Holy Cross, Regional euthanasia review committees. Code of Practice. Eduard Verhagen and Pieter J. New England Journal of Medicine, , No. See for example the Code of Practice ,p.

Patients no more have the right to a lethal injection from their physician than they have to the amputa- tion of a healthy limb. Patients have a right to refuse treatment, but that is a negative right, not a positive right; a shield, not a sword. Laws in most countries of the world continue to prohibit a choice to be killed. This prohibition is grounded in a recognition of our fundamental equality- in-dignity, however sick or disabled we may be. It protects each one of us impartially, embodying the belief that all are equal [5]. The Select Committee concluded: [W]e do not think it possible to set secure limits on voluntary euthanasia…It would be next to impossible to ensure that all acts of euthanasia were truly voluntary, and that any liberalisation of the law was not abused [6].

In other words, doctors would have to judge which autonomous requests to grant, and which to refuse. It is trumped by the duty not intention- ally to kill patients. The core vocation of the physician is to heal, to make whole, not to make dead [11]. This vocation includes a duty to alleviate suffering even if, as an unintended side-ef- fect, life is shortened. But it rules out inten- tional killing. As Alexander Capron, the leading US health lawyer, once starkly put it, he never wanted to have to wonder whether the physician entering his room was wearing the white coat of the healer or the black hood of the executioner [12].

The enormous progress that has been made in palliative care, not least since the establishment of the hospice movement by Dame Cicely Saunders 50 years ago, means that no patient need suffer unbearably. Even in rare cases of refractory pain, there is the option of palliative sedation. Although euthanasia advocates typically use emotionally-charged cases of dying patients with painful symptoms to front their cam- paign, the reality is that after decriminalisa- tion VE and PAS come to be condoned a much wider range of cases. In the Court held that purely mental suffering could qualify [15].

Cases such as the purblind twins [18], the distressed transsexual [19], and the grieving mother [20], have all illus- trated the disturbing elasticity of the legal criteria. Why should compassion be con- fined to the competent? Chief Justice Rehnquist noted that the fact that General Eisenhower foresaw on D-Day that he was sending many American soldiers to certain death did not mean he intended their death: his purpose was to liberate Europe from the Nazis [25]. Even the Dutch and the Belgians euthana- sia laws, which reject the Hippocractic ethic against medical killing, agree that eutha- nasia involves intentional, and not merely foreseen, life-shortening [26].

This means that the law now recognises a right to commit suicide. If there is a right to commit suicide, it should be legal to assist some- one to exercise that right. In the UK, for ex- ample, legislators made it crystal clear that decriminalisation did not imply condona- tion [27]. The explanation for decriminali- sation lay elsewhere.

Legislators increasingly appreciated, thanks to the development of the specialty of psy- chiatry, that suicidal ideation is associated with psychiatric disturbance, and that the suicidal would be better diverted from sui- cide by the mental health system than by the criminal justice system. Moreover, the crime stigmatised family members and led to the unfortunate consequence of pros- ecuting attempted suicides [28]. The law should reflect the will of the people.

But, first, polls can be misleading. Much can de- pend on the phrasing of questions and on the amount of background information, if any, given to those polled. Second, it may well be that the majority of the public support the restoration of capital and corporal punishment. Is that a sound argument for their restoration? Decriminalisation would bring them out into the open and subject them to effective legal control. There will be breaches of the law, to a greater or lesser extent, in different jurisdictions,depending on a range of cultural factors. The Dutch in particular have carried out valuable surveys into end-of-life decision- making.

Those surveys have shown that doctors have failed to report thousands of cases to the Dutch monitoring authorities. In the Com- mittee expressed concern not only about the adequacy of the regulatory system, but about the extension of the law to minors, and the practice of infanticide [33]. As for Oregon, there have been no compre- hensive surveys, so any claims that its law is achieving effective control lack substan- tiation.

The regulatory mechanism in all three ju- risdictions depends on self-reporting by physicians. It is, therefore, intrinsically inef- fective. How many physicians are going to report that they have broken the law? However, three judges of the Irish High Court,who later carefully reviewed the same evidence as the trial judge, rejected her find- ing [38].

And rightly so. Moreover, many secular bodies have op- posed decriminalisation. One example is the UK Parliament, which has repeatedly rejected the case for decriminalisation, most recently in , when the House of Com- mons voted by a margin of against a Bill to decriminalise PAS [41]. Another exam- ple is the World Medical Association itself. Those ar- guments are, however, unpersuasive. For a fuller treatment of these arguments see Keown, John. Debating Euthanasia. See also Keown, John. In: Heneghan, Mark and Wall, Jesse. See also Keown,John. Euthanasia,Ethics and Public Policy.

Cambridge: Cambridge University Press, ; 2nd ed forthcoming See generally Keown, John. Oxford: Oxford University Press, ; chapter 1. United Nations.

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Report of the Select Committee on Medical Ethics. London: HMSO. Paper I of 94; para. Hip- pocratic Oath. See Kass, Leon R. Compassion is Not Enough. In ibid. Quoted in DE RCP affirms position against assisted dying [In- ternet] [cited Oct 3]. Euthanasia, Ethics and Public Policy. Dordrecht: Kluwer, ; Griffiths, John et al.

Euthanasia and Law in Europe. Oxford: Hart Publishing, ; part I. Keown, John. Cambridge: Cambridge University Press, The Chicago Tribune. The Belgian experience of euthanasia: 14 years of legal implementation. Cambridge: Cambridge University Press, forthcoming.

I am grateful to Professors Jones and Montero for a view of this essay. Waterfield, Bruno. The Daily Telegraph. Belgian killed by euthanasia after a botched sex change operation. The subject of a disturbing documentary on Australian channel SBS. Allow Me to Die. Oregon Health Authority.

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  4. Table 1. End of life concerns. New Engl J Med ; Twycross, Robert. Where there is hope there is life: a view from the hospice. In: Keown, John ed Euthanasia Examined. Cambridge: Cam- bridge University Press, , Vacco v Quill US , Nys, Herman. European Journal of Health Law ; , See Keown, John. See ibid. See DE Seale, Clive. National survey of end-of-life deci- sions made by UK medical practitioners.

    Pallia- tive Medicine ; 3, 6. Griffiths, John et al. Euthanasia and Law in Eu- rope. Oxford: Hart Publishing, Chambaere, K et al. New Engl J Med ; ; UN Press Release. UN Human Rights Committee. Capron, Alexander M. Legalizing Physician- Aided Death. Camb Q Healthc Ethics ; 5 1 ; Carter v. A Right to Voluntary Eutha- nasia? Confusion in Canada in Carter.

    Minnesota Law Review ; 42 6 ; Gallagher, James and Roxby, Philippa. BBC News 11 September Savulescu, Julian and Schuklenk, Udo. Bioethics It has been demonstrated to be on a steady rise and new mechanisms of resistance are emerging every day,exhausting the antibiotic options currently available. AMR has both health and economic im- plications. Increasing evidence that the overuse and misuse of antibiotics in food animal produc- tion is contributing to this rise in resistance has also emerged. In November , re- searchers in China discovered mcr-1, a gene conferring plasmid mediated resistance to colistin in pigs, which since has been found in humans as well.

    The root cause of rising resistance has many facets and involves a multitude of stake- holders from different sectors, however today, an overwhelming proportion of the worldwide consumption of antibiotics is for animal use. This puts the veterinary and agricultural sector use at the essence of the fight against AMR. Ob- jective four more notably focuses on opti- mizing the use of antibiotics in both human and animal health [2]. At this stage of the action plan implementation, it is critical for all stakeholders to engage and commit to combat the rampant AMR threat.

    These esti- mates may be underreported, however, since they do not account for pathogens that cause chronic diseases e. As global mortality trends due to infectious diseases have declined over the past decade, public health leaders should quickly identify economic, environmental, political and social challenges encountered in disease control and form multi-sectoral collabora- tions to continue this downhill disease trend. Since the s, globalization has facilitated the spread of infectious diseases, especially through increased travel for humans,expand- ed geographic boundaries for commerce and trade for animal products and other goods, and anthropogenic changes to the physi- cal environment such as deforestation or air and water pollution [5].

    These new environ- ments have facilitated the emergence and re- emergence of infectious diseases which add to the global health burden. Zoonot- ic disease transmission may include contact with domestic or wild animals or exposure to animal products, vectors or contaminated environments. Among these factors, the com- mon element lies in the potential of increased proximity to domestic or wild animals.

    First, companion animals, primarily dogs and cats, may enhance the human-animal emotional bond, but remain a threat for various zoonot- ic disease transmission, such as bartonellosis, giardiasis and toxoplasmosis [10]. Second, animal husbandry or caring for and manag- ing livestock represents a significant source of food security and economic sustainability for livestock owners and families. Thus,public health programs can effectively prepare and educate their local communities about health hazards if they understand this interplay be- tween zoonotic disease transmission and un- derlying cultural, economic and environmen- tal influences related to animal contact.

    More specifically, three specific challenges should be addressed. First, food- borne zoonoses are increasing in incidence and becoming more resistant to antibiot- ics [12]. Thus, food safety education and proper hygiene when handling domestic or livestock animals can inform communities about the health risks of food-borne zoo- noses.

    Second, specific driving factors that influence the spread of emerging diseases in target communities should be identi- fied [13]. Public health practitioners can then be prepared to act promptly and ap- propriately to reduce disease transmission or propagation to new geographic areas. Since complex epidemiol- ogy describes pathogen transmission in the human-animal interface, which challenges the formal assessment of AMR [16], estab- lishing the infrastructure of the surveillance system should be a priority for the health sector. Antibiotics for non- Therapeutic Use When discussing AMR, another essential point to mention would be Antibiotics for non-therapeutic use, which is a practice pe- culiar to the animal sector.

    Non therapeutic indications for antibiotic use in animal agriculture and aquaculture involve administering antimicrobial drugs to healthy animals for prophylaxis or growth production. Hypothesized mechanisms in- clude a more rapid growth of animals while preventing disease. There are several pathways for transmission of antibiotic resistant bacteria from food animal production to humans. These might include transmission of resistant pathogens from food animals to producers and proces- sors, through contaminated food or animal products, environmental releases from pro- duction facilities,poor control of waste man- agement and non-domesticated animals [19].

    Clinical studies have confirmed that the use of antibiotics in agricultural settings contributes to the development and spread of resistant bacteria. In , antibiotic use to increase the amount of meat produced in animals was found to be effective. This constituted the first step into widely using antibiotics as growth promoters, despite some early studies like Levy et al. This study tested a long course of low-dose tetracycline in chickens; this led to single drug resistance which rapidly devel- oped into multidrug resistance that spread beyond individual animals exposed and into humans.

    A more recent study performed by Price et al. Many governments have taken actions into this matter. One of the first countries to ad- dress this issue was Denmark. By they banned avoparcin, one of many antibiotics used for growth promotion; this was the be- ginning of a series of regulations which lead to the European Union EU in banning feeding of antibiotics to animals that are valu- able to human health.

    Denmark also created DANMAP in , their own system for monitoring antibiotic resistance in farm animals with the objective of following the outcomes of banning anti- biotic drugs for growth promotion which through VETSTAT, a monitoring system which task was to gather and process records of drug use in animal herds. They also creat- ed the Yellow Card scheme which decreased the total consumption of antibiotics in pigs by implementing a monitoring system with penalties and regular visits to producers.

    When measuring its effect, antimicrobial agent usage dropped and AMR for growth promotion also decreased. These actions did not have a negative effect in Danish swine and poultry production. In a scientific assessment by the Food and Agriculture Or- ganization and the WHO determined that the use of antibiotics in the agricultural set- ting is the principal contributing factor to the emergence and dissemination of AMR [24]. Many recommendations have been made to incorporate surveillance in all countries using antibiotics for non-therapeutic uses, but only a limited number of countries have complied.

    Starting in , a combined report with animal and human data is now being compiled. All improvements in monitoring and regula- tion lead up to the concept of integrated sur- veillance of antimicrobial resistance in food- borne bacteria. This covers testing of bacteria from food animals, foods, environmental sources and clinically ill humans and the antibiotic resistance found during the proce- dures that encompass this elements.

    WHO has recommended the use of this integrated surveillance in all countries to monitor and control the spread of resistant bacteria in animal products [18]. One of the biggest challenges to perform and share this infor- mation globally is the lack of harmonization between reports in different countries.

    Their main objective being to minimize the public health impact of AMR associated with food producing animals. A major part of Danish export is based on swine production, and the demand of ani- mal export is increasing. Increased produc- tion has led to a rise in the use of antibiotics, especially tetracyclines, which holds a central role in the treatment of animal infections in Denmark.

    Religion, Spirituality, and Health: The Research and Clinical Implications

    A consequence of rising demands is an increased number of animals per area in piggeries, and hence, a higher possibility of animal-to-animal transmitted infections. This has led to a general increase in the use of broad-spectrum antibiotics, which started in Despite that,the total use of antibiotics in was 86 tonnes which is five percent lower than in when adjusted for the in- creased export [25].

    In the past five years, the total use in swine production has been stable, and there has been a small increase in the use of antibiotics for pig finishers, but a signifi- cant decrease in the use of systematic use of cephalosporins for pigs in general. Based on these data, it is fair to conclude that Danish farmers are balancing the use of antibiotics responsibly, but that the guidance of DAN- MAP surveillance and regulations are critical to secure a sustainable development.

    The pressure on lowering use of antibiotics has created an incentive to use zinc-based agents, such as zinc oxide or zinc chloride. Alongside this, new cases of animal- human transmitted infections appeared country wide, leading to an increasing number of deaths in the years , in particular due to MRSA ST A series of screenings and quarantine regu- lations for people living in close proximity to animal production facilities was imple- mented, and a mandatory screening for farmers at the admission to hospitals was initiated. Conclusion It is evident today that the issue of AMR cannot be restricted to the silo of human or animal health.

    Stronger policies and innova- tive research to address the use of antibiotics and to explore new solutions to minimize the development of resistance in the ani- mal and agricultural sector are needed. The World Medical Association and the World Veterinary Medicine Association have initi- ated this dialogue several years ago, and will continue this academic exchange during the second One Health Conference in Novem- ber Tackling drug-resistant infections globally: Final report and recommendations. Accessed June 27, World Health Organization. Global action plan on antimicrobial resistance.

    Geneva, Switzer- land: World Health Organization; Global health es- timates summary tables: Deaths by cause, age and sex, Geneva, Switzerland: World Health Organization; Accessed Septem- ber 10, The chal- lenge of emerging and re-emerging infectious diseases. Microbial threats to health: Emergence, detection, and response. Morse SS. Factors in the emergence of infectious diseases. Emerg Infect Dis. Veterinary public health. Accessed September 10, Sustain- ing global surveillance and response to emerging zoonotic diseases. Saf Health Work. Day MJ. Human-animal health interactions: The role of One Health.

    Am Fam Physician.

    1. Historical Background and Introduction

    Antibiotic resistance is the quintessential One Health issue. Food-borne diseases — the chal- lenges of 20 years ago still persist while new ones continue to emerge. Int J Food Microbio. Global trends in emerging infectious diseases. Emerging or re-emerging bacterial zoonoses: Factors of emergence, surveillance and control. Vet Res. Wegener HC. Antibiotic resistance — linking human and animal health. Im- proving food safety through a One Health ap- proach: A workshop summary. Washington DC: Institute of Medicine; Antibiotics in early life alter the murine colonic microbiome and adiposity.

    Na- ture. World Health Or- ganization. Antimicrobial resistance: Global re- port on surveillance Geneva, Switzerland: World Health Organization; Industrial food animal production, antimicrobial resist- ance, and human health. Annu Rev Public Health. Changes in intestinal flora of farm personnel after intro- duction of a tetracycline-supplemented feed on a farm. N Engl J Med. Staphylococcus au- reus CC Host adaptation and emergence of methicillin resistance in livestock. Multidrug- resistant Staphylococcus aureus in US meat and poultry.

    Clin Infect Dis. Levy S. Reduced antibiotic use in livestock: How Denmark tackled resistance. Environ Health Perspect. DANMAP — Use of anti- microbial agents and occurrence of antimicrobial resistance in bacteria from food animals, food and humans in Denmark. Heavy metal and disinfectant resist- ance genes among livestock-associated methicil- lin-resistant Staphylococcus aureus isolates.

    Vet Microbiol. DANMAP — Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, food and humans in Denmark. Accessed September 13, Vet Micro- biol. New requirements for zoonotic infection pro- tection in pigs MRSA. Ac- cessed September 10, Caline Mattar M. Fagerberg, M. Chapman M. More than 1. Sweeping changes are impacting the practice of medicine and medical research, and in turn impacting the world of Journal publishing. Scientific journals have a long and proud history since the first scientific journal was published; the longest lived Journal is the Philosophical Transactions started by the Royal Society of London in and there are now thousands of medical journals with new ones added every week.

    As a front line clinician and active medical researcher, I rely on the published literature to guide my practice, update me on the latest developments and hopefully inspire me. And I rely on the Journals I publish in to disseminate the research findings with the hope that the results will influence and perhaps change my field.

    But the world of research and publishing as we know them is changing, and here I will discuss some of the emerg- ing outcomes. More and more medical research is pro- duced and published each year. As an expe- rienced journal editor I know authors want to publish in the most prestigious journal possible. The reasons are obvious; publish- ing in one of the best journals in the field is more likely to be noticed, the paper may be more likely to be read, and it adds greater weight to a promotion application, to name a few. In many parts of the world authors base their decision to submit on the jour- nals impact factor a metric based on the number of cited articles in the prior two years divided by the number of published citable articles in the journal ; the higher the impact factor, the more prestigious the journal in the eyes of many, a fact editors recognise and fret over annually.

    However, the im- pact factor is obviously a flawed measure; even in the New England Journal of Medi- cine, only a minority of articles are highly cited which drives up the impact factor while many papers attract little attention. Further, journal editors can manipulate the metric e. When I began my first Co-Editor-in- Chief role in at the American Jour- nal of Gastroenterology AJG , open access journals were in their infancy, print was still dominant, and advertising revenue was still strong.

    Richard Smith, the former editor of the British Medical Journal BMJ has recently blogged most if not all national Journals potentially face failing too if they do not adapt, as submis- sions fall because authors will only send their best work to more prestigious Jour- nals blogs. The underlying business model of traditional Journals is indeed under threat; there is in- creasing competition from other Journals, and falling advertising revenue as advertis- ers flee from print and Journals to inter- net rivals.

    Print is declining although older readers still prefer it. Despite all of these trends I expect the top Journals will sur- vive or be the last to disappear. Journal rankings like University rankings matter and for Journals despite all the acknowl- edged limitations and flaws, the impact factor remains the most widely accepted measure authors consider and Editors live and die by.

    Not everyone can publish their work in one of the top Journals. The new world of open access Journals had the noble aim of de- mocratising research, of trying to ensure all sound research is published even if negative or relatively uninteresting and made avail- able for everyone, applying an author pays model. A noble aim but flawed. By , over 10, journals were listed in the Di- rectory of Open Access Journals. There are now high ranking open access megajournals such as PLoS Medicine which have shaken the publishing world.

    But publishing high volumes negatively affects the rankings based on impact factor as for example the journal PLoS One has found out; their huge submission rates are now falling as their impact factor, once quite high, steadily declines. More and more open access Jour- nals are opening; I now receive every single Nicholas J.

    Publishing in open access journals with du- bious business models that may not exist to- morrow in an era of intense Darwinian style competition is a risk for emerging research- ers. Predator journals have also been a seri- ous contaminating influence; these are jour- nals that charge a fee for publishing yet fail to carry out any or adequate peer review or careful editorial oversight, which is likely to promote the publication of false or mislead- ing data.

    I predict many of the open access Journals will disappear and I fear it will take decades to undo the damage of publishing poor quality research. The counter argument has been that jour- nal peer review is inadequate anyway and just openly publishing all available research undertaken is a better model.

    I know the research into journal peer review has not provided convincing evidence flaws are all or even mostly detected although this needs looking at across a range of journals [3, 4]. Many published articles with positive find- ings are later shown to be incorrect [5]. However, I am still convinced strong review and editorial processes minimise obvious mistakes and improve articles, and I am committed to research into strengthening the model.

    No one can now read everything published in their field today even if it is a very highly specialized one; how generalists can be ex- pected to maintain very broad expertise is becoming more and more troublesome even though the generalist represents a key player in the delivery of best medical care. While already an excellent journal admired by the community and government, the challenge I face is how to maximise the relevance of the Journal, better educate clinicians, disseminate and showcase clini- cally impactful research, accelerate change in practice and positively influence health policy.

    I relish the challenge. In my Jour- nal now, for example, all original research is published in full and is available for free to all with no author charges, a challenge to the open access user pays model. This is consistent with the European Competitive Council recommendation that all publicly funded research be made freely available by We also conduct blinded peer review and routine statistical review as part of our quality processes.

    One of my goals is to measure the impact of the Medical Journal of Australia in terms of changing practice or policy. It is generally stated it takes 17 years to translate research into practice but this is highly variable and excellent data are unavailable, plus our in- terest is post publication impact [6].

    Rather than focussing on an artificial metric like the impact factor, instead our interest should be in knowing is our Journal pro- moting translation because funders, gov- ernments and the public do now want to know about this today. In my view transla- tion should be the true Journal value added metric. In conclusion, I would suggest that science is permanently about self-correction and testing the evidence, and Journal Editors play a key gatekeeper role in the process. Any study can be wrong despite the best possible peer review, but it is the accumula- tion and synthesis of new knowledge that we as editors proudly contribute to dissemi- nating.

    General medical journals like the Medical Journal of Australia play a special role in presenting and explaining research, making research and data accessible, edu- cating, translating, engaging the public and shaping health policy. Finally, I would argue we are all still failing to help translate new medical knowledge quickly enough, and it is here as a profession we can and must aim to do better. Ware M, Mabe M. The STM report. An over- view of scientific and scholarly journal publish- ing.

    Nail salon trend drives category interest with a 35% increase in gel manicures 2013-2015

    Kassirer JP. Editorial independence: painful les- sons. Lancet ; : Effects of editorial peer review: a systematic re- view. JAMA ; 21 Smith R. Peer review: a flawed process at the heart of science and journals. J R Soc Med. Ioannidis JP. Why most published research find- ings are false. PLoS Med. The answer is 17 years, what is the question: understanding time lags in translational research. Nicholas J. Distinguished specialists and experts, such as Acad. Vladimir Ovcharov, Bulgaria, Prof. Gligor Tofoski of the Medical Faculty of the University of Skopje,Macedonia,and over a hundred of medical specialists pre- sented reports on the latest achievements and innovations and shared experience and views in different medical fields such as surgery, oncology, neurology, pediatrics and endocrinology among others.

    The scientific program of the VII Congress of SEEMF was dominated by lectures, reports and presentations, striving to outline the nov- elties, to discuss achievements, to track the prospects of application in practice of the conclusions of fundamental discoveries and clinical trials. Impressive was the presenta- tion of Georgian researchers from medical schools in Tbilisi, Batumi, medical centers and research institutes.

    The Board voted on the traditional award nominations in the field of medicine. Peteris Apinis and Assoc. Tatiana Tserekhovich, Belarus, were awarded for their contribution to the development of public health, Prof. Alexander Tsiskaradze, Georgia, and Prof. Two new members were elected to the Board of the Organization — Acad. Vladimir Ovcha- rov and Assoc. Todor Cherkezov. The Board of SEEMF approved an open letter to the Albanian Order of Physicians declar- ing that SEEMF firmly supports the pro- fessional independence and self-governance of the medical profession and considers any kind of administrative interference in the work of professional organizations of phy- sicians unacceptable and inappropriate and that governmental bodies, including Health Ministries,should respect the independence of such organizations and develop partner- ship with them.

    The VII Congress of SEEMF in Batumi proved the strength and meaningfulness of cooperation between doctors and medi- cal scientists from different countries with different specialties for the achievement of common goals — better health systems, progress in medical science, faster imple- mentation of medical achievements in practice.

    Once again the SEEMF Congress reaffirmed its unique role and proved that such an international organization can sig- nificantly contribute to the health and wel- fare of millions of people in the region. Today in the process of global changes in state structures and policies, more than ever SEEMF proves its constructive role and influence in the medical community — to bring together physicians and scientists and commit to the mission of being a peace- maker of the future.

    This is an achievement that demonstrate that the efforts of Dr. With the mission of peacekeepers The VII Congress of SEEMF is further evi- dence of the progress of our organization,of proven benefits of the unification of medi- cal professionals from different countries united by core values of the profession. Be- cause only the medical profession uniquely brings together science, law, ethics.

    Once again the variety and richness of the scientific program determine the appear- ance of the event. The presence of outstanding speakers from other countries and the latest developments in the field of socially significant diseases represent impetus to improve practice.

    I am very glad that young physicians and researchers attended this year. Yet we intend to work hard in this direction. During the traditional board meeting im- portant decisions were taken about the special SEEMF awards. Ovcharov and Assoc. The award voting is extremely enjoyable because the number of nominees from different organizations and countries is growing and scientific reports are becoming more profound.

    And partici- pants in the general discussion on the cur- rent problems in health systems express very wise and bold ideas. Part of the mission of SEEMF is to make these ideas available to governments and health politicians,to insist and work for their implementation in the member-countries of our organization. In the complex global environment in terms of the ever-changing governmental structures and policies in SEEMF member countries, our organization proves its con- structive role. SEEMF doctors and scien- tists confirm daily their mission of peace- keepers in the region and the world.

    I dream of a better world! Andrey Kehayov, SEEMF President, Bulgaria Factor on the European map Now we can say with pleasure that our Southeast European Medical Forum is among the fastest growing organizations and is a factor in the scientific medical community in Europe because it is a multi- disciplinary structure that deals with vari- ous fields of medicine, and also discusses organizational aspects of health systems in different countries, seeking ever better solu- tions for millions of patients. The Seventh Congress of our forum can be described as highly successful since it confirmed its specificity by combining science, profes- sionalism and friendship in a joint effort to better health.

    The rapid development of our forum is a prerequisite to establish more intense con- nections with European scientific and med- ical societies and organizations to show that we live actively and physicians of Southeast Europe are working hard to get evaluation and support from European centers and networks. The congresses of the organization fulfill the mission to contrib- ute to the development of medical science and the organization of health systems, to influence public health of millions of people in a vast area of the world. This global change poses new conditions and requires unconventional approaches by doctors, by health politicians, by the governments of all countries.

    I am glad that what we have achieved today is far beyond the wildest expectations of the time when we created SEEMF. Andrey Kehayev, September Prof. We have regional structures. Now we are in Regional News Adjara, where our organization is good and strong. The objectives of the Association are: as- sistance to doctors, post-graduate educa- tion,work with patients,social protection of doctors.

    We help our members to improve their skills abroad, assist post- and under- graduate students. We regularly organize scientific conferences and publish a journal. And do you participate in making the health- care policy of Georgia? In our country we have the opportunity to interact with the government and parliament repre- sentatives.

    There are parliamentary commit- tees on health and social security, we offer specific amendments, bills. Therefore there is a need for the State University to build a new hospital. Today the Ministry of Health faces difficulties because little has remained under their control as everything has been sold. Of course, in private hands hospitals thrive. But they have no interest in education and training; they do not accept undergraduate or graduate students for training.

    I think that after the Oc- tober elections it will be decided to create such public hospitals in large cities. Four years ago the government adopted a program of universal health care to provide for all peo- ple who have no private insurance. There are changes in store, but the government has not yet decided what is to be done. First, we heard a lot of good lecturers from abroad; it had an ex- tremely strong scientific program with renowned lecturers. The Congress is an incredible platform for exchange of expe- rience. Wu T, Hallett M. The cerebellum in Parkinson's disease.

    Parkinson disease: diagnostic utility of diffusion kurtosis imaging. A preliminary diffusional kurtosis imaging study of Parkinson disease: comparison with conventional diffusion tensor imaging. Favorable toxicology has been observed in chronic exposure studies in rats and monkeys. Participants with early, untreated PD recruited at approximately 90 international sites will receive randomized treatment monthly IV infusions for two years. Secondary objectives are to assess the pharmacodynamic effects of BIIB through dopaminergic imaging and clinical symptom burden. Enrollment is expected to continue through The design and status of the study will be presented.

    Background: Parkinson's disease poses significant health burden worldwide owing to increase in global aging population and chronic illnesses. Mobility and balance limitations are some of the most significant effects of Parkinson's Disease. Virtual reality gaming is emerging as an effective tool in rehabilitation especially in the Caucasian population.

    AGBT had 8weeks of conventional activity based training which included Treadmill training and balance board training. These interventions were carried out for both groups twice weekly for 8weeks. Data were analysed using descriptive statistics and inferential statistics. Results: Both groups were comparable in physical and clincal characteristics. AGBT led to higher improvements in the stride length and gait velocity.

    The challenge of Parkinson's disease management in Africa Virtual Reality for Rehabilitation in Parkinson's disease. Cochrane database systematic review. Two electrophysiological techniques aid identification of the optimal target. One is to record neuronal activity with microelectrodes MER. The relative predictive value of the two techniques is to be established. Surgical targeting of the area is commonly facilitated by MER of single units and background neuronal activity.

    The upper border of the STN identified by MER and the depth of the highest beta peak HBP recorded by the DBS electrode were correlated with the depth of chronic stimulation and with stimulation efficacy determined later. Synchronized neuronal discharge in the basal ganglia of parkinsonian patients is limited to oscillatory activity. The relationship between local field potential and neuronal discharge in the subthalamic nucleus of patients with Parkinson's disease.

    Intraoperative local field recording for deep brain stimulation in Parkinson's disease and essential tremor. Selection of optimal programming contacts based on local field potential recordings from subthalamic nucleus in patients with Parkinson's disease. Value of subthalamic nucleus local field potentials recordings in predicting stimulation parameters for deep brain stimulation in Parkinson's disease.

    Spatial steering of deep brain stimulation volumes using a novel lead design. Atlas for stereotaxy of the human brain. Thieme Medical Publishers, Stuttgart 2nd ed. Calculating total electrical energy delivered by deep brain stimulation systems. What brain signals are suitable for feedback control of deep brain stimulation in Parkinson's disease? Stimulation of the caudal zona incerta is superior to stimulation of the subthalamic nucleus in improving contralateral parkinsonism.

    Subthalamic nucleus stimulation in Parkinson's disease: Correlation of active electrode contacts with intraoperative microrecordings. Most effective stimulation site in subthalamic deep brain stimulation for Parkinson's disease. Subthalamic nucleus stimulation in Parkinson's disease: anatomical and electrophysiological localization of active contacts. Optimal target localization for subthalamic stimulation in patients with Parkinson's disease.

    Brain shift: an error factor during implantation of deep brain stimulation electrodes. Postoperative curving and upward displacement of deep brain stimulation electrodes caused by brain shift. The impact of brain shift in deep brain stimulation surgery: observation and obviation. The role of brain shift, patient age, and Parkinson's disease duration in the difference between anatomical and electrophysiological targets for subthalamic stimulation. Maximal subthalamic beta hypersynchrony of the local field potential in Parkinson's disease is located in the central region of the nucleus.

    Beta oscillatory activity in the subthalamic nucleus and its relation to dopaminergic response in Parkinson's disease. Subthalamic nucleus functional organization revealed by parkinsonian neuronal oscillations and synchrony. Delimiting subterritories of the human subthalamic nucleus by means of microelectrode recordings and a Hidden Markov Model. Parkinsonian impairment correlates with spatially extensive subthalamic oscillatory synchronization.

    Methods: To develop the present CPG for PD, the development group defined clinical questions through analysis of current research. A literature search was conducted using several electronic databases. The GRADE evaluation process is divided into two stages, assessment of evidence level and recommendation grade.

    Level of evidence is classified as high, moderate, low, or insufficient. The Delphi technique was adopted as the method of formal expert and clinician consensus. A questionnaire on the initial draft of the recommendation was prepared, and a panel of nine experts in various fields was established under the recommendation of the Review Committee of the CPG Development Group for PD. The expert panel answered questionnaires in two rounds, after which the final recommendation was drafted.

    Results: A total of 23 clinical questions were defined. Results: By data cutoff, 12 The most common AE was fall One participant died from PSP progression. November 1—4, Background: PD is not only a movement disorder, but a disease that involves a large number of NMS as well. NMS are common in late stage PD, as the frequency and severity of most of these symptoms increase with advancing disease.

    It is therefore of importance to optimize dopaminergic therapy in order to give the most effective symptomatic treatment possible. Background: PhEEG concerns the description and the quantitative analysis of the effects of substances on the CNS by means of electrophysiological methods. EEG data from the electrode sites were scored by blinded personnel. Results: Twenty participants with DLB Objective: To determine whether cognitive domain impairment of visuospatial, memory, attention is related to dysfunction of brain cholinergic neurotransmitter system in mild cognitive impairment of Parkinson's disease.

    Background: In recent years, more and more attention has been paid to the cognitive impairment of Parkinson's disease. However, the pathogenesis of cognitive impairment of Parkinson's disease remains unclear. Methods: Seventy patients with Parkinson's disease were collected. All subjects underwent 3. Conclusions: Cognitive domains impairments in memory, visuospatial and attention in patients who has mild cognitive impairment in Parkinson's disease are closely related to cholinergic system dysfunction.

    References: [1]. Neurodegenerative Diseases. Parkinson's disease dementia: a neural networks perspective. Background: Due to significant health and socioeconomic impact of cognitive impairment, it is important to discover easily accessible markers or predictors of cognitive decline for early detection and intervention. Prior studies have suggested that impairment in smell is associated with neurodegenerative disorders such as Parkinson disease and normal aging.

    However, it is uncertain if smell dysfunction is a predictive factor of cognitive impairment in older individuals. Other covariates include age, sex, education level, smoking, history of head trauma. Linear regression was used to assess relationship between continuous outcome variable and predictor variables.

    Results: The total analytic sample included subjects, Mean score on DSST was Subjective hyposmia, history of loss of consciousness, history of smoking, and history of serious skull injury were found to be not significantly associated with cognitive test score. Conclusions: There is a discrepancy between self report and objective measurement of olfactory function in older individuals.

    Hyposmia and anosmia measured objectively as opposed to by self report, along with male sex, age, below high school education, are statistically significant predictors for decreased cognitive function. Background: Normal pressure hydrocephalus NPH is not only an important treatable cause of dementia in the elderly population but also an important entity in the list of differential diagnosis of degenerative atypical parkinsonism.

    J Neurol. J Clin Neurol. Background: The neurobiological processes of normal aging and Parkinson's disease PD share common features [1]. Meanwhile, the declined function neuromuscular junction is common in ageing people and PD patients [3], which represented with frailty, such as handgrip strength. According to the criteria of Fried et al [4], frailty was evaluated by handgrip strength in kg using a digital dynamometer Takei Digital Dynamometer, Japan. Pearson correlation coefficient was employed to test the relationship between age, frailty, and IIV of RT. References: [1] Lu, H. The neuromuscular junction: aging at the crossroad between nerves and muscle.

    Frontiers in aging neuroscience, 6, Frailty in older adults: evidence for a phenotype. Scientific reports, 7 1 , Background: The Montreal Cognitive Assessment MoCA is a brief cognitive screening tool with high sensitivity for screening paitents with early cognitive dysfunction.

    Methods: We examined consecutive participants with Parkinson's disease 1 16 control, with MCI, and 92 with dementia. Receiver operating characteristic ROC curves determined dichotomous classification parameters. Background: Alzheimer's disease is unrestored yet now.

    Relieving the life upset of patient and postponing the disease progression are the most reasonable treatment targets. Methods: We reviewed the records of specific outpatient department for memory disorder patients, and included clinical possible Alzheimer's disease who had been pursued for at least 1 year, study the relationship between MMSE annual decrease and the number of patients' long term caregivers. We exclude patients who have combined with severe out of control chronic disease, cardiac or cerebral accident, severe injury or surgical events.

    Results: Among possible AD patient, the number of long term caregivers is related with progression of AD. Conclusions: Sufficient long term caregivers number is possible correlated with better outcome of AD patients. ACE inhibitors are neuroprotective for patients with AD, possibly by way of central cholinergic effects or boosted neprilysin activity, or by way of peripheral enhancement of insulin sensitivity. Results: Overall, 27 participants with DLB Objective: This study performed to access caregiver's satisfaction and preference of the Rivastigmine patch for treatment of Alzheimer's disease and Parkinson's disease dementia patients to maximize the intervention effectiveness, compare to conventional oral formulations.

    Background: Family caregivers are responsible for administering and managing medications in the care of Alzheimer's disease AD and Parkinson's disease dementia PDD patients. Safety and tolerability were also observed. The patch was significantly preferred to the capsule and donepezil tablet with respect to ease of use and the reason for preference was visually verify of compliance by patch attachment. Conclusions: Both caregivers of AD and PDD patients preferred the rivastigmine patch to the rivastigmine capsule and donepezil tablet for convenience and satisfied with improving their quality of life, which could potentially lead to improved clinical benefits.

    Caregiver preference for rivastigmine patch relative to capsules for treatment of probable Alzheimer's disease. Alzheimer's disease treatment: assessing caregiver preferences for mode of treatment delivery. Objective: Evaluate cognition and emotion regulation of patients with early onset ataxia EOA.

    Background: Early onset ataxia EOA is a movement disorder caused by a dysfunction of the cerebellum or its networks, developing before the age of Recent research has emphasized the cerebellum's role in cognition and emotion regulation. Deficits concerning executive functioning, language, working memory, and spatial perception have been reported, but systematic evaluation and an investigation of the relation with emotion regulation is lacking. Other tests did not differ between the two groups. Conclusions: Apart from deficits in verbal learning, our patients showed intact cognitive functions.

    Deficits in verbal learning have not been reported earlier in EOA. This finding can have implications for treatment as studies on other patient groups have shown that deficits in verbal learning can hinder treatment compliance. In addition, we found an association of social cognition and emotion regulation in EOA patients. Future research needs to find out more about consequences of this relation. Objective: We aimed to investigate the efficacy and safety of rasagiline in addition to levodopa in patients with dementia with Lewy bodies DLB.

    Background: Management of motor symptoms in DLB remains a challenge due to frequent adverse effects. Some patients have modest effect of levodopa while others do not respond to treatment. Therefore, it is necessary to modify an approach to antiparkinsonian drug administration in patients with DLB. Methods: An open observational study included 12 patients with probable DLB received rasagiline 1 mg once daily during 12 weeks.

    Results: All patients completed treatment. After 12 weeks of treatment with rasagiline the patients have shown some improvement of gait disturbances. TUG test tended to be improved but not significantly. Rasagiline did not worsen cognitive function. One patient had clinical significant episode of orthostatic hypotension. Hallucinations were appeared in one patient.

    Conclusions: Rasagiline has shown safety and some clinical benefit for gait disturbances in patients with DLB. Background: RBD and fluctuations and hypersomnolence are core and supportive diagnostic features for DLB, respectively. DLB clinical features, as described in the consensus report criteria, were collected from patients files. Results: Compared to normative data, DCL presented with decreased total sleep time DLB patients presented significantly higher sleep latency compared to PD no other significant differences.

    Severity of motor events was worse in iRBD v. Conclusions: DLB patients present a reduction of sleep efficiency and REM sleep duration and an increase in superficial sleep. These alterations are similar or worse than in PD patients, possibly reflecting a common neurodegenerative pathophysiology. Fluctuations were related to a significant reduction in REM sleep latency, implying a possible connection between vigilance and REM sleep regulation. Objective: Aberrant eating behaviour and swallowing difficulties are reported in the conditions associated with frontotemporal lobar degeneration FTLD neuropathology.

    Here we review and summarize the literature on eating behaviour and swallow impairments dysphagia in each of the syndromes caused by FTLD. Background: FTLD refers to the underlying pathological profile of a group of neurodegenerative disorders where progressive atrophy occurs in the frontal or temporal lobes of the brain. Mealtime disturbances are found to occur in all clinical syndromes associated with FTLD. Changes in eating behaviour and swallow function may lead to aspirated food and drink. Aspiration pneumonia is a common cause of death in disorders associated with FTLD.

    Behaviours includes continued eating despite reported satiety, eating rapidly, rigid eating behaviour, changes in diet preferences or food seeking behaviour. Conclusions: Few studies have evaluated eating behaviour or dysphagia in individuals with FTLD neuropathology. An improved understanding of the pathology and symptomatology that contribute to mealtime disturbances in FTLD may lead to enhanced diagnostic accuracy, improved disease management and a better understanding of the underlying neural mechanisms involved in the feeding process.

    References: Langmore, S. Archives of neurology, Ikeda, M. Journal of Neurology, Neurosurgery and Psychiatry, Neary, D. Neurology, FIG 1. Background: Recent evidence show that astrocytes are important for higher brain function, and may be pivotal for learning and memory. Astroglial release of neurotrophic factors and cytokines alters the survival and function of neurons.

    There is a growing body of evidence that SIRT6 affects longevity and metabolic profile. Brains of aged mice were dyed using immunohistochemistry. SIRT6 expression levels significantly increased in the hippocampus and frontal cortex. A significant increase in newly generated neurons, stained with doublecortin DCX was found in the hippocampus of SIRT6 overexpressing mice. The effects of SIRT6 may be partially conveyed by astrocytes function. Background: Visual recognition of objects relies not only on their shape but also on their color or texture.

    When shape is not perceived sufficiently, e. Patients were classified according to the clinical dementia rating CDR scale. Combined effects of viewpoint and visual texture on visual object recognition were more evident in DLB than AD, which might be related to the fact that there are visual hallucinations or pareidolia in DLB patients. Background: Galantamine an acetylcholinesterase AChEs inhibitor used for the symptomatic treatment of Alzheimer's disease. Auld, T.

    Kornecook, S. Bastianetto, R. Albuquerque, M. Alkondon, E. Pereira, N. Castro, A. Schrattenholz, C. Barbosa, R. Aracava, H. Eisenberg, A. Maelicke, Properties of neuronal nicotinic acetylcholine receptors: pharmacological characterization and modulation of synaptic function. Amenta, S. Anand, K. Gill, A. Mahdi, Therapeutics of Alzheimer's disease: Past, present and future. Association, , Alzheimer's disease facts and figures. Alzheimer's Dement. Braak, K. Del Tredici, Alzheimer's disease: pathogenesis and prevention.

    Aisen, K. Davis, Inflammatory mechanisms in Alzheimer's disease. Bonda, H. Lee, H. Lee, A. Friedlich, G. Perry, X. Zhu, M. Smith, Novel therapeutics for Alzheimer's disease: an update. Drug Discov. Eikelenboom, C. Bate, W. Van Gool, J. Hoozemans, J. Rozemuller, R. Veerhuis, A. Williams, Neuroinflammation in Alzheimer's disease and prion disease.

    Francis, A. Palmer, M. Snape, G. Wilcock, The cholinergic hypothesis of Alzheimer's disease: a review of progress. Hampel, D. Prvulovic, S. Teipel, F. Jessen, C. Luckhaus, L. Riepe, R. Dodel, T. Leyhe, L. Bertram, The future of Alzheimer's disease: the next 10 years. Barnes, J. Meltzer, F. Houston, G. Orr, K. McGann, G.

    Table of contents

    Wenk, Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity and nicotinic receptors. Kumar, A. Prakash, D. Zvaifler, Update in rheumatology—focus on hydroxychloroquine. American J. Van Gool, H. Weinstein, P. Scheltens, G. Wu, T. Wang, Fractionation of crude soybean lecithin with aqueous ethanol. Bruni, E. Bigon, E. Boarato, L.

    Mietto, A. Leon, G. Toffano, Interaction between nerve growth factor and lysophosphatidylserine on rat peritoneal mast cells. Bruni, G. Casamenti, P. Mantovani, L. Amaducci, G. Pepeu, Effect of phosphatidylserine on acetylcholine output from the cerebral cortex of the rat. Higgins, L. Flicker, Lecithin for dementia and cognitive impairment. The Cochrane Library. Surh, Y. Jeong, G. Food Eng. Furushiro, S. Suzuki, Y. Shishido, M. Sakai, H. Yamatoya, S. Kudo, S. Hashimoto, T. Yokokura, Effects of oral administration of soybean lecithin transphosphatidylated phosphatidylserine on impaired learning of passive avoidance in mice.

    Gutierres, F.

    23% Of Global Disease Burden Due To Behavioral Disorders

    Carvalho, M. Schetinger, P. Marisco, P. Agostinho, M. Rodrigues, M. Rubin, R. Schmatz, C. Life Sci. Singh, A. Ishrat, M. Khan, M. Hoda, S. Yousuf, M. Ahmad, M. Ansari, A. Ahmad, F. Islam, Coenzyme Q10 modulates cognitive impairment against intracerebroventricular injection of streptozotocin in rats. Paxinos, C. Watson, The rat brain in stereotaxic coordinates 2nd edn. Academic Press, New York. Rasoolijazi, H. Iran Biomed. Kumar, N. Sharma, J.

    Mishra, H. Kalonia, Synergistical neuroprotection of rofecoxib and statins against malonic acid induced Huntington's disease like symptoms and related cognitive dysfunction in rats. Wills, Mechanisms of lipid peroxide formation in animal tissues, Biochem. Ellman, A spectrophotometric method for determination of reduced glutathione in tissues, Anal.

    Green, D. Wagner, J. Glogowski, P. Skipper, J. Wishnok, S. Tannenbaum, et al. Analysis of nitrate, nitrite, and [15 N] nitrate in biological fluids, Anal. Kono, Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase, Arch. Luck, Catalase. Ellman, K. Courtney, V. Andres, R. A new and rapid colorimetric determination of acetylcholinesterase activity, Biochem. Gornall, C. Bardawill, M. David, Determination of serum proteins by means of the biuret reaction, J. Berman, T. Hastings, Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria, J.

    King, R. King, [58] Preparation of succinate dehydrogenase and reconstitution of succinate oxidase, Method. Liu, D. Peterson, H. Kimura, D. Sotocassa, E. Bokuylenstiema, L. Ernster, A. Bergstrand, An electron transport system associated with the outer membrane of liver mitochondria, J. Prakash, A. Rajasekar, S. Dwivedi, C. Nath, K. Hanif, R. Shukla, Protection of streptozotocin induced insulin receptor dysfunction, neuroinflammation and amyloidogenesis in astrocytes by insulin. Reeta, D. Singh, Y. Gupta, Chronic treatment with taurine after intracerebroventricular streptozotocin injection improves cognitive dysfunction in rats by modulating oxidative stress, cholinergic functions and neuroinflammation.

    Sharma, Y. Gupta, Effect of alpha lipoic acid on intracerebroventricular streptozotocin model of cognitive impairment in rats. Objective: The objective of this study is to evaluate the correlation between screening tool for dementia and gait status. Background: Gait impairment in patient with cognitive decline has been much focused in last decades.

    However, gait disturbance in dementia is usually underdiagnosed clinically. The purpose of our study is to investigate the correlation between gait status and screening test for dementia. Methods: We recruited 24 patients diagnosed with MCI, 22 patients diagnosed with early stage of dementia. We evaluated the correlation between score of screening tool and gait parameters.

    In neuropsychological test, stride length and walking speed were significantly correlated with memory and frontal lobe function. Results were compare to patients with Alzheimer's disease AD with the objective of understanding structural changes subserving memory deficits specific to DLB. Background: DLB is the second most common neurodegenerative dementia in the elderly. Although the neuropsychological phenotype of DLB has been distinguished from AD on the basis of more pronounced executive and visuospatial dysfunction, it is well known that DLB can often also present with significant memory disturbance akin to AD[1].

    Previous in vivo studies have shown relative preservation of medial temporal lobe structures including the hippocampus in DLB relative to AD[2]. However, the hippocampus is only one component of a distributed network of structures subserving memory known as the Papez circuit. Projections within the Papez circuit involve the hippocampus, mammillary bodies, anterior thalamus and cingulate cortex. Significant atrophy[3] and hypometabolism[4] has been found across this network of regions in AD patients but to the best of our knowledge atrophy in the Papez circuit is yet to be investigated in DLB.

    The subregions of the hippocampus, mammillary bodies, anterior thalamus, and cingulate cortex were analysed using standard volumetric techniques[5]. DLB cases had significantly more atrophy in the hippocampus, cingulate cortex and the anterior thalamus compared to controls. AD cases demonstrated significantly more volume loss than DLB and controls in all regions except the anterior thalamus which was similar to controls Table 1. Subregion analysis revealed that hippocampal atrophy in DLB was concentrated in the body whilst AD patients had atrophy across all regions Table 2.

    Our findings suggest that the neural substrates of episodic memory impairment in DLB is subserved by a different pattern of memory network dysfunction to AD and provides clues towards potential in vivo imaging biomarkers that may differentiate between these conditions.

    A review of cognitive impairments in dementia with Lewy bodies relative to Alzheimer's disease and Parkinson's disease with dementia. Medial temporal lobe atrophy on MRI differentiates Alzheimer's disease from dementia with Lewy bodies and vascular cognitive impairment: a prospective study with pathological verification of diagnosis. Limbic hypometabolism in Alzheimer's disease and mild cognitive impairment.

    Identifying severely atrophic cortical subregions in Alzheimer's disease. Objective: We sought to characterize the prevalence of color vision impairment in DLB patients and investigate how color vision impairment in DLB patients was associated with other features of the disease. Background: Dementia with Lewy Bodies DLB is frequently misdiagnosed for other dementias such as Alzheimer dementia, especially in its earlier stages. Therefore identification of novel and distinguishing features of this disease can improve accuracy of early diagnosis. Finally, we performed a multivariate stepwise logistic regression to predict which factors were significantly associated with CVI in our cohort.

    Further studies are needed to determine relationships between CVI and volumetric changes on MRI and prospectively validate its diagnostic utility. Background: Alzheimer's disease AD is a chronic debilitating neurodegenerative disease for which there is no cure and no single diagnostic test. Blood plasma was collected for determination of protein activity using a microwave technique. Conclusions: This study provides a new method of predicting cognitive impairment associated with AD. Objective: We aimed to assess the relationship between EEG abnormalities and MTLA, and its clinical validity in Parkinson's disease with behavioral and psychological symptoms.

    Background: Behavioral and psychological symptoms in dementia are often seen in patients with Parkinson's disease. The electroencephalogram EEG abnormalities in dementia have been widely reported and medial temporal lobe atrophy MTLA is one of the hallmarks in early stage of dementia. Methods: A total of 20 Parkinson's disease patients with behavioral and psychological symptoms were recruited the mean age: Baseline EEGs were analyzed with quantitative spectral analysis.

    These results suggest that quantitative EEG abnormalities are correlated with the MTLA, which may play a important role in Parkinson's disease patients with behavioral and psychological symptoms. Valbenazine dosing was initiated at 40 mg, with escalation to 80 mg at Week 4 based on clinical assessment of TD and tolerability. The main reason for discontinuation prior to Week 48 was adverse events AIMS response was found in PGIC response was found in Objective: To investigate the neurochemical basis of tardive dyskinesia TD in an experimental primate model.

    The induction and maintenance mechanisms remain elusive. Multiple kinase pathways are modulated by antipsychotic drugs, but the distinct impact of conventional vs. Six unmedicated animals served as controls. Total protein kinase levels were not altered by any treatment. Phosphorylated protein kinases levels in the clozapine group were similar to controls, but GRK6 protein levels were upregulated 1. If confirmed, these changes may offer novel avenues for preventing or palliating TD. Supported by the Canadian Institutes for Health Research. Upregulation of dopamine D3, not D2, receptors correlates with tardive dyskinesia in a primate model.

    Mov Disord ;— Objective: Present and discuss fasciculations in the setting of acetylcholinesterase inhibitors. Background: Specific acetylcholinesterase AChE inhibitors e. The fasciculations stopped within 24 hours of discontinuing Donepezil. There were no other peripheral cholinergic side effects reported such as nausea, vomiting, dizziness, and diarrhea. He denies any prior history of fasciculations or neuropathy.

    Conclusions: AChE is an efficient enzyme and rapidly degrades acetylcholine and limits its effective bioavailability in the synaptic cleft to approximately microseconds. The incidence of fasciculations with AChE inhibitors depends on specificity and pharmacokinetic profile. Donepezil has a limited peripheral side effect profile due to its higher affinity for central nervous system acetylcholinesterases.

    Fasciculations have however been reported in rat studies though they were more frequent with other agents such as Tacrine the first FDA approved agent for the treatment of Alzheimer's disease. In the prescribing information of donepezil, muscle cramps occurred in 6 of patients and were directly related to the rate of titration faster titration with higher rates of cramping. This case illustrates the importance for clinical providers to be aware of this possible side effect of donepezil given the current widespread use of this agent in multiple on and off label indications. Central and peripheral activity of cholinesterase inhibitors as revealed by yawning and fasciculation in rats.

    Eur J Pharmacol. Aricept donepezil hydrochloride Label. It has been associated with virtually all neuroleptics, including newer atypical antipsychotics, as well as a variety of other medications that affect central dopaminergic neurotransmission. Even Mortality and morbidity attributed to this syndrome have recently declined markedly due to greater awareness, earlier diagnosis, and intensive care intervention but early detection is important. Ballismus is a rare symptom of Neuroleptic malignant syndrome NMS. This case demonstrated that Ballism could exactly occur as major and early manifestation in a patient with Neuroleptic Malignant Syndrome NMS.

    All clinical criteria was complied for Neuroleptic malignant syndrome NMS , then haloperidol drug was stopped, the patient gave agresif rehydration protocol,and clonazepam 2mg OD at night as long as 2 weeks. Ballism and hyperthermia gradually decreased and then ceased after 2 weeks of daycare from the established diagnosed of NMS. Conclusions: Our case highlights ballism could be the first presenting sign of NMS other than stereotypical clinical presentation of NMS including high fever, muscle rigidity and dysautonomia.

    Ramadhan O, Ian F. P, Bernt A. E, et al. Neuroleptic malignant syndrome: an easily overlooked neurologic emergency. Neuropsychiatr Dis Treat. Neuroleptic malignant syndrome. A review from a clinically oriented perspective. As a result, clinicians tend to delay its use in the treatment of PD, despite its proven higher efficacy to counteract disabling PD symptoms. Nevertheless, it seems that many patients facing dyskinesia are still able to function adequately, leading to hypothesize that these patients have strategies to alleviate the impact of dyskinesia on their ability to function.

    Energy deployed by each body segment during the task was extracted from accelerometric data, and its distribution among the body segments with time, analyzed. Results: At initial glass stabilisation, most of the energy was allocated to segments other than the one specifically involved in the movement i.

    Although steady for the first few seconds of the stabilisation phase, data revealed that there was a progressive transfer of energy distribution with the hand taking most of the energy, hence generating displacement of the glass of water. Subset analysis using the energy level at rest to divide the group into quartiles have shown that patients with lower levels of dyskinesia at rest behaved differently from the rest of the group; most of the energy remained at hand level throughout the stabilisation phase, although the importance of the hand also increased after a certain stabilisation period.

    Background: The management of LID in one of the greatest challenges in PD research because to date there are no available pharmacological alternative therapies to PD with full clinical efficacy. We selected the one with the highest silencing proficiency and used Western blot to validate Fyn knockdown in vivo.

    LID were registered every 3 days for 2 weeks. Postmortem dopaminergic denervation was carefully determined by tyrosine hydroxylase TH immunodetection to ensure an equal level of degeneration between groups. Conclusions: Our data demonstrate that Fyn is a potential target to control LID and set the grounds for its putative therapeutic use in PD. Mol Neurobiol.

    Toward a New Global Architecture? America’s Role in a Changing World - Radcliffe Day 2018

    Objective: We present a case of an oculogyric crisis OGC after administration of alizapride. Curious about this case is that the OGC only happened after she received this pharmaceutical more than times. Background: An oculogyric crisis OGC is a dystonic movement of the extraocular muscles, presenting mostly with an upward tonic deviation of the eyes. The upward gaze deviation can be briefly suppressed and lasts from a few minutes to multiple hours. Most often an oculogyric crisis is elicited by a pharmacological agent such as antipsychotics e.

    Methods: We present a 57 year old lady that was seen for an urgent neurological consult. Since 30 minutes, she was complaining that she was forced to look at the ceiling with her eyes. Results: The complaint was a clinical presentation of an oculogyric crisis after administration of alizapride. Alizapride serves as an antiemetic by antagonizing the D2 receptors in the chemoreceptor trigger zone of the central nervous system. We administered 2 mg of biperiden which led to the resolution of the complaints quickly.

    Review of the recent literature did not show any case report of OGC by this agent. OGC is thought to be caused by an imbalance between dopamine and acetylcholine in the striatum, though the exact mechanism is still debated. Conclusions: We describe an OGC after administration of alizapride. Interesting is the fact that the OGC only occurred after multiple administrations of this agent.

    This is why we consider this OGC a tardive phenomenon. Background: The use of antipsychotic drugs AP may result in a variety of tardive involuntary movements. They typically present as a classical tardive dyskinesia orobuccolinguomasticatory dyskinesia , but also can manifest as dystonia, tremor, tics or myoclonus. However, myoclonus is rarely reported as a predominant feature. She continued using PPLAI for 1 year despite involuntary movements and had no other investigation or treatment for involuntary movements. Because of health insurance problems she stopped taking PPLAI and started using low dose oral risperidone.

    Despite the modification of the treatment, the myoclonic jerks persisted and the patient was referred to our neurology department. A neurological examination was normal except spontaneous myoclonic jerks in the face, neck, shoulder muscles and upper limbs. Serum biochemistry, blood count, thyroid tests and urine copper and ceruloplasmin levels were normal.

    Results: Based on the clinical features and investigations a diagnosis of tardive myoclonus TM was made. After the initiation of low dose clonazepam pharmacotheraphy, symptoms resolved completely and she had no further myoclonic jerks. Conclusions: In conclusion, clinicians should keep in mind that beside the classical tardive dyskinesia, different types of movement disorders may develop as a tardive syndrome after long exposure to antipsychotics. TM is a rare variant of tardive movement disorders and clonazepam has been considered to be effective in the management of TM.

    Tardive myoclonus. Lancet 7: , Objective: Through this article we want to highlight extrapyramidal side effects of levosulpiride and need of its awareness among treating physicians. Background: Levosulpiride is a newer prokinetic agent with increasingly extensive use in India by general physicians.

    All of them were prescribed tetrabenazine and clonazepam, 4 patients received additional baclofen details in table1. Conclusions: Our article invite attention on LIM, a disabling condition caused by drugs used for relatively minor condition. We want to highlight the long latency in diagnosing LIM, a potentially treatable condition. Though, in our patents none had completely improved after mean follow up of 5. This warrants the need for awareness about extrapyramidal side effects of Levosulpiride among physicians. The offending drug to be stopped at slightest suspicion of LIM.

    Shin, H. Disord ; — Objective: To investigate the clinical manifestations of neuropsychiatric side effects after the Human papillomavirus HPV vaccine, and to investigate the immunological actions and epigenetic modification. Background: Human papillomavirus HPV typically causes chronic infections, which can be isolated from skin swabs and hair from normal immunocompetent individuals.

    Prophylactic vaccine of HPV for cervical cancer was discovered with recombinant gene technology in , and it was adopted in preventive vaccination law in in Japan. Methods: The cohort comprised 7 patients mean age; Immunological and epigenetic biomarkers with their blood and CSF samples were evaluated. Molecular analysis were conducted with illumine multiplexed sequencing. References: 1 Y Takahashi, et al. Immunological studied of cerebrospinal fluid from patients with CNS symptoms after human papillomavirus vaccination.

    Evidence has shown that dysfunction of the glutamatergic system plays a key role in the development of LID and that the use of metabotropic glutamate receptor 5 mGluR5 antagonists can significantly improve dyskinesia. However, the mechanisms underlying this alleviation are not well understood. In addition, the interaction of glutamate receptors in the striatum appears to be critical for the development of LID. Levels of DID, tremor and bradykinesia were measured using inertial sensors positioned on each body limb.

    Rigidity and postural instability were assessed using clinical evaluations.

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    Health related QoL was assessed using the SF12 version 2. Patients were separated into 2 groups depending on the level of DID recorded during the experiment present or not. Results: Patients had a significantly lower activity engagement than controls and were significantly affected by PD. Tremor, postural instability, cognition, and depression were all related with lower activity engagement, affected activities and QoL. Background: The anatomical distribution and severity of TD can be variable.

    However, because the AIMS is not a linear scale, such results provide limited information about which body regions were most affected. Stable regimens of concomitant psychiatric medications were allowed. Shift analyses were conducted for each AIMS item, as scored by site raters. A loss of effect was seen after washout, suggesting that patients may require ongoing VBZ therapy to maintain TD improvements.

    Objective: To describe the new observation of Kratom withdrawal that presented with the choreiform movement of lips and tongue. It can be associated with some heredodegenerative diseases such as Huntington's disease, and neuroacanthocytosis, while occasionally found in patients with liver cirrhosis. However, various medications and substances such as antidepressants, antiemetics, anticonvulsants, calcium channel blockers, cocaine, and amphetamine are also reported as an etiology. The abnormal movement was the chorea of the tongue, lips, and cheeks.

    No movement disorders involved limbs or other parts of his body. Gait and posture were normal. There was no other neurological deficit or cognitive impairment. He reported the suicidal idea and labile mood, however, there was no lethal attempt. Neither psychiatric medication use nor underlying disease was documented. He had a positive history of substances abuse which started when he was 16 years ago.

    The first one was heroin addiction ten years ago. Later, he used amphetamine to achieve the work tolerance for eight years. His routine labs CBC, creatinine, and liver function test were normal as well as the creatine phosphokinase test CPK , thyroid function test and serology for autoimmune diseases. The ceruloplasmin and urine copper level was normal. Paraneoplastic antibodies were all negative. A genetic test for Huntington's disease was negative. MRI brain showed no abnormality detected.