Spousal violence against women is a serious public-health issue. Although there is a growing body of literature on this subject, there are still many unanswered questions regarding the prevalence of this violence, the risk factors, the consequences, and how to address the issue. The purpose of this literature review is to organize and synthesize the empirical evidence on spousal violence against women in Bangladesh and to provide direction for both researchers and practitioners for future work in this area. The review suggests that spousal violence against women is high in Bangladesh. The list of correlates is long and inconclusive. Although there is evidence on adverse consequences of this violence on health of women and their children, more research is needed to explore the multifaceted consequences of violence for women, children, families, and communities. Action research is needed to develop and test preventive and curative interventions. Over the past 15 years, the growing body of research on violence against women has brought the issue from a position of near-invisibility to being recognized as having far-reaching health and economic impacts for women and societies , The Prevention of Women and Child Repression Act (2000), and The Cruelty to Women Ordinance (1983). Furthermore, Bangladesh has ratified the Convention on the Elimination of All Forms of Discrimination against Women (1979), which calls for the protection of women from gender-based abuse and negligence. The Government is committed to eliminating violence against women by 2015 in Bangladesh, as stated by the Minister of Health and Family Welfare and as detailed in Target 6 of Millennium Development Goal 5 to improve maternal health . Although domestic violence, particularly violence perpetrated by husbands, is the most common violence against women in Bangladesh  among women of reproductive age in Bangladesh; and original analysis of ICDDR, B surveillance data on deaths from intentional injury. We included data on deaths from intentional injury since spousal violence can result in either suicide or homicide; furthermore, intimate partner homicides may be labelled as suicides, and actual suicides may be an indicator of mental instability resulting from violence and other causes . Data onThe growing body of research suggests that spousal violence is highly prevalent in Bangladesh. In 2001, about 60%  of women reported having ever-experienced physical or sexual spousal violence. Consistent with the global trend, the overwhelming majority of physical and sexual violence against women was perpetrated by husbands, not by other persons . While det al. found that 47% of women of lower socioeconomic status in six villages in three districts of Bangladesh reported ever having experienced physical domestic violence  of rural and urban Bangladeshi women who experienced physical violence within the past year reported that the violence was severe, including having been hit with a fist, dragged, kicked, or threatened with a weapon . Eighty-Available data indicate strong associations between violence by intimate partners and physical health of women. While similar to other countries, most injuries reported to a large 2001 WHO study on spousal violence in rural Bangladesh were minor , and the majority of ever-injured women reported losing consciousness due to a violent incident, which was quite uncommon for other countries covered by the WHO study. Eighty percent of rural women who reported ever having been injured by their husbands reported having needed healthcare for an injury  Table)..Table).Spousal violence can result in death, but as the social stigma associated with homicide are strong and official penalties are very severe, deaths attributable to and associated with domestic violence are difficult to enumerate even in surveillance systems. In a study of deaths from intentional injury to women aged 15-44 years registered in the ICDDR, B's Health and Demographic Surveillance System in Matlab from 1992 to 1998, verbal autopsy data linked violence by husbands and/or other relatives to 10% of homicides. The investigators suggested that this is probably an underestimate of spousal violence-related homicide .While physical violence is well-documented in Bangladesh, a very few studies have investigated sexual violence. The WHO study of 2001 found that 37% of women in the urban study site and 50% of women in the rural study site reported having been sexually violated by their husbands at some point in the past, and 20% of urban and 24% of rural Bangladeshi women reported having been sexually violated by their husbands in the previous year  to end their lives compared to women who had not experienced spousal violence . Sexual Suicide is an issue of growing concern in Bangladesh with some areas reporting 37% of all deaths of women aged 15-44 years attributable to suicide. Longitudinal data suggest that the percentage of deaths attributable to suicide among women, particularly young women of reproductive age, is increasing , the number and sex of children, whether or not the mother of the wife was abused by her father, whether or not the mother of the husband was abused by his father, membership of wife in savings and/or microcredit groups, and income generation of women.The strongest factor associated with violence of husbands towards their wives in both urban and rural areas was a history of abuse of the husband's mother by his father, according to analysis of Naved and Persson . The relper se but the patriarchal attitude of the families demanding the dowry that is positively associated with physical violence against women —impact on spousal relations and deserve to be taken into account in future quantitative research .Attitudes of women towards spousal violence vary by whether or not they have experienced spousal violence. An association between experience of physical or sexual violence and agreeing that violence is sometimes justified has been identified, but the direction of the association is not known. Sixty-four percent of urban women and 86% of rural women who have ever experienced spousal violence reported that a husband has the right to beat his wife under certain circumstances. These circumstances range from not completing housework adequately to refusing sex, to disobeying her husband, to being unfaithful. In contrast, of women who have never experienced spousal violence, 45% of urban women and 73% of rural women agreed that violence was sometimes justified .There are official channels of conflict resolution, but these are not yet well-understood or accessible to women who need to use them. The Government has established One-stop Crisis Centres in different districts in Bangladesh which facilitate person-centred counselling to abused women. A substantial barrier to institutionalizing counselling in all health-delivery points is the lack of trained professionals in this field, and this problem is more acute in rural areas as psychologists are reluctant to work in rural areas for extended periods. In an operations research context, ICDDR, B trained paramedics in spousal violence counselling. Preliminary findings from a study comparing the quality of counselling delivered by psychologists and paramedics in Matlab suggested that, with careful training and close supervision, primary-level healthcare professionals were able to provide some spousal violence counselling services ; expectations of sexual relations within marriage; and marital conflict and communication within marriage ,11,26.Research is required to explore the multifaceted consequences of violence for women, their children, their families, and communities. One of the consequences highlighted in this paper is suicide. Suicide is the number one cause of death among women of reproductive age in some age-groups in certain areas of Bangladesh. Suicide and associated factors need to be better understood as does the relationship between spousal violence and suicide. The very high and increasing rates of suicide among young unmarried women suggest that the relationships among premarital intimate partnerships, unwanted pregnancy, and suicide should be explored.To facilitate the measurement trends of spousal violence and its correlates over time, spousal violence should be included in the existing public-health surveillance systems. One important lesson from this paper is that, without consistent methods applied to the same population over time, it is impossible to document the trends over time.Action research to develop and test interventions (preventive and curative) involving the Government of Bangladesh, health systems, women, men, communities, NGOs, and private-sector businesses is required to facilitate means of preventing spousal violence and of providing care, counselling, shelter, and rehabilitation for women who experience spousal violence and their children. For these activities to have a maximum impact, monitoring, evaluation, and sharing results efficiently are critical.Programmes can address spousal violence on tertiary, secondary, and primary levels. Tertiary and secondary-level programmes aim at providing care and resources to women who have experienced spousal violence or are identified to be at risk of spousal violence. Primary prevention aims at behaviour change to prevent spousal violence .Tertiary or secondary prevention measures can be developed and/or streamlined based on the information already available. Tertiary prevention measures include facility- or community-based screening of women with visible signs of abuse. Health systems are ideally positioned to screen such women for spousal violence, but to be effective on such a socially- and culturally-sensitive issue, these require staff competent in counselling, a working referral system, and active support of the social and legal systems. Systems need to be in place to demonstrate the benefits to woman of using such spousal violence support services. Because women often cite ‘shame to family’ as a barrier to seeking care for spousal violence, such programmes might demonstrate how they can have a positive impact on the family.Bangladesh currently has a very few counsellors trained on issues around spousal violence. Operations research on a counselling initiative might include testing the impact of individual and group therapy counselling for victims.Secondary prevention measures include identifying women most at risk of being exposed to spousal violence and providing them with the tools to seek help and support before they require assistance. Mechanisms for secondary prevention include facility- or community-based screening of women who may be most at risk—for example, young newly-married women, pregnant women, women with minimal or no formal education, and women who have recently joined the paid labour force.Primary prevention to reduce spousal violence requires changing societal attitudes and behaviour to prevent spousal violence from occurring at all. One possible mechanism for primary prevention is universal screening of women. Such screening will facilitate the identification of women who have experienced spousal violence who may not otherwise have been identified and also will give the message to all women screened that spousal violence is an unacceptable behaviour, and a violation of women's rights for which women have recourse. Family-life education courses, including strategies for spousal communication and conflict resolution, particularly community-based, are important forums for spreading messages aiming at reducing spousal violence.Primary prevention activities should also target men and boys who perpetrate or are at risk of perpetrating violence. Punitive measures against men who perpetrate spousal violence must be accompanied by rehabilitation and reintegration programmes. There are no systems in place in Bangladesh to help perpetrators of spousal violence develop or turn to strategies other than violence. Such systems need to be developed and carefully implemented and monitored.Unfortunately, there are minimal data on the training received by medical service providers in responding to persons who have been victims of spousal violence or the perpetrators of spousal violence. Few resources are available from the health systems to provide counselling or otherwise help women and their husbands to address the abuse. Much research is needed to understand how to help clinicians provide proper services to these patients, and how the health and legal systems should cooperate effectively and efficiently to reduce the incidence of spousal violence.The issue of spousal violence against women is complex and is culturally and socially sensitive. Nonetheless, the Government has demonstrated its commitment to eliminating violence against women in a short time. Research institutions, non-governmental and civil society organizations have critical roles to play in working with the Government of Bangladesh as a united front to reduce violence against women and the associated and unnecessary physical and mental anguish, death, and disability.


Early family-level and social-level stressors are both assumed to be the components of two main path models explaining the association between exposure to interparental violence in childhood and its long-term consequences on mental health explored through life-course epidemiological studies.To investigate the association between exposure to interparental violence in childhood and mental health outcomes in adulthood when taking into account early family and social stressors.A retrospective French cohort study of 3023 adults representative of the general population in the Paris metropolitan area was conducted in 2005 through at-home, face-to-face interviews. The outcomes measures were current depression and lifetime suicide attempt, intimate partner violence, violence against children and alcohol dependence.The adults exposed to interparental violence during childhood had a higher risk of psychosocial maladjustment. After adjusting for family- and social-level stressors in childhood, this risk was, respectively, 1.44 (95% CI 1.03 to 2.00) for depression, 3.17 (1.75 to 5.73) for conjugal violence, 4.75 (1.60 to 14.14) for child maltreatment and 1.75 (1.19 to 2.57) for alcohol dependence.The adult consequences of parental violence in childhood—and this independently of the other forms of domestic violence and the related psychosocial risks—should lead to intensifying the prevention of and screening for this form of maltreatment of children. Domestic violence, including exposure to interparental violence, has been identified and reported in US surveys over the last three decades. They showed the extent of this societal problem,5–Despite different methodological concerns,10Intimate partner violence has been described in an integrated, ecological framework where personal, situational and sociocultural factors interact.The main limitations of the studies conducted in this research field are the lack of large-scale longitudinal datasets including relevant social factors. Moreover, very little is known about how interparental violence combines with other adversities in childhood to promote adult psychosocial maladjustment.The aim of our study was to investigate the association between interparental violence exposure in childhood and mental health outcomes in adulthood when simultaneously taking into account other family and social stressors in childhood. Our hypothesis was that this adverse early life event has a negative impact on different mental health outcomes throughout the individual’s lifetime, over and above both coexisting familial and social stressors during childhood.The SIRS  cohort study is a longitudinal epidemiological survey of the general adult population of the Paris metropolitan area, conducted since 2005 by the National Institute of Health and Medical Research (INSERM). This cohort study was approved by the French authority that protects privacy and personal data .This survey, which has been described elsewhere,Of the 4560 selected adults, 28.6% refused to participate, and 3.1% who did not speak French and 1.8% who were too sick or unable to answer the survey were excluded from the study population. Overall, 3023 subjects were included in the cohort, for a participation rate of 71.4%. No individual data were collected from the non-respondents, but according to the four-level socioeconomic categorisation of neighbourhoods used for sample stratification, the response rates were higher in both extreme categories, ie, the richest and poorest neighbourhoods (73.9% and 76.5% respectively), than in the two intermediate categories .We used the retrospective data on childhood circumstances and the cross-sectional data on adulthood indicators collected at that time.et al.Witnessing interparental violence in childhood before the age of 18 years was our main independent variable. It was defined according to the answer to the following question: “Did you witness interparental violence before the age of 18?” (yes/no). Five mental health outcomes were studied: depression, lifetime suicide attempt, two violent intrafamilial conduct disorders and alcohol dependence. Depression was investigated by the Mini-International Neuropsychiatric Interview. The depression index was evaluated by a seven-item scale for measuring the occurrence of depressive symptoms during the last 15 days. The scale’s internal and external validity has been demonstrated in the French population by Lecrubier Family-level stressors included parent–child relationships and childhood adversities. The perceived quality of parent–child relationships was assessed separately for both the mother and the father by the following question: “Before the age of 18, how would you rate your relationship with (1) your father and (2) your mother?”, reported and then dichotomised as very good or good vs poor or very poor. Childhood adversities before the age of 18 were the following: parental separation or divorce, parental death, parental incarceration, the occurrence of a parental suicide attempt, parental alcoholism and other forms of domestic violence, with respect to which the respondents were asked if they had been physically abused and/or sexually abused before the age of 18. The questions used to assess these characteristics were standard questions about childhood living arrangements used in previous French sociological and health surveys. Social-level stressors during childhood were poor parental health status, housing problems, prolonged parental unemployment and family financial problems during childhood.In addition to age and gender, we adjusted for socioeconomic factors in adulthood recorded at the time of the survey. Individual socioeconomic status (SES) was assessed on the basis of the following variables: level of education, monthly household income per consumer unit and occupational status .We investigated the association between exposure to interparental violence during childhood prior to age 18 and psychosocial adjustment outcomes in adulthood. The first step in the analysis consisted of examining the past social and family characteristics of the adults who had been exposed to interparental violence during childhood compared with those who had not, and in analysing the bivariate association between having witnessed interparental violence and mental health outcomes in adulthood by age group. Second, we used a binary logistic regression model for each of these outcomes (baseline model) while controlling for age, gender and adult SES. Third, we introduced in the baseline model: (1) the family-level stressors after adjusting for child sexual abuse and/or physical maltreatment; and (2) the social-level stressors in childhood. Interactions between exposure to interparental violence and significant predictive variables in the final model were systematically tested. The data were weighted in order to take into account the sampling design (which combined multistage random clustering and oversampling of poor neighbourhoods during stratification) and then the post-stratification adjustment according to the general population census data. SPSS 15.0 procedures  were used to perform the statistical analysis.The study population included 3023 subjects (53% women and 47% men), 29 of whom  did not provide information about past parental violence. Among the respondents, 16% reported having witnessed interparental violence before the age of 18. This prevalence decreased with subject age, from 18.8% in the 18–36 age group to 13.5% in the 55 and over age group. There were neither gender- or nationality-related differences in interparental violence exposure, except in the oldest age group, where French people reported more exposure to interparental violence than did foreigners. The current SES was the same in both groups, except for the level of education. The respondents with the lowest level of education were more likely to have witnessed interparental violence than those with an intermediate or the highest level of education.Exposure to interparental violence during childhood was significantly associated with all five adulthood mental health outcomes that were studied, with higher odds ratios for intimate partner violence and perpetrating child maltreatment, but also a significant association with depression, lifetime suicide attempt and alcohol dependence , the risk of depression was higher in women exposed to interparental violence in childhood. On the other hand, the men had a 15-fold higher risk of committing violent acts against their children, women a two-fold higher risk. But intimate partner violence was the same for both genders. Finally, the risk of alcohol dependence was higher in the male respondents from high-conflict families and/or with a parental history of alcoholism, and it was also higher after adjusting for depression. This risk was not observed in the women.Interparental violence is now widely documented as an adverse childhood experienceHowever, the limitations of our study warrant some consideration. First, the marital discord variable was not quantified by means of a standardised scale. Nonetheless, the odds ratios were strong enough to suggest that even mildly violent acts, such as verbal rather than physical acts, have negative consequences in adulthood. In the present study, our goal was not to determine a prevalence rate for this event in the general population, but rather to assess the adulthood consequences of a climate of parental violence perceived by the respondents when they were children. Second, with regard to potential non-response bias in such a population-based cohort study, we indicated above that the response rates were higher in the neighbourhoods in both extreme social categories. If one assumes that negative early life events are more frequent in families living in the poorest neighbourhoods, such differences in response rates would not have biased our estimates. On the other hand, we cannot ascertain the number of subjects who did not respond for reasons associated with parental violence during childhood . Third, retrospective reports of adverse childhood experiences could be subject to recall bias. In the literature, the analysis of the validity of retrospective studies has shown that the prevalence of past events is underestimated.We found that adults who had witnessed interparental violence during childhood had had numerous other adverse familial and social experiences and had a higher risk of negative mental health outcomes in adulthood. These associations could be explained by the emotional security hypothesis developed by Davies and Cummings.Numerous types of adverse childhood experiences, such as parental divorce,Our second indicator of psychosocial functioning was intrafamilial conduct disorders. The strength of the association between parental discord and both child and intimate partner violence partially concurs with the notion of intergenerational transmission of violence. Indeed, physical abuse and/or sexual abuse during childhood were independently associated, respectively, with both outcomes and with child maltreatment. This intergenerational cycle of maltreatment and violence has been explained by different theoretical approaches, most of which are based on a general family of cognitive/behavioural paradigms.Our study sought to demonstrate the potential harm of interparental violence to children for their future adulthood life, and this independently of other forms of domestic violence and related psychosocial risks. Such a demonstration warrants further research studies so that these consequences become a cornerstone of any risk–benefit analysis of screening interventions towards intimate partner violence.Children’s exposure to interparental violence is a form of maltreatment and has consequences on child’s development.Early family-level and social-level stressors are both assumed to be the components of two main hypotheses explaining the association between exposure to interparental violence and negative health outcomes in children and later in adulthood.The adults exposed to interparental violence in childhood have a higher risk of mental health disorders in adulthood than those not exposed, and even after adjusting for other forms of domestic violence.Family- and social-level stressors in childhood do not explain this association.Intensification of prevention of and screening for domestic violence including interparental violence is a public health issue for the well-being of future generations.


This is possibly due to exogenous polyamine salvage from the host, which replenishes the intracellular polyamine pool. This implies that disruption of polyamine metabolism as an antimalarial chemotherapy strategy may require targeting both polyamine biosynthesis and transport simultaneously. In the absence of a clear understanding of the uptake mechanism of polyamines into Plasmodium falciparum parasites, polyamine transport into both the infected erythrocytes and parasites isolated from the erythrocyte were investigated using radioisotope flux techniques. While the characteristics of transport of putrescine into infected erythrocytes (iRBC) were similar to those of transport into uninfected erythrocytes (RBC) spermidine uptake occurred via the new permeability pathways (NPP) induced by the parasite in the erythrocyte membrane. Once inside the erythrocyte cytoplasm, both putrescine and spermidine are taken up by the parasite via a temperature- and glucose-dependent, saturable process. The uptake of both these polyamines was competed for by other polyamines and biosynthesis inhibition led to increased total uptake of both putrescine and spermidine. Polyamine uptake was pH dependent with uptake increasing with increasing pH, but did not appear to be coupled to the Na+ or K+ gradients. Membrane potential perturbations influenced polyamine uptake, consistent with the transport being an electrogenic process.Polyamines are present at high levels in proliferating cells, including cancerous cells and protozoan parasites and the inhibition of their synthesis has been exploited in antiproliferative strategies. Inhibition of the malaria parasite's polyamine biosynthetic pathway causes cytostatic arrest in the trophozoite stage but does not cure


The lack of conceptual references for these expressions complicates the organization of literature. Furthermore, the absence of clear concepts may be an obstacle to clinical treatment because the use of these words by the patients does not necessarily point to a diagnosis of posttraumatic stress disorder.Several terms in the scientific literature about posttraumatic stress disorder are used with different meanings in studies conducted by different authors. Words such as A critical review of scientific literature showed that stress can be divided in stages to facilitate specific terminological adjustments to the event itself, to the subject-event interaction and to psychological responses. Moreover, it demonstrated that the varying concept of trauma expands into fundamental psychotherapeutic definitions and that the meanings of violence associated with barbarism are an obstacle to resilience. Therefore, this study updates the etymological origins and applications of these words, connects them to the expansions of meanings that can be operated in the clinical care of patients with posttraumatic stress disorder, and analyzes them critically according to the criterion A of DSM-IV and ICD-10.trauma led to a broader understanding of this phenomenon in its psychic dimensions, that a barbarian type of violence constitutes an obstacle to resilience, and that the criterion A of the DSM-IV and ICD-10 shows imprecision and conceptual fragilities.The terminology in the literature about posttraumatic stress disorder includes a plethora of terms whose meanings are not fully understood, and that, therefore, limit this terminology. The analysis of these terms suggested that the transformation of the concept of conceptual approach in any part of the paper. Researches that relied solely on empirical indicators, like psychopathological, neurobiological or pharmacological aspects, were excluded. The focus here was in conceptual aspects, even when some few empirical studies were included.To develop this debate article, a current specialized literature review was achieved by searching and retrieving the key terms from two major databases: PubMed and PsycINFO. The key terms included "disaster", "catastrophe", "barbarism", "terrorism", "trauma", "psychic trauma" and "violence", also in combination with the terms "PTSD", "concept" and "conceptual aspects". The data were captured specially from review articles. The included studies were those mostly identified by the authors as relevant by the presence of a As it was noted a paucity of medical references related to conceptual aspects of these terms, a wider literature needed to be included, including chapters, books and articles proceeded from the Humanities areas. "Interdisciplinary research is needed in this area to include perspectives from a range of different disciplines" once that "to promote public health (...) new dimensions of such interactions and the implications thereof should be pursued in collaboration with researchers from broader areas" . Posttraumatic stress disorder (PTSD) was defined as a psychiatric disease in 1980 and included in the third edition of the DSM by the American Psychiatric Association (APA) . ConsideThe plethora of terms used in PTSD literature, such as aggression, violence, disaster, catastrophe, barbarism, stressful event and trauma, do not point to a corresponding understanding of the meanings, applications and limits of these constructs. These terms are often vaguely used, meanings change in different studies, and there is a lack of conceptual references to guide their use in scientific literature. Some of the most common expressions define events according to consequences, such as in the case of the word "stressor", and not according to the characteristics of that single event ,8.An initial attempt to undo such terminological confusion is to refer to etymology and to retrace the path of the concept into clinical practice. Rather than to establish definitive positions about this topic, the purpose of this study is to promote a discussion of conceptual questions about PTSD terms. Therefore, this study presents definitions of catastrophe, disaster, trauma, violence and barbarism from a clinical perspective to clarify their scope and limitations.disastro  [The word disaster has its origin in the Italian word d star") , and refd star") . "Disastd star") .Disasters tend to expose unselected populations to trauma, randomly. Within a given community, individuals can be directly, indirectly or remotely exposed to the event. The medical model focuses on specific intervention for each of these groups, aiming to prevention, healing and recovery of PTSD and other psychiatric disorders. On the other hand, the wellness models comprehend disasters from the distress challenge, focusing on restoring homeostasis . Therefocatastrophe is Greek (kata + strophein) and its literal meaning was "overturn". According to its definition, it is an event that causes trauma [Ecological disasters may also be called catastrophes, events of great proportions usually associated with natural phenomena that cause death and destruction. The origin of s trauma  due to iA careful examination of the words used by patients is fundamental to understand the psychological impact of events that may trigger traumatic responses. Situations described as "catastrophic" may not necessarily indicate that the situation that the patients experienced was a "catastrophe", although it may have an equally devastating psychological representation.The event alone has importance to the mental healthcare professional only when it is a situation that can produce psychopathological responses from the patient. The idea of a "disaster taxonomy" is based on the principle that there are variable emotional responses that depend on the type of disaster, the degree of personal impact, the size of the group affected, and the geographical and temporal range of the event .The "disaster taxonomy" stresses the importance of avoiding overlapping or confusing terms to define events because their different aspects may trigger different psychological responses. The use of an adequate terminology requires the understanding of how a traumatic situation causes and becomes part of a stressful process, which may be divided intro three major stages: 1) environmental input in the form of an event; 2) immediate apprehension of the event; and 3) psychological responses after the event .The first stage is restricted to the event itself, and may be objectively measured in number of victims, degrees in the Richter scale, or square kilometers of affected area. "Pure" words, without qualifiers, such as "event", "stimulus", "loss", "disaster" or "catastrophe" are used for such description. The second stage goes beyond the isolated event and incorporates the initial perceptions of the victim. Words such as "danger", "shock", "risk of death", "threat" or "stressor" illustrate the interaction between the stimulus and the person that experiences it. The third stage corresponds to the psychological response to the event, and words such as "mourning", "response to stress" or "trauma" are used . Intensetrauma, originally used in medicine, has an Indo-European root with a double meaning: a) to rub, grind, perforate; and b) overcome, to go through [Trauma is a violent shock that is capable of producing an impact that the individual cannot resist. Therefore, trauma that "perforates" is the same that makes "go through", which describe the two possible psychic developments seen in a traumatic situation: the development of PTSD or of resilience – the ability to go through trauma and to introject meaning into one's own life.The word  through ,14. Trautrauma. In the 19th Century, except in the psychoanalytic literature, the word trauma referred primarily to wounds or violent tissue rupture and had no psychological connotations. The hypothesis that a terrible event might cause effects other than those merely physical was developed in the 1860's, with the description of the "Railroad Spinal Syndrome" by John Eric Erichsen [The formal recognition of PTSD in 1980 changed the conceptual understanding of Erichsen . Since tErichsen diáthese". Therefore, he described the "névrose traumatique" or "hystérie traumatique" to classify these cases. Charcot concluded that a physical trauma could produce emotional disorders [In 1882, Jean-Martin Charcot studied patients whose psychic symptoms appeared after severe trauma, such as train crashes or wars, and served as traumatic triggers in individuals that had a certain inherited predisposition or "isorders .On the psychical mechanism of hysterical phenomena (1893), Freud expanded on the concept of traumatic neurosis. The conceptual fluctuations of the word trauma in Freudian works suggest that the relative difficulties to establish this definition are much older than the conceptual confusion observed in PTSD. In his early papers, Freud used trauma as a key to explain the etiology of neurosis. From 1897 on, the concept loses importance as the concept of fantasy develops and takes the place previously held by traumatic events. However, the infamy of the First World War brought back the problems of "traumatic neurosis" to Freudian works, particularly in Introduction to psychoanalysis and the war neurosis (1919) [Beyond the pleasure principle (1920) [In henomena 93, Freudneurosis 19 [BeyonTrauma was understood by psychoanalysis as an unspeakable experience, not elaborated, not signified, that was incorporated but could not be introjected, according to Nicolas Abraham (1919–1975) and Maria Torok (1925–1998) [introjected trauma. In contrast, the paralyzing expansion of the incorporated trauma perpetuates the symptomatic reliving of suffering disconnected from language and, thus, far from the attribution of meaning to experience. Therefore, the way the event is treated or elaborated may become the traumatic element itself [25–1998) . The bart itself .Violence may be understood as the action of force or the act of violation. From Latin, violentia carries the broad meaning of behaviors with an origin in vis  and refers to "vehemence; passionate and uncontrolled force." Acts of excessive violence may result in the violation of rules, rights and norms, in which cases violence is understood as violare  [raction) . The defviolentia), which is restricted to an act that should meet three conditions: deliberate attitude of the perpetrator, physical force, and destructive intent. Episodic violence corresponds to this concept and is characterized by the fact that it is direct and perpetrated fast and intermittently as an acute insult to a person's well being by means of a dramatic form of violence.Violence may be initially understood according to a minimalist concept (violence as violentia) includes psychic and subjective elements and stresses the victim's perspective. Its standard form is structural violence, an indirect form of violence whose norms are established socially and that is defined as a chronic insult to well being that kills or harms people slowly by continuous deprivation of basic human needs [On the other side, the comprehensive concept : "Violence is the intentional use of physical force or power, threatened or real, against oneself, another person, or against a group or community, that either results in or has a high likelihood of resulting in injury, death, psychological harm, maldevelopment, or deprivation" . Accordiintention adds complexity to this concept because intention is not always identifiable in a violent act [The WHO definition validates the concept of violence as an international, and not only local, problem, and prescribes the protection of vulnerable populations. However, the incorporation of the notion of lent act . The reslent act .The depth and breadth of the WHO definition are adequate to that organization's purposes, which require an ecological model of violence centered on multiple levels. However, when the breadth of what is denoted in a term expands, its descriptive power is retracted . A comprThe application of this comprehensive concept of violence to PTSD would result in very permissive boundaries for the definition of a phenomenon as violent. Traumatic situations that have social, political or economic origins are beyond the reach of psychiatric and psychological treatments. Moreover, evil-minded individuals could distort the use of this broader sense of the word to claim medical benefits and secondary gains based on this "happy combination of a vague descriptive content and a negative emotional connotation" .The concept of violence as force  was refuted by Hannah Arendt, who established the distinction between power, potency (vigor), force, authority and violence. In the common sense, these terms are usually misunderstood or mistaken because are comprehended as a whole from the aspects of the domination of someone or something over others -30. ArenArendt's theory of violence, although developed in the field of political science, also enriches the clinical care to victims of violence. The idea of denaturalization of violence destroys positivist references and inspires practices that go farther then a merely organicistic or psychologizing understanding of traumatic phenomena.The notion of depersonalization of violence adds new meanings to the psychotherapy of domestic violence victims, who usually have ambiguous feelings for the perpetrators, which complicates their psychotherapeutic implication in the process of elaborating trauma. To understand violence by means of its instrumental character and not by personification of evil allows the victims to elaborate on their suffering based on the functions that violence operates in that relationship, and not based on a moral judgment of the aggressor.Finally, demythification of violence indicates the "banalization of evil" and has clear implications on psychotherapeutic care because a barbarian type of violence is a barrier to the process of understanding the traumatic experience, as will be seen next.Iliad. This term was used by ancient Greeks to refer to foreign peoples. The term, originally not disqualifying, referred to those that did not understand Greek and pronounced inarticulate and incomprehensible sounds, such as onomatopoeias: "bar-bar-bar". Barbarians only became dangerous and culturally inferior enemies after the Greco-Persian Wars (5th Century B.C.). The notion of barbarism as a clear opposition to civilization is assigned to Romans, who borrowed the term "barbarism" from the Greek and for the first time raised an insurmountable barrier between Romans and Barbarians [The first appearance of the word "barbarism", associated with rude, brutal and unintelligible speech, is found in Homer's rbarians .socialization; (b) culture; or, more importantly, (c) in a pre-human (savage) stage in relation to those that called them barbarians [Romans started using the term not only to describe peoples beyond their borders, but also for those in their own world who did not belong to the Greek-Roman cultural world . Thereforbarians .It is no longer startling that a highly refined and educated civilization may reach the worst of barbarism, such as in Nazi Germany, which used the advancement of their techniques and knowledge to exterminate human beings rationally and in an industrial scale. Therefore, the simple and single definitions of barbarism and civilization as opposites do not exist . The terThis dialectical trap may be avoided by defining a culture as barbarian if it lacks structures to recognize the alterity of things, by defining customs as barbarian if their effects deny a specific form of human existence, and by describing individuals as barbarian if they are incapable of tolerating diversity. The meaning of barbarism is more clearly defined when a culture is analyzed in relation to itself, not by classifying as barbarian those who were left out of any civilization process, but by recognizing barbarism when people fall behind, in a peculiarly hideous way, their own civilization even though this civilization has achieved the highest levels of development .In general, terrorist attacks can be considered as one specific form of barbarism, once "attackers tend to use horrific violence to cause massive destruction and death and to use other tactics  to terrify the public" , and mosThe terrorism and other barbarian aspects of violence imply a lack of meaning rather than some symbolic construction that "justifies" the traumatic event that affected the victims or their relatives. Finding a "justification" for violence outlines a symbolic shield against terror, the initial mechanism of assigning meaning to traumatic experiences. Conversely, lack of meaning is the trademark of barbarian violence and an obstacle to the elaboration of trauma and its consequent symbolic integration in the victim's life. This significant gap is filled by the abundance of symptoms that result from the persistence of the traumatic memory.The tenth edition of the International Classification of Diseases (ICD-10) and the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) describe similar criteria to diagnose PTSD. According to criterion A of DSM-IV, a diagnosis of PTSD should be made when "the person has experienced, witnessed, or been confronted with an event or events that involve actual or threatened death or serious injury, or a threat to the physical integrity of oneself or others" (criterion A1), and whose response to the event "involved intense fear, helplessness or horror" (criterion A2) . Accordideath, serious injury or a threat to physical integrity. In regard to the first stage of the process of stress – the isolated environmental input – the criterion A1 indicates a return to the older meaning of the word "trauma", which refers exclusively to a bodily wound, as originally used in medicine.The historical trajectory of the concept of PTSD, from DSM-III to the revised edition of DSM-IV, attests to "the centrality of the stressor criterion in the definition of this disorder" . In the The second stage in the process of stress can be found in criterion A2 of the DSM-IV, and reflects the psychological dimension of trauma through the immediate apprehension of the event by the victim in the form a response of "intense fear, helplessness or horror." Some authors question the restriction of criterion A2 to only these trauma-related emotions, "when there is recent evidence that both anger with others and shame" are also "strong predictors of PTSD symptoms longitudinally" .The criterion A1 excludes the situations that do not involve direct physical violence or "threat to physical integrity", but that are capable of producing psychopathological responses of reliving, avoidance, and hyperarousal. The point here is not to artificially expand the criterion to include the more questionable dimensions of a broader concept of violence. The purpose is to rectify, from a nosographic perspective, the conclusion that, if an event can be simply characterized as a "threat", such threat may be defined not only as physical threat, but also as moral coercion, psychic intimidation, or symbolic coercion. A good example of such is the development of PTSD by some victims of bullying, a type of violence that is perpetrated not necessarily and only by means of threat to physical integrity, but that may occur by means of systematic psychological attacks that take the form of verbal offense, acts with the intent to ridicule in front of others, and social isolation from youth groups with certain physical or psychic characteristics.indirect exposure, largely through the media, questions the "perhaps outdated stimulus-response model" based on the "conventional assumptions that a disaster should be defined as local and must be directed experienced to cause psychopathology" [Furthermore, in the context of ongoing terrorist threats, especially after the 9/11 attacks, the presence of widespread posttraumatic stress disorder symptoms among individuals not directly exposed to the attacks was documented and replicated in independent cross-sectional and longitudinal studies . This inthology" .stress disorder, the patient should have "been exposed to a stressful event or situation." Besides, the description of the nature of this stressor as "something exceptionally threatening or catastrophic" evokes the conceptual weakness of this criterion rather than is an attempt to outline or characterize the type of event. After all, if the notion of exceptionality refers to something that is "out of the ordinary" and that "occurs beyond the limits of what is usual, normal, frequent or ordinary" [The fragility of the ICD-10 approach to the event itself is shown, initially, in the circularity of its definition, once it is based on the response elicited, which leads to a tautology: to develop posttraumatic rdinary" , what woexceptionally threatening a situation that might not cause pervasive distress "in almost anyone." The perspective adopted in the ICD-10 is in disagreement with a decisive factor in clinical practice: for patients that present typical PTSD symptoms, the traumatic factor is not necessarily identified in the reality that they can share, but maybe only in their personal and subjective experiences.Moreover, this construct becomes even more complex when analyzed according to an individual perspective. A person with PTSD symptoms may have perceived as The conceptual inaccuracy of criterion A of the ICD-10 may also be found in the specification of the nature of the event as "catastrophic" or "threatening". How to discuss, then, the barbarian forms of violence that are not a catastrophe or do not constitute a direct threat, but that are capable of triggering PTSD? Barbarism may be described as a type of violence that, in some cases, prescinds from the association with "exceptional threat" for its perpetration. Barbarism may simply be a paroxysmal form of violence, an act without warning, without threat, whose only objective is destruction and death of another human being.Not infrequent are cases of people that get together to perpetrate acts of violence against homeless, black or native people, gays or members of other minorities by ambushing the victims, sometimes when asleep, without any type of previous threat. Because of the barbarian death of one of their members, these minorities may develop chronic hyperarousal, avoidance and intrusive thoughts of situations associated with that barbarism, and, therefore, meet all the criteria for a PTSD diagnosis although they have not concretely experienced a direct threat. In such situations, something that should be perceived as normal by most anyone, such as belonging to a minority group , is experienced as an "exceptionally threatening" situation.In the same manner, "there are now replicated findings that PTSD symptoms related to the September 11, 2001, attacks occurred in large numbers of persons who did not fit the traditional definition of exposure to a traumatic event" . It is lA careful analysis of the criteria currently used by the APA and WHO psychiatric guidelines shows inaccurate definitions of violence, disaster, catastrophe, trauma and barbarism. Such critical appraisal should inspire new studies to improve diagnostic and therapeutic parameters used in clinical practice.physical aspect of trauma. According to the considerations above, violence prescinds from force and physical damage, and the psychological dimension of a threat may be the most devastating face of violence. The restriction of this criterion to the minimalist concept of violence may exclude diagnoses and treatment of a significant number of patients with PTSD. At the same time, a broad understanding of violence exceeds the limits of clinical practice, as demonstrated in the discussion of the concept established by the WHO. Between these two concepts, there is an alternative: to include the aspect of psychological violence as one more possible trigger of PTSD without expanding the concept to the point of introducing aspects that are too broad for clinical practice.In the analysis of the DSM-IV criteria, such improvement should focus on the fact that this classification limits the real event or threat to the The ICD-10 also shows misconceptions in its criterion A, such as the generalizing definitions discussed above. New definitions of this diagnostic category should necessarily include the "impossibility of symbolic elaboration" as a condition for the development of this disorder. This is a dimension that includes the senses of "trauma", "barbarism" and, many times, "catastrophe", and replaces vague expressions such as "exceptionally threatening."The difficulty in understanding and elaborating an event adds an important diagnostic value to this criterion because it assigns priority to a person's individual psychic response rather than to the effects found in "almost anyone." This latter expression is not only imprecise, but may also exclude PTSD cases that, although originated in individual situations, may result in psychic sequelae of traumatic characteristics.In summary, the aspects discussed may be organized as a blueprint for the changes in criterion A of the diagnostic classifications as follows:A) Delayed psychic response to a situation or event (either short- or long-lasting) whose understanding or symbolic elaboration is not possible for the person because of the magnitude of physical or psychological threat or the actual presence of death, injury or severe psychological distress, with an immediate response of intense fear, helplessness, dissociation or horror.The examination of PTSD terminology defined two completely different tasks: the understanding of the meaning of the expressions used by the patient; and the search for terms that translate such expressions into medical language. The "disaster" described by the patient may be only an unexpected experience that requires an intense existential implication for which this person does not feel prepared. A situation referred to as "traumatic" raises the examiner's interest in obtaining details of the circumstances of the event described because the extension and intensity of the stimulus may reflect differently in psyche. A more severe psychopathological presentation is marked by silence and difficulty in elaboration, which may indicate experiences of severe contact with a form of violence, such as barbarism.The purpose of clarifying the terms used in the field of PTSD is to provide a resource for conceptual clarity, terminological precision, and understanding of meaningful nuances of the words used in clinical practice. Patients seen after an experience of imminent death do not need therapists that operate according to a good-versus-evil system, or who assign all evil to the perpetrator and reinforce the patient's role as a victim. These patients have already "faced death" and, therefore, therapy should not be conducted through the personalization of violence; it is not the positivist naturalization of violence that provides the theoretical basis for the clinical treatment of PTSD; and, finally, it is not the mythification of violence that will enable society to overcome this phenomenon.1. The plethora of terms used in PTSD literature does not reflect the understanding of meanings, applications and limits of these concepts.2. The "disaster taxonomy" indicates event characteristics that may generate different psychic responses and, therefore, requires precise terms to describe the three stages of the process of stress.3. Because of changes in the concept of trauma along time, it can now be understood in its integrative or paralyzing psychic dimensions depending on how the traumatic experience is elaborated.4. The use of a broad concept of violence in PTSD leads to questions out of the range of psychotherapy, and the barbarian type of violence functions as a barrier to resilience.5. The criterion A of the ICD-10 and DSM-IV show conceptual imprecision and fragilities that may have effects on the diagnosis and treatment of victims of violence.The authors declare that they have no competing interests.LLB conceived of the study, performed the literature search, participated in the interpretation and discussion of data, drafted and wrote the manuscript. JPF performed the literature search, participated in the interpretation and discussion of data, coordinated the multiple revisions of the manuscript. MFM conceived of the study, participated in the interpretation of data and coordinated the multiple revisions of the manuscript. JJM participated in the interpretation of data and critically revised the first versions of the manuscript. All authors read and approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:


Biomass has been studied as biomarker to evaluate the effect of heavy metals on microbial communities. Nevertheless, the most important methodological problem when working with natural and artificial microbial mats is the difficulty to evaluate changes produced on microorganism populations that are found in thicknesses of just a few mm depth.in situ the effect of Pb and Cu stress in cyanobacterial populations.Here, we applied for first time a recently published new method based on confocal laser scanning microscopy and image-program analysis to determine Microcoleus sp.  was detected within a week. According to the data presented in this report, this biomass inspection has a main advantage: besides total biomass, diversity, individual biomass of each population and their position can be analysed at microscale level. CLSM-IA could be a good method for analyzing changes in microbial biomass as a response to the addition of heavy metals and also to other kind of pollutants.The results showed that both in the microcosm polluted by Cu and by Pb, a drastic reduction in total biomass for cyanobacterial and  Microcoleus chthonoplastes is dominant in marine intertidal microbial mats, hypersaline environments and hot deserts Benthic stratified sediments  that cover kilometer long areas of coastal territory are made up of a dense biomass of microorganisms Nevertheless, the most important methodological problem when working with microbial mats is the difficulty to evaluate changes produced on cyanobacterial populations that are found in thicknesses of just a few mm depth. One of the main goals of assessing the effects of heavy metals on microbial communities in natural and artificial ecosystems in the laboratory is the search for an effective and reliable bioindicator. Changes in diversity or biomass can usually be considered good indicators for evaluating the effect of metals on bacterial populations. Amongst those most used are molecular techniques and biochemical analysis Optical microscopy techniques such as fluorescence microscopy have also been used −3 mgC/cm3 of sediment. This method was especially suitable for the quantitative analysis of a large number of CLSM images generated from benthic sediments in which complex populations of cyanobacteria were abundant, such as unpolluted an oil-polluted microbial mats We have recently published a new method based on determining cyanobacterial bimass by the Confocal Laser Scanning Microscopy- Image Analysis (CLSM-IA). This method has made it possible to characterize and identify the photoautotrophic microorganisms and also, with the aid of image-analysis computer systems, to determine their biomass In this study, we applied CLSM-IA for first time to cyanobacterial populations living in microcosms in order to determine the effect of heavy metals on these microorganisms, specifically in terms of biomass.Microcoleus sp. in microcosms. In order to do so, we have used Confocal Laser Scanning Microscopy (CLSM), which detects the natural fluorescence of photosynthetic pigments, and we have determined the total and differentiated biomass of the cyanobacteria by means of an image analysis program, Image J v1.37 (CLSM-IA) In this paper, we have studied the effect of lead (Pb) and copper (Cu) on the cyanobacteria population, and mainly on Microcoleus sp. and Halomicronema-like were the most abundant filamentous cyanobacteria. Microcoleus sp. presents its trichomes oriented in parallel, enclosed in a common homogenous sheath and the mature end cells are conical. Cells (diameter 3–6 µm) composing the trichomes are longer than they are wide  and end cells are rounded  from the first mm of depth, as it was in this layer that the greatest cyanobacteria growth was observed  to 0.507±0.25 mgC ·cm−3 of sediment (day 10). Microcoleus sp. was not detected at t = 112, therefore, the biomass determined at the end of the study was probably mainly due to Halomicronema-like. In the microcosm polluted by Cu, the same effect was noticed, a reduction of the total biomass (from 3.813±3.20 to 0.409±0.38 mgC ·cm−3 of sediment), and Microcoleus sp. biomass (from 3.622±3.14 to 0.199±0.25 mgC ·cm−3 of sediment) 7 days after beginning the experiment.In the microcosm polluted by Pb, a drastic reduction in total biomass from 9.275±4.62 to 1.265±0.38 mgC ·cmMicrocoleus sp. after only one week. In Microcoleus sp. biomass values are expressed in mg C· cm−2 of sediment. This figure shows the lethal effect of Pb and Cu in the above mentioned populations, similar to those represented in Microcoleus consortium, a degradation of the photosynthetic pigments, which can be seen through the absence of fluorescence in the emission spectra, and alterations of the cell ultrastructure, such as expanded thylakoids and large intrathylakoidal spaces, in cultures treated with Pb and Cu respectively .In both cases it is shown that, in the doses of metals used, both Pb and Cu are lethal for cyanobacterial populations and a quantification Certain reports use changes in community composition and biomass as useful bioindicators for determining the effect of heavy metals on different ecosystems in situ cyanobacterial biomass determination, especially in the application to various benthic sediment samples. According to the data presented in this report, this biomass inspection has two main advantages: first, in addition to total biomass, diversity, individual biomass of each population and their position can be analysed; second, this method can be applied to different kind of natural and artificial ecosystems, including polluted mats. The overall results shown in this paper indicate that Pb and Cu in the concentrations used in this study have a drastic effect on cyanobacterial biomass and mainly on Microcoleus sp. in only one week, and that CLSM-IA is a good method for analyzing changes in microbial biomass as a response to the addition of heavy metals and also to other kind of pollutants. Although the method applied would not be suitable to analyse the physiologic state of the cells, we are currently applying the lambda scan function of CLSM to analyse the physiological state of the photosynthetic pigments.In conclusion, we believe that CLSM-IA is the best method for estimating cyanobacterial biomass in microbial mats. The method takes advantage of the accurate and nondestructive optical sectioning of confocal microscopy, and autofluorescence of cyanobacteria, presenting a good technique for Samples from microbial mats were obtained from the Ebro delta, located in the northeast of Spain , near the Salines de la Trinitat, in the Alfacs Peninsula, on May 2006. Samples were taken in 17 cm×12 cm×8 cm polypropylene boxes and carried to the laboratory. Once in the laboratory, different microcosm experiments were prepared, one of them unpolluted and used as a control experiment, and the other two polluted with 25 mM Pb and 10 mM Cu, respectively. The latter microcosms were maintained in polluted conditions for three days, and afterwards metal solutions were removed. Samples from microcosms were taken with glass cores of diameter of 6 cm on days 0 (before contamination), 7, 10 and 112 for further analysis.3)2 and CuSO4  with deionized water and were sterilized by filtration with polycarbonate membrane filters. Heavy metal stock solutions were prepared 24 hours before to be used and kept in darkness at 4°C.We selected copper and lead on the basis of their biological functions and effects. Copper is an essential metal with known biological functions (micronutrient) in all organisms. In cyanobacteria, copper is a component of plastocyanin in the photosynthetic electron-transport chain; however, at high concentrations, it has toxic effects both on animals and plants. Lead is a toxic metal with no biological function. Lead and copper stock solutions were prepared as Pb oil immersion objective lens, excited with a diode 561 nm, and were viewed in a Leica TCS SP2 AOBS . The emission fluorescence was captured between 590 and 800 nm (autofluorescence). Natural fluorescence of chlorophyll xyz function of CLSM was used. Images were acquired in 512×512 pixel and 8 bit format. Each stack consisted of 21 optical sections (image xy) on the z dimension, whose value corresponded to a thickness of 20 µm. The samples from microcosms were taken at depth intervals (at each 250 µm) from the first mm of depth and four replicates of each depth were done. The images obtained were used to determine cyanobacterial biomass in the first mm of depth of the microcosms, where cyanobacteria were dominant.In order to obtain optical series (stacks of images), the ImageJ v1.37, was used to determine cyanobacterial and Microcoleus sp. biomass from mat samples, according to Solé et al. −3 to convert it to biomass Once the images of cyanobacteria were obtained by CLSM, a free image-processing and analysis program, Microcoleus sp. biomass determination, the binary stacks were obtained using the same optimum threshold as in total biomass determination. In this case, Microcoleus sp. was selected from the stack of images, whilst the remaining genera of cyanobacteria were erased. Finally, the Microcoleus sp. biomass was determined following the same protocol used for total cyanobacterial biomass estimation.For Microcoleus sp. biomass profiles were represented using KaleidaGraphs software .Total cyanobacterial biomass and the


Currently the majority of cancer patients are considered ineligible for intensive care treatment and oncologists are struggling to get their patients admitted to intensive care units. Critical care and oncology are frequently two separate worlds that communicate rarely and thus do not share novel developments in their fields. However, cancer medicine is rapidly improving and cancer is eventually becoming a chronic disease. Oncology is therefore characterized by a growing number of older and medically unfit patients that receive numerous novel drug classes with unexpected side effects.All of these changes will generate more medically challenging patients in acute distress that need to be considered for intensive care. An intense exchange between intensivists, oncologists, psychologists and palliative care specialists is warranted to communicate the developments in each field in order to improve triage and patient treatment. Here, we argue that "critical care of cancer patients" needs to be recognized as a medical subspecialty and that there is an urgent need to develop it systematically.As prognosis of cancer improves, novel therapeutic concepts are being introduced and more and more older cancer patients receive full treatment the number of acutely ill patients is growing significantly. This development a major challenge to current concepts of intensive care and it needs to be redefined who of these patients should be treated, for how long and how intensively. The discovery of the human genome and the development of high-power bioinfomatics tools have led to an exponential growth of biomedical knowledge. One of the areas that has benefited the most over the last few years has been cancer research which is now translating into a dramatic development of clinical oncology. As a result targeted therapy and personalized medicine will eventually transform cancer into a chronic or even curable disease.While improved overall survival and reduced acute toxicities are already visible in certain, defined clinical scenarios -3, seconHere, we propose that one of the most striking consequences is the urgent need for new critical care concepts for cancer patients. This hypothesis is supported by the following arguments:chronic disease. However, in accordance with current recommendations advanced stage cancer patients are frequently denied admission by intensive care units that are normally run by non-oncologists [Some cancers are likely to become a ologists -6. When palliative care need to step back or even come closer? In terminally ill lung cancer patients for example the frequency of end-of-life-admissions to hospices as well as ICUs have been reported to increase substantially suggesting that both specialities are needed for this patient cohort [When critical care comes into play does t cohort . Early it cohort . This emscoring systems appears to be difficult as they are not developed for this cohort and often lead to wrong predictions. Therefore, they are the subject of an ongoing debate and further improvement appears necessary [In cancer patients neutropenia, autologous bone marrow transplantation and the characteristics of the underlying malignancy now have limited influence on the acute outcome while the number of organ failures and severity of infection are correlate with survival -12. ICU ecessary -22. Evenecessary ,22.physician's perception of a critically ill patient's prognosis has been shown to influence survival more strongly than the baseline disease severity, development of organ dysfunction or use of vasopressors [This is of particular importance as the treating pressors . The propressors . A reappinternal and geriatric medicine into the world of cancer treatment [Life expectancy is rising globally and in 2025 1.2 billion people will be older than 60 years of age [reatment . So far These issues can only be addressed when medical oncology and geriatric as well as intensive care medicine start working closely together to develop common, interdisciplinary algorithms.novel drug classes is entering the market and novel, unexpected serious adverse events (SAE) are encountered [An increasing number of ountered -29. A clpersonal relationships with the treating nurses and physicians are common. If such patients enter the ICU the physician-patient relationship becomes extraordinarily difficult as the ICU days mean much more suffering and pain than regular treatment. It is hard to imagine that this stress can be tolerated by the caregivers without long-term psychological damage or at least specialized psychological guidance. ICUs specialized in the challenges of cancer medicine would have the opportunity to develop psychological support strategies so far not existent in critical care.To date future intensive care patients frequently enter the hospital via the emergency room in critical conditions necessitating sedation and respiratory support. A personal relationship to the ICU staff is therefore only developed in select cases. Cancer patients are treated long-term and The dynamic of this development is underlined by the fact that substantial progress has already been made both in intensive care and hematology/oncology which already results in an improved survival of critically ill cancer patients -32.To best address the above challenges we propose a four step strategy:early and aggressive treatment has been reported to be beneficial for cancer and non-cancer patients alike [reevaluation after a limited treatment phase appears to allow for more solid judgment.1. Permissive ICU admission policies for cancer patients and ts alike ,33,34. Dts alike ,30,35. Taddress ICU admission and code orders early to learn the patient's and family's opinion and to give them time to consider. This information should help define preliminary treatment goals upon admission and refine them after an early treatment phase of 4-6 days.2. Oncologists spend more time talking to the patients and their families than colleagues from many other specialties. However, the aspect of intensive care and resuscitation are rarely addressed in these discussions. Therefore, end-of-life decisions and do-not-resuscitate orders are often issued by the treating intensivist alone ,37. This3. How can oncological knowledge best be brought to the ICU and how can critical care be optimized for cancer patients? The already growing number of cancer patients undergoing critical care currently necessitates a 'distribution' of these patients to IC wards of various specialties. This development is viewed with concern, not only by the patients and their families, but also by the responsible physicians, and is certainly not a desirable development.Oncologists and intensivists are usually distinct types of physicians that clearly know why they do not want to perform their colleagues' work. While oncologist have significant time to research and identify the optimal strategies for their patients, intensivists sometimes need to make quick decisions based on little or -on the contrary-, extremely complex, but inconclusive information. Oncologists spend a lot of their time talking with patients and families while intensivists focus on delicate, invasive procedures. Therefore, they share little common ground and patients either benefit from the one set of skills or the other, rarely both at the same time.The most obvious solution would be to have common rounds and prime different mind sets by common rotations during training. Intensivists should be encouraged to acquire practical and theoretical knowledge of haematology and oncology as part of their specialty training and vice versa.An alternative approach is being pursued at our institution where a medical ICU (MICU) is integrated into the oncology service. The department of medical oncology is part of a regional comprehensive cancer center and the MICU part of a portal for emergency medicine and intensive care. Thus there are closest interactions with neighboring specialties e.g. radiotherapy, gastroenterology, palliative care, surgery, psychology on the one hand and anesthesia, emergency medicine, general as well as specialized surgical, neurological and cardiac intensive care on the other. The ICU is directed by physicians that are trained medical oncologists and intensive care specialists. An increasing number of interns that were once dedicated to become oncologists have now discovered their interest and talent for the other specialty and are pursuing such a double qualification. This is a development we have anecdotally seen in the field of bone marrow transplantation where haematologist had become familiar with the treatment of their critically ill patients due to isolation policies. However, in this scenario few doctors treat highly selected, fit patients for a limited number of ICU diagnoses such as sepsis or neutropenic colitis. A third approach would be a core training in one specialty and an supplementary education in the other. Best such training should be implemented in major medical centers as these often have a culture of intensive training and sufficient resources to develop and implement novel structures. If successful this process can spread to other tertiary and even secondary medical centers. "Critical Cancer Care" can only be developed as a joint effort by intensivists and oncologists. Depending on the national system it could be a two year secondary subspecialty training after internal medicine/hematology/oncology or internal medicine/intensive care or anesthesiology/intensive care. Training should be organized by both specialities and should consist of theoretical instruction in the new subject and a common practical training including rotations of e.g. six months to non critical cancer care e.g. oncology clinic for intensivists and anesthesiology for the oncologists. This is in contrast to other subspecialties such as neurosurgical or cardiac critical care that are based on skills taught in the "mother" specialty and that are linked to acute medicine and critical care on a daily basis. Also knowledge relevant to the treatment of cardiologic patients is more familiar to intensivists than the treatment of solid tumors.To measure the impact of such a structure pilot medical centers should determine the ICU length of stay, respirator days and in hospital mortality as well as patient and referring oncologist satisfaction. The period prior to the implementation of this specialty program should be compared to the period thereafter.'critical care of cancer patients' needs to be recognized, defined and developed. The foreseeable development of cancer medicine necessitates that qualified critical care will eventually be available for a rapidly growing number of cancer patients.Whichever approach will demonstrate successful it is clear that the specialty of physicians specialized in defined organ systems such as urologists, pulmologists, gastroenterologists, gynecologists etc. It appears to be most beneficial for the critically ill cancer patients to bring these specialties into the above scenario e.g. by regular consultations. First, they are needed to participate in the treatment as referring oncologists and second they can contribute expertise concerning organ-specific complications such as airway stenosis, bleeding from gastrointestinal tumors, urinary tract obstruction etc.4. Most patients with advanced cancers are treated in an outpatient setting by medical oncologists. However, inpatient treatment is often performed by Taken together, the number of cancer patients needing critical care is dramatically rising and as a consequence the array of open questions regarding the optimal management of such patients is growing. These uncertainties can only be addressed successfully when the oncology and intensive care communities start developing 'critical cancer care' concepts as a long-term, joint effort.Cancer medicine is rapidly improving and cancer is eventually becoming a chronic disease. Oncology is therefore characterized by a growing number of older and medically unfit patients that receive numerous novel drug classes with unexpected side effects. These changes will most likely generate more medically challenging patients in acute distress that need to be considered for intensive care. An intense exchange between intensivists, oncologists, psychologists and palliative care specialists is warranted to communicate the developments in each field in order to improve triage and patient treatment. We postulate that "critical care of cancer patients" needs to be recognized as a medical subspecialty and that there is an urgent need to develop it systematically.The authors declare that they have no competing interests.This manuscript has not previously been presented nor is it currently under consideration elsewhere.MK, ASV, MBB and MH all wrote the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/10/612/prepub


Plasmodium falciparum-infected erythrocytes (IE) plays a crucial role in anti-malarial immunity by promoting clearance of blood-stage infection by monocytes and macrophages. The effects of phagocytosis of opsonized IE on macrophage pro-inflammatory cytokine responses are poorly understood.Antibody opsonization of Phagocytic clearance, cytokine response and intracellular signalling were measured using IFN-γ-primed human monocyte-derived macrophages (MDM) incubated with opsonized and unopsonized trophozoite-stage CS2 IE, a chondroitin sulphate-binding malaria strain. Cytokine secretion was measured by bead array or ELISA, mRNA using quantitative PCR, and activation of NF-κB by Western blot and electrophoretic mobility shift assay. Data were analysed using the Mann–Whitney U test or the Wilcoxon signed rank test as appropriate.Unopsonized CS2 IE were not phagocytosed whereas IE opsonized with pooled patient immune serum (PPS) were (Phagocytic index (PI)=18.4, [SE 0.38] n=3). Unopsonized and opsonized IE induced expression of TNF, IL-1β and IL-6 mRNA by MDM and activated NF-κB to a similar extent. Unopsonized IE induced secretion of IL-6  but no IL-1β or TNF, whereas PPS-opsonized IE induced secretion of IL-1β (18.6 pg/mL [34.2-14.4]) and TNF (113 pg/ml [421–17.0]) and increased IL-6 secretion . Opsonized, but not unopsonized, CS2 IE activated caspase-1 cleavage and enzymatic activity in MDM showing that Fc receptor-mediated phagocytosis activates the inflammasome. MDM attached to IgG-coated surfaces however secreted IL-1β in response to unopsonized IE, suggesting that internalization of IE is not absolutely required to activate the inflammasome and stimulate IL-1β secretion.It is concluded that IL-6 secretion from MDM in response to CS2 IE does not require phagocytosis, whereas secretion of TNF and IL-1β is dependent on Fcγ receptor-mediated phagocytosis; for IL-1β, this occurs by activation of the inflammasome. The data presented in this paper show that generating antibody responses to blood-stage malaria parasites is potentially beneficial both in reducing parasitaemia via Fcγ receptor-dependent macrophage phagocytosis and in generating a robust pro-inflammatory response. Unprimed MDM exposed to human erythrocytes as a negative control secreted no IL-1β and this was not increased following incubation with CS2 IE  activation by the inflammasome . Since IP. falciparum IE are well understood, however the pathways regulating the subsequent inflammatory response, important for control of parasitaemia, are not. Here it is shown that unopsonized CS2 IE, although not internalized by human MDM, stimulate pro-inflammatory cytokine mRNA expression. This is associated with a low level of IL-6 secretion but no IL-1β or TNF secretion. Opsonization by immune serum increases IE internalization via Fcγ receptors without increasing cytokine mRNA levels, and activates components of the inflammasome leading to IL-1β secretion. These data are consistent with recently published studies [The mechanisms of phagocytosis of  studies  in whichP. falciparum strain, obtained by selection for CSA binding [The present study investigated cytokine responses to purified CS2 trophozoite-infected erythrocytes. CS2 is a laboratory-derived  binding  similar et al. demonstrated that cytokine production by murine bone marrow-derived dendritic cells, in response to schizont bursts, were mainly due to recognition by a TLR9-dependent mechanism of protein DNA complexes released from merozoites [These observations may suggest that surface pattern recognition receptors, in addition to endosomal receptors, play a role in cytokine elicitation in response to IE. It has been shown that toll-like receptor 2 (TLR2) stimulates pro-inflammatory cytokine production in response to parasite-derived glycosylphosphatidylinositol  and TLR4rozoites ,49 and trozoites . In the rozoites . The lacrozoites .Additional signalling required for robust pro-inflammatory responses may be downstream of Fcγ receptors and/or be activated by internal pattern recognition receptors recognizing ligands in the IE that are released following ingestion of the cells. Whether there is a qualitative difference in the cytokines produced in response to these different pathways remains to be determined. Recent studies have suggested that murine dendritic cells require the presence of multiple Toll-like receptors to induce TNF secretion in response to schizont stage murine malaria parasites since NF-κB nuclear translocation, TNF secretion and dendritic cell activation are abrogated in bone marrow-derived dendritic cells obtained from TLR9, TLR4 and MyD88 knockout mice . These dData reported herein, using the CS2 parasite strain, differ from those reported using CD36-binding isolates . In the The data presented in this paper show that generating antibody responses to blood-stage malaria parasites is potentially beneficial both in reducing parasitaemia via Fcγ receptor-dependent macrophage phagocytosis and in generating a robust pro-inflammatory response.CSA: Chondroitin sulphate A; IE: Trophozoite-stage infected erythrocytes; IE-PPS: IE opsonized with pooled immune serum; EMSA: Electrophoretic mobility shift assay; MDM: Monocyte-derived macrophages; IQR: Interquartile range; IRAK4: Interleukin-1 receptor-associated kinase-4; IL-1β: Interleukin-1β; TNF: Tumour necrosis factor ; IL-6: Interleukin-6.The authors declare that they have no competing interests.JZ and LEL performed experiments and participated in data analysis. WH performed experiments. SJR designed the study, participated in data analysis and helped to draft the manuscript. AJ designed the study and drafted the manuscript. All authors read and approved the final manuscript.


Brassica plants. We also specify the advantages and disadvantages of PTR-MS analyses and new technological developments to overcome their limitations.Root herbivores are notoriously difficult to study, as they feed hidden in the soil. However, root herbivores may be traced by analyzing specific volatile organic compounds (VOCs) that are produced by damaged roots. These VOCs not only support parasitoids in the localization of their host, but also may help scientists study belowground plant-herbivore interactions. Herbivore-induced VOCs are usually analyzed by gas-chromatography mass spectrometry (GC-MS), but with this off-line method, the gases of interest need to be preconcentrated, and destructive sampling is required to assess the level of damage to the roots. In contrast to this, proton-transfer-reaction mass spectrometry (PTR-MS) is a very sensitive on-line, non-invasive method. PTR-MS already has been successfully applied to analyze VOCs produced by aboveground (infested) plant parts. In this review, we provide a brief overview of PTR-MS and illustrate how this technology can be applied to detect specific root-herbivore induced VOCs from  We can approximately convert emissions by the following formulaA conversion of the unit commonly used for VOC emissions, in ng·gZ)-3-Hexenol, for example, was emitted at a rate of 153.6 ng·g−1 [dw]·h−1, which is 43 % of all GLVs in the herbivore treatment, but when expressed as a mixing ratio (ppbv), the same compound constitutes 53 % of all GLVs , which are one of the most widespread VOC classes in the plant kingdom, at least above ground Table . BecauseDue to low emission rates, the VOCs sampled from the plant headspace usually need to be pre-concentrated on adsorbents before they can be analyzed on gas chromatography (GC) platforms. Most commonly, plant VOCs are sampled on tubes filled with polymer materials, such as Tenax, Porapaq, Carbopack, and charcoal, or on solid phase micro-extraction fibers , which results in extensive fragmentation providing rich ion fragments, PTR-MS relies on chemical ionization (CI), a soft ionization method with few or no ion fragments in the mass spectra. A detailed description of the PTR-MS technology has been published elsewhere . Typically, only molecules with a proton affinity higher than that of water  will be ionized by proton-transfer-reactions with H3O+ ions. Organic compounds such as aldehydes, ketones, alcohols, oxygenated aromatic and aliphatic compounds will be readily protonated .In addition to the normal proton-transfer-reaction, the Hber Fig. , no. 3. via dehydration, whereas acetaldehyde or acetone is less likely to dissociate , each at a concentration of 1 ppmv . The calibration factors obtained for the fixed set of compounds in the certified gas mixture can be used to calculate the calibration factors of other compounds, by taking into account their collision rate constants, transmission efficiency factors, and fragmentation ratios. In this way, ion intensities  can be converted to absolute concentrations as gas mixing ratios . PTR-MS can operate in two modes, namely the full mass scan and selective ion monitoring (SIM). The first scans the relative abundance of all detectable masses, and should be regarded as a fingerprint of a given trace gas sample . Association processes with water are quite sensitive to higher collision energies (E/N), thus, if the intensity of a signal decreases with higher E/N, the signal is contributed by a compound associated with one or more water molecules.13C incorporation into a molecule rises in a linear fashion with the number of carbon atoms in that molecule. For example, with the natural 13C abundance of 1.1 %, a molecule containing 5 carbon atoms, such as isoprene (M = 68) has a chance of 5.5 % to contain exactly one 13C. With PTR-MS, isoprene is detected as C5H9+ at m/z = 69, however, this signal also can be attributed to a water–methanol cluster-ion, CH3OH (H2O)H+. If the ratio between m/z = 69 and its isotope at m/z = 70 indicates a 13C abundance close to the expected value for a 5-carbon compound (5.5 %) the signal measured at m/z = 69 is more likely to be derived from isoprene. Additionally, in complex gas mixtures, such as the ones derived from plant headspaces or human breath, it is common practice to proceed along these lines for compound identification . To overcome these limitations, several new technologies have been developed. Combining PTR-MS with a GC, in which the VOCs are first separated by their retention time in the GC and then detected one by one by PTR-MS, avoids the overlap of different compounds and fragments  is commonly employed to ionize compounds. In addition, other ions such as NO+ and O2+ can be produced in the ion source with the switchable reagent ions (SRI) technology  from different compounds can be superimposed on one Since its development, PTR-MS has found many applications in a wide range of fields, including medicine  immediately after leaf wounding. With PTR-MS, this process has been studied at a high time-resolution, which yielded new insight into the regulation of this pathway  during infestation with a belowground herbivore, the larvae of the cabbage root fly (Delia radicum). The root headspace of infested and non-infested plants was sampled from a cuvette fitted around the base of the stem  and dimethyltrisulfide  displayed considerable increases in emission rates due to herbivore feeding. In addition, we also found that the biosynthetically related compound methanethiol (m/z = 49) was emitted at higher rates when root fly larvae were feeding. Previous GC analyses have not detected methanethiol, which might originate from the compound selectivity of the adsorbents that have been used for collection. Interestingly, we also found a considerable increase in m/z = 60, which is related to glucosinolate breakdown products  converts the glucosinolates that are stored in the vacuoles into toxic and volatile products, such as isothiocyanates and nitriles  or of jewel beetles (Phaenops cyanea), demonstrates that insect antennae are capable of detecting, for instance, the GLV (Z)-3-hexen-1-ol at around 1 ppmv and 1 pptv, for the two species, respectively. Compared to that, the detection limits in PTR-MS already are in a similar range of several parts per trillion volume, depending on the properties of the instrumentation.As outlined, PTR-MS has in the recent years opened an avenue for new insight into fast changing, highly dynamic processes involved in plant VOC emissions caused by plant-environment interactions. Here, we show that, due to its sensitivity and the ability to record real-time responses, PTR-MS is an excellent technique to non-invasively trace the feeding activities of cryptically feeding root herbivores by measuring VOC emissions from the root headspace. Certainly, PTR-MS also has its practical and technical limitations. Besides difficulties in linking masses without doubt to compounds, many quadrupole-based systems lack sensitivity in the higher mass range (above 120 amu), which is relevant for plant-herbivore interactions, as many biologically important compounds, such as several isothiocyanates or generally hemiterpenoids and sesquiterpenoids are difficult to detect. These shortcomings can be overcome partially by combining on-line sampling with PTR-MS and off-line GC-MS methods, or by use of high sensitivity PTR-MS instruments with mass analyzers, such as distinctive quadrupoles, triple quadrupole technology, ion trap, or time-of-flight, which can provide sensitivity also in the higher mass range (Tani et al., Finally, time-resolved and sensitive on-line sampling of root-induced volatiles with PTR-MS will certainly contribute to our understanding of the role of VOCs in belowground multi-trophic interactions. In particular, linking real-time responses in the emission of VOCs to immediate behavioral responses of herbivores, and to the higher trophic levels of parasitoids and predators will unravel further details of the VOC ‘language’ among plants and between plants and insects. This may be achieved by ‘sniffing out’ the VOCs in parallel with olfactometer assays, a prime example of which is the development of a six-arm olfactometer, simultaneously equipped with a VOC sampling unit (Turlings et al.,


R2 is =0.616. In this erratum we report corrected In the paper titled “Reference Values of Pulse Wave Velocity in Healthy People from an Urban and Rural Argentinean Population” there was an error in Figure 1. The correct value of In the paper entitled “Reference Values of Pulse Wave Velocity in Healthy People from an Urban and Rural Argentinean Population” a mistake was introduced in Figure 3. In this erratum we report modified