Social and behavior change approaches have shown promise for addressing the demand- and supply-side challenges in postabortion care. As implementers seek to improve the quality of postabortion care, systematically integrating long-standing models and emerging approaches, including behavioral economics, human-centered design, and attribute-based models of behavior change, can promote positive health outcomes. Social and behavior change approaches have shown promise for addressing the demand- and supply-side challenges in postabortion care. As implementers seek to improve the quality of postabortion care, systematically integrating long-standing models and emerging approaches, including behavioral economics, human-centered design, and attribute-based models of behavior change, can promote positive health outcomes. Unsafe abortion is the fifth leading direct cause of maternal deaths globally and in developing countries.Programmatic experience suggests that key behavior-related challenges in the delivery of high-quality PAC services arise before the PAC client reaches a facility, during her visit to a facility, and after she leaves a facility. These challenges include the followingBefore:Ensuring timely care seeking by women and their partnersDuring:Promoting respectful treatment of PAC clients by providers and addressing the stigma that specific client groups may experience in interactions with providersEnsuring that during counseling, providers address client needs for clear information about return to fertility and family planning options and acknowledge barriers to postabortion family planningEnsuring providers offer a full range of voluntary family planning methods prior to discharging the client, including long-acting reversible contraceptives and permanent methodsAfter:Supporting clients in returning to services to facilitate both voluntary contraceptive continuation and follow-up for clients whose treatment requires return visitsKey challenges in the delivery of high-quality PAC services arise before, during, and after a PAC client’s visit to a facility.While additional formal evaluation of social and behavior change in the context of PAC is needed, lessons learned from programmatic experience in this and other areas of reproductive health suggest that intentional use of behavior change principles and approaches is necessary to address common challenges in PAC programming.,,Seeking care at the first sign of complication is essential to effective treatment of spontaneous and induced abortions. Facilitating timely care seeking requires attention to barriers to accessing services, which may be specific to a given context or client group. Lack of information about the warning signs of spontaneous abortion, dangerous complications of spontaneous and induced abortion, and where to seek PAC prevents women from seeking help.––PAC programs have successfully intervened at the community level to address barriers to care seeking and reinforce supportive norms. In Kenya and Somalia, community education, training of community health workers and community preparedness have effectively increased awareness, acceptance, and utilization of PAC, including voluntary use of postabortion family planning.PAC programs have successfully intervened to address community-level barriers to care seeking and reinforce supportive norms.–before emergency care is required. PAC programs must consistently apply proven practices in behavioral design, including systematic diagnosis of barriers to service utilization among key client groups. In addition to addressing the common barriers cited above, implementers should employ formative research approaches used in behavioral programming as a means to generate insights about client perceptions and motivations. In particular, immersive and participatory approaches grounded in human-centered design show promise as a means to better understand and address barriers to care seeking. Human-centered design is an iterative process that includes developing a deep understanding of the people affected by a problem, identifying opportunities for design to address that problem, prototyping potential solutions, and repeatedly testing and refining those prototypes.providers may treat clients with disrespect or restrict care due to norms or attitudes associated with abortion, sexuality, and sexual health among specific client groups; circumstances such as a subsequent abortion or failure to use family planning; and/or use of family planning after pregnancy loss.,–providers may not adequately explain healthy spacing of pregnancy. The World Health Organization recommends women delay pregnancy for at least 6 months after an abortionproviders may not adequately explain return to fertility, which can occur within 2 weeks after a first trimester spontaneous or induced abortion.providers may fail to counsel PAC clients on the full range of family planning methods available to them and fail to offer these methods prior to discharging the client.,–The client-provider interaction during health care provision represents a critical opportunity to build trust and establish healthy behaviors pertaining to family planning and reproductive health care seeking. Four distinct but interrelated challenges may influence the quality of care offered during a PAC client’s visit to a health facility. Failing to prevent these challenges can ultimately hinder adoption of voluntary family planning methods that enable women and their partners to achieve their desired fertility. First, ,,,To prevent these challenges, PAC programming has successfully employed a range of approaches to influence provider behaviors pertaining to counseling PAC clients, particularly about postabortion family planning. Many PAC programs have integrated discussions of provider attitudes and values into trainings that seek to reduce stigma toward women and adolescents who need reproductive health services, dispel misconceptions about contraceptive methods, and build effective counseling skills. These discussions offer opportunities for providers to reflect on how their own values and beliefs influence their interactions with clients.PAC programming has successfully employed several approaches to influence provider behaviors in counseling PAC clients.PAC programs can build on the rapidly growing evidence base for provider behavior change as a means to improve not only the knowledge and skills that underpin effective counseling, but the full range of motivational and normative influences affecting providers. To do so, implementers must use formative research to analyze specific drivers of provider behavior. As with programs targeting PAC clients themselves, the insights derived from this research can inform segmentationBehavioral design may deepen the impact of traditional knowledge- and skills-based interventions to improve client-provider interaction.PAC programs can further improve the quality of client-provider interaction through continued attention to the drivers of client behavior, specificity in behavior change messaging, and promotion of client engagement during care and counseling. Counseling and other communication approaches should acknowledge and address barriers to postabortion family planning, including social norms regarding fertility and couples’ communication.PAC programming must address challenges relating to support for voluntary contraceptive initiation or continuation and care for clients who require follow-up treatment. Clients who receive counseling and choose a voluntary family planning method may require assistance with accessing ongoing supplies of short-acting methods,Social and behavior change interventions within PAC programs enhance a client’s follow-up care, including family planning, and reinforce linkages between the client’s home and health care workers. Client communication materials facilitate follow-up care. Several international professional associations and development partners recommend that PAC clients should receive simple written instructions for the use of their method, along with concise information about common side effects and benefits.Social and behavior change interventions within PAC programs enhance a client’s follow-up care.Mobile phone-based communication has shown promise to facilitate access to health information and services in low-resource settings. A randomized control trial in Cambodia found that follow-up communication through mobile phones supports postabortion contraceptive use. It helped women retain family planning information provided during PAC and prompted women who wanted a long-acting method but did not receive one during the initial PAC visit to return for an implant or intrauterine device.,,Evidence suggests that engaging the male partners of PAC clients in counseling, when acceptable to clients themselves, can improve health outcomes. PAC programs in Bolivia and Tanzania found that engaging partners by informing them of the client’s condition and providing both with family planning counseling helped to ensure safe recovery and increased voluntary family planning continuation.In general, promotion of voluntary contraceptive continuation or return to services remains less understood than either creation of initial demand for services or improvement of client-provider interaction. Improved design and measurement of activities addressing behavioral initiation or maintenance after a client leaves a facility is an area of increasing collaboration between social and behavior change and service delivery professionals. The concerns of PAC program implementers constitute an important component of this discourse. The rapidly evolving thinking in this area affords PAC program implementers an opportunity to build upon emerging practices and develop innovative solutions to the challenges they face. For example, a growing body of gray literature pertaining to understanding and grouping similar behaviors and the attributes of those behaviors,We should build our understanding of how to address behavioral initiation or maintenance after a client leaves a facility.PAC programs have successfully used community-based social and behavior change approaches and provider behavior change interventions to support clients in accessing postabortion services and adopting voluntary family planning. To ensure that all women have access to high-quality PAC, implementers must build upon this important foundation through continued application of proven practices in behavior change, including formative research, audience segmentation, and the use of iterative, multichannel communication approaches that target clients, providers, and community members. Concomitantly, implementers should seize the opportunity to play a leading role in the application of social and behavior change approaches for PAC by leveraging new trends in behavioral economics, human-centered design, and attribute-based models of behavior change and increasing alignment between demand-side and supply-side programming.


Plant growth dynamics are shaped by the diversity of associating pathogenic, saprotrophic, and mutualistic soil fungi. Feedbacks between plants and soil microbial communities play an important role in vegetation dynamics, but the underlying mechanisms remain unresolved. Here, we show that the diversity of putative pathogenic, mycorrhizal, and saprotrophic fungi is a primary regulator of plant-soil feedbacks across a broad range of temperate grassland plant species. We show that plant species with resource-acquisitive traits, such as high shoot nitrogen concentrations and thin roots, attract diverse communities of putative fungal pathogens and specialist saprotrophs, and a lower diversity of mycorrhizal fungi, resulting in strong plant growth suppression on soil occupied by the same species. Moreover, soil properties modulate feedbacks with fertile soils, promoting antagonistic relationships between soil fungi and plants. This study advances our capacity to predict plant-soil feedbacks and vegetation dynamics by revealing fundamental links between soil properties, plant resource acquisition strategies, and the diversity of fungal guilds in soil. The accumulation of host-specific pathogenic fungi in plant rhizospheres has been identified as an important driver of negative density dependence in plant populations. These negative plant-soil feedbacks underlie plant species coexistence and positive diversity-productivity relationships . Physicochemical properties, such as cation exchange capacity, pH, and soil carbon (C), nitrogen (N), and phosphorus (P) concentrations, formed another axis of variation reflecting inherent soil fertility that was not significantly affected by conditioning with different plant species . Therefore, the experiment captured variation in soil abiotic properties resulting from both plant species conditioning and inherent variability in soil fertility at the site of soil collection. This enabled us to gauge the relative importance of both biotic and abiotic drivers of plant-soil feedbacks.Replicated monocultures of 14 common temperate grassland species, encompassing a broad spectrum of functional traits . After tR2 = 0.32, F13,41 = 2.9, P = 0.004) but not in the accumulation of specialist AM and saprotrophic fungi . Plant species identity had little influence on soil bacterial communities, which were primarily determined by soil abiotic conditions (fig. S1). The distinct effects of plant species on soil fungal communities became more pronounced when fungi were split into putative plant pathogens and saprotrophs  released into the soil , but the effect was considerably weaker than that of the richness of putative pathogens and AM fungi . In support of this conclusion, variation in biotic feedback was more correlated with differences in the richness of putative pathogenic  and AM fungi  than with differences in the composition of these fungal groups . These findings provide compelling evidence that plant-soil feedback is regulated by the diversity of soil fungi and indicate that diversity effects of soil organisms are not only positive . Soil collected from the grassland site exhibited natural spatial heterogeneity in soil properties, and this variation was preserved when filling the mesocosms with soil collected randomly from across the grassland. Plant traits, soil abiotic properties, and microbial communities were measured for each mesocosm at the end of the conditioning stage  were polymerase chain reaction amplified and used to characterize the microbial communities. The amplicons were sequenced on an Illumina MiSeq instrument with 2 × 151 base pair kits.Microbial community structure was determined as in . AM fungi were represented with 126 ESVs . Saprotrophs were represented by 338 ESVs . Detailed functional data are not currently available for soil bacteria and protists. We therefore only assessed the composition of bacterial and protist communities, and the relative abundance and richness of well-known pathogenic oomycete ESVs (Pythium and Phytophthora genera), as predictors of plant-soil feedbacks. We found that the composition of bacterial and protist communities was strongly correlated with that of saprotrophic fungi (table S2). Only the latter was included in the subsequent path analysis as a representative characteristic of overall microbial community composition.Exact sequence variant  counts were determined from raw sequence data using the DADA2 pipeline . For each soil sample, the relative abundance, ESV richness, and exponential Shannon diversity (effective species number) were calculated for each fungal functional group and specialist and generalist sequences within each functional group. Asymptotic exponential Shannon diversity was calculated for each fungal group using the package iNEXT in R  was characterized using principal coordinate analysis (using Bray-Curtis distances and Hellinger transformation of read abundance data). The first two principal coordinates for each fungal group and the first two principal component axes of plant traits and soil abiotic properties were used as predictors of plant-soil feedback in the analysis described below. The importance of plant species identity and the first principal component of abiotic soil properties in explaining variation in plant traits and soil microbial properties was analyzed using variance partitioning for univariate traits (comparison of linear fixed-effects models) and redundancy analysis for multivariate data [package vegan, function dbrda in R 3.4.0 (The best predictors of soil feedback were selected on the basis of Akaike information criterion (AIC) from five groups of variables: plant traits, soil abiotic properties, and soil fungal community properties . Each variable was tested in a separate linear model as a predictor of soil feedback, and predictors yielding the lowest AIC scores within each variable set were retained for use in the path analysis to explore possible paths by which plant traits and soil properties jointly affect soil feedback (table S1). Additional variables explaining more than 10% of variation in the feedback index, and not strongly correlated with the best predictor within each variable group, were also included in the path analysis. Within the set of abiotic soil properties, many variables were highly correlated and aligned closely with the first principal component. Hence, the latter was included in the path analysis to reflect the major axis of variation in abiotic soil properties. For the analysis of specific feedback, AIC scores with a sample size of 55 were calculated, as our dataset contained 55 mesocosms in the conditioning stage, representing true replicates in plant trait and soil measurements.P values higher than 0.1 were sequentially dropped (table S4).Path analysis was used to test whether fungal communities  in conspecific and heterospecific soil affected plant-soil feedback and whether soil abiotic properties and plant traits have a direct or microbially mediated indirect effect on plant-soil feedback. Plant traits could be affected by soil abiotic conditions [i.e., phenotypic plasticity . For conspecific soil properties, paths significant at To confirm that the diversity of putative pathogens and AM fungi were better predictors of biotic feedback than differences in fungal composition, Mantel tests were performed to assess the correlation between biotic feedback and fungal composition (based on Bray-Curtis distances and Hellinger-transformed data). The strength of this correlation was compared to the correlation between biotic feedback and fungal diversity obtained from the analogous Mantel test.To test for the sensitivity of specific soil feedback to variation in soil fungal composition, pairwise dissimilarities between individuals of each species grown in conspecific versus heterospecific soils were calculated using log-transformed biomass and fungal sequencing data. Microbial dissimilarity was calculated as the Bray-Curtis distance based on the relative abundance data with Hellinger transformation [package vegan, function vegdist in R 3.4.0 (


Habitat contamination can alter numerous biological processes in individual organisms. Examining multiple individual-level responses in an integrative fashion is necessary to understand how individual health or fitness reflects environmental contamination. Here we provide an example of such an integrated perspective based upon recent studies of an amphibian  that experiences several, disparate changes when larval development occurs in a trace element–contaminated habitat. First, we present an overview of studies focused on specific responses of individuals collected from, or transplanted into, a habitat contaminated by coal combustion residues (CCR). These studies have reported morphological, behavioral, and physiological modifications to individuals chronically interacting with sediments in the CCR-contaminated site. Morphological abnormalities in the oral and tail regions in contaminant-exposed individuals influenced other properties such as grazing, growth, and swimming performance. Behavioral changes in swimming activities and responses to stimuli appear to influence predation risk in the contaminant-exposed population. Significant changes in bioenergetics in the contaminated habitat, evident as abnormally high energetic expenditures for survival (maintenance) costs, may ultimately influence production pathways  in individuals. We then present a conceptual model to examine how interactions among the affected systems  may ultimately bring about more severe effects than would be predicted if the responses were considered in isolation. A complex interplay among simultaneously occurring biological changes emerges in which multiple, sublethal effects ultimately can translate into reductions in larval or juvenile survival, and thus reduced recruitment of juveniles into the population. In systems where individuals are exposed to low concentrations of contaminants for long periods of time, research focused on one or few sublethal responses could substantially underestimate overall effects on individuals. We suggest that investigators adopt a more integrated perspective on contaminant-induced biological changes so that studies of individual-based effects can be better integrated into analyses of mechanisms of population change.


Relationships with adult children play an important role in older adults’ well-being. However, little is known about the association between parent-child relations and aging parents’ sleep quality, which is an emerging health issue that is closely related to individuals’ physical and mental well-being in later life. With the largest aging population, China has experienced rapid changes of family structure and traditional norms regarding parent-child ties. This study focused on different dimensions of parent-child relationships  in Chinese aging families. This study examined the association between parent-child relationships and older parents’ sleep quality, comparing one-child and multiple-children Chinese families. Utilizing the 2014 wave of the Chinese Longitudinal Aging and Social Survey, we analyze data from 8,450 respondents (aged 60+) who had at least one living child. Descriptive analysis showed that parents with multiple children engaged in more intense financial exchanges, less frequent instrumental support, and lower levels of emotional closeness with their adult children compared to their counterparts with only one child. Logistic regression models revealed that older parents who received more instrumental support were more likely to report sleep difficulty in both one-child and multiple-children families. For parents with multiple children, the overall level of financial transfers from children was negatively associated with having sleep difficulties, while the variability of financial transfers across multiple children was positively associated with having sleep difficulty. Findings highlight the importance of considering family dynamics in studying sleep quality among Chinese older adults.


To review recent studies investigating hypothalamic-pituitary-adrenal axis function in children and adolescents with disruptive behavior disorders (DBDs) and adults with antisocial personality disorder. We consider key concepts and methodological issues in cortisol assessment and review studies investigating basal cortisol secretion and stress reactivity in antisocial populations. Lastly, we consider whether cortisol abnormalities predict prognosis or treatment outcomes and the impact of exposure to adversity on hypothalamic-pituitary-adrena (HPA) axis activity.Studies tracking cortisol levels across the day and assessing cortisol awakening responses (CARs) have reported broadly intact, but flatter, diurnal rhythms and lower CARs in children and adolescents with DBDs, whereas findings in antisocial adults have been mixed. Cortisol hyporeactivity to stress is consistently reported in male antisocial populations, whereas no comparable data exist in females.Severe antisocial behavior is associated with cortisol hyporeactivity to stress, and such hyporeactivity predicts poor treatment outcomes. Further research investigating sex differences and the impact of adversity is needed. Harmonization of methods for assessing hypothalamic-pituitary-adrenal axis function and antisocial behavior would enhance progress in this area. In this article, we review recent research on hypothalamic-pituitary-adrenal (HPA) axis function in child and adult antisocial populations, focusing particularly on conduct disorder (CD) in children and antisocial personality disorder (ASPD) and psychopathy in adults. To test theories proposing that low physiological arousal or hyporeactivity is causally related to the etiology of antisocial behavior, researchers have investigated whether CD or ASPD is associated with lower basal cortisol levels or blunted cortisol responses to stress. We start by providing an overview of the HPA axis and its functions, and outline key methodological developments in this area. We then review evidence for disturbances in basal cortisol secretion and cortisol hyporeactivity in children and adolescents with CD and disruptive behavior disorders (DBDs) more generally . We subsequently consider studies on cortisol secretion under basal conditions and stress reactivity in adults with ASPD or psychopathy. Finally, we discuss whether HPA axis abnormalities predict treatment outcomes or normalize following successful treatment, and also whether such abnormalities reflect the consequences of exposure to early adversity which is frequently present in these individual backgrounds.The HPA axis is the main physiological system which mediates the body’s stress response. The paraventricular nucleus of the hypothalamus releases corticotrophin-releasing hormone in response to threat signals from brain regions such as the amygdala . CorticoGiven this rhythmicity and physiological response to waking, it is important to assess patterns of cortisol secretion across the day (including the CAR) when assessing whether individuals with psychiatric disorders display HPA axis abnormalities. However, relatively few studies on antisocial behavior have adopted such methodological approaches, instead largely relying on single-point determinations of cortisol levels . In fact, rather than just assessing cortisol several times within the same day, some researchers have argued that cortisol should be measured over multiple days to yield robust findings . It is aIn the following sections, we consider recent studies investigating diurnal cortisol secretion and the CAR, as well as cortisol reactivity to stress, in children and adolescents with DBDs and adults with ASPD or psychopathy. Given that the ASPD diagnostic criteria require the individual to have had CD prior to age 15 , substanIn an important early study, Popma et al. (2007) investigated diurnal cortisol secretion and the CAR in adolescent boys attending a delinquency diversion program, comparing those with and without DBD diagnoses with healthy controls •. AlthouFairchild et al. (2008) adopted a similar design, investigating diurnal cortisol rhythms and the CAR over three consecutive days in males with either childhood-onset or adolescence-onset CD and healthy controls. The aim was to assess whether cortisol abnormalities were specific to childhood-onset CD . There were no significant group differences in morning cortisol levels or CAR magnitudes, although evening cortisol levels were elevated in both CD subgroups, consistent with a flatter diurnal rhythm overall •.n = 36) and typically developing boys (n = 36). Although broadly similar cortisol diurnal rhythms were observed in both groups, there was some evidence for an attenuated CAR and lower cortisol levels at 12:00 h in the CD group. When the childhood-onset CD group was split into those with versus without callous-unemotional (CU traits), the CD/CU+ group showed a smaller CAR than the controls, although there were no group differences in diurnal cortisol secretion [Extending this work, von Polier et al. (2013) investigated the CAR and diurnal rhythm in boys with childhood-onset CD  of detained adolescents and healthy controls . The authors assessed the impact of CU traits and impulsivity to examine whether low cortisol was specifically associated with CU traits. There were no group differences in overall cortisol secretion or diurnal slope, and no significant associations between CU traits or impulsivity and cortisol levels. However, the study relied on self-report measures of CU traits and impulsivity did not assess the CAR, and the ‘healthy control’ group included participants with subclinical levels of CD symptoms.Another recent study  investigAlthough they did not use categorical CD/ODD diagnoses, Ruttle et al. (2011) and Salis et al. (2016) examined concurrent and longitudinal associations between externalizing behavior and cortisol secretion in children. Ruttle et al. (2011) found that externalizing behavior was related to blunted cortisol rhythms, both concurrently and longitudinally, but the longitudinal associations with cortisol were stronger •. This iIn another important study, Platje et al. (2013) examined longitudinal relationships between the CAR and aggressive and rule-breaking behavior in a large community sample of adolescents. Persistently elevated aggression was associated with smaller CARs over a 3-year period, whereas there was no association between rule-breaking behavior and CAR magnitudes ••, suggecortisol reactivity to stress in children and adolescents with DBDs. These studies have yielded a more consistent pattern of results—particularly those using effective stressors such as the trier social stress test for children Trier Social Stress Test for Children (TSST-C) or the frustration/provocation task.Having reviewed recent work investigating basal cortisol secretion, we now consider studies examining Van Goozen and colleagues , 21 condPopma et al. (2006) investigated cortisol and subjective responses to stress  in adolescents referred to a delinquency diversion program, with versus without DBD diagnoses, and a healthy control group. The DBD+ group again showed lower cortisol responses to stress than the controls, despite displaying the expected increase in negative mood . On the n = 165), but was limited by relying on retrospective reports regarding the age-of-onset of CD (thus some participants may have been misclassified), and did not investigate the impact of CU traits on cortisol reactivity.Fairchild et al. (2008) extended this work by examining whether cortisol hyporeactivity to stress was specific to childhood-onset CD. The authors compared male adolescents with childhood-onset and adolescence-onset forms of CD and a healthy control group. Both CD subgroups showed attenuated cortisol (and cardiovascular) responses to stress compared with controls, despite reporting strong increases in negative feelings during the experiment, which used the frustration/provocation task •. This sStadler et al. (2011) addressed the latter issue when examining cortisol reactivity to stress in a sample of children with a primary diagnosis of ADHD, many of whom had comorbid DBDs, by splitting their sample into those with high versus low levels of CU traits. The participants with elevated CU traits showed weaker cortisol responses to the TSST-C than the low CU traits subgroup, even though these subgroups did not differ in subjective mood responses . Unfortucortisol recovery following stress. Lower basal cortisol levels were observed in the pure ODD/CD group alone. No differences in cortisol reactivity were observed between the ODD/CD and control groups, although CD symptoms were inversely related to reactivity on a dimensional level and ODD/CD + ANX participants tended to show higher  cortisol reactivity than their pure ODD/CD counterparts [cortisol recovery following stress, and distinguishing between those with and without comorbid anxiety disorders. It suggests that failing to take account of internalizing comorbidity might explain some of the inconsistent findings in the DBD literature. Hartman et al. (2013) provided further evidence to support this notion by studying a large, mixed-sex sample of adolescents with preadolescent externalizing or internalizing diagnoses. Self-reported internalizing symptoms predicted greater cortisol secretion, whereas self-reported externalizing symptoms predicted lower cortisol secretion under stressful conditions [Recent studies have examined the impact of common comorbidities on cortisol reactivity to stress in CD. Schoorl et al. (2016) compared boys with ODD/CD alone and ODD/CD plus comorbid anxiety disorders (ODD/CD + ANX) in terms of basal cortisol, cortisol reactivity to stress, and terparts •. Finallnditions . Associan = 95) and those with ADHD+CD (n = 107) in terms of basal cortisol levels and cortisol reactivity to stress. There were no differences between these groups in basal cortisol, whereas the ADHD+CD group showed blunted cortisol reactivity to stress relative to the ADHD-only group [positively related to baseline cortisol, but negatively related to cortisol reactivity to stress. CU traits were not significantly related to either cortisol measures. This study provides further evidence that ADHD is not associated with cortisol reactivity in its own right, rather, it is CD/ODD that leads to cortisol hyporeactivity.In another interesting study, Northover et al. (2016) compared male children and adolescents with pure ADHD  are associated with cortisol hyporeactivity to stress . Such hyporeactivity is observed in children and adolescents and appears to be present in both childhood-onset and adolescence-onset forms of CD. As some studies have indicated that CU traits may be an important determinant of cortisol hyporeactivity, whereas others have shown no impact of CU traits, an important issue for future research is whether CD symptoms or CU traits are more influential in determining cortisol reactivity. This should be addressed in both clinical samples in which the full range of CD symptoms and CU traits are observed and in high-risk and community samples. The statistical analyses should also test whether CD symptoms and CU traits exert effects in opposite directions . Furthermore, as previous studies focused largely on males, cortisol diurnal rhythms and stress reactivity should be investigated in females with DBDs and varying levels of CU traits.Cima and colleagues (2008) investigated morning and afternoon cortisol secretion in male psychopathic and nonpsychopathic prisoners and a healthy control group . All three groups showed a normal diurnal profile, with cortisol levels being significantly higher in the morning than in the afternoon. Neither prisoner group differed from controls at any time-point, but the nonpsychopathic prisoners had higher cortisol levels than the psychopathic prisoners at two of the four time-points (8:00 and 14:00 h), suggesting hyperarousal in the former group •. HoweveSimilarly to Cima, Loomans et al. (2016) measured the CAR and afternoon and evening cortisol levels in male psychiatric inpatients and two healthy comparison groups . The authors investigated whether diurnal cortisol rhythms could differentiate between ASPD and psychopathic patients, and also between those with personality disorders and the general population. No differences in cortisol secretion between the personality-disordered groups were found, whereas both the ASPD and psychopathic groups  tended to show higher cortisol levels than the general population sample . This wan = 49) [A few studies have investigated relationships between psychopathic traits and cortisol reactivity to stress. For example, Johnson et al. (2015) assessed baseline cortisol levels and cortisol responses to the TSST in young adult male offenders (n = 49) . There wn = 49) , whereasn = 49) . A limitpositive associations. Nevertheless, studies with stronger methodological designs (including measurements of the CAR) are needed to draw firmer conclusions and investigate which aspects of the diurnal profile are affected.The majority of the studies described above investigated HPA axis activity in males alone. However, both sexes may display severe antisocial behavior and it is therefore important to consider similarities and differences between the sexes. Studies examining relationships between basal cortisol and CD symptoms in community samples have yielded mixed results, with Young et al. (2012) finding a positive association between CD symptoms and salivary cortisol levels in females, whereas a nonsignificant negative association was observed in males . SimilarIn terms of cortisol reactivity to stress, Kobak et al. (2009) found that sex moderated associations between antisocial behavior and cortisol responses to conflict discussions with caregivers in a community sample of adolescents . SpecifiAn early study by van der Wiel et al. (2004) investigated this important issue, examining whether cortisol reactivity to stress predicted treatment response in boys with oppositional defiant disorder. Lower cortisol reactivity at baseline predicted higher posttreatment aggression levels , suggestMore recently, Schoorl et al. (2017) investigated whether cortisol reactivity to stress or recovery after stress predicted outcomes in boys with DBDs who were treated using a parent training intervention. Boys who showed higher reactivity and more pronounced recovery following stress at baseline showed greater reductions in aggression over a 1-year period . Althougadaptation to early life stress or chronic adversity that would otherwise overwhelm the HPA axis and lead to neurotoxic effects of elevated stress hormones on the developing brain [An important question is whether cortisol hyporeactivity to stress or lower CARs in those with antisocial behavior are genetically determined or whether such abnormalities represent an ng brain ••. Exposng brain , 41, andng brain •. It theng brain , may undng brain •. A corosubjective responses to stress or lower basal cortisol, is difficult to reconcile with existing theoretical models, such as the sensation-seeking, underarousal, or fearlessness models of antisocial behavior [The finding that severe antisocial behavior is associated with cortisol hyporeactivity to stress, but not attenuated behavior , 45. Thebehavior , it seembehavior . Blair hbehavior . In contbehavior . HoweverIn summary, recent research using state-of-the-art methods to characterize the cortisol diurnal rhythm and CAR in children, adolescents, and adults with severe antisocial behavior has yielded mixed findings. Overall, the diurnal rhythm appears to be intact in antisocial populations, although flatter diurnal slopes and smaller CARs have been reported—especially in adolescents with DBDs. In contrast to these mixed, but mostly negative, findings for basal cortisol, studies investigating cortisol reactivity to stress have yielded consistent evidence for hyporeactivity in children and adolescents with DBDs and adults with ASPD or psychopathy. Nevertheless, heterogeneity within antisocial behavior and psychiatric comorbidity both appear to influence cortisol reactivity, as CU traits appear to be associated with a more pronounced pattern of hyporeactivity whereas comorbid internalizing disorders predict heightened cortisol reactivity and impaired recovery following stress. As most research has focused on males, an important direction for future research is to investigate diurnal cortisol rhythms and stress reactivity in girls with DBDs and women with APSD. Researchers should also move away from using single-point determinations of cortisol, instead tracking cortisol levels across the day and the CAR to deepen our understanding of HPA axis-antisocial behavior relationships. Finally, longitudinal research designs that allow researchers to examine whether cortisol abnormalities predict the emergence or escalation of antisocial behavior over time, and also whether cortisol secretion normalizes in those who desist from antisocial behavior, will be important in understanding causal relationships between these constructs and identifying intervention targets.


Although life longevity has increased across the world, evidence suggests some heterogeneity of the ageing process across individuals. To investigate different ageing patterns, the ATHLOS project harmonised data from 411,000 individuals across 17 existing cohort studies. The harmonised dataset provides comparable information on functioning measures, cognition, mental health, sociodemographic and lifestyle behaviours. To measure the process of healthy ageing across time and cohorts, we employed a Bayesian Multilevel Item Response Theory(IRT) and created a common metric of health status by using items of functioning. The IRT measurement model includes parameters describing the difficulty and discriminatory power of each item. We adopted the Bayesian Multilevel framework as it allows item parameters to vary among studies and the simultaneous estimation of all parameters under a Markov Chain Monte Carlo(MCMC) method. Finally, we assessed the predictive validity of the metric against mortality by performing a Receiver Operating Characteristic(ROC) curve analysis.


Factor V Leiden (FVL) is the most common inherited hypercoagulable condition. It is a genetic disorder caused by a missense mutation that prevents inactivation of Factor V in the clotting cascade, leading to overproduction of thrombin and excess clotting. This pathophysiological process is especially unfavorable in patients undergoing free tissue transfer. Many authors have noted a propensity for both venous and arterial thrombosis leading to partial or complete flap loss. To date, there have been no published reports of patients with FVL undergoing deep inferior epigastric perforator flap reconstruction without flap complications. Here, the authors present two cases of successful free tissue transfer for breast reconstruction in patients with diagnosed FVL. The perioperative thromboelastography lab values are evaluated to help guide anticoagulation regimen for these high-risk procedures. Microsurgical procedures performed by skilled surgeons have shown a relatively low complication rate. In those rare instances of adverse events, the most common indication for reoperation in microvascular surgery is pedicle thrombosis . Most miThe first case describes a 48-year-old female who had an established diagnosis of heterozygous FVL with a positive family history and was diagnosed with left breast cancer in October 2010. She presented to our institution in November 2013 with painful capsular contracture from prior implant-based reconstruction and a desire for bilateral autologous reconstruction. After detailed counseling regarding her operative risks, she underwent bilateral implant removal, capsulectomy and bilateral sensate DIEP flaps. There were no significant perioperative adverse events. The patient received 3000 IU of intravenous unfractionated heparin (UFH) after both sets of anastomoses were performed. At her 2-year follow-up at our institution in early 2016, the patient was in good health with her flaps sensate and well-perfused . The authors adhered to the Declaration of Helsinki at all times.


OBJECTIVES/SPECIFIC AIMS: Incomplete spinal cord injury (iSCI) is a life-long disability that typically results in a profound loss of locomotion capability. Current rehabilitation methods rarely restore full community ambulation, which in turn limits quality of life. Most individuals with iSCI exhibit persistent deficits in eccentric muscle control and reach recovery plateaus below the levels necessary for independent community ambulation. Eccentric motor control is essential during the weight acceptance phase of gait, which is emphasized during downhill walking. METHODS/STUDY POPULATION: The overground locomotion of subjects with chronic iSCI was analyzed both prior to and following a 12-week downhill body-weight-supported treadmill training regimen and compared to that of matched healthy controls in terms of kinematics, kinetics, and EMG activation. RESULTS/ANTICIPATED RESULTS: We expect to find significant differences between the controls and subjects with iSCI, with deficits in eccentric motor control accounting for some of these differences. In addition, we expect the downhill training to yield significant improvement in eccentric muscle control that translates into improvements in functional, overground walking for the subjects with iSCI. DISCUSSION/SIGNIFICANCE OF IMPACT: The goal is to determine if downhill training can improve eccentric motor control and extend recovery beyond established plateaus. OpenSim modeling of the experimental data will help quantify changes in eccentric control of individual muscles to clarify where specific gains are made.


Transcranial Doppler (TCD) is a bedside, low-cost, and non-invasive technique able to evaluate cerebral hemodynamics ; the impWe discussed herein on how we use TCD in neuro-critically ill patients for hemodynamic indications; some of these proposals could also be used in non-brain injured critically ill patients at a high risk of cerebral complications.When the indications for invasive intracranial pressure (ICP) monitoring are met, we recommend intraparenchymal or intraventricular probes, as TCD cannot substitute invasive ICP measurement . HoweverAlthough the diagnosis of brain death is based on neurological examination, we use routinely TCD as an ancillary test to demonstrate the absence of cerebral blood flow (CBF) . We use We assess cerebral autoregulation (CA) at the bedside as altered CA is related with a poor outcome in many diseases and may increase the risk of cerebral damage . In caseDetection of cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) is crucial as this is one of the main determinants of delayed cerebral ischemia and poor neurological outcome in this setting . AlthougWe often use TCD to monitor brain hemodynamics in critically ill patients. Future TCD development, such as the assessment of the compliance of arterial and cerebrospinal fluid compartment as well as critical capillary closing pressure, will further expand its use in this setting .Additional file 1: Table S1. Factors that may influence pulsatility index (PI) and flow velocities. (DOCX 13 kb)


Tribulus terrestris were more prominent in raising LH and Testosterone levels  whileThe mechanisms of action of these phytotherapics are poorly understood, especially for the less-studied Anacyclus pyrethrum. This herb has been proposed for different conditions , althprimum non nocere which should be always applied when proposing any therapy, including herbal therapies. When studying any treatment for a specific condition, is important to have a more global perspective, evaluating potential side-effects of the proposed medication. Specifically, for Tribulus terrestris, our group recently showed this herb leads to arterial blood pressure increase and renal morphology alteration with glomerular loss (Since the ancient Greece Hippocrates advocated the principle of lar loss . This ki


Dear Editor,Organophosphate insecticides (OPI), derived from phosphoric, phosphonic or phosphinic acids, find application as agents for controlling insect pest populations. OPIs elicit their characteristic toxicity by phosphorylating and inhibiting the enzyme, acetylcholinesterase (AChE). Cholinergic stress resulting from overstimulation of nicotinic- and muscarinic acetylcholine receptors is the chief mechanism of acute toxicity of OPI (Fukuto, 1990; Abou-DoA large number of animal studies explicitly demonstrate that OPIs have the propensity to cause hyperglycemia, perturbations in carbohydrate metabolism and endocrine dysregulations. Repeated exposure to OPI precipitates insulin resistance (studies listed in Table 1Authors are thankful to Jain University, Bangalore for the support.The authors declare no conflict of interest.


This research examined the relation between physical activity, pain, and mood among older adults with osteoarthritis (OA). Physical activity is associated with long-term maintenance of function in persons with chronic pain , but less is known about the association between objective measures of activity and transient mood states. Therefore, we captured the activity and mood levels of 218 older adults with knee OA over a seven-day period. Wrist and waist accelerometers captured small and large motor movements. Self-reported momentary pain and affect were collected through phone calls four times daily. We examined average and peak activity levels over the 4-hour windows between self-reports. Cross-sectionally, there was no association between momentary pain and activity. Average large motor movement was positively associated with positive affect and negatively associated with negative affect. Analyses revealed one association between affect and average previous activity; small motor movements predicted greater positive affect. Peak levels of both movements predicted greater positive affect, but only peak wrist activity predicted negative affect. Peak small motor movement at the previous call was associated with both positive and negative affect. These results provide insight into the unique contributions of small and large motor activity to mood and pain states. It appears that average large motor movements and prior small motor activity may have the greatest impact on momentary affect. Further study of distinct activity types and mood will be important for understanding and improving the quality of life among individuals diagnosed with OA (Supported by R01-AG041655).


Individuals who identify as lesbian, gay, bisexual, transgender or other non-heterosexual or binary gender identifiers (LGBTQ) face tremendous obstacles in search of quality healthcare. Older LGBTQ adults face these obstacles in the setting of more complex health problems with few social services and support. Negative treatment from healthcare professionals has proven to be one of the most pervasive barriers to care faced by older LGBTQ adults. Sensitization training with the film, Gen Silent, is one way knowledge gaps and biases of healthcare professionals has been addressed. By utilizing the survey previously validated by Porter et al., health professionals’ knowledge, perceptions, and attitudes toward LGBTQ older adults before and after viewing Gen Silent were assessed in Lehigh Valley Health Network (LVHN)-affiliated primary care practices. The principle outcome of this study was a statistically significant change in responses. Primary care practices were recruited for 45-minute sessions that included the showing of an educational, abbreviated version of Gen Silent to available staff. It was preceded by administration of a pretest survey and followed by a posttest survey and discussion. A paired t-test was conducted to determine significance of differences between pre- and posttest responses. Seventeen individuals (N=17) viewed the film and finished pre- and posttest surveys. Nearly all questions exhibited changes between pre- and posttests. Significantly, respondents indicated increased awareness of additional barriers to care faced by LGBTQ older adults compared to heterosexual peers. While limited, these results indicate that primary care professionals would benefit from training specific to the aging LGBT population.


This study operationalized the third dimension of Rowe & Khan’s Successful Aging model, social engagement, as neighborhood connectedness. We examined 2820 older adults in the MIDUS III dataset to assess the impact of neighborhood connectedness on life satisfaction and daily spiritual experiences. A composite scale for neighborhood connectedness (Cronbach = .745) was created. Linear regression analysis was undertaken for life satisfaction on daily spiritual experience, neighborhood connectedness, neighborhood environment and age controlling for gender, co-habitation, income, and disability. Regression analysis was also conducted for daily spiritual experience on the same variables. Analysis for each outcome variable was run three times to explore changes across three age groups of older adults . Results of regression analysis found frequency of daily spiritual experience was a substantial and significant predictor of life satisfaction for all age groups  Additionally, regression analysis revealed a higher level of neighborhood connectedness was the most powerful predictor of daily spiritual experience across all age groups  This study demonstrates the applicability of operationalizing the Successful Aging model’s social engagement dimension as neighborhood connectedness. This study also contributes evidence of the impact of daily spiritual experience on life satisfaction. Finally, the study supplies promising new evidence linking neighborhood connectedness with spiritual well-being.


The benefits of mobility devices for knee Osteoarthritis Patients include reducing burden of knee joint, enhancing confidence and increasing autonomy, yet many who might benefit from using mobility devices do not use them. The purpose of this study is to explore the cognition and using experiences about mobility devices use in patients with knee osteoarthritis of China. Naturalistic inquiry research was adopted, 15 patients with knee osteoarthritis were recruited and Semi-structured interviews were conducted. Data were analyzed based on conventional content analysis methodology. Two themes of using experiences about mobility devices were extracted, including positive feelings, negative feelings. Cognition about mobility devices use included light consciousness, incorrect attitude. Mobility devices have a positive effect on knee osteoarthritis patients, but some patients lack sufficient understanding and face many problems in the use of mobility devices. Policy Support, greater physician involvement, positive peer modules, and safe, visually appealing devices would promote greater acceptance and satisfaction of mobility devices with knee osteoarthritis patients.


Transcranial Direct Current Stimulation (tDCS) is a potentially useful tool to improve upper limb rehabilitation outcomes after stroke, although its effects in this regard have shown to be limited so far. Additional increases in effectiveness of tDCS in upper limb rehabilitation after stroke may for example be achieved by (1) applying a more focal stimulation approach like high definition tDCS (HD-tDCS), (2) involving functional imaging techniques during stimulation to identify target areas more exactly, (3) applying tDCS during Electroencephalography (EEG) (EEG-tDCS), (4) focusing on an effective upper limb rehabilitation strategy as an effective base treatment after stroke. Perhaps going even beyond the application of tDCS and applying alternative stimulation techniques such as transcranial Alternating Current Stimulation (tACS) or transcranial Random Noise Stimulation (tRNS) will further increase effectiveness of upper limb rehabilitation after stroke. Impaired arm function after stroke is both frequent and a considerable burden for people with stroke and their caregivers. An emerging approach for enhancing neural plasticity after acute and chronic brain damage, thus enhancing rehabilitation outcomes in the upper limb rehabilitation after stroke, is non-invasive brain stimulation (NIBS), for example delivered by transcranial direct current stimulation (tDCS) . tDCS isMany small trials regarding the effects of tDCS on arm motor function poststroke were undertaken in the past with partly promising but not conclusive results , 3. BaseThe problem of limited focal specificity of tDCS may lead to an ineffective stimulation and in turn may be reduced by the application of HD-tDCS, which involves up to five small electrodes, arranged in a ring, instead of two big conventional sponge electrodes for delivering direct current. The positioning of HD-tDCS for improving arm motor function after stroke has been described elsewhere.  On the oTDCS during fMRI has already successfully been applied in language production tasks in healthy people and in people with stroke . MeinzerBased on EEG data, it is possible to measure cortical activity after or even during tDCS with superior temporal resolution . There aSince tDCS enhances neuroplasticity by modulating cortical activity, the application of an efficient base therapy, resulting in sufficient cortical activity, is still crucial. Therefore is has to be kept in mind that tDCS has to be applied in combination with an appropriate and individually selected and effective arm training: For instance in people with severe arm paresis it makes sense to apply electromechanically-assisted arm training whereas in people with only minor arm paresis a forced use paradigm seems to be promising to improve arm function and to overcome learned non use. There is a considerable evidence base regarding effective base treatments during tDCS for improving upper limb rehabilitation outcomes poststroke.An alternative to tDCS could be the application of transcranial Alternating Current Stimulation (tACS) to increase excitability . tACS aiAnother recent non-invasive approach to brain stimulation is transcranial Random Noise Stimulation (tRNS) . tRNS deThe mode of action of tDCS is not fully understood yet, which has implications for its clinical application: for example, tDCS suffers from a lack of focality of stimulation, and attaining neurophysiological data in adequate spatial and temporal resolution for further exploration of its mode of action remains challenging. HD-tDCS may be a one tool for reducing variability in future tDCS trials in upper limb rehabilitation after stroke by increasing focality of stimulation. Together with tDCS during fMRI, which allows for superior spatial resolution, online EEG-tDCS delivering superior temporal resolution could give valuable insights into tDCS mechanisms. Hopefully, this will improve our understanding of tDCS in upper limb rehabilitation in people with stroke and corollary also its clinical application. However, with tDCS being rather a facilitatory intervention thus needing an effective base treatment resulting in sufficient neuroplasticity, it requires efficient interventions delivered by therapists .Particularly from the perspective of clinicians, it eventually should be kept in mind that despite the currently considerable research interest in tDCS, it is still likely that tDCS reveals only small or even no additional benefits to arm rehabilitation after stroke.


There is solid epidemiological evidence demonstrating that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing colorectal cancer, and to a lesser extent gastric and esophageal cancers[1]. Importantly, NSAIDs suppress colon polyp formation and progression in patients diagnosed with familial adenomatous polyposis coli (APC)[2]. In many animal studies, NSAIDs have been shown to prevent tumor formation and slow tumor progression, thus confirming and extending the clinical observations. Recent findings have demonstrated that NSAIDs inhibit angiogenesis, suggesting that the tumor suppressive activity of these drugs may be due, at least in part, to their ability to inhibit tumor angiogenesis[6]. The study of the mechanism by which NSAIDs suppress tumor angiogenesis, is matter of intense research.


Cognitive health, physical function, and chronic disease represent interdependent health outcomes that may exert influence on the course of each other’s development. To investigate the association between baseline health in each domain and developmental change across domains, we estimated trajectories of working memory, mobility limitations, and comorbidity among US adults age 65 and older over 18 years. We drew observations from the nationally-representative Health and Retirement Study with an analytic sample consisting of 5,963 adults age 65 and over in 1998. Immediate word recall, an 11-item Nagi scale of mobility limitations, and a summary count of eight doctor-diagnosed chronic conditions were measured biennially from 1998 to 2016. Parallel-process quadratic growth models with individually-varying time scores were used to estimate non-linear trajectories of each health measure, allowing identification of associations between baseline health and developmental change in each health process at both earlier and later stages of older adulthood. All estimates adjusted for covariates, complex survey design, and missing data. Greater baseline immediate word recall was associated with less rapid increase in mobility limitations at earlier ages. More baseline mobility limitations were associated with faster increase in comorbidity at earlier ages. Greater baseline chronic conditions were associated with more rapid increase in mobility limitations at later ages. These results highlight the importance of conceptualizing health among older adults as an interdependent and developmental process and should help clinicians recognize that single-domain health status may influence the progression of other health outcomes at different stages of older adulthood.


Background: Thoracic Aortic Injury (TAI) due to penetrating or blunt chest trauma is a critical life-threatening aortic injury. Its diagnosis and treatment always is challenging.mmHg despite multiple anti-hypertensive drugs. Trans-Thoracic Echocardiography (TTE) revealed abnormal Doppler flow pattern in proximal descending thoracic aorta suggestive for probable coarctation of aorta. Chest CT scan revealed pseudoaneurysm of the descending thoracic aorta just below the isthmus. Due to uncontrolled hypertension, persistent hemothorax and probable aortic pseudoaneurysm presenting as aortic luminal narrowing, surgical resection of the aneurysm was planned.An 18-year-old male was admitted due to blunt chest trauma after a high-impact road traffic collision. According to presenting dyspnea, an emergency chest-x-ray revealed left hemothorax for which chest tube was inserted. Hemodynamic monitoring demonstrated uncontrolled hypertension with systolic blood pressure of 200–220 The postoperative course was uneventful and blood pressure normalized without any drugs. Patient is normotensive after 8 years follow up. Thoracic Aortic Injury (TAI) due to penetrating or blunt (more common) chest trauma is the most frequent type of traumatic aortic injury and is a catastrophic and also final scenario in most circumstances . Blunt TAs aortic dissection may be associated with a hypertensive crisis, the patients must be ICU admitted and dedicated control of blood pressure is very important to reduce the progressive process of dissection.Once the clinical suspicion of acute aortic dissection is suggested, intravenous (IV) antihypertensive regimen should be started as soon as possible in emergency department in all non-hypotensive patients and continued in the intensive care unit or the operation room. Systemic blood pressures, urine output, consciousness, and focal neurologic signs should be regularly checked for any derangement owing to complications.Surgical techniques can be open surgery with a clamp-and-sew technique, surgery with the use of a vascular graft, and using heparin-less partial cardiopulmonary bypass. Recently new endovascular techniques have been largely introduced as a therapeutic choice in traumatic and non-traumatic aortic injury in descending and abdominal aorta.mmHg despite multiple anti-hypertensive drugs. Another CT scan revealed pseudoaneurysm of the descending thoracic aorta.An 18-year-old man with shortness of breath and left sided bloody pleural effusion was admitted in this center. The patient did not have any underlying disease. The patient was pale and bilateral lower extremity pulses were not palpable. There was history of blunt chest trauma after an acceleration- deceleration traffic collision 12 days ago. After resuscitation and stabilization of the patient, because of dyspnea and hemothorax, an emergency chest-x-ray showed left hemothorax and chest tube was inserted. Patient referred to tertiary lung disease center due to persistent dyspnea and admitted to ICU because of low O2 saturation. Hemodynamic monitoring in ICU demonstrated severe refractory uncontrolled hypertension with systolic blood pressure of 200–220 Bedside Trans-Thoracic Echocardiography (TTE) from suprasternal notch revealed abnormal continuous Doppler flow pattern in proximal descending thoracic aorta suggestive for probable coarctation of aorta  and aortThe patient underwent left sided thoracotomy and a transection of aorta in the posterior surface of aorta just after the isthmus was found which resulted in pseudoaneurysm formation. After excision, the aorta was repaired with a 16 mm Gore-Tex interposing graft .th post-operative day. Follow up imaging with Magnetic Resonance Imaging (MRI) revealed normal anatomy of the aorta without luminal narrowing two weeks after operation. No complication occurred and patient had normal blood pressure after 8 years follow up.The postoperative course was uneventful and blood pressure normalized without any drugs and the patient had full recovery on the 7Traumatic damages to aorta are accomplished with wide range of aortic damages including minimal aortic injury, aortic laceration or transverse aortic tearing. Aortic transection is also known as aortic rupture, aortic pseudoaneurysm and aortic intramural hematoma.Supine chest-x-ray is the initial screening test in the traumatic patient. A large autopsy survey reported that 97% of victims of aortic injury had additional traumatic damages in other regions. Indirect signs suggestive for aortic injury are mediastinal hematoma and widening or concomitant multiple rib fractures. Other imaging tests such as contrast enhanced-CT scan, Magnetic Resonance Angiogram (MRA), or aortic angiogram may be used to determine if aortic tear is present. Another noninvasive diagnostic test that may be used is bedside echocardiography that had been conducted for this patient and demonstrated TAI.Regarding the mechanism of refractory hypertension in this case, aortic luminal narrowing or kinking just after aortic injury site in isthmus with a pseudocoarctation physiology presenting as continuous Doppler flow pattern in descending aorta was completely normalized after successful surgical aortic repair.There are different guidelines for medical treatment of hypertension in these patients . Over thThe striking aspects of the case were new-onset refractory hypertension in previously normotensive young man and echocardiographic findings mimicking aortic coarctation as result of traumatic transection of aorta and amenability of lesion to surgery and complete correction of hypertension after surgical repair.Blunt traumatic TAI is a deadly catastrophe with disappointing survival rates, as confirmed by previous studies and immediate death rate of more than 75% , 12. In


Active citizenship is romanticized in policy for its role in keeping older adults healthy, and rural communities sustainable. However, as proportions of older adults resident in rural communities continue to increase, the gerontological literature has begun to highlight challenges associated with both the capacity and desire of rural older adults to be active citizens. Through an integrative review of the international literature, this paper interrogates how active citizenship trends among rural older adults support or hinder healthy aging in rural settings. Findings indicate that active citizenship among older adults can increase rural age-friendliness and facilitate individual wellbeing. However, practices associated with active citizenship among this cohort can disenfranchise certain groups of older adults, through reshaping societal norms relating to citizenship, age-friendliness and rurality. These findings indicate that programs designed to promote active citizenship must both consider, and account for, diverse capacities and desires for active citizenship among rural older adults.


Resting-state functional connectivity (FC), which measures the temporal correlation of spontaneous hemodynamic activity between distant brain areas, is a widely accepted method in functional magnetic resonance imaging (fMRI) to assess the connectome of healthy and diseased human brains. A common assumption underlying FC is that it reflects the temporal structure of large-scale neuronal activity that is converted into large-scale hemodynamic activity. However, direct observation of such relationship has been difficult. In this commentary, we describe our recent progress regarding this topic. Recently, transgenic mice that express a genetically encoded calcium indicator (GCaMP) in neocortical neurons are enabling the optical recording of neuronal activity in large-scale with high spatiotemporal resolution. Using these mice, we devised a method to simultaneously monitor neuronal and hemodynamic activity and addressed some key issues related to the neuronal basis of FC. We propose that many important questions about human resting-state fMRI can be answered using GCaMP expressing transgenic mice as a model system. Temporal correlation of spontaneous hemodynamic signals, commonly referred to as FC , is one Several groups have recently used transgenic mice expressing a genetically encoded calcium indicator (GCaMP) in neocortical neurons  to simulUsing this method, we examined the relationship between fast spatiotemporal patterns of neuronal calcium activity and the spatial pattern of FC. We found a significant relationship between two seemingly different types of large-scale spontaneous neuronal activities – namely, global waves propagating across the neocortex and transient coactivations among cortical areas sharing high FC. Different sets of cortical areas, sharing high FC within each set, were coactivated at different timings of the propagating global waves, suggesting that spatial information of cortical network characterized by FC was embedded in the phase of the global waves . FurtherThe proposed method also allows us to ask questions related to newly developed analyses methods for FC in human fMRI . In contThe temporal fluctuation of FC across short time-windows does not necessarily indicate non-stationary FC. Indeed, recent studies using resting-state fMRI in humans reported that the temporal fluctuation of FC cannot be distinguished from that in a model assuming stationary FC and statistical sampling error ,24. ApplThere are several future applications of the proposed method. For example, resting-state FC in mouse models of mental diseases can be used to examine the possibility of diagnosis based on resting-state FC . Genetic


Gerardo Ferbeyre , Francis Rodier,  and Daohong Zhou . In his welcoming speech, Dr. Ferbeyre summarized the key aspects that have attracted so much interest in cellular senescence including its ability to act as a tumor suppressor mechanism but also to promote aging and age-linked diseases , ICSA president Manuel Serrano  and NCI director Ned Sharpless . Dr. Sharpless presented in his keynote lecture how the key senescence gene and tumor suppressor p16INK4A acts as a double-edged sword to regulate aging, health span and cancer incidence.More than two hundred scientists gathered in Montreal on July 8, 2018 for the International Cellular Senescence Association (ICSA) Meeting to discuss the biological and medical impact of cellular senescence. The meeting was organized by diseases . The duaFrederic Lessard from the Ferbeyre laboratory , described the senescence-associated ribosome biogenesis defects and how they are linked to the inhibition of CDK4 via accumulation of ribosome-free RPS14. This work expands the extraribosomal functions of ribosomal proteins, which are now linked to both the p53 and the RB tumor suppressor pathways [Guadalupe-Elizabeth Jimenez  showed an intriguing connection between B-distroglycan and the nucleolus in senescent cells. Jiri Bartek , delivered the EMBO Keynote lecture summarizing the role of replication stress and the DNA damage response in cellular senescence [Fred Dick , presented novel roles of RB suppressing the expression of satellite repeats and regulating chromosome condensation [Karl Riabowol  presented a link between senescence and endocytosis via RB in cells that express the ING1a epigenetic regulator. Jesus Gil  and Mathieu Deschênes  presented data linking the control of alternative splicing to cellular senescence.nescence . Recent Xiaolu Yang  explained how p53 represses major forms of NADPH generation via distinct mechanisms, clarifying why reactive oxygen species and oxidative damage accumulate in senescent cells. Talks form Eiji Hara , Maria Grazia Vizioli  and Andrea Ablasser , provided links between DNA metabolism, the activation of the cGAS-STING pathway and the regulation of the senescence-associated secretory phenotype (SASP). Masashi Narita  summarized the dual role of autophagy in cancer and presented a mouse model where conditional inactivation of ATG5 altered cancer susceptibility. Frédérick A. Mallette  presented an intriguing connection between cholesterol 25-hydroxylase (CH25H) and cellular senescence. In a mouse model of retinopathy [Ch25h mRNA levels increased and correlated with induction of features of cellular senescence in the retina. Perhaps, related to this discovery, Dr. Hara presented evidence that another cholesterol metabolite, deoxycholic acid (DCA), induced senescence in liver cells; interestingly, DCA is produced by the gut microbiota during obesity in mice and facilitates the development of hepatocellular carcinoma [Several talks described a clear connection between senescence and metabolism. arcinoma .Andrei Gudkov  challenged several existing views of senescence from the analysis of the transcriptome of senescent cells and cells arrested by contact inhibition. Using principal component analysis he proposed that the gene expression pattern of senescent cells is a superposition of two components: one, which depends on the time cells are in culture without dividing, and the other one, which depends on the type of treatment. Oliver Bishof  also presented a kinetic transcriptome analysis of cells rendered senescent by oncogenic ras. He described an intriguing dynamic gene expression program driven by a hierarchical network of transcription factors reminiscent of a developmental process. Along the same lines, Judith Campisi discussed how multiple functional senescence-associated phenotypes are interlaced and dynamic in the senescence program, particularly in different cells types and tissue contexts, and presented a new effort to globally identify senescent cells surface molecules.Scott Lowe , who together with Manuel Serrano discovered the process of oncogene induced senescence, presented data explaining how cancer cells can be forced into an RB-dependent but p53-independent senescence using a combination of a MEK inhibitor with the CDK4 inhibitor palbociclib. Intriguingly, this treatment also engages NK cells to kill senescent tumor cells, underscoring the view that pro-senescence cancer therapies benefit from immune surveillance mechanisms. Regarding immune clearance of senescent cells, Christian Beausejour  revealed his efforts to develop novel humanized mouse models to better mimic interactions between senescent cells and immune cells. He showed that senescent human cells are not always immunogenic in this context, suggesting strong context-dependent effects and the importance of using relevant models. The importance of the elimination of senescent cells after treatment was highlighted in several talks. Clemens Schmitt  was the first keynote speaker of the meeting. He presented evidence for an underlying stemness gene expression signature in senescent cells. Cells that managed to escape from senescence, take advantage of this stemness program to form aggressive cancers [Konstantinos Evangelou  also focused on cells that escaped from senescence as demonstrated with a novel senescence biomarker (SenTraGorTM) [Corinne Abbadie  characterized the senescence response to irradiation in fibroblasts at the margin of an irradiated field. She explained that these cells accumulate single- stranded breaks but not double-stranded DNA breaks and they were able to escape from senescence giving rise to a progeny of mutated cells. From a more clinical angle, Francis Rodier explored the occurrence of therapy-induced senescence in human cancer patients particularly demonstrating that senescence occurs in response to ovarian cancer chemotherapy. Interestingly, the presence of senescence hallmarks in treated ovarian tumors predicted beneficial outcomes in patients, suggesting that senescence biomarkers could help inform cancer treatment strategies and that senescence becomes a target for pharmacological manipulation in human ovarian cancer therapy. Olivier Coqueret  presented data on TSP1 acting as a cytokine that prevents escape from senescence and described how its receptor CD47 regulates escape from the senescent arrest. Dr. Serrano presented data indicating that palbociclib, a CDK4 inhibitor approved for the treatment of some cancers, accumulates in lysosomes and this prolongs its biochemical effects explaining the induction of senescence even after a short period of exposure to the drug. The storage of palbociclib into lysosomes also accounts for its delayed and long-term release to the external milieu and the efficient induction of paracrine senescence, which in this case is mostly due to the drug and not to the SASP. Marco Demaria  further expanded on the use of CDKi to induce a potentially less inflammatory senescence response in normal and cancer cells, as he demonstrated the lack of a typical SASP in this context. He suggested that this could be beneficial in some therapeutic contexts, but harmful in others, as SASP-less senescence might alter normal immune clearance of senescent cancer cells. In summary, a theme emerged that any therapy that aims to induce or reinforce senescence in tumors should also be combined with strategies to prevent escape from senescence or to stimulate the elimination of senescent cells.A number of talks solidified the view that senescence is a powerful tumor suppressor mechanism.  cancers . KonstanraGorTM) . EscapedraGorTM) ,10. CoriJan Van Deursen  presented recent evidence that the elimination of senescent cells can induce regression of advanced atherosclerosis without any detectable side effects. Jennifer Hartt Elisseeff  showed that clearance of senescent cells using senolytics attenuates osteoarthritis development. The connection between senescent cells and immune responses to injury and repair was presented. Darren Baker  presented experimental evidence that senescent cells promote neurodegeneration in mutant tau mice [James Kirkland , showed that transplanting senescent cells to young mice caused frailty, diabetes and osteoporosis accelerating death from all causes. A cocktail of quercetin and dasatinib, a SRC-family kinase inhibitor, can kill senescent cells and revert their pathological effects both in senescent-cells transplanted young mice or in naturally aged mice, extending median life span up to 36% [Salvador Macip  found another kinase, BTK, which activates the tumor suppressor p53 inducing senescence [Irina Conboy  used parabiosis to demonstrate the presence of factors in the serum of old mice that can induce senescence in young mice suggesting that some senescent cells in vivo may originate from extrinsic factors. She also presented interesting data on enhanced myogenesis and reduced liver adiposity, but no improvement in hippocampal neurogenesis in the old 3MR mice, when p16-high cells were experimentally ablated. Albert Davalos (Buck Institute for Research on Aging) followed-up on his earlier discovery that the alarmin HMGB1 is a key regulator of the proinflammatory SASP [Myriam Gorospe,  identified proteins expressed at the surface of senescent cells. SCAMP4 was found to favor the SASP [Mei Wang  presented her work showing that mesenchymal stem/progenitor cells (MSPCs) in primary spongiosa of long bone during late puberty undergo a normal programed senescence. MSPC senescence is epigenetically controlled by the polycomb histone methyltransferase Ezh2 and its H3K27me3 mark. Loss of Ezh2-H3K27me3 in young mice leads to premature cellular senescence followed by impaired osteogenesis and bone loss, and antagonizing cellular senescence by manipulating epigenetic factors may be a potential approach to treat pediatric or juvenile osteoporosis. Maria Almeida  discussed the role of senescent osteocytes in age-related bone loss via production of increased levels of RANKL and the therapeutic potential of senolytic agents in preventing and treating osteoporosis by targeting senescent cells in the bones [Claude LeSaux  reported some new interesting findings that eicosanoids such as prostaglandins and leukotrienes may function as new SASP factors and play an important role in the pathogenesis of pulmonary fibrosis. Together these studies show the tremendous potential of senolytics to improve health at old ages.One of the most exiting trends in senescence research is the concept of senolysis or the specific elimination of senescent cells . Jan Vantau mice  and theip to 36% . Salvadonescence . Ibrutinory SASP  by showithe SASP . Mei Wanhe bones . Claude Daohong Zhou  presented some new development of Bcl-xl-targeted senolytic agents using proteolysis targeting chimera (PROTAC) technology. These Bcl-xl PROTACs that target Bcl-xl to an E3 ligase for ubiquitination and degradation exhibit an improved potency against senescent cells but reduced toxicity to normal cells and platelets compared to navitoclax or ABT-263 and thus have the potential to be developed as a safer senolytic agent. John Lewis  described a clinically viable gene therapy consisting of a suicide gene under a senescent cell promoter delivered in vivo with fusogenic lipid nanoparticles (LNPs) to deplete senescent cells. This approach represents a first-in-class therapeutic that targets cells based on transcriptional activity, rather than surface markers or metabolism. Guangrong Zheng  identified a dietary natural product, piperlongumine, as a novel senolytic agent. It can selectively kill senescent cells by targeting oxidation resistance 1 (OXR1), an important oxidative stress sensor that regulates the expression of a variety of antioxidant enzymes. His finding may lead to the development of better senolytic agents [Daniel Munoz-Espin  described the design of a new targeted-drug delivery system to senescent cells using the technology of the encapsulation of drugs with galacto-oligosaccharides because of the high lysosomal β-galactosidase activity of senescent cells. He showed that gal-encapsulated cytotoxic drugs can selectively target senescent cells in a tumor xenograft mouse model to improve tumor regression and toxicity. This senescent cell selective drug delivery method opens new diagnostic and therapeutic applications for senescence-associated disorders. At the end of the meeting Ned David  delivered a talk summarizing how his company is translating basic research on senescence into clinical trials using several senolytics. Senescence is undoubtedly at the forefront of biomedical research. The next ICSA meeting in Athens 2019 will reveal additional exiting research: stay tuned!The promise that clearance of senescent cells with a therapeutic agent may prolong the health span and treat age-related diseases stimulates the research in finding new senolytic agents, therapeutic strategies, and delivery methods. c agents . Daniel


Aging of the vasculature is the leading risk factor for cardiovascular and cerebrovascular disease . As suchThe healthy artery comprises endothelial cells (ECs), vascular smooth muscle cells (VSMCs) and the extracellular matrix (ECM), all of which are susceptible to damage or disruption during aging . The intRapid advances in geroscience have identified a ‘Molecular Signature’ for the aged vessel that represents distinct underlying intracellular and extracellular molecular processes . IntraceAlthough all of these processes are associated with vascular aging, it is unclear whether they are a cause or consequence of aging, how they are inter-related, and whether targeting one or more is sufficient to prevent or delay vascular aging. For example, we recently reported that mitochondrial function progressively deteriorates with aging of mouse arteries, associated with reduced mitochondrial DNA copy number (mtCN) and expression of enzymes that regulate mitochondrial DNA synthesis; we showed that increasing mtCN enhanced mitochondrial function and delayed the onset of multiple structural and functional parameters of vascular aging . Althoug+) booster nicotinamide mononucleotide (NMN) promoted angiogenesis and recapitulated the benefits of exercise via sirtuin 1-mediated inhibition of Notch signalling in aged exercised mice [In contrast, the ability of enhanced mitochondrial function since birth  to delay vascular decline suggests that preventative and early intervention are key to delay vascular aging. Indeed, several studies have demonstrated beneficial effects of long-standing lifestyle changes such as caloric restriction (CR) and exercise, and compounds that mimic these processes. For example, β-hydroxybutyrate, a ketone released naturally during CR, enhances cell division and protects against DNA damage and cellular senescence in ECs and VSMCs in older fasted mice via the Oct4-mediated LaminB1 pathway [sed mice .Vascular stiffness is a major link between normal vascular aging and development of vascular complications. Although the marked changes in ECM content and structure in aging influence vascular mechanical properties directly, aging also affects cell-ECM interactions, and the stiffness of VSMCs themselves. For example, VSMCs can take on a stiffness phenotype  dependenIn summary, identification of the distinct molecular pathways involved in vascular aging provides great potential for therapeutics. Research efforts should focus on disentangling the complex interactions between the molecular processes involved, and testing the feasibility and timing of administration of potential therapeutics that can limit the effects of oxidative stress, mitochondrial dysfunction, cellular senescence, and DNA damage. Arterial stiffness and central blood pressure (cBP) are excellent predictors of age-related complications  and can


Older adults are increasingly occupying multiple life roles, including working, caregiving, and volunteering, creating the opportunity for role conflict. Such conflict occurs when stress and strain created by the demands of multiple life roles outstrips an individual’s resources to successfully manage such demands. A two-phase research study was recently completed with 1,697 RSVP volunteers drawn from 55 RSVP program sites across the country (Phase I) with a follow-up survey of RSVP programs conducted with 17 sites (Phase II). Grounded in role theory, the Phase I volunteer survey explored role conflict in addition to self-reported strategies used to mitigate the experience of role conflict. The Phase II program survey gathered responses from volunteer managers and staff about the strategies used by their older adult volunteers to avoid and address role conflict. Based on findings from both surveys, caregivers engaged the following strategies in order to minimize role conflict: obtaining respite care, and volunteering alongside their care recipient. Worker-specific strategies focused largely on time management and included volunteering during off-work hours and completing time-limited volunteer assignments. While a high level of convergence was noted between volunteer manager and volunteer perspectives, two themes emerged from the volunteer survey that were not identified in program survey responses: seeking volunteer opportunities that leverage similar skills and experiences across roles and seeking volunteer opportunities that provide a different experience from that of other roles. Implications for future research and volunteer management strategies will be discussed.


This presentation will review the design, methods, and early lessons learned from the Making Engagement Meaningful through Organized Routine Interaction (MEMORI) Corps trial recently funded by NIA. This trial is evaluating the feasibility and efficacy of the MEMORI Corps program, a novel 12-week activity-based companion care model designed to mobilize and equip senior volunteers to deliver individualized, evidence-based activity programming to persons with dementia PWD living at home and offer family CGs needed respite. The intervention synthesizes and adapts prior evidence-based work from the Tailored Activities Program® (an activity-based intervention persons with dementia), Experience Corps® , and MIND at Home® (a home-based dementia care coordination program) to simultaneously address unmet respite care needs of family CGs, provide PWD structured meaningful activities and social engagement, and provide meaningful engagement and peer support opportunities for senior volunteers.


The Florida Department of Elder Affairs (DOEA) provides programs and services for over 65,300 older people and adults with disabilities. These individuals are uniquely vulnerable and may be displaced, and/or disoriented during natural disasters. DOEA clients are dependent upon community-based services to provide supervision or assistance to perform basic self-care, which often makes sheltering in place alone a danger to their health and well-being. During Hurricane Michael (2018) many older adults who previously were independent sought help for many issues including property damage, utility interruption, food and medicine scarcity, and physical or mental health problems associated with the storm and its aftermath. In normal conditions, DOEA identifies older populations via Census tracts and then conducts outreach events to inform the public how to access social services. However, after the widespread displacement post-storm, traditional outreach approaches were insufficient. A method was needed to remove areas that were rendered uninhabitable and find who remained in place. DOEA identified viable neighborhoods by overlaying property damage locations on base layers of Census tracts with concentrations of older adults and polling places with high percentage of age 60+ voter participation in the subsequent November election. Then in partnership with Feeding Florida, we provided information and registration assistance via local food distribution sites in those areas. This methodology of overlaying Division of Emergency Management property damage records and voter participation records against publicly available Census tract files is a strategy that could be replicated by other disaster and flood-prone communities or organizations that have similar needs.


Caring relationships between older residents and nurse aides are fundamental in terms of service delivery in nursing homes. However, little is known for the nuanced dynamics of this relationship in China. The purpose of this study is to explore how caring relationships develop between older residents and nurse aides in the nursing home setting in urban China. Informed by the dyadic perspective, this study illustrates the development process and relational nuances by simultaneously eliciting residents’ and nurse aides’ perceptions. This qualitative study purposively sampled 20 matched resident-nurse aide dyads (N= 40) in a government-sponsored nursing home in Shanghai. Participants participated in semi-structured, in-depth interviews from January to June 2017. Thematic analysis was performed. The findings reveal that the caring relationship began with nursing home assignment and primarily focused on instrumental assistance. Gradually, emotional involvement grew within dyads and reciprocity emerged. Based on different dyadic perceptions, this study conceptualized four types of caring relationships: (a) parent-child alike, (b) mutually respectful, (c) solo performance, and (d) reasonably detached. The findings suggest that residents and nurse aides could have different views on caring relationships, which further influenced the relationship development. The four types of caring relationships shared some similar traits while differentiating from some of the common types of interactions found in the existing nursing evidence across the world. Chinese filial tradition also influenced the relationship dynamics.


Purpose. to report malignant glaucoma and infectious crystalline keratopathy as complications after an uneventful Descemet Membrane Endothelial Keratoplasty (DMEK), and corneal clearance despite graft detachment after the surgery in a patient with pseudophakic bullous keratopathy. Method. A 81-year-old patient with high Intraocular Pressure (IOP) and flat anterior chamber with patent iridotomies after DMEK was diagnosed of malignant glaucoma. The medical approach being insufficient, the patient required a pars-plana vitrectomy, capsulo-hyaloidectomy, and surgical iridectomy. Results. The IOP was reduced and anterior chamber was repositioned after surgical management. Corneal clearance was observed despite graft detachment. The patient developed an infectious crystalline keratopathy after the resolution of malignant glaucoma. Conclusions. malignant glaucoma is a rare complication following DMEK. Corneal clearance can be attained despite graft detachment after DMEK probably due to an unintentional Descemet Membrane Endothelial Transfer (DMET). However, in low dosage, steroid treatment remains a risk factor for developing ICK. Abbreviations: PBK = Pseudophakic Bullous Keratopathy, DMEK = Descemet Membrane Endothelial Keratoplasty, DMET = Descemet Membrane Endothelial Transfer, IOP = Intraocular Pressure, BCVA = Best Corrected Visual Acuity, AC = Anterior Chamber, MG = Malignant Glaucoma, ICK = Infectious Crystalline Keratopathy  Nevertheless, DMEK is not without complications [2], graft detachment being the most common complication. Either air or expandable gas is used both in the straightforward surgery and in the “re-bubbling” procedure to treat graft detachment. The main cause of raised Intraocular Pressure (IOP) in the early postoperative period is usually a reverse pupillary block secondary to a full air or gas fill that pushes the iris backwards .Pseudophakic Bullous Keratopathy (PBK) is a common indication of corneal transplantation. Descemet Membrane Endothelial Keratoplasty (DMEK) is increasingly performed due to its excellent results, low graft rejection rate and reduced need of steroids . A careful differential diagnosis of MG should be undergone. Pupillary block presents a moderate depth of the central AC and iris bombée. Choroidal detachments and effusions are typically hypotonic. Suprachoroidal haemorrhage usually presents severe pain and is often preceded by hypotony [5]. Medical approach of MG is recommended during the first five days using mydriatic and cycloplegic agents in order to relax the ciliary muscle and retracting the lens-iris diaphragm. This can also be achieved by dehydrating the vitreous using hyperosmotics. Aqueous suppressants are used to decrease posterior pooling of aqueous humour. In refractory cases, Nd:YAG anterior hyaloidotomy should be considered in pseudophakic and aphakic eyes, allowing movement of fluid between the posterior and anterior segments of the eye. If ineffective, pars plana vitrectomy with capsulo-hyaloidectomy and lensectomy should be considered [5]. MG is defined as a uniform flattening of the AC in an eye with raised IOP in the presence of a patent iridotomy. It is thought that the cause is a misdirection of the aqueous humour towards the vitreous cavity, shifting the lens-iris diaphragm forward. MG is described as a complication of most intraocular surgeries, especially glaucoma surgery in patients with prior angle closure, being more frequent in hyperopic eyes . In the case we presented, we hypothesized that the irido-corneal contact, in the context of MG after DMEK, caused an almost fully detached graft, hence, the procedure ended up being an unintentional DMET. Interestingly, the corneal oedema improved in the following months. Several cases of corneal oedema resolution in presence of DMEK graft detachment, or even descemetorhexis with no posterior graft transplant have been reported. Dirisamer et al. proposed that contact between donor and host cornea is required to achieve corneal clearance as they reported successful results in patients with partial or large detachments, but not in eyes with a “free-floating graft roll” in the anterior chamber . Our case matched these findings, as the graft was not completely detached. Descemet Membrane Endothelial Transfer (DMET) is performed by injecting the donor graft consisting in Descemet Membrane and endothelium into the anterior chamber after descemetorhexis, without fully unfolding it, but with some contact area between graft and host cornea [8]. Shah et al. reported an increase in endothelial population despite the extraction of the graft and in descematorrhexis-alone procedures, suggesting a possible mechanism of host endothelial cell migration [9]. Dirisamer also had similar results and hypothesized that the recipient endothelium must be primarily involved due to the difference in clinical outcome of DMET in PBK and FED. Hence, DMET is ineffective in eyes with total deficiency of endothelial cells (PBK), yet if performed after descematorrhexis in patients with a pathologically altered subcellular matrix (FED) results in re-endothelialization and corneal clearance [9]. However, in our patient with severe PBK the corneal oedema improvement was evident despite the graft being detached. Although the mechanism is uncertain, we reason that DMET might have contributed to recover partially the corneal transparency [6].Birbal et al. reported unsuccessful long-term results in eight patients receiving DMET. They experienced corneal clearance in eyes with Fuchs endothelial dystrophy (FED) but not PBK, suggesting that the mechanism of DMET might be to stimulate host endothelial migratory response rather than to supply functional cells .One year after the surgery, our patient developed ICK, probably because of the combination of topical corticosteroids and bandage contact lens, as ICK typically occurs after an epithelial defect from a surgical procedure and is potentiated by localized immunosuppression, commonly steroids. Many pathogens can cause ICK although Although rare, malignant glaucoma can be a complication after DMEK surgery, and we must suspect it in postoperative patients with high IOP and flat AC in the presence of a patent iridotomy. Although steroid dosage is usually lower after DMEK compared to other keratoplasty techniques, it remains a risk factor for the growth of stromal biofilm that could ultimately lead to ICK, especially if bandage contact lens is worn.DisclosuresPatient informed consent was obtained.Conflict of interestConflicts of interest and source of funding: none.AcknowledgementsNone.