Impact of breast cancer on prospective memory functioning assessed by virtual reality and influence of sleep quality and hormonal therapy: PROSOM-K study.

BACKGROUND: Breast cancer (BC) is the most frequent cancer in women with more than 70% of BC patients being treated with hormonal therapy (HT). Among these patients, some report difficulties in remembering what they are supposed to do at the right moment, referring to prospective memory (PM). PM is essential for autonomy and medical adherence of patients, and requires an ecological assessment. Virtual reality, that recreates naturalistic environment, seems to be a promising method to evaluate PM. Several BC patients also report sleep disturbances. Given the role of sleep on memory consolidation, it is imperative to explore the influence of sleep quality on PM in BC patients treated with HT. The purpose of PROSOM-K study is to assess PM functioning using virtual reality and sleep quality in BC treated or not with HT. METHODS: PROSOM-K is a prospective study including post-menopausal BC patients ≤70 years old treated with radiotherapy (n = 25) or with radiotherapy and HT (n = 25), and healthy post-menopausal women (n = 25) matched for age and education. PM will be assessed using a virtual reality based task. Other cognitive functions and psychosocial factors will be assessed with validated questionnaires and neuropsychological tests. The study is divided in 3 sessions: a session of familiarisation with the virtual environment and the PM task: a day-time session during which participants learn intentions during the morning and recall them in the evening; and a night-time session during which participants learn intentions in the evening and recall them the following morning. Women will be monitored by wrist actigraphy; during the night-time session, objective sleep quality and quantity will be measured by polysomnography. DISCUSSION: This is a novel study aiming to assess PM using virtual reality, coupled with the evaluation of other cognitive functions. Polysomnographic study of sleep will provide further information about architectural sleep disturbances in BC. Association between sleep architecture parameters and PM mechanism in BC women treated with HT will be described in detail. We expect our results will provide knowledge for patients and clinicians and further help to improve patient care and cognitive therapy. TRIAL REGISTRATION: NCT03420105 , registered: January 10, 2018.

Differences in predictive factors for post-traumatic stress disorder encompassing partial PTSD and full PTSD: a cross-sectional study among individuals exposed to the November 13, 2015 Paris attacks.

Background: When faced with a surge of physically injured individuals, especially following a traumatic event like an attack, frontline practitioners prioritize early triage. Detecting potential psychological injuries soon after such events remains challenging. Some individuals might develop post-traumatic stress disorder (PTSD) according to DSM-V criteria. Others may exhibit PTSD symptoms without meeting full diagnostic criteria, termed partial or sub-syndromal PTSD, a less-explored area in literature. This study aims to identify predictive factors for both full and partial PTSD. Method: In a cohort of victims of the 2015 Paris attacks, multinomial logistic regressions explored predictive factors for partial or full PTSD status 8 to 18 months post-attacks. Analyses considered pre, peri, and posttraumatic factors chosen from literature review and univariate analysis within each group. Results: Within the cohort, 50 individuals showed no signs of PTSD, 35 experienced partial PTSD, and 30 presented with full PTSD. After logistic regression, risk factors associated with full PTSD included a history of trauma (OR = 1.30, CI [1.02-1.66], p < 0.05), the intensity of peri-traumatic physical reactions (OR = 1.22, CI [1.09-1.36], p < 0.001), the difficulties in suppressing intrusive thoughts (OR = 1.11, CI [1.02-1.21], p < 0.013). Only the intensity of peri-traumatic physical reactions emerged as a risk factor for partial PTSD (OR = 1.13, [CI 1.02-1.24], p < 0.001). Discussion: This study revealed that a history of trauma, the intensity of peri-traumatic physical reactions (e.g., tachycardia, trembling, flushes, numbness.), and the difficulties in suppressing intrusive thoughts constitute risk factors for the development of full PTSD. Moreover, the study identified that only the intensity of peri-traumatic physical reactions emerged as a risk factor for partial PTSD. These findings seem to underscore the significance of peri-traumatic experiences in influencing the development of post-traumatic stress symptoms. Conclusion: This study emphasizes the significance of examining peri-traumatic reactions in PTSD development, suggesting its potential as a straightforward screening tool for post-traumatic stress disorder. It also underscores the influence of prior traumatic experiences, before de novo traumatization, in shaping vulnerability to PTSD and illuminates the crucial role of compromised control of intrusive thoughts that could perpetuate PTSD.

A history of PTSD changes the way people express themselves during the COVID-19 pandemic.

Background: The words people use in everyday life tell us about their emotions, their mental state and allow us to understand how people process and interpret an event. Previous research has established a link between the content analysis of narrative texts and the psychopathology of people who have experienced trauma.Objectives: This study examines whether the development of PTSD following exposure to a previous traumatic event alters the way people express themselves in the context of an anxiety-provoking event, the COVID-19 pandemic.Methods: This study is based on semi-structured interviews conducted during the first lockdown period in France (23 April-16 May 2020) with people exposed to the 13 November 2015 attacks (N = 31) and nonexposed people (N = 57).Results: People with PTSD had longer narratives and used more first-person singular pronouns, lower first-person plural pronouns, more words related to negative emotions and anxiety compared to the nonexposed group. Within the PTSD group, there was no significant difference between the use of words related to the attacks and the pandemic. Conversely, the nonexposed group used more words related to the COVID-19 pandemic compared to words related to the attacks.Conclusion: These results confirm, as have other studies, that a history of PTSD can specifically modify the style and narrative of past experiences. They underline the importance of including linguistic analyses in psychological assessments of PTSD.

The PTSD group has a longer narrative compared to the nonexposed group.The PTSD group narrative was more individualistic and emotionally focused than the nonexposed group.The lexical field of the attacks relatively to the field of pandemic seems to occupy the same place in the accounts of people suffering from PTSD.

Peritraumatic physical symptoms and the clinical trajectory of PTSD after a terrorist attack: a network model approach.

Introduction: Following a mass casualty event, such as the Paris terrorist attacks of 13 November 2015, first responders need to identify individuals at risk of PTSD. Physical peritraumatic symptoms involving the autonomic nervous system may be useful in this task.Objective: We sought to determine the trajectory of physical response intensity in individuals exposed to the Paris terrorist attacks using repeated measures, and to examine its associations with PTSD. Using network modelling, we examined whether peritraumatic physical symptom associations differed by PTSD status.Methods: Physical reactions were assessed using the Subjective Physical Reactions Scale at three time points: peritraumatic by retrospective recall, then current at one year (8-18 months) and three years (30-42 months) after the attacks. Interaction networks between peritraumatic physical reactions were compared according to PTSD status.Results: On the one hand, the reported intensity of physical reactions was significantly higher in the PTSD group at all time points. On the other hand, using the dynamic approach, more robust positive interactions between peritraumatic physical reactions were found in the PTSD group one and three years after the attacks. Negative interactions were found in the no-PTSD group at one year. Peritraumatic physical numbness was found to be the most central network symptom in the PTSD group, whereas it was least central in the no-PTSD group.Discussion: Network analysis of the interaction between peritraumatic physical subjective responses, particularly physical numbness, may provide insight into the clinical course of PTSD. Our knowledge of the brain regions involved in dissociation supports the hypothesis that the periaqueductal grey may contribute to the process leading to physical numbing.Conclusions: Our findings highlight the role of peritraumatic somatic symptoms in the course of PTSD. Peritraumatic physical numbness appears to be a key marker of PTSD and its identification may help to improve early triage.

Physical numbness was found to be a central symptom in people developing PTSD in our study examining peritraumatic physical symptoms related to the 2015 Paris terrorist attacks.

Avoidance behaviour generalizes to eye processing in posttraumatic stress disorder.

Background: Avoidance describes any action designed to prevent an uncomfortable situation or emotion from occurring. Although it is a common reaction to trauma, avoidance becomes problematic when it is the primary coping strategy, and plays a major role in the development and maintenance of posttraumatic stress disorder (PTSD). Avoidance in PTSD may generalize to non-harmful environmental cues that are perceived to be unsafe. Objective: We tested whether avoidance extends to social cues (i.e. emotional gazes) that are unrelated to trauma. Method: A total of 159 participants (103 who had been exposed to the 2015 Paris terrorist attacks and 56 who had not) performed a gaze-cueing task featuring sad, happy and neutral faces. Attention to the eye area was recorded using an eyetracker. Of the exposed participants, 52 had been diagnosed with PTSD (PTSD+) and 51 had not developed PTSD (PTSD-). As a result of the preprocessing stages, 52 PTSD+ (29 women), 50 PTSD- (20 women) and 53 nonexposed (31 women) participants were included in the final analyses. Results: PTSD+ participants looked at sad eyes for significantly less time than PTSD- and nonexposed individuals. This effect was negatively correlated with the intensity of avoidance symptoms. No difference was found for neutral and happy faces. Conclusions: These findings suggest that maladaptive avoidance in PTSD extends to social processing, in terms of eye contact and others' emotions that are unrelated to trauma. New therapeutic directions could include targeting sociocognitive deficits. Our findings open up new and indirect avenues for overcoming maladaptive avoidance behaviours by remediating eye processing.Trial registration: ClinicalTrials.gov identifier: NCT02810197. HIGHLIGHTS: Avoidance is a key symptom of posttraumatic stress disorder (PTSD).Avoidance is often viewed as limited to reminders linked to the trauma.Results show that attention to the eyes of sad faces is also affected by PTSD. This effect is correlated with avoidance symptoms in PTSD.

Antecedentes: La evitación describe cualquier acción diseñada para prevenir una situación o emoción desagradable. Aunque es una reacción común al trauma, la evitación se vuelve problemática cuando es la principal estrategia de afrontamiento, y desempeña un papel importante en el desarrollo y mantenimiento del trastorno de estrés postraumático (TEPT). La evitación en el TEPT puede generalizarse a señales ambientales no dañinas que se perciben como inseguras. Objetivo: Probamos si la evitación se extiende a las señales sociales (es decir, las miradas emocionales) que no están relacionadas con el trauma. Método: Un total de 159 participantes (103 que habían estado expuestos a los atentados terroristas de París del 2015 y 56 que no lo habían estado) realizaron una tarea de captación de miradas con rostros tristes, felices y neutros. La atención a la zona de los ojos se registró mediante un rastreador ocular. De los participantes expuestos, 52 habían sido diagnosticados con TEPT (TEPT+) y 51 no habían desarrollado TEPT (TEPT-). Resultados: Los participantes con TEPT+ miraron los ojos tristes durante un tiempo significativamente menor que los individuos con TEPT- y los no expuestos. Este efecto se correlacionó negativamente con la intensidad de los síntomas de evitación. No se encontraron diferencias para las caras neutras y felices Conclusiones: Estos hallazgos sugieren que la evitación desadaptativa en el TEPT se extiende al procesamiento social, en cuanto al contacto visual y las emociones de los demás que no están relacionadas con el trauma. Las nuevas direcciones terapéuticas podrían incluir centrarse en los déficits sociocognitivos. Nuestros hallazgos abren vías nuevas e indirectas para superar las conductas de evitación desadaptativas mediante la remediación del procesamiento ocular.

Altered predictive control during memory suppression in PTSD.

Aberrant predictions of future threat lead to maladaptive avoidance in individuals with post-traumatic stress disorder (PTSD). How this disruption in prediction influences the control of memory states orchestrated by the dorsolateral prefrontal cortex is unknown. We combined computational modeling and brain connectivity analyses to reveal how individuals exposed and nonexposed to the 2015 Paris terrorist attacks formed and controlled beliefs about future intrusive re-experiencing implemented in the laboratory during a memory suppression task. Exposed individuals with PTSD used beliefs excessively to control hippocampal activity during the task. When this predictive control failed, the prediction-error associated with unwanted intrusions was poorly downregulated by reactive mechanisms. This imbalance was linked to higher severity of avoidance symptoms, but not to general disturbances such as anxiety or negative affect. Conversely, trauma-exposed participants without PTSD and nonexposed individuals were able to optimally balance predictive and reactive control during the memory suppression task. These findings highlight a potential pathological mechanism occurring in individuals with PTSD rooted in the relationship between the brain's predictive and control mechanisms.

Variations in response to trauma and hippocampal subfield changes.

Models of posttraumatic stress disorder (PTSD) suggest that the hippocampus is key to the persistence of traumatic memory. Yet very little is known about the precise changes that take place in this structure, nor their relation with PTSD symptoms. Previous studies have mostly used magnetic resonance imaging (MRI) at low resolutions, making it impossible to identify sensitive anatomical landmarks, or compared groups often unequally matched in terms of traumatic exposure. The present cross-sectional study included 92 individuals who had all been exposed to the terrorist attacks in Paris on November 13, 2015 (53 of whom subsequently developed PTSD) and 56 individuals who had not been exposed. Hippocampal subfield volumes were estimated using cross-validated automatic segmentation of high-resolution MRI images. Results revealed changes in CA1 and CA2-3/dentate gyrus (DG) volumes in individuals with PTSD, but not in resilient (i.e., exposed but without PTSD) individuals, after controlling for potential nuisance variables such as previous traumatic exposure and substance abuse. In line with current models of hippocampal subfield functions, CA1 changes were linked to the uncontrollable re-experiencing of intrusive memories, while CA2-3/DG changes, potentially exacerbated by comorbid depression, fostered the overgeneralization of fear linked to avoidance and hypervigilance behaviors. Additional analyses revealed that CA1 integrity was linked to optimum functioning of the memory control network in resilient individuals. These findings shed new light on potential pathophysiological mechanisms in the hippocampus subtending the development of PTSD and the failure to recover from trauma.

Gamithromycin in swine: Pharmacokinetics and clinical evaluation against swine respiratory disease.

The pharmacokinetics of gamithromycin were evaluated in 26 male castrated and female crossbred swine administered gamithromycin 15% w/v (Zactran®, Boehringer Ingelheim) intravenously at 6 mg/kg bodyweight or intramuscularly at 3, 6 or 12 mg/kg bodyweight. Blood samples were collected up to Day 10 to establish the plasma profile of gamithromycin, bioavailability and dose proportionality. When administered by intramuscular injection at 6 mg/kg BWT, pharmacokinetic parameters were as follows: area under the curve until last quantifiable plasma concentration, 5.13 ± 0.957 µg*hours/ml; maximum plasma concentration, 960 ± 153 ng/ml at 5 to 15 min; terminal half-life of 94.1 ± 20.4 hr. Absolute bioavailability was 92.2%. Increase in systemic exposure was proportional to the gamithromycin dose level over the range 3-12 mg/kg BWT. No gender-related statistically significant difference in exposure was observed. For clinical evaluation of Zactran® against swine respiratory disease, 305 pigs from six commercial farms in three countries in Europe with signs associated with Actinobacillus pleuropneumoniae and/or Haemophilus parasuis and/or Pasteurella multocida and/or Bordetella bronchiseptica were used. At each site, animals were treated once in a 1:1 ratio with a single intramuscular dose of Zactran® (6 mg gamithromycin/kg bodyweight) or Zuprevo® (4% w/v tildipirosin at 4 mg/kg bodyweight; MSD Animal Health) at the recommended dose respectively. Animals were observed and scored daily for 10 consecutive days for signs of swine respiratory disease (depression, respiration and rectal temperature), and animals presenting signs of clinical swine respiratory disease (Depression Score 3 and/or Respiratory Score 3 associated with Rectal Temperature > 40.0°C) were removed from the study and considered as treatment failure. Animals which remained in the study were individually assessed for 'treatment success' or 'treatment failure' (Depression Score ≥ 1 and Rectal Temperature > 40.0°C or Respiratory Score ≥ 1 and Rectal Temperature > 40.0°C). Using a non-inferiority hypothesis test (non-inferiority margin = 0.10), the proportion of treatment successes in the Zactran® group (97%) was equivalent to or better than that in the Zuprevo® group (93%).

Resilience after trauma: The role of memory suppression.

In the aftermath of trauma, little is known about why the unwanted and unbidden recollection of traumatic memories persists in some individuals but not others. We implemented neutral and inoffensive intrusive memories in the laboratory in a group of 102 individuals exposed to the 2015 Paris terrorist attacks and 73 nonexposed individuals, who were not in Paris during the attacks. While reexperiencing these intrusive memories, nonexposed individuals and exposed individuals without posttraumatic stress disorder (PTSD) could adaptively suppress memory activity, but exposed individuals with PTSD could not. These findings suggest that the capacity to suppress memory is central to positive posttraumatic adaptation. A generalized disruption of the memory control system could explain the maladaptive and unsuccessful suppression attempts often seen in PTSD, and this disruption should be targeted by specific treatments.

Corruption kills: estimating the global impact of corruption on children deaths.

BACKGROUND: Information on the global risk factors of children mortality is crucial to guide global efforts to improve survival. Corruption has been previously shown to significantly impact on child mortality. However no recent quantification of its current impact is available. METHODS: The impact of corruption was assessed through crude Pearson's correlation, univariate and multivariate linear models coupling national under-five mortality rates in 2008 to the national "perceived level of corruption" (CPI) and a large set of adjustment variables measured during the same period. FINDINGS: The final multivariable model (adjusted R(2)= 0.89) included the following significant variables: percentage of people with improved sanitation (p.value<0.001), logarithm of total health expenditure (p.value = 0.006), Corruption Perception Index (p.value<0.001), presence of an arid climate on the national territory (p = 0.006), and the dependency ratio (p.value<0.001). A decrease in CPI of one point (i.e. a more important perceived corruption) was associated with an increase in the log of national under-five mortality rate of 0.0644. According to this result, it could be roughly hypothesized that more than 140000 annual children deaths could be indirectly attributed to corruption. INTERPRETATIONS: Global response to children mortality must involve a necessary increase in funds available to develop water and sanitation access and purchase new methods for prevention, management, and treatment of major diseases drawing the global pattern of children deaths. However without paying regard to the anti-corruption mechanisms needed to ensure their proper use, it will also provide further opportunity for corruption. Policies and interventions supported by governments and donors must integrate initiatives that recognise how they are inter-related.