'Hidden' anger as a risk factor for operational health: An exploratory approach among French military personnel.

Military personnel are repeatedly exposed to multiple stressors, and are sometimes characterized by high levels of anger. Evidence suggests that this anger can become dysfunctional, and impact the health status of populations chronically exposed to stress. In particular, rumination (understood as perseverative thoughts about a past event), provides a theoretical framework for investigating how anger may impact stress regulation abilities in military personnel declared fit for deployment. This exploratory study aimed therefore to examine the impact of the anger profile on psychological suffering in terms of burnout and post-traumatic stress disorder (PTSD), along with the reactivity of the autonomic nervous system, measured as cardiac variability. One hundred and seventeen French soldiers were tested before deployment to Operation BARKHANE. Anger rumination, burnout, and PTSD symptoms were assessed using questionnaires, and cardiac variability was measured as the questionnaires were completed. The results revealed two profiles related to anger trait and anger rumination. Burnout and PTSD scores were higher among military personnel with high levels of anger trait and rumination, and this group also had lower parasympathetic activity and flexibility after completing the questionnaires. These results suggest that there may be a link between an angry profile and psychological suffering, notably burnout and PTSD. Rumination could be involved in this link, as it is associated with poor adaptation to stress in a military context. Prospective researches including post-deployment will establish whether this ruminative response can account for the relationship between problematic anger, stress regulatory capacities and psychological health in military populations.

Implementation of a Primary Prevention Program for Posttraumatic Stress Disorder in a Cohort of Professional Soldiers (PREPAR): Protocol for a Randomized Controlled Trial.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a psychiatric disorder that can manifest after a traumatic event where the individual perceives a threat to his or her life or that of others. Its estimated prevalence in the European population is 0.7% to 1.9%. According to the "dose-response" model, individuals who are most exposed to traumatic events are most at risk of developing PTSD. Hence, it is unsurprising that studies have observed a higher prevalence among the military population, ranging from 10% to 18%, or even up to 45%. This project's overall goal is to evaluate the primary prevention actions that can strengthen the resilience of at-risk professionals, notably military personnel, in the short term, with the medium- to long-term aim of preventing the occurrence of PTSD and improving the patient's prognosis. OBJECTIVE: This study's objectives are (1) to design a primary prevention program for PTSD, tailored to the studied military population and compatible with operational constraints; and (2) to implement and validate the Primary Prevention of Posttraumatic Stress Disorder in Military Professionals (PREPARE) program in the short term with operational personnel belonging to the French Mountain Infantry Brigade. METHODS: This is a single-center, prospective, randomized, parallel-group controlled cohort study. The cohort is divided into 2 groups: the nonintervention group receives no training, and the intervention group follows a dedicated prevention program (structured into 8 workshops and 2 debriefing and practice reinforcement workshops). Each participant is evaluated 4 times (at inclusion, +4 months, +6 months, and +12 months). During each visit, participants complete several psychosocial questionnaires (which take 15-80 minutes to complete). Samples (a 30-mL blood sample and three 5-mL saliva samples) are collected on 3 occasions: at inclusion, +4 months, and +12 months. Emotional reactivity (electrocardiogram and electrodermal activity) is measured before, during, and after the classic and the emotional Stroop task. RESULTS: The project is currently ongoing, and results are expected to be published by the end of 2024. CONCLUSIONS: The study adopts an integrative approach to the processes that play a role in the risk of developing PTSD. Our biopsychosocial perspective makes it possible to target levers related to factors specific to the individual and socio-professional factors. The following dimensions are addressed: (1) biophysiology (by studying markers of the neurobiological stress response, wear and tear, and vulnerability phenomena and reinforcing the flexibility of the autonomic nervous system), (2) psychology (by facilitating and measuring the development of flexible coping strategies to deal with stress and evaluating the moderating role of the individual's sense of duty in the development of PTSD), and (3) social (by facilitating community strategies aimed at reducing stigmatization and supporting the use of care by professionals in difficulty, in the institutional context). TRIAL REGISTRATION: ClinicalTrials.gov NCT05094531; https://clinicaltrials.gov/study/NCT05094531. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47175.

Evaluation of taVNS for extreme environments: an exploration study of health benefits and stress operationality.

Introduction: Long-duration space missions will be a real challenge for maintaining astronauts' adaptability. Research on transcutaneous vagus nerve stimulation (taVNS) is expanding rapidly, and its modalities constitute a major research challenge. A growing number of reviews stress the need to validate biomarkers for monitoring effects to enhance our understanding of the processes by which taVNS acts. Heart rate variability (HRV) appears to be a relevant candidate that informs on the autonomic nervous system (ANS). This is a promising technique to minimize the pathogenic effects of such large-scale missions and thus might be a relevant countermeasure. This study aimed to investigate the impact of taVNS on cognitive, psychological, and physiological functioning, including ANS functioning, and the benefits of increasing the number of taVNS sessions. Method: A total of 44 healthy participants were randomly assigned to one of the two cross-over protocols: a single session protocol (one taVNS and one sham simulation) or a repeated session protocol (three taVNS and three sham simulations). Cognitive, psychological, and physiological measures were performed before (pre) and after (post) each intervention. Sleep monitoring was only recorded before the first and after the last intervention in each protocol. For the repeated session protocol only, participants were allocated to two groups according to their parasympathetic activation gain during the three interventions: high parasympathetic delta (HPd) and low parasympathetic delta (LPd). Results: Participants in the repeated session protocol increased their HRV, cognitive performance, and sleep efficiency. In particular, taVNS induced higher parasympathetic activation and cardiac flexibility compared to the sham simulation in the repeated session protocol. Nevertheless, the perception of stress may indicate a nocebo effect of the repeated session. The HPd profile had higher interoceptive awareness, HRV highlighted by non-linear measures, and cognitive performance, but presented a decrease in some indicators of sleep efficiency compared to the LPd profile. Conclusion: taVNS seems to induce positive health outcomes, especially when the stimulation is repeated three times per week. Our findings highlight the benefits of parasympathetic activation during taVNS on psychophysiological and cognitive functioning. Further research is needed to validate these results on a large sample, using longitudinal measures over several months. This intervention appears promising as a countermeasure to extreme missions and occupations.

Environment and body-brain interplay affect inhibition and decision-making.

The fine-tuned interplay of brain and body underlies human ability to cope with changes in the internal and external milieus. Previous research showed that cardiac interoceptive changes (e.g., cardiac phase) affect cognitive functions, notably inhibition that is a key element for adaptive behaviour. Here we investigated the influence on cognition of vestibular signal, which provides the brain with sensory information about body position and movement. We used a centrifuge-based design to disrupt vestibular signal in healthy human volunteers while their inhibition and decision-making functions were assessed with the stop-signal paradigm. Participants performed the standard and a novel, sensorial version of the stop-signal task to determine whether disrupted vestibular signal influences cognition as a function of its relevance to the context. First, we showed that disrupted vestibular signal was associated with a larger variability of longest inhibition latencies, meaning that participants were even slower to inhibit in the trials where they had the most difficulty inhibiting. Second, we revealed that processing of bodily information, as required in the sensorial stop-signal task, also led to a larger variability of longest inhibition latencies, which was all the more important when vestibular signal was disrupted. Lastly, we found that such a degraded response inhibition performance was due in part to the acceleration of decision-making process, meaning that participants made a decision more quickly even when strength of sensory evidence was reduced. Taken together, these novel findings provide direct evidence that vestibular signal affects the cognitive functions of inhibition and decision-making.

Self-Representations of Military Veterans Suffering From Chronic Post-traumatic Stress Disorder: The Role of Sport.

Background: Post-traumatic stress disorder (PTSD) is a psychiatric illness that is very prevalent in both civilian and military environments. The clinical course, regardless of management, is chronic for a number of patients, especially veterans. Persistent PTSD symptoms interact with representations of the person and their body, and may negatively impact rehabilitation. Sport is known to help psychiatric patients such as those suffering from PTSD, as it improves the connection with the body, and supports physiological and emotional regulation. However, the impact of sport on self-representations has not yet been studied. The first aim of this study is to explore person and body representations in a population of military veterans suffering from chronic PTSD, as a function of clinical severity. Second, it aims to explore how a 9-day sport program, which includes an element of socio-professional rehabilitation, changes representations of the person and their body. Methods: This exploratory qualitative study examined the self-representation of veterans with chronic PTSD before a sport rehabilitation program. Veterans were given the prompts "body" and "person" and asked to free associate. PTSD severity and the mind-body connection were assessed using the Posttraumatic Stress Disorder Checklist for DSM-5, and the Freiburg Mindfulness Inventory, respectively. Parasympathetic activity was recorded at rest. A subgroup of the population volunteered to participate in a post-program session to record the same semantic, psychological, and physiological variables. Results: Although before the program, veterans gave more negatively than positively valenced words, no relation was observed between the overall number of negative words and PTSD severity. Post-program, changes were observed in terms of valence. Specifically, some negatively-valenced categories of words disappeared, and some positive categories appeared. At the same time, there was a fall in PTSD severity, an increase in the mind-body connection, and a decrease in parasympathetic activation. Conclusions: This study highlighted that veterans with chronic PTSD have a negative representation of the self. A dedicated, 9-day program that included regular sport improved self-representations related to both the person and their body, and reduced PTSD symptoms. The findings underline the importance of ensuring that programs for patients suffering from chronic PTSD should include sporting activity, and highlight the benefits. Sport appears to be a path to the reappropriation of a positive image of the self, by improving the representation of the body. This relationship could be consistent with improved interoception, but our results need further investigation.

[Improving parasympathetic functioning to contain the inflammatory response of COVID-19 infection]. / Améliorer le fonctionnement parasympathique pour contenir l'effet inflammatoire de la Covid-19.

COVID-19 infection results in an unrestrained inflammatory reaction in serious cases. The autonomic nervous system (ANS), in particular the parasympathetic branch, helps to regulate the inflammatory response. A dysfunction of this branch, frequent in people at risk of developing COVID-19, favours a pro-inflammatory effect. Reinforcing and stimulating the parasympathetic ANS is possible and accessible to paramedical and medical professionals.

Underexpression and abnormal localization of ATM products in ataxia telangiectasia patients bearing ATM missense mutations.

Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, immune defects and predisposition to malignancies. A-T is caused by biallelic inactivation of the ATM gene, in most cases by frameshift or nonsense mutations. More rarely, ATM missense mutations with unknown consequences on ATM function are found, making definitive diagnosis more challenging. In this study, a series of 15 missense mutations, including 11 not previously reported, were identified in 16 patients with clinical diagnosis of A-T belonging to 14 families and 1 patient with atypical clinical features. ATM function was evaluated in patient lymphoblastoid cell lines by measuring H2AX and KAP1 phosphorylation in response to ionizing radiation, confirming the A-T diagnosis for 16 cases. In accordance with previous studies, we showed that missense mutations associated with A-T often lead to ATM protein underexpression (15 out of 16 cases). In addition, we demonstrated that most missense mutations lead to an abnormal cytoplasmic localization of ATM, correlated with its decreased expression. This new finding highlights ATM mislocalization as a new mechanism of ATM dysfunction, which may lead to therapeutic strategies for missense mutation associated A-T.

The tailless ortholog nhr-67 functions in the development of the C. elegans ventral uterus.

The development of the C. elegans uterus provides a model for understanding the regulatory pathways that control organogenesis. In C. elegans, the ventral uterus develops through coordinated signaling between the uterine anchor cell (AC) and a ventral uterine (VU) cell. The nhr-67 gene encodes the nematode ortholog of the tailless nuclear receptor gene. Fly and vertebrate tailless genes function in neuronal and ectodermal developmental pathways. We show that nhr-67 functions in multiple steps in the development of the C. elegans uterus. First, it functions in the differentiation of the AC. Second, it functions in reciprocal signaling between the AC and an equipotent VU cell. Third, it is required for a later signaling event between the AC and VU descendants. nhr-67 is required for the expression of both the lag-2/Delta signal in the AC and the lin-12/Notch receptor in all three VU cells and their descendants, suggesting that nhr-67 may be a key regulator of Notch-signaling components. We discuss the implications of these findings for proposed developmental regulatory pathways that include the helix-loop-helix regulator hlh-2/daughterless and transcription factor egl-43/Evi1 in the differentiation of ventral uterine cell types.

Complications associated with transobturator sling procedures: analysis of 233 consecutive cases with a 27 months follow-up.

BACKGROUND: The transobturator tape procedure (TOT) is an effective surgical treatment of female stress urinary incontinence. However data concerning safety are rare, follow-up is often less than two years, and complications are probably underreported. The aim of this study was to describe early and late complications associated with TOT procedures and identify risk factors for erosions. METHODS: It was a 27 months follow-up of a cohort of 233 women who underwent TOT with three different types of slings (Aris, Obtape, TVT-O). Follow-up information was available for 225 (96.6%) women. RESULTS: There were few per operative complications. Forty-eight women (21.3%) reported late complications including de novo or worsening of preexisting urgencies (10.2%), perineal pain (2.2%), de novo dyspareunia (9%), and vaginal erosion (7.6%). The risk of erosion significantly differed between the three types of slings and was 4%, 17% and 0% for Aris, Obtape and TVT-O respectively (P = 0.001). The overall proportion of women satisfied by the procedure was 72.1%. The percentage of women satisfied was significantly lower in women who experienced erosion (29.4%) compared to women who did not (78.4%) (RR 0.14, 95% CI 0.05-0.38, P < 0.001). CONCLUSION: Late post operative complications are relatively frequent after TOT and can impair patient's satisfaction. Women should be informed of these potential complications preoperatively and require careful follow-up after the procedure. Choice of the safest sling material is crucial as it is a risk factor for erosion.

Anatomic distribution of posterior deeply infiltrating endometriosis on MRI after vaginal and rectal gel opacification.

OBJECTIVE: The challenges of imaging posterior deeply infiltrating endometriosis with MRI are to image a small anatomic area encompassing several thin fibromuscular anatomic structures such as uterosacral ligaments, and the vaginal and rectal walls; and to image endometriotic lesions, which are fibromuscular structures and have an MRI signal intensity very close to those of surrounding fibromuscular anatomic structures. CONCLUSION: We show the capability and potential of MRI in diagnosing and staging of posterior deeply infiltrating endometriosis after vaginal and rectal gel opacification.

Magnetic resonance imaging to identify risk of lymph node metastasis in patients with endometrial cancer.

OBJECTIVE: To assess the value of magnetic resonance imaging (MRI) to identify endometrial cancer patients at risk of lymph node metastasis. METHODS: Retrospective review of data from 108 patients with clinical stage I endometrial cancer who underwent preoperative MRI and were treated surgically. Patients at risk of lymph node metastasis were defined as those who had more than 50% myometrial infiltration or cervical invasion. Preoperative MRI reports were compared with final pathologic results. RESULTS: The mean age of the patients was 69.5 years and most patients had endometrioid cancer. On final pathologic analysis, 59 patients had deep myometrial infiltration or cervical invasion. For diagnosis of deep myometrial infiltration, cervical invasion, or both, MRI sensitivity and specificity were 56% and 85%; 47% and 83%; and 67% and 77%, respectively. CONCLUSION: MRI has limited value in identifying patients with endometrial cancer who are at risk of lymph node metastasis. Minimally invasive laparoscopic lymph node staging should be undertaken when it is feasible.

Incidence rate and risk factors for vaginal vault prolapse repair after hysterectomy.

Our objective was to estimate the incidence and identify the risk factors for vaginal vault prolapse repair after hysterectomy. We conducted a case control study among 6,214 women who underwent hysterectomy from 1982 to 2002. Cases (n = 32) were women who required vaginal vault suspension following the hysterectomy through December 2005. Controls (n = 236) were women, randomly selected from the same cohort, who did not require pelvic organ prolapse surgery. The incidence of vaginal vault prolapse repair was 0.36 per 1,000 women-years. The cumulative incidence was 0.5%. Risk factors included preoperative prolapse (odds ratio (OR) 6.6; 95% confidence interval (CI) 1.5-28.4) and sexual activity (OR 1.3; 95% CI 1.0-1.5). Vaginal hysterectomy was not a risk factor when preoperative prolapse was taken into account (OR 0.9; 95% CI 0.5-1.8).Vaginal vault prolapse repair after hysterectomy is an infrequent event and is due to preexisting weakness of pelvic tissues.

Treatment of genital prolapse by laparoscopic lateral suspension using mesh: a series of 73 patients.

STUDY OBJECTIVE: To evaluate the efficacy of laparoscopic lateral suspension using mesh in patients with pelvic organ prolapse (POP). DESIGN: A prospective cohort study (Canadian Task Force classification II-2). SETTING: A tertiary referral center for operative laparoscopy. PATIENTS: In all, 73 patients with POP were assessed in the preoperative and postoperative stages. The assessment included a description of their functional symptoms and the degree of their POP condition, established according to the Baden-Walker prolapse classification system. The patients were followed in the postoperative stage for a median of 19 (range 12-41) months. INTERVENTIONS: Laparoscopic lateral suspension of pelvic organs using mesh carried out from January 2004 through September 2006. MEASUREMENTS AND MAIN RESULTS: Satisfactory anatomic results were obtained in 64 (87.7%) patients. Neither major complications, nor postoperative pelvic infection were reported. None of the operations required laparotomy. CONCLUSION: Laparoscopic lateral suspension using mesh effectively treats POP with low morbidity.

Xeno-free derivation and culture of human embryonic stem cells: current status, problems and challenges.

Human embryonic stem cells (hESC) not only hold great promise for the treatment of degenerative diseases but also provide a valuable tool for developmental studies. However, the clinical applications of hESC are at present limited by xeno-contamination during the in vitro derivation and propagation of these cells. In this review, we summarize the current methodologies for the derivation and the propagation of hESC in conditions that will eventually enable the generation of clinical-grade cells for future therapeutic applications.

CoREST-like complexes regulate chromatin modification and neuronal gene expression.

The mammalian CoREST ([co]repressor for element-1-silencing transcription factor) complex was first identified associated with the repressor for element-1 silencing transcription factor (REST)/neuronal restrictive silencing factor. The CoREST complex is a chromatin-modifying corepressor complex that acts with REST to regulate neuronal gene expression and neuronal stem cell fate. Components of a CoREST-like complex have been identified recently in Xenopus laevis, Caenorhabditis elegans, and Drosophila melanogaster. Like the mammalian complex, the Drosophila complex is required to regulate neuronal gene expression, whereas the C. elegans homologs regulate the expression of the hop-1 presenilin gene, suggesting an ancient conserved function of CoREST complexes in regulating neuronal gene expression.

[Laparoscopic treatment of genital prolapse]. / Traitement laparoscopique des prolapsus génitaux.

Progresses performed in laparoscopic surgery during the last ten years offer the possibility to do complex and difficult gynaecologic operations by laparoscopy, specially surgical treatment of genital prolapse, with interesting results. We report the main laparoscopic techniques to treat genital prolapse. It is clear that most of the laparoscopic procedures are the same than the classical operations performed by laparotomy. The main techniques that we report treat completely the pelvic organ prolapse (POP), without any vaginal scar, avoiding the risks of the dyspareunia in the sexually active patients.

Effects of camptothecin on double-strand break repair by non-homologous end-joining in DNA mismatch repair-deficient human colorectal cancer cell lines.

Loss of a functional mismatch repair (MMR) system in colorectal cancer (CRC) cells is associated with microsatellite instability and increased sensitivity to topoisomerase inhibitors. In this study, we have investigated whether a defect in double-strand break (DSB) repair by non-homologous end-joining (NHEJ) could explain why MMR-deficient CRC cells are hypersensitive to camptothecin (CPT), a topoisomerase I inhibitor. To evaluate the efficiency and the fidelity of DSB repair, we have transiently transfected plasmids containing cohesive or non-complementary ends in cells with various MMR defects. We have observed that the repair efficiency of DSB with cohesive and non-complementary ends is comparable in all cell lines. In contrast to the MMR-proficient cell line HT29, the MMR-deficient cell lines were highly accurate in repairing DSB with cohesive ends, but this characteristic could not be directly assigned to the primary MMR deficiency. Furthermore, CPT treatment had no detectable effect on the repair of cohesive ends but significantly decreased the repair efficiency of non-complementary DSB. In conclusion, although our observations show that DSB repair efficiency by NHEJ decreases upon treatment with CPT, which possibly contributes to its cytotoxicity, it is quite unlikely that it accounts for the hypersensitivity of MMR-deficient cells to topoisomerase inhibitors.

Microsatellite instability is a predictive factor of the tumor response to irinotecan in patients with advanced colorectal cancer.

The aim of our study was to assess the relationship between colorectal tumor responsiveness to irinotecan and microsatellite instability (MSI), a feature of colorectal tumors with DNA mismatch repair defect. Seventy-two patients with metastatic colorectal cancer were included in our retrospective study. A complete response to irinotecan was observed in 1 patient and a partial response in 10 patients, whereas 61 patients did not respond to this treatment. We analyzed the protein expression of hMLH1, hMSH2, and BAX by immunohistochemistry, determined the MSI phenotype, and looked for mutations in the coding repeats located in the transforming growth factor beta-RII, BAX, hMSH3, and hMSH6 genes. All 44 tumors analyzed expressed detectable levels of hMLH1; 1 tumor lacked hMSH2 staining, whereas 4 tumors showed a marked decrease in BAX expression. A better response to irinotecan was observed in the patients whose tumors have lost BAX expression (P < 0.001). Among the 7 tumors that displayed a MSI-H phenotype, 4 responded to irinotecan, whereas only 7 of the 65 MSI-L/ microsatellite stable tumors did (P = 0.009). Seven of the 72 tumors had inactivating mutations in the coding repeats of the target genes. Three tumors displayed a mutation in the poly-A10 tract of the transforming growth factor beta-RII gene, associated with a 1-bp deletion in the poly-A8 tract of hMSH3 in one tumor and with a 1-bp deletion in the poly-G8 tract of BAX in another. Four tumors displayed mutations in the poly-G8 repeat of BAX, whereas 2 mutations in hMSH6 and hMSH3 were characterized. Among the 7 tumors with mutations in these target genes, 5 responded to irinotecan, whereas only 6 of the other 65 tumors did (P < 0.001), indicating that MSI-driven inactivation of target genes modifies tumor chemosensitivity. Our observations allowed us to define the first useful predictive criteria for irinotecan response in patients with colorectal cancer.

DNA mismatch repair defects: role in colorectal carcinogenesis.

The inactivation of the DNA mismah repair (MMR) system, which is associated with the predisposition to the hereditary non-polyposis colorectal cancer (HNPCC), has also been documented in nearly 20% of the sporadic colorectal cancers. These tumors are characterized by a high frequency of microsatellite instability (MSI(+) phenotype), resulting from the accumulation of small insertions or deletions that frequently arise during replication of these short repeated sequences. A germline mutation of one of the two major MMR genes (hMSH2 or hMLH1) is found in half to two-thirds of the patients with HNPCC, whereas in sporadic cases hypermethylation of the hMLH1 promoter is the major cause of the MMR defect. Germline mutations in hMSH6 are rare and rather confer predisposition to late-onset familial colorectal cancer, and frequent extracolonic tumors. Yet, the genetic background of a number of HNPCC patients remains unexplained, indicating that other genes participate in MMR and play important roles in cancer susceptibility. The tumor-suppressor genes that are potential targets for the MSI-driven mutations because they contain hypermutable repeated sequences are likely to contribute to the etiology and tissue specificity of the MSI-associated carcinogenesis. Because the prognosis and the chemosensitivity of the MSI(+) colorectal tumors differ from those without instability, the determination of the MSI phenotype is expected to improve the clinical management of patients. This review gives an overview of various aspects of the biochemistry and genetics of the DNA mismah repair system, with particular emphasis in its role in colorectal carcinogenesis.