Skin Wound following Irradiation Aggravates Radiation-Induced Brain Injury in a Mouse Model.

Radiation injury- and radiation combined with skin injury-induced inflammatory responses in the mouse brain were evaluated in this study. Female B6D2F1/J mice were subjected to a sham, a skin wound (SW), 9.5 Gy 60Co total-body gamma irradiation (RI), or 9.5 Gy RI combined with a skin puncture wound (RCI). Survival, body weight, and wound healing were tracked for 30 days, and mouse brain samples were collected on day 30 after SW, RI, RCI, and the sham control. Our results showed that RCI caused more severe animal death and body weight loss compared with RI, and skin wound healing was significantly delayed by RCI compared to SW. RCI and RI increased the chemokines Eotaxin, IP-10, MIG, 6Ckine/Exodus2, MCP-5, and TIMP-1 in the brain compared to SW and the sham control mice, and the Western blot results showed that IP-10 and p21 were significantly upregulated in brain cells post-RI or -RCI. RI and RCI activated both astrocytes and endothelial cells in the mouse brain, subsequently inducing blood-brain barrier (BBB) leakage, as shown by the increased ICAM1 and GFAP proteins in the brain and GFAP in the serum. The Doublecortin (DCX) protein, the "gold standard" for measuring neurogenesis, was significantly downregulated by RI and RCI compared with the sham group. Furthermore, RI and RCI decreased the expression of the neural stem cell marker E-cadherin, the intermediate progenitor marker MASH1, the immature neuron cell marker NeuroD1, and the mature neuron cell marker NeuN, indicating neural cell damage in all development stages after RI and RCI. Immunohistochemistry (IHC) staining further confirmed the significant loss of neural cells in RCI. Our data demonstrated that RI and RCI induced brain injury through inflammatory pathways, and RCI exacerbated neural cell damage more than RI.

Relationship conflict and partner violence by UK military personnel following return from deployment in Iraq and Afghanistan.

PURPOSE: Risk of violence by UK military personnel, both towards non-family and family, has been found to be higher post-deployment. However, no UK research to date has attempted to examine relationship conflict and intimate partner violence (IPV) in this period. This study estimated the prevalence of and risk factors for post-deployment relationship conflict and partner violence in UK military personnel. METHODS: We utilised data on military personnel who had deployed to Iraq and/or Afghanistan (n = 5437), drawn from a large cohort study into the health and well-being of UK military personnel. RESULTS: 34.7% reported relationship conflict (arguing with partner) and 3.4% reported perpetrating physical IPV post-deployment. Males were more likely than females to report relationship conflict. There were similar rates of self-reported physical IPV perpetration among males and females. Among our male sample, factors associated with both relationship conflict and physical IPV perpetration post-deployment included being in the Army compared with the Royal Air Force, higher levels of childhood adversity, higher levels of military trauma exposure and recent mental health and alcohol misuse problems. Being over 40 at time of deployment (vs being under 25) and having deployed in a combat role were also associated with relationship conflict, but not physical IPV perpetration. CONCLUSIONS: Deployment-related variables and mental health and alcohol misuse problems were found to be key factors associated with post-deployment relationship conflict and IPV. Services providing health or welfare support to military personnel must collaborate with mental health services and consider history of deployment, and particularly deployment-related trauma, in their assessments to improve identification and management of intimate partner violence and abuse in military communities.

Risk and protective factors for offending among UK Armed Forces personnel after they leave service: a data linkage study.

BACKGROUND: A proportion of ex-military personnel who develop mental health and social problems end up in the Criminal Justice System. A government review called for better understanding of pathways to offending among ex-military personnel to improve services and reduce reoffending. We utilised data linkage with criminal records to examine the patterns of offending among military personnel after they leave service and the associated risk (including mental health and alcohol problems) and socio-economic protective factors. METHOD: Questionnaire data from a cohort study of 13 856 randomly selected UK military personnel were linked with national criminal records to examine changes in the rates of offending after leaving service. RESULTS: All types of offending increased after leaving service, with violent offending being the most prevalent. Offending was predicted by mental health and alcohol problems: probable PTSD, symptoms of common mental disorder and aggressive behaviour (verbal, property and threatened or actual physical aggression). Reduced risk of offending was associated with post-service socio-economic factors: absence of debt, stable housing and relationship satisfaction. These factors were associated with a reduced risk of offending in the presence of mental health risk factors. CONCLUSIONS: Ex-military personnel are more likely to commit violent offences after leaving service than other offence-types. Mental health and alcohol problems are associated with increased risk of post-service offending, and socio-economic stability is associated with reduced risk of offending among military veterans with these problems. Efforts to reduce post-service offending should encompass management of socio-economic risk factors as well as mental health.

Mental health outcomes at the end of the British involvement in the Iraq and Afghanistan conflicts: a cohort study.

BACKGROUND: Little is known about the prevalence of mental health outcomes in UK personnel at the end of the British involvement in the Iraq and Afghanistan conflicts.AimsWe examined the prevalence of mental disorders and alcohol misuse, whether this differed between serving and ex-serving regular personnel and by deployment status. METHOD: This is the third phase of a military cohort study (2014-2016; n = 8093). The sample was based on participants from previous phases (2004-2006 and 2007-2009) and a new randomly selected sample of those who had joined the UK armed forces since 2009. RESULTS: The prevalence was 6.2% for probable post-traumatic stress disorder, 21.9% for common mental disorders and 10.0% for alcohol misuse. Deployment to Iraq or Afghanistan and a combat role during deployment were associated with significantly worse mental health outcomes and alcohol misuse in ex-serving regular personnel but not in currently serving regular personnel. CONCLUSIONS: The findings highlight an increasing prevalence of post-traumatic stress disorder and a lowering prevalence of alcohol misuse compared with our previous findings and stresses the importance of continued surveillance during service and beyond. DECLARATION OF INTEREST: All authors are based at King's College London which, for the purpose of this study and other military-related studies, receives funding from the UK Ministry of Defence (MoD). S.A.M.S., M.J., L.H., D.P., S.M. and R.J.R. salaries were totally or partially paid by the UK MoD. The UK MoD provides support to the Academic Department of Military Mental Health, and the salaries of N.J., N.G. and N.T.F. are covered totally or partly by this contribution. D.Mu. is employed by Combat Stress, a national UK charity that provides clinical mental health services to veterans. D.MacM. is the lead consultant for an NHS Veteran Mental Health Service. N.G. is the Royal College of Psychiatrists' Lead for Military and Veterans' Health, a trustee of Walking with the Wounded, and an independent director at the Forces in Mind Trust; however, he was not directed by these organisations in any way in relation to his contribution to this paper. N.J. is a full-time member of the armed forces seconded to King's College London. N.T.F. reports grants from the US Department of Defense and the UK MoD, is a trustee (unpaid) of The Warrior Programme and an independent advisor to the Independent Group Advising on the Release of Data (IGARD). S.W. is a trustee (unpaid) of Combat Stress and Honorary Civilian Consultant Advisor in Psychiatry for the British Army (unpaid). S.W. is affiliated to the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emergency Preparedness and Response at King's College London in partnership with Public Health England, in collaboration with the University of East Anglia and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, the Department of Health, Public Health England or the UK MoD.

Post-deployment family violence among UK military personnel.

BACKGROUND: Research into violence among military personnel has not differentiated between stranger- and family-directed violence. While military factors (combat exposure and post-deployment mental health problems) are risk factors for general violence, there has been limited research on their impact on violence within the family environment. This study aims to compare the prevalence of family-directed and stranger-directed violence among a deployed sample of UK military personnel and to explore risk factors associated with both family- and stranger-directed violence. METHOD: This study utilised data from a large cohort study which collected information by questionnaire from a representative sample of randomly selected deployed UK military personnel (n = 6711). RESULTS: The prevalence of family violence immediately following return from deployment was 3.6% and 7.8% for stranger violence. Family violence was significantly associated with having left service, while stranger violence was associated with younger age, male gender, being single, having a history of antisocial behaviour as well as having left service. Deployment in a combat role was significantly associated with both family and stranger violence after adjustment for confounders [adjusted odds ratio (aOR) = 1.92 (1.25-2.94), p = 0.003 and aOR = 1.77 (1.31-2.40), p < 0.001, respectively], as was the presence of symptoms of post-traumatic stress disorder, common mental disorders and aggression. CONCLUSIONS: Exposure to combat and post-deployment mental health problems are risk factors for violence both inside and outside the family environment and should be considered in violence reduction programmes for military personnel. Further research using a validated measurement tool for family violence would improve comparability with other research.

Violent behavior among military reservists.

Large numbers of British and American Reservists have been deployed to operations in Iraq and Afghanistan. Little is known about the impact of deployment and combat exposure on violent behavior in Reservists. The purpose of this study was to determine the prevalence of self-reported violent behavior among a representative sample of United Kingdom Reservists, the risk factors associated with violence and the impact of deployment and combat exposure on violence. This study used data from a large cohort study of randomly selected UK military personnel and included Reservists who were in service at the time of sampling (n = 1710). Data were collected by questionnaires that asked about socio-demographic and military characteristics, pre-enlistment antisocial behavior, deployment experiences, post-deployment mental health, and self-reported interpersonal violent behavior. The prevalence of violence among Reservists was 3.5%. Deployment was found to be a risk factor for violent behavior even after adjustment for confounders. The association with violence was similar for those deployed in either a combat role or non-combat role. Violence was also strongly associated with mental health risk factors (PTSD, common mental disorders, and alcohol misuse). This study demonstrated higher levels of self-reported post-deployment violence in UK Reservists who had served in either Iraq or Afghanistan. Deployment, irrespective of the role was associated with higher levels of violent behavior among Reservists. The results also emphasize the risk of violent behavior associated with post-deployment mental health problems. Aggr. Behav. 43:273-280, 2017. © 2016 Wiley Periodicals, Inc.

Anger in the UK Armed Forces: strong association with mental health, childhood antisocial behavior, and combat role.

We assessed the strength of the association of several mental health problems, childhood difficulties, and combat role with anger, as well as the contribution of these factors to explain anger assessed by population attributable fraction (PAF). A total of 9885 UK service personnel, some of them deployed to Iraq and Afghanistan, participated in the study. There was a strong or intermediate association between cases and subthreshold cases of symptoms of posttraumatic stress disorder, psychological distress, multiple physical symptoms and alcohol misuse, having a combat role, childhood adversity, and childhood antisocial behavior with anger. The PAF for any mental health problem and combat role and childhood difficulties was 0.64 (95% confidence interval [CI], 0.56-0.70) and increased to 0.77 (95% CI, 0.69-0.83) if subthreshold cases were included. Anger is a frequent component of mental disorders; health care professionals need to be aware of the interference of anger in the management of mental illness and that anger infrequently presents as an isolated phenomenon.

Violent offending by UK military personnel deployed to Iraq and Afghanistan: a data linkage cohort study.

BACKGROUND: Violent offending by veterans of the Iraq and Afghanistan conflicts is a cause for concern and there is much public debate about the proportion of ex-military personnel in the criminal justice system for violent offences. Although the psychological effects of conflict are well documented, the potential legacy of violent offending has yet to be ascertained. We describe our use of criminal records to investigate the effect of deployment, combat, and post-deployment mental health problems on violent offending among military personnel relative to pre-existing risk factors. METHODS: In this cohort study, we linked data from 13,856 randomly selected, serving and ex-serving UK military personnel with national criminal records stored on the Ministry of Justice Police National Computer database. We describe offending during the lifetime of the participants and assess the risk factors for violent offending. FINDINGS: 2,139 (weighted 17.0%) of 12,359 male UK military personnel had a criminal record for any offence during their lifetime. Violent offenders (1,369 [11.0%]) were the most prevalent offender types; prevalence was highest in men aged 30 years or younger (521 [20.6%] of 2,728) and fell with age (164 [4.7%] of 3027 at age >45 years). Deployment was not independently associated with increased risk of violent offending, but serving in a combat role conferred an additional risk, even after adjustment for confounders (violent offending in 137 [6.3%] of 2178 men deployed in a combat role vs 140 (2.4%) of 5,797 deployed in a non-combat role; adjusted hazard ratio 1.53, 95% CI 1.15-2.03; p=0.003). Increased exposure to traumatic events during deployment also increased risk of violent offending (violent offending in 104 [4.1%] of 2753 men with exposure to two to four traumatic events vs 56 [1.6%] of 2944 with zero to one traumatic event, 1.77, 1.21-2.58, p=0.003; and violent offending in 122 [5.1%] of 2582 men with exposure to five to 16 traumatic events, 1.65, 1.12-2.40, p=0.01; test for trend, p=0.032). Violent offending was strongly associated with post-deployment alcohol misuse (violent offending in 120 [9.0%] of 1363 men with alcohol misuse vs 155 [2.3%] of 6768 with no alcohol misuse; 2.16, 1.62-2.90; p<0.0001), post-traumatic stress disorder (violent offending in 25 [8.6%] of 344 men with post-traumatic stress disorder vs 221 [3.0%] of 7256 with no symptoms of post-traumatic stress disorder; 2.20, 1.36-3.55; p=0.001), and high levels of self-reported aggressive behaviour (violent offending in 56 [6.7%] of 856 men with an aggression score of six to 16 vs 22 [1.2%] of 1685 with an aggression score of zero; 2.47, 1.37-4.46; p=0.003). Of the post-traumatic stress disorder symptoms, the hyperarousal cluster was most strongly associated with violent offending (2.01, 1.50-2.70; p<0.0001). INTERPRETATION: Alcohol misuse and aggressive behaviour might be appropriate targets for interventions, but any action must be evidence based. Post-traumatic stress disorder, though less prevalent, is also a risk factor for violence, especially hyperarousal symptoms, so if diagnosed it should be appropriately treated and associated risk monitored. FUNDING: Medical Research Council and the UK Ministry of Defence.

Effects of radiation mitigating amino acid mixture on mice of different sexes.

To date, few FDA-approved medical countermeasures are available for addressing hematopoietic acute radiation syndrome (H-ARS). In this study, we present our latest research findings focusing on the evaluation of a novel radiation mitigator known as the mitigating amino acid mixture (MAAM). MAAM is composed of five amino acids as the recently reported amino acid-based oral rehydration solution for mitigating gastrointestinal (GI)-ARS. CD2F1 male and female mice were exposed to 60Co-γ total body irradiation (TBI) at 9.0 or 9.5 Gy. Following irradiation, mice were orally administered with MAAM or a saline vehicle control once daily for a duration of 14 days, commencing 24 h after TBI. Mouse survival and body weight change were monitored for 30 days after irradiation. Complete blood counts (CBCs), bone marrow (BM) stem and progenitor cell survival (clonogenicity), and a serum cytokine antibody array were analyzed using samples from day 30 surviving mice. Our data revealed that MAAM treatment significantly enhanced survival rates in irradiated male CD2F1 mice, and the survival rate increased from 25% in the vehicle control group to 60% in the MAAM-treated group (p < 0.05) after 9.0 Gy TBI. The number of BM colonies significantly increased from 41.8 ± 6.4 /104 cells (in the vehicle group) to 78.5 ± 17.0 /104 cells (in the MAAM group) following 9.0 Gy TBI. Furthermore, MAAM treatment led to a decrease in the levels of six cytokines/proteins [cluster of differentiation 40 (CD40), interleukin (IL)-17A, C-X-C motif chemokine 10 (CXCL10/CRG-2), cutaneous T cell-attracting chemokine (CTACK), macrophage inflammatory protein (MIP)-3ß, and IL-1ß] and an increase in the levels of five other cytokines/proteins [IL-3Rß, IL-5, leptin, IL-6, and stem cell factor (SCF)] in mouse serum compared to the vehicle group after 9.0 Gy TBI. However, similar alleviating effects of MAAM were not observed in the irradiated CD2F1 female mice. The serum cytokine profile in the irradiated female mice was different compared to the irradiated male mice. In summary, our data suggest that the beneficial effects of the mitigative amino acid combination treatment after radiation exposure may depend on sex.

Effects of combined ciprofloxacin and Neulasta therapy on intestinal pathology and gut microbiota after high-dose irradiation in mice.

Introduction: Treatments that currently exist in the strategic national stockpile for acute radiation syndrome (ARS) focus on the hematopoietic subsyndrome, with no treatments on gastrointestinal (GI)-ARS. While the gut microbiota helps maintain host homeostasis by mediating GI epithelial and mucosal integrity, radiation exposure can alter gut commensal microbiota which may leave the host susceptible to opportunistic pathogens and serious sequelae such as sepsis. To mitigate the effects of hematopoietic ARS irradiation, currently approved treatments exist in the form of colony stimulating factors and antibiotics: however, there are few studies examining how these therapeutics affect GI-ARS and the gut microbiota. The aim of our study was to examine the longitudinal effects of Neulasta and/or ciprofloxacin treatment on the gut microbiota after exposure to 9.5 Gy 60Co gamma-radiation in mice. Methods: The gut microbiota of vehicle and drug-treated mice exposed to sham or gamma-radiation was characterized by shotgun sequencing with alpha diversity, beta diversity, and taxonomy analyzed on days 2, 4, 9, and 15 post-irradiation. Results: No significant alpha diversity differences were observed following radiation, while beta diversity shifts and taxonomic profiles revealed significant alterations in Akkermansia, Bacteroides, and Lactobacillus. Ciprofloxacin generally led to lower Shannon diversity and Bacteroides prevalence with increases in Akkermansia and Lactobacillus compared to vehicle treated and irradiated mice. While Neulasta increased Shannon diversity and by day 9 had more similar taxonomic profiles to sham than ciprofloxacin-or vehicle-treated irradiated animals. Combined therapy of Neulasta and ciprofloxacin induced a decrease in Shannon diversity and resulted in unique taxonomic profiles early post-irradiation, returning closer to vehicle-treated levels over time, but persistent increases in Akkermansia and Bacteroides compared to Neulasta alone. Discussion: This study provides a framework for the identification of microbial elements that may influence radiosensitivity, biodosimetry and the efficacy of potential therapeutics. Moreover, increased survival from H-ARS using these therapeutics may affect the symptoms and appearance of what may have been subclinical GI-ARS.

Risk factors for headache in the UK military: cross-sectional and longitudinal analyses.

AIMS: To assess the importance of service demographic, mental disorders, and deployment factors on headache severity and prevalence, and to assess the impact of headache on functional impairment. BACKGROUND: There is no information on prevalence and risk factors of headache in the UK military. Recent US reports suggest that deployment, especially a combat role, is associated with headache. Such an association may have serious consequences on personnel during deployment. METHODS: A survey was carried out between 2004 and 2006 (phase 1) and again between 2007 and 2009 (phase 2) of randomly selected UK military personnel to study the health consequences of the Iraq and Afghanistan wars. This study is based on those who participated in phase 2 and includes cross-sectional and longitudinal analyses. Headache severity in the last month and functional impairment at phase 2 were the main outcomes. RESULTS: Forty-six percent complained of headache in phase 2, half of whom endorsed moderate or severe headache. Severe headache was strongly associated with probable post-traumatic stress disorder (multinomial odds ratio [MOR] 9.6, 95% confidence interval [CI] 6.4-14.2), psychological distress (MOR 6.15, 95% CI 4.8-7.9), multiple physical symptoms (MOR 18.2, 95% CI 13.4-24.6) and self-reported mild traumatic brain injury (MOR 3.5, 95% CI 1.4-8.6) after adjustment for service demographic factors. Mild headache was also associated with these variables but at a lower level. Moderate and severe headache were associated with functional impairment, but the association was partially explained by mental disorders. Mental ill health was also associated with reporting moderate and severe headache at both phase 1 and phase 2. Deployment and a combat role were not associated with headache. CONCLUSION: Moderate and severe headache are common in the military and have an impact on functional impairment. They are more strongly associated with mental disorders than with mild traumatic brain injury.

Early Service leavers: a study of the factors associated with premature separation from the UK Armed Forces and the mental health of those that leave early.

BACKGROUND: Approximately 18,000 personnel leave the UK Armed Forces annually. Those leaving before completing the minimum term of their contracts are called early Service leavers (ESLs). This study aims to identify characteristics associated with being an ESL, and compare the post-discharge mental health of ESLs and other Service leavers (non-ESLs). METHOD: A cross-sectional study used data on ex-Serving UK Armed Forces personnel. ESLs were personnel leaving before completing their 3-4.5 years minimum Service contracts and were compared with non-ESLs. Multivariable logistic regression was used to estimate odds ratios and 95% confidence intervals for the associations between Service leaving status with socio-demographics, military characteristics and mental health outcomes. RESULTS: Of 845 Service leavers, 80 (9.5%) were ESLs. Being an ESL was associated with younger age, female sex, not being in a relationship, lower rank, serving in the Army and with a trend of reporting higher levels of childhood adversity, but not with deployment to Iraq. ESLs were at an increased risk of probable post-traumatic stress disorder (PTSD), common mental disorders, fatigue and multiple physical symptoms, but not alcohol misuse. CONCLUSIONS: The study suggests that operational Service is not a factor causing personnel to become an ESL. Current mental health problems were more commonly reported among ESLs than other Service leavers. There may be a need to target interventions to ESLs on leaving Service to smooth their transition to civilian life and prevent the negative mental health outcomes experienced by ESLs further down the line.

Irritable bowel syndrome in the UK military after deployment to Iraq: what are the risk factors?

PURPOSE: Diarrhoea and vomiting (D & V) was common in military personnel during deployment to the initial phases of the Iraq war. D & V is an established risk factor for irritable bowel syndrome (IBS). This study examined the prevalence of IBS in a military sample with a history of deployment to Iraq and the association between D & V and common mental disorder (CMD) with IBS. METHODS: The study used data from a two-phase cohort study of military/personnel. The sample was restricted to individuals who had been deployed to Iraq before phase 1 of the study and who had completed the self-report D & V question. A measure of probable IBS was derived at both phases of the study based on self-reported symptoms in the previous month. CMD was assessed by the General Health Questionnaire (GHQ-12). RESULTS: Fifty-nine percent of the sample reported a D & V event and 6.6 % met the criteria for probable IBS at phase 1. Reporting D & V, thinking one might be killed on deployment, poor physical health and CMD were associated with probable IBS at phase 1. CMD at phase 1 was strongly associated with chronic symptoms of IBS. CONCLUSIONS: There was a high prevalence of D & V during deployment to the early stages of the Iraq war, yet the prevalence of probable IBS on return from deployment was relatively low. D & V was strongly associated with IBS after deployment, and CMD was a risk factor for chronic symptoms of IBS.

The gut microbiome changes in wild type and IL-18 knockout mice after 9.0 Gy total body irradiation.

BACKGROUND: Recent studies have shown that gut microbiome plays important roles in response to radiation exposure. IL-18, an inflammatory cytokine, is highly elevated in mice, mini-pigs and nonhuman primates after radiation exposure. Blocking IL-18 using its endogenous binding protein (IL-18BP) increases mice survival after radiation exposure by decreasing bone marrow interferon-gamma levels. METHODS: To further characterize the roles of IL-18 in response to radiation, both wild type and IL-18 knockout (IL-18 KO) mice were exposed to 9.0 Gy total body irradiation (TBI). The 30-day survival result demonstrated that IL-18 KO mice were significantly more resistant to radiation compared to the wild type mice (p < 0.0001). Mouse faecal samples were collected at pre-radiation (d0), d1, d3, d7, d14, d21 and d29 after radiation exposure. Microbiome profiling was performed on the faecal samples using 16S and ITS sequencing technology. RESULTS: Data analysis showed that there was significant difference in the bacterial microbiome between wild type and IL-18 KO mice. Cohousing of wild type and IL-18 KO mice decreased the bacterial microbiome difference between the two genotypes. Much fewer bacterial genera were significantly changed in wild type mice than the IL-18 KO mice after radiation exposure. The different composition of the IL-18 KO mice and wild type mice persisted even after radiation exposure. Bacterial genera that significantly correlated with other genera were identified in the IL-18 KO and wild type mice. The metabolic pathways that differentially expressed in both genotypes were identified. The animal bacterial microbiome data could be used to predict the animal's radiation status. The fungal microbiome had no significant difference regarding genotype or time after radiation exposure. CONCLUSION: The current study helps understand the gut microbiome in different genetic backgrounds and its temporal changes after radiation exposure. Our data provide insight into the mechanisms underlying radiation-induced toxicity and help identify bacteria important in response to radiation.

The Roles of IL-18 in a Realistic Partial Body Irradiation with 5% Bone Marrow Sparing (PBI/BM5) Model.

IL-18 has been shown to play important roles in response to total body irradiation. However, homogenous total body irradiation is not a realistic model to reflect the radiation exposure in a real nuclear event. To further study the roles of IL-18 in a real nuclear scenario, we developed a mouse partial body irradiation with 5% bone marrow sparing (PBI/BM5) model to mimic the inhomogeneous radiation exposure. We established the dose response curves of PBI/BM5 using different radiation doses ranging from 12 to 16 Gy. Using the PBI/BM5 model, we showed that IL-18 knockout mice were significantly more radiation resistant than the wild-type mice at 14.73 Gy. We further studied the hematopoietic changes using a complete blood count, bone marrow colony-forming assays, and serum cytokine assays on the mice exposed to PBI/BM5 with IL-18BP treatment and wild-type/IL-18 knockout mice. In conclusion, our data suggest that IL-18 plays important roles in mouse survival in a realistic nuclear exposure model, potentially through the IL-18/IFNγ pathway.

Health and well-being of serving and ex-serving UK Armed Forces personnel: protocol for the fourth phase of a longitudinal cohort study.

INTRODUCTION: This is the fourth phase of a longitudinal cohort study (2022-2023) to investigate the health and well-being of UK serving (Regulars and Reservists) and ex-serving personnel (veterans) who served during the era of the Iraq and Afghanistan conflicts. The cohort was established in 2003 and has collected data over three previous phases including Phase 1 (2004-2006), Phase 2 (2007-2009) and Phase 3 (2014-2016). METHODS AND ANALYSIS: Participants are eligible to take part if they completed the King's Centre for Military Health Research Health and Wellbeing Cohort Study at Phase 3 (2014-2016) and consented to be recontacted (N=7608). Participants will be recruited through email, post and text message to complete an online or paper questionnaire. Data are being collected between January 2022 and September 2023. Health and well-being measures include measures used in previous phases that assess common mental disorders, post-traumatic stress disorder (PTSD) and alcohol misuse. Other areas of interest assess employment, help-seeking and family relationships. New topics include the impact of the British withdrawal from Afghanistan in 2021, complex PTSD (C-PTSD), illicit drug use, gambling and loneliness. Analyses will describe the effect size between groups deployed to Iraq and/or Afghanistan or not deployed, and those who are currently in service versus ex-service personnel, respectively, reporting prevalences with 95% CIs, and ORs with 95% CI. Multivariable logistic and multiple linear regression analyses will be conducted to assess various health and well-being outcomes and associations with risk and protective factors. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Ministry of Defence Research Ethics Committee (Ref: 2061/MODREC/21). Participants are provided with information and agree to a series of consent statements before taking part. Findings will be disseminated to UK Armed Forces stakeholders and international research institutions through stakeholder meetings, project reports and scientific publications.

Ciprofloxacin and pegylated G-CSF combined therapy mitigates brain hemorrhage and mortality induced by ionizing irradiation.

Introduction: Brain hemorrhage was found between 13 and 16 days after acute whole-body 9.5 Gy 60Co-γ irradiation (IR). This study tested countermeasures mitigating brain hemorrhage and increasing survival from IR. Previously, we found that pegylated G-CSF therapy (PEG) (i.e., Neulasta®, an FDA-approved drug) improved survival post-IR by 20-40%. This study investigated whether Ciprofloxacin (CIP) could enhance PEG-induced survival and whether IR-induced brain hemorrhage could be mitigated by PEG alone or combined with CIP. Methods: B6D2F1 female mice were exposed to 60Co-γ-radiation. CIP was fed to mice for 21 days. PEG was injected on days 1, 8, and 15. 30-day survival and weight loss were studied in mice treated with vehicles, CIP, PEG, or PEG + CIP. For the early time point study, blood and sternums on days 2, 4, 9, and 15 and brains on day 15 post-IR were collected. Platelet numbers, brain hemorrhage, and histopathology were analyzed. The cerebellum/pons/medulla oblongata were detected with glial fibrillary acidic protein (GFAP), p53, p16, interleukin-18 (IL-18), ICAM1, Claudin 2, ZO-1, and complement protein 3 (C3). Results: CIP + PEG enhanced survival after IR by 85% vs. the 30% improvement by PEG alone. IR depleted platelets, which was mitigated by PEG or CIP + PEG. Brain hemorrhage, both surface and intracranial, was observed, whereas the sham mice displayed no hemorrhage. CIP or CIP + PEG significantly mitigated brain hemorrhage. IR reduced GFAP levels that were recovered by CIP or CIP + PEG, but not by PEG alone. IR increased IL-18 levels on day 4 only, which was inhibited by CIP alone, PEG alone, or PEG + CIP. IR increased C3 on day 4 and day 15 and that coincided with the occurrence of brain hemorrhage on day 15. IR increased phosphorylated p53 and p53 levels, which was mitigated by CIP, PEG or PEG + CIP. P16, Claudin 2, and ZO-1 were not altered; ICAM1 was increased. Discussion: CIP + PEG enhanced survival post-IR more than PEG alone. The Concurrence of brain hemorrhage, C3 increases and p53 activation post-IR suggests their involvement in the IR-induced brain impairment. CIP + PEG effectively mitigated the brain lesions, suggesting effectiveness of CIP + PEG therapy for treating the IR-induced brain hemorrhage by recovering GFAP and platelets and reducing C3 and p53.

The long-term consequences of military deployment: a 5-year cohort study of United kingdom reservists deployed to Iraq in 2003.

Reserve and National Guard forces have been mobilized to an unprecedented degree in recent overseas conflicts. There is concern that rates of psychological problems may continue to rise for many years after deployment. The authors conducted a cohort study of 552 United Kingdom Reservists who deployed to Iraq in 2003 and 391 nondeployed Reservists. Measures of mental health and social functioning were collected a mean of 16 months and 4.8 years after return from possible deployment. At the first follow-up, deployment was associated with increased common mental disorder, post-traumatic stress disorder (PTSD), and poor general health. By the second follow-up, those who had deployed were no longer at increased risk for common mental disorder or poor general health and had good levels of social functioning. However, those who deployed continued to have over twice the odds of PTSD (odds ratio = 2.42, 95% confidence interval: 1.04, 5.62) and were more likely to report actual or serious consideration of separation from their partner. In conclusion, the authors found that the majority of mental health and social problems following deployment are transient. However, Reservists who deployed in the Iraq War remain at increased risk of PTSD and relationship problems 5 years after their tour of duty.

Frequency of mild traumatic brain injury in Iraq and Afghanistan: are we measuring incidence or prevalence?

OBJECTIVE: : Rates of mild traumatic brain injury (mTBI) differ considerably between US and UK forces, despite similar methodology and similar exposure risks. We assessed, in the UK forces, if the differences in rates based on last deployment can be explained by differences in deployment length, given that US forces deploy for approximately twice as long as UK forces. PARTICIPANTS: : A total of 3763 personnel deployed to Iraq or Afghanistan who completed a questionnaire between 2007 and 2009. MAIN OUTCOME MEASURES: : Mild traumatic brain injury in the last deployment contrasted to current posttraumatic stress disorder, psychological distress (General Health Questionnaire-12), multiple physical symptoms, and alcohol misuse. RESULTS: : In the Army and Royal Marines, there was an association between length of deployment (per month) and mTBI (odds ratio: 1.31, 95% confidence interval: 1.13-1.51), which remained significant after adjustment for confounders (odds ratio: 1.25, 95% confidence interval: 1.08-1.45). No other outcome was associated with length of deployment. Results based on the total sample were similar to those in the Royal Marine and Army sample, except for adjusted multiple physical symptoms. CONCLUSIONS: : Comparisons of mTBI rates should take account of length of deployment when based on last deployment. Doing so reduces but does not eliminate the differences between UK and US forces.