Upper Limb Function in People With Upper and Lower Limb Loss 8 Years Postinjury: The Armed Services Trauma Outcome Study (ADVANCE) Cohort Study.

OBJECTIVE: Upper limb (UL) disability in people with UL amputation/s is well reported in the literature, less so for people with lower limb amputation/s. This study aimed to compare UL disability in injured (major trauma) and uninjured UK military personnel, with particular focus on people with upper and lower limb amputation/s. METHODS: A volunteer sample of injured (n = 579) and uninjured (n = 566) UK military personnel who served in a combat role in the Afghanistan war were frequency matched on age, sex, service, rank, regiment, role, and deployment period and recruited to the Armed Services Trauma Rehabilitation Outcome (ADVANCE) longitudinal cohort study. Participants completed the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire, scored from 0 (no disability) to 100 (maximum disability) 8 years postinjury. Mann-Whitney U and Kruskal Wallis tests were used to compared DASH scores between groups. An ordinal model was used to assess the effect of injury and amputation on DASH scores. RESULTS: DASH scores were higher in the group with injuries compared to the group without injuries (3.33 vs 0.00) and higher in people with lower limb loss compared to the group without injuries (0.83 vs 0.00), although this was not statistically significant. In the adjusted ordinal model, the odds of having a higher DASH score was 1.70 (95% CI = 1.18-2.47) times higher for people with lower limb loss compared to the group without injuries. DASH score was not significantly different between people with major and partial UL loss (15.42 vs 12.92). The odds of having a higher DASH score was 8.30 (95% CI = 5.07-13.60) times higher for people with UL loss compared to the uninjured group. CONCLUSION: People with lower limb loss have increased odds of having more UL disability than the uninjured population 8 years postinjury. People with major and partial UL loss have similar UL disability. The ADVANCE study will continue to follow this population for the next 20 years. IMPACT: For the first time, potential for greater upper limb disability has been shown in people with lower limb loss long-term, likely resulting from daily biomechanical compensations such as weight-bearing, balance, and power generation. This population may benefit from prophylactic upper limb rehabilitation, strength, and technique.

The effects of music-based interventions on behavioural and psychological symptoms of people living with dementia: a systematic review and network meta-analysis protocol.

OBJECTIVES: People living with dementia often experience behavioural and psychological symptoms of dementia (BPSD), which severely affect their well-being during the course of the disease. Particularly for BPSD outcomes, there is a high demand for increasing the evidence-based knowledge of non-pharmacological approaches, such as music-based interventions. Although previous reviews emphasize the potential effects of music-based interventions in people with dementia, they cover a wide range of different interventions and outcomes. METHOD: Therefore, this systematic review (SR) and network meta-analysis (NMA) aims to not only investigate the efficacy of music-based interventions on BPSD, but also to compare the impact of different types of music-based interventions on outcomes. Preferred reporting items for SR and meta-analysis protocols (PRISMA-P) and the PRISMA NMA extension were followed. Several databases will be searched from inception to the date the search will be performed, for relevant randomized or non-randomized controlled trials comparing a music-based intervention with treatment as usual, active controls, or another music-based intervention. Multivariate pairwise meta-analyses will be conducted for each outcome. NMA based on a frequentist random-effects model will be used to estimate the comparative effects of each type of music-based intervention and related components across outcomes. Heterogeneity will be investigated by meta-regression models. CONCLUSION: Based on our knowledge, this may be the first SR and NMA study to compare the efficacy of different types of music-based interventions. In addition, combined with our multivariate analysis approach, it will allow us to identify potential effect modifiers in music-based intervention for treating BPSD.

Validity of Ultra-Short-Term Heart Rate Variability Derived from Femoral Arterial Pulse Waveform in a British Military Cohort.

Various non-electrocardiogram (ECG) based methods are considered reliable sources of heart rate variability (HRV) measurement. However, the ultra-short recording of a femoral arterial waveform has never been validated against the gold-standard ECG-based 300s HRV and was the aim of this study.A validity study was conducted using a sample from the first follow-up of the longitudinal ADVANCE study UK. The participants were adult servicemen (n = 100); similar in age, rank, and deployment period (Afghanistan 2003-2014). The femoral arterial waveforms (14s) from the pulse wave velocity (PWV) assessment, and ECG (300s) were recorded at rest in the supine position using the Vicorder™ and Bittium Faros™ devices, respectively, in the same session. HRV analysis was performed using Kubios Premium. Resting heart rate (HR) and root mean square of successive differences (RMSSD) were reported. The Bland-Altman %plots were constructed to explore the PWV-ECG agreement in HRV measurement. A further exploratory analysis was conducted across methods and durations.The participants' mean age was 38.0 ± 5.3 years. Both PWV-derived HR (r = 0.85) and RMSSD (rs=0.84) showed strong correlations with their 300s-ECG counterparts (p < 0.001). Mean HR was significantly higher with ECG than PWV (mean bias: -12.71 ± 7.73%, 95%CI: -14.25%, -11.18%). In contrast, the difference in RMSSD between the two methods was non-significant [mean bias: -2.90 ± 37.82% (95%CI: -10.40%, 4.60%)] indicating good agreement. An exploratory analysis of 14s ECG-vs-300s ECG measurement revealed strong agreement in both RMSSD and HR.The 14s PWV-derived RMSSD strongly agrees with the gold-standard (300s-ECG-based) RMSSD at rest. Conversely, HR appears method sensitive.

The Putative Prenyltransferase Nus1 is Required for Filamentation in the Human Fungal Pathogen Candida albicans.

Candida albicans is a major fungal pathogen of humans that can cause serious systemic infections in vulnerable immunocompromised populations. One of its virulence attributes is its capacity to transition between yeast and filamentous morphologies, but our understanding of this process remains incomplete. Here, we analyzed data from a functional genomic screen performed with the C. albicans Gene Replacement And Conditional Expression (GRACE) collection to identify genes crucial for morphogenesis in host-relevant conditions. Through manual scoring of microscopy images coupled with analysis of each image using a deep learning-based method termed Candescence, we identified 307 genes important for filamentation in tissue culture medium at 37 °C with 5% CO2. One such factor was orf19.5963, which is predicted to encode the prenyltransferase Nus1 based on sequence homology to Saccharomyces cerevisiae. We further showed that Nus1 and its predicted interacting partner Rer2 are important for filamentation in multiple liquid filament-inducing conditions as well as for wrinkly colony formation on solid agar. Finally, we highlight that Nus1 and Rer2 likely govern C. albicans morphogenesis due to their importance in intracellular trafficking, as well as maintaining lipid homeostasis. Overall, this work identifies Nus1 and Rer2 as important regulators of C. albicans filamentation and highlights the power of functional genomic screens in advancing our understanding of gene function in human fungal pathogens.

Lifestyle Dimensions of Public Safety Personnel Families: There's No Life Like It.

PURPOSE: The nature and cumulative occupational demands imposed on families of public safety personnel (PSP) are substantial, in many cases non-negotiable, and distinct from the general population accentuating risk factors for family well-being. Despite this reality, the contributions of PSP families are not well understood, and a conceptual framework is needed. The aim of this paper is to summarize contextual factors (lifestyle dimensions) that shape the lives of PSP families; factors supported in the existing, albeit limited, body of research. METHODS: Grounded in the interpretive/constructivist paradigm, a synthesis was central to understanding the lived experiences of PSP families. An interdisciplinary research team engaged in an iterative process of framework analysis to capture the variability and complexity of PSP family life and distilled the overarching lifestyle dimensions. RESULTS: Three lifestyle dimensions-logistics, risks, and identities-emerged from contextual factors and represent distinct aspects of PSP family life. PSP families play a crucial role in that their capacity to accommodate the lifestyle dimensions (i.e., logistics, risks, and identities), without which the PSP could not meet the demands of the profession. CONCLUSION: Promoting awareness of these dimensions and their consequent demands underscores the cumulative demands that put PSP families at risk. Responses from governments, public safety organizations, and communities are required to help PSP families manage non-negotiable elements of the public safety occupation that spill over into family life over which they have no control.

Universal Credit receipt among working-age patients who are accessing specialist mental health services: results from a novel data linkage study.

BACKGROUND: In 2013, Universal Credit (UC) was introduced by the UK Government. Understanding of how UC provision is allocated among people with mental disorders, and its intersection with protected characteristics is limited. This study aimed to explore (1) how UC receipt, including UC conditionality regime, varied among users of specialist mental health services between 2013 and 2019 and (2) associations between sociodemographic and diagnostic patient characteristics and UC receipt. METHODS: Working-age individuals who had accessed specialist mental health services were included if they had their mental health record data successfully linked with administrative benefits data. Associations between sociodemographic, diagnostic patient characteristics and UC receipt were explored using logistic regression models. RESULTS: Of the 143 715 patients, 26.9% had received UC between 2013 and 2019. Four in five patients were allocated to the searching for work conditionality regime during their time on UC. Females were less likely to have received UC (adjusted OR (AOR) 0.87, 95% CI 0.85 to 0.89) than males, and UC receipt decreased with age. Black patients (AOR 1.39, 95% CI 1.34 to 1.44) and patients from mixed and multiple ethnic backgrounds (AOR 1.27, 95% CI 1.18 to 1.38) had a higher likelihood of UC receipt than White patients. UC receipt was lower among patients diagnosed with severe mental illness compared with other psychiatric diagnoses (AOR 0.74, 95% CI 0.71 to 0.77). CONCLUSION: One in four specialist mental health service users had received UC and a large majority were subject to conditionality. The temporality of UC conditionality and mental health service presentation needs further exploration.

Level of perceived social support, and associated factors, in combat-exposed (ex-)military personnel: a systematic review and meta-analysis.

PURPOSE: Combat deployment increases exposure to potentially traumatic events. Perceived social support (PSS) may promote health and recovery from combat trauma. This systematic review and meta-analysis aimed to synthesize studies investigating the level of PSS and associated factors among (ex-)military personnel who served in the Iraq/Afghanistan conflicts. METHODS: Five electronic databases were searched in August 2023 and searches were restricted to the beginning of the Iraq/Afghanistan conflicts in 2001. The search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A quality assessment was carried out, and a meta-analysis and narrative synthesis were performed. RESULTS: In total, 35 papers consisting of 19,073 participants were included. Of these, 31 studies were conducted in the United States (US) and 23 were cross-sectional. The pooled mean PSS score was 54.40 (95% CI: 51.78 to 57.01). Samples with probable post-traumatic stress disorder had a lower mean PSS score (44.40, 95% CI: 39.10 to 49.70). Approximately half of the included studies (n = 19) investigated mental health in relation to PSS, whilst only four explored physical health. The most frequently reported risk factors for low PSS included post-traumatic stress disorder, depression and anxiety, whilst post-traumatic growth and unit support were protective factors. CONCLUSION: Higher levels of PSS were generally associated with more positive psychosocial and mental health-related outcomes following deployment. PSS should be targeted in psychosocial interventions and education programmes. Future research should investigate PSS in (ex-)military personnel across other countries and cultures, based on the lack of studies that focused on PSS in countries outside of the US.

Shorter communications: Exploring the impact of a brief smartphone-based alcohol intervention app (DrinksRation) on the quality of life of UK military veterans.

Alcohol misuse - defined as consuming more than 14 units of alcohol per week - is a well-established problem among veterans. This study investigated the change in quality of life among help-seeking UK veterans who completed a 28-day brief alcohol intervention delivered via a digital smartphone application (called DrinksRation) and have previously sought clinical help for a mental health disorder. This study was a secondary outcome analysis of data collected during a randomised control trial. In total, 123 UK veterans participated in the study and were randomly allocated to either the intervention or control arm. Participants completed self-report questionnaires regarding their alcohol use and quality of life (WHOQOL-BREF) at baseline, day 28 (end of intervention), day 84, and day 168. At the primary endpoint (day 84), we found significantly greater improvements in the intervention arm compared to the control arm for psychological quality of life (Cohen's d = 0.47), and environmental quality of life (d = 0.34). However, we observed no statistically significant differences between the intervention and control arm for social relationships and physical quality of life. Further, for day 168 we found no significant differences. Findings suggest that DrinksRation can increase quality of life among help-seeking veterans who have previously sought help for a mental health disorder, but the increases were modest and restricted to certain domains. Additional treatment may be needed for long-term and sustained improvements in quality of life.

The underlying mechanisms by which Post-Traumatic Growth is associated with cardiovascular health in male UK military personnel: The ADVANCE cohort study.

Post-Traumatic Growth (PTG) is associated with good cardiovascular health, but the mechanisms of this are poorly understood. This cross-sectional analysis assessed whether factors of PTG (Appreciation of Life (AOL), New Possibilities (NP), Personal Strength (PS), Relating to Others (RTO) and Spiritual Change (SC)) are associated with cardiovascular health in a cohort of 1006 male UK military personnel (median age 34). The findings suggest AOL, PS and RTO are associated with better cardiovascular health through cardiometabolic effects (lower levels of triglycerides, and total cholesterol) and haemodynamic functioning (lower diastolic blood pressure), but not inflammation. However, NP and SC were associated with poorer cardiovascular health through cardiometabolic effects (lower levels of high-density lipoproteins and higher levels of total cholesterol) and AOL had a non-linear association with low-density lipoproteins. These findings suggest that the relationship between PTG and cardiovascular functioning is complex and in need of further scrutiny.

Exploratory analysis of spontaneous versus paced breathing on heart rate variability in veterans with combat-related traumatic injury.

BACKGROUND: Respiration is a crucial determinant of autonomic balance and heart rate variability (HRV). The comparative effect of spontaneous versus paced breathing on HRV has been almost exclusively explored in healthy adults and never been investigated in an injured military cohort. OBJECTIVE: To examine the effect of spontaneous versus paced breathing on HRV in veterans with combat-related traumatic injury (CRTI). DESIGN: Observational cohort study. SETTING: ArmeD serVices trAuma rehabilitatioN outComE (ADVANCE) study, Stanford Hall, UK. PARTICIPANTS: The sample consisted of 100 randomly selected participants who sustained CRTI (eg, amputation) during their deployment (Afghanistan 2003-2014) and were recruited into the ongoing ADVANCE prospective cohort study. INTERVENTION: Not applicable. MAIN OUTCOME MEASURE: HRV was recorded using a single-lead ECG. HRV data were acquired during a sequential protocol of 5-minute spontaneous breathing followed immediately by 5 minutes of paced breathing (six cycles/minute) among fully rested and supine participants. HRV was reported using time domain (root mean square of successive differences), frequency domain (low frequency and high frequency) and nonlinear (sample entropy) measures. The agreement between HRV during spontaneous versus paced breathing was examined using the Bland-Altman analysis. RESULTS: The mean age of participants was 36.5 ± 4.6 years. Resting respiratory rate was significantly higher with spontaneous versus paced breathing (13.4 ± 3.4 vs. 7.6 ± 2.0 breaths/minute; p < .001), respectively. Resting mean heart rate and root mean square of successive differences were significantly higher with paced breathing than spontaneous breathing (p < .001). Paced breathing significantly increased median low frequency power than spontaneous breathing (p < .001). No significant difference was found in the absolute power of high frequency between the two breathing protocols. The Bland-Altman analysis revealed poor agreement between HRV values during spontaneous and paced breathing conditions with wide limits of agreement. CONCLUSION: Slow-paced breathing leads to higher HRV than spontaneous breathing and could overestimate resting "natural-state" HRV.

Risk and protective factors for self-harm and suicide behaviours among serving and ex-serving personnel of the UK Armed Forces, Canadian Armed Forces, Australian Defence Force and New Zealand Defence Force: A systematic review.

BACKGROUND: Self-harm and suicide behaviours are a major public health concern. Several factors are associated with these behaviours among military communities. Identifying these factors may have important implications for policy and clinical services. The aim of this review was to identify the risk and protective factors associated with self-harm and suicide behaviours among serving and ex-serving personnel of the United Kingdom Armed Forces, Canadian Armed Forces, Australian Defence Force and New Zealand Defence Force. METHODS: A systematic search of seven online databases (PubMed, Web of Science, Embase, Global Health, PsycINFO, PTSDpubs and CINAHL) was conducted alongside cross-referencing, in October 2022. Following an a priori PROSPERO approved protocol (CRD42022348867), papers were independently screened and assessed for quality. Data were synthesised using a narrative approach. RESULTS: Overall, 28 papers were included: 13 from Canada, 10 from the United Kingdom, five from Australia and none from New Zealand. Identified risk factors included being single/ex-relationship, early service leavers, shorter length of service (but not necessarily early service leavers), junior ranks, exposure to deployment-related traumatic events, physical and mental health diagnoses, and experience of childhood adversity. Protective factors included being married/in a relationship, higher educational attainment, employment, senior ranks, and higher levels of perceived social support. CONCLUSION: Adequate care and support are a necessity for the military community. Prevention and intervention strategies for self-harm and suicide behaviours may be introduced early and may promote social networks as a key source of support. This review found a paucity of peer-reviewed research within some populations. More peer-reviewed research is needed, particularly among these populations where current work is limited, and regarding modifiable risk and protective factors.

Exploring the Occupational Lifestyle Experiences of the Families of Public Safety Personnel.

PURPOSE: Public safety personnel, including first responders, are regularly exposed to physical, social, and psychological risks and occupational requirements. These risks and requirements extend beyond the employee and may also impact the families (for example, work-family conflict, compassion fatigue). Despite recent attention directed at the population's wellness, considerably less attention is directed towards the family. This review investigates how the risks and requirements associated with these occupations affect families' lives and experiences, and correspondingly, how families respond and adapt to these risks. METHODS: In the current qualitative review, we sought to identify and describe the lifestyle experiences of public safety families as they navigate the occupational risks and requirements of public safety work. The inclusion criteria resulted in an analysis of 18 articles, representing only police (n = 11), paramedics (n = 7), and firefighting (n = 10) sectors. RESULTS: We identified and described the experiences of public safety families both by occupation and familial role. Shared familial themes across occupational groups included 'Worry', 'Communication', 'Where do I turn', 'Are they okay', 'Serving alongside', and '(Over)Protective'. However, distinct themes also emerged between different occupational groups and family configurations. Themes prevalent amongst primarily children of police included: 'Worry', 'Let's Laugh Instead', '(Over)Protective', and 'I'm not the Police, my Parent is!'. Experiences differed if the family contained on serving public safety personnel or multiple. CONCLUSION: We identified the shared and unique occupational experiences of public safety families. This review normalizes these experiences and emphasizes the need to develop initiatives to improve the well-being of families and safety employees.

Pain after combat injury in male UK military personnel deployed to Afghanistan.

BACKGROUND: Chronic pain after injury poses a serious health burden. As a result of advances in medical technology, ever more military personnel survive severe combat injuries, but long-term pain outcomes are unknown. We aimed to assess rates of pain in a representative sample of UK military personnel with and without combat injuries. METHODS: We used data from the ADVANCE cohort study (ISRCTN57285353). Individuals deployed as UK armed forces to Afghanistan were recruited to include those with physical combat injuries, and a frequency-matched uninjured comparison group. Participants completed self-reported questionnaires, including 'overall' pain intensity and self-assessment of post-traumatic stress disorder, anxiety, and depression. RESULTS: A total of 579 participants with combat injury, including 161 with amputations, and 565 uninjured participants were included in the analysis (median 8 yr since injury/deployment). Frequency of moderate or severe pain was 18% (n=202), and was higher in the injured group (n=140, 24%) compared with the uninjured group (n=62, 11%, relative risk: 1.1, 95% confidence interval [CI]: 1.0-1.2, P<0.001), and lower in the amputation injury subgroup (n=31, 19%) compared with the non-amputation injury subgroup (n=109, 26%, relative risk: 0.9, 95% CI: 0.9-1.0, P=0.034). Presence of at least moderate pain was associated with higher rates of post-traumatic stress (RR: 3.7, 95% CI: 2.7-5.0), anxiety (RR: 3.2, 95% CI: 2.4-4.3), and depression (RR: 3.4, 95% CI: 2.7-4.5) after accounting for injury. CONCLUSION: Combat injury, but not amputation, was associated with a higher frequency of moderate to severe pain intensity in this cohort, and pain was associated with adverse mental health outcomes.

UBE2A and UBE2B are recruited by an atypical E3 ligase module in UBR4.

UBR4 is a 574 kDa E3 ligase (E3) of the N-degron pathway with roles in neurodevelopment, age-associated muscular atrophy and cancer. The catalytic module that carries out ubiquitin (Ub) transfer remains unknown. Here we identify and characterize a distinct E3 module within human UBR4 consisting of a 'hemiRING' zinc finger, a helical-rich UBR zinc-finger interacting (UZI) subdomain, and an N-terminal region that can serve as an affinity factor for the E2 conjugating enzyme (E2). The structure of an E2-E3 complex provides atomic-level insight into the specificity determinants of the hemiRING toward the cognate E2s UBE2A/UBE2B. Via an allosteric mechanism, the UZI subdomain modestly activates the Ub-loaded E2 (E2∼Ub). We propose attenuated activation is complemented by the intrinsically high lysine reactivity of UBE2A, and their cooperation imparts a reactivity profile important for substrate specificity and optimal degradation kinetics. These findings reveal the mechanistic underpinnings of a neuronal N-degron E3, its specific recruitment of UBE2A, and highlight the underappreciated architectural diversity of cross-brace domains with Ub E3 activity.

Effects of physical activity on depressive symptoms in older caregivers: The IMPACCT randomized controlled trial.

OBJECTIVES: Physical activity (PA) can reduce depressive symptoms but has not been tested amongst depressed older caregivers and their care-recipients. The aim of this single-blind randomized controlled trial was to investigate the effect of a 6-month tailored PA program on depressive symptoms in older caregivers. METHOD: Caregivers were included if they had scores of ≥5 on the 15-item geriatric depression scale (GDS-15). Care-recipients could have any type of physical, mental or cognitive condition requiring support. The PA intervention group completed an individualized program based on the Otago-Plus Exercise Program. The primary outcome was improvement in depressive symptoms in caregivers measured at six and 12 months. RESULTS: Two hundred and twelve participants (91 dyads and 30 caregivers only) were randomized using a 3:3:1 ratio to PA intervention, social-control, and usual-care control groups. There were no significant differences in depressive symptoms of the caregivers between the three groups at 6 months or 12 months. However, more than 50% of caregivers in all three groups no longer had a GDS-15 score ≥5 at 6 months. Further analysis revealed that caregivers in the PA group caring for someone with a standardised mini-mental state examination (SMMSE) score ≥24 had significantly less depressive symptoms than those caring for someone with a SMMSE score <24 compared with social-control (p < 0.02) and usual-care groups (p < 0.02). CONCLUSIONS: A PA intervention may be beneficial for some caregivers in reducing symptoms of depression but may not be as beneficial to caregivers of people living with cognitive impairment.

Factors associated with wearing a facemask in shops in England following removal of a legal requirement to do so during the COVID-19 pandemic.

OBJECTIVES: We aimed to identify psychological factors associated with the use of facemasks in shops in England following removal of legal requirements to do so, and to compare associations with and without legal restrictions. DESIGN: Repeated cross-sectional online surveys (n ≈ 2000 adults) between August 2020 and April 2022 (68,716 responses from 45,682 participants) using quota sampling. METHODS: The outcome measure was whether those who had visited a shop for essentials in the previous seven days reported always having worn a facemask versus sometimes or not at all. Psychological predictor variables included worry, perceived risk and severity of COVID-19 and the perceived effectiveness of facemasks. Socio-demographic variables and measures of clinical vulnerability were also measured. For the period following removal of legal restrictions, multivariable regression was used to assess associations between the primary outcome variable and predictors adjusting for socio-demographic and clinical vulnerability measures. The analysis was repeated including interactions between psychological predictors and presence versus absence of legal restrictions. RESULTS: Worry about COVID-19, beliefs about risks and severity of COVID-19 and effectiveness of facemasks were substantially and independently associated with the use of facemasks. Removal of legal obligations to wear facemasks was associated with a 25% decrease in wearing facemasks and stronger associations between psychological predictors and wearing facemasks. CONCLUSIONS: Legal obligations increase rates of wearing a facemask. Psychological factors associated with wearing a facemask could be targets for interventions aiming to alter rates of wearing a facemask. These interventions may be more effective when there are no legal obligations to wear a face covering in place.

The Influence of Physical and Mental Health Mediators on the Relationship Between Combat-Related Traumatic Injury and Ultra-Short-Term Heart Rate Variability in a U.K. Military Cohort: A Structural Equation Modeling Approach.

INTRODUCTION: Combat-related traumatic injury (CRTI) adversely affects heart rate variability (HRV). The mediating effect of mental and physical health factors on the relationship between CRTI, its severity and HRV has not been previously studied and investigated. MATERIALS AND METHODS: A cross-sectional mediation analysis of the ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE) prospective cohort study was performed. The sample consisted of injured and uninjured British male servicemen who were frequency-matched based on their age, rank, role-in-theater, and deployment to Afghanistan (2003-2014). CRTI and injury severity (the New Injury Severity Scores [NISS] [NISS < 25 and NISS ≥ 25]) were included as exposure variables. HRV was quantified using the root mean square of successive differences (RMSSD) obtained using pulse waveform analysis. Depression and anxiety mediators were quantified using the Patient Health Questionnaire and Generalized Anxiety Disorder, respectively. Body mass index and the 6-minute walk test (6MWT) represented physical health measures. Two mediation pathways between exposure and outcome variables were examined in comparison with the uninjured group using structural equation modeling. RESULTS: Of 862 servicemen, 428 were injured and 434 were uninjured with the mean age at assessment of 33.9 ± 5.4 (range 23-59) years. Structural equation modeling revealed that depression, anxiety, and body mass index did not significantly mediate the relationship between injury/injury severity and RMSSD. However, the 6MWT significantly mediated the relationship between CRTI and RMSSD (27% mediation). The indirect effect of 6MWT on the relationship between injury severity (NISS ≥ 25 vs. uninjured) and RMSSD was -0.06 (95% CI: -0.12, -0.00, P < .05). CONCLUSIONS: The findings suggest that greater physical function may improve HRV following CRTI. Longitudinal studies are warranted to further validate these findings.

Impact of Water- and Land-Based Exercise Training on Risk Factors and Vascular Function in Middle-Aged and Older Men and Women.

INTRODUCTION: Exercise improves vascular function, but it is unclear whether benefits are mediated by traditional cardiovascular risk factors or whether sex differences in training effects exist in older adults. We hypothesized that exercise would improve cardiovascular risk factors, that males and females would benefit similarly, and that improvements in risk factors would correlate with changes in vascular function. METHODS: Seventy-two healthy middle-aged/older adults (age, 62 ± 7 yr; 26%♂) were randomized to a land-walking ( n = 23), water-walking ( n = 25), or a nonexercise control group (C; n = 23). The exercise groups undertook supervised and monitored training three times a week for 50 min per session, across 24 wk. Blood pressure, body composition (dual x-ray absorptiometry), blood lipids and glucose, and flow-mediated brachial artery dilation were assessed in all participants at weeks 0 and 24. To maximize power for sex differences and correlation analyses, we pooled the training groups (land-walking + water-walking). RESULTS: Training prevented increases in LDL and total cholesterol/HDL ratio observed in the nonexercise control group. No group by time interactions were observed for other risk factors. Sex differences in training effects existed for visceral fat (-187 ± 189 g♂ vs -15 ± 161 g♀; P = 0.006) and lean mass (-352 ± 1045 g♂ vs 601 ± 1178 g♀; P = 0.008). Improvement in flow-mediated brachial artery dilation was correlated with decreased waist girth ( r = -0.450, P = 0.036), but not with other risk factors. CONCLUSIONS: Exercise training prevented deterioration in lipid levels, whereas sex differences existed for body composition changes with training. Improvement in vascular function was not dependent on changes in risk factors in middle-aged/older adults, suggesting that artery health may be dependent on other exercise-related stimuli.

Transsphenoidal hypophysectomy for the treatment of hypersomatotropism secondary to a pituitary somatotroph adenoma in a dog.

Pituitary-dependent hypersomatotropism is rarely diagnosed in dogs and surgical treatment is not reported. A 6-year-10-month male neutered Patterdale Terrier presented with polyuria, polydipsia, progressive pharyngeal stertor, excessive hair growth and widened facial features and paws. Serum insulin-like growth factor-1 concentration via radioimmunoassay was consistent with hypersomatotropism (1783 ng/mL). A pituitary mass was identified on magnetic resonance and computed tomography imaging. Six weeks later, glucosuria, starved hyperglycemia and serum fructosamine above the reference range (467.6 µmol/L, RI 177-314) were documented, consistent with diabetes mellitus. Transsphenoidal hypophysectomy was performed under general anesthesia without complications. Pituitary histopathology identified an acidophil neoplasm, with positive immunostaining for growth hormone. Postoperatively, there was rapid resolution of clinical, biochemical and morphologic changes of hypersomatotropism with persistence of diabetes mellitus. This case demonstrates successful resolution of hypersomatotropism with ongoing diabetes mellitus in a dog after surgical treatment by transsphenoidal hypophysectomy.

ALPK1 mutants causing ROSAH syndrome or Spiradenoma are activated by human nucleotide sugars.

The atypical protein kinase ALPK1 is activated by the bacterial nucleotide sugar ADP-heptose and phosphorylates TIFA to switch on a signaling pathway that combats microbial infection. In contrast, ALPK1 mutations cause two human diseases: the ALPK1[T237M] and ALPK1[Y254C] mutations underlie ROSAH syndrome (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis, and migraine headache), while the ALPK1[V1092A] mutation accounts for 45% of spiradenoma and 30% of spiradenocarcinoma cases studied. In this study, we demonstrate that unlike wild-type (WT) ALPK1, the disease-causing ALPK1 mutants trigger the TIFA-dependent activation of an NF-κB/activator protein 1 reporter gene in the absence of ADP-heptose, which can be suppressed by either of two additional mutations in the ADP-heptose binding site that prevent the activation of WT ALPK1 by ADP-heptose. These observations are explained by our key finding that although ALPK1[T237M] and ALPK1[V1092A] are activated by bacterial ADP-heptose, they can also be activated by nucleotide sugars present in human cells (UDP-mannose, ADP-ribose, and cyclic ADP-ribose) which can be prevented by disruption of the ADP-heptose binding site. The ALPK1[V1092A] mutant was also activated by GDP-mannose, which did not activate ALPK1[T237M]. These are new examples of disease-causing mutations permitting the allosteric activation of an enzyme by endogenous molecules that the WT enzyme does not respond to. We propose that the loss of the specificity of ALPK1 for bacterial ADP-heptose underlies ROSAH syndrome and spiradenoma/spiradenocarcinoma caused by ALPK1 mutation.