Use of GLP-1 agonists in high risk patients prior to bariatric surgery: a cohort study.

INTRODUCTION: Body mass index (BMI) > 50 kg/m2 is associated with relatively increased morbidity and mortality with bariatric surgery (BS). There is reluctance to consider these patients operative candidates without preoperative weight loss. Glucagon-like peptide-1 (GLP-1) agonists have demonstrated effective weight loss in the post-BS setting. This study aims to determine the safety and efficacy of GLP-1 agonists in the pre-habilitation of patients with BMI > 50 kg/m2. METHODS: This is a retrospective review of bariatric surgery patients with BMI > 50 kg/m2 from a single bariatric center. Patients were compared by preoperative GLP-1 therapy status. All patients received medical, surgical, psychiatric, and nutritional evaluation and counseling. Preoperative BMI, change in weight from program intake until surgery, time to surgery, and perioperative complications were evaluated. RESULTS: 31 patients were included in the analysis. 18 (58%) received a GLP-1 agonist preoperatively. GLP-1 agonist use was associated with a 5.5 ± 3.2-point reduction in BMI compared to 2.9 ± 2.4 amongst controls (p = 0.026). There was no difference in the mean length of time in the bariatric program prior to surgery between groups (p = 0.332). There were no reported complications related to GLP-1 use in the preoperative setting and no difference in perioperative complications between groups (p = 0.245). DISCUSSION: GLP-1 agonist use in patients with a BMI > 50 kg/m2 results in significantly more weight loss prior to bariatric surgery, without increased time to surgery or complication rate. Further study is required to evaluate the long-term impact of preoperative GLP-1 agonist use prior to bariatric surgery. This therapy may improve perioperative and long-term outcomes in the very high-risk BMI population.

Investigating the impact of fluid status on the ultrasound assessment of muscle quantity and quality in the diagnosis of sarcopenia - a multidimensional cross-sectional study.

BACKGROUND: Sarcopenia is a clinical manifestation of adverse ageing, characterised by progressive loss of muscle mass and function. Diagnosis requires assessment of muscle quantity and quality; ultrasound represents an emerging tool for this. However, ultrasound muscle assessment may be impacted by fluid balance. This is particularly important when assessing for acute sarcopenia in hospitalised patients, where fluid disturbance often occurs. The primary aim of this study was to characterise the impact of fluid status on ultrasound muscle assessment, such that this may be accounted for in sarcopenia diagnostics. METHODS: This Multidimensional Cross-sectional study involved 80 participants, who were inpatients at QEHB, a large UK tertiary centre. Fluid status was evaluated clinically and quantified using Bioelectrical Impedance Analysis (BIA). Muscle quantity was measured using Bilateral Anterior Thigh Thickness (BATT) with Rectus Femoris (RF) echogenicity used to assesses muscle adiposity and hence provide an inverse measure of muscle quality. RESULTS: A significant positive correlation was found between fluid status, measured using BIA, and BATT as a measure of muscle quantity, in males (rs = 0.662, p < 0.001) and females (rs = 0.638, p < 0.001). A significant negative correlation was found between fluid status and RF echogenicity (rs=-0.448, p < 0.001). CONCLUSIONS: These findings demonstrate associations between fluid balance and ultrasound assessment of muscle quantity and quality. Given the emerging use of ultrasound muscle assessment in sarcopenia diagnosis, there is a need to account for this in clinical practice. Future research should focus on the development of a corrective equation allowing assessment of muscle quantity and quality which account for changes in fluid status, hence aiding accurate diagnosis of sarcopenia.

Effects of high intensity interval training on cardiorespiratory fitness and salivary levels of IL-8, IL-1ra, and IP-10 in adults with asthma and non-asthma controls.

OBJECTIVE: The purpose of this study was to determine whether high intensity interval training (HIIT) would lead to improvements in 1) maximal VO2, VE, VE/VCO2, and VE/MVV, and/or 2) resting salivary concentrations of pro-inflammatory markers Interleukin (IL-8), interferon-gamma-inducible-protein (CXCL10/IP-10)) and anti-inflammatory marker IL-1 receptor antagonist (IL-1ra) in adults with well-controlled asthma compared to non-asthma controls. METHODS: Participants completed a maximal exercise test at the beginning (T1) and end (T2) of a 6-week HIIT intervention; saliva samples were obtained at the beginning and 30 min following the first (T1) and last (T2) exercise session. RESULTS: Adults with asthma (n = 20; age: 21.4 ± 2.4 years) and non-asthma controls (n = 12; age: 22.5 ± 3.4 years) completed the intervention. VO2max increased from T1 to T2 in both groups (asthma T1 32.9 ± 8, T2 38.6 ± 8.2 ml/kg/min; controls T1 34.5 ± 11.8, T2 38.9 ± 12.3 ml/kg/min). VEmax also increased in both groups (asthma T1 97.7, T2 110.8 units, p < 0.001, hp2 = <0.04; control T1 106.3, T2 118.1, p < 0.001, hp2 0.02). An increase in VE/VCO2 (F(1, 10)=22.11, p = 0.001) and VE/MVV (F(1, 10) = 111.30, p < 0.001) was observed in the control group; no differences were observed in the asthma group. No differences in IL-8 or IL-1ra were observed between groups. In the asthma group, resting salivary IP-10 concentrations significantly decreased from T1 (0.025 pg/ug protein) to T2 (0.015 pg/ug protein, p = 0.039, hp2 = 0.3 (moderate effect)). CONCLUSION: A 6-week HIIT intervention led to a similar increase in VO2max and VEmax in those with and without asthma, and a decrease in resting salivary IP-10 levels among adults with asthma.

Attention-Deficit/Hyperactivity Disorder and Alcohol and Other Substance Use Disorders in Young Adulthood: Findings from a Canadian Nationally Representative Survey.

AIM: (a) To document the prevalence and odds of (i) alcohol use disorders, (ii) cannabis use disorders, (iii) other drug use disorders and (iv) any substance use disorder (SUD), among young adults with and without ADHD, and (b) to investigate the degree to which the association between ADHD and SUDs is attenuated by socio-demographics, early adversities and mental health. METHOD: Secondary analysis of the nationally representative Canadian Community Health Survey-Mental Health (CCHS-MH). The sample included 6872 respondents aged 20-39, of whom 270 had ADHD. The survey response rate was 68.9%. MEASUREMENTS: Substance Use Disorder: World Health Organization's Composite International Diagnostic Interview criteria, SUDs, were derived from lifetime algorithms for alcohol, cannabis and other substance abuse or dependence. ADHD was based on self-report of a health professional's diagnosis. FINDINGS: One in three young adults with ADHD had a lifetime alcohol use disorder (36%) compared to 19% of those without ADHD (P < 0.001). After adjusting for all control variables, those with ADHD had higher odds of developing alcohol use disorders (OR = 1.38, 95% CI: 1.05, 1.81), cannabis use disorders (OR = 1.46, 95% CI: 1.06, 2.00), other drug use disorders (OR = 2.07, 95% CI: 1.46, 2.95) and any SUD (OR = 1.69, 95% CI: 1.28, 2.23). History of depression and anxiety led to the largest attenuation of the ADHD-SUD relationship, followed by childhood adversities and socioeconomic status. CONCLUSIONS: Young adults with ADHD have a high prevalence of alcohol and other SUDs. Targeted outreach and interventions for this extremely vulnerable population are warranted.

ADVANCE integrated group intervention to address both substance use and intimate partner abuse perpetration by men in substance use treatment: a feasibility randomised controlled trial.

BACKGROUND: Substance use is a risk factor for intimate partner abuse (IPA) perpetration. Delivering perpetrator interventions concurrently with substance use treatment shows promise. METHODS: The feasibility of conducting an efficacy and cost-effectiveness trial of the ADVANCE 16-week intervention to reduce IPA by men in substance use treatment was explored. A multicentre, parallel group individually randomised controlled feasibility trial and formative evaluation was conducted. Over three temporal cycles, 104 men who had perpetrated IPA towards a female (ex) partner in the past year were randomly allocated to receive the ADVANCE intervention + substance use treatment as usual (TAU) (n = 54) or TAU only (n = 50) and assessed 16-weeks post-randomisation. Participants' (ex) partners were offered support and 27 provided outcome data. Thirty-one staff and 12 men who attended the intervention participated in focus groups or interviews that were analysed using the framework approach. Pre-specified criteria assessed the feasibility of progression to a definitive trial: 1) ≥ 60% of eligible male participants recruited; 2) intervention acceptable to staff and male participants; 3) ≥ 70% of participants followed-up and 4) levels of substance use and 5) IPA perpetrated by men in the intervention arm did not increase from average baseline level at 16-weeks post-randomisation. RESULTS: 70.7% (104/147) of eligible men were recruited. The formative evaluation confirmed the intervention's acceptability. Therapeutic alliance and session satisfaction were rated highly. The overall median rate of intervention session attendance (of 14 compulsory sessions) was 28.6% (range 14.3-64.3% by the third cycle). 49.0% (51/104) of men and 63.0% (17/27) of their (ex) partners were followed-up 16-weeks post-randomisation. This increased to 100% of men and women by cycle three. At follow-up, neither substance use nor IPA perpetration had worsened for men in the intervention arm. CONCLUSIONS: It was feasible to deliver the ADVANCE intervention in substance use treatment services, although it proved difficult to collect data from female (ex)partners. While some progression criteria were met, others were not, although improvements were demonstrated by the third cycle. Lessons learned will be implemented into the study design for a definitive trial of the ADVANCE intervention. TRIAL REGISTRATION: ISRCTN79435190 prospectively registered 22nd May 2018.

The Challenges of Conducting Qualitative Research on "couples" in Abusive Intimate Partner Relationships Involving Substance Use.

Undertaking qualitative dyad or couple interviews involving intimate partner abuse and substance use presents considerable ethical, safeguarding, and theoretical challenges throughout the research process from recruitment to conducting interviews and analysis. These challenges and how they were managed are outlined using the experience from a qualitative study of 14 heterosexual "couples" that explored the complex interplay between intimate partner abuse and substance use. Managing these challenges for participants, their families, and researchers included the use of safeguarding protocols and procedures to manage risk and the provision of clinical support for experienced researchers. Researchers often felt drawn into the conflicts and complex dynamics of opposing accounts from the male and females' relationship which could be emotionally and methodologically taxing. Researchers discussing their analysis and felt experiences with each other provided a reflexive space to manage emotions and stay close to the theoretical underpinnings.

'Obedient, but cheeky': Human expectations of canine behaviour and companionship.

Whilst dogs are adored companions worldwide, high numbers continue to be relinquished each year due to perceived behavioral concerns. Subsequently, this paper addresses the question; What are guardian's expectations of canine behavior and companionship? A total of 175 participants responded to a qualitative semi-structured survey, distributed online. Following a reflexive thematic analysis , five themes are discussed; A well-balanced dog, Obedient, Affection and Connection, Shared Interests, and Commitment. The findings highlight a wide range of expectations typically moving beyond realistic behavior and capabilities for both dogs and guardians. Resultantly, we call for clearer conceptualization of canine behavior, particularly in relation to the distinction between observable behavior and behavioral interpretations (personality, temperament etc.). Clarification on the facets of dog behavior, in addition to better understanding guardian expectations, will aid the development of educational materials aimed at supporting existing human-dog relationships and the adoption matching process within canine adoptions. Cumulatively, this would aid successful human-dog bonding, reducing the risk for relinquishment. These findings build on the recently proposed Perceived Canine Reactivity Framework.

Baseline Nutritional Status and In-Hospital Step Count are Associated with Muscle Quantity, Quality, and Function: Results of an Exploratory Study.

This exploratory study aimed to assess associations of baseline nutritional status and in-hospital step count with muscle quantity, quality, and function. Seventy-nine participants aged ≥70 years (mean age 79.1 years, 44.3% female) were recruited (elective colorectal surgery, emergency abdominal surgery, and general medical patients with infections). Baseline nutrition (Mini Nutritional Assessment) and in-hospital step count (Fitbit Inspire devices) were assessed. Ultrasound quadriceps, bioelectrical impedance analysis, and physical function were assessed at baseline and 7 (±2) days and 13 (±1) weeks post-admission/post-operatively. Baseline nutritional status was associated with baseline rectus femoris ultrasound echogenicity (normal: 58.5, at risk: 68.5, malnourished: 81.2; p = 0.025), bilateral anterior thigh thickness (normal: 5.07 cm, at risk: 4.03 cm, malnourished: 3.05 cm; p = 0.021), and skeletal muscle mass (Sergi equation) (normal: 21.6 kg, at risk: 18.2 kg, malnourished: 12.0 kg; p = 0.007). Step count was associated with baseline patient-reported physical function (<900 37.1, ≥900 44.5; p = 0.010). There was a significant interaction between nutrition, step count, and time for skeletal muscle mass (Janssen equation) (p = 0.022).

Trajectories of muscle quantity, quality and function measurements in hospitalized older adults.

AIM: Acute sarcopenia is defined by the development of incident sarcopenia (low muscle quantity/quality and function) within 6 months of a stressor event. However, outcome measures for clinical trials have not been validated. This study aimed to characterize changes in muscle quantity, quality, strength, and physical function during and after hospitalization. METHODS: Patients aged ≥70 years admitted for elective colorectal surgery, emergency abdominal surgery or acute infections were recruited from a single university hospital. Assessments were carried out at baseline, and within 7 ± 2 days and 13 ± 1 weeks postoperatively or post-admission. RESULTS: A total of 79 participants (mean age 79 years, 39% female) were included. Physical function defined by the Patient-Reported Outcome Measures Information System T-score declined from baseline (42.3, 95% CI 40.2-44.3) to 7 days (36.6, 95% CI 34.5-38.8; P = 0.001), with improvement after 13 weeks (40.5, 95% CI 37.9-43.0). Changes in muscle quantity, quality and function measurements were overall heterogeneous, with few significant changes at the study population level. Change in rectus femoris echogenicity over 13 weeks correlated with changes in handgrip strength (r = 0.53; P < 0.001) and gait speed (r = 0.59; P = 0.003) over the same period. CONCLUSIONS: Patient-Reported Outcome Measures Information System T-score provides a sensitive measure of change in physical function in hospitalized older patients. However, changes in muscle quantity, quality and function measurements were heterogeneous, and not significant at the study population level. Further research should assess for factors that might be predictive of changes within individuals to enable stratified interventions. Geriatr Gerontol Int 2022; 22: 311-318.

Understanding Canine 'Reactivity': Species-Specific Behaviour or Human Inconvenience?

Dogs are often referred to as "human's best friend," with many households in the United Kingdom and worldwide including a dog. Yet, whilst research highlights the myriad of human health benefits associated with canine companionship, many dogs are relinquished, or euthanized, for purported behavioral problems. A key behavior often cited in these situations is Reactivity, despite a lack of consensus in the literature (or in the lay population) as to exactly what is encompassed within this term. Resultantly, this paper reports on an online survey to investigate how the term Reactivity is understood by humans. Following the completion of a thematic analysis, six sub-themes were developed, forming three overarching theme clusters, namely; Canine Characteristics, The Importance of Human Perception and Human Capability. In sum, this research highlights the complex, nuanced and, sometimes, contradictory nature of understanding around the label of Reactivity, encompassing both canine and human factors. As such, conclusions include the proposal of a preliminary Perceived Reactivity Framework to conceptualize this seemingly multi-faceted concept.

Using the Behaviour Change Wheel to design an intervention for partner abusive men in drug and alcohol treatment.

BACKGROUND: We aimed to establish what core elements were required in a group therapy programme for men who disclose perpetrating intimate partner abuse in a substance use setting and develop, and test the feasibility of delivering an intervention in this setting. METHODS: We describe the theoretical development and feasibility testing of an integrated substance use and intimate partner abuse intervention ('ADVANCE') for delivery in substance use services. We employed a comprehensive eight-stage process to guide this development applying the 'COM-B' ('capability', 'opportunity', 'motivation' and 'behaviour') model for intervention design which specifies the following: (1) define the problem, (2) select the target behaviour, (3) specify the target behaviour, (4) identify what needs to change, (5) identify intervention functions, (6) identify policy categories, (7) select behaviour change techniques, and (8) design a mode of delivery. The development was informed by primary research conducted by the authors, consulting with organisation steering groups and by those with personal experiences. The identified targets for intervention and mode and method of delivery were then refined over 4 intervention development meetings, using the nominal group technique with the ADVANCE experts, then further refined following consultation with service user groups and wider expert groups via a learning alliance meetings. RESULTS: Our final intervention, the ADVANCE intervention consisted of a group intervention comprising of up to four pre-group individual interviews, followed by 12 × 2-h group sessions supported by integrated safety work for victim/survivors, and risk and safety support and integrity support for the professionals. The main targets for change were personal goal planning, self-regulation, and attitudes and beliefs supporting intimate partner abuse. The intervention was regarded as very acceptable to both staff and clients in substance use services, with group attendees reported positive behaviour changes and development of new skills. CONCLUSION: We have demonstrated the ability to employ a structured eight-step process to develop an integrated intervention to address substance use-related intimate partner abuse that is acceptable to staff and clients in substance use services. This led to a feasibility study (ISRCTN 79435190) involving 104 men and 30 staff at three different locations across the UK was conducted to assess the feasibility and acceptability of the intervention and to refine the content and approach to delivery (BMC Public Health, 21: 980, 2021).

What Role Does Substance Use Play in Intimate Partner Violence? A Narrative Analysis of In-Depth Interviews With Men in Substance Use Treatment and Their Current or Former Female Partner.

Few studies have examined intimate partner violence (IPV) in relationships where one or both partners are in treatment for substance use, from the perspectives of both members of a couple. This study used thematic and narrative analysis of the accounts of 14 men recruited from substance use services and 14 women who were their current or former intimate partners. Separate researchers interviewed men and women from the same dyad pair. The psychopharmacological effects of substance use (including intoxication, craving, and withdrawal) were rarely the only explanation offered for IPV. Violence was reported to be primed and entangled with sexual jealousy, with perceptions of female impropriety and with women's opposition to male authority. Both partners reported adversities and psychological vulnerabilities that they considered relevant to conflict and abuse. Male participants were more likely to describe IPV as uncharacteristic isolated events that arose from specific disputes-either aggravated by intoxication or withdrawal or about substance use and its resourcing-whereas women described enduring patterns of abusive behavior often linked to intoxication, craving, withdrawal, and to disputes linked to raising funds for substances. In relationships where both partners used substances, men described the need to protect their partners from addiction and from unscrupulous others while women described highly controlling behavior. In relationships where women were not dependent substance users, they reported the combined effects of psychological and financial abuse often linked to recurring patterns of substance use and relapse. These findings highlight the challenges faced by practitioners working with male perpetrators who use substances as well as the need of those working with women who have been abused to engage with the ways in which hesitance to leave male abusers can be complicated by shared drug dependency.

Interventions to Reduce Intimate Partner Violence Perpetration by Men Who Use Substances: A Systematic Review and Meta-Analysis of Efficacy.

INTRODUCTION: Despite the high prevalence of intimate partner violence (IPV) perpetration by men who use substances, limited evidence exists about how best to reduce IPV among this group. METHOD: A systematic narrative review with meta-analysis determined the effectiveness of interventions to reduce IPV by men who use substances. Inclusion criteria were randomized and nonrandomized controlled trials; adult heterosexual male IPV perpetrators where at least 60% of participants were alcohol and/or drug users; the intervention targeted IPV with or without targeting substance use (SU); outcomes included perpetrator and/or victim reports of IPV, SU, or both. Methodological quality was assessed. RESULTS: Nine trials (n = 1,014 men) were identified. Interventions were grouped into (1) integrated IPV and SU interventions (n = 5), (2) IPV interventions with adjunct SU interventions (n = 2), and (3) stand-alone IPV interventions (n = 2). Cognitive behavioral and motivational interviewing therapies were the most common approaches. Data from individual trials showed a reduction in SU outcomes in the short term (≤3months; n = 2 trials) and IPV perpetration at different time points (n = 3 trials) for interventions compared with treatment as usual (TAU). Meta-analysis with integrated IPV and SU interventions showed no difference in SU (n = 3 trials) or IPV outcomes (n = 4 trials) versus SU TAU. CONCLUSIONS: Little evidence exists for effective interventions for male IPV perpetrators who use substances. Outcomes in integrated interventions were not superior to TAU in meta-analysis. Future trials should consider the nature of the relationship between IPV and SU in intervention design, duration of intervention, and type and timing of outcome measures. .

Better Together? Combining Cover Crop Mulches, Organic Herbicides, and Weed Seed Biological Control in Reduced-Tillage Systems.

Organic vegetable farmers rely heavily on labor-intensive tillage for weed management, which adversely affects soil health and harms beneficial insects that consume crop pests and weed seeds. Using cover crop residues as a weed-suppressive mulch enables some reduction in tillage, and combining this tool with recently developed organic herbicides may further enhance weed suppression in vegetable production. However, organic herbicides may also adversely affect beneficial insects, and their nontarget effects are unknown. Here, we examine the combined impacts of cultural and chemical tools on weed cover while monitoring activity of beneficial epigeal insects and measuring rates of weed seed biological control to assess potential nontarget effects of organic herbicides. In a 2-yr experiment, we compared three cover crop mulch treatments and three organic herbicide treatments (capric/caprylic acid, corn gluten meal, and herbicide-free) in a reduced-tillage system. Organic herbicides led to no reductions in beneficial insect activity nor weed seed biocontrol. In both years, capric/caprylic acid herbicide and cover crop mulches reduced weed pressure relative to a fallow control treatment, whereas corn gluten meal had no effect. In year 2, a combination of cover crop mulch with organic herbicide had the greatest weed suppression relative to the fallow control. Integrated weed management is a perpetual challenge, but our results suggest that organic herbicides used in concert with cover crop mulch may enhance weed control and reduce the need for tillage, with limited collateral damage to natural enemies.

A study protocol to assess the feasibility of conducting an evaluation trial of the ADVANCE integrated intervention to address both substance use and intimate partner abuse perpetration to men in substance use treatment.

BACKGROUND: Strong evidence exists that substance use is a contributory risk factor for intimate partner abuse (IPA) perpetration. Men in substance use treatment are more likely to perpetrate IPA than men from the general population. Despite this, referral pathways are lacking for this group. This trial will assess the feasibility of conducting an evaluation trial of a tailored integrated intervention to address substance use and IPA perpetration to men in substance use treatment. METHODS/DESIGN: ADVANCE is a multicentre, parallel-group individually randomised controlled feasibility trial, with a nested formative evaluation, comparing an integrated intervention to reduce IPA + substance use treatment as usual (TAU) to TAU only. One hundred and eight men who have perpetrated IPA in the past 12 months from community substance use treatment in London, the West Midlands, and the South West will be recruited. ADVANCE is a manualised intervention comprising 2-4 individual sessions (2 compulsory) with a keyworker to set goals, develop a personal safety plan and increase motivation and readiness, followed by a 12-session weekly group intervention delivered in substance use services. Men will be randomly allocated (ratio 1:1) to receive the ADVANCE intervention + TAU or TAU only. Men's female (ex) partners will be invited to provide outcome data and offered support from integrated safety services (ISS). Regular case management meetings between substance use and ISS will manage risk. Outcome measures will be obtained at the end of the intervention (approximately 4 months post-randomisation) for all male and female participants. The main objective of this feasibility trial is to estimate parameters required for planning a definitive trial including rates of consent, recruitment, and follow-up by site and group allocation. Nested formative evaluation including focus groups and in-depth interviews will explore the intervention's acceptability to participants, group facilitators, keyworkers and ISS workers. Secondary outcomes include substance use, IPA, mental health, self-management, health and social care service use, criminal justice contacts, and quality of life. DISCUSSION: Findings from this feasibility trial will inform the design of a multicentre randomised controlled trial evaluating the efficacy and cost-effectiveness of the ADVANCE intervention for reducing IPA and improving the well-being of female (ex)partners. TRIAL REGISTRATION: ISRCTN79435190.

Effects of estrogen receptor agonists on regulation of the inflammatory response in astrocytes from young adult and middle-aged female rats.

Estrogen has been shown to attenuate the inflammatory response following injury or lipopolysaccharide treatment in several organ systems. Estrogen's actions are transduced through two estrogen receptor sub-types, estrogen receptor (ER) -alpha and estrogen receptor-beta, whose actions may be overlapping or independent of each other. The present study examined the effects of ERalpha- and ERbeta-specific ligands in regulating the inflammatory response in primary astrocyte cultures. Pre-treatment with 17beta-estradiol (ERalpha/ERbeta agonist), HPTE (ERalpha agonist/ERbeta antagonist) and DPN (ERbeta agonist) led to attenuation of IL-1beta, TNFalpha, and MMP-9 in astrocyte media derived from young adult (3-4 mos.) and reproductive senescent female (9-11 mos., acyclic) astrocyte cultures, while pretreatment with PPT (ERalpha agonist) attenuated IL-1beta (but not MMP-9) in both young and senescent-derived astrocyte cultures. Our previous work determined that 17beta-estradiol was unable to attenuate the LPS-induced increase in IL-1beta in olfactory bulb primary microglial cultures derived from either young adult or reproductive senescent females. In young adult-derived microglial cultures, the LPS-induced increase in IL-1beta was not attenuated by pre-treatment with 17beta-estradiol, PPT or HPTE. Interestingly, the ERbeta agonist, DPN significantly decreased IL-1beta following LPS treatment in young adult-derived microglia. Thus while both microglia and astrocytes synthesize and release inflammatory mediators, the present data shows that compounds which bind ERbeta are more effective in attenuating proinflammatory cytokines in both cell types and may therefore be a more effective agent for future therapeutic use.

Bronchopneumonia associated with Mannheimia granulomatis infection in a Belgian hare ( Lepus europaeus).

Mannheimia granulomatis was first isolated from pneumonic European hares in the 1980s and has since been reported sporadically in pneumonic Swedish roe deer and Australian cattle. Although the pneumonic lesions caused by M. haemolytica in livestock have been extensively studied and reported, little is published with regard to the pneumonic lesions associated with M. granulomatis infection in any species. We describe the histopathology of purulent bronchopneumonia associated with M. granulomatis in a Belgian hare ( Lepus europaeus) resident in British Columbia, Canada, and compare the lesions with those caused by M. haemolytica in livestock.

Temporal expression of IL-1beta protein and mRNA in the brain after systemic LPS injection is affected by age and estrogen.

Estrogen has been shown to suppress neural inflammation in vivo in response to intracerebral LPS injections or by intraparenchymal injections of NMDA. Using the latter approach, we have shown that estrogen suppresses inflammatory cytokine expression in lesioned ovariectomized young adult females but not reproductive senescent animals. However, in cultured microglia derived from either young or senescent animals, estrogen fails to suppress LPS-induced cytokine expression. These data suggest that estrogen's effects on the neural inflammatory response may result from its actions on blood-borne immune cells or its actions at the blood brain barrier or both. This hypothesis was directly tested here using a systemic injury model and comparing the neural inflammatory response in the olfactory bulb, which is protected by the blood brain barrier, and in the pituitary gland, which is incompletely protected by the blood brain barrier. Young and senescent Sprague-Dawley female rats were ovariectomized and replaced with either an estrogen or placebo pellet. Three weeks later, animals received a single i.p. injection of LPS (or vehicle) and were terminated 0.5, 2 or 3h later. Systemic injections of LPS increased IL-1beta expression in the liver in a time-dependent manner in young and senescent females. In young adults, LPS increased cytokine expression in both the bulb and the pituitary gland. However, estrogen treatment attenuated IL-1beta expression in the olfactory bulb but not in the pituitary gland. In senescent animals, estrogen completely suppressed IL-1beta expression in the bulb and the pituitary gland, while placebo-replaced animals responded normally. This age-related difference in cytokine induction by LPS was also seen in mRNA regulation, such that LPS induced IL-1beta mRNA in the olfactory bulb of young adults but not in the senescent female. Age and hormone effects on pituitary cytokines were also mirrored in plasma corticosterone (CORT) levels, such that estrogen treatment to senescent females attenuated LPS-induced CORT. These data suggest that the central inflammatory response to a systemic insult can be modulated by estrogen although the mechanism underlying the initiation of this response varies with reproductive age.

The neurotrophin receptor p75NTR mediates early anti-inflammatory effects of estrogen in the forebrain of young adult rats.

BACKGROUND: Estrogen suppresses microglial activation and extravasation of circulating monocytes in young animals, supporting an anti-inflammatory role for this hormone. However, the mechanisms underlying estrogen's anti-inflammatory effects, especially in vivo, are not well understood. The present study tests the hypothesis that anti-inflammatory effects of estrogen are mediated by the pan-neurotrophin receptor p75NTR. Previously, we reported that estrogen attenuated local increases of interleukin(IL)-1beta in the NMDA-lesioned olfactory bulb, while further increasing NGF expression. RESULTS: The present studies show that this lesion enhances expression of the neurotrophin receptor p75NTR at the lesion site, and p75NTR expression is further enhanced by estrogen treatment to lesioned animals. Specifically, estrogen stimulates p75NTR expression in cells of microvessels adjacent to the lesion site. To determine the role of this receptor in mediating estrogen's anti-inflammatory effects, a p75NTR neutralizing antibody was administered at the same time the lesion was created (by stereotaxic injections of NMDA) and specific markers of the inflammatory cascade were measured. Olfactory bulb injections of NMDA+vehicle (preimmune serum) increased IL-1beta and activated the signaling molecule c-jun terminal kinase (JNK)-2 at 6 h. At 24 h, the lesion significantly increased matrix metalloproteinase (MMP)-9 and prostaglandin (PG)E2, a COX-2 mediated metabolite of arachadonic acid. All of these markers were significantly attenuated by estrogen in a time-dependent manner. However, estrogen's effects on all these markers were abolished in animals that received anti-p75NTR. CONCLUSION: These data support the hypothesis that estrogen's anti-inflammatory effects may be, in part, mediated by this neurotrophin receptor. In view of the novel estrogen-dependent expression of p75NTR in cells associated with microvessels, these data also suggest that the blood brain barrier is a critical locus of estrogen's neuro-immune effects.

The relationship between early adversities and attention-deficit/hyperactivity disorder.

This study examined whether retrospectively reported childhood physical abuse, childhood sexual abuse and/or exposure to parental domestic violence were associated with self-report of a health-professional diagnosis of attention-deficit/hyperactivity disorder (ADHD) among adults. We analyzed nationally representative data from the 2012 Canadian Community Health Survey-Mental Health using gender-specific bivariate and logistic regression analyses (n=10,496 men; n=12,877 women). For both men and women, childhood physical abuse was associated with significantly higher odds of reporting ADHD (men odds ratio [OR]=1.66, p<.001; women OR=1.95, p<.001). For both genders, childhood sexual abuse was also significantly related to higher odds of ADHD (men OR=2.57, p<.001; women OR=2.55, p<.001); however, exposure to parental domestic violence was only associated with elevated odds of ADHD among women (men OR=0.89, p=.60; women OR=1.54, p=.03). The results demonstrate a link between childhood physical and sexual abuse and ADHD for both men and women. Future prospective studies are required to further understand this interesting relationship.