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We introduce the new, substantially updated, and revised version of the Dyadic Militarized Interstate Disputes (MIDs) dataset. We discuss the underlying logic of constructing dyadic MIDs and demonstrate that these operations generate significant differences between the actual occurrence and properties of MID dyads and those extracted from machine-generated programs such as EUGene, or from the MID participant dataset. We provide some descriptive measures of dyadic MIDs over the period of 1816 to 2010 and compare some of the key dyadic results on the correlates of MIDs using different datasets. We discuss the theoretical and empirical implications of our results.

Byline: PL Johnson (Departments of Psychiatry and Biochemistry, Indiana University School of Medicine, Indianapolis, IN 46223, USA); CA Lowry (Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, [...]

Background: Allelic variations in TPH2, the gene encoding tryptophan hydroxylase 2, the rate-limiting enzyme for brain serotonin (5-HT) biosynthesis, may be genetic predictors of panic disorder and panic responses to panicogenic challenges in healthy volunteers. To test the hypothesis that tph2 mRNA is altered in chronic anxiety states, we measured tph2 expression in an established rat model of panic disorder.Methods: We implanted 16 adult, male rats with bilateral guide cannulae and then primed them with daily injections of the corticotropin-releasing factor (CRF) receptor agonist, urocortin 1 (UCN1, 6 fmoles/100 nl per side, n = 8) or vehicle (n = 8) into the basolateral amygdaloid complex (BL) for 5 consecutive days. Anxiety-like behavior was assessed, 24 hr prior to and 48 hr following priming, in the social interaction (SI) test. A third group (n = 7) served as undisturbed home cage controls. All rats were killed 3 days after the last intra-BL injection to analyze tph2 and slc6a4 (gene encoding the serotonin transporter, SERT) mRNA expression in the dorsal raphe nucleus (DR), the main source of serotonergic projections to anxiety-related brain regions, using in situ hybridization histochemistry.Results: UCN1 priming increased anxiety-related behavior in the SI test compared to vehicle-injected controls and elevated tph2, but not slc6a4, mRNA expression in DR subregions, including the ventrolateral DR/ventrolateral periaqueductal gray (DRVL/VLPAG), a subregion previously implicated in control of panic-related physiologic responses. Tph2 mRNA expression in the DRVL/VLPAG was correlated with increased anxiety-related behavior.Conclusion: Our data support the hypothesis that chronic anxiety states are associated with dysregulated tph2 expression. [ABSTRACT FROM AUTHOR]

Given the high rate of morbidity and mortality associated with abdominal aortic aneurysms (AAAs), accurate diagnosis and preoperative evaluation are essential for improved patient outcomes. Ultrasonography is the standard method of screening and monitoring AAAs that have not ruptured. In the past, aortography was commonly used for preoperative planning in the repair of AAAs. More recently, computed tomography (CT) has largely replaced older, more invasive methods. Recent advances in CT imaging technology, such as helical CT and CT angiography, offer significant advantages over traditional CT. These methods allow for more rapid scans and can produce three-dimensional images of the AAA and important adjacent vascular structures. Use of endovascular stent grafts has increased recently and is less invasive for the repair of AAAs in selected cases. Aortography and CT angiography can precisely determine the size and surrounding anatomy of the AAA to identify appropriate candidates for the use of endovascular stent grafts. Helical CT and CT angiography represent an exciting future in the preoperative evaluation of AAAs. However, this technology is not the standard of care because of the lack of widespread availability, the cost associated with obtaining new equipment, and the lack of universal protocols necessary for acquisition and reconstruction of these images. [ABSTRACT FROM AUTHOR]

Capillary blood glucose monitoring devices (CBGMs) that incorporate 'wipeless' technology recently have been designed and marketed for hospital use. Our objective was to evaluate three such devices for accuracy and precision, comparing them to a popular device that utilizes older technology and to a reference standard. Blood glucose level was simultaneously determined on the CBGMs and a reference standard. Results were analyzed for precision by performing repeated measurements of a single sample and for accuracy across the entire range or determinations. Clinically relevant subsets of the entire range also were determined as low (<60 mg/dL), normal (60 to 140 mg/dL), high (141 to 300 mg/dL), and very high (>300 mg/dL). We found that accuracy and precision of these devices varied considerably. Lack of accuracy was particuarly evident upon analysis of the clinically relevant subset ranges of blood glucose levels. Consequently, routine evaluation of CBGMs should include analysis of clinically relevant subset ranges of blood glucose levels. The marked differences in accuracy and precision between CBGMs that are currently [sic]. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing active cancer therapy or with metastatic cancer are at increased risk for acute cholecystitis and often present to general surgeons for evaluation and management. There is a paucity of data regarding the treatment processes used in these patients and the clinical outcomes achieved. Optimal management of acute cholecystitis in patients with cancer requires understanding their unique risk profile and options for treatment., Methods: Emergency general surgery data were collected at 10 hospitals from July 1, 2019, to February 29, 2024. Patients presenting with acute cholecystitis were selected for analysis. Propensity score matching was used to create matched cohorts of patients by the presence or absence of an active malignancy. The primary outcome was 30-day mortality. Secondary outcomes included complications, length of stay, readmission, and discharge disposition. Processes investigated include treatment modality, time to operation, and surgical technique., Results: The analysis included 8,673 patients. Mean age was 53.2 ± 19 years, 61.4% were female, and 17.8% were non-White. In total, 3.3% of patients had an active malignancy. Risk-adjusted 30-day mortality was higher in the cancer cohort (odds ratio: 5.85, 95% confidence interval: 2.38-14.4, P < .001). Patients with cancer also had higher rates of infectious complications (odds ratio: 2.55, 95% confidence interval: 1.54-4.2, P < .001), including sepsis (odds ratio: 2.95, 95% confidence interval: 1.61-5.39, P < .001) and pneumonia (odds ratio: 6.67, 95% confidence interval: 1.75-25.3, P < .005). Patients with cancer were more likely to receive nonoperative management (odds ratio: 2.85, 95% confidence interval: 2.11-3.84, P < .001)., Conclusion: Patients with cancer presenting with acute cholecystitis experience worse clinical outcomes after controlling for other factors. Furthermore, there is variation in the treatment process with increased rates of nonoperative management. These results have implications for the management of this population, particularly in relation to the impact on concurrent oncologic treatment plans., Competing Interests: Conflict of Interest/Disclosure Patrick L. Johnson and Jonathan Williams receive funding from grant NIH T32-DK108740 from the National Institutes of Health. Sara L. Schaefer receives funding from grant T32-CA-236621 and personal fees from the Journal of American Medical Association Network for serving as a visual abstract editor. Laura Gerhardinger and Mark R. Hemmila receive grant funding from Blue Cross Blue Shield of Michigan and Blue Care Network (a nonprofit mutual company) and the Michigan Department of Health and Human Services for support of the Michigan Trauma Quality Improvement Program. Mark R. Hemmila receives grant funding from General Motors Corporation, Toyota North America, and the Insurance Institute for Highway Safety for support of the International Center for Automotive Medicine. Mark R. Hemmila receives grant funding from the Uniformed Services University of the Health Sciences and the H M Jackson Foundation for the Advancement of Military Medicine for support of an evidence-based assessment of combat wound infection management. The remaining authors have no conflicts to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Trauma patients are at increased risk for venous thromboembolism events (VTEs). The decision of when to initiate VTE chemoprophylaxis (VTEP) and with what agent remains controversial in patients with severe traumatic brain injury (TBI)., Methods: This comparative effectiveness study evaluated the impact of timing and agent for VTEP on outcomes for patients with severe TBI (Abbreviated Injury Scale head score of 3, 4, or 5). Data were collected at 35 Level 1 and 2 trauma centers from January 1, 2017, to June 1, 2022. Patients were placed into analysis cohorts: no VTEP, low-molecular-weight heparin (LMWH) ≤48 hours, LMWH >48 hours, heparin ≤48 hours, and heparin >48 hours. Propensity score matching accounting for patient factors and injury characteristics was used with logistic regression modeling to evaluate in-hospital mortality, VTEs, and discharge disposition. Neurosurgical intervention after initiation of VTEP was used to evaluate extension of intracranial hemorrhage., Results: Of 12,879 patients, 32% had no VTEP, 36% had LMWH, and 32% had heparin. Overall mortality was 8.3% and lowest among patients receiving LMWH ≤48 hours (4.1%). Venous thromboembolism event rates were lower with use of LMWH (1.6% vs. 4.5%; odds ratio, 2.98; 95% confidence interval, 1.40-6.34; p = 0.005) without increasing mortality or neurosurgical interventions. Venous thromboembolism event rates were lower with early prophylaxis (2.0% vs. 3.5%; odds ratio, 1.76; 95% confidence interval, 1.15-2.71; p = 0.01) without increasing mortality ( p = 1.0). Early VTEP was associated with more nonfatal intracranial operations ( p < 0.001). However, patients undergoing neurosurgical intervention after VTEP initiation had no difference in rates of mortality, withdrawal of care, or unfavorable discharge disposition ( p = 0.7, p = 0.1, p = 0.5)., Conclusion: In patients with severe TBI, LMWH usage was associated with lower VTE incidence without increasing mortality or neurosurgical interventions. Initiation of VTEP ≤48 hours decreased VTE incidence and increased nonfatal neurosurgical interventions without affecting mortality. Low-molecular-weight heparin is the preferred VTEP agent for severe TBI, and initiation ≤48 hours should be considered in relation to these risks and benefits., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To assess the association between ambient heat and all-cause and cause-specific emergency department (ED) visits and acute hospitalizations among Medicare beneficiaries in the conterminous United States., Design: Retrospective cohort study., Setting: Conterminous US from 2008 and 2019., Participants: 2% random sample of all Medicare fee-for-service beneficiaries eligible for Parts A, B, and D., Main Outcome Measures: All-cause and cause-specific (cardiovascular, renal, and heat-related) ED visits and unplanned hospitalizations were identified using primary ICD-9 or ICD-10 diagnosis codes. We measured the association between ambient temperature - defined as daily mean temperature percentile of summer (June through September) - and the outcomes. Hazard ratios and their associated 95% confidence intervals were estimated using multivariable Cox proportional hazards regression, adjusting for individual level demographics, comorbidities, healthcare utilization factors and zip-code level social factors., Results: Among 809,636 Medicare beneficiaries (58% female, 81% non-Hispanic White, 24% <65), older beneficiaries (aged ≥65) exposed to >95th percentile temperature had a 64% elevated adjusted risk of heat-related ED visits (HR [95% CI], 1.64 [1.46,1.85]) and a 4% higher risk of all-cause acute hospitalization (1.04 [1.01,1.06]) relative to <25th temperature percentile. Younger beneficiaries (aged <65) showed increased risk of heat-related ED visits (2.69 [2.23,3.23]) and all-cause ED visits (1.03 [1.01,1.05]). The associations with heat related events were stronger in males and individuals dually eligible for Medicare and Medicaid. No significant differences were observed by climatic region. We observed no significant relationship between temperature percentile and risk of CV-related ED visits or renal-related ED visits., Conclusions: Among Medicare beneficiaries from 2008 to 2019, exposure to daily mean temperature ≥ 95th percentile was associated with increased risk of heat-related ED visits, with stronger associations seen among beneficiaries <65, males, and patients with low socioeconomic position. Further longitudinal studies are needed to understand the impact of heat duration, intensity, and frequency on cause-specific hospitalization outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Urinary tract infections (UTIs) are commonly treated in the emergency department (ED), and unfortunately, resistance to first-line agents is increasing., Objectives: To characterize treatment of pyelonephritis in a nationally representative sample of ED patients and to identify patient- and treatment-specific factors associated with receiving initial inactive antibiotics., Methods: We conducted a multicentre, observational cohort study utilizing the Emergency Medicine PHARMacotherapy Research NETwork (EMPHARM-NET), comprising 15 geographically diverse US EDs. All patients ≥18 years of age with a diagnosis of pyelonephritis between 2018 and 2020 were included. The primary endpoint was the proportion of patients who received initial inactive empirical antibiotic therapy and to identify predictive factors of inactive antibiotic therapy., Results: Of the 3714 patients evaluated, 223 had culture-positive pyelonephritis. Median patient age was 50.1 years and patients were mostly female (78.3%). Overall, 40.4% of patients received an IV antibiotic, most commonly ceftriaxone (86.7%). The most frequently prescribed antibiotics were cefalexin (31.8%), ciprofloxacin (14.3%), cefdinir (13.5%) and trimethoprim/sulfamethoxazole (12.6%). Overall, 10.3% of patients received initial inactive therapy. After adjustment in a multivariable analysis, long-acting IV antibiotic was predictive of inactive therapy (OR 0.23, 95% CI 0.07-0.83)., Conclusions: In our prospective, multicentre observational study, we found that only 40.4% of patients with pyelonephritis received empirical IV antibiotics in the ED, contributing to inactive therapy. Receipt of long-acting IV antibiotics was independently associated with a decreased rate of initial inactive therapy. This reinforces guideline recommendations to administer long-acting IV antibiotics empirically in the ED upon suspicion of pyelonephritis., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Women experiencing homelessness are marginalized not only through their housing status but also through their access and ability to manage their menstrual health. Currently, there are no existing published reviews exploring this topic. This study aimed to begin closing that gap, by systematically reviewing the literature examining women's experiences of menstruation whilst being homeless. In June 2020 (and updated in December 2022), we conducted comprehensive and systematic searches of four electronic databases: Medline, Web of Science, CINAHL, and PsychINFO, from which nine studies were found. The findings were thematically analyzed, using the enhancing transparency in reporting the synthesis of qualitative research tools (ENTREQ) guidelines. Three themes related to menstrual experiences were found: (1) challenges in the logistics of managing menstruation while homeless, (2) feelings of embarrassment, shame, and dignity linked to maintaining menstrual health, and (3) making do: how people experiencing homelessness manage challenges related to menstruation. We discuss barriers women face in getting necessary products and in accessing private, safe, and clean facilities to manage menstrual health. The study found that women living with homelessness often abandon other basic needs in favor of managing menstruation (i.e. using unsuitable materials, stealing, etc.), which furthers their risk. The findings highlight the need for future research to investigate the experiences of women who are menstruating while being homeless and what support they would find helpful. Results show that it is high time for commissioners and policy-makers to address the provision of menstrual resources as a basic human right.

The serotonin (5-HT) system is heavily implicated in the regulation of anxiety and trauma-related disorders such as panic disorder and post-traumatic stress disorder, respectively. However, the neural mechanisms of how serotonergic neurotransmission regulates innate panic and fear brain networks are poorly understood. Our earlier studies have identified that orexin (OX)/glutamate neurons within the perifornical hypothalamic area (PFA) play a critical role in adaptive and pathological panic and fear. While site-specific and electrophysiological studies have shown that intracranial injection and bath application of 5-HT inhibits PFA neurons via 5-HT 1a receptors, they largely ignore circuit-specific neurotransmission and its physiological properties that occur in vivo. Here, we investigate the role of raphe nuclei 5-HT inputs into the PFA in panic and fear behaviors. We initially confirmed that photostimulation of glutamatergic neurons in the PFA of rats produces robust cardioexcitation and flight/aversive behaviors resembling panic-like responses. Using the retrograde tracer cholera toxin B, we determined that the PFA receives discrete innervation of serotonergic neurons clustered in the lateral wings of the dorsal (lwDRN) and in the median (MRN) raphe nuclei. Selective lesions of these serotonergic projections with saporin toxin resulted in similar panic-like responses during the suffocation-related CO 2 challenge and increased freezing to fear-conditioning paradigm. Conversely, selective stimulation of serotonergic fibers in the PFA attenuated both flight/escape behaviors and cardioexcitation responses elicited by the CO 2 challenge and induced conditioned place preference. The data here support the hypothesis that PFA projecting 5-HT neurons in the lwDRN/MRN represents a panic/fear-off circuit and may also play a role in reward behavior., (© 2024. The Author(s).)

Background: Unemployment associated with the coronavirus disease 2019 (COVID-19) pandemic was linked to financial insecurity and disruptions in access to health care., Objective: To explore whether expanded access to Medicaid mitigated the likelihood of health and non-health financial hardship associated with pandemic-linked job loss., Design: We estimate linear regression models comparing differences in the levels of outcomes attributable to pandemic-linked joblessness in Medicaid expansion and nonexpansion states., Observations: A total of 20,281 adults aged 19-64 were in the 2021 National Financial Capability Study., Measures: Our key exposure was job loss, layoffs, and furloughs, attributable to the COVID-19 pandemic. Outcomes under evaluation include indicators of health care access and household financial health., Results: Relative to persons reporting pandemic-linked unemployment in nonexpansion states, adults experiencing pandemic-linked job loss in expansion states were less likely to report as uninsured [-6.2 percentage points (PPs); 95% CI: -10.8, -1.6; P < 0.01], having unpaid medical bills (-4.3 PP; 95% CI: -8, -0.6; P < 0.05), having unmet medical needs due to cost (-5.3 PP; 95% CI: -10.1, -0.5; P < 0.05), and having calls from debt collection agencies (-6.9 PP; 95% CI: -10.6, -3.1; P < 0.01). Patterns consistent with Medicaid acting as a safety net for the adverse financial effects of job loss were more pronounced for middle-income households., Conclusions: In economic downturns, such as the COVID-19 crisis, Medicaid can help insulate households from diminished health care access and financial distress associated with job loss., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Producing animal protein while reducing the animal's impact on the environment, e.g., through improved feed efficiency and lowered methane emissions, has gained interest in recent years. Genetic selection is one possible path to reduce the environmental impact of livestock production, but these traits are difficult and expensive to measure on many animals. The rumen microbiome may serve as a proxy for these traits due to its role in feed digestion. Restriction enzyme-reduced representation sequencing (RE-RRS) is a high-throughput and cost-effective approach to rumen metagenome profiling, but the systematic (e.g., sequencing) and biological factors influencing the resulting reference based (RB) and reference free (RF) profiles need to be explored before widespread industry adoption is possible., Results: Metagenome profiles were generated by RE-RRS of 4,479 rumen samples collected from 1,708 sheep, and assigned to eight groups based on diet, age, time off feed, and country (New Zealand or Australia) at the time of sample collection. Systematic effects were found to have minimal influence on metagenome profiles. Diet was a major driver of differences between samples, followed by time off feed, then age of the sheep. The RF approach resulted in more reads being assigned per sample and afforded greater resolution when distinguishing between groups than the RB approach. Normalizing relative abundances within the sampling Cohort abolished structures related to age, diet, and time off feed, allowing a clear signal based on methane emissions to be elucidated. Genus-level abundances of rumen microbes showed low-to-moderate heritability and repeatability and were consistent between diets., Conclusions: Variation in rumen metagenomic profiles was influenced by diet, age, time off feed and genetics. Not accounting for environmental factors may limit the ability to associate the profile with traits of interest. However, these differences can be accounted for by adjusting for Cohort effects, revealing robust biological signals. The abundances of some genera were consistently heritable and repeatable across different environments, suggesting that metagenomic profiles could be used to predict an individual's future performance, or performance of its offspring, in a range of environments. These results highlight the potential of using rumen metagenomic profiles for selection purposes in a practical, agricultural setting., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Rumen microbes break down complex dietary carbohydrates into energy sources for the host and are increasingly shown to be a key aspect of animal performance. Host genotypes can be combined with microbial DNA sequencing to predict performance traits or traits related to environmental impact, such as enteric methane emissions. Metagenome profiles were generated from 3139 rumen samples, collected from 1200 dual purpose ewes, using restriction enzyme-reduced representation sequencing (RE-RRS). Phenotypes were available for methane (CH4) and carbon dioxide (CO2) emissions, the ratio of CH4 to CH4 plus CO2 (CH4Ratio), feed efficiency (residual feed intake: RFI), liveweight at the time of methane collection (LW), liveweight at 8 months (LW8), fleece weight at 12 months (FW12) and parasite resistance measured by faecal egg count (FEC1). We estimated the proportion of phenotypic variance explained by host genetics and the rumen microbiome, as well as prediction accuracies for each of these traits., Results: Incorporating metagenome profiles increased the variance explained and prediction accuracy compared to fitting only genomics for all traits except for CO2 emissions when animals were on a grass diet. Combining the metagenome profile with host genotype from lambs explained more than 70% of the variation in methane emissions and residual feed intake. Predictions were generally more accurate when incorporating metagenome profiles compared to genetics alone, even when considering profiles collected at different ages (lamb vs adult), or on different feeds (grass vs lucerne pellet). A reference-free approach to metagenome profiling performed better than metagenome profiles that were restricted to capturing genera from a reference database. We hypothesise that our reference-free approach is likely to outperform other reference-based approaches such as 16S rRNA gene sequencing for use in prediction of individual animal performance., Conclusions: This paper shows the potential of using RE-RRS as a low-cost, high-throughput approach for generating metagenome profiles on thousands of animals for improved prediction of economically and environmentally important traits. A reference-free approach using a microbial relationship matrix from log 10 proportions of each tag normalized within cohort (i.e., the group of animals sampled at the same time) is recommended for future predictions using RE-RRS metagenome profiles., (© 2023. The Author(s).)

Tracheobronchomalacia (TBM) is an increasingly recognized abnormality of the central airways in patients with respiratory symptoms. Severe TBM in symptomatic patients warrants screening dynamic CT of the chest and/or awake dynamic bronchoscopy. The goal of surgical repair is to restore the C-shaped configuration of the airway lumen and splint or secure the lax posterior membrane to the mesh to ameliorate symptoms. Robotic tracheobronchoplasty is safe and associated with improvements in pulmonary function and subjective improvement in quality of life., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The inclusion of eating quality traits in sheep genetic improvement programmes is desirable. Intramuscular fat (IMF) plays a key role in ensuring consumer satisfaction when eating lamb, but genetic progress for IMF is constrained by a lack of routine data collection. This study investigated the potential for IMF predictor traits to substitute for measured IMF in genetic improvement programmes. Carcass and predicted IMF (near-infrared estimated IMF and marbling score) data were available on 10,113 New Zealand lambs, 1678 of which also had measured chemical IMF on a slice of M. longissimus lumborum on which the predictions of IMF had been made. Genetic antagonisms were observed between carcass lean traits and IMF. The genetic correlation between the predictors and measured IMF approached one, indicating that predictors of IMF can be used in genetic improvement programmes. Through using selection indexes, simultaneous increases in IMF and the existing terminal selection index are possible, provided all traits are measured. This study highlights the importance and potential of predicted IMF to achieve genetic improvement in traits of importance to consumers., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest associated with the manuscript ‘Potential of in-plant intramuscular fat measures to enable sheep breeders to incorporate consumer preferences in breeding programmes’., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cues associated with alcohol use can readily enhance self-reported cravings for alcohol, which increases the likelihood of reusing alcohol. Understanding the neuronal mechanisms involved in alcohol-seeking behavior is important for developing strategies to treat alcohol use disorder. In all experiments, adult female alcohol-preferring (P) rats were exposed to three conditioned odor cues; CS+ associated with EtOH self-administration, CS- associated with the absence of EtOH (extinction training), and a CS 0, a neutral stimulus. The data indicated that presentation of an excitatory conditioned cue (CS+) can enhance EtOH- seeking while the CS- can inhibit EtOH-seeking under multiple test conditions. Presentation of the CS+ activates a subpopulation of dopamine neurons within the interfascicular nucleus of the posterior ventral tegmental area (posterior VTA) and basolateral amygdala (BLA). Pharmacological inactivation of the BLA with GABA agonists inhibits the ability of the CS+ to enhance EtOH-seeking but does not alter context-induced EtOH-seeking or the ability of the CS- to inhibit EtOH-seeking. Presentation of the conditioned odor cues in a non-drug-paired environment indicated that presentation of the CS+ increased dopamine levels in the BLA. In contrast, presentation of the CS- decreased both glutamate and dopamine levels in the BLA. Further analysis revealed that presentation of a CS+ EtOH-associated conditioned cue activates GABA interneurons but not glutamate projection neurons. Overall, the data indicate that excitatory and inhibitory conditioned cues can contrarily alter EtOH-seeking behaviors and that different neurocircuitries are mediating these distinct cues in critical brain regions. Pharmacotherapeutics for craving should inhibit the CS+ and enhance the CS- neurocircuits., Competing Interests: Conflict of interest None of the authors has a conflict of interest associated with this research., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Corticotropin-releasing factor (CRF) is essential for coordinating endocrine and neural responses to stress, frequently facilitated by vasopressin (AVP). Previous work has linked CRF hypersecretion, binding site changes, and dysfunctional serotonergic transmission with anxiety and affective disorders, including clinical depression. Crucially, CRF can alter serotonergic activity. In the dorsal raphé nucleus and serotonin (5-HT) terminal regions, CRF effects can be stimulatory or inhibitory, depending on the dose, site, and receptor type activated. Prior stress alters CRF neurotransmission and CRF-mediated behaviors. Lateral, medial, and ventral subdivisions of the central nucleus of the amygdala (CeA) produce CRF and coordinate stress responsiveness. The purpose of these experiments was to determine the effect of intracerebroventricular (icv) administration of CRF and AVP on extracellular 5-HT as an index of 5-HT release in the CeA, using in vivo microdialysis in freely moving rats and high performance liquid chromatography (HPLC) analysis. We also examined the effect of prior stress (1 h restraint, 24 h prior) on CRF- and AVP-mediated release of 5-HT within the CeA. Our results show that icv CRF infusion in unstressed animals had no effect on 5-HT release in the CeA. Conversely, in rats with prior stress, CRF caused a profound dose-dependent decrease in 5-HT release within the CeA. This effect was long-lasting (240 min) and was mimicked by CRF plus AVP infusion without stress. Thus, prior stress and AVP functionally alter CRF-mediated neurotransmission and sensitize CRF-induced inhibition of 5-HT release, suggesting that this is a potential mechanism underlying stress-induced affective reactivity in humans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ronan, Korzan, Johnson, Lowry, Renner and Summers.)

Physical traits that improve welfare and disease outcomes for sheep are becoming increasingly important due to both increased climate challenges and societal expectations. Such traits include tail length, the amount of skin (vs. wool) on the underside of the tail, and the area of no-wool (hair) on the belly and breech areas (surrounding the anus) of the animal. An industry dataset consisting of records from individual stud breeders and industry progeny tests was available to estimate the genetic parameters associated with these traits and to investigate the potential for within-breed genetic selection. The heritability estimate for tail length was 0.68 ± 0.01 when breed was not fitted, and 0.63 ± 0.01 when breed was fitted. Similar trends were observed for breech and belly bareness which had heritability estimates around 0.50 (± 0.01). The estimates for these bareness traits are both higher than previous reports from animals of the same age. There was, however, between breed variation in the starting point for these traits, with some breeds having significantly longer tails and a wooly breech and belly, and limited variability. Overall, the results of this study show that flocks exhibiting some variation will be able to make rapid genetic progress in selecting for bareness and tail length traits, and therefore have the potential to make progress towards a sheep that is easier to look after and suffers fewer welfare insults. For those breeds that showed limited within-breed variation, outcrossing may be required to introduce genotypes that exhibit shorter tail length and bareness of belly and breech to increase the rate of genetic gain. Whatever approach is taken by the industry, these results support that genetic improvement can be used to breed "ethically improved sheep"., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Global agreements in place to reduce methane emissions in livestock are a potential threat to food security. Successful but independent breeding strategies for improved production and lower methane are in place. The unanswered questions are whether these strategies can be combined and how they impact one another, physically and economically. The New Zealand economy is largely dependent on pastoral agriculture from grazing ruminants. The sheep industry produces ∼20 million lamb carcasses for export each year primarily from grass. Methane emitted from the fermentation of forage by grazing ruminants accounts for one-third of all New Zealand's greenhouse gas emissions. Here, we use sheep selection lines bred for divergent methane production and large numbers of their relatives to determine the genetic and phenotypic correlations between enteric methane emissions, carcass yield, and meat quality. The primary objectives were to determine whether previously shown physiological differences between methane selection lines (differing by ∼12% in methane) result in a negative impact on meat production and quality by measuring close relatives. The results show no negative effects of breeding for lowered methane on meat and carcass quality. Gross methane emissions were highly correlated with liveweight and measures of carcass weight and negatively correlated with dressing-out percentage and fat yield (GR). Trends were similar but not significant for methane yield (g CH 4 /kg DMI). Preliminary evidence, to date, shows that breeding for low methane may result in animals with higher lean yields that are economically favorable even before carbon costs and environmental benefits are taken into account. These benefits were seen in animals measured for methane on fixed intakes and require validation on intakes that are allowed to vary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rowe, Hickey, Bain, Greer, Johnson, Elmes, Pinares-Patiño, Young, Dodds, Knowler, Pickering, Jonker and McEwan.)

There is simultaneous interest in improving the feed efficiency of ruminant livestock and reducing methane (CH 4 ) emissions. The relationship (genetic and phenotypic) between feed efficiency (characterized as residual feed intake: RFI) and greenhouse gases [methane (CH 4 ) and carbon dioxide (CO 2 )] traits in New Zealand (NZ) maternal sheep has not previously been investigated, nor has their relationship with detailed estimates of body composition. To investigate these relationships in NZ maternal sheep, a feed intake facility was established at AgResearch Invermay, Mosgiel, NZ in 2015, comprising automated feeders that record individual feeding events. Individual measures of feed intake, feeding behavior (length and duration of eating events), and gas emissions (estimated using portable accumulation chambers) were generated on 986 growing maternal ewe lambs sourced from three pedigree recorded flocks registered in the Sheep Improvement Limited database (www.sil.co.nz). Additional data were generated from a subset of 591 animals for body composition (estimated using ultrasound and computed tomography scanning). The heritability estimates for RFI, CH 4 , and CH 4 /(CH 4 +CO 2 ) were 0.42 ± 0.09, 0.32 ± 0.08, and 0.29 ± 0.06, respectively. The heritability estimates for the body composition traits were high for carcass lean and fat traits; for example, the heritability for visceral fat (adjusted for body weight) was 0.93 ± 0.19. The relationship between RFI and CH 4 emissions was complex, and although less feed eaten will lead to a lowered absolute amount of CH 4 emitted, there was a negative phenotypic and genetic correlation between RFI and CH 4 /(CH 4 +CO 2 ) of -0.13 ± 0.03 and -0.41 ± 0.15, respectively. There were also genetic correlations, that were different from zero, between both RFI and CH 4 traits with body composition including a negative correlation between the proportion of visceral fat in the body and RFI (-0.52 ± 0.16) and a positive correlation between the proportion of lean in the body and CH 4 (0.54 ± 0.12). Together the results provide the first accurate estimates of the genetic correlations between RFI, CH 4 emissions, and the body composition (lean and fat) in sheep. These correlations will need to be accounted for in genetic improvement programs., Competing Interests: PaJ, SH, KK, JW, BB, MH, AJ, PeJ, KD, JM, and SR were employed by AgResearch Ltd., (Copyright © 2022 Johnson, Hickey, Knowler, Wing, Bryson, Hall, Jonker, Janssen, Dodds, McEwan and Rowe.)

Purpose: Intraocular pressure (IOP) remains the only modifiable risk factor for glaucoma progression. Our previous discovery that stimulation of nuclei within the hypothalamus can modulate IOP, intracranial pressure (ICP), and translaminar pressure difference (TLPD) fluctuations led us to investigate this pathway further. Our purpose was to determine the role of orexin neurons, primarily located in the dorsomedial hypothalamus (DMH) and perifornical (PeF) regions of the hypothalamus, in modulating these pressures., Methods: Sprague Dawley rats were pretreated systemically with a dual orexin receptor antagonist (DORA-12) at 30 mg/Kg (n = 8), 10 mg/Kg (n = 8), or vehicle control (n = 8). The IOP, ICP, heart rate (HR), and mean arterial pressure (MAP) were recorded prior to and following excitation of the DMH/PeF using microinjection of the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline methiodide (BMI)., Results: Administration of the DORA at 30 mg/Kg significantly attenuated peak IOP by 5.2 ± 3.6 mm Hg (P = 0.007). During the peak response period (8-40 minutes), the area under the curve (AUC) for the 30 mg/Kg DORA cohort was significantly lower than the control cohort during the same period (P = 0.04). IOP responses for peak AUC versus DORA dose, from 0 to 30 mg/Kg, were linear (R2 = 0.18, P = 0.04). The ICP responses during the peak response period (4-16 minutes) versus DORA dose were also linear (R2 = 0.24, P = 0.014). Pretreatment with DORA significantly decreased AUC for the TLPD following stimulation of the DMH/PeF (10 mg/kg, P = 0.045 and 30 mg/kg, P = 0.015)., Conclusions: DORAs have the potential to attenuate asynchronous changes in IOP and in ICP and to lessen the extent of TLPDs that may result from central nervous system (CNS) activation.

This paper reports relationships between fatty acids (FAs) and intramuscular fat (IMF)% in M. longissimus lumborum samples from 108 pasture-fed ewe lambs. Samples ranged in IMF from 1 to 6%. Relationships between %FA with total IMF% were mainly linear with percentages of saturated and monounsaturated FAs (MUFA), including trans-FAs, increasing and polyunsaturated FAs decreasing as IMF% increased. Normalized FA content data at 5.5% relative to 1.5% IMF, showed the highest relative increase for C14:0 as rates of endogenous synthesis increase with higher IMF deposition. This can be related to enhanced C12:0 elongation and lower rates of C14:0 desaturation, supported by a preferential desaturation of C18:1 trans-11 and C18:0 compared with C14:0 and C16:0 as IMF increased. The greatest normalized increase after C14:0 was anteisoC17:0 followed by other branched chain FAs and then trans-MUFA and C18:2 cis-9,trans-11. Finally, C22:6 and C22:5 showed higher relative increase than C20:5 indicating greater rates of elongation and desaturation past C20:5 at higher levels of fatness., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Facial eczema (FE) is a significant metabolic disease that affects New Zealand ruminants. Ingestion of the mycotoxin sporidesmin leads to liver and bile duct damage, which can result in photosensitisation, reduced productivity and death. Strategies used to manage the incidence and severity of the disease include breeding. In sheep, there is considerable genetic variation in the response to FE. A commercial testing program is available for ram breeders who aim to increase tolerance, determined by the concentration of the serum enzyme, gamma-glutamyltransferase 21 days after a measured sporidesmin challenge (GGT21). Genome-wide association studies were carried out to determine regions of the genome associated with GGT21. Two regions on chromosomes 15 and 24 are reported, which explain 5% and 1% of the phenotypic variance in the response to FE, respectively. The region on chromosome 15 contains the β-globin locus. Of the significant SNPs in the region, one is a missense variant within the haemoglobin subunit β ( HBB ) gene. Mass spectrometry of haemoglobin from animals with differing genotypes at this locus indicated that genotypes are associated with different forms of adult β-globin. Haemoglobin haplotypes have previously been associated with variation in several health-related traits in sheep and warrant further investigation regarding their role in tolerance to FE in sheep. We show a strategic approach to the identification of regions of importance for commercial breeding programs with a combination of discovery, statistical and biological validation. This study highlights the power of using increased density genotyping for the identification of influential genomic regions, combined with subsequent inclusion on lower density genotyping platforms.

Loin sections (m. Longissimus lumborum ) were collected at slaughter from forty-eight lamb carcasses to evaluate consumer-liking scores of six types of typical New Zealand commercial lamb and to understand the possible underlying reasons for those ratings. A consumer panel ( n = 160) evaluated tenderness, juiciness, flavor liking, and overall liking of the different types of lamb loins. Consumer scores differed among the types of lamb meat for all the evaluated attributes ( p < 0.05). Further segmentation based on overall liking scores showed two consumer clusters with distinct ratings. Correlation and external preference map analyses indicated that one consumer cluster ( n = 75) liked lamb types that had lower total lipid content, a lower proportion of branched-chain fatty acids, oleic and heptadecanoic acids; and a higher proportion of polyunsaturated fatty acids and volatile compounds (green and fruity descriptors). Consumer liking of the other segment ( n = 85) was less influenced by fatty acids and volatiles, except hexanoic, heptanoic and octanoic acids (rancid, fatty, and sweaty descriptors). Thus, the fatty acid profile and the volatile compounds derived from their oxidation upon cooking seem to be a stronger driver of consumer liking of lamb for some consumers than others.

Palatability of meat is known to be affected by intramuscular fat (IMF), but the effect in relatively low-fat New Zealand lamb is unknown. This study evaluated the eating quality of 108 loins (M. longissimus lumborum) from a single flock of ewe-lambs. Loins ranged from 1.09-5.68% IMF and were stratified into 6 groups: 1.65, 2.12, 2.65, 3.20, 3.58 and 4.40%. Consumers' (n = 165) overall liking of lamb increased significantly at around 3% IMF, achieving maximum scores at 4% IMF. One consumer cluster (n = 111) showed a linear increase in overall liking with increasing IMF%, regarded as 'IMF lovers: the more the better', while a second cluster (n = 54) preferred 2.5-3.5% IMF, described as 'IMF optimizers: just the right amount'. IMF% was modestly correlated (~ + 0.25) with all sensory attributes except juiciness. Liking scores were modestly correlated with monounsaturated (~ + 0.25) and polyunsaturated (~ - 0.20) fatty acids. Results suggest aiming for IMF% levels in New Zealand lamb beyond 3% to maximize eating quality for premium markets in particular., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Adolescents are increasingly susceptible to obesity, and thus at risk of later non-communicable diseases, due to changes in food choices, physical activity levels and exposure to an obesogenic environment. This review aimed to synthesize the literature investigating the effectiveness of health education interventions delivered in school settings to prevent overweight and obesity and/ or reduce BMI in adolescents, and to explore the key features of effectiveness., Methods: A systematic search of electronic databases including MEDLINE, CINAHL, PsychINFO and ERIC for papers published from Jan 2006 was carried out in 2020, following PRISMA guidelines. Studies that evaluated health education interventions in 10-19-year-olds delivered in schools in high-income countries, with a control group and reported BMI/BMI z-score were selected. Three researchers screened titles and abstracts, conducted data extraction and assessed quality of the full text publications. A third of the papers from each set were cross-checked by another reviewer. A meta-analysis of a sub-set of studies was conducted for BMI z-score., Results: Thirty-three interventions based on 39 publications were included in the review. Most studies evaluated multi-component interventions using health education to improve behaviours related to diet, physical activity and body composition measures. Fourteen interventions were associated with reduced BMI/BMI z-score. Most interventions (n = 22) were delivered by teachers in classroom settings, 19 of which trained teachers before the intervention. The multi-component interventions (n = 26) included strategies such as environment modifications (n = 10), digital interventions (n = 15) and parent involvement (n = 16). Fourteen studies had a low risk of bias, followed by 10 with medium and nine with a high risk of bias. Fourteen studies were included in a random-effects meta-analysis for BMI z-score. The pooled estimate of this meta-analysis showed a small difference between intervention and control in change in BMI z-score (- 0.06 [95% CI -0.10, - 0.03]). A funnel plot indicated that some degree of publication bias was operating, and hence the effect size might be inflated., Conclusions: Findings from our review suggest that school-based health education interventions have the public health potential to lower BMI towards a healthier range in adolescents. Multi-component interventions involving key stakeholders such as teachers and parents and digital components are a promising strategy.

Animal production factors can affect the fatty acid and volatile profile of lamb meat. The fatty acid and volatile composition of the M. longissimus thoracis was evaluated from 150 lambs from 10 groups of commercial lambs that differed in age, sex, diet and breed, from three farms, which represent typical forage lamb production systems in New Zealand. The meat from 4-month-old composite lambs slaughtered at weaning had a similar polyunsaturated to saturated fatty acid ratio compared to 6- to 8-month-old composite lambs, but a greater ratio than that of 12-month-old Merino lambs ( p < 0.05), with all ratios being lower than the recommended ≥0.45. All lamb production systems produced meat with an omega-6 to omega-3 ratio below 1.5, well below the recommended ratio ≤ 4.0. Meat from 4-month-old lambs had higher C12:0, C14:0 and C16:0 and lower C18:0, reflecting the composition of the milk diet, resulting in higher atherogenic index than meat from other animal groups, while meat from 12-month-old Merino lambs, with lower content of polyunsaturated fatty acids, showed higher thrombogenic index. Meat from lambs processed at weaning contained the greatest concentration of eicosapentaenoic and docosahexaenoic acids, which would qualify as a 'source' or 'good source' of these target fatty acids based on the Commission of Regulation of the European Union or the Food Standards Australia New Zealand guidelines, respectively. Volatiles were extracted from the headspace of raw lean meat and 36 volatile compounds were identified. The abundance of carbon disulphide, isododecane, heptanal, 2,5-hexanediol and 3-octanone and pentanoic, octanoic, nonanoic and heptanoic acids was similar between all groups of lambs. Meat from 12-month-old Merino lambs had low abundance of acetic, propanoic, butanoic and hexanoic acids, and hexanal, octanal and dimethyl sulphide. For 6- to 8-month-old composite lambs, hexanal, octanal and nonanal were present at higher relative abundance in meat from lambs that grazed on chicory than perennial ryegrass. The significant differences in the fatty acid and volatile profiles in meat from 12-month-old Merino lambs compared with lambs slaughtered at weaning or further grazed on red clover, chicory or mixed pasture may result in distinctive nutritional value and lamb flavour.