Adult norms for the Corbett Targeted Coin Test.

STUDY DESIGN: Clinical measurement INTRODUCTION: Dexterity is important for daily activities. The Corbett Targeted Coin Test (CTCT) measures dexterity with palm-to-finger translation and proprioceptive target placement, but lacks established norms. PURPOSE OF THE STUDY: To establish norms for the CTCT with healthy adult subjects. METHODS: The inclusion criteria consisted of participants that were community dwelling, non-institutionalized, able to make a fist with both hands, perform finger-to-palm translation of twenty coins, and be at least 18 years of age. CTCT standardized testing procedures were followed. Quality of performance (QoP) scores were determined by speed in seconds and number of coin drops (each a 5-second penalty). QoP was summarized within each age, gender and hand dominance subgroup using the mean, median, minimum, and maximum. Correlation coefficients were computed for relationships between age and QoP, and between handspan and QoP. RESULTS: Of the 207 individuals who participated, 131 were females and 76 males with an age range of 18-86 and mean age of 37.16. Individual QoP scores ranged from 13.8 to 105.3 seconds, with median scores ranging from 28.7 to 53.3 seconds. The mean for males was 37.5 seconds for the dominant hand (range 15.7-105.3) and 42.3 seconds (range 17.9.-86.8) for the non-dominant hand. The mean for females was 34.7 seconds for the dominant hand (range 14.8-67.0) and 38.6 seconds (range 13.8.-82.7) for the non-dominant hand. Lower QoP scores indicate a faster and/or more accurate dexterity performance. Females showed better median QoP for most age groups. The best median QoP scores were seen in the 30-39 and 40-49 age ranges. DISCUSSION: Our study agrees to some extent with other research that reported dexterity decreases with age, and increases with smaller hand spans. CONCLUSION: Normative data for the CTCT can be a guide for clinicians evaluating and monitoring patient dexterity with palm-to-finger translation and proprioceptive target placement.

Adaptations in Nucleus Accumbens Neuron Subtypes Mediate Negative Affective Behaviors in Fentanyl Abstinence.

BACKGROUND: Opioid discontinuation generates a withdrawal syndrome marked by increased negative affect. Increased symptoms of anxiety and dysphoria during opioid discontinuation are significant barriers to achieving long-term abstinence in opioid-dependent individuals. While adaptations in the nucleus accumbens are implicated in opioid abstinence syndrome, the precise neural mechanisms are poorly understood. Additionally, our current knowledge is limited to changes following natural and semisynthetic opioids, despite recent increases in synthetic opioid use and overdose. METHODS: We used a combination of cell subtype-specific viral labeling and electrophysiology in male and female mice to investigate structural and functional plasticity in nucleus accumbens medium spiny neuron (MSN) subtypes after fentanyl abstinence. We characterized molecular adaptations after fentanyl abstinence with subtype-specific RNA sequencing and weighted gene co-expression network analysis. We used viral-mediated gene transfer to manipulate the molecular signature of fentanyl abstinence in D1-MSNs. RESULTS: Here, we show that fentanyl abstinence increases anxiety-like behavior, decreases social interaction, and engenders MSN subtype-specific plasticity in both sexes. D1-MSNs, but not D2-MSNs, exhibit dendritic atrophy and an increase in excitatory drive. We identified a cluster of coexpressed dendritic morphology genes downregulated selectively in D1-MSNs that are transcriptionally coregulated by E2F1. E2f1 expression in D1-MSNs protects against loss of dendritic complexity, altered physiology, and negative affect-like behaviors caused by fentanyl abstinence. CONCLUSIONS: Our findings indicate that fentanyl abstinence causes unique structural, functional, and molecular changes in nucleus accumbens D1-MSNs that can be targeted to alleviate negative affective symptoms during abstinence.

Periodicity Intensity of the 24 h Circadian Rhythm in Newborn Calves Show Indicators of Herd Welfare.

Circadian rhythms are a process of the sleep-wake cycle that regulates the physical, mental and behavioural changes in all living beings with a period of roughly 24 h. Wearable accelerometers are typically used in livestock applications to record animal movement from which we can estimate the activity type. Here, we use the overall movement recorded by accelerometers worn on the necks of newborn calves for a period of 8 weeks. From the movement data, we calculate 24 h periodicity intensities corresponding to circadian rhythms, from a 7-day window that slides through up to 8-weeks of data logging. The strength or intensity of the 24 h periodicity is computed at intervals as the calves become older, which is an indicator of individual calf welfare. We observe that the intensities of these 24 h periodicities for individual calves, derived from movement data, increase and decrease synchronously in a herd of 19 calves. Our results show that external factors affecting the welfare of the herd can be observed by processing and visualising movement data in this way and our method reveals insights that are not observable from movement data alone.

Factors affecting retention of veterinary practitioners in Ireland: a cross-sectional study with a focus on clinical practice.

BACKGROUND: Retention of veterinary practitioners has arisen as a significant problem in recent years in Ireland. No prior Irish peer-reviewed publications have addressed this problem. An online questionnaire was available through social media and via email to Irish vets from January to November 2019. The aim of this survey was to ascertain the factors contributing to the problem of vet retention in Ireland. RESULTS: A total of 370 eligible responses were received. The median age of respondents was 31 and the gender balance was 250 females (68%) to 118 males (32%). The majority of respondents worked in clinical practice 322 (89%), with 138 (42.8%) in mixed practice, 115 (35.7%) in small animal practice, 49 (15.2%) solely with farm animals and 20 (6.2%) in equine practice. Fifty-four percent of respondents described themselves as likely to be leaving their current job within two years and 32.8% as being likely to leave the profession. In total, 44 variables were assessed by univariate analysis and 27 variables were significantly (P < 0.05) associated with the likelihood of a respondent leaving their current job within 2 years (LCJ2), as a proxy measure of the problem of retention. All variables significant on univariate analysis at P < 0.2 were included in a multivariable logistic regression model. Factors associated with LCJ2 included satisfaction with work-life balance (Odds Ratio (OR) 0.33); satisfaction with working hours (OR 0.2); number of years qualified (OR 0.91); position as a practice owner/partner/director (OR 0.15); and log10salary (OR 0.03). Four variables were retained in a separate multivariable linear regression model as significant (P < 0.05) predictors of log10salary. Log10salary increased with years qualified. Males had an increased salary compared to females irrespective of years qualified. Part-time employees, vets on maternity leave or postgraduate vets had a lower log10salary. Compared to veterinary employees, self-employed or locum vets had a higher log10salary. CONCLUSIONS: Veterinary employers should consider salary, working hours and the facilitation of a good work-life balance in order to successfully retain veterinary employees. The significant difference in salaries currently offered to male and female vets, and the high percentage of respondents considering leaving the profession, are important findings and warrant further investigation.

Transcriptome profiling of the ventral pallidum reveals a role for pallido-thalamic neurons in cocaine reward.

Psychostimulant exposure alters the activity of ventral pallidum (VP) projection neurons. However, the molecular underpinnings of these circuit dysfunctions are unclear. We used RNA-sequencing to reveal alterations in the transcriptional landscape of the VP that are induced by cocaine self-administration in mice. We then probed gene expression in select VP neuronal subpopulations to isolate a circuit associated with cocaine intake. Finally, we used both overexpression and CRISPR-mediated knockdown to test the role of a gene target on cocaine-mediated behaviors as well as dendritic spine density. Our results showed that a large proportion (55%) of genes associated with structural plasticity were changed 24 h following cocaine intake. Among them, the transcription factor Nr4a1 (Nuclear receptor subfamily 4, group A, member 1, or Nur77) showed high expression levels. We found that the VP to mediodorsal thalamus (VP → MDT) projection neurons specifically were recapitulating this increase in Nr4a1 expression. Overexpressing Nr4a1 in VP → MDT neurons enhanced drug-seeking and drug-induced reinstatement, while Nr4a1 knockdown prevented self-administration acquisition and subsequent cocaine-mediated behaviors. Moreover, we showed that Nr4a1 negatively regulated spine dynamics in this specific cell subpopulation. Together, our study identifies for the first time the transcriptional mechanisms occurring in VP in drug exposure. Our study provides further understanding on the role of Nr4a1 in cocaine-related behaviors and identifies the crucial role of the VP → MDT circuit in drug intake and relapse-like behaviors.

Diagnosis of respiratory disease in preweaned dairy calves using sequential thoracic ultrasonography and clinical respiratory scoring: Temporal transitions and association with growth rates.

Bovine respiratory disease (BRD) in dairy calves is a multifactorial condition, involving environmental, host, and pathogen factors. Thoracic ultrasound scoring (TUS) has recently been validated as an accurate method of detecting BRD-related lung pathology in dairy calves. Previous studies investigating the use of TUS in preweaned dairy calves have largely been based on cross-sectional data from all-year production systems. The objectives of this longitudinal observational study were to characterize the temporal transitions in TUS scores in dairy calves from pasture-based, seasonal-calving herds using sequential examinations during the preweaning period, and to investigate the relationship between the presence and temporal pattern of BRD, diagnosed by TUS or clinical respiratory scoring (CRS), and average daily gain (ADG). In spring of 2019, 317 preweaned calves from 7 commercial dairy farms were recruited at less than 4 wk old (ranging from 1-27 d of age). Each farm was examined on at least 3 occasions at 20- to 28-d intervals and housed indoors in group or individual pens. At each visit TUS scores, CRS scores based on the University of Wisconsin Calf Respiratory Score Chart (https://www.vetmed.wisc.edu/fapm/wp-content/uploads/2020/01/calf_respiratory_scoring_chart.pdf), and live weight using a dairy breed-specific weigh band were recorded. All data were recorded by the same 2 veterinarians over the course of the study. The final data set consisted of 966 TUS and CRS scores collected from 317 calves over a period of approximately 6 wk from 7 farms. The data were analyzed in multivariable, mixed effects, linear regression models, with separate models constructed for TUS and CRS scores. Random effects (intercepts) were included for calf, farm, and visit week. Additionally, a random slope was included for age at sampling by farm. Median farm TUS score ranged from 0 to 2.5 over the 3 visits (possible range: 0-5). The percentage of calves with a TUS score ≥3 (consolidation of the full thickness of 1 lung lobe), on each farm ranged from 0 to 50%. The median CRS in calves on individual farms ranged from 1 to 3 over the 3 visits (possible range: 0-12). The percentage of calves on each farm with a CRS score ≥5 (possible range: 0-12) ranged from 0 to 26%. The TUS and CRS scores were weakly correlated. The TUS was associated with reduced ADG. Calves with TUS scores ≥3 grew at 126 g/d less than unaffected calves over the 3-wk period before examination. The predicted effect on ADG was dependent on the age and duration over which the animal was affected. Calves affected later (i.e., between visits 2 and 3) had lower predicted weights at 63 d compared with calves with increased TUS scores earlier in the study period. Calves with a TUS score ≥3 at each of the 3 sampling points had the lowest weight at 63 d of age. There was no association of CRS with ADG. This study showed that in contrast to CRS, higher TUS scores are associated with lower ADG, with weight loss being more pronounced in chronic cases.

The interplay between dose and immune system activation determines fungal infection outcome in the African malaria mosquito, Anopheles gambiae.

The Toll pathway is a central regulator of antifungal immunity in insects. In mosquitoes, the Toll pathway affects infections with the fungal entomopathogen, Beauveria bassiana, which is considered a potential mosquito biopesticide. We report here the use of B. bassiana strain I93-825 in Anopheles gambiae to analyze the impact of Toll pathway modulation on mosquito survival. Exposure to a narrow dose range of conidia by direct contact decreased mosquito longevity and median survival. In addition, fungal exposure dose correlated positively and linearly with hazard ratio. Increased Toll signaling by knockdown of its inhibitor, cactus, decreased survivorship of uninfected females, increased mosquito survival after low dose B. bassiana exposure, but had little effect following exposure to higher doses. This observed trade-off could have implications for development of B. bassiana as a prospective vector control tool. On the one hand, selection for small increases in mosquito immune signaling across a narrow dose range could impair efficacy of B. bassiana. On the other hand, costs of immunity and the capacity for higher doses of fungus to overwhelm immune responses could limit evolution of resistance.