Brain activity changes associated with pain perception variability.

Pain perception can be modulated by several factors. Phenomena like temporal summation leads to increased perceived pain, whereas behavioral conditioning can result in analgesic responses. Furthermore, during repeated, identical noxious stimuli, pain intensity can vary greatly in some individuals. Understanding these variations is important, given the increase in investigations that assume stable baseline pain for accurate response profiles, such as studies of analgesic mechanisms. We utilized functional magnetic resonance imaging to examine the differences in neural circuitry between individuals displaying consistent pain ratings and those who experienced variable pain during a series of identical noxious stimuli. We investigated 63 healthy participants: 31 were assigned to a "consistent" group, and 32 were assigned to a "variable" group dependent on pain rating variability. Variable pain ratings were associated with reduced signal intensity in the dorsolateral prefrontal cortex (dlPFC). Furthermore, the dlPFC connectivity with the primary somatosensory cortex and temperoparietal junction was significantly reduced in variable participants. Our results suggest that investigators should consider variability of baseline pain when investigating pain modulatory paradigms. Additionally, individuals with consistent and variable pain ratings differ in their dlPFC activity and connectivity with pain-sensitive regions during noxious stimulation, possibly reflecting the differences in attentional processing and catastrophizing during pain.

Predictors of firearm purchasing during the coronavirus pandemic in the United States: a cross-sectional study.

OBJECTIVES: This study aimed to compare determinants of firearm purchasing related to the pandemic. STUDY DESIGN: This was a cross-sectional survey. METHODS: A total of 3853 online panel participants completed a survey between December 22, 2020, and January 2, 2021, to approximate a nationally representative sample of US adults (aged ≥18 years). Four firearm ownership groups were created: non-owners, a proxy for first-time COVID-19 owners, prepandemic owners with COVID-19 purchase, and prepandemic owners without COVID-19 purchase. Explanatory variables were in four domains: demographics, concern about the pandemic, actions taken in response to COVID-19, and emotional response to COVID-19. Multivariate analysis estimated the adjusted odds of the outcomes. RESULTS: Respondents were categorized as non-owners (n = 2440), pandemic-related purchasers with no other firearms (n = 257), pandemic-related purchasers with other firearms (n = 350), and those who did not purchase in response to the pandemic but have other firearms (n = 806). Multivariable logistic regression found that compared with non-owners, those who had firearms at home with no pandemic-related purchases are more likely to be male, live in rural settings, have higher income, and be Republican. CONCLUSIONS: The results highlight the changing profile of American firearm owners and identify that those who purchased firearms for the first time (in response to the pandemic) should be the focus of tailored public health interventions, including provision of education about recommended firearm storage to reduce firearm violence, particularly because they are more likely to have children at home, and belong to demographic groups that may have less experience with firearm safety.

Environmental conditions and serotype affect Listeria monocytogenes susceptibility to phage treatment in a laboratory cheese model.

Listeria monocytogenes can survive and grow in a variety of environments, including refrigeration, making it difficult to control and highlighting the importance of optimizing control strategies against this pathogen. Listeria phages are attractive biocontrol agents because phages bind to specific wall teichoic acids (WTA) on the bacterial cell wall, inhibiting pathogens without disrupting the normal microbiota or structure of the food. Common stresses found on dairy products can affect cell wall composition and structure and subsequently affect the efficiency of control strategies that target the cell wall. The goal of this study was to determine the effect of a range of pH and temperatures on the effectiveness of a commercial phage cocktail treatment against several strains of L. monocytogenes in a cheese matrix. We developed a laboratory-scale cheese model that was made at different pH, treated with phage, and then inoculated with L. monocytogenes. Cheeses were incubated at 6, 14, or 22°C for 14 d, and bacterial counts were determined on d 1, 7, and 14. Our data show that phage treatment has a limited ability to reduce L. monocytogenes counts at each temperature tested; however, it was more effective on specific strains of L. monocytogenes when cheese was stored at higher temperatures. More specifically, the average counts of L. monocytogenes on phage-treated cheese stored at 22°C were significantly lower than those on phage-treated cheese stored at 6 or 14°C. Similarly, phage treatment was significantly more effective at inhibiting L. monocytogenes on cheese made at higher pH (6 and 6.5) compared with counts on cheese made at pH 5.5, where L. monocytogenes did not grow. Furthermore, serotype was found to affect the susceptibility of L. monocytogenes to phage treatment; serotype 1/2 strains showed significantly higher susceptibility to phage treatment than serotype 4b strains. Overall, our results suggest the importance of considering the efficacy of phage under conditions (i.e., temperature and pH) specific to a given food matrix when applying interventions against this important foodborne pathogen.

Preoperative breast MRI and mortality in older women with breast cancer.

PURPOSE: The survival benefit from detecting additional breast cancers by preoperative magnetic resonance imaging (MRI) continues to be controversial. METHODS: We followed a cohort of 4454 women diagnosed with non-metastatic breast cancer (stage I-III) from 2/2005-6/2010 in five registries of the breast cancer surveillance consortium (BCSC). BCSC clinical and registry data were linked to Medicare claims and enrollment data. We estimated the cumulative probability of breast cancer-specific and all-cause mortality. We tested the association of preoperative MRI with all-cause mortality using a Cox proportional hazards model. RESULTS: 917 (20.6%) women underwent preoperative MRI. No significant difference in the cumulative probability of breast cancer-specific mortality was found. We observed no significant difference in the hazard of all-cause mortality during the follow-up period after adjusting for sociodemographic and clinical factors among women with MRI (HR 0.90; 95% CI 0.72-1.12) compared to those without MRI. CONCLUSION: Our findings of no breast cancer-specific or all-cause mortality benefit supplement prior results that indicate a lack of improvement in surgical outcomes associated with use of preoperative MRI. In combination with other reports, the results of this analysis highlight the importance of exploring the benefit of preoperative MRI in patient-reported outcomes such as women's decision quality and confidence levels with decisions involving treatment choices.

Plumage coloration and social context influence male investment in song.

Animals use multiple signals to attract mates, including elaborate song, brightly coloured ornaments and physical displays. Female birds often prefer both elaborate male song and intense carotenoid-based plumage coloration. This could lead less visually ornamented males to increase song production to maximize their attractiveness to females. We tested this possibility in the highly social and non-territorial house finch (Haemorhous mexicanus), in which females discriminate among males based on both song and on the intensity of red carotenoid-based plumage coloration. We manipulated male plumage coloration through carotenoid supplementation during moult, so that males were either red or yellow. Males were then housed under three social environments: (i) all red birds, (ii) all yellow birds or (iii) a mixture of red/yellow birds. We recorded song after presentation of a female. Red males produced more song than yellow males. But when yellow males were housed with red conspecifics, they produced more song relative to yellow males housed with equally unattractive yellow males. This study provides novel evidence that a male's plumage coloration and the plumage colour of his social competitors influence investment in song.

Anti-TNF therapy is not associated with an increased risk of post-colectomy complications, a population-based study.

AIM: Previous studies have raised concerns that the use of anti-tumour necrosis factor (anti-TNF) therapy in patients with ulcerative colitis (UC) undergoing surgery may increase the risk of postoperative complications. We have taken a population-based approach to investigate whether there is an association between anti-TNF therapy and postoperative complications in UC patients undergoing subtotal colectomy. METHOD: Hospital Episode Statistics (HES) data and procedural coding were used to identify all patients in England between April 2006 and March 2015 undergoing subtotal colectomy for UC. Patients were grouped into those who received anti-TNF therapy within 12 or 4 weeks of surgery and those who did not. The incidence of postoperative complications was evaluated by HES coding and compared between groups. RESULTS: In all, 6225 UC patients underwent subtotal colectomy. 753 patients received anti-TNF therapy within 12 weeks prior to surgery (418 within 4 weeks). There was no difference in postoperative complications between groups although groups were not comparable for age and comorbidities. Logistic regression with complications as the outcome variable did not show any significant association between anti-TNF therapy and complications. Colectomy performed during an unplanned admission (vs planned admission) and smoking were associated with complications. CONCLUSION: This large population-based study does not demonstrate any association between preoperative anti-TNF therapy and postoperative complications in UC patients undergoing subtotal colectomy. The only variables associated with complications were colectomy performed during an unplanned admission and smoking.

Consolidating new words from repetitive versus multiple stories: Prior knowledge matters.

Prior knowledge is proposed to support the consolidation of newly acquired material. The current study examined whether children with superior vocabulary knowledge show enhanced overnight consolidation, particularly when new words are encountered in varying stories. Children aged 10 and 11 years (N = 42) were exposed to two sets of eight spoken novel words (e.g., "crocodol"), with one set embedded in the same story presented twice and the other presented in two different stories. Children with superior vocabulary knowledge showed larger overnight gains in explicit phonological and semantic knowledge when novel words had been encountered in multiple stories. However, when novel words had been encountered in repetitive stories, existing knowledge exerted no influence on the consolidation of explicit phonological knowledge and had a negative impact on the consolidation of semantic knowledge. One full day (24 h) after story exposure, only very weak evidence of lexical integration (i.e., slower animacy decisions toward the basewords [e.g., "crocodile"] than toward the control words) was observed for novel words learned via repetitive (but not multiple) stories. These data suggest that although the consolidation of explicit new word knowledge learned through multiple contexts is supported by prior knowledge, lexical integration might benefit more from repetition.

RISUS study: Rugby Injury Surveillance in Ulster Schools.

OBJECTIVE: To examine injury patterns in adolescent rugby players and determine factors associated with injury risk. DESIGN: Prospective injury surveillance study. SETTING: N=28 Grammar Schools in Ulster, Ireland (2014-2015 playing season). PARTICIPANTS: 825 adolescent rugby players, across in 28 school first XV rugby squads; mean age 16.9 years. MAIN OUTCOME MEASURES: Injuries were classified by body part and diagnosis, and injury incidence using injuries per 1000 match hours of exposure. HRs for injury were calculated through Cox proportional hazard regression after correction for influential covariates. RESULTS: A total of n=426 injuries were reported across the playing season. Over 50% of injuries occurred in the tackle situation or during collisions (270/426), with few reported during set plays. The 3 most common injury sites were head/face (n=102, 23.9%), clavicle/shoulder (n=65, 15.3%) and the knee (n=56, 13.1%). Sprain (n=133, 31.2%), concussion (n=81, 19%) and muscle injury (n=65, 15.3%) were the most common diagnoses. Injury incidence is calculated at 29.06 injuries per 1000 match hours. There were no catastrophic injuries. A large percentage of injuries (208/424) resulted in absence from play for more than 28 days. Concussion carried the most significant time out from play (n=33; 15.9%), followed by dislocations of the shoulder (n=22; 10.6%), knee sprains (n=19, 9.1%), ankle sprains (n=14, 6.7%), hand/finger/thumb (n=11; 5.3%). 36.8% of participants in the study (304/825) suffered at least one injury during the playing season. Multivariate models found higher risk of injury (adjusted HR (AHR); 95% CI) with: higher age (AHR 1.45; 1.14 to 1.83), heavier weight (AHR 1.32; 1.04 to 1.69), playing representative rugby (AHR 1.42; 1.06 to 1.90) and undertaking regular strength training (AHR 1.65; 1.11 to 2.46). Playing for a lower ranked team (AHR 0.67; 0.49 to 0.90) and wearing a mouthguard (AHR 0.70; 0.54 to 0.92) were associated with lower risk of injury. CONCLUSIONS: There was a high incidence of severe injuries, with concussion, ankle and knee ligament injuries and upper limb fractures/dislocations causing greatest time loss. Players were compliant with current graduated return-to-play regulations following concussion. Physical stature and levels of competition were important risk factors and there was limited evidence for protective equipment.

Pain inhibits pain; human brainstem mechanisms.

Conditioned pain modulation is a powerful analgesic mechanism, occurring when a painful stimulus is inhibited by a second painful stimulus delivered at a different body location. Reduced conditioned pain modulation capacity is associated with the development of some chronic pain conditions and the effectiveness of some analgesic medications. Human lesion studies show that the circuitry responsible for conditioned pain modulation lies within the caudal brainstem, although the precise nuclei in humans remain unknown. We employed brain imaging to determine brainstem sites responsible for conditioned pain modulation in 54 healthy individuals. In all subjects, 8 noxious heat stimuli (test stimuli) were applied to the right side of the mouth and brain activity measured using functional magnetic resonance imaging. This paradigm was then repeated. However, following the fourth noxious stimulus, a separate noxious stimulus, consisting of an intramuscular injection of hypertonic saline into the leg, was delivered (conditioning stimulus). During this test and conditioning stimulus period, 23 subjects displayed conditioned pain modulation analgesia whereas 31 subjects did not. An individual's analgesic ability was not influenced by gender, pain intensity levels of the test or conditioning stimuli or by psychological variables such as pain catastrophizing or fear of pain. Brain images were processed using SPM8 and the brainstem isolated using the SUIT toolbox. Significant increases in signal intensity were determined during each test stimulus and compared between subjects that did and did not display CPM analgesia (p<0.05, small volume correction). The expression of analgesia was associated with reduction in signal intensity increases during each test stimulus in the presence of the conditioning stimulus in three brainstem regions: the caudalis subdivision of the spinal trigeminal nucleus, i.e., the primary synapse, the region of the subnucleus reticularis dorsalis and in the dorsolateral pons in the region of the parabrachial nucleus. Furthermore, the magnitudes of these signal reductions in all three brainstem regions were significantly correlated to analgesia magnitude. Defining conditioned pain modulation circuitry provides a framework for the future investigations into the neural mechanisms responsible for the maintenance of persistent pain conditions thought to involve altered analgesic circuitry.

Dorsal raphe nucleus and harm avoidance: A resting-state investigation.

The temperament dimension of harm avoidance defines an individual's biological tendency to exhibit altering levels of anxious, inhibiting, and cautious behavior. High harm avoidance and anxiety are highly comorbid, likely due to activity in similar neural circuitries involving the dorsal raphe nucleus. Despite the many investigations that have explored personality factors and brain function, none have determined the influence of ongoing activity within dorsal raphe networks on harm avoidance. The aim of this study was to explore such a relationship. In 62 healthy subjects, a series of 180 functional magnetic resonance images covering the entire brain were collected, and each subject completed the 240-item TCI-R questionnaire. Independent component analyses were performed to define the dorsal raphe network and then to determine the regions significantly correlated with harm avoidance. The independent component analyses revealed three signal intensity fluctuation maps encompassing the dorsal raphe nucleus, showing interactions with regions of the amygdala, hippocampus, nucleus accumbens, and prefrontal, insular, and cingulate cortices. Within these systems, the resting signal intensity was significantly coupled to harm avoidance in the bilateral basal amygdala, bilateral ventral hippocampus, bilateral insula, bilateral nucleus accumbens, and medial prefrontal cortex. Note that we could not measure serotonergic output, but instead measured signal changes in the dorsal raphe that likely reflect synaptic activity. These data provide evidence that at rest, signal intensity fluctuations within the dorsal raphe networks are related to harm avoidance. Given the strong relationship between harm avoidance and anxiety-like behaviors, it is possible that ongoing activity within this identified neural circuitry can contribute to an individual developing anxiety disorders.

Anatomical changes within the medullary dorsal horn in chronic temporomandibular disorder pain.

Accumulated evidence from experimental animal models suggests that neuroplastic changes at the dorsal horn are critical for the maintenance of various chronic musculoskeletal pain conditions. However, to date, no study has specifically investigated whether neuroplastic changes also occur at this level in humans. Using brain imaging techniques, we sought to determine whether anatomical changes were present in the medullary dorsal horn (spinal trigeminal nucleus caudalis) in subjects with the chronic musculoskeletal pain. In twenty-two subjects with painful temporomandibular disorders (TMDs) and forty pain-free controls voxel based morphometry of T1-weighted anatomical images and diffusion tensor images were used to assess regional grey matter volume and microstructural changes within the brainstem and, in addition, the integrity of ascending pain pathways. Voxel based morphometry revealed significant regional grey matter volume decreases in the medullary dorsal horn, in conjunction with alterations in diffusivity properties, namely an increase in mean diffusivity, in TMD subjects. Volumetric and mean diffusivity changes also occurred in TMD subjects in regions of the descending pain modulation system, including the midbrain periaqueductal grey matter and nucleus raphe magnus. Finally, tractography revealed altered diffusivity properties, namely decreased fractional anisotropy, in the root entry zone of the trigeminal nerve, the spinal trigeminal tract and the ventral trigeminothalamic tracts of TMD subjects. These data reveal that chronic musculoskeletal pain in humans is associated with discrete alterations in the anatomy of the medullary dorsal horn, as well as its afferent and efferent projections. These neural changes may be critical for the maintenance of pathological pain.

Trainee as trainer in paediatric laparoscopic appendicectomy.

BACKGROUND: Intraoperative teaching is an essential surgical skill, but there is little literature regarding trainees acting as trainers; we characterised these cases in paediatric laparoscopic appendicectomy. METHODS: This is a retrospective review of casenotes over two years (2015-2017) in a single tertiary paediatric surgical centre in the UK. Operating were: paediatric surgery Core Trainees (CT) (postgraduate year (PGY)3-4), Junior Registrars (JR) (PGY5-6) and Senior Registrars (SR) (PGY7+); collectively described as trainees. RESULTS: A total of 53 (20.7%) of 256 appendicectomies were trainee as trainer (TT) cases; 22 cases (41.5%) were performed by a CT supervised by a Registrar, and 31 (58.4%) by a JR supervised by a SR. Among the cases, 17 (32.1%) were complex, 47 (88.7%) were in working hours (8am-5pm), and 50 (94.3%) took place Monday to Friday. Median (interquartile range) duration of surgery was 65 (52-77) minutes. In the first year, 60 (47%) appendicectomies were performed by JRs. JR 1 was TT in three cases (8.8%) and JR 2 in five cases (19.2%); in all cases, the learner was a CT. Overall, there were 26 (10.6%) negative appendicectomies, 8 (3%) conversions, 19 (7%) readmissions within 30 days of discharge and 3 (1.1%) required reoperation; there was no statistically significant difference in complications between TT and non-TT cases. CONCLUSION: Laparoscopic appendicectomy is an excellent model for trainees to act as trainer; case selection included simple cases during daylight hours. Our outcomes are comparable with published literature, suggesting that this teaching method is safe for patients.

Do naps benefit novel word learning? Developmental differences and white matter correlates.

Memory representations of newly learned words undergo changes during nocturnal sleep, as evidenced by improvements in explicit recall and lexical integration (i.e., after sleep, novel words compete with existing words during online word recognition). Some studies have revealed larger sleep-benefits in children relative to adults. However, whether daytime naps play a similar facilitatory role is unclear. We investigated the effect of a daytime nap (relative to wake) on explicit memory (recall/recognition) and lexical integration (lexical competition) of newly learned novel words in young adults and children aged 10-12 years, also exploring white matter correlates of the pre- and post-nap effects of word learning in the child group with diffusion weighted MRI. In both age groups, a nap maintained explicit memory of novel words and wake led to forgetting. However, there was an age group interaction when comparing change in recall over the nap: children showed a slight improvement whereas adults showed a slight decline. There was no evidence of lexical integration at any point. Although children spent proportionally more time in slow-wave sleep (SWS) than adults, neither SWS nor spindle parameters correlated with over-nap changes in word learning. For children, increased fractional anisotropy (FA) in the uncinate fasciculus and arcuate fasciculus were associated with the recognition of novel words immediately after learning, and FA in the right arcuate fasciculus was further associated with changes in recall of novel words over a nap, supporting the importance of these tracts in the word learning and consolidation process. These findings point to a protective role of naps in word learning (at least under the present conditions), and emphasize the need to better understand both the active and passive roles that sleep plays in supporting vocabulary consolidation over development.

Quantifying graft impingement in anterior cruciate ligament reconstruction.

BACKGROUND: Anterior cruciate ligament reconstructions (ACLR) fail at a rate of 10-15%, with graft impingement often a cause. In this study we investigate the prevalence and causes of impingement seen during ACLR surgery. METHODS: We reviewed consecutive primary ACLR from 2012-2018. Graft impingement was estimated intraoperatively by placing the arthroscope through the tibial tunnel and passively extending the knee, observing how much was obscured by the lateral femoral condyle from an anterior and lateral direction. Preoperative MRI scans were used to measure the intercondylar notch; Notch Width Index (NWI) and Notch Depth Index (NDI). Positioning of the tunnels was determined on postoperative radiographs. RESULTS: There were 283 ACLRs performed with 33 failures diagnosed on MRI (11.7%). 257 patients had complete imaging and follow up (91%). The mean age was 28 (±9) years and mean follow-up 5.3 (±1.8) years. The mean NWI was 0.26(±0.03), and NDI was 0.49(±0.06). The tibial tunnel aperture was located 42(±6) % of the way from anterior-posterior and 39(±6) % from medial-lateral. Impingement requiring a notchplasty was observed in 80% of cases, with lateral impingement more prominent. CONCLUSIONS: The amount of impingement did not correlate with tunnel position, which was located within the recommended area. There was a weak negative correlation between NWI and lateral impingement (rs = -0.16, p = 0.01), and NDI and anterior impingement (rs = -0.12, p = 0.04), therefore a smaller notch is associated with greater impingement. Despite optimal tunnel positioning, impingement still occurs in a significant number of cases therefore notchplasty should always be considered to keep revision rates low.

Surveillance protocol kidney transplant biopsies: their evolving role in clinical practice.

Protocol renal allograft biopsies at fixed time points from transplantation have aided research and provided insights into the pathogenesis of early and late allograft injury. Their role is evolving from research to a clinical management tool needed to detect subclinical pathology requiring treatment adjustment. They frequently reveal unexpected findings and influence therapy in the majority of patients. Detection of subclinical rejection (SCR) remains important despite declining prevalence with triple therapy, the evidence favors treatment, if found. Surveillance biopsies in steroid avoidance and calcineurin inhibitor (CNI) withdrawal programs provide an important safety net against the increased rates of late acute and SCR. Individualization of therapy in high-risk patients and safe reduction of immunosuppression in standard risk individuals becomes possible. Other potentially reversible chronic pathologies that may be detected, include chronic T-cell or antibody-mediated rejection, recurrent disease, BK virus-associated nephropathy, interstitial fibrosis and tubular atrophy and CNI nephrotoxicity, allowing modifications of therapy to limit ongoing graft injury. Biopsy is safe and inexpensive compared with costs of earlier graft failure and return to dialysis. This review summarizes current evidence on use of surveillance histology for the clinical practice of renal transplantation.

Accessing and selecting word meaning in autism spectrum disorder.

BACKGROUND: Comprehension difficulties are commonly reported in autism spectrum disorder (ASD) but the causes of these difficulties are poorly understood. This study investigates how children with ASD access and select meanings of ambiguous words to test four hypotheses regarding the nature of their comprehension difficulties: semantic deficit, weak central coherence, reduced top-down control and inhibition deficit. METHODS: The cross-modal semantic priming paradigm was used. Children heard homonym primes in isolation or as final words in sentences biased towards the subordinate meaning and then named picture targets depicting dominant or subordinate associates of homonyms. RESULTS: When homonyms were presented in isolation, children with ASD and controls showed priming for dominant and subordinate pictures at 250ms ISI. At 1,000ms ISI, the controls showed dominant (but not subordinate) priming whilst the ASD group did not show any priming. When homonyms were presented in subordinate sentence contexts, both groups only showed priming for context-appropriate (subordinate) meanings at 250ms ISI, suggesting that context has an early influence on meaning selection. At 1,000ms ISI the controls showed context-appropriate (but not inappropriate) priming whereas the ASD group showed both appropriate and inappropriate priming. CONCLUSIONS: Children with ASD showed intact access to semantic information early in the time course of processing; however, they showed impairments in the selection of semantic representations later in processing. These findings suggest that a difficulty with initiating top-down strategies to modulate online semantic processing may compromise language comprehension in ASD. Implications for intervention are discussed.

Brain anatomy changes associated with persistent neuropathic pain following spinal cord injury.

Persistent neuropathic pain commonly occurs following spinal cord injury (SCI). It remains one of the most challenging management problems in this condition. In order to develop more effective treatments, a better understanding of the neural changes associated with neuropathic SCI pain is required. The aim of this investigation was to use diffusion tensor imaging (DTI) to determine if persistent neuropathic pain following SCI is associated with changes in regional brain anatomy and connectivity. In 23 subjects with complete thoracic SCI, 12 with below-level neuropathic pain and 11 without pain, and 45 healthy control subjects, a series of whole-brain DTI scans were performed. The mean diffusivity (MD) of each voxel was calculated and values compared between groups. This analysis revealed that neuropathic pain following SCI is associated with significant differences in regional brain anatomy. These anatomical changes were located in pain-related regions as well as regions of the classic reward circuitry, that is, the nucleus accumbens and orbitofrontal, dorsolateral prefrontal, and posterior parietal cortices. The right posterior parietal cortex projected to most regions that displayed an anatomical change. Analysis of the fiber tracts connecting areas of MD differences revealed no significance differences in MD values between the SCI pain, SCI no pain, and control groups.

Short communication: genetic parameters for measures of calf health in a population of Holstein calves in New York State.

The objectives of this study were to estimate the genetic parameters of preweaning undifferentiated bovine respiratory disease (BRD), umbilical diseases (UMB), and bloat (BLT) for a population of Holstein calves from New York State, as well as to associate the estimated breeding values determined in the current study with traits from ongoing genetic evaluations used in Canada and the United States. Data were recorded for 7,372 heifer calves at a commercial rearing facility in New York State, from arrival at 1 to 7d of age for the duration of stay at the facility. Performance and disease up to weaning and mortality before and after weaning were recorded. The 3 traits of interest, BRD, UMB, and BLT, were scored as 0 or 1 and analyzed using a multivariate linear sire model. The model included fixed effects of arrival weight, serum total protein, weaning weight, and season and year of birth; herd and sire were included as random effects. The heritabilities of the 3 health traits of interest were estimated at 0.09 for BRD, 0.14 for UMB, and 0.04 for BLT. The genetic correlation between the calf health traits BRD and BLT was 0.62. Correlations between BRD and UMB and between BLT and UMB were close to zero. Breeding values were estimated for the 3 calf health traits and correlated with routinely evaluated traits from Canadian and US genetic evaluations (correlations ranged from -0.42 to 0.32). Significant differences existed among Holstein sires for calf health during the preweaning period.

Estimation of genetic parameters for measures of calf survival in a population of Holstein heifer calves from a heifer-raising facility in New York State.

The objectives of this study were to estimate the genetic parameters of survival to weaning and survival to exit for a population of Holstein calves from New York State, as well as to associate the estimated breeding values determined in the current study with traits from ongoing genetic evaluations used in Canada and the United States. Data were recorded for 7,372 heifer calves at a commercial rearing facility in New York State from arrival at 1 to 7 d of age for the duration of stay at the facility (on average, heifers departed the facility 1 mo before calving). Performance and disease up to weaning and mortality before and after weaning were recorded. Analyzed data were limited to daughters of sires with at least 10 calves originating from farms that had sent a minimum of 5 calves to be raised at the facility. As such, calves from 264 sires and 36 herds were studied using 2 statistical methods. The first method, calf survival, used a Weibull proportional hazards model, with survival defined as age at culling, death, or censoring. The second method, a 2-trait sire model, included survival from arrival to weaning (SUV1) and survival from weaning to exit (SUV2). Both models included fixed effects of arrival weight, serum total protein, weaning weight, season and year of birth, and calving ease score. Herd and sire were included as random effects. Significant associations among all fixed effects and calf survival were observed. In general, very light or heavy weight at arrival, low total protein, low weaning weight, and difficult birth increased risk of mortality for calves. The heritability of survival from the first method was 0.063. The heritabilities from the linear model were 0.001 for SUV1 and 0.036 for SUV2. The genetic correlation between SUV1 and SUV2 was 0.58. Genetic variance was close to zero for survival of calves to weaning, but was greater for survival after weaning through the growing period. Breeding values were estimated for SUV1 and SUV2 and correlated with routinely evaluated traits from Canadian and US genetic evaluations. Significant associations between genetic evaluations for survival traits and routinely evaluated traits in Canada and the United States were found, in particular with conformation body traits, somatic cell score, fertility, and longevity.

In situ labeling of non-accommodating interneurons based on metabolic rates.

Maintaining high frequency firing of narrow action potentials puts a large metabolic load on fast spiking (FS), perisomatic-inhibitory interneurons compared to their slow-spiking, dendrite targeting counterparts. Although the relationship of action potential (AP) firing and metabolism is firmly established, there is no single method to differentiate interneurons in situ based on their firing properties. In this study, we explore a novel strategy to easily identify the metabolically active FS cells among different classes of interneurons. We found that the oxidation of the fluorescent free radical marker 2,7-dichlorodihydrofluorescein (H2DCF) preferentially occurs in interneurons both in slice cultures and acute brain slices. Despite their morphological heterogeneity, almost all DCF-positive (DCF+) neurons belonged to the cluster of non-accommodating FS interneurons. Furthermore, all FS interneurons expressing parvalbumin (PV) both in slice cultures and in acute slices from tdTomato-PVCre transgenic mice were also DCF+. However, only half of the recorded DCF + cells were also PV+, indicating that H2DCF-oxidation occurs in different interneuron classes characterized by non-accomodating AP-firing. Comprehensively enhancing spontaneous neuronal activity led to mitochondrial oxidation of DCF in pyramidal cells as well as interneurons, suggesting that the apparent selectivity towards interneurons represents differences in the underlying metabolic load. While radical-scavenging, inhibition of APs or NO-synthesis, and iron chelation had no effect on the staining pattern, exposure to the complex-I inhibitor, rotenone, prevented interneuronal DCF accumulation. We conclude that H2DCF oxidation is independent of free radicals but correlates with the intensive oxidative energy metabolism and high mitochondrial mass in interneurons sharing the non-accommodating FS phenotype.