The indirect pathway of the basal ganglia promotes transient punishment but not motor suppression.

Optogenetic stimulation of Adora2a receptor-expressing spiny projection neurons (A2A-SPNs) in the striatum drives locomotor suppression and transient punishment, results attributed to activation of the indirect pathway. The sole long-range projection target of A2A-SPNs is the external globus pallidus (GPe). Unexpectedly, we found that inhibition of the GPe drove transient punishment but not suppression of movement. Within the striatum, A2A-SPNs inhibit other SPNs through a short-range inhibitory collateral network, and we found that optogenetic stimuli that drove motor suppression shared a common mechanism of recruiting this inhibitory collateral network. Our results suggest that the indirect pathway plays a more prominent role in transient punishment than in motor control and challenges the assumption that activity of A2A-SPNs is synonymous with indirect pathway activity.

Inter- and Intra-Observer Variability and the Effect of Experience in Cine-MRI for Adhesion Detection.

Cine-MRI for adhesion detection is a promising novel modality that can help the large group of patients developing pain after abdominal surgery. Few studies into its diagnostic accuracy are available, and none address observer variability. This retrospective study explores the inter- and intra-observer variability, diagnostic accuracy, and the effect of experience. A total of 15 observers with a variety of experience reviewed 61 sagittal cine-MRI slices, placing box annotations with a confidence score at locations suspect for adhesions. Five observers reviewed the slices again one year later. Inter- and intra-observer variability are quantified using Fleiss' (inter) and Cohen's (intra) κ and percentage agreement. Diagnostic accuracy is quantified with receiver operating characteristic (ROC) analysis based on a consensus standard. Inter-observer Fleiss' κ values range from 0.04 to 0.34, showing poor to fair agreement. High general and cine-MRI experience led to significantly (p < 0.001) better agreement among observers. The intra-observer results show Cohen's κ values between 0.37 and 0.53 for all observers, except one with a low κ of -0.11. Group AUC scores lie between 0.66 and 0.72, with individual observers reaching 0.78. This study confirms that cine-MRI can diagnose adhesions, with respect to a radiologist consensus panel and shows that experience improves reading cine-MRI. Observers without specific experience adapt to this modality quickly after a short online tutorial. Observer agreement is fair at best and area under the receiver operating characteristic curve (AUC) scores leave room for improvement. Consistently interpreting this novel modality needs further research, for instance, by developing reporting guidelines or artificial intelligence-based methods.

Prevalence of Echocardiographic Evidence of Trace Mitral and Aortic Valve Regurgitation in 50 Clinically Healthy, Young Adult Labrador Retrievers without Heart Murmur.

Background-Though physiologic regurgitation of the right-sided cardiac valves is well recognized in dogs and other mammals, the prevalence of trace insufficiency of the mitral and aortic valves in clinically healthy, young adult dogs is unknown. Methods-In this observational cross-sectional study, 50 clinically healthy, young adult Labrador retrievers without an audible heart murmur were enrolled. All dogs were bred and owned by a single organization. Cardiac screening was requested for all dogs that were intended for breeding. These dogs underwent a cardiac auscultation and transthoracic echocardiography by a veterinary cardiology specialist. If mitral or aortic valve regurgitation was noticed, the jet size was subjectively assessed on color Doppler echocardiography. Pedigree analysis was performed to reveal a possible hereditary background of mitral valve regurgitation. Results-The prevalence of trivial mitral valve regurgitation was 52% with no significant predisposition to gender (p = 0.86) or haircoat color (p = 0.68). The prevalence of aortic valve regurgitation was 4%. Pedigree analysis for mitral valve regurgitation showed familial clustering, suggesting a hereditary background of the trait. Conclusions-The prevalence of silent trace mitral valve regurgitation in young adult Labrador retrievers was high. Because the regurgitant jet was trivial in all dogs, it is probably physiologic.

Intra-rater Reliability of a Qualitative Landing Scale for the Single-Hop Test: A Pilot Study.

Background: The test battery classically used for return-to-sport (RTS) decision-making after anterior cruciate ligament (ACL) reconstruction (ACLR) may not be sufficient, as it does not include a qualitative analysis of movement. Therefore, the Landing Error Scoring System (LESS) scale was adapted to a primary functional test in the typical RTS test battery: the single leg hop for distance (SHD). Hypothesis/ Purpose: The aim of this study was to determine the intra-rater reliability of the LESS scale adapted to the SHD (SHD-LESS scale) in healthy young athletes. Study Design: Reliability analysis. Methods: Nineteen healthy individuals (14 men, 5 women; mean age: 22.4 years) participated in the study. Participants performed the SHD tasks on both limbs (dominant and non-dominant) using a standardized protocol in two sessions that were one week apart (single reviewer; 2-dimensional video). Intra-class correlation coefficients (ICC2,1) were used to measure the reproducibility of the scale in the dominant (dom) and non-dominant (nondom) limbs. Additionally, limb data (dom and nondom) were pooled and evaluated collectively with intra-class correlation coefficients. The Kappa coefficient was used to assess the reproducibility of each individual item of SHD-LESS scale. Results: The intra-rater reliability was good (ICCdom = 0.77; ICCnondom = 0.87; ICCpooled = 0.87) for the overall SHD-LESS scale scores. Agreement of SHD-LESS individual items ranged from 62% to 100%. Dorsiflexion at initial contact (97% agreement; kappa value=0.79) and knee valgus after landing (88% agreement; kappa value=0.65) had excellent agreement and kappa values. Conclusion: The newly-adapted SHD-LESS scale showed good intra-rater reliability overall. Further studies should evaluate the impact of using the SHD-LESS scale within the RTS test battery on outcomes in patients after ACLR. Level of Evidence: 3.

Correlation Between Quantitative MRI and Muscle Histopathology in Muscle Biopsies from Healthy Controls and Patients with IBM, FSHD and OPMD.

BACKGROUND: Muscle MRI is increasingly used as a diagnostic and research tool in muscle disorders. However, the correlation between MRI abnormalities and histopathological severity is largely unknown. OBJECTIVE: To investigate correlations between muscle MRI abnormalities and histopathological severity in healthy controls and patients with muscle disease. METHODS: We performed quantitative MRI and histopathological analysis in 35 patients with inclusion body myositis, facioscapulohumeral muscular dystrophy or oculopharyngeal muscular dystrophy and 12 healthy controls. Participants contributed needle biopsies of the vastus lateralis and/or tibialis anterior, yielding 77 muscle biopsies with matched T1, T2 and TIRM MRI imaging. Muscle biopsies were evaluated with a semi-quantitative histopathology severity grading scale (range 0-12) and an inflammation severity grading scale (range 0-3). RESULTS: In muscle disease, histopathology sum scores ranged from 0 to 11 and correlated significantly with fat percentage as measured on MRI (Spearman's rho = 0.594, p < 0.001). Muscle edema on muscle MRI was associated with increased amounts of inflammation (p < 0.001). Mild abnormalities occured in 95% of control biopsies and were more pronounced in tibialis anterior (median sum score of 1±1 in vastus lateralis and 2±1 in tibialis anterior (p = 0.048)). CONCLUSION: In muscle disease, fatty infiltration on MRI correlates moderately with muscle histopathology. Histopathological abnormalities can occur prior to the onset of fatty infiltration. In middle-aged controls, almost all biopsies showed some histopathological abnormalities. The findings from this study may facilitate the choice for appropriate imaging sequences as outcome measures in therapeutic trials.

Diagnostic accuracy of office blood pressure compared to home blood pressure in patients with mild cognitive impairment and dementia.

BACKGROUND: Hypertension and cognitive impairment often coexist in older people. Office blood pressure measurement is a poor indicator for diagnosing hypertension in the general population. However, its diagnostic accuracy has not been substantially studied in patients with cognitive impairment. AIM: The aim of this study was to determine the proportion of misdiagnosis of hypertension in patients with mild cognitive impairment and dementia compared to no cognitive impairment, by comparing office blood pressure measurement with home blood pressure measurement. METHODS: A cross-sectional study including consecutive patients visiting a memory clinic between 2014 and 2017. Home blood pressure was measured for one week according to the European guidelines. Office blood pressure was assessed during routine clinical practice. Using guideline definitions for normal blood pressure and hypertension, we investigated the proportion of disagreement between office blood pressure measurement and home blood pressure measurement. Univariable and multivariable logistic regression compared disagreement in diagnosis between patients with dementia, mild cognitive impairment and no cognitive impairment. RESULTS: Of 213 patients (aged 73.4±9.0 years, 42% women) 82 had dementia, 65 had mild cognitive impairment and 66 had no cognitive impairment. Mean office blood pressure was 156/84±23/11 mmHg and mean home blood pressure was 139/79±16/10 mmHg. In 31% of patients, there was disagreement in hypertension diagnosis. This proportion was higher for mild cognitive impairment (38.5%) and dementia (35.4%) compared to no cognitive impairment (18.2%), with adjusted odds ratios of 3.7 (95% confidence interval 1.5-9.0), P=0.005 for mild cognitive impairment and 3.4 (1.3-8.6), P=0.011 for dementia. CONCLUSIONS: In memory clinic patients with dementia and mild cognitive impairment, the diagnostic accuracy of office blood pressure measurement is lower compared to patients without cognitive impairment. To avoid the risk of making improper treatment decisions in this vulnerable group, a diagnosis of hypertension should be based on home blood pressure measurement, not office blood pressure measurement.

Assessment and monitoring of water quality of the gulf of Morbihan, a littoral ecosystem under high anthropic pressure.

This field study is intended to propose a global methodology to assess and monitor the water quality of the gulf of Morbihan, a littoral ecosystem under increasing anthropic pressure. To this end, the Locmariaquer site, where Crassostrea gigas is extensively cultivated, was selected to perform a one-year follow-up of tissular glutathione S-transferase and acetylcholinesterase specific activities in this filter feeder organism. Calculation of an integrated index, corresponding to the ratio of the two enzymes activities, allowed to discriminate from the environmental noise, several clusters which could be representative environmental stress, potentially latent pollution. Moreover, the estrogenic activity was assessed in water samples collected at Locmariaquer and other strategic sites of the gulf. The results evidenced a low estrogenic-disrupting compound contamination of waters. Overall, this methodology produced an accurate outlook of a basal state for the gulf and could be developed in the context of a chronic monitoring of this site.

A Pilot Study Evaluating the Physiological Parameters of Performance-Induced Stress in Undergraduate Music Students.

Music performance anxiety (MPA) is a specific condition for musicians. Although it can have a negative influence on their music careers, little attention is paid to this phenomenon both in the professional environment and in stress research. In the current pilot study, insight was gained into the physiology of the autonomic stress response related to anxiety in musicians when performing on stage by using a wearable biosensor patch for registration of a range of physiological parameters. Also, the validity of two different psychometric questionnaires in objectifying the stress response on stage to predict the individual stress response was explored. The autonomic physiological parameters (heart rate, respiratory rate, skin temperature) of 11 violists and violinists were collected while performing on stage and in resting state using the VitalConnect HealthPatch®. In addition, scores on validated questionnaires in research on MPA (State Anxiety Inventory, Kenny Music Performance Anxiety Inventory, Short Form Health Survey) were collected in order to try to objectify the magnitude of the subjective level of both MPA and experienced stress. The registration of the autonomic parameters showed a significant increase in heart rate, respiratory rate, and stress level from resting state measurements during stage performance. Analysis of heart rate variability showed a shift from indices of parasympathetic nervous system activity during baseline measurements towards indices of sympathetic nervous system activity during stress measurements. Surprisingly, none of the questionnaires was correlated to the physiological stress parameters on stage. In conclusion, the wearable biosensor patch proved to be an adequate tool to assess physiological stress parameters on stage. The different questionnaires did not contribute to the prediction of its occurrence in a group of musicians.

Comparative efficacy of a recombinant feline interferon omega in refractory cases of calicivirus-positive cats with caudal stomatitis: a randomised, multi-centre, controlled, double-blind study in 39 cats.

Chronic caudal stomatitis with alveolar/buccal mucositis in calicivirus-positive cats is the most severe presentation of feline chronic gingivostomatitis. Refractory cases are helped by antibiotic and anti-inflammatory treatments often including glucocorticoids. In order to evaluate the comparative efficacy of oromucosal administration of recombinant feline interferon omega (rFeIFN-ω) versus oral administration of glucocorticoids, a randomised, multi-centre, controlled, double-blind study was performed in 39 cats. The progression of behavioural, clinical and lesional scores was assessed over 90 days. Daily oromucosal treatment with 0.1 MU of rFeIFN-ω was associated with a significant improvement of clinical lesions (caudal stomatitis and alveolar/buccal mucositis) and a decrease of pain scores from D0 to D90. Although no such statistical improvement was noticed in the prednisolone group, there was, however, no significant difference between the two groups for most of the parameters, except pain at D60 and D90.

Circulatory and respiratory effects of an hypoxic stress in the Siberian sturgeon.

Changes in circulatory, ventilatory and acid-base variables were studied in Siberian sturgeon (Acipenser baeri) exposed to acute and severe hypoxia (PWO2 = 10 torr), followed by a rapid return to normoxia. This treatment caused a significant stress, revealed by the high levels of plasma catecholamines and cortisol. The moderate circulatory changes firstly observed would represent the effects of increased plasma catecholamine levels together with an increased adrenergic nervous tone on the cardiovascular system. Then, these effects were masked by a possible vagal reflex resulting in bradycardia. Deep hypoxia induced a ventilatory alkalosis combined with a moderate metabolic acidosis. The latter amplified concomitantly with a massive flush of lactate into the blood stream. The initial hyperventilation was followed by a deep ventilatory depression. During return to normoxia, hyperventilation resumed consistent with the repayment of an oxygen debt. Thus, the sturgeon, although considered as an archaic fish, developed the same adaptative responses as teleosts submitted to comparable hypoxic conditions.

Effects of growth hormone on plasma ionic regulation, respiration and extracellular acid-base status in trout (Oncorhynchus mykiss) transferred to seawater.

The effects of trout recombinant growth hormone (rtGH) treatment (0.25 µg g(-1) by intraperitoneal implant) on plasma ionic regulation, extracellular acid-base status and respiration were investigated in freshwater rainbow trout and during a 4-day period after direct transfer into seawater (35 g 1(-1)).In freshwater, rtGH treatment resulted in a significant increase in gill (Na(+), K(+)) ATPase activity and in standard metabolism (MO2). The latter would mainly result from a higher rate of protein synthesis. Direct transfer from freshwater to seawater induced a decrease in arterial blood pH, far more pronounced in controls than in treated fish. This effect could be regarded in both groups mainly as a metabolic acidosis resulting from extracellular ion composition changes (i.e., an increase higher in chloride than in sodium, more marked in controls than in treated fish). As the rise in PaCO2, in spite of an increase in ventilatory activity, is more significant in controls than in treated fish, it can be assumed that rtGH treatment lightened the decrease in the gas diffusing capacity of gills induced by transfer to seawater. The initial increase in MO2 in both controls and treated fish could be the consequence of an increase in energetic cost of ventilation and osmoregulation. Then, in treated fish, the persistent high level of M may indicate a stimulation of intermediary metabolism by rtGH. In addition, the absence in treated fish of an increase in plasma lactate concentration, as observed in controls, would indicate that rtGH attenuated the decrease in O2 affinity of haemoglobin foreseeable from the metabolic acidosis.

Respiratory responses to progressive ambient hypoxia in the sturgeon, Acipenser baeri.

Changes in respiratory and acid-base variables were studied in siberian sturgeon, Acipenser baeri, during progressive deep hypoxia followed by recovery under normoxic conditions. During hypoxia, both ventilatory frequency and amplitude increased and this sturgeon was able to maintain standard oxygen consumption down to a low critical level of ambient PO2 (PWO2 < 40 mmHg). During the posthypoxic period, an O2 debt was repaid by an elevated oxygen consumption (nearly double control value at 1 h), indicating that a shift to anaerobic metabolism had occurred during exposure to severe hypoxia. Gradually increasing ambient hypoxia initially induced a respiratory alkalosis. Below the critical PWO2 level and during normoxic recovery, a sudden flush of lactate into the blood was associated with a typical metabolic acidosis which was almost totally compensated 3.5 h after return to normoxia. Thus, as for most other fish, respiratory responses of the sturgeon to progressive hypoxia reveal a typical O2 regulatory behavior.

Metabolic alkalosis and the response of the trout, Salmo fario, to acute severe hypoxia.

Trout (Salmo fario) were acutely transferred from seawater to freshwater in order to induce blood metabolic alkalosis (cf. Maxime et al., J. Comp. Physiol. 160: 31-39, 1990). After 2 weeks, the fish were exposed to severe environmental hypoxia (final water oxygen partial pressure, PWO2 = 25-45 Torr, reached within 20 min), to assess the impact of the experimentally induced alkalosis, and hence increased haemoglobin-oxygen (Hb-O2) affinity, on various aspects of the hypoxic response. This was accomplished by monitoring oxygen partial pressure and total oxygen content of arterial blood (PaO2 and CaO2), extracellular pH (pHe), red blood cell (RBC) intracellular pH (pHi), and the concentrations of plasma adrenaline, noradrenaline, lactate and haemoglobin (Hb) at 5 min intervals. Blood from normoxic fish exhibited high pHe and RBC pHi values (8.32 +/- 0.02 and 7.53 +/- 0.03, respectively). During hypoxia PaO2 declined to 10 Torr within 25 min; the first 5 min provoked increases of pHe and pHi to 8.43 +/- 0.03 and 7.71 +/- 0.03, respectively; thereafter, pHe decreased whilst pHi remained elevated. The blood lactate concentration increased from 2.30 +/- 0.76 mmol.L-1 in normoxia to 14.94 +/- 5.7 mmol.L-1 at the conclusion (60 min) of the hypoxic exposure and catecholamine levels also increased progressively (from 2.94 +/- 0.51 and 1.90 +/- 0.50 nmol.L-1, in normoxia, to 191.91 +/- 64.25 and 72.00 +/- 25.02 nmol.L-1, at their highest levels, for adrenaline and noradrenaline, respectively). Determination of the PaO2 thresholds for lactate and catecholamine release demonstrated that these substances appeared in the bloodstream when the degree of O2 saturation of the haemoglobin fell below 60%. The results demonstrate that initial blood alkalosis does not prevent the typical physiological responses of trout to hypoxia but simply shifts to lower PaO2 values the threshold at which these responses begin.