Summary Post anaesthetic myelopathy is a rare but devastating complication of equine anaesthesia and there is a need for better understanding of the condition and to raise veterinary awareness. The aim of this study was to collect data on unreported cases and combine those with reported cases to better identify possible risk factors and early clinical signs and outcomes of horses developing post anaesthetic myelopathy (PAM). A survey was conducted to identify cases of equine PAM. Records were also requested via the American College of Veterinary Anaesthesiologists listserve. Additional cases of PAM were located through review of the literature. Eighteen new cases and 12 published cases were identified. Large‐framed breeds between 6–24 months of age were more commonly affected (23/30). The majority of horses were positioned in dorsal recumbency during anaesthesia. Lack of movement and deep pain of the rear limbs, loss of anal tone and lack of panniculus response from the mid to caudal thorax distally were the most common clinical findings. Reported treatments resulted in no improvement of clinical signs and all horses died or were subjected to euthanasia from a few hours to 8 days post operatively. Poliomyelomalacia of the caudal spinal cord is the most common histopathological finding. Although a rare complication it is a catastrophic risk that can be eliminated by performing a standing operation. Hopefully in the future better understanding of this condition will lead to prevention and treatment strategies.

While commercial dietary weight-loss programs typically advise exercise, few provide actual programing. The goal of this study was to compare the Curves Complete 90-day Challenge (CC, n = 29), which incorporates exercising and diet, to programs advocating exercise (Weight Watchers Points Plus (WW, n = 29), Jenny Craig At Home (JC, n = 27), and Nutrisystem Advance Select (NS, n = 28)) or control (n = 20) on metabolic syndrome (MetS) and weight loss. We randomized 133 sedentary, overweight women (age, 47 ± 11 years; body mass, 86 ± 14 kg; body mass index, 35 ± 6 kg/m 2 ) into respective treatment groups for 12 weeks. Data were analyzed using chi square and general linear models adjusted for age and respective baseline measures. Data are means ± SD or mean change ± 95% confidence intervals (CIs). We observed a significant trend for a reduction in energy intake for all treatment groups and significant weight loss for all groups except control: CC (−4.32 kg; 95% CI, −5.75, −2.88), WW (−4.31 kg; 95% CI, −5.82, −2.96), JC (−5.34 kg; 95% CI, −6.86, −3.90), NS (−5.03 kg; 95% CI, −6.49, −3.56), and control (0.16 kg, 95% CI, −1.56, 1.89). Reduced MetS prevalence was observed at follow-up for CC (35% vs. 14%, adjusted standardized residuals (adjres.) = 3.1), but not WW (31% vs. 28% adjres. = 0.5), JC (37% vs. 42%, adjres. = −0.7), NS (39% vs. 50% adjres. = −1.5), or control (45% vs. 55% adjres. = −1.7). While all groups improved relative fitness (mL·kg −1 ·min −1 ) because of weight loss, only the CC group improved absolute fitness (L/min). In conclusion, commercial programs offering concurrent diet and exercise programming appear to offer greater improvements in MetS prevalence and cardiovascular function after 12 weeks of intervention.Key words: diet, exercise, metabolic syndrome.Résumé : Les programmes commerciaux de perte de poids recommandent généralement la pratique de l'exercice physique, mais peu offre une programmation réelle. Comparer sur les plans du syndrome métabolique (« MetS ») et de la perte de poids le programme Curves Complete 90-day Challenge (« CC », n = 29) qui incorpore une diète et des exercices physiques aux programmes qui recommandent l'exercice physique : Weight Watchers Points Plus (« WW », n = 29), Jenny Craig At Home (« JC », n = 27) et Nutrisystem Advance Select (« NS », n = 28) ou contrôle (n = 20). On répartit aléatoirement 133 femmes sédentaires et en surpoids (âge, 47 ± 11 ans; masse corporelle, 86 ± 14 kg; indice de masse corporelle, 35 ± 6 kg/m 2 ) dans les groupes de traitement respectif pour une période de 12 semaines. On effectue l'analyse du chi-carré et on utilise les modèles linéaires généraux ajustés à l'âge et aux mesures initiales respectives. Les données présentées sont la moyenne ± l'écart-type et la variation moyenne ± intervalle de confiance (IC) 95 %. Les résultats révèlent une tendance significative vers une diminution de l'apport énergétique dans tous les groupes de traitement et une perte de poids significative dans tous les groupes à l'exception du groupe de co...

Irreversible hypofunction of salivary glands is a common side effect of radiotherapy for head and neck cancer and is difficult to remedy. Recent studies indicate that transient activation of Hedgehog signaling rescues irradiation-impaired salivary function in animal models, but the underlying mechanisms are largely unclear. Here, we show in mice that activation of canonical Gli-dependent Hedgehog signaling by Gli1 gene transfer is sufficient to recover salivary function impaired by irradiation. Salivary gland cells responsive to Hedgehog/Gli signaling comprised small subsets of macrophages, epithelial cells, and endothelial cells, and their progeny remained relatively rare long after irradiation and transient Hedgehog activation. Quantities and activities of salivary gland resident macrophages were substantially and rapidly impaired by irradiation and restored by Hedgehog activation. Conversely, depletion of salivary gland macrophages by clodronate liposomes compromised the restoration of irradiation-impaired salivary function by transient Hedgehog activation. Single-cell RNA sequencing and qRT-PCR of sorted cells indicated that Hedgehog activation greatly enhances paracrine interactions between salivary gland resident macrophages, epithelial progenitors, and endothelial cells through Csf1, Hgf, and C1q signaling pathways. Consistently, expression of these paracrine factors and their receptors in salivary glands decreased following irradiation but were restored by transient Hedgehog activation. These findings reveal that resident macrophages and their prorepair paracrine factors are essential for the rescue of irradiation-impaired salivary function by transient Hedgehog activation and are promising therapeutic targets of radiotherapy-induced irreversible dry mouth. Significance: These findings illuminate a novel direction for developing effective treatment of irreversible dry mouth, which is common after radiotherapy for head and neck cancer and for which no effective treatments are available.

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To determine the effects of a dexmedetomidine slow bolus, administered prior to extubation, on recovery from sevoflurane-anesthesia and a fentanyl continuous rate infusion (CRI) in dogs undergoing orthopedic surgical procedures. Sixty-two client-owned, healthy dogs weighing 27.4 ± 11 kg undergoing elective orthopedic procedures were premedicated with: 0.1 mg/kg hydromorphone intramuscular, 0.05 mg/kg hydromorphone intravenously (IV) or 5 mcg/kg fentanyl IV. Following premedication, dogs were induced with propofol, administered locoregional anesthesia and maintained with sevoflurane and a fentanyl CRI (5–10 mcg/kg/hr). Dogs were randomly assigned to one of two treatment groups: 0.5 mcg/kg dexmedetomidine (DEX) or 0.5 ml/kg saline (SAL). Following surgery, patients were discontinued from the fentanyl CRI and administered DEX or SAL IV over 10 min. Following treatment, dogs were discontinued from sevoflurane and allowed to recover without interference. Recoveries were video recorded for 5 min following extubation and assessed by two blinded anesthesiologists using a visual analog scale (VAS; 0–10 cm) and a numerical rating scale (NRS; 1–10). Mean arterial pressure (MAP), heart rate (HR), pulse oximetry (SpO2), temperature, respiratory rate (RR), and end-tidal sevoflurane (EtSevo) and carbon dioxide (EtCO2) concentrations were recorded at specific time-points from induction to 5 min post-bolus administration and analyzed using linear mixed models. Fentanyl, propofol, and hydromorphone dose and the time to extubation were compared using an unpaired t-test. Differences in recovery scores between groups were evaluated with a Mann-Whitney test. Data reported as mean ± SD or median [interquartile range] when appropriate. A p < 0.05 was significant. There were no significant differences between groups in fentanyl, propofol, and hydromorphone dose, duration of anesthesia, intraoperative MAP, HR, RR, SpO2, temperature, EtCO2, EtSevo or anesthetic protocol. MAP was higher in DEX compared to SAL at 10 (104 ± 27 and 83 ± 23, respectively) and 15 (108 ± 28 and 86 ± 22, respectively) min after treatment. DEX had significantly lower VAS [0.88 (1.13)] and NRS [2.0 (1.5)] scores when compared to SAL [VAS = 1.56 (2.59); NRS = 2.5 (3.5)]. Time to extubation (min) was longer for DEX (19.7 ± 11) when compared to SAL (13.4 ± 10). Prophylactic dexmedetomidine improves recovery quality during the extubation period, but prolongs its duration, in sevoflurane-anesthetized healthy dogs administered fentanyl.

Heinz body formation has been reported in cats repeatedly administered propofol for anesthesia induction, although the resultant changes were deemed of little clinical significance (1, 2). This report suggests repeated propofol administration to some individual cats might induce anemia with clinical signs and cessation of propofol administration may result in rapid resolution. A 9-years-old American Domestic Shorthair cat receiving a 20-fraction radiation protocol for lateral thoracic fibrosarcoma showed lethargy, decreased appetite and activity, and Heinz body (3+ on blood smear examination) anemia (packed cell volume 22%; reference interval 24-45%) after 12 repeated propofol anesthesia inductions. The anesthesia induction protocol was adjusted to exclude propofol. Over the following week, the anemia resolved (packed cell volume, 30%), and the cat's activity level, appetite and attitude improved. The total dose of propofol received over the 12 treatments was 62.4 mg/kg.

Radiotherapy of head and neck cancers frequently leads to irreversible hypofunction of salivary glands, which severely compromises the quality of life and is extremely difficult to treat. We found recently that salivary gland resident macrophages are sensitive to radiation and interact with epithelial progenitors and endothelial cells through homeostatic paracrine factors. Heterogeneous subpopulations of resident macrophages are present in other organs with distinct functions, whereas subpopulations of salivary gland resident macrophages with distinct functions or transcriptional profiles have not been reported yet. Using single-cell RNA sequencing, we found that mouse submandibular glands (SMGs) contain 2 distinct self-renewing resident macrophage subsets, an MHC-IIhi subset present in many other organs and an uncommon Csf2r+ subset. The main source of Csf2 in SMGs are innate lymphoid cells (ILCs) that rely on IL15 for maintenance, while the main source of IL15 protein is Csf2r+ resident macrophages, indicating a homeostatic paracrine interaction between these cells. Csf2r+ resident macrophages are the major source of hepatocyte growth factor (Hgf) that regulates homeostasis of SMG epithelial progenitors. Meanwhile, Csf2r+ resident macrophages are responsive to Hedgehog signaling that can rescue salivary function impaired by radiation. Consistently, irradiation persistently decreased numbers of ILCs and levels of IL15 and Csf2 in SMGs, which were all recovered by transient activation of Hedgehog signaling after radiation. Csf2r+ resident macrophages and MHC-IIhi resident macrophages share transcriptome profiles of perivascular macrophages and macrophages associated with nerves and/or epithelial cells in other organs, respectively, and such niche preferences were supported by lineage tracing and immunofluorescent staining. These findings reveal an uncommon resident macrophage subset that regulates the homeostasis of the salivary gland and is promising as the target to restore salivary gland function impaired by radiation.