Multicenter Study of Long-Term Outcomes and Quality of Life in PHACE Syndrome after Age 10.

OBJECTIVE: To characterize long-term outcomes of PHACE syndrome. STUDY DESIGN: Multicenter study with cross-sectional interviews and chart review of individuals with definite PHACE syndrome ≥10 years of age. Data from charts were collected across multiple PHACE-related topics. Data not available in charts were collected from patients directly. Likert scales were used to assess the impact of specific findings. Patient-Reported Outcomes Measurement Information System (PROMIS) scales were used to assess quality of life domains. RESULTS: A total of 104/153 (68%) individuals contacted participated in the study at a median of 14 years of age (range 10-77 years). There were infantile hemangioma (IH) residua in 94.1%. Approximately one-half had received laser treatment for residual IH, and the majority (89.5%) of participants were satisfied or very satisfied with the appearance. Neurocognitive manifestations were common including headaches/migraines (72.1%), participant-reported learning differences (45.1%), and need for individualized education plans (39.4%). Cerebrovascular arteriopathy was present in 91.3%, with progression identified in 20/68 (29.4%) of those with available follow-up imaging reports. Among these, 6/68 (8.8%) developed moyamoya vasculopathy or progressive stenoocclusion, leading to isolated circulation at or above the level of the circle of Willis. Despite the prevalence of cerebrovascular arteriopathy, the proportion of those with ischemic stroke was low (2/104; 1.9%). PROMIS global health scores were lower than population norms by at least 1 SD. CONCLUSIONS: PHACE syndrome is associated with long-term, mild to severe morbidities including IH residua, headaches, learning differences, and progressive arteriopathy. Primary and specialty follow-up care is critical for PHACE patients into adulthood.

Atypical cutaneous manifestations of methicillin resistant Staphylococcus aureus infections in two immunocompetent pediatric patients: Case reports and review of the literature.

Although many clinical variants of Staphylococcus aureus infection are well-recognized, atypical presentations may mimic other conditions. We describe two cases of atypical S. aureus infections in pediatric patients: a S. aureus infection presenting with a vesicopustular rash mimicking varicella zoster virus and a case of multifocal panniculitis. Both of these cases were specifically caused by methicillin-resistant S. aureus (MRSA). Additional cases of atypical S. aureus infections and presenting features from the current literature are also discussed.

Rubella virus-associated necrotizing granulomatous inflammation with extensive eyelid, ocular, and orbital involvement.

We present a case of cutaneous granulomatous disease associated with rubella virus in a 4-year-old girl without an identifiable immunodeficiency. In this case, a combination of anti-inflammatory, anti-viral, and anti-neutrophil therapies successfully treated vision-threatening eyelid, conjunctival, scleral, and orbital inflammation.

Evaluation of a commercial electrical stunning method for farmed grower saltwater crocodiles (Crocodylus porosus) using non-invasive EEG measurements.

The aim of this study was to assess welfare outcomes of electrical stunning as a means of restraint in farmed grower saltwater crocodiles (Crocodylus porosus). Physical handling of a stunned, unconscious crocodile is far safer for the operator than handling a fully conscious animal. Electroencephalogram (EEG) was recorded before and after the application of electrical stunning at 50 Hz or 400 Hz using an electrical stunner applied to the cranial plate (Position 1: P1-50 Hz; n = 31, P1-400 Hz; n = 29) or immediately behind the skull (Position 2: P2-50 Hz; n = 29; P2-400 Hz; n = 30). For all electrical stuns, percentage total EEG power in a 10-s epoch decreased in the alpha and beta frequency bands; and increased in the delta and lower frequencies bands. All electrical stuns resulted in increased strength of signal, based on the quadratic mean EEG power in all frequency bands of the EEG. Greatest change in power occurred in the delta frequency band, with P1-50 Hz. This was greater than with P2-50 Hz; while decibel change using 400 Hz at either position was intermediate and not significantly different from either. Application of either electrical stunner at position 1 resulted in seizure-like activity and activation in low frequencies, but at position 2 this was not consistent across all animals. The ability of the electrical stunning equipment to consistently induce recoverable unconsciousness could be ranked in decreasing order as: P1-50 Hz > P1-400 Hz = P2-50 Hz > P2-400 Hz. Based on behavioural observations, all animals in the study appeared to stunned however evaluation of duration of EEG changes indicates that use of the electrical stunning equipment at 50 Hz would allow some margin for inaccuracies in tong placement, while achieving a consistently reliable stun.

Dual treatment of cutaneous leishmaniasis with topical amphotericin B and photodynamic therapy in a pediatric patient.

Cutaneous leishmaniasis is a parasitic infection that can result in scarring, contributing to significant morbidity when a cosmetically sensitive area is involved. We report a case of a 13-year-old boy with cutaneous leishmaniasis involving the face and arm. He was treated with a combination of photodynamic therapy as well as topical amphotericin with a cosmetically satisfying outcome. This combination of noninvasive treatment regimens has not been reported to our knowledge and merits further study in the pediatric population.

Measuring the impact of clinical practice guidelines on infantile hemangioma referrals.

High-risk infantile hemangiomas may be associated with significant patient comorbidity. The American Academy of Pediatrics published clinical practice guidelines with recommendations to refer high-risk hemangiomas early. The results of this study suggest that these guidelines may have resulted in an earlier referral age of patients with high-risk IH to hemangioma specialists.

Flawed mothering or infant signaling? The effects of deficient acoustic cues on ovine maternal response.

The neonate distress cry, which displays a similar acoustic structure across a range of mammalian species, is highly effective in attracting, even compelling, parental care. However, if this cry is defective, as found in human and rodent neonates with poor neurobehavioral function, is the signal less enticing? Using playback recordings of a ewe's own co-twins as stimuli in a two choice test, we compared the preference of each sheep dam for acoustic features of lamb distress calls to assess the impact of signal quality on maternal response. The results of this study indicate that lamb vocalizations with acoustic parameters reflecting poor vocal fold engagement and arousal were less likely to be preferred by their dam. Additionally, these calls were associated with delayed vocal initiation and poor infant survival behavior suggestive of subtle cognitive deficit; and support the possibility that, as in deer and rodents, ovine vocalizations within a specific fundamental frequency range may well be a trigger for optimal maternal behavior. This research has important implications for understanding failed maternal-young interactions in ungulate and other species, and for verifying standardization of infant stimuli used in maternal behavior studies.

Basin-Scale Observations of Monoterpenes in the Arctic and Atlantic Oceans.

We report novel in situ speciated observations of monoterpenes (α- and ß-pinene, myrcene, δ3-carene, ocimene, limonene) in seawater and air during three cruises in the Arctic and Atlantic Oceans, in/over generally oligotrophic waters. Oceanic concentrations of the individual monoterpenes ranged from below the detection limit of <1 pmol L-1 to 5 pmol L-1, with average concentrations of between 0.5 and 2.9 pmol L-1. After careful filtering for contamination, atmospheric mixing ratios varied from below the detection limit (<1 pptv) to 5 pptv, with averages of 0.05-5 pptv; these levels are up to 2 orders of magnitude lower than those reported previously. This could be at least partly due to sampling over waters with much lower biological activity than in previous studies. Unlike in previous studies, no clear relationships of the monoterpenes with biological variables were found. Based on our measured seawater concentrations and a global model simulation, we estimate total global marine monoterpene emissions of 0.16 Tg C yr-1, similar to a previous bottom-up estimate based on laboratory monoculture studies but 2 orders of magnitude lower than a previous top-down estimate of 29.5 Tg C yr-1.

Distress vocalization delay in the neonate lamb as a neurobehavioral assessment tool.

Acoustic features of infant distress vocalizations including latency and rate of emission are used as indices of neurological deficit and integrity in human and rodent neonates. This paper investigates the relationship between temporal characteristics of distress calls, elicited by an isolation stimulus, and indicators of neurobehavioral development over 12 hr postpartum in the neonate lamb. Delayed vocalization initiation was found to be associated with poor locomotor and orientation behavior reflecting the capacity of the lamb to reunite with and follow its dam, and a lowered rate of signal emission following commencement of vocalization. Animals demonstrating delayed vocalization initiation also appeared more likely to be of a birth weight predisposed to fetal distress, and to urinate when exposed to a novel environment. Based on these preliminary studies, we propose that compromised emission of vocal signals is indicative of neurobehavioral deficit in the neonate lamb.

Netherton Syndrome Mimicking Pustular Psoriasis: Clinical Implications and Response to Intravenous Immunoglobulin.

We present two cases of Netherton syndrome mimicking pustular psoriasis and discuss potential pathomechanisms of clinical and histologic similarities between Netherton syndrome and pustular psoriasis and implications for management.

The use of a penetrative captive bolt device during the killing of farmed saltwater crocodiles (Crocodylus porosus).

Killing of farmed saltwater crocodiles involve stunning with a penetrative captive bolt device, followed by a cut across the nape of the neck and physical destruction of the brain to ensure death. This study was a welfare-based assessment of the use of a penetrative captive bolt device in saltwater crocodiles, to determine whether it satisfies the criteria of a humane stunning method and can be regarded as a direct killing method without the need for the application of an adjunct method. Methods used were electroencephalogram (EEG), observation of post-stun behavior, and postmortem examination of gross pathology of the cranium and brain. 30 of 30 animals, demonstrated immediate and irreversible loss of consciousness. There was extensive damage to the brain in all animals, deemed to be inconsistent with cortical function and possible recovery. The CASH Special 0.22 penetrative captive bolt pistol (1.25 grain cartridge), applied to the top of the cranial plate, produced immediate and irreversible unconsciousness in all the animals studied. This method satisfies animal welfare expectations, providing crocodile processors with a technique that contributes to a humane killing process.

Behaviours of farmed saltwater crocodiles (Crocodylus porosus) housed individually or in groups.

Saltwater crocodiles (Crocodylus porosus) are farmed in Australia primarily for their skins and meat. Commercially, they are raised in group pens as hatchlings and grower crocodiles and then moved to unitised (individual) pens for the final finishing stage when they are several years old. They will exhibit aggressive behaviour towards each other in captivity. Unitised pens can prevent animal injury and teeth marks on the skins but may result in other social restrictions. Research into behavioural housing preferences could assist the industry and inform the process of guideline development for optimal crocodile management and welfare. This study assessed the impacts of two housing systems, unitised or group pens, in 20 commercial finishing crocodiles through measuring behavioural profiles of individuals from video recordings, including housing preference when given a choice. Both pens included water and an above-water shelf, but the crocodiles in unitised pens could also access underneath the shelf. A threat perception test was applied to assess anxiety when housed individually or in groups. However, it was difficult to apply a standardised stimulus to all animals that reliably elicited a behavioural response. Further work would be needed to validate this test for commercial reptiles as the outcomes were not robust. The behavioural observation results showed clear differences in where the crocodiles spent their time across the day and in their activity levels between the pen types. However, interpretation of this variation was confounded by the physical and social differences between the pen types given the inconsistency in shelf access. Behaviours exhibited also differed given there were social opportunities in the group pens where individuals were observed engaged in both aggressive and non-aggressive contact interactions. In the free choice environment, crocodiles spent similar amounts of time in both unitised and group pens, suggesting there were features of both pen types that were attractive to the animals. However, skins were damaged from teeth marks highlighting the physical and economical risks of group housing. Further work could validate behavioural tests to quantify affective state impacts in different housing environments and whether social interactions do provide benefits for improving crocodile welfare.

Sex impacts pain behaviour but not emotional reactivity of lambs following ring tail docking.

Studies in humans have shown sex differences in response to painful events, however, little is known in relation to sex differences in sheep. Understanding sex differences would enable improved experimental design and interpretation of studies of painful procedures in sheep. To examine sex differences in response to pain, 80 lambs were tested across five cohorts of 16. The lambs were penned in groups containing two male and two female lambs with their respective mothers. Lambs were randomly allocated from within each block to one of four treatment groups; FRing-Female lamb, ring tail docked without analgesia, MRing-Male lamb, ring tail docked without analgesia, FSham-Female lamb, tail manipulated and MSham-Male lamb, tail manipulated. Following treatment, lambs were returned to their pen and were video recorded for 45 mins for behavioural observations of acute pain and posture. An hour after treatment, lambs then underwent an emotional reactivity test that consisted of three phases: Isolation, Novelty and Startle. Following treatment, Ring lambs displayed more abnormal postures (mean = 2.5 ± 0.5) compared to Sham lambs (mean = 0.05 ± 0.4, P = 0.0001). There was an effect of sex on the display of acute pain-related behaviours in lambs that were tail docked (P < 0.001), with female lambs displaying more acute behaviours (mean count = +2.2). This difference in behaviour between sexes was not observed in Sham lambs. There was no effect of sex on display of postures related to pain (P = 0.99). During the Novelty and Startle phase of the emotional reactivity test, Ring lambs tended to (P = 0.084) or did (P = 0.018) show more fear related behaviours, respectively. However, no effect of sex was observed. The results of this study indicate that a pain state may alter the emotional response of lambs to novel objects and potential fearful situations. It was also demonstrated that female lambs display increased sensitivity to the acute pain caused by tail docking compared to males.

Evaluating a novel analgesic strategy for ring castration of ram lambs.

OBJECTIVE: To evaluate the analgesic efficacy of the NSAIDs flunixin and meloxicam administered locally to the scrotum before ring castration. STUDY DESIGN: Randomised, controlled, prospective study. ANIMALS: Forty eight single born male Merino lambs. METHODS: Lambs, aged approximately 4 weeks, were allocated to four groups for castration. Groups were: sham control; castration + saline; castration + flunixin; castration + meloxicam. Drugs (5 mL) were administered subcutaneously around the circumference of the scrotum immediately before castration. Cortisol, rectal temperature, haematology and plasma haptoglobin were measured before and up to 48 hours after treatment. Behaviour recorded by video for 12 hours after treatment was classified as pain avoidance behaviours in the first hour and postural behaviours in three 4 hour intervals. RESULTS: Ring castration (saline group) induced a bi-phasic increase in cortisol with peaks at 90 minutes and 24 hours but no significant changes in haematology, haptoglobin or rectal temperature. Pain avoidance behaviours were increased and teat seeking decreased. Normal lying and normal standing postures were decreased and abnormal ventral lying, statue standing, abnormal standing and total abnormal postures increased. Flunixin decreased cortisol at 90 minutes (60.3 versus 117.3 nmol L(-1) ) and cortisol AUC (0-6 hours), decreased elevated leg movement (2.5 versus 5.4 events) and sum of pain avoidance behaviours (8.5 versus 16.7 events), improved time spent in normal ventral lying and decreased abnormal ventral lying and total abnormal postures compared to saline treated lambs. In a similar contrast, meloxicam caused non-significant decreases in cortisol at 90 minutes, cortisol AUC (0-6 hours) and pain avoidance behaviours, and significantly improved the postural behaviours normal ventral lying (26.7 versus 15.4%) and normal standing (13.9 versus 7.5%), and reduced abnormal standing and total abnormal postures. Physiological and behavioural responses associated with ring castration for both NSAID treatment groups were generally greater than sham controls. CONCLUSIONS AND CLINICAL RELEVANCE: Locally administered NSAIDs provided partial analgesia for ring castration.

Perinatal Stress in Immature Foals May Lead to Subclinical Adrenocortical Dysregulation in Adult Horses: Pilot Study.

The persistent endocrinological effects of perinatal stress due to gestational immaturity in horses are unknown, although effects have been reported in other livestock species. This pilot study tested the hypothesis that persistent adrenocortical dysregulation is present in horses that were gestationally immature at birth by assessing the salivary cortisol response to exogenous ACTH. Case horses (n = 10) were recruited with histories of gestation length < 315 d or dysmaturity observable through neonatal signs. Positive controls (n = 7) and negative controls (n = 5) were recruited where possible from related horses at the same locations. Cases and positive controls received an intramuscular, low-dose (0.1 ug/kg) of synthetic ACTH (Tetracosactrin 250 mg/mL, Synacthen); negative controls received no ACTH. Saliva samples were collected from all horses at baseline T = 0 and at 30 min intervals post injection from T = 30 to T = 150. These were assayed for salivary cortisol concentration (SCC) using a commercially available ELISA kit (Salimetrics). All baseline values (T = 0) were within normal published ranges. Peak and AUC values (corrected for baseline) for case horses were significantly different (ANOVA P < .001) to positive controls, with either higher (H-cases) or lower (L-cases) SCC values, outside the 95% Confidence Interval of the reference population. There was no significant effect of breed, age, sex, test month, or location on results. The results suggest that gestational immaturity may lead to subclinical adrenocortical dysregulation, with affected horses presenting an elevated or blunted response to a low-dose ACTH stimulation, despite normal basal levels.

Sweet Syndrome in the Pediatric Population.

Pediatric Sweet syndrome (SS) is thought to be a hypersensitivity reaction to an underlying inflammatory or infectious state and typically is diagnosed using criteria created for adult patients. Although more studies are needed to understand the etiology and natural course of pediatric SS, guidelines for work-up and treatment have been suggested. Herein, the available literature is reviewed and guidelines summarized for the clinical evaluation and management of pediatric SS.

Welfare of Farmed Crocodilians: Identification of Potential Animal-Based Measures Using Elicitation of Expert Opinion.

Animal-based measures are the measure of choice in animal welfare assessment protocols as they can often be applied completely independently to the housing or production system employed. Although there has been a small body of work on potential animal-based measures for farmed crocodilians, they have not been studied in the context of an animal welfare assessment protocol. Potential animal-based measures that could be used to reflect the welfare state of farmed crocodilians were identified and aligned with the Welfare Quality® principles of good housing, good health, good feeding and appropriate behaviour. A consultation process with a panel of experts was used to evaluate and score the potential measures in terms of validity and feasibility. This resulted in a toolbox of measures being identified for further development and integration into animal welfare assessment on the farm. Animal-based measures related to 'good feeding' and 'good health' received the highest scores for validity and feasibility by the experts. There was less agreement on the animal-based measures that could be used to reflect 'appropriate behaviour'. Where no animal-based measures were deemed to reliably reflect a welfare criterion nor be useful as a measure on the farm, additional measures of resources or management were suggested as alternatives. Future work in this area should focus on the reliability of the proposed measures and involve further evaluation of their validity and feasibility as they relate to different species of crocodilian and farming system.

Three Studies Evaluating the Potential for Lidocaine, Bupivacaine or Procaine to Reduce Pain-Related Behaviors following Ring Castration and/or Tail Docking in Lambs.

The use of local anesthesia at the time of ring castration and tail docking can improve lamb welfare. However, few local anesthetics are registered for sheep, and data on their duration of effect is limited. Three studies were conducted to evaluate the efficacy of procaine (P), lidocaine (L), and bupivacaine (B) in terms of observed alleviation of behavioral responses to castration and/or tail docking in 10-min blocks in the first 60 min post-treatment. In each study, comparisons were made between two groups of lambs castrated and/or tail docked with rubber rings and either receiving the agent using the NUMNUTS® instrument (N) or receiving no anesthetic agent (RR). Acute pain behavior was lower in NL (n = 28) than RRL (n = 15) males in the first 10 min post-procedure (p < 0.05); lower in NB (n = 16) than RRB (n = 16) males in periods 10-20 min (0.05 < p < 0.01), 20-30 min (p < 0.05) and 40-50 min (0.05 < p < 0.01); lower in NB (n = 16) than RRB (n = 16) females between 20 and 40 min post-procedure (0.05 < p < 0.01); lower in NP (n = 8) than RRP (n = 7) males in period 10-20 min (0.05 < p < 0.01), and lower in NP (n = 9) than RRP (n = 9) females in periods 0-10 min (0.05 < p < 0.01), and 10-40 min (p < 0.05). Benefits were modest, and the effects of procaine appear to last longer than lidocaine, while bupivacaine is slower to take effect than either procaine or lidocaine but may provide longer-lasting pain relief. The duration of action of local anesthetics is short in sheep, and detailed behavioral evaluations are required in the first hour post-procedure to establish efficacy.

Local Anesthetic Delivered with a Dual Action Ring and Injection Applicator Reduces the Acute Pain Response of Lambs during Tail Docking.

Docking the tail of lambs is a standard husbandry procedure and is achieved through several techniques including clamps, hot or cold knives and latex rings, the last of which is the most popular. All tail docking methods cause acute pain which can be reduced by application of local anesthetic, however precise anatomical injection for optimal efficacy requires considerable skill. This pen trial evaluated the ability of local anesthetic (LA) delivered with a dual function ring applicator/injector to alleviate acute tail docking pain. Thirty ewe lambs were assigned to one of three treatment groups (n = 10 per group): ring plus local anesthetic (Ring LA), ring only (Ring) and sham handled control (Sham). Lambs were videoed and their behavior categorized every five minutes for the first hour and every 10 min for the subsequent two hours after treatment. There was a significant effect (p < 0.001) of treatment on total active pain related behaviors in the first hour, with Ring lambs showing higher counts compared to Ring LA or Sham. Ring lambs also displayed a significantly higher count of combined abnormal postures (p < 0.001) than Ring LA or Sham lambs. Delivery of 1.5 mL of 2% lignocaine via the dual action device abolished abnormal behaviors and signs of pain in Ring LA lambs. However, lambs in the Ring LA group spent less time attempting to suckle compared to Ring and Sham lambs, suggesting that some residual discomfort remained.