Australian and New Zealand consensus guideline for paediatric newly diagnosed immune thrombocytopaenia endorsed by Australian New Zealand Children's Haematology and Oncology Group.

In children, the majority of cases are self-limiting and thus many paediatric patients can be managed conservatively with minimal complications. This varies considerably compared to adult newly diagnosed immune thrombocytopaenia (NDITP) where, in most cases, thrombocytopaenia persists with higher risk of moderate to severe bleeding complications. In the past decade, local and international guidelines have emerged to support approaches to the investigation and management of NDITP, with a focus primarily on adult immune thrombocytopaenia (ITP). International consensus guidelines on paediatric NDITP have been developed, however gaps remain, and approaches vary between North American, Asia, Europe and the UK. There are no current Australian or New Zealand paediatric ITP guidelines readily available, rather differing guidelines for each state, territory or island. These inconsistencies cause uncertainty for patients, families and physicians managing cases. Subsequently, physicians, including paediatric haematologists and general paediatricians, have come together to provide a consensus approach guideline specific to paediatric NDITP for Australian or New Zealand. Persistent or chronic paediatric ITP remains a complex and separate entity and are not discussed here.

Pilot study supporting the existence of novel lymphatic channels within the canine anterior uveal tract using Lyve-1 and CD31.

OBJECTIVE: To demonstrate the existence of lymphatics in the canine anterior uvea using lymphatic-specific markers Lyve-1, Prox-1, and podoplanin, the endothelial cell marker CD31, and basement membrane matrix marker collagen IV. DESIGN: Prospective Study. ANIMALS: Eight normal globes from animals euthanized for unrelated health problems. PROCEDURES: Sagittally cut serial sections of six normal canine eyes were immunofluorescence double-stained with Lyve-1 and CD31 and single-stained with colorimetric Prox-1 and collagen IV. Three serial sections from 2 additional eyes were cut in the coronal plane at the level of the ciliary body and immunofluorescence double-stained with Lyve-1 and CD31 to map lymphatic channel distribution. Lymphatics from normal canine lymph nodes were used for validation of podoplanin. RESULTS: Four of 6 of the sagitally sectioned eyes had Lyve-1-positive lymphatic-like structures that were distinct from CD31-positive blood vessels in the iris base and ciliary body. Both of the coronally sectioned globes had Lyve-1-positive lymphatic-like structures in the ciliary body. The location of these structures was evaluated and found to be diffusely present circumferentially around the ciliary body. CONCLUSION AND CLINICAL RELEVANCE: These results support the existence of lymphatic channels in the anterior uveal tract of the canine eye. This could indicate the presence of a novel uveolymphatic outflow pathway, which may play a role in aqueous humor outflow. Future studies are needed to confirm the existence and elucidate the role of this proposed uveolymphatic outflow pathway and potentially develop novel treatment options for managing glaucoma.

Adaptations for amphibious vision in sea otters (Enhydra lutris): structural and functional observations.

Sea otters (Enhydra lutris) are amphibious mammals that maintain equal in-air and underwater visual acuity. However, their lens-based underwater accommodative mechanism presumably requires a small pupil that may limit sensitivity across light levels. In this study, we consider adaptations for amphibious living by assessing the tapetum lucidum, retina, and pupil dynamics in sea otters. The sea otter tapetum lucidum resembles that of terrestrial carnivores in thickness and fundic coverage. A heavily rod-dominated retina appears qualitatively similar to the ferret and domestic cat, and a thick outer nuclear layer relative to a thinner inner nuclear layer is consistent with nocturnal vertebrates and other amphibious carnivores. Pupil size range in two living sea otters is smaller relative to other amphibious marine carnivores (pinnipeds) when accounting for test conditions. The pupillary light response seems slower than other aquatic and terrestrial species tested in comparable brightness, although direct comparisons require further assessment. Our results suggest that sea otters have retained features for low-light vision but rapid adjustments and acute underwater vision may be constrained across varying light levels by a combination of pupil shape, absolute eye size, and the presumed coupling between anterior lens curvature and pupil size during accommodation.

OPHTHALMIC EXAMINATION FINDINGS AND INTRAOCULAR PRESSURE MEASUREMENTS IN SIX SPECIES OF ANURA.

A complete ophthalmic exam, including intraocular pressure (IOP) measurement, is key to diagnosing ocular diseases such as uveitis and glaucoma in frogs. We performed complete ophthalmic anterior segment examinations and IOP rebound tonometry measurements using two different settings (other "p" and canine "d") for six anuran species. The objectives were to describe common ocular abnormalities found in these species, to compare IOP values between different tonometer settings, and to compare IOPs between species. Examinations revealed abnormalities including cataracts (11/98 total eyes), lenticular sclerosis (10/98) and lipid keratopathy (9/98). IOP was measured with the TonoVet® and the ranges (oculus uterque, OU mm Hg other "p" setting, canine "d" setting) were giant waxy monkey tree frogs (Phyllomedusa bicolor) (3.5-7.6; 6.5-11.7; n = 5), mission golden-eyed tree frogs (Trachycephalus resinifictrix) (7.0-9.7, 13.2-15.7; n = 6), boreal toads (Bufo boreas boreas) (0.8-5.5, 5.7-10.5; n = 13), Mexican giant tree frogs (Pachymedusa dacnicolor) (3.8-5.0, 8.3-11.8; n = 3), Lake Titicaca frogs (Telmatobius culeus) (8.8-10.5, 14.0-17.2; n = 8), and mossy tree frogs (Theloderma corticale) (9.7-11.0, 15.7-17.0; n = 5). The TonoVet canine "d" setting IOP measurements were statistically higher (P = 0.01) than the other "p" setting measurements for all species except the giant waxy monkey tree frogs. IOP was significantly lower for giant waxy monkey tree frog eyes with cataracts (P < 0.05) with the other "p" setting. IOP did not statistically differ in eyes with lenticular sclerosis. IOP can be measured by rebound tonometer in anurans, but more research is needed for species-specific references using consistent settings.

Surgically induced astigmatism in canines following sutured dorsonasal vs dorsotemporal clear corneal incisions.

OBJECTIVES: To investigate use of the Pentacam® HR for evaluation of surgically induced corneal astigmatism (SIA) in canines undergoing bilateral phacoemulsification and determine differences between dorsonasal and dorsotemporal clear corneal incisions. ANIMALS: Client-owned canines undergoing bilateral phacoemulsification. PROCEDURES: Patients received anterior segment imaging pre-operatively, immediately post-operatively, and 2-4 months post-operatively (follow-up). Total corneal refractive power was used to determine SIA. Surgically induced astigmatism was compared between right and left eyes, representing dorsotemporal and dorsonasal incisions, respectively. Repeated measures analyses were used between time points and paired t test compared SIA between eyes. RESULTS: Complete imaging series were obtained for seven patients. Follow-up imaging occurred at a median of 112 days (range 60-132 days) post-operatively. For repeated measures analyses, significant differences were found between pre- and immediate post-operative values (P < 0.01), and between immediate post-operative and follow-up values (P < 0.01). There was no significant difference between pre-operative and follow-up values. Surgically induced astigmatism was significantly different between right and left eyes, with values of 2.01 ± 1.24 D and 3.05 ± 1.58 D at 3 mm radius (P < 0.05), and 2.04 ± 1.18 D and 3.06 ± 1.27 D at 4 mm radius (P < 0.05) for dorsotemporal and dorsonasal incisions, respectively. CONCLUSIONS: Preliminary investigation revealed improvement of corneal SIA 2-4 months post-operatively, but development of significantly more SIA in dorsonasal vs dorsotemporal incisions. This prompts consideration of patient or microscope rotation to create a more dorsotemporal incision when possible.

Anterior segment parameters in normal dogs using the Pentacam® HR Scheimpflug system.

OBJECTIVE: To describe and compare normative anterior segment parameters between canine age groups using the Pentacam® HR Scheimpflug camera (Pentacam). ANIMALS STUDIED: Thirty-six sedated dogs (60 eyes) of varying ages and breeds were imaged with the Pentacam; only nondiseased anterior segments were included. PROCEDURES: Dogs were divided into three age groups: Group 1 (1-5 years), Group 2 (6-10 years), and Group 3 (11-15 years). Values assessed included central corneal thickness (CCT), anterior and posterior corneal elevation (ACE/PCE), anterior and posterior corneal curvature metrics, corneal volume (CV), anterior and posterior corneal astigmatism (AA/PA), anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA). Tukey-adjusted pairwise comparisons were performed. RESULTS: Overall CCT (mean ± SD) was 631.07 ± 59.91 µm. Central corneal thickness was 608.60 ± 48.63 µm for Group 1, 648.57 ± 51.06 µm for Group 2, and 635.37 ± 73.71 µm for Group 3. Anterior corneal elevation (ACE) measured 9.08 ± 0.58 mm, PCE measured 8.04 ± 0.50 mm, and CV was 58.13 ± 5.39 mm3 . Astigmatism values were 1.34 ± 0.94 D for AA and 0.46 ± 0.44 D for PA. Anterior chamber values were 3.76 ± 0.56 mm for ACD, 383.68 ± 66.24 mm3 for ACV, and 23.62 ± 29.33˚ for ACA. Significant differences were found between Groups 1 and 2 for CV (55.08 ± 4.08 mm3 and 60.32 ± 4.19 mm3 , respectively), (P = 0.02). CONCLUSIONS: Corneal volume significantly increased between Group 1 and Group 2. Central corneal thickness increased from Group 1 to Group 3, but was not significant with the current sample size. There were no other differences between age groups.

Iridocorneal angle assessment of companion rabbits using gonioscopy, spectral-domain optical coherence tomography (Optovue iVue® ), high-resolution ultrasound, and Pentacam® HR imaging.

OBJECTIVE: Iridocorneal angle (ICA) narrowing is a known risk factor for primary glaucoma in multiple species, but has not been described in companion rabbits. This study aimed to develop an ICA grading scheme for companion rabbits to enable early glaucoma predisposition diagnosis. ANIMALS STUDIED: Twenty healthy rabbits of varying breeds and ages. PROCEDURES: Rabbits received complete ophthalmic examinations, including gonioscopy, and imaging of the ICA using spectral-domain optical coherence tomography (SD-OCT), Scheimpflug imaging (Pentacam® HR), and high-resolution ultrasound (HRUS). Angle opening distance (AOD) and angle recess area (ARA) of the ICA were measured and assessed for agreement using a Bland-Altman analysis. A five-stage gonioscopy grading scheme was created, and Spearman-rank test assessed for correlation between gonioscopy grades and ICA measurements. Differences among age and sex were analyzed with a nonparametric ANOVA and Wilcoxon rank-sum test, respectively. RESULTS: Analysis revealed AOD medians of 0.28mm for SD-OCT [95% CI: 0.24-0.31], 0.20mm for Pentacam® HR [95% CI: 0.18-0.21], and 0.25mm for HRUS [95% CI: 0.22-0.28]. The median ARA was 0.14mm2 for SD-OCT [95% CI: 0.117-0.163], 0.09mm2 for Pentacam® HR [95% CI: 0.082-0.100], and 0.06mm2 for HRUS [95% CI: 0.046-0.054]. The association between gonioscopy grade and SD-OCT ARA was significant (P < 0.05), and there was a significant difference (P < 0.001) between imaging modalities for both ARA and AOD. CONCLUSIONS: Gonioscopy grade correlated well with SD-OCT ARA. Therefore, SD-OCT is recommended as a noncontact method for evaluating companion rabbit ICA. Each imaging device should not be used interchangeably for ICA evaluation.

Favorable results from a prospective evaluation of 200 patients with large hiatal hernias undergoing LINX magnetic sphincter augmentation.

INTRODUCTION: Magnetic sphincter augmentation (MSA) of the lower esophageal sphincter restores the antireflux barrier in patients with hiatal hernias ≤3 cm. We performed a prospective study in patients undergoing MSA with the LINX device during repair of paraesophageal and hernias over 3 cm axial component. METHODS AND PROCEDURES: Multicenter, prospective study of consecutive patients treated with MSA at the time of repair of hiatal hernias >3 cm. RESULTS: 200 patients (110 female) were treated between March 2014 and February 2017 via laparoscopic hernia repair and MSA. Mean age was 59.5 years, mean BMI 29.4. 40% had esophagitis, 20% intestinal metaplasia, 72 of 77 tested had abnormal pH studies. Preoperative PPI use was reported by 87%. Eighteen patients had prior hiatal hernia/fundoplication. All had normal function. 78% of patients had axial hiatal hernia ≥5 cm or large paraesophageal component. Mean operative time was 81 min (38-193), EBL was 10 cc. Non-permanent mesh reinforcement of hiatal repair was performed in 83% of the patients. There were two readmissions for dehydration; 2 patients with pulmonary embolism, and 1 patient with cardiac ischemia. Nineteen patients required dilation. 156 pts were followed at a median of 8.6 months. GERD-HRQL scores improved from 26 preoperatively to 2 postoperatively. Complete PPI independence was achieved in 94% (147/156). Videoesophagram in 51 patients at median 11 months found 3 asymptomatic hernias <3 cm. One symptomatic patient underwent successful repair of the hernia without MSA manipulation. There have been no device explants, erosions, or migrations to date. CONCLUSIONS: This prospective study of 200 patients with >3 cm hernias undergoing MSA with hiatoplasty resulted in favorable outcomes with median of 9 months follow-up. Comparing this to published reports of MSA in patients with <3 cm hernias, the safety and clinical efficacy of MSA are independent of initial hernia size.

Comparison of anterior segment health in wild and captive common murres.

OBJECTIVE: To evaluate and compare the anterior segment health of wild and captive common murres. PROCEDURES: Thirty wild common murres (Uria aalge) were captured and housed in freshwater pools and had an adnexal and anterior segment exam performed prior to a subsequent wildlife health study. The examination included phenol red thread tear tests, fluorescein staining, slit-lamp biomicroscopy, rebound tonometry, and conjunctival culture sampling. Six captive common murres housed in natural seawater at the Monterey Bay Aquarium were examined in a similar manner. RESULTS: The most common ophthalmic lesion in the wild birds was corneal fibrosis with 55% prevalence, and over half of these were potentially vision threatening. Lenticular opacity (cataract or sclerosis or both) was the most common lesion in captive murres seen in 67% of the eyes. Mean phenol red tear test for all eyes without ulcers was 20 ± 3.6 mm. Mean intraocular pressure for all eyes without ulcers or flare was 23 ± 2.6 mmHg. The wild murres had a low percentage (17%) of positive conjunctival cultures. The captive murres had no growth on any culture. CONCLUSIONS: Wild murres are more likely to suffer corneal lesions, whereas captive murres are more likely to experience age-related lenticular diseases. Corneal scarring indicates that wild murres are frequently exposed to ocular trauma and the body condition scores indicate they appear to remain successful predators despite some vision compromise.

Causes and outcomes of dogs presenting with hyphema to a referral hospital in Colorado: a retrospective analysis of 99 cases.

OBJECTIVE: To investigate the causes of hyphema in dogs and identify factors associated with poor visual outcomes. ANIMALS STUDIED: Ninety-nine dogs (120 eyes) that presented with hyphema. PROCEDURE: Medical records from the Colorado State University Veterinary Teaching Hospital between the years 2004-2015 were reviewed. RESULTS: Overall, 36.4% of dogs were diagnosed with hyphema from systemic causes, 32.9% due to local ocular disease, 26.1% due to trauma, and 4.5% due to idiopathic causes. Regardless of cause, 55.4% of eyes were blind at their last recheck, but the percentage of eyes that lost vision ranged from 11.1 to 100%, depending on the cause. Causes of hyphema with poor outcomes were ocular neoplasia, chronic uveitis, and trauma. Enucleation was performed or recommended in 36 eyes (39.5%), and 27 eyes (31.4%) were diagnosed with glaucoma. Initial exam findings associated with a significantly increased risk of blindness were absent consensual PLR (odds ratio (OR) = 28.6), absent dazzle (OR = 19.4), elevated intraocular pressure (IOP) (OR = 9.1), presence of a retinal detachment (OR = 7.6), unilateral hyphema (OR = 5.8), and complete hyphema (OR = 3.9). Factors associated with a significantly increased risk of glaucoma included hyphema present for 8-30 days (OR > 6), absent consensual PLR (OR = 6.4), absent dazzle (OR = 5.3), and the presence of a retinal detachment at the final evaluation (OR = 5.8). CONCLUSION: Prognosis for vision is highly dependent on the cause of hyphema and initial exam findings. Poor prognostic factors on presentation include absent dazzle, absent consensual PLR, elevated IOP, unilateral hyphema, and complete hyphema.

Treatment of spontaneous chronic corneal epithelial defects (SCCEDs) with diamond burr debridement vs combination diamond burr debridement and superficial grid keratotomy.

OBJECTIVE: To evaluate the efficacy of diamond burr debridement (DBD) vs a combination of diamond burr debridement with superficial grid keratotomy (DBD+SGK) for the treatment of spontaneous chronic corneal epithelial defects (SCCEDs) in dogs. PROCEDURE: Medical records of dogs diagnosed with SCCEDs from three different institutions that received a DBD or DBD+SGK between 2003 and 2015 were reviewed. Age, breed, sex, history of a previous SCCED, procedures performed, time to healing, and complications were statistically analyzed. RESULTS: One hundred and ninety-four dogs met the inclusion criteria. Eighty-two of 106 eyes (77.4%) received a DBD and healed following the first treatment (13.3 ± 4.9 days to recheck, range 2-27). Sixty-eight of 88 eyes (77.3%) received a DBD+SGK and healed following the first treatment (15.4 ± 5.0 days to recheck, range 5-45). No significant difference in healing outcome was found between the two treatments (P = 1). For SCCEDs that healed after a single treatment (n = 150), complications occurred in 13.3% (n = 20) of eyes with no difference in complications between the DBD and DBD+SGK groups (P = .86). Thirty-five of 44 eyes (80.0%) healed after the second treatment (16 ± 8.2 days from second treatment to third visit, range 5-47); nine of 44 eyes (20.0%) were not healed (12 ± 6.2 days from second treatment to third visit, range 5-25). The second treatment method did not influence healing rates (P = .64). CONCLUSIONS: DBD and DBD+SGK are equally effective treatment methods for canine SCCEDs. No differences in complication rates after one treatment were observed between DBD and DBD+SGK.

Canine central corneal thickness measurements via Pentacam-HR® , optical coherence tomography (Optovue iVue® ), and high-resolution ultrasound biomicroscopy.

OBJECTIVE: To compare central corneal thickness (CCT) values in canine eyes using Pentacam-HR® Scheimpflug imaging (Pentacam), Optovue® iVue spectral-domain optical coherence tomography (SD-OCT), and high-resolution ultrasound biomicroscopy (UBM) and generate normative canine Pentacam CCT values. ANIMALS STUDIED: Twenty-four client-owned dogs (37 eyes) with nondiseased cornea(s) presenting to the Colorado State University Veterinary Teaching Hospital. PROCEDURES: Corneal images were acquired via Pentacam, SD-OCT, and UBM in the listed order. Machine-calculated values of CCT from Pentacam and SD-OCT were compared to operator-measured values from UBM. Bland-Altman analysis was performed to evaluate agreement between instruments. RESULTS: Mean CCT ± SD measured by Pentacam was 629.73 ± 64.57 µm, by SD-OCT was 610.56 ± 57.48 µm, and by UBM was 689.77 ± 55.93 µm. On average, Pentacam CCT was 19.17 ± 32.90 µm (3%) thicker than SD-OCT and 65.12 ± 44.52 µm (10.3%) thinner than UBM. SD-OCT was on average 82.47 µm (13.5% ) thinner than UBM. The 95% limits of agreement were (-45.31, 83.65), (-152.38, 22.13), and (-126.674, -38.270) for Pentacam vs. SD-OCT, Pentacam vs. UBM, and SD-OCT vs. UBM respectively. All differences were statistically significant (P < 0.01). CONCLUSIONS: Considering there is an average of 7.5% normal diurnal variation in canine CCT, a 3.0% difference between Pentacam and SD-OCT values is likely not clinically relevant. However, Pentacam measurements were both statistically and clinically significantly different from UBM and SD-OCT measurements.

Presumptive keratoglobus in a great horned owl (Bubo virginianus).

A juvenile to young adult, male, great horned owl (Bubo virginianus,GHOW) was presented to the wildlife rehabilitation hospital at Lindsay Wildlife Museum (WRHLWM) due to trauma to the right patagium from barbed wire entanglement. On presentation, both corneas were irregular, dry, and no movement of the third eyelid was noted. A severe corneal enlargement/globoid appearance was the predominant ophthalmic feature. The fundus was normal in both eyes (OU). Over the course of several days, both corneas developed edema combined with further dessication at the ocular surface associated with diffuse dorsal fluorescein stain uptake. Repeated ophthalmic examinations found normal intraocular pressures and an inability to move the third eyelid over the enlarged corneas. The bird was deemed nonreleasable due to severe wing damage and poor prognosis associated with eye abnormalities and was humanely euthanized. Postmortem CT, enucleation, and histopathology were performed to evaluate the ocular anatomical abnormality and confirm the suspected diagnosis of keratoglobus. This GHOW represents the first reported case of presumptive keratoglobus in a raptor.

Comparison between Pentacam-HR and optical coherence tomographycentral corneal thickness measurements in healthy feline eyes.

OBJECTIVES: To measure the central corneal thickness (CCT) in healthy feline eyes with Scheimpflug imaging (Pentacam, Pentacam(®) -HR) and to compare these values with those obtained with spectral-domain optical coherence tomography (OCT, Optovue(®) iVue). ANIMALS STUDIED: Thirty one sedated Domestic Short-haired cats. PROCEDURES: Two repeated CCT measurements were obtained from both eyes using Pentacam measured at the pupil center and corneal apex (CCTpupil and CCTapex ) and using SD-OCT (CCTOCT ). Agreement between the imaging modalities for CCT and intradevice repeatability was evaluated with Bland-Altman analysis. Mixed modeling was used to test for a difference between methods. RESULTS: The calculated mean ± SD CCT was CCTOCT  = 584.93 ± 39.05 µm, CCTpupil  = 608.25 ± 47.26 µm, and CCTapex  = 606.41 ± 44.18 µm. There was a statistically significant difference between CCTOCT vs. CCTpupil (P < 0.0007) and CCTOCT vs. CCTapex (P < 0.0003) (n = 59 eyes). The 95% limits of agreement (LoA) for CCTOCT vs. CCTpupil was (-89.57 µm, 40.04 µm) and for CCTOCT vs. CCTapex was (-79.62 µm, 33.79 µm) (n = 59 eyes). 95% LoA between repeated CCT measurements by SD-OCT was (-10.23 µm, 9.32 µm) and by Pentacam was (-22.66 µm, 18.30 µm) at pupil and (-15.81 µm, 16.17 µm) at corneal apex (n = 11 eyes). CONCLUSIONS: SD-OCT and Pentacam provide excellent CCT measurement repeatability. Pentacamapex is our recommended clinical setting for use of the Pentacam. The level of agreement between SD-OCT and Pentacam for CCT is good.

Medical management of acute ocular hypertension in a western screech owl (Megascops kennicottii).

A wild young adult western screech owl (Megascops kennicottii) of unknown sex was presented for evaluation of an abnormal left eye (OS). Ophthalmic examination OS revealed raised intraocular pressure (37 mm Hg; reference interval 7-16 mm Hg), mydriasis, conjunctival and episcleral hyperemia, shallow anterior chamber due to anterior displacement of the lens and iris, rubeosis iridis, and engorgement of the pecten. The intraocular pressure in the right eye (OD) was 11 mm Hg. Multifocal pale, variably translucent, curvilinear to vermiform opacities were observed in the medial and ventral peripheral regions of the retina OD, consistent with focal retinitis. Mannitol (0.46 g/kg IV) was administered over 10 minutes. Forty minutes later, the intraocular pressure was 27 mm Hg OS and 13 mm Hg OD. Dorzolamide (one drop OS q12h), diclofenac (one drop OU q8-12h), and meloxicam (0.5 mg/kg PO q24h) were administered for 3 days. The intraocular pressure OS was within normal limits 1 day (11 mm Hg), 7 days (13 mm Hg), and 4 weeks (14 mm Hg) after this treatment. Complications arising during hospitalization and rehabilitation included superficial corneal ulceration of both eyes presumed secondary to trauma on being caught and superficial damage to a talon. The owl was released after a period of rehabilitation. Characteristic presenting signs as well as response to therapy suggest aqueous misdirection was the cause of ocular hypertension in this owl. To our knowledge, this is the first report of suspected aqueous misdirection and its medical management in a raptor.

Coordinated dynamic gene expression changes in the central nucleus of the amygdala during alcohol withdrawal.

BACKGROUND: Chronic alcohol use causes widespread changes in the cellular biology of the amygdala's central nucleus (CeA), a GABAergic center that integrates autonomic physiology with the emotional aspects of motivation and learning. While alcohol-induced neurochemical changes play a role in dependence and drinking behavior, little is known about the CeA's dynamic changes during withdrawal, a period of emotional and physiologic disturbance. METHODS: We used a qRT-PCR platform to measure 139 transcripts in 92 rat CeA samples from control (N = 33), chronically alcohol exposed (N = 26), and withdrawn rats (t = 4, 8, 18, 32, and 48 hours; N = 5, 10, 7, 6, 5). This focused transcript set allowed us to identify significant dynamic expression patterns during the first 48 hours of withdrawal and propose potential regulatory mechanisms. RESULTS: Chronic alcohol exposure causes a limited number of small magnitude expression changes. In contrast, withdrawal results in a greater number of large changes within 4 hours of removal of the alcohol diet. Sixty-five of the 139 measured transcripts (47%) showed differential regulation during withdrawal. Over the 48-hour period, dynamic changes in the expression of γ-aminobutyric acid type A (GABA(A) ), ionotropic glutamate and neuropeptide system-related G-protein-coupled receptor subunits, and the Ras/Raf signaling pathway were seen as well as downstream transcription factors (TFs) and epigenetic regulators. Four temporally correlated gene clusters were identified with shared functional roles including NMDA receptors, MAPKKK and chemokine signaling cascades, and mediators of long-term potentiation, among others. Cluster promoter regions shared overrepresented binding sites for multiple TFs including Cebp, Usf-1, Smad3, Ap-2, and c-Ets, suggesting a potential regulatory role. CONCLUSIONS: During alcohol withdrawal, the CeA experiences rapid changes in mRNA expression of these functionally related transcripts that were not predicted by measurement during chronic exposure. This study provides new insight into dynamic expression changes during alcohol withdrawal and suggests novel regulatory relationships that potentially impact the aspects of emotional modulation.

Symblepharon in kittens: a retrospective study of 40 kittens and 54 eyes (2002-2022).

OBJECTIVES: The aim of this study was to retrospectively evaluate the signalment, treatment, surgical technique and outcomes for feline symblepharon. METHODS: A retrospective medical record review and standardized grading of clinical descriptions and photographs was undertaken. RESULTS: Forty kittens (54 eyes) aged 3-46 weeks had symblepharon of five types in various combinations: eyelid deformation (24 kittens; 32 eyes); ankyloblepharon (four kittens; four eyes); conjunctiva-to-conjunctiva (11 kittens; 12 eyes); third eyelid-to-conjunctiva (24 kittens; 29 eyes); and corneoconjunctival adhesions (14 kittens; 16 eyes). At initial presentation, 23 (43%) eyes were affected by one type of symblepharon, 25 (46%) eyes by two types and six (11%) eyes by three types; 11 (20%) corneas were ulcerated. Twenty-four (44%) eyes of 18 (45%) kittens were managed medically. Surgery was performed under general anesthesia/sedation (30 occasions) or topical anesthesia (21 occasions) on 30 (56%) eyes of 22 kittens; 12 eyes (40%) underwent multiple surgeries. Four techniques were commonly employed: separation of conjunctival-to-conjunctival adhesions ± eyelid margins (14 eyes); resection of third eyelid adhesions ± temporary tacking of the third eyelid (modified Arlt's pterygium technique; 18 eyes); en bloc resection of the third eyelid (two eyes); and separation of corneoconjunctival adhesions (14 eyes). Median duration of follow-up was 55 days (range 1-1051). Median symblepharon grade in kittens treated surgically improved for all types except corneoconjunctival symblepharon. Median symblepharon grade in kittens receiving medical management remained the same or improved. Corneoconjunctival symblepharon opacity decreased for eyes treated surgically but increased for eyes treated medically. Three eyes were enucleated due to complications of corneoconjunctival symblepharon. At final presentation, symblepharon persisted in 46 (85%) eyes; however, menace response was evident in 13/16 eyes and dazzle reflex in 23/23 eyes. CONCLUSIONS AND RELEVANCE: Symblepharon is a heterogeneous group of conditions with diverse anatomic involvement, clinical appearance and impact, optimal treatment and prognosis for vision.

Understanding the implementation of health checks in the prevention and early detection of chronic diseases among Aboriginal and Torres Strait Islander people in Australia: a realist review protocol.

INTRODUCTION: Chronic disease remains the leading cause of morbidity and mortality among Aboriginal and Torres Strait Islander peoples in Australia. Regular structured, comprehensive health assessments are available to Aboriginal and Torres Strait Islander people as annual health checks funded through the Medicare Benefits Schedule. This realist review aims to identify context-specific enablers and tensions and contribute to developing an evidence framework to guide the implementation of health checks in the prevention and early detection of chronic diseases for Aboriginal and Torres Strait Islander people. METHODS AND ANALYSIS: The review will involve the following steps: (1) Aboriginal and Torres Strait Islander engagement and research governance; (2) defining the scope of the review; (3) search strategy; (4) screening, study selection and appraisal; (5) data extraction and organisation of evidence; (6) data synthesis and drawing conclusions. This realist review will follow the Realist and MEta-narrative Evidence Syntheses: Evolving Standards guidance and will be reported as set up by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement. The realist programme theory will be developed through a literature review using multiple database searches from 1 November 1999 to 31 June 2022, limited to the English language, and stakeholder consultation, which will be refined throughout the review process. The study findings will be reported by applying the context-mechanism-outcome configuration to gain a deeper understanding of context and underlying mechanisms that influence the implementation of health checks in the prevention and early detection of chronic diseases among Aboriginal and Torres Strait Islander people in Australia. ETHICS AND DISSEMINATION: Ethical approval is not required as this review will be using secondary data. Findings will be published in a peer-reviewed journal and presented at scientific conferences. SYSTEMATIC REVIEW REGISTRATION: The review protocol has been registered on the international prospective register of systematic reviews: CRD42022326697.

Temporal changes in innate immune signals in a rat model of alcohol withdrawal in emotional and cardiorespiratory homeostatic nuclei.

BACKGROUND: Chronic alcohol use changes the brain's inflammatory state. However, there is little work examining the progression of the cytokine response during alcohol withdrawal, a period of profound autonomic and emotional upset. This study examines the inflammatory response in the central nucleus of the amygdala (CeA) and dorsal vagal complex (DVC), brain regions neuroanatomically associated with affective and cardiorespiratory regulation in an in vivo rat model of withdrawal following a single chronic exposure. METHODS: For qRT-PCR studies, we measured the expression of TNF-α, NOS-2, Ccl2 (MCP-1), MHC II invariant chain CD74, and the TNF receptor Tnfrsf1a in CeA and DVC samples from adult male rats exposed to a liquid alcohol diet for thirty-five days and in similarly treated animals at four hours and forty-eight hours following alcohol withdrawal. ANOVA was used to identify statistically significant treatment effects. Immunohistochemistry (IHC) and confocal microscopy were performed in a second set of animals during chronic alcohol exposure and subsequent 48-hour withdrawal. RESULTS: Following a chronic alcohol exposure, withdrawal resulted in a statistically significant increase in the expression of mRNAs specific for innate immune markers Ccl2, TNF-α, NOS-2, Tnfrsf1a, and CD74. This response was present in both the CeA and DVC and most prominent at 48 hours. Confocal IHC of samples taken 48 hours into withdrawal demonstrate the presence of TNF-α staining surrounding cells expressing the neural marker NeuN and endothelial cells colabeled with ICAM-1 (CD54) and RECA-1, markers associated with an inflammatory response. Again, findings were consistent in both brain regions. CONCLUSIONS: This study demonstrates the rapid induction of Ccl2, TNF-α, NOS-2, Tnfrsf1a and CD74 expression during alcohol withdrawal in both the CeA and DVC. IHC dual labeling showed an increase in TNF-α surrounding neurons and ICAM-1 on vascular endothelial cells 48 hours into withdrawal, confirming the inflammatory response at the protein level. These findings suggest that an abrupt cessation of alcohol intake leads to an acute central nervous system (CNS) inflammatory response in these regions that regulate autonomic and emotional state.

Rapid temporal changes in the expression of a set of neuromodulatory genes during alcohol withdrawal in the dorsal vagal complex: molecular evidence of homeostatic disturbance.

BACKGROUND: Chronic alcohol exposure produces neuroadaptation, which increases the risk of cellular excitotoxicity and autonomic dysfunction during withdrawal. The temporal progression and regulation of the gene expression that contributes to this physiologic and behavioral phenotype is poorly understood early in the withdrawal period. Further, it is unexplored in the dorsal vagal complex (DVC), a brainstem autonomic regulatory structure. METHODS: We use a quantitative polymerase chain reaction platform to precisely and simultaneously measure the expression of 145 neuromodulatory genes in more than 100 rat DVC samples from control, chronically alcohol-exposed, and withdrawn rats. To gain insight into the dynamic progression and regulation of withdrawal, we focus on the expression of a subset of functionally relevant genes during the first 48 hours, when behavioral symptoms are most severe. RESULTS: In the DVC, expression of this gene subset is essentially normal in chronically alcohol-exposed rats. However, withdrawal results in rapid, large-magnitude expression changes in this group. We observed differential regulation in 86 of the 145 genes measured (59%), some as early as 4 hours into withdrawal. Time series measurements (4, 8, 18, 32, and 48 hours after alcohol removal) revealed dynamic expression responses in immediate early genes, γ-aminobutyric acid type A, ionotropic glutamate, and G-protein coupled receptors and the Ras/Raf signaling pathway. Together, these changes elucidate a complex, temporally coordinated response that involves correlated expression of many functionally related groups. In particular, the expression patterns of Gabra1, Grin2a, Grin3a, and Grik3 were tightly correlated. These receptor subunits share overrepresented transcription factor binding sites for Pax-8 and other transcription factors, suggesting a common regulatory mechanism and a role for these transcription factors in the regulation of neurotransmission within the first 48 hours of alcohol withdrawal. CONCLUSIONS: Expression in this gene set is essentially normal in the alcohol-adapted DVC, but withdrawal results in immediate, large-magnitude, and dynamic changes. These data support both increased research focus on the biological ramifications of alcohol withdrawal and enable novel insights into the dynamic withdrawal expression response in this understudied homeostatic control center.