Brain iron deposition and movement disorders in hereditary haemochromatosis without liver failure: A cross-sectional study.

BACKGROUND AND PURPOSE: Hereditary haemochromatosis (HH) is the most common inherited disorder of systemic iron excess in Northern Europeans. Emerging evidence indicates that brain iron overload occurs in HH. Despite this observation, there is a paucity of literature regarding central neurological manifestations, in particular movement disorders, in HH. The current study documents deep gray matter (DGM) nuclei iron deposition, movement disorders, and clinicoradiological correlations in HH without liver failure. METHODS: This is a cross-sectional study. Consecutive subjects with HFE-haemochromatosis without liver disease were recruited from an outpatient gastroenterology clinic. Age- and sex-matched healthy controls (HCs) were enrolled. Iron content in individual DGM nuclei was measured as mean susceptibility on magnetic resonance imaging using quantitative susceptibility mapping-based regions of interest analysis. Occurrence and phenotype of movement disorders were documented and correlated with patterns of DGM nuclei iron deposition in subjects with HH. RESULTS: Fifty-two subjects with HH and 47 HCs were recruited. High magnetic susceptibility was demonstrated in several DGM nuclei in all HH subjects compared to HCs. Thirty-five subjects with HH had movement disorders. Magnetic susceptibility in specific DGM nuclei correlated with individual movement disorder phenotypes. Serum ferritin, phlebotomy frequency, and duration were poor predictors of brain iron deposition. CONCLUSIONS: Abnormal brain iron deposition can be demonstrated on imaging in all subjects with HH without liver failure. A significant proportion of these subjects manifest movement disorders. Peripheral iron measurements appear not to correlate with brain iron deposition. Therefore, routine neurological examination and quantitative brain iron imaging are recommended in all subjects with HH.

Osseous Migration of a Perforating Gastrointestinal Foreign Body in an Indian Runner Duck (Anas platyrhynchos domesticus).

An Indian runner duck (Anas platyrhynchos domesticus) was presented for a second opinion after a linear, metallic foreign body was identified on radiographic images. The primary veterinarian performed diagnostic imaging while investigating the presenting complaint of the duck's left pelvic limb lameness. The images obtained from a computed tomography scan performed during the second-opinion visit revealed a linear, metallic foreign body with an associated migration tract originating from the ventriculus and terminating in the proximal left femur. Significant osteomyelitis was noted at the proximal left femur associated with the presence of the linear, metallic object. The foreign body and the adhesions associated with its migration were removed in 2, staged, surgical procedures. Although penetrating ventricular foreign bodies have been previously reported, migration through the cortex of a long bone is an unusual presentation. This case demonstrates that perforating, migrating, gastrointestinal foreign bodies can result in lameness refractory to analgesia and ancillary supportive care.

Surgical treatment and outcome of complete unilateral urinary tract duplication in a dog.

OBJECTIVE: To report the surgical technique and outcome for correction of complete unilateral duplication of the left urinary tract in a dog. ANIMALS: One 7-month-old entire male Jack Russell terrier. STUDY DESIGN: Case report METHODS: A dog was referred for investigation because of urinary incontinence (UI), preputial irritation (pruritus), diphallia, and cryptorchidism. Computed tomography including urethrographic studies revealed a left duplex kidney, double ectopic left ureters, and a duplex urinary bladder comprising two halves separated by a median septum, each of which emptied into a separate urethra which coursed through separate penises. The left testis was abdominally retained. The right upper urinary tract was considered normal, and the right testis was within the scrotum. Left sided ureteronephrectomy was performed, the median bladder septum was ablated, and the left urethra was ligated. The left penis was partially amputated, and the dog was castrated. RESULTS: Urinary incontinence was improved but persisted after surgery. After repeat imaging, revision surgery was performed 3 months later in which the distal stumps of the (left) ectopic ureters were found to be filling with urine from the right urethra. Urinary incontinence resolved after resection of these ureteric stumps from the prostate and complete transection of the left urethra. CONCLUSION: Extensive surgery with resection and correction of urinary tract duplication was successful in resolving UI in this case. Urogenital duplication should be considered a rare cause of UI. The presence of external congenital deformity (eg, diphallia) should alert clinicians to the possibility of significant concurrent internal abnormalities.

Identifying Community Perspectives for a Lung Cancer Screening Awareness Campaign in Appalachia Kentucky: The Terminate Lung Cancer (TLC) Study.

Lung cancer screening with low-dose computed tomography (LDCT) scan is now covered by Centers for Medicare & Medicaid Services following an evidence-based recommendation, but a shared decision making process should inform patients of risks and limitations. An awareness campaign promoting LDCT screenings is an opportunity to elicit patient engagement with health providers about the risks and benefits. Focus groups representing three regions of Appalachian Kentucky known for high lung cancer rates discussed development of a lung cancer screening campaign. Recommendations included messaging content, appeals or design, campaign implementation, and trusted information or communication sources. Community health workers (CHWs) from three Eastern Kentucky regions recruited individuals from their local communities using established client files. CHWs hosted six total focus groups (7-11 participants each) using questions guided by the Communication-Persuasion Matrix framework. All sessions were recorded and transcribed for independent content analysis. A total of 54 individuals (61.1 % female; >55 pack year history) were participated. Prior to discussion, most participants had not heard of lung cancer screening. Cited needs for content of a campaign included benefits of early detection and payment information. Messages considered most persuasive were those that include personal testimony, messages of hope, prolonged life, and an emphasis on family and the ambition to survive. Having information come from one's family doctor or specialty provider was considered important to message communication. Messages about survivorship, family, and prolonged life should be considered in lung cancer screening awareness campaigns. Our results provide community input about messages regarding screening options.

The STRAT-PARK cohort: A personalized initiative to stratify Parkinson's disease.

The STRAT-PARK initiative aims to provide a platform for stratifying Parkinson's disease (PD) into biological subtypes, using a bottom-up, multidisciplinary biomarker-based and data-driven approach. PD is a heterogeneous entity, exhibiting high interindividual clinicopathological variability. This diversity suggests that PD may encompass multiple distinct biological entities, each driven by different molecular mechanisms. Molecular stratification and identification of disease subtypes is therefore a key priority for understanding and treating PD. STRAT-PARK is a multi-center longitudinal cohort aiming to recruit a total of 2000 individuals with PD and neurologically healthy controls from Norway and Canada, for the purpose of identifying molecular disease subtypes. Clinical assessment is performed annually, whereas biosampling, imaging, and digital and neurophysiological phenotyping occur every second year. The unique feature of STRAT-PARK is the diversity of collected biological material, including muscle biopsies and platelets, tissues particularly useful for mitochondrial biomarker research. Recruitment rate is ∼150 participants per year. By March 2023, 252 participants were included, comprising 204 cases and 48 controls. STRAT-PARK is a powerful stratification initiative anticipated to become a global research resource, contributing to personalized care in PD.

A screen for disruptors of the retinol (vitamin A) signaling pathway.

The pathway through which retinol (vitamin A) is converted to its active metabolite, all-trans-retinoic acid (atRA), and subsequent receptor-mediated regulation of gene transcription by atRA is essential for all mammal life stages. This pathway is required for normal embryonic development and maintenance of cellular phenotype in adult organisms; chemicals that cause even minor interference with its normal function are potential developmental and adult toxicants. A short-term (24 h) in vitro mode-of-action screen for detecting chemicals that disrupt this essential pathway is described. It uses the mouse pluripotent P19 stem cell in a 96-well format, RT-qPCR gene-expression assay that does not require RNA purification to detect chemicals that interfere with retinol-induced Hoxa1 gene expression, a target of retinol signaling in mammals. A total of 21 chemicals were screened at a single 45 µM concentration. Four chemicals known to disrupt the pathway in the rodent embryo (citral, disulfiram, and two rodent teratogens, nitrofen and bisdiamine) all significantly inhibited Hoxa1 upregulation by retinol. An additional four of seven chemicals with varying degrees of structural similarity to known disruptors or to the retinoid side chain, but not previously known to disrupt the pathway, were positive in the screen. The xenoestrogens, diethylstilbestrol, bisphenol A, 4-n-nonylphenol, and genistein and the phthalate esters, dibutyl phthalate and dipentyl phthalate, but not diethylhexyl phthalate, also significantly disrupted the pathway. Of the 21 chemicals tested, diethylstilbestrol was the only chemical that showed evidence in the MTT assay that cytotoxicity may have contributed to disruption of the pathway.

Bifocal femoral deformity correction and lengthening using a circular fixator construct in a dog.

A 7 mo old male rottweiler was evaluated for a right hind limb lameness caused by malunion of a Salter-Harris type II fracture. Radiographs and computed tomography (CT) revealed that the right distal femur had valgus, procurvatum, external rotation, and was 35% (70 mm) shorter than the contralateral femur. Distal femoral wedge ostectomies were performed to acutely correct the angular and rotational deformities. Lengthening of the femur was accomplished by distraction osteogenesis performed over 53 days at a second, proximal diaphyseal osteotomy using a circular fixator construct. This bifocal approach yielded approximately 30 mm of femoral lengthening and a confluent column of regenerate bone that bridged the distraction gap. When evaluated 14 mo after surgery, the dog held the right hip, stifle, and hock in a slightly extended posture when standing and had a subtle asymmetric hind limb gait. The stride of the right hind limb was slightly shortened with compensatory circumduction of the left hind limb during the swing phase of the stride.

Multiple congenital PSS in a dog: case report and literature review.

A 4 yr old spayed female mixed-breed dog presented with a 2 yr history of recurring increases in liver enzymes. Two congenital portosystemic shunts (PSSs) were identified using computed tomography (CT) angiography, which included a portoazygous and portorenal extrahepatic shunt. Double right renal veins were also identified. The shunts were successfully identified and attenuated with cellophane banding. Multiple congenital PSS is a rare phenomenon, but should be considered during exploratory laparotomy for PSS and in dogs with poor response to surgical attenuation of a single PSS. CT proved to be a crucial part of accurate diagnosis and surgical planning for this dog with multiple congenital PSS.

Radiographic characterization of presumed plate-like atelectasis in 75 nonanesthetized dogs and 15 cats.

Discrete discoid or linear areas of increased soft opacity have been observed within the pulmonary parenchyma in thoracic radiographs of dogs and cats. Similar radiographic findings have been described in humans and termed plate-like atelectasis. The purpose of this retrospective study was to describe locations and characteristics of presumed plate-like atelectasis, presence of concurrent thoracic disease(s), and presence of persistent pulmonary changes on recheck thoracic radiographic studies in a cohort of dogs and cats. Hospital records between 2004 and 2011 were searched and a total of 90 cases were included (75 dogs and 15 cats, 2-17 years of age). Plate-like atelectasis was most commonly found in left lateral radiographs. Plate-like atelectasis was observed in the cranial thorax and was oriented in a dorsocranial to ventrocaudal direction in 68 (75%) patients. Plate-like atelectasis averaged 29.6 ± 14.4 mm in length and 2.6 ± 1.3 mm in width. In 57 of the 90 patients (63%), plate-like atelectasis was the only abnormality found. Plate-like atelectasis was present in 7 of 22 cases where follow-up radiographs were available. Findings from the current study indicated that, while the etiology of plate-like atelectasis remains unknown, anatomic variations in sublobar pulmonary anatomy might account for pleural areas of atelectasis. The authors propose that the presence of plate-like atelectasis may represent areas of atelectasis that track along sublobar lung lobe separations, an area of hypoventilation or decreased collateral ventilation, and/or area of decreased localized surfactant deficiency.

Comparison of computed tomographic angiography and ultrasonography for the detection and characterization of portosystemic shunts in dogs.

The purpose of this retrospective study was to compare the accuracy of computed tomographic angiography (CTA) and abdominal ultrasonography in detecting and characterizing portosystemic shunts (PSS) in dogs. Medical records of 76 dogs that underwent CTA and/or abdominal ultrasonography suspected to have PSS were reviewed. Presence or absence, and characterization of PSS (when present) on CTA were reviewed by a board-certified veterinary radiologist that was blinded to the clinical findings. The abdominal ultrasonography findings were reviewed from the medical records. Visualization and description of the origin and insertion of PSS on CTA and abdominal ultrasonography were related with laboratory, surgical, or mesenteric portographic confirmation of the presence or absence of PSS. The sensitivity for detection of PSS with CTA (96%) was significantly higher than abdominal ultrasonography (68%; P < 0.001). The specificities for CTA and abdominal ultrasonography were 89% and 84%, respectively (P = 0.727). Computed tomographic angiography detected the correct origin in 15 of 16 dogs and correct insertion in 15 of 16 dogs with congenital PSS. Abdominal ultrasonography detected the correct origin in 24 of 30 dogs and correct insertion in 20 of 33 dogs with congenital PSS. Multiple acquired PSS were seen in four of five dogs and in one of six dogs on CTA and abdominal ultrasonography, respectively. Computed tomographic angiography was 5.5 times more likely to correctly ascertain the presence or absence of PSS when compared to abdominal ultrasonography (P = 0.02). Findings indicated that CTA is a noninvasive diagnostic modality that is superior to abdominal ultrasonography for the detection and characterization of PSS in dogs.

Intestinal and cloacal strictures in free-ranging and aquarium-maintained green sea turtles (Chelonia mydas).

Intestinal or cloacal strictures that resulted in intestinal obstruction were diagnosed in six green sea turtles (Chelonia mydas) from three rehabilitation facilities and two zoologic parks. The etiologies of the strictures were unknown in these cases. It is likely that anatomic adaptations of the gastrointestinal tract unique to the green sea turtle's herbivorous diet, paired with causes of reduced intestinal motility, may predispose the species to intestinal damage and subsequent obstructive intestinal disease. In aquarium-maintained green sea turtles, obesity, diet, reduced physical activity, chronic intestinal disease, and inappropriate or inadequate antibiotics might also be potential contributing factors. Clinical, radiographic, and hematologic abnormalities common among most of these sea turtles include the following: positive buoyancy; lethargy; inappetence; regurgitation; obstipation; dilated bowel and accumulation of oral contrast material; anemia; hypoglycemia; hypoalbuminemia; hypocalcemia; and elevated creatine kinase, aspartate aminotransferase, and blood urea nitrogen. Although these abnormalities are nonspecific with many possible contributing factors, intestinal disease, including strictures, should be considered a differential in green sea turtles that demonstrate all or a combination of these clinical findings. Although diagnostic imaging, including radiographs, computed tomography, or magnetic resonance imaging, are important in determining a cause for suspected gastrointestinal disease and identifying an anatomic location of obstruction, intestinal strictures were not successfully identified when using these imaging modalities. Lower gastrointestinal contrast radiography, paired with the use of oral contrast, was useful in identifying the suspected site of intestinal obstruction in two cases. Colonoscopy was instrumental in visually diagnosing intestinal stricture in one case. Therefore, lower gastrointestinal contrast radiography and colonoscopy should be considered in green turtles when gastrointestinal obstructions are suspected. Although partial strictures of the cloacal opening may be identified on gross examination and might be managed with appropriate medical treatment, surgical intervention or humane euthanasia are likely the only options for sea turtles once small or large intestinal strictures have formed.

Diagnosis and management of atypical hypoadrenocorticism in a variable flying fox (Pteropus hypomelanus).

A 19-yr-old intact female variable flying fox (Pteropus hypomelanus) presented with lethargy, behavior changes, and substantial weight loss. Initial clinical pathology revealed hypoglycemia and reduced ionized serum calcium, and imaging, including computed tomography, did not lead to a diagnosis. An adrenocorticotropic hormone (ACTH) stimulation test revealed baseline and post-ACTH cortisol concentrations that were lower than reported normal baseline cortisol concentrations in this species. Treatment with prednisolone resolved the clinical signs and laboratory abnormalities. Repeated attempts to decrease the prednisolone dose caused recurrence of clinical signs and weight loss. Based on diagnostic test results and response to therapy, a diagnosis of atypical hypoadrenocorticism was made.

Achieving health for a lifetime: a community engagement assessment focusing on school-age children to decrease obesity in Durham, North Carolina.

BACKGROUND: Obesity is a prominent problem in the United States and in North Carolina. One way of combating it is with community-engaged interventions that foster collaboration between health-oriented organizations and community residents. PURPOSE: Our purpose was to assemble a multifaceted group in Durham, North Carolina, to identify factors affecting obesity-related lifestyle behaviors; assess policies, resources, and the population's perception of the problem of obesity; and develop plans to improve health outcomes related to obesity. METHODS: A team consisting of more than 2 dozen partners was assembled to form Achieving Health for a Lifetime (AHL) in order to study and address obesity in the community, initially focusing on elementary school-age children. The team developed a resource guide by collecting information by telephone interviews of provider organizations; geospatial resource maps were created using high-resolution geographic information systems, Duke's Data Support Repository, and county and city records; and focus groups were conducted using the nominal group technique. RESULTS: The AHL team, in collaboration with 2 other teams focused on diabetes and cardiovascular disease, identified 32 resources for diabetes, 20 for obesity, and 13 for cardiovascular disease. Using Geographic Information Systems (GIS), the team identified an area of Durham that had only 1 supermarket, but 34 fast-food restaurants and 84 convenience stores. LIMITATIONS: The focus on particular neighborhoods means that the information obtained might not pertain to all neighborhoods. CONCLUSION: The AHL team was able to assemble a large community partnership in Durham that will allow the members of the community to continue to work toward making residents healthier. Communities facing similar challenges can learn from this experience.

Making ties and social identities: Drawing connections between PPNB communities as based on shell bead typology.

People tend to belong to multiple social circles, which construct and reflect a person's social identity. Group affiliation is embodied and may be expressed by personal adornment. Personal adornment in general has multiple functions in human societies, among them the assimilation and transmission of different aspects of personal and collective, social and cultural identity. Beads in general, including shell beads, often constitute parcels of composite adornment, and as such are used in different configurations to portray these messages. The shared use of similar bead types by different individuals and communities indicates the mutual affiliation of the sharing parties to the same cultural circles and reflects social ties and relationships. The Pre-Pottery Neolithic B (PPNB) period in the Levant is a time of pivotal changes to human lifeways necessitating profound adjustments in all aspects of life, including social relations and networks. Here we use the shell bead assemblage from the cultic-mortuary aggregation site of Kfar HaHoresh, in comparison to shell bead assemblages from multiple other sites in the Levant, as a proxy for the exploration of local and regional networks and connections between PPNB communities. Multivariate analyses of shell bead type distribution patterns across the Levant demonstrate that some types were widely shared among different communities, characterising different geographic regions, while others were rare or unique, highlighting relationships between sites and regions, which are occasionally independent of geographic proximity. Specific occurrences of shared shell bead types between Kfar HaHoresh and compared sites further illuminate the web of connections between PPNB communities in the Levant and the varying breadths of sharing-patterns reflect the hierarchical nature of the underlying social circles. Outlining these widening social affiliations sheds light on the complex structure of Neolithic social identity.

Digital radiography for the equine practitioner: basic principles and recent advances.

As availability increases and cost decreases, digital radiograph systems become more common in equine practice. Technological advances provide an array of choices for the equine practitioner considering purchase. Two classes of systems are available: computed radiography and flat-panel systems (direct radiography). Image processing encompasses all manipulations performed on an image at acquisition and can have a profound effect on the final digital radiograph. Consideration should be given to the type of display monitor because many options are now available. The type of display monitor and the viewing environment have an effect on interpretation performance.

Fungal Rhinosinusitis Caused by a Curvularia sp. Infection in a Female Sumatran Orangutan: A Case Report.

Mycotic nasal cavity and paranasal sinus infections in non-human primates (NHPs) are relatively uncommon diseases of the upper respiratory tract. This case study describes the clinical and pathological features as well as the diagnostic techniques and interventions applied to treat the associated disease. A 23-year-old primiparous female Sumatran orangutan residing at Perth Zoo in Western Australia developed intermittent episodes of right-sided epistaxis. An ulcerative nasal mass was identified from a diagnostic endoscopy. The mass was initially biopsied and showed the morphological characteristics of a dematiaceous fungal organism upon a histological examination. There were prominent mucosal and submucosal granulomatous infiltrates containing histocytes, giant cells, and lymphocytes admixed with fewer numbers of neutrophils and eosinophils surrounding the fungal organism. The organism was identified as Curvularia sp. by the fungal characteristics associated with the histopathology, culture growth, and PCR analysis. The mass was subsequently removed with endoscopic sinus surgery (ESS) and the orangutan was medically treated with itraconazole for several months. The recovery was uneventful and the orangutan returned to full health.

The retinol signaling pathway in mouse pluripotent P19 cells.

atRA (all-trans-retinoic acid), the active metabolite of retinol (vitamin A), is essential for embryogenesis and maintenance of cellular phenotype in adults. Chemicals that interfere with the metabolism of retinol to atRA, therefore, are a human health concern. During development of a screen for disruptors of this signaling pathway, we investigated whether the mouse pluripotent P19 cell metabolizes retinol to atRA and thus can be used in a cell-based screen for disruptors of the pathway. We found that retinol induced the identical pattern of homeobox gene expression as atRA and its precursor, retinal. Retinol was 160-fold less potent than atRA as an inducer, however. In spite of its lower potency, increased Hoxa1 gene expression was detected 30 min after retinol exposure and increased 40-fold by 2 h. Rdh10 and Aldh1a2/Raldh2, which together convert retinol to atRA in the embryo, were the predominant alcohol and aldehyde dehydrogenases expressed in P19 cells. The cell expressed high mRNA levels of retinol binding proteins, Rbp1 and Rbp4, and the 13,14-dihydroretinol saturase, Retsat. It also expressed all Rar and Rxr isotypes, Crabp1&2, the three Cyp26 genes, and both ß-carotene-cleaving genes, Bcmo1 and Bco2. The basal expression levels and retinol responsiveness of 25 pathway-related genes were quantitated by RT-qPCR. A test of the Aldh1a2 inhibitor, citral, showed that the disruption of the pathway was easily detected and quantitated showing that the P19 cell provides an in vitro model system for identifying and exploring the mechanism of action of chemicals that interfere with this critical cellular pathway.

Intra- and interobserver variability of board-certified veterinary radiologists and veterinary general practitioners for pulmonary nodule detection in standard and inverted display mode images of digital thoracic radiographs of dogs.

OBJECTIVE: To determine intra- and interobserver variability of 2 veterinary radiologists and 2 veterinary general practitioners for detection of pulmonary nodules in standard and inverted (reversed grayscale) displays of digital thoracic radiographs of dogs. DESIGN: Evaluation study. SAMPLE: 114 sets of 3-view (right lateral, left lateral, and ventrodorsal or dorsoventral views) digital thoracic radiographs from 114 dogs. PROCEDURES: 2 experienced board-certified veterinary radiologists and 2 experienced veterinary general practitioners individually evaluated 114 randomized sets of radiographs. Pulmonary nodules were present in radiographs of 60 of 114 dogs. Each reviewer examined all images in standard or inverted display mode and scored nodule detection on a confidence scale of 1 to 5. After ≥ 2 months, the same individuals evaluated the same images in the remaining display mode. Intraobserver agreement for each display mode was determined via a κ statistic; results between the 2 groups of reviewers were compared via receiver operator curve analysis. RESULTS: There was no significant intraobserver variability in pulmonary nodule detection between the 2 display modes. Detection accuracy for board-certified radiologists was significantly greater than that of veterinary general practitioners for both display modes. Near-perfect intraobserver agreement was detected between the 2 display modes for board-certified radiologists, whereas moderate to slight intraobserver agreement was detected for the veterinary general practitioners. CONCLUSIONS AND CLINICAL RELEVANCE: Detection of pulmonary nodules in digital thoracic radiographs was comparable, whether a standard or inverted mode was used for evaluations. However, the board-certified radiologists had greater detection accuracy than did veterinary general practitioners.

Computed tomographic assessment of lung aeration at different positive end-expiratory pressures in a porcine model of intra-abdominal hypertension and lung injury.

BACKGROUND: Intra-abdominal hypertension (IAH) is common in critically ill patients and is associated with increased morbidity and mortality. High positive end-expiratory pressures (PEEP) can reverse lung volume and oxygenation decline caused by IAH, but its impact on alveolar overdistension is less clear. We aimed to find a PEEP range that would be high enough to reduce atelectasis, while low enough to minimize alveolar overdistention in the presence of IAH and lung injury. METHODS: Five anesthetized pigs received standardized anesthesia and mechanical ventilation. Peritoneal insufflation of air was used to generate intra-abdominal pressure of 27 cmH2O. Lung injury was created by intravenous oleic acid. PEEP levels of 5, 12, 17, 22, and 27 cmH2O were applied. We performed computed tomography and measured arterial oxygen levels, respiratory mechanics, and cardiac output 5 min after each new PEEP level. The proportion of overdistended, normally aerated, poorly aerated, and non-aerated atelectatic lung tissue was calculated based on Hounsfield units. RESULTS: PEEP decreased the proportion of poorly aerated and atelectatic lung, while increasing normally aerated lung. Overdistension increased with each incremental increase in applied PEEP. "Best PEEP" (respiratory mechanics or oxygenation) was higher than the "optimal CT inflation PEEP range" (difference between lower inflection points of atelectatic and overdistended lung) in healthy and injured lungs. CONCLUSIONS: Our findings in a large animal model suggest that titrating a PEEP to respiratory mechanics or oxygenation in the presence of IAH is associated with increased alveolar overdistension.