Favorable outcome of pheochromocytoma in a dog with atypical Cushing's syndrome and diabetes mellitus following medical treatment: a case report.

BACKGROUND: Pheochromocytoma (PCC) has poor prognosis and adrenalectomy is hard to be performed, in case of caudal vena cava invasion. The long-term administration of phenoxybenzamine in PCC has not been reported in dogs. CASE PRESENTATION: A 14-year-old castrated male Poodle dog presented with an abdominal mass. On physical examination, hypertension, increased lens opacity, calcinosis cutis, generalized alopecia, and systolic murmur were observed. Serum chemistry and urinalysis profiles revealed hyperglycemia, hypercholesterolemia, elevated liver enzymes, and glucosuria. Abdominal ultrasonography showed a right adrenal mass with invasion of the caudal vena cava, which was cytologically diagnosed as suspected PCC. An adrenal mass (width × height × length, 28 × 26 × 48 mm3) was found on computed tomography and diagnosed as PCC with increased plasma metanephrines and normetanephrines. An adrenocorticotropin hormone stimulation test showed elevated adrenal hormones (androstenedione, estradiol, progesterone, and 17-OH progesterone) with normal cortisol, compatible with atypical Cushing's syndrome. The dog was managed with trilostane, phenoxybenzamine, and insulin therapy. Glycosylated hemoglobin and fructosamine levels gradually decreased, and hypertension resolved. In the 10-month follow-up period, the liver enzymes levels gradually decreased, and the clinical signs of the dog were well-controlled without deterioration. CONCLUSIONS: This case report describes long-term medical management without adrenalectomy of PCC complicated with atypical Cushing's syndrome and DM.

Antimicrobial resistance and novel mutations detected in the gyrA and parC genes of Pseudomonas aeruginosa strains isolated from companion dogs.

BACKGROUND: Fluoroquinolone agents, such as enrofloxacin and marbofloxacin, are commonly used for pseudomonal infection in veterinary medicine. However, the rate of resistance to fluoroquinolones is rapidly increasing, according to multiple studies in various countries. Point mutations in the quinolone resistance-determining region (QRDR) are closely related to the increased fluoroquinolone resistance of Pseudomonas aeruginosa. The aim of this study was to investigate current antimicrobial susceptibility and fluoroquinolone resistance in P. aeruginosa strains isolated from dogs. The presence of point mutations in the QRDR was confirmed by gyrA and parC polymerase chain reaction and nucleotide sequencing analysis. RESULTS: A total of 84 nonduplicated P. aeruginosa strains were obtained from 228 healthy dogs (healthy group) and 260 dogs with clinical signs (infected group). Among these isolates, 38 strains from the healthy group were detected in several sample types, whereas 46 strains from the infected group were obtained mostly from dogs' ears with otitis externa (41/260, 15.8%). All strains were resistant to nalidixic acid, while some were also resistant to enrofloxacin (23/84, 27.4%), marbofloxacin (17/84, 20.2%), levofloxacin (12/84, 14.3%), or ciprofloxacin (11/84, 13.1%). Enrofloxacin resistance was significantly higher in strains from the infected group than in those from the healthy group (p < 0.05). Among the 23 fluoroquinolone-resistant strains, 8 and 4 different mutations were detected in the gyrA and parC genes, respectively. Mutations in gyrA were significantly common in the infected group (p < 0.05). Hotspots for the gyrA and parC mutations were Thr83 (34.8%, 8/23) and Pro116 (91.3%, 21/23), respectively. Double and triple mutations were also found in 5 of the strains. CONCLUSION: Novel mutations in the gyrA and parC genes were first found in P. aeruginosa isolated from companion dogs in South Korea. These findings suggest that it is important to encourage prudent use of fluoroquinolone antibiotics in canine pseudomonal infection treatment.

Clinical response to isotretinoin and interferon-α of two dogs with cutaneous epitheliotropic T-cell lymphoma: a case report.

BACKGROUND: There is no specific therapy for cutaneous epitheliotropic T-cell lymphoma (CETL). The administration of retinoids in conjunction with interferon-α (IFN-α) in CETL has not been reported in dogs. CASE PRESENTATION: Two dogs (Shih tzu and Miniature pinscher) presented with multiple nodular skin lesions. Histopathological examination revealed diffuse infiltrations of lymphocytes in the epidermis and dermis, with a CD3-positive immunophenotypic profile. Based on the clinical and histopathological examination, CETL was diagnosed. Both dogs were treated with isotretinoin in combination with IFN-α and showed clinical improvement with complete or partial remission. The disease in these dogs was well-controlled for more than 264 days of overall median survival time without any additional clinical signs after initiation of the treatment. In both the cases, the dogs were followed up for 27 months, and 10 months without any evidence of recurrence or metastasis, respectively. CONCLUSIONS: We describe the clinical efficacy of isotretinoin combined with IFN-α in 2 dogs with CETL. Long-term management with isotretinoin combined with IFN-α was effective in treating CETL in these cases.

First report in a dog model of atopic dermatitis: expression patterns of protease-activated receptor-2 and thymic stromal lymphopoietin.

BACKGROUND: Protease-activated receptor (PAR)-2 plays a crucial role in inflammation and the skin barrier. Protease-activated receptor-2 is activated by proteolytic enzymes of allergens and stimulates thymic stromal lymphopoietin (TSLP), promoting T-helper 2 cytokines. In humans with atopic dermatitis (AD), increased expression of PAR-2 and TSLP has been reported. HYPOTHESIS/OBJECTIVES: To compare the pattern of staining of PAR-2 and TSLP between normal and atopic beagle dogs. The hypothesis tested was that increased expression is present in atopic dog skin compared with healthy control skin. ANIMALS: Eight atopic and five normal dogs were challenged for 3 days with house dust mites. METHODS: Skin biopsies were taken to measure the intensity, distribution, integrity and cell staining pattern on days 0, 3 and 10, both objectively and subjectively. Clinical signs were scored and compared between groups. RESULTS: Atopic dogs showed a significant increase in clinical scores on days 3 (peak of challenge) and 10 (resolution) and a significant condensed staining pattern for TSLP in the stratum basale at all times in comparison to normal dogs. They showed a significant patchy pattern for PAR-2 on days 0 and 3 and for TSLP at all times compared with normal dogs. The intensity itself was not significantly increased in atopic dogs compared with normal animals for both PAR-2 and TSLP. CONCLUSIONS AND CLINICAL IMPORTANCE: These preliminary findings do not confirm a difference in the amount of expression but rather in its pattern. Studies using PAR-2 or TSLP inhibitors could shed light on their clinical relevance.

Anthracycline-induced cardiomyopathy in a dog treated with epirubicin.

An 8-year-old American cocker spaniel dog was diagnosed with dilated cardiomyopathy. Four years earlier, the dog had been diagnosed with multicentric lymphoma and had received 4 cycles of multi-agent chemotherapy, including doxorubicin and epirubicin. The total cumulative dose of epirubicin was 168 mg/m(2). Dilated cardiomyopathy was considered a consequence of epirubicin toxicity.

Cardiomyopathie induite par l'anthracycline chez un chien traité à l'épirubicine. Un chien Épagneul cocker américain a été diagnostiqué avec une cardiomyopathie dilatée. Quatre années plus tôt, le chien avait été diagnostiqué avec un lymphome multicentrique et avait reçu 4 cycles de chimiothérapie multi-agents, y compris la doxorubicine et l'épirubicine. La dose cumulative totale d'épirubicine était de 168 mg/m2. La cardiomyopathie dilatée est considérée comme une conséquence de la toxicité de l'épirubicine.(Traduit par Isabelle Vallières).

Uveodermatologic syndrome concurrent with keratoconjunctivitis sicca in a miniature poodle dog.

A 5-year-old, intact female miniature poodle dog was presented with chronic ophthalmic problems, facial poliosis, nasal depigmentation and multiple areas of alopecia over the trunk. Bilateral uveitis preceded dermatologic signs by 5 months and gradually worsened. The dog was diagnosed as having uveodermatologic syndrome (UDS) concurrent with keratoconjunctivitis sicca (KCS). Treatment with immunosuppressive drugs resolved the dermatologic lesions, but uveitis continued to progress.

Syndrome uvéodermatologique concomitant à une kératoconjonctivite sèche chez un caniche miniature. Une chienne caniche miniature intacte âgée de 5 ans a été présentée avec des problèmes ophtalmiques chroniques, une poliose faciale, une dépigmentation nasale et plusieurs plaques d'alopécie sur le tronc. L'uvéite bilatérale a précédé les signes dermatologiques 5 mois auparavant et elle s'est graduellement aggravée. La chienne a été diagnostiquée comme atteinte du syndrome uvéodermatologique concomitant à une kératoconjonctivite sèche. Le traitement avec des immunodépresseurs a résolu les lésions dermatologiques, mais l'uvéite a continué de progresser.(Traduit par Isabelle Vallières).

Staphylococcus pseudintermedius infection associated with nodular skin lesions and systemic inflammatory response syndrome in a dog.

A 10-year-old Pekingese dog with atopic dermatitis was referred due to pyrexia, multiple skin nodules, anorexia, and depression. The dog was diagnosed as having systemic inflammatory response syndrome (SIRS) induced by bacterial dermatitis. This case presents diagnosis and treatment of SIRS with staphylococcal skin infection in a dog that was immunosuppressed due to long-term use of corticosteroid.

Infection parStaphylococcus pseudintermediusassociée à des lésions cutanées nodulaires et à un syndrome de réaction inflammatoire systémique chez un chien. Un chien Pékinois âgé de 10 ans atteint de dermatite atopique a été référé en raison d'une pyrexie, de nodules cutanés multiples, d'anorexie et de dépression. Le chien a été diagnostiqué comme ayant un syndrome de réaction inflammatoire systémique (SRIS) induit par une dermatite bactérienne. Ce cas présente le diagnostic et le traitement du SRIS avec une infection aux staphylocoques cutanés chez un chien ayant une immunodépression causée par l'utilisation à long terme de corticostéroïdes.(Traduit par Isabelle Vallières).

Resistance to fluoroquinolones and methicillin in ophthalmic isolates of Staphylococcus pseudintermedius from companion animals.

Resistance to fluoroquinolones and methicillin was determined for 49 ophthalmic isolates of Staphylococcus pseudintermedius from dogs with and without ophthalmic disease. Resistance was observed for ciprofloxacin (40.8%), ofloxacin (38.8%), enrofloxacin (38.8%), levofloxacin (34.7%), and moxifloxacin (4.1%). Eighteen isolates, 16 of which were resistant to oxacillin, were mecA-positive. Nine of the 16 oxacillin-resistant mecA-positive S. pseudintermedius isolates were resistant to more than one fluoroquinolone and 2 isolates were resistant to 5 fluoroquinolones. The frequency of mecA gene occurrence and fluoroquinolone resistance was twice as high among S. pseudintermedius isolates derived from dogs with ophthalmic disease compared with isolates for dogs without ophthalmic disease. The high prevalence of methicillin and fluoroquinolone resistance in S. pseudintermedius from dogs with ophthalmic disease is a concern.

Résistance aux fluoroquinolones et à la méthicilline dans les isolats oculaires deStaphylococcus pseudintermediusdes animaux de compagnie. La résistance aux fluoroquinolones et à la méthicilline a été déterminée pour 49 isolats oculaires de Staphylococcus pseudintermedius provenant de chiens atteints et exempts d'une maladie ophtalmique. La résistance a été observée pour la ciprofloxacine (40,8 %), l'ofloxacine (38,8 %), l'enrofloxacine (38,8 %), la levofloxacine (34,7 %) et la moxifloxacine (4,1 %). Dix-huit isolats, dont 16 étaient résistants à l'oxacilline, étaient positifs pour mecA. Neuf des 16 isolats de S. pseudintermedius positifs pour mecA résistants à l'oxacilline et étaient résistants à plus d'une fluoroquinolone et 2 isolats étaient résistants à 5 fluoroquinolones. La fréquence de l'occurrence du gène mecA et de la résistance aux fluoroquinolones était deux fois supérieure pour les isolats S. pseudintermedius dérivés de chiens atteints d'une maladie ophtalmique comparativement aux chiens sans maladie ophtalmique. La prévalence élevée de la résistance à la méthicilline et à la fluoroquinolone pour S. pseudintermedius chez les chiens atteints d'une maladie ophtalmique est préoccupante.(Traduit par Isabelle Vallières).

Case report: Small bowel obstruction secondary to congenital transmesenteric internal hernia in a cat.

An 8-month-old castrated male British Shorthair cat presented with acute anorexia and vomiting. The overall clinical presentation included generalized depression. Physical examination revealed palpable abdominal mass, thus foreign body or intussusception was suspected. Abdominal radiographs showed segmental dilation of small intestine and ultrasonography revealed target lesion with dilated small bowel loops and disrupted normal wall layering, suggestive of intussusception. Exploratory laparotomy confirmed congenital mesenteric defects associated with small intestinal obstruction. Surgical intervention involved dissection, ligation of encircling blood vessels, and closure of mesenteric defects. The cat was discharged after 3 days, exhibiting normal postoperative recovery. To our knowledge, this is the first case report of congenital mesenteric defect associated with small intestinal obstruction in a cat. While internal hernias are rare, it is essential to include them in the differential diagnosis for cases of intestinal obstruction, particularly in patients with no history of previous surgery or trauma. The potential for strangulation and ischemia in the affected loops elevates internal hernias to a critical, life-threatening condition, emphasizing the need for prompt recognition and urgent surgical intervention as an emergency.

Evaluation of autologous blood clot subsegmental pulmonary thromboembolism in minimally invasive experimental canine model.

The incidence and significance of subsegmental pulmonary (SSP) thromboembolism is currently under investigation. We aimed to evaluate the clinical and diagnostic features of SSP thromboembolism in an experimental canine model. Obstruction of pulmonary arterial branches was induced in three beagle dogs by intravenous injection of a barium-coated autologous blood clot (size, approximately 1.7 × 5 mm). The clinical signs, haemodynamic changes (blood pressure, electrocardiogram, echocardiography), coagulation (aPTT, PT, FDPs and D-dimer test) and cytokine variations (TNF-a, IL-4, IL-6, and IL-10) were evaluated over a 24-hour period. Multidetector computed tomography (MDCT) with contrast was conducted to evaluate the pulmonary obstruction, and histopathological confirmation was performed. Pulmonary artery pressure gradient (PAPG) was increased 12 h after the autologous blood clot injection (14.2 ± 2.8 mmHg to 23.6 ± 1.7 mmHg, P = 0.003) and normalized 24 h later (P < 0.01). Infused radiopaque clots were confirmed with MDCT and histopathological examination. Pulmonary parenchymal changes such as arterial dilation and inflammatory reactions were also confirmed in histopathological examinations and were barely observable in MDCT. Usually small emboli are not easily detected through CT imaging, and the clinical relevance of these emboli is controversial. In this experimental study, we made radiopaque small emboli and induced SSP thromboembolism. Thus, we infer that obstruction of the small segmental and subsegmental pulmonary arteries does result in a pulmonary thromboembolism (PTE) and PTE-related pulmonary parenchymal changes which could be clinically significant.

The effects of topical mesenchymal stem cell transplantation in canine experimental cutaneous wounds.

BACKGROUND: Adult stem cells have been widely investigated in bioengineering approaches for tissue repair therapy. We evaluated the clinical value and safety of the application of cultured bone marrow-derived allogenic mesenchymal stem cells (MSCs) for treating skin wounds in a canine model. HYPOTHESIS: Topical allogenic MSC transplantation can accelerate the closure of experimental full-thickness cutaneous wounds and attenuate local inflammation. ANIMALS: Adult healthy beagle dogs (n = 10; 3-6 years old; 7.2-13.1 kg) were studied. METHODS: Full-thickness skin wounds were created on the dorsum of healthy beagles, and allogenic MSCs were injected intradermally. The rate of wound closure and the degree of collagen production were analysed histologically using haematoxylin and eosin staining and trichrome staining. The degree of cellular proliferation and angiogenesis was evaluated by immunocytochemistry using proliferating cell nuclear antigen-, vimentin- and α-smooth muscle actin-specific antibodies. Local mRNA expression levels of interleukin-2, interferon-γ, basic fibroblast growth factor and matrix metalloproteinase-2 were evaluated by RT-PCR. RESULTS: Compared with the vehicle-treated wounds, MSC-treated wounds showed more rapid wound closure and increased collagen synthesis, cellular proliferation and angiogenesis. Moreover, MSC-treated wounds showed decreased expression of pro-inflammatory cytokines (interleukin-2 and interferon-γ) and wound healing-related factors (basic fibroblast growth factor and matrix metalloproteinase-2). CONCLUSION AND CLINICAL IMPORTANCE: Topical transplantation of MSCs results in paracrine effects on cellular proliferation and angiogenesis, as well as modulation of local mRNA expression of several factors related to cutaneous wound healing.

Assessment of dental abnormalities by full-mouth radiography in small breed dogs.

This study was performed to evaluate full-mouth radiographic findings to determine the prevalence of dental abnormalities and analyze the relationship between dental abnormalities and age in small breed dogs. Sixteen predetermined categories of abnormal radiographic findings were evaluated in 233 small breed dogs. In total, 9,786 possible permanent teeth could be evaluated. Of those, 8,308 teeth were evaluated and abnormal radiographic findings were found in 2,458 teeth (29.6%). The most common teeth with abnormal radiographic findings were the mandibular first molars (74.5% on the left and 63.9% on the right) and the maxillary fourth premolars (40.5% on the left and 38.2% on the right). Bone loss of any type (15.8%) was the most commonly detected radiographic abnormal finding among the 16 categories. Dental conditions with a genetic predisposition were frequently occurred in the mandibular premolar teeth. Shih tzu frequently had unerupted teeth and dentigerous cysts. Among the teeth with abnormal radiographic findings, 4.5%, 19.8%, and 5.3% were considered incidental, additional, and important, respectively. Findings that were only detected on radiographs, which were not noted on routine oral examination, were more common in older dogs. Full-mouth radiographic evaluation should be performed to obtain important information for making accurate diagnoses.

Case report: Villaret's syndrome caused by middle ear adenocarcinoma in a cat.

A 7-year-old castrated male American Shorthair cat presented with left-side Horner's syndrome and voice change. The overall clinical presentation included dysphagia, intermittent coughing, unilateral miosis, and third eyelid protrusion of the left eye. A topical 1% phenylephrine was applied, and miosis and protrusion of the third eyelid disappeared within 20 min which suggested a post-ganglionic lesion. Laryngoscopy showed left-sided laryngeal paralysis. Computed tomography (CT) identified a mass lesion invading outside of the left tympanic bulla with osteolysis. Endoscopically assisted ventral bulla osteotomy was performed for tumor resection and definitive diagnosis. Middle ear adenocarcinoma was diagnosed based on histopathology. It appears that these neurological signs occurred due to adenocarcinoma in the tympanic bulla, penetrating the jugular foramen and the hypoglossal canal and damaging the cranial nerve IX (glossopharyngeal nerve), X (vagus nerve), XI (accessory nerve), and XII (hypoglossal nerve) and the sympathetic nerve. To the best of our knowledge, this is the first case report of Villaret's syndrome associated with middle ear adenocarcinoma affecting the nerves passing through the jugular foramen and hypoglossal canal in cats.

Case report: A novel occurrence of persistent left cranial vena cava coexisting with polycystic kidney disease in a cat.

A 7-year-old castrated male Munchkin cat was presented with anorexia. This cat had been diagnosed with chronic kidney disease due to polycystic kidney disease. Tachycardia with a systolic murmur (grade III/VI) was auscultated and for further diagnosis, echocardiography was performed. Based on echocardiography, persistent left cranial vena cava (PLCVC) was suspected due to enlargement of the coronary sinus and confirmed by saline contrast echocardiography. The dilated coronary sinus compressed the left atrium, and left ventricular hypertrophy with the systolic anterior motion of the mitral valve, aortic regurgitation, and mitral regurgitation were identified. After medical management using atenolol, left atrial function and other hemodynamics of the heart were improved, including the disappearance of regurgitation and normalization of left ventricular wall thickness. This case report describes the echocardiographic characteristics, diagnostic procedures, and disease progression in a cat with PLCVC after medical management using atenolol. Additionally, this is the first report of a cat with PLCVC, coexisting with polycystic kidney disease.

Case report: Ghost cell odontogenic carcinoma in a dog: diagnostics and surgical outcome.

A 6 year-old spayed female Poodle presented with a mandibular mass. Radiographic examination revealed osteolysis from the right mandibular canine to the fourth premolar, along with horizontal bone loss and dorsal displacement of the right mandibular first and second premolars. Skull cone beam computed tomography revealed osteolysis at the level of the right mandibular canine and fourth premolar. A destructive bone lesion was observed in the apical area of the right mandibular canine, with mass invasion of the interradicular bone of the right mandibular first molar near the mandibular canal. Consequently, unilateral total mandibulectomy and skin flap surgery were performed. Histopathological examination revealed poorly demarcated and infiltrative neoplastic epithelial cells that formed small islands and trabeculae. Neoplastic cells exhibited the malignant features of cytological atypia and high mitotic activity. Furthermore, the neoplastic epithelial cells frequently showed ghost cell changes and were diagnosed as ghost cell odontogenic carcinoma (GCOC). The dog was followed up for 1 year, during which no severe complications or local recurrence was observed, except for slight mandibular drift, tongue protrusion, and drooling. This case report describes the clinical features, diagnostic imaging, and histologic features of an unreported GCOC in a dog and the favorable outcome following surgical resection.

Successful Surgical Outcome of Feline Inductive Odontogenic Tumor in Three Cats.

BACKGROUND/AIM: A feline inductive odontogenic tumor (FIOT) is a rare type of tumor that is unique to young cats. CASE REPORT: Herein, we report on three cats (aged 6 months to 2.5 years) that had a bulging mass on the maxilla. On diagnostic imaging, cases 1 and 3 had bone expansion in the affected area, and all three cats were diagnosed with FIOT by histological examination. Maxillectomy and/or incisivectomy techniques were performed according to the tumor site with an intended surgical margin of 5 mm. To increase both precision and safety, a piezoelectric surgical instrument was used. The local advancement flaps were used to repair the surgical sites. The surgical outcomes were excellent, and there were no major complications related to the surgery or tumor recurrences during long-term follow-up (3-5 years) for any of the cats. CONCLUSION: The results from this study were excellent, which may have been due in part to the choice of the surgical instrument that allowed for the implementation of precise and accurate surgical excision and the tension-free flap method for preventing dehiscence of the surgical site.

Ectopic thyroid carcinoma infiltrating the right atrium of the heart in a dog.

A 12-year-old intact female shih tzu dog was diagnosed with an ectopic thyroid carcinoma infiltrating the right atrium of the heart. Echocardiography and computed tomography were helpful in diagnosis; a definitive diagnosis was made based on postmortem histopathology and immunohistochemistry. The patient lived 428 days beyond diagnosis with only medical management.

Application of carvedilol in a dog with pseudoephedrine toxicosis-induced tachycardia.

A 15-year-old Yorkshire terrier dog was presented after ingesting 1 capsule of an over-the-counter cold medication containing pseudoephedrine (120 mg/capsule) and cetirizine (5 mg/capsule). Treatment was initiated with acepromazine and carvedilol. The dog responded well to treatment. This is the first known case report using carvedilol to control pseudoephedrine toxicosis.

Putative peanut allergy-induced urticaria in a dog.

A 9-year-old, spayed male schnauzer dog was presented with vomiting, diarrhea, generalized erythema, pruritic urticaria and conjunctival hyperemia after ingestion of peanut. The history, clinical signs, and histopathology of the lesions were compatible with a hypersensitivity reaction. The clinical signs resolved rapidly after treatment with prednisolone and antihistamine. This is the first report of urticaria caused by peanut ingestion in a dog.

Urticaire putative induite par une allergie aux arachides chez un chien. Un chien mâle Schnauzer stérilisé âgé de 9 ans est présenté avec des vomissements, de la diarrhée, un érythème généralisé, de l'urticaire pruritique et une hyperémie conjonctivale après l'ingestion d'arachides. L'anamnèse, les signes cliniques et l'histopathologie des lésions sont compatibles avec une réaction d'hypersensibilité. Les signes cliniques se sont résorbés rapidement après le traitement avec de la prednisolone et des antihistaminiques. Il s'agit du premier rapport d'urticaire causé par l'ingestion d'arachides chez un chien.(Traduit par Isabelle Vallières).

Clinical and magnetic resonance imaging (MRI) findings of idiopathic aplastic pancytopenia in a dog treated with cyclosporine and azathioprine.

A dog was referred for pancytopenia. Bone marrow biopsy showed hypocellular fatty marrow. Magnetic resonance imaging had a high signal on T1-weighted image in the metaphyseal region of the femur. We suggest that MRI could be a valuable supportive diagnostic method and introduce a strategy of treatment with cyclosporine and azathioprine in canine aplastic pancytopenia.