SIV Infection Is Associated with Transient Acute-Phase Steatosis in Hepatocytes In Vivo.

Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a major cause of morbidity and mortality in HIV-infected individuals, even those receiving optimal antiretroviral therapy. Here, we utilized the SIV rhesus macaque model and advanced laparoscopic techniques for longitudinal collection of liver tissue to elucidate the timing of pathologic changes. The livers of both SIV-infected (N = 9) and SIV-naïve uninfected (N = 8) macaques were biopsied and evaluated at four time points (weeks -4, 2, 6, and 16-20 post-infection) and at necropsy (week 32). SIV DNA within the macaques' livers varied by over 4 logs at necropsy, and liver SIV DNA significantly correlated with SIV RNA in the plasma throughout the study. Acute phase liver pathology (2 weeks post-infection) was characterized by evidence for fat accumulation (microvesicular steatosis), a transient elevation in both AST and cholesterol levels within the serum, and increased hepatic expression of the PPARA gene associated with cholesterol metabolism and beta oxidation. By contrast, the chronic phase of the SIV infection (32 weeks post-infection) was associated with sinusoidal dilatation, while steatosis resolved and concentrations of AST and cholesterol remained similar to those in uninfected macaques. These findings suggest differential liver pathologies associated with the acute and chronic phases of infection and the possibility that therapeutic interventions targeting metabolic function may benefit liver health in people newly diagnosed with HIV.

An Unusual Case of Extranodal Marginal Zone Lymphoma Mimicking Abdominal Cocoon Syndrome in an Adolescent Patient.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is an indolent non-Hodgkin lymphoma rarely seen in pediatric patients. MALT lymphoma most commonly involves the gastrointestinal tract or peri-orbital tissues, potentially as sequela of chronic antigenic stimulation or immune dysregulation. Rare cases of MALT lymphoma arising from the gynecologic tract have been reported in older adult patients. We present the unique case of a 16-year-old postpubescent female with MALT lymphoma localized to the gynecologic tract, who initially presented with abdominal fullness, abnormal uterine bleeding, and obstructive acute kidney injury secondary to urinary outflow obstruction. Intraoperatively, dense fibrosis of the uterus and left fallopian tube was noted which mimicked abdominal cocoon syndrome. She was treated with 6 cycles of bendamustine and rituximab with complete anatomic and metabolic remission. In this report we highlight a very unusual presentation of a rare malignancy in the pediatric population as well as unique treatment considerations given this patient's young age and tumor location.

Diabetes exacerbates inflammatory bowel disease in mice with diet-induced obesity.

BACKGROUND: The increased prevalence of inflammatory bowel disease (IBD) among patients with obesity and type 2 diabetes suggests a causal link between these diseases, potentially involving the effect of hyperglycemia to disrupt intestinal barrier integrity. AIM: To investigate whether the deleterious impact of diabetes on the intestinal barrier is associated with increased IBD severity in a murine model of colitis in mice with and without diet-induced obesity. METHODS: Mice were fed chow or a high-fat diet and subsequently received streptozotocin to induce diabetic-range hyperglycemia. Six weeks later, dextran sodium sulfate was given to induce colitis. In select experiments, a subset of diabetic mice was treated with the antidiabetic drug dapagliflozin prior to colitis onset. Endpoints included both clinical and histological measures of colitis activity as well as histochemical markers of colonic epithelial barrier integrity. RESULTS: In mice given a high-fat diet, but not chow-fed animals, diabetes was associated with significantly increased clinical colitis activity and histopathologic markers of disease severity. Diabetes was also associated with a decrease in key components that regulate colonic epithelial barrier integrity (colonic mucin layer content and epithelial tight junction proteins) in diet-induced obese mice. Each of these effects of diabetes in diet-induced obese mice was ameliorated by restoring normoglycemia. CONCLUSION: In obese mice, diabetes worsened clinical and pathologic outcomes of colitis via mechanisms that are reversible with treatment of hyperglycemia. Hyperglycemia-induced intestinal barrier dysfunction offers a plausible mechanism linking diabetes to increased colitis severity. These findings suggest that effective diabetes management may decrease the clinical severity of IBD.

Focal Nodular Hyperplasia in the Pediatric Population: A Multicenter Experience.

BACKGROUND: Focal nodular hyperplasia (FNH) is a benign liver lesion classically presenting in young females. In children, FNH is rare and its detailed clinicopathologic characteristics remain largely unknown. Furthermore, there are no studies comparing pediatric FNH features to those presenting in adults. METHODS: In this study, we analyzed a total of 47 FNH cases in pediatric patients (age range: 23 days to 18 years) from 3 centers and compared them to a cohort of 31 FNH cases in adult patients (age range: 20-64 years). RESULTS: Of the pediatric cases, 13 cases (28%) had a history of a prior malignancy of which 4 were treated with chemoradiation and stem cell transplantation (SCT), 5 with chemoradiation alone and 3 with chemotherapy and SCT. In the pediatric cases 41 (87%) had a central scar and 46 (98%) had fibrous septa. Both pediatric and adult FNH were more common in female patients. Cases in pediatric patients were also significantly associated with larger size (P = .047), absence of dystrophic vessels (P = .001), absence of sinusoidal dilatation (P = .029), pseudoacini formation (P = .013), and steatosis (P = .029). CONCLUSION: In our experience although most cases of pediatric FNH show the classic histologic features seen in adults, some significant differences exist, and awareness of these findings could aid in the evaluation of these rare cases.

Primary Ewing Sarcoma of the Testicle in an Adolescent Patient.

Extraosseous Ewing sarcoma with genitourinary tract involvement is rare. We present a case of primary Ewing sarcoma of the testis with review of the literature. While primary Ewing sarcoma of the testis is unusual, it is important to appropriately diagnose. This case emphasizes the benefits of prompt and appropriate evaluation, pathologic work-up, and treatment of testicular tumors.

Pediatric Hepatocellular Adenomas: The Influence of Age and Syndrome on Subtype.

Hepatocellular adenomas are rare in children. A large study focused on pediatric patients has not been undertaken. A natural language search was performed at 5 institutions for hepatocellular adenomas in patients younger than 21 years old. Clinical characteristics as well as immunohistochemical staining profile was reviewed and adenomas subtyped per standard classification. Patients were divided into prepubescent and postpubescent age group. Thirty-one patients were included. Eleven (35%) were male and 10 (32%) were prepubescent. Fifteen (54%) of 28 patients with known clinical histories had adenomas associated with a syndrome. The percentage of the different adenoma subtypes was: 16% ß-catenin activated, 10% combined inflammatory and ß-catenin activated, 29% HFN1α-inactivated, 35% inflammatory, and 10% unclassified subtype by immunohistochemical staining. Interestingly 53% of patients with syndromes were male, while 85% of patients in the nonsyndromic group were female. The total number of ß-catenin activated tumors was greater in the syndromic group (5/15, 33%) and prepubescent group (5/10, 50%) than in the nonsyndromic group (2/13, 16%) and postpubescent group (3/21, 14%), P=0.4 and 0.07, respectively. Inflammatory type adenoma was more frequent in the postpubescent (10/21, 48%) than in the prepubescent group (1/10, 10%), P=0.06, trending toward significance. Pediatric patients with hepatocellular adenomas frequently have syndromes, especially in the prepubescent group. In patients with syndromes a greater percentage of adenomas were ß-catenin activated. In patients without a known syndrome the distribution of hepatocellular adenoma subtypes appears similar to adults.

CD8+ T cells regulate liver injury in obesity-related nonalcoholic fatty liver disease.

Nonalcoholic steatohepatitis (NASH) has increased in Western countries due to the prevalence of obesity. Current interests are aimed at identifying the type and function of immune cells that infiltrate the liver and key factors responsible for mediating their recruitment and activation in NASH. We investigated the function and phenotype of CD8+ T cells under obese and nonobese NASH conditions. We found an elevation in CD8 staining in livers from obese human subjects with NASH and cirrhosis that positively correlated with α-smooth muscle actin, a marker of hepatic stellate cell (HSC) activation. CD8+ T cells were elevated 3.5-fold in the livers of obese and hyperlipidemic NASH mice compared with obese hepatic steatosis mice. Isolated hepatic CD8+ T cells from these mice expressed a cytotoxic IL-10-expressing phenotype, and depletion of CD8+ T cells led to significant reductions in hepatic inflammation, HSC activation, and macrophage accumulation. Furthermore, hepatic CD8+ T cells from obese and hyperlipidemic NASH mice activated HSCs in vitro and in vivo. Interestingly, in the lean NASH mouse model, depletion and knockdown of CD8+ T cells did not impact liver inflammation or HSC activation. We demonstrated that under obese/hyperlipidemia conditions, CD8+ T cell are key regulators of the progression of NASH, while under nonobese conditions they play a minimal role in driving the disease. Thus, therapies targeting CD8+ T cells may be a novel approach for treatment of obesity-associated NASH.NEW & NOTEWORTHY Our study demonstrates that CD8+ T cells are the primary hepatic T cell population, are elevated in obese models of NASH, and directly activate hepatic stellate cells. In contrast, we find CD8+ T cells from lean NASH models do not regulate NASH-associated inflammation or stellate cell activation. Thus, for the first time to our knowledge, we demonstrate that hepatic CD8+ T cells are key players in obesity-associated NASH.

Concordance between original screening and final diagnosis using imager vs. manual screen of cervical liquid-based cytology slides.

OBJECTIVE: To compare agreement of pathologists and cytotechnologists and technologist productivity before and after implementation of the Cytyc ThinPrep Imager. STUDY DESIGN: Using the Cytyc ThinPrep Imaging System, a retrospective analysis was conducted, from the first 6 months in 2004 and in 2005. Total cases in January through June were 79,791 in 2004 and 76,887 in 2005. Data on the number and type of changes from one impression to another were collected in a "confusion matrix". The chi2 test with 1 degree of freedom was used to calculate the significance of the difference between the groups. RESULTS: Changes in diagnosis were most frequently seen in negative for intraepithelial lesion, atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion. Interobserver agreement before the imager (weighted kappa) was 0.74 and after was 0.73. CONCLUSIONS: The number of high-grade lesions detected increased with the imager (p < 0.01). Technologist productivity increased by an average of 2.2 slides/hour.

Emergencia de las capacidades metalingüísticas / The emergence of metalinguistic abilities

The goal in this research was to explore the emergence of metalinguistic capability in three groups: normal, institutionalized and with intellectual lacks. All of their members are from three to four years old in linguistic age. Thirty-six children, 18 girls and 18 boys, participated and they were taken from five institutions, two regular education schools, two social welfare institutions and one special education institute. A story titled El pinguino Piti y la ballena (The penguin Piti and the whale), composed by fifteen scenes, was designed as a methodological device. A scriptguided conversational strategy was used to obtain metalinguistic verbal production in children; their verbal responses were registered and analyzed from videtaped conversations. Results showed that typical and institutionalized children groups have a better metalinguistic performance compared with intelligence handicapped children, despite having a similar linguistic age. Data analysis endorsed the narrow relationship between metalinguistic capability and a general cognitive domain. Concerning the methodological device, it was shown that it has some drawbacks to obtain evidence on children metalinguistic abilities although it promotes a wide linguistic production. In spite of obstacles created by the experimental situation used to get the analyzed corpus, there were found evidence on metalinguistic abilities emergence at the third year of linguistic age.

El propósito de esta investigación fue explorar la emergencia de las capacidades metalingüísticas en tres grupos de sujetos: típicos, institucionalizados y con deficiencia intelectual, con edad lingüística de tres a cuatro años. Participaron 36 sujetos, 18 niñas y 18 niños, seleccionados de cinco instituciones: dos de educación regular, dos de asistencia social y una de educación especial. Como estrategia metodológica se construyó la historia El pingüino Piti y la ballena conformada por quince escenas con imágenes. Se utilizó una estrategia conversacional, orientada por un guión previamente establecido para obtener producciones metalingüísticas por parte de los niños; los comportamientos verbales de los niños fueron registrados y analizados a partir de las conversaciones videograbadas. Los resultados mostraron que los sujetos típicos e institucionalizados tienen un mejor desempeño metalingüístico frente a los sujetos con deficiencia intelectual, a pesar de que estos últimos tienen una edad lingüística similar. El análisis de los datos confirma la estrecha relación entre la capacidad metalingüística y el dominio cognitivo general. En relación con la estrategia metodológica, se apreció que aunque promueve una verbalización amplia, ésta presenta algunas dificultades para obtener evidencia de las habilidades metalingüísticas de los niños. A pesar de las dificultades generadas por la situación empleada para obtener el corpus objeto de análisis, se encontraron evidencias sobre la emergencia de las habilidades metalingüísticas en el tercer año de edad lingüística.