Renal candidiasis associated with papillary necrosis in a captive tiger (Panthera tigris).

A 14-year-old male tiger developed anorexia with elevated blood urea nitrogen and creatinine levels. The patient had a palpable abdominal mass and demonstrated neutrophilic leukocytosis and anaemia. Leukocytes, yeast and bacteria were present in the urine. The animal was non-responsive to therapy and was subsequently euthanised. Extensive acute renal papillary necrosis (RPN) with pyelonephritis, chronic nephritis and polycystic renal disease were evident during gross and microscopic pathology examinations. The histologic occurrence of fungal spores and pseudohyphae morphologically consistent with Candida species were observed within the necrotic papillary regions of the kidney and within multiple foci of mild parakeratotic hyperkeratosis present in the gingiva and tongue. Candida albicans along with a slight growth of Escherichia coli were recovered from kidney cultures. Possible contributory factors for the renal candidiasis and associated RPN include predisposing oral candidiasis, polycystic renal disease, ischaemic nephrosclerosis, age-associated or other forms of immunodeficiency and therapy with meloxicam, a non-steroidal anti-inflammatory drug. The absence of apparent lower urinary tract involvement coupled with the presence of intravascular renal 'Candida emboli' suggest that chronic oral candidiasis was the probable source of the kidney infection.

Depletion of JunB increases adipocyte thermogenic capacity and ameliorates diet-induced insulin resistance.

The coexistence of brown adipocytes with low and high thermogenic activity is a fundamental feature of brown adipose tissue heterogeneity and plasticity. However, the mechanisms that govern thermogenic adipocyte heterogeneity and its significance in obesity and metabolic disease remain poorly understood. Here we show that in male mice, a population of transcription factor jun-B (JunB)-enriched (JunB+) adipocytes within the brown adipose tissue exhibits lower thermogenic capacity compared to high-thermogenic adipocytes. The JunB+ adipocyte population expands in obesity. Depletion of JunB in adipocytes increases the fraction of adipocytes exhibiting high thermogenic capacity, leading to enhanced basal and cold-induced energy expenditure and protection against diet-induced obesity and insulin resistance. Mechanistically, JunB antagonizes the stimulatory effects of PPARγ coactivator-1α on high-thermogenic adipocyte formation by directly binding to the promoter of oestrogen-related receptor alpha, a PPARγ coactivator-1α downstream effector. Taken together, our study uncovers that JunB shapes thermogenic adipocyte heterogeneity, serving a critical role in maintaining systemic metabolic health.

Preoperative CT imaging as a tool to predict incisional hernia outcomes following abdominal wall reconstruction: A retrospective cohort analysis.

INTRODUCTION: Ventral wall hernia often causes significant morbidity and requires complex abdominal wall reconstruction (AWR). This study aims to determine whether subcutaneous abdominal fat thickness (AFT) measured with preoperative CT scans could predict postoperative outcomes in patients undergoing AWR. METHODS: A retrospective cohort study was conducted on all patients who underwent AWR at our institution between 2009 and 2021, with a minimum follow-up of 12 months. Using preoperative CT scans, AFT was measured at the xiphoid process, umbilicus, and pubic tubercle, as well as the hernia dimensions. Demographic, operative, and surgical outcome data were also collected and analyzed using statistical tests. RESULTS: The results showed that 9 of 101 patients (8.9%) experienced hernia recurrence. Smoking was associated with an increased risk of hernia recurrence (p < 0.001) with a predictive odds ratio (OR) of 18.27 (p = 0.041). Increased AFT at the xiphoid (p = 0.005), umbilicus (p < 0.001), and pubic tubercle (p < 0.001) were also associated with hernia recurrence and risk of infection. Only AFT at the pubic tubercle reached significance in the regression model predicting recurrence (OR=1.10; p = 0.030) and infection (OR=1.04; p = 0.021). A cut-off value of 67 mm was associated with a positive predictive value of 42.14% (sensitivity of 67% and specificity of 91%). Hernia defect area was not associated with risk of recurrence or infection. CONCLUSIONS: Smoking and increased AFT at the pubic tubercle are significant predictive factors for recurrence and infection in patients undergoing AWR, and preoperative optimization should focus on reducing these factors.

Gender parity in high impact neurology journals.

Background: Although female representation has been growing among physicians, women continue to be underrepresented in neurology, particularly regarding academic research in authorship and leadership. Analyzing recent trends in high-impact neurology journals highlights the underrepresentation of women and helps explore barriers to female representation in academic neurology. Methods and results: Journal Citation Reports (JCR) for 2021 was used to screen neurology journals for selection. The first 15 journals with the highest impact factors (JIF) were included. 15,404 total articles in neurology were examined for gender distribution of editorial staff and authorship with the highest total citations from January 1st, 2018 to October 31st, 2021. Gender was classified using biographical information from public and personal media sources. Genderize.io was used in cases of ambiguity, predicting gender at probability of ≥95%. Our data demonstrated that these journals only had 13% female editor-in-chiefs and 35% female editorial staff. The data further demonstrated that females accounted for 39% of first authors and 26% for last authors. During the four years examined males continued to account for the vast majority of both first and last authors for publications accepted and journal editorial staff members. Conclusion: Women are significantly under-represented in the field of neurological research in leadership positions as editor-in-chiefs, editorial board members as well as first or senior authors in top neurology medical journals. With continued underrepresentation of women occupying leading publishing roles, parity with men is still a work in progress. Additional work is needed to identify and address barriers to academic advancement for women physicians in academic neurology.

Histomorphometric lung density evaluation of Immulina treatment using a murine influenza pneumonia model.

Histomorphometric lung density measurements were used to evaluate the effects of Immulina on mouse pneumonia. Mice were intra-nasally exposed to H1N1 influenza virus at a dose of 5 × 104 PFU/50 µL/mouse. Lung density was measured using the NIH ImageJ software program. Density values were compared to semiquantitative pneumonia severity scores. Lung photomicrographs were evaluated at 25-×, 40-× and 400-× magnification. The study included viral inoculated controls (IC) and non-inoculated controls (NC) and mice either treated or not treated with Immulina. Three doses of Immulina were included (25, 50 or 100 mg/kg) and administered using 3 protocols: prophylactic treatment (P), prodromal treatment (PD) and therapeutic treatment (TH) (note that in most of the evaluations of the data for the three treatment protocols were combined). Groups of mice were evaluated on days 3, 5, 7, 10 and 15 following exposure. The occurrence of "digital pneumonia" (DP) was defined as a density measurement above the 95% confidence limit of the corresponding NC values. A significant reduction in the occurrence of DP with Immulina treatment at the higher doses compared to IC was seen as early as day 3 and persisted up to day 15. There were also statistically significant dose-variable reductions in lung density in response to Immulina. The study suggests early administration of Immulina (P or PD protocols) may enhance resistance against influenza-induced viral pneumonia. A moderate correlation between pneumonia severity scores and lung density was observed for the 25-× and 40-× images (R = 0.56 and 0.53 respectively), and a strong correlation (R = 0.68) for 400-× images.

Using Artificial Intelligence in Predicting Ischemic Stroke Events After Percutaneous Coronary Intervention.

BACKGROUND: Ischemic stroke (IS) is an uncommon but severe complication in patients undergoing percutaneous coronary intervention (PCI). Despite significant morbidity and economic cost associated with post PCI IS, a validated risk prediction model is not currently available. AIMS: We aim to develop a machine learning model that predicts IS after PCI. METHODS: We analyzed data from Mayo Clinic CathPCI registry from 2003 to 2018. Baseline clinical and demographic data, electrocardiography (ECG), intra/post-procedural data, and echocardiographic variables were abstracted. A random forest (RF) machine learning model and a logistic regression (LR) model were developed. The receiver operator characteristic (ROC) analysis was used to assess model performance in predicting IS at 6-month, 1-, 2-, and 5-years post-PCI. RESULTS: A total of 17,356 patients were included in the final analysis. The mean age of this cohort was 66.9 ± 12.5 years, and 70.7% were male. Post-PCI IS was noted in 109 patients (.6%) at 6 months, 132 patients (.8%) at 1 year, 175 patients (1%) at 2 years, and 264 patients (1.5%) at 5 years. The area under the curve of the RF model was superior to the LR model in predicting ischemic stroke at 6 months, 1-, 2-, and 5-years. Periprocedural stroke was the strongest predictor of IS post discharge. CONCLUSIONS: The RF model accurately predicts short- and long-term risk of IS and outperforms logistic regression analysis in patients undergoing PCI. Patients with periprocedural stroke may benefit from aggressive management to reduce the future risk of IS.

Cerebral venous sinus thrombosis associated with SRA-negative heparin-induced thrombocytopenia: case report.

BACKGROUND: There are very few documented reports in literature of cerebral venous sinus thrombosis (CVST) caused by immune-mediated heparin-induced thrombocytopenia (HIT). Further, there are very few reports of false negative serotonin release assays (SRAs) when testing for immune-mediated HIT. CASE PRESENTATION: We present a case of a 60- year-old male with recent unfractionated heparin administration for venous thromboembolism prophylaxis, an elevated 4T score of 5 and acute CVST in which immune-mediated HIT was suspected. The enzyme-linked immunosorbent assay (ELISA) screening assay was positive for PF4 antibodies and subsequent reflexive SRA testing was negative. However, given the clinical picture, a false-negative SRA was suspected (and eventually confirmed), prompting use of the alternative PF4-dependent p-selectin expression assay (PEA) which was confirmed to be positive. The patient was successfully managed with a bivalirudin infusion and eventually transitioned to apixaban. CONCLUSION: It is uncommon for immune-mediated HIT with thrombosis to manifest as CVST. Similarly, false-negative SRA is uncommon in immune-mediated HIT. Take-away lessons from our case report include considering HIT in CVST patients with an elevated 4T score and considering the entire clinical picture and degree of suspicion for HIT when interpreting negative HIT testing results. The PEA, in conjunction with the 4Ts score, may be considered as an alternate diagnostic assay for HIT.

Histopathologic Lesion Scoring and Histomorphometric Methods for Measuring Vaccine Reactions in the Trachea of Broiler Chickens.

Severity of the tracheal histologic inflammatory response induced in broilers by ocular inoculation of two infectious bronchitis (IBV) and three Newcastle disease virus (NDV) commercial vaccines were evaluated. The vaccine was delivered by eye drop with a coarse spray to day-old chicks. The vaccines were given individually or in various combinations and were evaluated relative to nonvaccinated controls. Evaluations were performed on postvaccination (PV) days 7 and 14. Histologic endpoints included semiquantitative severity scoring of inflammatory components and quantitative morphometric determinations of inflammatory cell concentration, mucosal thickness, and percentage of ciliated mucosal surface. Strong positive correlations were observed between routine severity scoring and morphometric inflammatory parameters, whereas a negative correlation was present between inflammation severity and the percentage of mucosal ciliation. Variable, sometimes extensive, and often statistically significant differences in inflammatory responses were observed between the various vaccines. One IBV Massachusetts strain vaccine (IBV-A) produced the greatest overall inflammatory response when given alone or in combination with the NDV vaccines. Enhancement of tracheitis was seen on PV day 14 by covaccination of IBV-A with the NDV vaccines, but not by covaccination of another IBV Massachusetts strain vaccine (IBV-B) with NDV. Reduction in cilia percentage was observed for all vaccine groups relative to controls on PV day 7. However, although reactive cilia regeneration occurred on PV day 14 for most vaccine groups, a cilia regenerative response was not apparent for individual or NDV combination vaccination for IBV-A. The study also demonstrates that substantial microscopic trachea pathology may be present in vaccinated birds not exhibiting apparent clinical respiratory signs.

Artículo regular­Métodos de calificación de lesiones histológicas e histomorfométricos para medir las reacciones a las vacunas en la tráquea de pollos de engorde. Se evaluó la gravedad de la respuesta inflamatoria histológica traqueal en pollos de engorde inducida mediante la inoculación ocular de dos vacunas comerciales contra la bronquitis infecciosa (IBV) y tres vacunas del virus de la enfermedad de Newcastle (NDV). Las vacunas se administraron mediante aplicación ocular a pollitos de un día de edad. Las vacunas se administraron individualmente o en varias combinaciones y se evaluaron en relación con los controles no vacunados. Las evaluaciones se realizaron en los días 7 y 14 después de la vacunación (PV). Los criterios de valoración histológicos incluyeron puntuación semicuantitativa de la severidad de los componentes inflamatorios y determinaciones morfométricas cuantitativas de la concentración de células inflamatorias, el grosor de la mucosa y el porcentaje de superficie de la mucosa con cilios. Se observaron fuertes correlaciones positivas entre la puntuación rutinaria de severidad y los parámetros morfométricos inflamatorios, mientras que se observó una correlación negativa entre la severidad de la inflamación y el porcentaje de la superficie con cilios en la mucosa. Se observaron diferencias variables, a veces extensas y a menudo estadísticamente significativas en las respuestas inflamatorias entre las diversas vacunas. Una vacuna de la cepa de Massachusetts del virus de la bronquitis infecciosa (IBV-A) produjo la mayor respuesta inflamatoria general cuando se administró sola o en combinación con las vacunas de Newcastle. Se observó un aumento de la traqueítis en el día 14 después de la vacunación mediante la vacunación simultánea de la vacuna de bronquitis infecciosa A con las vacunas de Newcastle, pero no mediante la vacunación simultánea de la otra vacuna de la cepa Massachusetts (IBV-B) con Newcastle. Se observó una reducción en el porcentaje de los cilios para todos los grupos vacunados en comparación con los controles en el día siete después de la vacunación. Sin embargo, aunque la regeneración de cilios reactivos ocurrió en el día 14 después de la vacunación para la mayoría de los grupos vacunados, no fue evidente una respuesta de regeneración de cilios para la vacunación individual o combinada de Newcastle con la vacuna de bronquitis infecciosa Massachusetts A. El estudio también demuestra que puede estar presente una patología microscópica sustancial de la tráquea en aves vacunadas que no presentan signos respiratorios clínicos aparentes.

Incision planning in complex abdominal wall reconstruction.

BACKGROUND: Complex abdominal wall reconstruction (CAWR) has evolved dramatically over the last 10 years and has become a speciality in its own right. Usually surgery is carried out by a General Surgeon, sometimes alone and sometimes in combination with a Plastic Surgeon. Patients frequently have multiple incisions over the abdomen, soft tissue excess and skin redundancy and planning the incisions to allow for a comprehensive abdominal wall reconstruction can be a challenge.In order to help simplify incision planning we examined our personal series of 150 cases to formulate a classification system for the incision and provide a simple algorithm. METHODS: Over an 8 year period from 2007 to 2015, 150 patients underwent complex abdominal wall reconstruction, patient demographics, outcome and complications were recorded. Preoperative photographs of the planned incisions were reviewed by the senior author and classified into 4 groups. RESULTS: All patients fell into one of four groups. Type 1, using existing incisions (28%). Type 2, using an abdominoplasty approach (26%). Type 3, a fleur-de-lys approach (43%). Type 4, a free style group where the incisions are so complex that the above three categories are not suitable (3%). CONCLUSION: Soft tissue management in CAWR can be challenging with the primary objective to achieve uncomplicated primary wound healing while optimising the aesthetic outcome. We present a simple classification system and associated algorithm, which can help surgical planning and identify cases that may benefit from a joint procedure with a Plastic Surgeon.

Artificial Intelligence Trumps TAVI2-SCORE and CoreValve Score in Predicting 1-Year Mortality Post-Transcatheter Aortic Valve Replacement.

BACKGROUND/PURPOSE: Machine learning has been used to predict procedural risk in patients undergoing various medical interventions and procedures. One-year mortality in patients after Transcatheter Aortic Valve Replacement (TAVR) has a wide range (from 8.5 to 24% in various studies). We sought to apply machine learning to determine predictors of one year mortality in patients undergoing TAVR. METHODS/MATERIALS: A retrospective study of 1055 patients who underwent TAVR (Jan 2014-June 2017) with one-year follow up was completed. Baseline demographics, clinical, electrocardiography (ECG), Computed Tomography (CT) and echocardiography data were abstracted. Variables with near zero variance or ≥50% missing data were excluded. The Gradient Boosting Machine learning (GBM) prediction model included 163 variables and was optimized using 5-fold cross-validation repeated 10-times. The receiver operator characteristic (ROC) for the GBM model was calculated to predict one-year mortality post TAVR, and then compared to the TAVI2-SCORE and CoreValve score. RESULTS: Among 1055 TAVR patients (mean age 80.9 ± 7.9 years, 42% female), 14.02% died at one year. 78% had balloon expandable valves placed. Based on GBM, the ten most predictive variables for one-year survival were cardiac power index, hemoglobin, systolic blood pressure, INR, diastolic blood pressure, body mass index, valve calcium score, serum creatinine, aortic annulus area, and albumin. The area under ROC to predict survival for the GBM model vs TAVI2-SCORE and CoreValve Score was 0.72 (95% CI 0.68-0.78) vs 0.56 (95%CI 0.51-0.62) and 0.53 (95% CI 0.47-0.59) respectively with p < 0.0001. CONCLUSION: The GBM model outperforms TAVI2-SCORE and CoreValve Score in predicting mortality one-year post TAVR.

Principals navigating discipline decisions for social justice: An informed grounded theory study.

PURPOSE: School leaders are charged with making equitable decisions almost daily, but little about this process is known. Due to research suggesting principal implicit bias, or the stereotypes and attitudes held by individuals unconsciously that may or may not reflect actual preferences, may contribute to discipline gaps, the present study aimed to better understand how principals make discipline decisions and how implicit bias might interfere in these decisions. RESEARCH METHODS: This qualitative study used in-depth interviews and document analysis with six mid-Atlantic principals to explore their discipline decision-making processes. Constant comparative analysis inclusive of explicit coding and analytical procedures supported the development of an informed grounded theory. FINDINGS: The data revealed a four-part recursive process of discipline decision-making inclusive of four themes relevant to equity. Principals used communication and data to gather information in a first step driven by relationships, reflected on considerations and policy to develop options in a second step driven by flexibility, selected an outcome in a third step driven by morality, and evaluated their efficacy in the recursive loop driven by experience. IMPLICATIONS FOR RESEARCH AND PRACTICE: The findings allow for targeted research of the discipline decision-making process and potential consideration of practical interventions and curricular design for principal preparation programs that would allow for greater equity in discipline following office referrals.

Development of advanced conduction disturbances following balloon-expandable transcatheter aortic valve replacement leads to poorer clinical outcomes.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a reliable method of treating patients with severe aortic stenosis, but is associated with postprocedure conduction defects. OBJECTIVE: The purpose of this study was to compare clinical outcomes in patients who developed advanced conduction defects post-TAVR to those who did not. METHODS: We conducted a retrospective chart review of 243 patients who underwent balloon-expandable TAVR with the Edwards Sapien valve to determine the incidence of advanced conduction defects in our cohort. We compared clinical outcomes including overall mortality, improvement in symptomatology, and improvement in left ventricular ejection fraction. RESULTS: Among the 243 patients included in the study, 9.1% (22/243) required permanent pacemaker (PPM); 19.8% (48/243) developed left bundle branch block (LBBB), and 71.2% (173/243) did not develop any permanent advanced conduction defects. Overall 1-year mortality was similar across all three groups. There was significant improvement in New York Heart Association functional capacity of all groups post-TAVR, but this was much less in the PPM group (45.5% vs 68.8%, P = .04). Postprocedure from TAVR, patients with LBBB or PM were less likely to have improvement in their ejection fraction (net loss of -0.7% for LBBB and -5.7% for PPM compared to a net gain of 2.3% for no-LBBB/PM (P = .02). CONCLUSION: Patients who develop LBBB or require PM post-TAVR with Edwards Sapien valves are less likely to improve New York Heart Association functional capacity and more likely to have no improvement or deterioration of their pre-TAVR left ventricular ejection fraction.

A Field Study of Histologic and Bacteriologic Characterization of Femoral Head Separation and Femoral Head Necrosis.

Histologic and bacteriologic features for groups of average 31-day-old broilers displaying three gross categories of femoral head alterations were documented. Categories included simple femoral head separation (FHS), femoral head transitional changes (FHT), and femoral head necrosis (FHN). Groups with grossly normal (NORM) femoral heads and cull birds with FHN and having gross signs of sepsis (Cull-FHN) were also included in the study. There was a 10% occurrence of positive bacterial cultures for all birds tested. Most positive cultures (33%) were found in the Cull-FHN group, while only a 12% occurrence was seen in the FHS group, and no positives were present in the FHT or FHN groups. A 14% total occurrence of femoral bacterial chondronecrosis with osteomyelitis or simple osteomyelitis (BCO-O) was observed. A progressive increase in the prevalence of BCO-O was apparent between groups going from NORM (0%), FHS (4%), FHT (14%), FHN (13%), and reaching a maximum of 67% in the Cull-FHN group. Minimal to mild femoral head cartilage necrosis was present in 40% of NORM broilers and 100% of the FHS, FHT, and FHN groups, but at moderate severity in 20% of the Cull-FHN group. Thus, the majority of FHN cases were associated with aseptic cartilage necrosis rather than BCO-O. These findings suggest that aseptic cartilage necrosis may be as important as septic necrosis as a cause of gross femoral head disease. A 26% overall occurrence was seen for hip synovitis-arthritis, but group differences were not statistically significant. Synovitis was not seen in the NORM group and was present in some (12%) of the FHS group but was observed at a high rate in both the FHN (43%) and the Cull-FHN (50%) groups. Morphometric measurements demonstrated that the area size of femoral fibrous cortical defects or "cutback zones" were generally larger for all gross categories relative to NORM, with a significant difference between NORM and FHS groups. This study underscores the multifactorial etiology of FHN and the importance of conducting both histologic and bacteriologic evaluations in which gross evidence of FHN or BCO-O occurs.

Conformal Radiation Therapy for Pediatric Ependymoma, Chemotherapy for Incompletely Resected Ependymoma, and Observation for Completely Resected, Supratentorial Ependymoma.

PURPOSE: The Children's Oncology Group trial ACNS0121 estimated event-free survival (EFS) and overall survival for children with intracranial ependymoma treated with surgery, radiation therapy, and-selectively-with chemotherapy. Treatment was administered according to tumor location, histologic grade, and extent of resection. The impacts of histologic grade, focal copy number gain on chromosome 1q, and DNA methylation profiles were studied for those undergoing surgery and immediate postoperative conformal radiation therapy (CRT). METHODS: ACNS0121 included 356 newly diagnosed patients (ages 1 to 21 years). Patients with classic supratentorial ependymoma were observed after gross total resection (GTR). Those undergoing subtotal resection received chemotherapy, second surgery, and CRT. The remaining patients received immediate postoperative CRT after near-total resection or GTR. CRT was administered with a 1.0-cm clinical target volume margin. The cumulative total dose was 59.4 Gy, except for patients who underwent GTR and were younger than age 18 months (who received 54 Gy). Patients were enrolled between October 2003 and September 2007 and were observed for 5 years. Supratentorial tumors were evaluated for RELA fusion; infratentorial tumors, for chromosome 1q gain. Classification of posterior fossa groups A and B was made by methylation profiles. RESULTS: The 5-year EFS rates were 61.4% (95% CI, 34.5% to 89.6%), 37.2% (95% CI, 24.8% to 49.6%), and 68.5% (95% CI, 62.8% to 74.2%) for observation, subtotal resection, and near-total resection/GTR groups given immediate postoperative CRT, respectively. The 5-year EFS rates differed significantly by tumor grade (P = .0044) but not by age, location, RELA fusion status, or posterior fossa A/posterior fossa B grouping. EFS was higher for patients with infratentorial tumors without 1q gain than with 1q gain (82.8% [95% CI, 74.4% to 91.2%] v 47.4% [95% CI, 26.0% to 68.8%]; P = .0013). CONCLUSION: The EFS for patients with ependymoma younger than 3 years of age who received immediate postoperative CRT and for older patients is similar. Irradiation should remain the mainstay of care for most subtypes.

Disarticulation-Associated Femoral Head Separation in Clinically Normal Broilers: Histologic Documentation of Underlying and Predisposing Cartilage Abnormalities.

Routine and quantitative histologic studies on femoral head separation (FHS) associated with coxofemoral joint disarticulation at necropsy were conducted on 125 femoral heads collected from 21- to 50-day-old clinically normal broilers. The study compared groups demonstrating grossly detached femoral heads (DFHs) with those having attached femoral heads (AFHs). Marked microscopic lesions compatible with osteochondrosis (OCD) consistently occurred along the separation surface in the DFH population. The histologic changes consisted of cartilage degeneration and necrosis sometimes forming small clefts or microfractures. Hemorrhage and less frequent inflammatory cells were often present along the separation surfaces. Small foci of OCD in the femur occurred in the AFH group with lesser frequency and severity. The histologic changes were mainly found within the proximal proliferative zone of the physis near the epiphyseal junction. Histomorphometry disclosed significant quantitative reductions in chondrocyte density with increased pyknosis occurring adjacent to the separation site and to a lesser extent in deeper regions of the growth plate for the DFH compared with AFH. Measurements made along the separation surface of the percentage length occupied by osteochondrotic defects and actual separated cartilage disclosed significant differences between evaluation groups. However, determinations of vascular canal areas present within two or more regions of the growth plate revealed a slight and significant increased area for DFH compared with AFH. Severity scores for the occurrence of microthrombi within the growth plate showed no difference between the groups. The pathogenesis of FHS in broilers is related to defective cartilage production or degeneration resulting in increased fragility. This contrasts with the proposed pathogenesis of OCD in mammals, which involves ischemic necrosis due to underlying vascular defects. The results for the FHS-disarticulation model also differ from those reported for glucorticoid-induced femoral head necrosis in broilers. The FHS-associated lesions occurred without histologic evidence of bacterial chondritis or osteomyelitis.

Separación de la cabeza femoral asociada a la desarticulación en pollos de engorde clínicamente normales: documentación histológica de anomalías del cartílago subyacentes y predisponentes. Estudios histológicos de rutina y cuantitativos sobre la separación de la cabeza femoral (FHS) asociados con la desarticulación de la articulación coxofemoral durante la necropsia se realizaron en 125 cabezas femorales recolectadas de pollos de engorde clínicamente normales de 21 a 50 días de edad. El estudio comparó los grupos que demostraron cabezas femorales separadas (DFH) con los que tenían cabezas femorales unidas (AFH). Lesiones microscópicas marcadas compatibles con osteocondrosis (OCD) ocurrieron consistentemente a lo largo de la superficie de separación en la población de aves con cabezas femorales separadas. Los cambios histológicos consistieron en degeneración del cartílago y necrosis, formando a veces pequeñas hendiduras o microfracturas. La hemorragia y la presencia menos frecuente de células inflamatorias estaban presentes a lo largo de las superficies de separación. Se produjeron con menor frecuencia y gravedad, focos pequeños de osteocondrosis en el fémur en el grupo de aves con cabezas femorales unidas. Los cambios histológicos se encontraron principalmente en la zona proliferativa proximal de la fisis cerca de la unión epifisaria. La histomorfometría reveló reducciones cuantitativas significativas en la densidad de condrocitos con un aumento de la picnosis que ocurrió adyacente al sitio de separación y en menor medida en regiones más profundas de la placa de crecimiento en las aves con cabezas femorales separadas en comparación con las aves con cabezas femorales unidas. Las mediciones realizadas a lo largo de la superficie de separación del porcentaje de longitud ocupada por defectos osteocondróticos y con cartílago separado revelaron diferencias significativas entre los grupos de evaluación. Sin embargo, las determinaciones de las áreas del canal vascular presentes dentro de dos o más regiones de la placa de crecimiento revelaron un aumento leve y significativo del área para las aves con cabezas femorales separadas en comparación con las aves con cabezas femorales unidas. Las puntuaciones de severidad para la aparición de microtrombos dentro de la placa de crecimiento no mostraron diferencias entre los grupos. La patogenia de la separación de la cabeza femoral en pollos de engorde se relaciona con la producción o degeneración de cartílago defectuoso que resulta en un aumento de la fragilidad. Esto contrasta con la patogénesis propuesta para la osteocondrosis en mamíferos, que involucra necrosis isquémica debido a defectos vasculares subyacentes. Los resultados para el modelo de desarticulación-separación de la cabeza femoral también difieren de los reportados para la necrosis de la cabeza femoral inducida por glucorticoides en pollos de engorde. Las lesiones asociadas con la separación de la cabeza femoral ocurrieron sin evidencia histológica de condritis bacteriana u osteomielitis.

Reduced skeletal muscle phosphocreatine concentration in type 2 diabetic patients: a quantitative image-based phosphorus-31 MR spectroscopy study.

Mitochondrial function has been examined in insulin-resistant (IR) states including type 2 diabetes mellitus (T2DM). Previous studies using phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in T2DM reported results as relative concentrations of metabolite ratios, which could obscure differences in phosphocreatine ([PCr]) and adenosine triphosphate concentrations ([ATP]) between T2DM and normal glucose tolerance (NGT) individuals. We used an image-guided 31P-MRS method to quantitate [PCr], inorganic phosphate [Pi], phosphodiester [PDE], and [ATP] in vastus lateralis (VL) muscle in 11 T2DM and 14 NGT subjects. Subjects also received oral glucose tolerance test, euglycemic insulin clamp, 1H-MRS to measure intramyocellular lipids [IMCL], and VL muscle biopsy to evaluate mitochondrial density. T2DM subjects had lower absolute [PCr] and [ATP] than NGT subjects (PCr 28.6 ± 3.2 vs. 24.6 ± 2.4, P < 0.002, and ATP 7.18 ± 0.6 vs. 6.37 ± 1.1, P < 0.02) while [PDE] was higher, but not significantly. [PCr], obtained using the traditional ratio method, showed no significant difference between groups. [PCr] was negatively correlated with HbA1c ( r = -0.63, P < 0.01) and fasting plasma glucose ( r = -0.51, P = 0.01). [PDE] was negatively correlated with Matsuda index ( r = -0.43, P = 0.03) and M/I ( r = -0.46, P = 0.04), but was positively correlated with [IMCL] ( r = 0.64, P < 0.005), HbA1c, and FPG ( r = 0.60, P = 0.001). To summarize, using a modified, in vivo quantitative 31P-MRS method, skeletal muscle [PCr] and [ATP] are reduced in T2DM, while this difference was not observed with the traditional ratio method. The strong inverse correlation between [PCr] vs. HbA1c, FPG, and insulin sensitivity supports the concept that lower baseline skeletal muscle [PCr] is related to key determinants of glucose homeostasis.

Testicular histomorphometrics including Sertoli cell quantitation for evaluating hatchability and fertility issues in commercial breeder-broiler roosters.

Testicular histomorphometric methods were developed for the investigation of fertility and hatchability problems in commercial broiler-breeder roosters. Sertoli cell (SC) evaluations were emphasized in view of their role in influencing embryonic testicular organogenesis and spermatogenesis in adults. H&E stained sections prepared from formalized tissues were examined. SC evaluations were mostly made from computer generated images using image analysis software, but were also compared to direct counting with ocular grid reticle. Other measurements were germinal epithelial and total seminiferous tubule widths, quantification of individual spermatozoa and sperm clusters, and determinations of stromal area. Age-associated changes in SC occurred between 15 to 54 wk of age. A significant reduction in SC concentration occurred at 29 wk of age (P < 0.001) that corresponded with the histologic initiation of spermatogenesis. Expanded morphometric evaluations were performed on 59-week-old roosters comparing a flock having good body condition and footpad scores with normal testicular and body weights (optimal profile or OP group) to a second flock demonstrating relatively poor expression of these parameters and decreased fertility (sub-optimal profile or SOP group). Significant reductions (P < 0.05) in SC concentration, spermatozoa, and tubular widths, but an increased percentage of stroma area occurred in SOP compared to OP flocks. SC results also correlated well with testes weight. A unique finding was a significant relationship between decreasing SC concentration and increasing severity scores for footpad lesions. Differences in all histomorphometric parameters occurred between flocks demonstrating good hatchability compared to flocks exhibiting either low or decreasing hatchability. Significant reductions in SC and other morphometric parameters were observed for the poor relative to good hatchability group. A strong positive association was observed for SC results using computer generated images and direct reticle ocular counting (R = 0.80). Replicate counts on control sections demonstrated generally good reproducibility of methods between experiments. The findings are supportive of the value of testicular histomorphometrics for evaluations of hatchability issues in commercial roosters.

Morphometric Documentation of a High Prevalence of Left Ventricular Dilated Cardiomyopathy in Both Clinically Normal and Cyanotic Mature Commercial Broiler Breeder Roosters with Comparisons to Market-Age Broilers.

Previous studies documented the common occurrence of transitory cyanosis and echocardiographic aortic insufficiency in mature commercial broiler breeder roosters. During further investigations, we observed a high prevalence of hearts exhibiting extensive dilation of the left ventricle chamber compatible with dilated left ventricular cardiomyopathy present in both cyanotic and normal subpopulations. We conducted quantitative studies focused on documentation of cardiac ventricle parameters by using simple gross morphometric methods performed on formalin-fixed hearts obtained from both clinically normal roosters and those exhibiting variable transitory cyanosis, echocardiographic aortic insufficiency, or both. A high prevalence of often dramatic left ventricular dilation reflected in enlarged left ventricular chamber areas and elevated left ventricle-to-total ventricle area ratios was morphometrically documented. However, no statistically significant differences in the occurrence of ventricular abnormalities were observed between normal and cyanotic roosters. Age-associated changes were also demonstrated by comparative morphometric studies on hearts from normal market-age broilers (average age of 7 wk) and those of mature roosters (average age of 42 wk). Elevation in both left and right ventricular weight-to-total heart weight ratios dramatically increased with aging. In addition, values (average ± SD) for the left ventricle chamber area-to-total ventricle area ratios increased from 3.2 ± 2.0% in broilers up to 10.0 ± 8.8% in roosters. None of the normal broilers studied demonstrated left ventricular volume ratios above 10%, whereas 33% of the roosters had left ventricular volume ratios above 10%, including 13% with ratios of 20% or higher. However, the left ventricle wall area-to-body weight ratios were much closer for the two age groups (0.85 ± 0.18 cm(2)/kg in broilers and 0.79 ± 0.13 cm(2)/kg in roosters). Also, the standard right ventricle-to-total ventricle weight ratio (RV/TV) went from 0.18 ± 0.04 in broilers to 0.25 ± 0.12 in roosters, whereas the left ventricle-to-total ventricle weight ratios were similar for the two age groups (0.74 ± 0.12 and 0.75 ± 0.08 in broilers and roosters, respectively). Our results for RV/TV in normal broilers were similar to the reported values for normal market-age broilers. In contrast, 36% of the roosters had RV/TV above values reported for broilers considered reflective of right ventricular hypertrophy due to pulmonary hypertension, whereas 4% had values above the reported threshold for broilers dying with ascites (ratios greater than 0.0249 and 0.299, respectively). However, ascites was not observed for any of the roosters. Although essentially all cardiac morphometric parameters demonstrated statistically significant correlations with the age-class group comparisons, significance could not be documented for comparisons between cardiomorphometrics and the subjective occurrences of transitory cyanosis or echocardiographic aortic insufficiency.

Failed detection of Bovine viral diarrhea virus 2 subgenotype a (BVDV-2a) by direct fluorescent antibody test on tissue samples due to reduced reactivity of field isolates to raw anti-BVDV antibody.

Bovine viral diarrhea virus 1 (BVDV-1) is associated with mild or subclinical infections, whereas BVDV-2 is frequently implicated in outbreaks of severe thrombocytopenia and acute fatal disease. In the present study, the carcass of a beef breed cow and tissue samples of a beef calf were received for laboratory diagnosis. Both animals exhibited severe clinical signs compatible with thrombocytopenia or hemorrhagic syndrome. Direct fluorescent antibody test (DFAT) failed to detect BVDV antigen in the tissue specimens of both cases. However, immunohistochemistry (IHC) revealed the presence of BVDV antigen in oral and esophageal mucosa and Peyer patches of the beef breed cow. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) detected BVDV-2 in selected tissues of both animals. Subsequently, BVDV was isolated from both cases and subjected to genetic and serologic characterizations. Mutations in the 5'-untranslated genomic region (5'-UTR) primer and probe binding sites and the E2 gene were associated with reduced efficiency of an established real-time RT-PCR assay and amino acid alterations in the E2 glycoprotein, respectively. Both viral isolates were classified by real-time RT-PCR and phylogenetic analysis as BVDV-2 subgenotype a. Unlike BVDV reference strains Singer and 125c, the isolates cross-reacted with anti-BVDV-1 and anti-BVDV-2 reference sera, indicating antigenic variations in field isolates. The isolates also showed reduced reactivity to porcine anti-BVDV antiserum (the raw serum used to produce BVDV DFA conjugate). In summary, data from the present investigation indicated that genetic and antigenic variations affected the performance of detection assays, especially DFAT, highlighting the need for regular evaluation and modification of BVDV tests.