Financial assistance and other financial coping strategies after a pediatric cancer diagnosis.

BACKGROUND: Families experience financial burden and household material hardship (HMH) after a pediatric cancer diagnosis. This study investigates types of financial assistance and other financial coping strategies (FCS) adopted by families during the first year after diagnosis. METHODS: Retrospective survey of caregivers of pediatric patients diagnosed with cancer from 2015 to 2019. The survey collected data on demographics, diagnosis, income, HMH, and private, hospital, and government assistance received and other FCS adopted after diagnosis. Bivariate and multivariable logistic regressions were used to analyze FCS by income. Subgroup analysis of families experiencing HMH was used to identify predictors of receiving government assistance. RESULTS: Of 156 respondents, 52% were low-to-middle income, 29% had public insurance, and 22% had non-English language preference. Low-to-middle-income families were more likely to incur debt (odds ratio [OR] 6.24, p < .001) and reduce consumption (OR 2.16, p = .03) than high-income families, and this association persisted in multivariable analysis. Among families with housing, food, and energy insecurity, 40%, 70%, and 39%, respectively, received hospital or government assistance specific to the experienced hardship. In subgroup analysis of families with HMH, after adjusting for income and other confounders, non-English language preference was associated with lower odds of receiving government assistance. CONCLUSIONS: After a pediatric cancer diagnosis, low-to-middle-income families are more likely to incur debt than high-income families. Most families experiencing food insecurity received some food assistance, while housing and energy assistance were less common. Future studies should investigate methods to equitably improve access to financial assistance and minimize long-term financial consequences.

A Novel Machine Learning Approach to Predict Textbook Outcome in Colectomy.

BACKGROUND: Several calculators exist to predict risk of postoperative complications. However, in low-risk procedures such as colectomy, a tool to determine the probability of achieving the ideal outcome could better aid clinical decision-making, especially for high-risk patients. A textbook outcome is a composite measure that serves as a surrogate for the ideal surgical outcome. OBJECTIVE: To identify the most important factors for predicting textbook outcomes in patients with nonmetastatic colon cancer undergoing colectomy and to create a textbook outcome decision support tool using machine learning algorithms. DESIGN: This was a retrospective analysis study. SETTINGS: Data were collected from the American College of Surgeons National Surgical Quality Improvement Program database. PATIENTS: Adult patients undergoing elective colectomy for nonmetastatic colon cancer (2014-2020) were included. MAIN OUTCOME MEASURES: Textbook outcome was the main outcome, defined as no mortality, no 30-day readmission, no postoperative complications, no 30-day reinterventions, and a hospital length of stay of ≤5 days. Four models (logistic regression, decision tree, random forest, and eXtreme Gradient Boosting) were trained and validated. Ultimately, a web-based calculator was developed as proof of concept for clinical application. RESULTS: A total of 20,498 patients who underwent colectomy for nonmetastatic colon cancer were included. Overall, textbook outcome was achieved in 66% of patients. Textbook outcome was more frequently achieved after robotic colectomy (77%), followed by laparoscopic colectomy (68%) and open colectomy (39%, p < 0.001). eXtreme Gradient Boosting was the best performing model (area under the curve = 0.72). The top 5 preoperative variables to predict textbook outcome were surgical approach, patient age, preoperative hematocrit, preoperative oral antibiotic bowel preparation, and patient sex. LIMITATIONS: This study was limited by its retrospective nature of the analysis. CONCLUSIONS: Using textbook outcome as the preferred outcome may be a useful tool in relatively low-risk procedures such as colectomy, and the proposed web-based calculator may aid surgeons in preoperative evaluation and counseling, especially for high-risk patients. See Video Abstract . UN NUEVO ENFOQUE DE APRENDIZAJE AUTOMTICO PARA PREDECIR EL RESULTADO DE LOS LIBROS DE TEXTO EN COLECTOMA: ANTECEDENTES:Existen varias calculadoras para predecir el riesgo de complicaciones posoperatorias. Sin embargo, en procedimientos de bajo riesgo como la colectomía, una herramienta para determinar la probabilidad de lograr el resultado ideal podría ayudar mejor a la toma de decisiones clínicas, especialmente para pacientes de alto riesgo. Un resultado de libro de texto es una medida compuesta que sirve como sustituto del resultado quirúrgico ideal.OBJETIVO:Identificar los factores más importantes para predecir el resultado de los libros de texto en pacientes con cáncer de colon no metastásico sometidos a colectomía y crear una herramienta de apoyo a la toma de decisiones sobre los resultados de los libros de texto utilizando algoritmos de aprendizaje automático.DISEÑO:Este fue un estudio de análisis retrospectivo.AJUSTES:Los datos se obtuvieron de la base de datos del Programa Nacional de Mejora de la Calidad del Colegio Americano de Cirujanos.PACIENTES:Se incluyeron pacientes adultos sometidos a colectomía electiva por cáncer de colon no metastásico (2014-2020).MEDIDAS PRINCIPALES DE RESULTADO:El resultado de los libros de texto fue el resultado principal, definido como ausencia de mortalidad, reingreso a los 30 días, complicaciones posoperatorias, reintervenciones a los 30 días y una estancia hospitalaria ≤5 días. Se entrenaron y validaron cuatro modelos (regresión logística, árbol de decisión, bosque aleatorio y XGBoost). Finalmente, se desarrolló una calculadora basada en la web como prueba de concepto para su aplicación clínica.RESULTADOS:Se incluyeron un total de 20.498 pacientes sometidos a colectomía por cáncer de colon no metastásico. En general, el resultado de los libros de texto se logró en el 66% de los pacientes. Los resultados de los libros de texto se lograron con mayor frecuencia después de la colectomía robótica (77%), seguida de la colectomía laparoscópica (68%) y la colectomía abierta (39%) (p<0,001). XGBoost fue el modelo con mejor rendimiento (AUC=0,72). Los cinco principales variables preoperatorias para predecir el resultado en los libros de texto fueron el abordaje quirúrgico, la edad del paciente, el hematocrito preoperatorio, la preparación intestinal con antibióticos orales preoperatorios y el sexo femenino.LIMITACIONES:Este estudio estuvo limitado por la naturaleza retrospectiva del análisis.CONCLUSIONES:El uso de los resultados de los libros de texto como resultado preferido puede ser una herramienta útil en procedimientos de riesgo relativamente bajo, como la colectomía, y la calculadora basada en la web propuesta puede ayudar a los cirujanos en la evaluación y el asesoramiento preoperatorios, especialmente para pacientes de alto riesgo. (Traducción-Yesenia Rojas-Khalil ).

Stereotype Threat and Gender Bias in Internal Medicine Residency: It is Still Hard to be in Charge.

BACKGROUND: Despite similar numbers of women and men in internal medicine (IM) residency, women face unique challenges. Stereotype threat is hypothesized to contribute to underrepresentation of women in academic leadership, and exploring how it manifests in residency may provide insight into forces that perpetuate gender disparities. OBJECTIVE: To quantify the prevalence of stereotype threat in IM residency and explore experiences contributing to that stereotype threat. DESIGN: We used a mixed methods study design. First, we surveyed IM residents using the Stereotype Vulnerability Scale (SVS) to screen for stereotype threat. Second, we conducted focus groups with women who scored high on the SVS to understand experiences that led to stereotype threat. PARTICIPANTS: The survey was sent to all IM residents at University of California, San Francisco (UCSF), in September-November 2019. Focus groups were conducted at UCSF in Spring 2020. APPROACH: The survey included an adapted version of the SVS. For focus groups, we developed a focus group guide informed by literature on stereotype threat. We used a thematic approach to data analysis. The mixed methods design enabled us to draw metainferences by integrating the two data sources. KEY RESULTS: Survey response rate was 61% (110/181). Women were significantly more likely than men to have a score indicating stereotype threat vulnerability (77% vs 0%, p < 0.001). Four themes from focus groups characterized women's experiences of gender bias and stereotype threat: gender norm tension, microaggressions and sexual harassment, authority questioned, and support and allyship. CONCLUSIONS: Gender-based stereotype threat is highly prevalent among women IM residents. This phenomenon poses a threat to confidence and ability to execute patient care responsibilities, detracting from well-being and professional development. These findings indicate that, despite robust representation of women in IM training, further attention is needed to address gendered experiences and contributors to women's vulnerability to stereotype threat.

Disparities in household material hardship, financial toxicity, and income loss in pediatric cancer.

BACKGROUND: Based on previous reports of disparities in financial burden following a cancer diagnosis, this study aims to characterize mechanisms of disparities experienced by caregivers of children with cancer, including the impact of work flexibility and social support. METHODS: Cross-sectional survey (in English or Spanish) of caregivers of children with cancer that assessed household material hardship (HMH), financial toxicity, and income change. RESULTS: Of 156 caregivers surveyed, 32% were Hispanic and 32% were low income. Hispanic caregivers were more likely to report HMH and financial toxicity compared to non-Hispanic White and Asian (HMH: 57% vs. 21% vs. 19%, p < .001; financial toxicity: 73% vs. 52% vs. 53%, p = .07). Low- and middle-income caregivers were more likely to experience HMH and financial toxicity compared to high-income caregivers (HMH: 68% low vs. 38% middle vs. 8.7% high, p < .001; financial toxicity: 81% vs. 68% vs. 44%, p < .001). All income categories demonstrated significant increases in HMH 1 year after diagnosis. Seventeen percent reported more than 40% income loss, more of whom were low income than high income (27% vs. 12%, p = .20). Work flexibility and social support were associated with income and financial toxicity. CONCLUSION: HMH, financial toxicity, and income loss are prevalent after a child's cancer diagnosis, suggesting that screening should be incorporated into routine care. This financial burden disproportionately affects low-income and Hispanic caregivers. Further research is needed to elucidate the roles of work flexibility and social support, how safety net services are utilized by families, and how best to support families with HMH.

Hypertension Requiring Medication Use: a Silent Predictor of Poor Outcomes After Pancreaticoduodenectomy.

BACKGROUND: Although hypertension requiring medication (HTNm) is a well-known cardiovascular comorbidity, its association with postoperative outcomes is understudied. This study aimed to evaluate whether preoperative HTNm is independently associated with specific complications after pancreaticoduodenectomy. STUDY DESIGN: Adults undergoing elective pancreaticoduodenectomy were included from the 2014-2019 NSQIP-targeted pancreatectomy dataset. Multivariable regression models compared outcomes between patients with and without HTNm. Endpoints included significant complications, any complication, unplanned readmissions, length of stay (LOS), clinically relevant postoperative pancreatic fistula (CR-POPF), and cardiovascular and renal complications. A subgroup analysis excluded patients with diabetes, heart failure, chronic obstructive pulmonary disease, estimated glomerular filtration rate from serum creatinine (eGFRCr) < 60 ml/min per 1.73 m2, bleeding disorder, or steroid use. RESULTS: Among 14,806 patients, 52% had HTNm. HTNm was more common among older male patients with obesity, diabetes, congestive heart failure, chronic obstructive pulmonary disease, functional dependency, hard pancreatic glands, and cancer. After adjusting for demographics, preoperative comorbidities, and laboratory values, HTNm was independently associated with higher odds of significant complications (aOR 1.12, p = 0.020), any complication (aOR 1.11, p = 0.030), cardiovascular (aOR 1.78, p = 0.002) and renal (aOR 1.60, p = 0.020) complications, and unplanned readmissions (aOR 1.14, p = 0.040). In a subgroup analysis of patients without major preoperative comorbidity, HTNm remained associated with higher odds of significant complications (aOR 1.14, p = 0.030) and cardiovascular complications (aOR 1.76, p = 0.033). CONCLUSIONS: HTNm is independently associated with cardiovascular and renal complications after pancreaticoduodenectomy and may need to be considered in preoperative risk stratification. Future studies are necessary to explore associations among underlying hypertension, specific antihypertensive medications, and postoperative outcomes to investigate potential risk mitigation strategies.

Comparing Dermabond PRINEO versus Dermabond or staples for wound closure: a randomized control trial following total shoulder arthroplasty.

BACKGROUND: The method of surgical incision closure after total shoulder arthroplasty is an important factor to consider, as it affects operating room time, procedure cost, cosmetic outcomes, and patient satisfaction. The optimal method of wound management is unknown, but should be cost-effective, reproducible, and provide a reliable clinical result. This study aimed to compare the following wound closure methods after total shoulder arthroplasty: staples, Dermabond, and Dermabond PRINEO. We hypothesized that wound closure time for Dermabond PRINEO would be faster than Dermabond and comparable to that of staples, and Dermabond PRINEO would be more cost-effective than Dermabond and staples, and provide equal or superior closure outcomes to Dermabond and staples. METHODS: A randomized, prospective clinical trial comparing wound closure time and cost for 2 surgeons' traditional technique with that of Dermabond PRINEO was conducted. This study included at least 18 subjects in each group. Surgeon 1's patients were randomized to traditional Dermabond or Dermabond PRINEO, whereas surgeon 2's patients were randomized to staples or Dermabond PRINEO. Cosmetic outcomes and satisfaction scores were collected at 6 weeks and 3 months, postoperatively. Incisions were photographed, at both the 6-week and 3-month visits, and subsequently evaluated by a plastic surgeon blinded to the treatment method. RESULTS: The wound closure time for surgeon 1 was significantly faster for Dermabond PRINEO vs. Dermabond, and surgeon 2 closed significantly faster with staples vs. Dermabond PRINEO. The mean cost of closure was significantly less with Dermabond PRINEO compared with Dermabond, whereas the mean cost of staples was significantly less than Dermabond PRINEO. For both surgeons 1 and 2, there were no significant differences in patient satisfaction at 6 weeks or 3 months. In addition, the wound closure methods did not produce differing cosmetic outcomes. CONCLUSIONS: Although significant, the closing time for each method did not differ by a clinically relevant amount. Staples were the most cost-effective closing method, followed by Dermabond PRINEO. As neither method was superior over the other in terms of patient satisfaction, adverse events, and cosmetic outcomes, cost-effectiveness may be the greatest differentiator between the 3 methods.

Shoulder Position During Magnetic Resonance Arthrogram Significantly Affects Capsular Measurements.

PURPOSE: To determine whether change in shoulder position between internal rotation (IR) and external rotation (ER) during magnetic resonance arthrography (MRA) affects previously defined capsular measurements and to determine the utility of rotation in the diagnosis of instability. METHODS: A retrospective study was conducted of patients who received a shoulder MRA with humeral IR and ER views. Patients with an arthroscopically confirmed diagnosis of instability and those with clinically stable shoulders, no history of instability, and no MRA findings of instability were identified and compared. Humeral rotation, glenoid retroversion, humeral head subluxation, capsular length, and capsular area using axial sequences of IR and ER views were recorded. Analysis compared IR, ER, and Δ capsular measurements between groups using independent t tests and univariate and multivariate regression. RESULTS: Thirty-one subjects who were diagnosed with instability were included, along with 28 control subjects. Capsular length, capsular area, and humeral subluxations were significantly greater with ER compared with IR views (P < .001, P < .001, P < .001). Patients with instability displayed greater ER capsular length (P = .0006) and ER capsular area (P = .005) relative to controls. Multivariate logistic regression identified age, weight, sex, ER capsular length, and retroversion to be significant predictors of instability. ER capsular length independently predicts instability with 86% sensitivity and 84% specificity. Interobserver reliability using the intraclass correlation coefficient was rated good or excellent on all measurements. CONCLUSION: Variance in humeral rotation during shoulder MRA significantly affects capsular measurements. Rotational views increase the utility of capsular measurements when assessing for instability, particularly capsular length and capsular area. The implementation of ER positioning enhances the ability to examine capsular changes of the shoulder joint and can assist in the diagnosis of instability. LEVEL OF EVIDENCE: III, retrospective comparative study.

The effect of body mass index on internal rotation and function following anatomic and reverse total shoulder arthroplasty.

BACKGROUND: The exact relationship between body mass index (BMI) and internal rotation (IR) before and after total shoulder arthroplasty has not been studied to date. The purpose of this study was to determine the effects of BMI on the preoperative and postoperative shoulder range of motion and function in anatomic (aTSA) and reverse total shoulder arthroplasty (rTSA), and specifically how IR affects patient ability to perform IR-related activities of daily living (ADLs). METHODS: Patients from a prospective multicenter international shoulder arthroplasty registry who underwent primary rTSA (n=1171) and primary aTSA (n=883) were scored preoperatively and at latest follow-up (2-10 years, mean = 3 years) using the Simple Shoulder Test, University of California-Los Angeles shoulder score, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, Constant score, and Shoulder Pain and Disability Index patient-reported outcome measures (PROMs). Measured active abduction, forward flexion, IR, and active and passive external rotation were recorded, and BMI was evaluated as a predictor of motion and patient-reported outcomes. Patient responses to questions regarding the difficulty level of IR-related ADLs were studied. The relationships between BMI, IR, and ability to perform IR-related ADLs were quantified through analysis of variance with post hoc comparisons by Tukey honestly significant difference tests, where significance was denoted as P < .05. RESULTS: BMI was found to be inversely correlated with IR in patients undergoing both aTSA and rTSA, both preoperatively (P < .001 and P = .002) and postoperatively (P < .001 and P < .001). BMI affected the range of motion parameters of forward flexion abduction and external rotation but to a lesser extent than that of IR. Nonobese patients demonstrated significantly greater IR than overweight, obese, and morbidly obese patients postoperatively for aTSA (P < .001). For rTSA, nonobese patients had a significantly greater postoperative IR than obese and morbidly obese patients (P < .001 and P = .011, respectively). For both aTSA and rTSA patients, mean IR scores significantly differed between patients reporting normal function vs. patients reporting slight difficulty, considerable difficulty, or inability to perform IR-related ADLs. Increasing IR demonstrated a significant, positive correlation with all PROMs for both aTSA and rTSA patients (Pearson correlation, P < .001). CONCLUSIONS: BMI is an independent predictor of IR, even when controlling for age, gender, glenosphere size, and subscapularis repair. BMI was inversely correlated with the degree of IR, and decreased IR significantly negatively affected the ability to perform IR-related ADLs. CLINICAL RELEVANCE: Increasing BMI adversely affects shoulder ROM, particularly IR. IR is correlated with the ability to perform ADLs requiring IR in both aTSA and rTSA patients.

Shoulder motion decreases as body mass increases in patients with asymptomatic shoulders.

BACKGROUND: Higher complication rates are reported after shoulder arthroplasty in obese patients. Understanding the effect of body mass index (BMI) on range of motion (ROM) in asymptomatic shoulders may be useful in evaluating clinical outcomes for patients of varying BMIs presenting with shoulder pathology. The purpose of this study is to investigate patient characteristics, in particular BMI, that may affect ROM outcomes after shoulder arthroplasty. METHODS: Individuals aged 18 years or older (mean 57.21 ± 16.27 years) were recruited with asymptomatic shoulder presentation and without history of shoulder injury. A total of 224 shoulders were grouped into 4 BMI categories, and ROM was measured with a goniometer. Analysis was performed between patient demographics and ROM. RESULTS: Analyzed continuously, BMI negatively correlated with ROM for internal rotation (IR; r = -0.511, P < .01), forward elevation (FE; r = -0.418, P < .01), and external rotation (ER; r = -0.328, P < .01). ROM analyzed by BMI category revealed a dose effect of BMI vs ROM. Obese patients demonstrated a significant decrease in IR whereas morbidly obese patients had significant decreases for all ranges: IR (r = -0.469, P < .01), FE (r = -0.452, P < .01), and ER (r = -0.33, P < .01). Normal- and overweight patients revealed no significant correlations with ROM. CONCLUSION: As BMI is negatively correlated with ROM of the asymptomatic shoulder, patients with higher BMIs may be predisposed to diminished outcomes postoperatively. These baseline correlations will allow surgeons to make postoperative expectations and anticipate poorer outcomes of shoulder ROM in obese patients.

Pitch count adherence and injury assessment of youth baseball in South Carolina.

INTRODUCTION: Overuse injury in youth overhead athletes remains a concern. The introduction of pitch count guidelines was designed to limit the number of pitches per game. South Carolina is considered a warm weather climate which has been proven to expose overhead athletes to higher risk for injury. The purpose of this study was to detect baseline rates of arm pain and sequelae (injury, surgery, impact on participation) among southern youth baseball/softball players to better counsel players, parents, coaches and league administration on the prevention of arm injury. METHODS: A survey was distributed to 14 pediatric practices within the South Carolina Pediatric Practice Research Network. The 2-page survey included 28 closed-ended and descriptive questions that investigated physical and psychosocial responses during and after play. Additional questions were conducted on adherence and understanding of USA Baseball guidelines and pitch counting behavior. RESULTS: Two hundred and seventy three surveys were completed by parents of baseball/softball players. The players' average age was 11.6 years, who played on an average of 1.78 teams/leagues for 5.2 months each year. Only 26% of baseball players answered "Sometimes", "Often" or "Always" to their arm hurting. Arm fatigue, older age, parent/coach frustration with play, and months played were statistically significantly associated with arm pain. The survey revealed 58.9% of families were familiar with pitch count guidelines. DISCUSSION: Arm pain is relatively prevalent among the South Carolina youth baseball community and worse in older players and experience fatigue. This survey found lower percentage of youth overhead athletes experiencing arm discomfort when compared to prior studies. It is important for warm weather climate athletes to abide by guidelines, as they are more susceptible to arm injury. Increased recognition, education and compliance with pitch count guidelines will help protect these youth athletes from overuse injury. LEVEL OF EVIDENCE: IV, Descriptive Epidemiology Study.

The Effect of Screw Design and Cortical Augmentation on Insertional Torque and Compression in Coracoid-Glenoid Fixation in a Sawbones Model.

PURPOSE: To compare screw insertional torque and coracoid-glenoid compression from 4 fixation techniques with different screw design parameters and cortical augmentation for the Latarjet procedure. METHODS: Simulated Latarjet procedures were performed with 4 fixation techniques using laminated polyurethane blocks with dimensions similar to the coracoid-glenoid construct. The groups included DePuy Synthes Mitek 3.5-mm partially threaded screws with top hats, Arthrex 3.75-mm fully threaded screws with a 2-hole plate, Arthrex 3.75-mm fully threaded screws, and Smith & Nephew 4.0-mm partially threaded screws. Screws were inserted using a digital torque-measuring screwdriver to determine maximum insertional torque. Pressure-sensitive film was used to measure the maximum contact pressure and the effective pressure distribution (EPD) between the coracoid and glenoid; the EPD represents the percentage of the film's surface area that experienced pressure greater than 10 MPa. One-way analysis of variance and post hoc tests were used for statistical analysis. RESULTS: Significant differences were found between the 4 fixation groups for each variable measured. The 2 cortically augmented systems produced significantly higher maximum insertional torque than the non-cortically augmented systems (P < .001 for both). The 3.75-mm screws with a 2-hole plate yielded significantly higher contact pressures than the 4.0-mm screws (P = .028). This group also had a high EPD, with a mean value more than double the values of the non-cortically augmented systems (P = .037 and P < .001). CONCLUSIONS: Cortically augmented fixation methods showed higher maximum insertional torque, maximum contact pressure, and EPD between the surfaces of the coracoid and glenoid in this Sawbones model. CLINICAL RELEVANCE: Various implants are available for the Latarjet procedure, but their biomechanical characteristics have not yet been fully elucidated. Graft fracture and nonunion represent 2 modes of failure that may be related to insertional torque and coracoid-glenoid compression. This study compared screw insertional torque and compression achieved using 4 fixation techniques with different screw design parameters and cortical augmentation in a Sawbones model.

Harnessing calcineurin-FK506-FKBP12 crystal structures from invasive fungal pathogens to develop antifungal agents.

Calcineurin is important for fungal virulence and a potential antifungal target, but compounds targeting calcineurin, such as FK506, are immunosuppressive. Here we report the crystal structures of calcineurin catalytic (CnA) and regulatory (CnB) subunits complexed with FK506 and the FK506-binding protein (FKBP12) from human fungal pathogens (Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans and Coccidioides immitis). Fungal calcineurin complexes are similar to the mammalian complex, but comparison of fungal and human FKBP12 (hFKBP12) reveals conformational differences in the 40s and 80s loops. NMR analysis, molecular dynamic simulations, and mutations of the A. fumigatus CnA/CnB-FK506-FKBP12-complex identify a Phe88 residue, not conserved in hFKBP12, as critical for binding and inhibition of fungal calcineurin. These differences enable us to develop a less immunosuppressive FK506 analog, APX879, with an acetohydrazine substitution of the C22-carbonyl of FK506. APX879 exhibits reduced immunosuppressive activity and retains broad-spectrum antifungal activity and efficacy in a murine model of invasive fungal infection.

Aroclor 1254 causes atrophy of exocrine pancreas in mice and the mechanism involved.

Polychlorinated biphenyls (PCBs) are a class of organic pollutants that have been linked to pancreatic disease. However, their role in affecting the exocrine function of pancreas and the underlying mechanism remains elusive. In the present study, male C57 mice were treated with Aroclor 1254, a commercially available PCBs mixture, at a dosage of 0.5, 5, 50, or 500 µg kg(-1) every 3 days by oral gavage. Decrease in pancreas/soma index and acinar atrophy were observed in the mice after exposure for 50 days. Aroclor 1254 exposure significantly decreased the PCNA-positive cells in the pancreatic acini in a dose-dependent manner. In addition, western blot analysis showed that PCNA expression was decreased in pancreas in the presence of Aroclor 1254, which suggests that Aroclor 1254 suppresses cell proliferation. TUNEL-positive apoptotic cells as well as the expression of Bcl2, BclXL, BAX, and Bad of exocrine pancreas did not show significant changes in the treated mice, indicating that Aroclor 1254 has no effect on apoptosis. We also found that phosphorylation of ERK1/2, P90RSK1 and Bad was increased in the treated groups; this compensatory activation of phosphorylation in ERK1/2-P90RSK1-Bad signaling cascade could protect cell from apoptosis to maintain the cell numbers and function of exocrine pancreas. Moreover, we found that the expression of Kras and TNFα was increased in the pancreas, indicating that Aroclor 1254 exposure could result in increased risk of inflammation and carcinoma. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 671-678, 2016.

Use of toxicogenomics to predict the potential toxic effect of Benzo(a)pyrene on zebrafish embryos: ocular developmental toxicity.

Benzo(a)pyrene (BaP) is a representative polycyclic aromatic hydrocarbon (PAH), which is ubiquitous in the environment. The toxic effects of BaP on fish embryos have been described in detail, but some potentially toxic effects of BaP might have been neglected owing to the limitations of traditional techniques. In the present research, global transcriptional patterns were used to study the potentially toxic effects of BaP, as well as its underlying toxicological mechanisms. The expression levels of multiple genes were significantly changed by BaP exposure. The results of ontology assignments and cluster analysis showed that BaP could affect the processes of photoreceptor maintenance and phototransduction. We also conducted an experiment on phototactic response and found that larvae exposed to BaP displayed a decreasing response to light. In addition, BaP exposure decreased the cellular density of the ganglion cell layer (GCL) significantly. These results suggested that BaP exposure induced visual system developmental defects and dysfunction by perturbation of photoreceptor development related genes. Our results were helpful for an understanding of the toxicity of BaP. This study also indicated that microarray analysis was effective for predicting the potential toxicity of chemicals with high sensitivity and accuracy.

Effect of cell passage and density on protein kinase G expression and activation in vascular smooth muscle cells.

It has been shown that rat aortic smooth muscle cells (AoSMCs) lost PKG-I expression when propagated repetitively or grown at low densities. Conversely, AoSMCs isolated from PKG-I deficient mice are indistinguishable from those isolated from normal mice in morphology and growth characteristics. In this study, human AoSMCs were grown from passage 9 (p9) to passage 15 (p15) and rat AoSMCs were isolated and cultured from p1 through p15. Western blotting and immunofluorescence microscopy showed little difference in PKG-I expression among different passages. Next, rat AoSMCs of p4 were grown and harvested at different cell densities. Western blotting again showed little difference among cells seeded or harvested at different densities. To test the effect of cell passage on PKG-I activation, rat AoSMCs of p4 and p11 were treated with cGMP and analyzed by Western blotting for phosphorylated vasodilator-stimulated phosphoprotein (P-VASP). The results showed that p4 had higher level of PKG-I activation than p11.