Study Characteristics and Impact of Pediatric Orthopaedic Society of North America Annual Meeting's "Best Papers" From 2009 to 2019.

OBJECTIVE: Award-winning abstracts are selected every year at the Pediatric Orthopaedic Society of North America (POSNA) annual meeting as "best paper" or poster. It is unknown how many achieve publication in peer-reviewed journals and the impact they have. We sought to determine the characteristics, including the level of evidence (LoE), publication rates, and the impact of award-winning abstracts on pediatric orthopaedic surgery practice from 2009 to 2019. METHODS: Award-winning abstracts or "best papers" from 2009 to 2019 were retrospectively reviewed from the POSNA website from abstract publication to manuscript publication. A search across Pubmed was used to match abstracts to their publications by comparing author names, titles, study design and methodology, results, and conclusions. Area of focus, abstract authors, institutions, publication status, LoE, time to publication, authors of publication, journals of publication, and the journal's latest Hirsch Index and impact factor were recorded. RESULTS: There have been 54 "best papers" at the POSNA annual meeting from 2009 to 2019. Of those, 39 have been published across 17 different journals for a publication rate of 72%. The average time from abstract presentation to publication was 21.2 months with a range of 0 to 121 months. Of the published award-winning abstracts, 64% (25) were published within 2 years, 87% (34) within 3 years, and 95% (37) within 4 years. Out of the published abstracts, 26% (10) were in the Journal of Pediatric Orthopaedics , 23% (9) were in the Journal of Bone and Joint Surgery , and 10% (4) were in the Journal of Child Orthopaedics . The median number of abstract authors was 4 and increased to a median of 6 authors once published. Most award-winning abstracts had a LoE of 3. The average journal impact factor for all publications was 4; the average Hirsch Index for the corresponding author was 29.9, and the average number of citations for a publication was 41 with a range of 0 to 270. CONCLUSIONS: The majority of the "best papers" presented at POSNA annual meetings from 2009 to 2019 were published in peer-reviewed journals within 2 years of presentation, with approximately half being published in the Journal of Pediatric Orthopaedics or Journal of Bone and Joint Surgery . The publication rate of "best papers" at the POSNA annual meeting was found to be higher than rates reported for abstracts presented at the annual meetings of POSNA, American Society for Surgery of the Hand and European Pediatric Orthopaedic Society, but similar to the rates observed for American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, and Orthopaedic Trauma Association. Most of the selected "best papers" at the POSNA annual meeting are published and have a substantial impact on pediatric orthopaedic surgery practice. LEVEL OF EVIDENCE: Level IV.

Brachmann-Cornelia de Lange syndrome with a papilloma of the choroid plexus: analyses of molecular genetic characteristics of the patient and the tumor. A single-case study.

PURPOSE: A 10-month-old girl with a Brachmann-Cornelia de Lange syndrome and a choroid plexus papilloma of the brain was studied at the Hospital Infantil de México Federico Gómez (HIMFG) in Mexico City. METHODS AND RESULTS: Presumptive papilloma of the third ventricle was evidenced on CT and MR images and removed. Pathological analysis confirmed its origin. A posterior radiosurgery was required due to a tumor relapse. Karyotypes (GTG bands) of the patient and her parents undertaken at HIMFG were normal. Array comparative genomic hybridization (array CGH) analyses of blood DNA of the patient and her parents carried out at BlueGnome's Laboratory in Cambridge, UK, set in evidence amplification of genes SPNS2, GGT6, SMTNL2, PELP1, MYBBP1A, and ALOX15 in chromosome 17p of the patient. Since MYBBP1A is a proto-oncogene and ALOX15 participates in the development of cancer and metastases of tumors, further fluorescent in situ hybridization (FISH) analyses of these two genes were implemented at HIMFG. Amplification of the two genes was found in the tumor of the case under study but not in an unrelated papilloma of the choroid plexus. DISCUSSION: Further analyses of the association of choroid plexus papillomas with disorders of psycho-neural development and its relationship to molecular genetic modifications at chromosome 17p are now under way at HIMFG.

[Febrile cholestatic jaundice as an initial manifestation of Hodgkin's disease]. / Ictericia febril colestásica como forma de presentación de linfoma de Hodgkin.

The febrile cholestatic disease as a presentation of Hodgkin's lymphoma is a very unusual condition. We describe here the case of a patient with prolonged fever of unknown origin and progressive jaundice, in whom the diagnosis was made with the analysis of a liver biopsy, given the absence of lymph node involvement that characterizes this disease. We remark the severe and multisystemic involvement of this rapidly progressive disease.

Study Characteristics and Impact of the "Best Papers" Presented at ASSH Annual Meetings Over the Past Decade.

Purpose: Each year, the American Society for Surgery of the Hand (ASSH) selects several abstracts for podium presentations during a "Best Papers" session. We examined these papers to better understand their characteristics and impact on the field of hand surgery. Methods: "Best Papers" from the 2010 to 2020 ASSH Annual Meetings were reviewed. Online databases were searched to find matching publications. Descriptive data were collected from the publications. The Hirsch index value for each corresponding author and the number of citations for each publication were recorded. Descriptive statistics were used to analyze the data. Results: Fifty-nine "Best Papers" were awarded during the study period. Forty-nine (83%) were clinical and 10 were basic science studies. A total of 39 observational studies, 11 human trials, 8 experimental studies, and 1 case series were present. Fifty-four (91.5%) were published at the time of our review. Twenty-six of those (48%) were multicenter studies, and the remaining 28 were from a single institution. The average time from presentation to publication was 16 months. The top three journals of publication were the Journal of Hand Surgery (33%), the Journal of Bone and Joint Surgery (9%), and the Journal of Hand Surgery, European (7%). The median level of evidence for all "Best Papers" was 3, with a trend toward a higher level of evidence during the study period. The average h-index value of all corresponding authors was 27.3. The average number of citations per publication was 37. Conclusions: The ASSH "Best Papers" were primarily clinical studies with an increasingly strong level of evidence and were likely led by an author with a history of research productivity. Selection as a "Best Paper" at ASSH Annual Meetings is a strong predictor of future publication and impact. Clinical relevance: This study evaluates the "value" of the best paper designation at the ASSH annual meeting.

NBN Pathogenic Germline Variants are Associated with Pan-Cancer Susceptibility and In Vitro DNA Damage Response Defects.

PURPOSE: To explore the role of NBN as a pan-cancer susceptibility gene. EXPERIMENTAL DESIGN: Matched germline and somatic DNA samples from 34,046 patients were sequenced using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets and presumed pathogenic germline variants (PGV) identified. Allele-specific and gene-centered analysis of enrichment was conducted and a validation cohort of 26,407 pan-cancer patients was analyzed. Functional studies utilized cellular models with analysis of protein expression, MRN complex formation/localization, and viability assessment following treatment with γ-irradiation. RESULTS: We identified 83 carriers of 32 NBN PGVs (0.25% of the studied series), 40% of which (33/83) carried the Slavic founder p.K219fs. The frequency of PGVs varied across cancer types. Patients harboring NBN PGVs demonstrated increased loss of the wild-type allele in their tumors [OR = 2.7; confidence interval (CI): 1.4-5.5; P = 0.0024; pan-cancer], including lung and pancreatic tumors compared with breast and colorectal cancers. p.K219fs was enriched across all tumor types (OR = 2.22; CI: 1.3-3.6; P = 0.0018). Gene-centered analysis revealed enrichment of PGVs in cases compared with controls in the European population (OR = 1.9; CI: 1.3-2.7; P = 0.0004), a finding confirmed in the replication cohort (OR = 1.8; CI: 1.2-2.6; P = 0.003). Two novel truncating variants, p.L19* and p.N71fs, produced a 45 kDa fragment generated by alternative translation initiation that maintained binding to MRE11. Cells expressing these fragments showed higher sensitivity to γ-irradiation and lower levels of radiation-induced KAP1 phosphorylation. CONCLUSIONS: Burden analyses, biallelic inactivation, and functional evidence support the role of NBN as contributing to a broad cancer spectrum. Further studies in large pan-cancer series and the assessment of epistatic and environmental interactions are warranted to further define these associations.

DNA methylation and gene expression integration in cardiovascular disease.

BACKGROUND: The integration of different layers of omics information is an opportunity to tackle the complexity of cardiovascular diseases (CVD) and to identify new predictive biomarkers and potential therapeutic targets. Our aim was to integrate DNA methylation and gene expression data in an effort to identify biomarkers related to cardiovascular disease risk in a community-based population. We accessed data from the Framingham Offspring Study, a cohort study with data on DNA methylation (Infinium HumanMethylation450 BeadChip; Illumina) and gene expression (Human Exon 1.0 ST Array; Affymetrix). Using the MOFA2 R package, we integrated these data to identify biomarkers related to the risk of presenting a cardiovascular event. RESULTS: Four independent latent factors (9, 19, 21-only in women-and 27), driven by DNA methylation, were associated with cardiovascular disease independently of classical risk factors and cell-type counts. In a sensitivity analysis, we also identified factor 21 as associated with CVD in women. Factors 9, 21 and 27 were also associated with coronary heart disease risk. Moreover, in a replication effort in an independent study three of the genes included in factor 27 were also present in a factor identified to be associated with myocardial infarction (CDC42BPB, MAN2A2 and RPTOR). Factor 9 was related to age and cell-type proportions; factor 19 was related to age and B cells count; factor 21 pointed to human immunodeficiency virus infection-related pathways and inflammation; and factor 27 was related to lifestyle factors such as alcohol consumption, smoking and body mass index. Inclusion of factor 21 (only in women) improved the discriminative and reclassification capacity of the Framingham classical risk function and factor 27 improved its discrimination. CONCLUSIONS: Unsupervised multi-omics data integration methods have the potential to provide insights into the pathogenesis of cardiovascular diseases. We identified four independent factors (one only in women) pointing to inflammation, endothelium homeostasis, visceral fat, cardiac remodeling and lifestyles as key players in the determination of cardiovascular risk. Moreover, two of these factors improved the predictive capacity of a classical risk function.

Prediagnostic Image Data, Artificial Intelligence, and Pancreatic Cancer: A Tell-Tale Sign to Early Detection.

Pancreatic cancer continues to be one of the deadliest malignancies and is the third leading cause of cancer-related mortality in the United States. Based on several models, it is projected to become the second leading cause of cancer-related deaths by 2030. Although the overall survival rate for patients diagnosed with pancreatic cancer is less than 10%, survival rates are increasing in those whose cancers are detected at an early stage, when intervention is possible. There are, however, no reliable biomarkers or imaging technology that can detect early-stage pancreatic cancer or accurately identify precursors that are likely to progress to malignancy. The Alliance of Pancreatic Cancer Consortia, a virtual consortium of researchers, clinicians, and advocacies focused on early diagnosis of pancreatic cancer, was formed in 2016 to provide a platform and resources to discover and validate biomarkers and imaging methods for early detection. The focus of discussion at the most recent alliance meeting was on imaging methods and the use of artificial intelligence for early detection of pancreatic cancer.

Collecting 48,000 CT exams for the lung screening study of the National Lung Screening Trial.

From 2002-2004, the Lung Screening Study (LSS) of the National Lung Screening Trial (NLST) enrolled 34,614 participants, aged 55-74 years, at increased risk for lung cancer due to heavy cigarette smoking. Participants, randomized to standard chest X-ray (CXR) or computed tomography (CT) arms at ten screening centers, received up to three imaging screens for lung cancer at annual intervals. Participant medical histories and radiologist-interpreted screening results were transmitted to the LSS coordinating center, while all images were retained at local screening centers. From 2005-2007, all CT exams were uniformly de-identified and delivered to a central repository, the CT Image Library (CTIL), on external hard drives (94%) or CD/DVD (5.9%), or over a secure Internet connection (0.1%). Of 48,723 CT screens performed, only 176 (0.3%) were unavailable (lost, corrupted, compressed) while 48,547 (99.7%) were delivered to the CTIL. Described here is the experience organizing, implementing, and adapting the clinical-trial workflow surrounding the image retrieval, de-identification, delivery, and archiving of available LSS-NLST CT exams for the CTIL, together with the quality assurance procedures associated with those collection tasks. This collection of CT exams, obtained in a specific, well-defined participant population under a common protocol at evenly spaced intervals, and its attending demographic and clinical information, are now available to lung-disease investigators and developers of computer-aided-diagnosis algorithms. The approach to large scale, multi-center trial CT image collection detailed here may serve as a useful model, while the experience reported should be valuable in the planning and execution of future equivalent endeavors.

Clinical factors associated with adherence to aerobic and resistance physical activity guidelines among cancer prevention patients and survivors.

Physical activity (PA) is a known behavior to reduce cancer risk and improve cancer survivorship, yet adherence to PA guidelines is poor among the general population and cancer survivors. The purpose of this study was to determine the extent to which patients referred for exercise consultation within a clinical cancer prevention setting were meeting aerobic and resistance physical activity (PA) guidelines and to identify factors associated with guideline adherence. Between 2013 and 2015, cancer prevention patients and cancer survivors were interviewed by an exercise physiologist within an Integrative Health Program at The University of Texas MD Anderson Cancer Prevention Center. PA adherence was defined as at least 150-minutes of moderate-intensity or 75-minutes of vigorous-intensity PA per week, along with resistance training at least 2 days per week. Logistic regression was used to determine factors associated with meeting or not meeting PA guidelines for aerobic exercise, resistance exercise, and aerobic and resistance exercise combined. Among 1,024 cancer prevention patients and survivors, 9% of patients adhered to guideline-based PA. Adherence to aerobic and resistance guidelines were 20% and 12%, respectively. Overweight or obesity was associated with not meeting guideline-based PA in both cancer prevention patients and cancer survivors. Among breast cancer survivors, combination treatment with surgery, radiation, and chemotherapy ('multimodal therapy') was robustly associated with not meeting aerobic guidelines (OR 2.20, 95% CI: 1.17 to 4.16). BMI and breast cancer treatment history are key determinants of PA behavior among cancer prevention patients and survivors. Poor adherence to PA guidelines is a key issue for cancer prevention patients and survivors, particularly obese patients and women who receive multimodal therapy for breast cancer. Identifying and connecting patients at highest risk of poor PA adherence with exercise programs is needed to improve PA, a key modifiable cancer risk factor.

[Reliability for detection of developmental problems using the semaphore from the Child Development Evaluation test: Is a yellow result different from a red result?] / Confiabilidad de la detección de problemas de desarrollo mediante el semáforo de la prueba de Evaluación del Desarrollo Infantil: ¿es diferente un resultado amarillo de uno rojo?

BACKGROUND: The Child Development Evaluation (CDE) is a screening tool designed and validated in Mexico for detecting developmental problems. The result is expressed through a semaphore. In the CDE test, both yellow and red results are considered positive, although a different intervention is proposed for each. The aim of this work was to evaluate the reliability of the CDE test to discriminate between children with yellow/red result based on the developmental domain quotient (DDQ) obtained through the Battelle Development Inventory, 2nd edition (in Spanish) (BDI-2). METHODS: The information was obtained for the study from the validation. Children with a normal (green) result in the CDE were excluded. Two different cut-off points of the DDQ were used (BDI-2): <90 to include low average, and developmental delay was considered with a cut-off<80 per domain. Results were analyzed based on the correlation of the CDE test and each domain from the BDI-2 and by subgroups of age. RESULTS: With a cut-off DDQ<90, 86.8% of tests with yellow result (CDE) indicated at least one domain affected and 50% 3 or more compared with 93.8% and 78.8% for red result, respectively. There were differences in every domain (P<0.001) for the percent of children with DDQ<80 between yellow and red result (CDE): cognitive 36.1% vs. 61.9%; communication: 27.8% vs. 50.4%, motor: 18.1% vs. 39.9%; personal-social: 20.1% vs. 28.9%; and adaptive: 6.9% vs. 20.4%. CONCLUSIONS: The semaphore result yellow/red allows identifying different magnitudes of delay in developmental domains or subdomains, supporting the recommendation of different interventions for each one.

TCIA: An information resource to enable open science.

Reusable, publicly available data is a pillar of open science. The Cancer Imaging Archive (TCIA) is an open image archive service supporting cancer research. TCIA collects, de-identifies, curates and manages rich collections of oncology image data. Image data sets have been contributed by 28 institutions and additional image collections are underway. Since June of 2011, more than 2,000 users have registered to search and access data from this freely available resource. TCIA encourages and supports cancer-related open science communities by hosting and managing the image archive, providing project wiki space and searchable metadata repositories. The success of TCIA is measured by the number of active research projects it enables (>40) and the number of scientific publications and presentations that are produced using data from TCIA collections (39).

Curcumin reverses glomerular hemodynamic alterations and oxidant stress in 5/6 nephrectomized rats.

The administration of curcumin before and throughout the study attenuates oxidant stress and glomerular hemodynamic alterations induced by 5/6 nephrectomy (5/6NX). The purpose of this work was to study if curcumin is able to reverse established glomerular hemodynamic alterations (e.g. hyperfiltration and glomerular hypertension) and oxidant stress in rats with 5/6NX. Curcumin (120 mg/kg) was given to rats with established renal injury (30 days after surgery) and continued for 30 days (days 31-60 of the study). All rats were studied on day 60 after surgery. Curcumin was able (a) to reverse 5/6NX-induced glomerular hypertension and hyperfiltration, (b) to induce cell proliferation and nuclear translocation of Nrf2 and (c) to reverse 5/6NX-induced oxidant stress and decrease in antioxidant enzymes. These beneficial effects of curcumin were associated with the ability of this antioxidant to reverse renal structural alterations, proteinuria, hypertension, interstitial fibrosis, fibrotic glomeruli, tubular atrophy and mesangial expansion. It has been shown for the first time that curcumin is able to reverse established oxidants stress glomerular hypertension and hyperfiltration in rats with 5/6NX. These novel findings may play a key role in the attenuation of proteinuria and progression of renal damage in rats with 5/6NX. These data suggest that curcumin may be useful to reverse established hemodynamic alterations and renal injury in patients with chronic renal failure.

Deferoxamine pretreatment prevents Cr(VI)-induced nephrotoxicity and oxidant stress: role of Cr(VI) chelation.

Deferoxamine (DFO) is a recognized iron chelator which has been shown to exert nephroprotection in models of toxic nephropathies. In the present work the potential protective effects of DFO against Cr(VI)-induced nephrotoxicity and oxidant stress were evaluated. Rats were injected with a single injection (15mg/kg, s.c.) of potassium dichromate (K(2)Cr(2)O(7)). DFO was given as a single i.p. injection 30min before K(2)Cr(2)O(7) administration at three different doses (100, 200 and 400mg/kg). It was found that DFO pretreatment attenuated, in a dose-dependent way, K(2)Cr(2)O(7)-induced renal dysfunction and structural alterations evaluated by serum creatinine, blood urea nitrogen, creatinine clearance, proteinuria, plasma glutathione peroxidase activity, urinary excretion of N-acetyl-ß-d-glucosaminidase and histological analyses. Furthermore, DFO prevented the K(2)Cr(2)O(7)-induced renal oxidant stress and the decrease in the activity of the antioxidant enzymes superoxide dismutase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase and catalase. Finally it was found that DFO, at 400mg/kg, decreases renal Cr(VI) content which prompted us to evaluate the potential Cr(VI) chelating properties of this compound. Indeed was found in an in vitro assay that DFO was an effective Cr(VI) chelator with an IC(50) of 800µg. In additional groups of rats was found that DFO posttreatment was ineffective to attenuate K(2)Cr(2)O(7)-induced nephrotoxicity and renal oxidant stress. Furthermore, DFO was unable to modify urinary excretion of total chromium. The nephroprotective effect of DFO against Cr(VI)-induced nephrotoxicity and oxidant stress may be explained, at least partially, by the ability of DFO to chelate Cr(VI) and to attenuate renal Cr(VI) content. However, it cannot be excluded that the ability of DFO to chelate iron may also be involved in the protection observed in our study.

Curcumin induces Nrf2 nuclear translocation and prevents glomerular hypertension, hyperfiltration, oxidant stress, and the decrease in antioxidant enzymes in 5/6 nephrectomized rats.

Renal injury resulting from renal ablation induced by 5/6 nephrectomy (5/6NX) is associated with oxidant stress, glomerular hypertension, hyperfiltration, and impaired Nrf2-Keap1 pathway. The purpose of this work was to know if the bifunctional antioxidant curcumin may induce nuclear translocation of Nrf2 and prevents 5/6NX-induced oxidant stress, renal injury, decrease in antioxidant enzymes, and glomerular hypertension and hyperfiltration. Four groups of rats were studied: (1) control, (2) 5/6NX, (3) 5/6NX +CUR, and (4) CUR (n = 8-10). Curcumin was given by gavage to NX5/6 +CUR and CUR groups (60 mg/kg/day) starting seven days before surgery. Rats were studied 30 days after NX5/6 or sham surgery. Curcumin attenuated 5/6NX-induced proteinuria, systemic and glomerular hypertension, hyperfiltration, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and increase in plasma creatinine and blood urea nitrogen. This protective effect was associated with enhanced nuclear translocation of Nrf2 and with prevention of 5/6NX-induced oxidant stress and decrease in the activity of antioxidant enzymes. It is concluded that the protective effect of curcumin against 5/6NX-induced glomerular and systemic hypertension, hyperfiltration, renal dysfunction, and renal injury was associated with the nuclear translocation of Nrf2 and the prevention of both oxidant stress and the decrease of antioxidant enzymes.

Curcumin protects from cardiac reperfusion damage by attenuation of oxidant stress and mitochondrial dysfunction.

This study was designed to investigate whether the pretreatment with curcumin, a yellow pigment from turmeric (Curcuma longa) known for its potent antioxidant capacity, was able to protect against the oxidant damage and mitochondrial dysfunction induced by reperfusion injury in isolated hearts. Rats were treated with a daily intragastric dose of curcumin (200 mg/kg) for 7 days prior to experimental ischemia (30 min) and reperfusion (60 min) (I/R). Cardiac mechanical work was measured during periods of stabilization, ischemia, and reperfusion. Oxidant stress and activity of antioxidant enzymes were measured in both homogenates of cardiac tissue and in isolated mitochondria. In addition, oxygen consumption was measured in isolated mitochondria. It was found that curcumin pretreatment attenuates the I/R injury as evidenced by (a) loss of cardiac mechanical work, (b) oxidant stress (increase in lipid peroxidation and decrease in reduced glutathione content) and (c) decrease in the activity of the antioxidant enzymes superoxide dismutase and glutathione reductase in both cardiac tissue and isolated mitochondria, and (d) decrease in mitochondrial respiratory capacity. In conclusion, the protective effect of curcumin was associated with the attenuation of oxidant stress and mitochondrial dysfunction secondary to I/R injury.

Protective effect of sulforaphane pretreatment against cisplatin-induced liver and mitochondrial oxidant damage in rats.

In the present work was analyzed whether sulforaphane (SFN) may protect against cisplatin (CIS)-induced hepatic damage, oxidant stress and mitochondrial dysfunction. Four groups of male Wistar rats were studied: control, CIS, CIS+SFN and SFN. SFN was given i.p. (500 µg/kg/d × 3 days) before CIS administration (single i.p. injection, 10mg/kg). Rats were sacrificed 3 days after CIS injection to evaluate hepatic damage (histological analysis, liver/body weight ratio and serum activity of aspartate aminotransferase and alanine aminotransferase), oxidant stress (lipid peroxidation and protein carbonyl and glutathione content), antioxidant enzymes (catalase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase and superoxide dismutase) in liver homogenates and isolated mitochondria and mitochondrial function (oxygen consumption using either malate/glutamate or succinate as substrates and the activity of mitochondrial complex I, II, II-III, IV and V). Furthermore it was evaluated if SFN is able to scavenge some reactive oxygen species in vitro. It was found that SFN prevents CIS-induced (a) hepatic damage, (b) oxidant stress and decreased activity of antioxidant enzymes in liver and mitochondria and (c) mitochondrial alterations in oxygen consumption and decreased activity of mitochondrial complex I. It was also found that the scavenging ability of SFN for peroxynitrite anion, superoxide anion, singlet oxygen, peroxyl radicals, hydrogen peroxide and hydroxyl radicals was very low or negligible. The hepatoprotective effect of SFN was associated to the preservation of mitochondrial function, antioxidant enzymes and prevention of liver and mitochondrial oxidant stress.

Curcumin prevents Cr(VI)-induced renal oxidant damage by a mitochondrial pathway.

We report the role of mitochondria in the protective effects of curcumin, a well-known direct and indirect antioxidant, against the renal oxidant damage induced by the hexavalent chromium [Cr(VI)] compound potassium dichromate (K(2)Cr(2)O(7)) in rats. Curcumin was given daily by gavage using three different schemes: (1) complete treatment (100, 200, and 400 mg/kg bw 10 days before and 2 days after K(2)Cr(2)O(7) injection), (2) pretreatment (400 mg/kg bw for 10 days before K(2)Cr(2)O(7) injection), and (3) posttreatment (400 mg/kg bw 2 days after K(2)Cr(2)O(7) injection). Rats were sacrificed 48 h later after a single K(2)Cr(2)O(7) injection (15 mg/kg, sc) to evaluate renal and mitochondrial function and oxidant stress. Curcumin treatment (schemes 1 and 2) attenuated K(2)Cr(2)O(7)-induced renal dysfunction, histological damage, oxidant stress, and the decrease in antioxidant enzyme activity both in kidney tissue and in mitochondria. Curcumin pretreatment attenuated K(2)Cr(2)O(7)-induced mitochondrial dysfunction (alterations in oxygen consumption, ATP content, calcium retention, and mitochondrial membrane potential and decreased activity of complexes I, II, II-III, and V) but was unable to modify renal and mitochondrial Cr(VI) content or to chelate chromium. Curcumin posttreatment was unable to prevent K(2)Cr(2)O(7)-induced renal dysfunction. In further experiments performed in curcumin (400 mg/kg)-pretreated rats it was found that this antioxidant accumulated in kidney and activated Nrf2 at the time when K(2)Cr(2)O(7) was injected, suggesting that both direct and indirect antioxidant effects are involved in the protective effects of curcumin. These findings suggest that the preservation of mitochondrial function plays a key role in the protective effects of curcumin pretreatment against K(2)Cr(2)O(7)-induced renal oxidant damage.

Protective effect of sulforaphane against cisplatin-induced mitochondrial alterations and impairment in the activity of NAD(P)H: quinone oxidoreductase 1 and γ glutamyl cysteine ligase: studies in mitochondria isolated from rat kidney and in LLC-PK1 cells.

This work was designed to further study the mechanism by which sulforaphane (SFN) exerts a renoprotective effect against cisplatin (CIS)-induced damage. It was evaluated whether SFN attenuates the CIS-induced mitochondrial alterations and the impairment in the activity of the cytoprotective enzymes NAD(P)H: quinone oxidoreductase 1 (NQO1) and γ glutamyl cysteine ligase (γGCL). Studies were performed in renal epithelial LLC-PK1 cells and in isolated renal mitochondria from CIS, SFN or CIS+SFN treated rats. SFN effectively prevented the CIS-induced increase in reactive oxygen species (ROS) production and the decrease in NQO1 and γGCL activities and in glutathione (GSH) content. The protective effect of SFN on ROS production and cell viability was prevented by buthionine sulfoximine (BSO), an inhibitor of γGCL, and by dicoumarol, an inhibitor of NQO1. SFN was also able to prevent the CIS-induced mitochondrial alterations both in LLC-PK1 cells (loss of membrane potential) and in isolated mitochondria (inhibition of mitochondrial calcium uptake, release of cytochrome c, and decrease in GSH content, aconitase activity, adenosine triphosphate (ATP) content and oxygen consumption). It is concluded that the protection exerted by SFN on mitochondrial alterations and NQO1 and γGCL enzymes may be involved in the renoprotection of SFN against CIS.

Potential of computer-aided diagnosis to improve CT lung cancer screening.

The development of low-dose spiral computed tomography (CT) has rekindled hope that effective lung cancer screening might yet be found. Screening is justified when there is evidence that it will extend lives at reasonable cost and acceptable levels of risk. A screening test should detect all extant cancers while avoiding unnecessary workups. Thus optimal screening modalities have both high sensitivity and specificity. Due to the present state of technology, radiologists must opt to increase sensitivity and rely on follow-up diagnostic procedures to rule out the incurred false positives. There is evidence in published reports that computer-aided diagnosis technology may help radiologists alter the benefit-cost calculus of CT sensitivity and specificity in lung cancer screening protocols. This review will provide insight into the current discussion of the effectiveness of lung cancer screening and assesses the potential of state-of-the-art computer-aided design developments.