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Background: In the US, little is known about aspirin use as a preventive measure for cardiovascular disease by immigration status., Methods: Combined data from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 and 2017- March 2020 (pre-pandemic data) were analyzed. Persons were asked about demographics including country of birth and those aged 40 years and older were asked about current use of aspirin to prevent cardiovascular disease (CVD)., Results: Among 2,321 born in the US, preventive aspirin use was significantly more prevalent (39.6%) than among 910 others (27.5%, p < 0.01). However, after stratifying by race/ethnicity and history of CVD, the difference was significant only in Hispanics with CVD. In logistic regression analyses in Hispanics controlling for age, gender and education, the US born had significantly higher odds of aspirin use in those with or without CVD., Discussion: Among US Hispanics, use of aspirin for prevention of CVD was more prevalent in those born in the US than in others., (Copyright © 2023 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Objective: To explore and catalog ways Indigenous Traditional Healing practices are supported within the mainstream healthcare system through policies and programs in Canada, Australia, and New Zealand., Data Sources: A scoping review was conducted, guided by the PRISMA extension for Scoping Reviews. Databases for sources of information include CINAHL, Medline, Embase, Web of Science, Public Health ProQuest, Global Health EBSCO, iPortal, and grey literature., Study Selection: 2 reviewers screened the titles and abstracts of the studies for inclusion against the selection criteria independently. Studies that met the inclusion criteria were transferred to Covidence for further abstract and full-text review., Data Extraction: Of a total of 2,017 articles identified, 22 met the inclusion criteria for data extraction for this scoping review. Data items extracted include study title, authors, year of publication, publication type, publication source, support policy or program, health system or service, Indigenous Traditional Healing practices, and significant findings., Data Synthesis: 2 categories emerged from the analysis of the source of evidence. That is, healthcare systems and services with programs and policies supporting Indigenous Traditional Healing practices, and ways Indigenous Traditional Healing was adopted and utilized within the identified support programs., Conclusions: This study demonstrated the various ways Indigenous Traditional Healing practices are supported within the mainstream healthcare systems in Canada, Australia, and New Zealand. Indigenous Traditional Healing practices can be utilized as either the primary choice of treatment, to support Western biomedical treatment or through the adoption of Indigenous Traditional knowledge within the mainstream healthcare system., (Copyright © 2022. Published by Elsevier Inc.)

Background: Rising rates of fentanyl- and polydrug-involved drug overdose deaths have prompted inquiry into the role of drug supply in fatal overdose outcomes in the United States. To date, however, there have been few empirical investigations of drug enforcement strategies on fatal overdose rates, despite knowledge that both drug use and supply are often geographically distributed. To address this limitation, we examined measures of drug enforcement as predictors of next-year fatal overdose rates in the Washington/Baltimore High Intensity Drug Trafficking Area (W/B HIDTA)., Methods: We conducted mixed-effects models to examine the role of drug seizures and disruption in drug trafficking organizations (DTOs) and money laundering organizations (MLOs) on fatal overdose rates over a 5-year period (2016-2020) across 45 local jurisdictions in the W/B HIDTA region. Outcomes included any, opioid-involved, and fentanyl-involved fatal overdose., Results: Adjusting for covariates, both the total number of drug seizures and amount of cocaine seized (in dosage units per capita) positively predicted next-year opioid- and fentanyl-involved fatal overdose rates. Disruption to DTO and MLO operations did not significantly predict next-year fatal overdose rates for any outcome., Conclusion: Supply-side enforcement activities alone may have limited impact on reducing fatal overdose rates, but may serve as important markers to identify communities at high risk of fatal overdose and facilitate targeted intervention. Our findings underscore the importance of comprehensive law enforcement approaches that extend beyond drug enforcement to integrate prevention, linkage to treatment, and harm reduction strategies as needed to address the overdose epidemic., Competing Interests: Declarations of Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: At the time of this study, Lora Peppard, Rebecca Bates, and Thomas Carr were employed with the Washington/Baltimore HIDTA. The authors report no other conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of interests CL reports royalties from Western Psychological Services for diagnostic instruments; is on scientific advisory boards or projects for Tilray, Roche, Gateway, Springtide, and Greenwich Biosciences; and is supported by grants from the US National Institute of Mental Health (R01HD081199, R01MH115363, R01MH104423–02, and R01MH114925). TCh reports consultancy fees from Roche and Servier; royalties from Sage Publications and Guilford Publications; grants from the UK Medical Research Council (grants number MR/K021389/1 and MR/R011427/1), the UK National Institute for Health Research (grants number 13/119/18 and RP-PG-1211–20016), the EU Horizon 2020 programme (grant number 814302), Innovative Medicines Initiative (grant agreement number 777394 and AIMS-2-TRIALS, which receives support from the EU Horizon 2020 programme, European Federation of Pharmaceutical Industries and Associations, Autism Speaks, Autistica, and Simons Foundation Autism Research Initiative); and grant support from MQ Mental Health Research, The Waterloo Foundation, Epilepsy Research UK, the Charles Hawkins Fund, and the Baily Thomas Foundation. EA reports consulting fees from Roche and Quadrant; funding from Roche and SynapDx; non-financial support from AMO Pharma; book royalties from APPI and Springer; editorial board honoraria from Wiley; a patent (US20160000365A1) for an anxiety meter; is supported by the Ontario Brain Institute (POND network), Canadian Institutes of Health Research, Autism Intervention Research Network on Physical Health (funded by the Health Resources and Services Administration), US National Institutes of Health, Brain Canada, and the Azrieli Foundation; and is the Canada Research Chair in translational therapeutics in autism spectrum disorder and Dr Stuart D Sims endowed chair in Autism. BB is supported by US National Institute of Mental Health grant (1R01HD82127). AHa was supported by grants from the South-Eastern Norway Regional Health Authority (grant numbers 2018059 and 2020022) and by the Research Council of Norway (grants number 274611 and 288083). RJ reports funding from Australia's National Health and Medical Research Council. JC is supported by National Institute of Mental Health grants NIMH09902, NIMH081148, NIMH083707, NIMH80011, and U10MH66764. PC is supported by Simons Foundation Powering Autism Research and the Maternal and Child Health Bureau of the Leadership Education in Neurodevelopmental Disability. TCa reports personal fees from Western Psychological Services. LS reports being a consultant for Roche, Yamo, Teva, Impel, and Janssen Pharmaceuticals; book royalties from Oxford University Press, Guilford Press, and American Psychological Association Press; and licensing royalties for the Parent-Rated Anxiety Scale for Autism Spectrum Disorder from Cogstate and Yamo. PPW reports being employed by Clinical Research Associates, a non-profit organisation that is developing an experimental drug treatment for autism. CMF receives royalties for books on autism spectrum disorder, attention-deficit hyperactivity disorder, and major depressive disorder; grants for the A-FIPP randomised controlled trial (FR2069/8–1, 8-2), awarded by the German Research Foundation, and for the EU-AIMS2-TRIALS (H2020 777394) and EU STIPED (H2020 731827), awarded by the EU. CK is supported by grants from the Health Resources and Services Administration of the US Department of Health and Human Services (UA3MC11055), the US National Institutes of Health (R01HD098248, R01HD095973, P50DC018006), the US Department of Defense, and the Goldman Foundation (3104). APi receives questionnaire royalties from WPS. AHo reports personal fees from GW Pharmaceuticals. PSz receives research funding from the Canadian Institutes of Health Research and royalties from Guilford Press and Simon & Schuster for books. PSh reports support from the Health Resources and Services Administration of the US Department of Health and Human Services under the Autism Transitions Research Project (UJ2MC31073). VS is supported by the National Institute for Health Research (grant numbers EME 13/119/18, RP-PG-1211–20016, and 15/162) and a grant from Autistica (number 7262). GD reports grants from the UK Medical Research Council and Grand Challenges Canada, outside the submitted work. All other authors declare no competing interests.

Introduction: SCLC accounts for approximately 250,000 deaths worldwide each year. Acquisition of adequate tumor biopsy samples is challenging, and liquid biopsies present an alternative option for patient stratification and response monitoring., Methods: We applied whole genome next-generation sequencing to circulating free DNA (cfDNA) from 39 patients with limited-stage (LS) SCLC and 30 patients with extensive-stage SCLC to establish genome-wide copy number aberrations and also performed targeted mutation analysis of 110 SCLC associated genes. Quantitative metrics were calculated for copy number aberrations, including percent genome amplified (PGA [the percentage of genomic regions amplified]), Z-score (a measure of standard deviation), and Moran's I (a measure of spatial autocorrelation). In addition CellSearch, an epitope-dependent enrichment platform, was used to enumerate circulating tumor cells (CTCs) from a parallel blood sample., Results: Genome-wide and targeted cfDNA sequencing data identified tumor-related changes in 94% of patients with LS SCLC and 100% of patients with extensive-stage SCLC. Parallel analysis of CTCs based on at least 1 CTC/7.5 mL of blood increased tumor detection frequencies to 95% for LS SCLC. Both CTC counts and cfDNA readouts correlated with disease stage and overall survival., Conclusions: We demonstrate that a simple cfDNA genome-wide copy number approach provides an effective means of monitoring patients through treatment and show that targeted cfDNA sequencing identifies potential therapeutic targets in more than 50% of patients. We are now incorporating this approach into additional studies and trials of targeted therapies., (Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Dynamic changes in circulating tumour DNA (ctDNA) levels may predict long-term outcome. We utilised samples from a phase I/II randomised trial (BEECH) to assess ctDNA dynamics as a surrogate for progression-free survival (PFS) and early predictor of drug efficacy., Patients and Methods: Patients with estrogen receptor-positive advanced metastatic breast cancer (ER+ mBC) in the BEECH study, paclitaxel plus placebo versus paclitaxel plus AKT inhibitor capivasertib, had plasma samples collected for ctDNA analysis at baseline and at multiple time points in the development cohort (safety run-in, part A) and validation cohort (randomised, part B). Baseline sample ctDNA sequencing identified mutations for longitudinal analysis and mutation-specific digital droplet PCR (ddPCR) assays were utilised to assess change in ctDNA abundance (allele fraction) between baseline and 872 on-treatment samples. Primary objective was to assess whether early suppression of ctDNA, based on pre-defined criteria from the development cohort, independently predicted outcome in the validation cohort., Results: In the development cohort, suppression of ctDNA was apparent after 8 days of treatment (P = 0.014), with cycle 2 day 1 (4 weeks) identified as the optimal time point to predict PFS from early ctDNA dynamics. In the validation cohort, median PFS was 11.1 months in patients with suppressed ctDNA at 4 weeks and 6.4 months in patients with high ctDNA (hazard ratio = 0.20, 95% confidence interval 0.083-0.50, P < 0.0001). There was no difference in the level of ctDNA suppression between patients randomised to capivasertib or placebo overall (P = 0.904) nor in the PIK3CA mutant subpopulation (P = 0.071). Clonal haematopoiesis of indeterminate potential (CHIP) was evident in 30% (18/59) baseline samples, although CHIP had no effect on tolerance of chemotherapy nor on PFS., Conclusion: Early on-treatment ctDNA dynamics are a surrogate for PFS. Dynamic ctDNA assessment has the potential to substantially enhance early drug development., Clinical Registration Number: NCT01625286., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Cigarette smoking is a major risk factor for many adverse health conditions. Novel tobacco heating products (THPs) heat tobacco, reducing exposure to many of the harmful combustion toxicants in conventional cigarette emissions. In vitro studies have been employed to support the toxicological evaluation of chemicals and complex mixtures, including cigarette smoke. The use of automated robotics platforms for in vitro toxicological screening complements traditional testing approaches. Multiparametric toxicity and oxidative stress endpoints were used to assess in vitro biological responses elicited after exposure to total particulate matter (TPM) from two commercially available THPs, and the reference tobacco product 3R4F, in human bronchial epithelial cells. A luciferase-based reporter gene assay was used to assess antioxidant response element (ARE) transcriptional activation in stably transfected H292 cells after 6 and 24 h exposures. High-content screening was used to assess 10 endpoints normal human bronchial epithelial cells after 4 or 24 h exposures. 3R4F TPM stimulated significant increases in ARE activation (p < 0.005) and moderate activity in HCS cell-based assays compared to THP at comparable doses. THPs showed little or no activity in all assays. HCS techniques can extend safety assessments providing information quickly in the early stages of product innovation and development., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to evaluate the effects of feeding wet distillers grains plus solubles (WDGS) on quality attributes of three beef muscles (longissimus lumborum, psoas major, and infraspinatus). Ninety-six, yearlings crossbred steers were randomly assigned to one of three dietary treatments (Corn, 15%, or 30% WDGS - DM basis) and fed for 133 d. No significant differences were observed in marbling score (P=0.89), marbling texture (P=0.70), and marbling distribution (P=0.36). Greater concentrations of PUFA and lower levels of 18:1(n-7) were observed in beef from steers fed 30% WDGS when compared to other treatments. Lipid oxidation was also greater in beef from steers fed 30% WDGS (P≤0.05). No significant differences were observed in sensorial attributes and Warner-Bratzler shear force (WBSF) for all muscles (P>0.05). Feeding WDGS increased PUFA and lipid oxidation, which may lead to shorter shelf life., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To develop and internally validate a nomogram using biparametric magnetic resonance imaging (B-MRI)-derived variables for the prediction of prostate cancer at transperineal sector-guided prostate biopsy (TPSB)., Subjects/patients and Methods: Consecutive patients referred to our institution with raised prostate-specific antigen (PSA), abnormal prostate examination, or persistent suspicion of prostate cancer after previous transrectal biopsy between July 2012 and November 2015 were reviewed from a prospective database. All patients underwent prebiopsy B-MRI with T2-weighted and diffusion-weighted imaging sequences, followed by 24 to 40 core TPSB with additional targeted cores using cognitive registration. Univariable and multivariable logistic regression analysis was used to determine predictors of prostate cancer outcomes. Multivariable coefficients were used to construct 2 MRI-based nomograms to predict any and significant (Gleason 4 or maximum cancer core length ≥6mm) prostate cancer at TPSB. Bootstrap resamples were used for internal validation. Accuracy was assessed by calculating the concordance index., Results: In total, 615 men were included in the study. Prostate cancer was diagnosed in 317 (51.5%) men with significant cancer diagnosed in 237 (38.5%) men. Age, Prostate Imaging Reporting and Data System (PI-RADS) score, PSA, PSA density, and primary biopsy were predictors of prostate cancer at TPSB on univariable analysis (P<0.0001). PSA showed strong correlation with PSA density and was excluded. The remaining variables were all independent predictors of prostate cancer on multivariable analysis (P<0.0001) and used to generate the nomograms. Both nomograms showed good discrimination for prostate cancer, with a concordance index of 87% for any cancer and 92% for significant disease. Using a nomogram-derived probability threshold of<15%, 111 (18.0%) biopsies can be saved, at the expense of 3 missed significant prostate cancers., Conclusions: These internally validated MR-based nomograms were able to accurately predict TPSB outcomes for prostate cancer, especially significant disease. Our findings support the combination of prebiopsy MRI results and clinical factors as part of the biopsy decision-making process., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Relatively little research about autism early intervention has occurred in families of low socioeconomic status. Barriers to participation for under-resourced families (i.e., families with low incomes or limited education), pose a significant problem. The purpose of this pilot study was to apply empirically supported methods promoting participation of families with low-income and low-education levels to an established intervention for children with autism spectrum disorder (ASD)., Method: Participant recruitment specifically targeted families whose income was equal to or below two times the federal poverty line and whose caregiver(s) had no more than two years of college attendance. An evidence-based intervention was modified to be more accessible to participating families. Adaptations focused on decreasing access barriers, decreasing attrition, and promoting positive change within families. Success of the program was measured quantitatively and qualitatively., Results: Twenty-seven families were referred to the project, 13 of which did not meet eligibility requirements. Eight families enrolled, maintained participation for the majority of the project and provided positive qualitative feedback of their experiences. Project and treatment attrition were calculated at 62% and 12.5%, respectively. Treatment attendance was high, but length of time to complete treatment was greatly influenced by the number of session cancellations., Conclusions: The exploratory project demonstrated that practical modifications to standard early intervention protocols can promote engagement in families with limited resources. Recommendations for programs seeking to implement interventions in under-resourced communities are discussed.

Background: The management of NSCLC has been transformed by stratified medicine. The National Lung Matrix Trial (NLMT) is a UK-wide study exploring the activity of rationally selected biomarker/targeted therapy combinations., Patients and Methods: The Cancer Research UK (CRUK) Stratified Medicine Programme 2 is undertaking the large volume national molecular pre-screening which integrates with the NLMT. At study initiation, there are eight drugs being used to target 18 molecular cohorts. The aim is to determine whether there is sufficient signal of activity in any drug-biomarker combination to warrant further investigation. A Bayesian adaptive design that gives a more realistic approach to decision making and flexibility to make conclusions without fixing the sample size was chosen. The screening platform is an adaptable 28-gene Nextera next-generation sequencing platform designed by Illumina, covering the range of molecular abnormalities being targeted. The adaptive design allows new biomarker-drug combination cohorts to be incorporated by substantial amendment. The pre-clinical justification for each biomarker-drug combination has been rigorously assessed creating molecular exclusion rules and a trumping strategy in patients harbouring concomitant actionable genetic abnormalities. Discrete routes of pathway activation or inactivation determined by cancer genome aberrations are treated as separate cohorts. Key translational analyses include the deep genomic analysis of pre- and post-treatment biopsies, the establishment of patient-derived xenograft models and longitudinal ctDNA collection, in order to define predictive biomarkers, mechanisms of resistance and early markers of response and relapse., Conclusion: The SMP2 platform will provide large scale genetic screening to inform entry into the NLMT, a trial explicitly aimed at discovering novel actionable cohorts in NSCLC., Clinical Trial Isrctn: 38344105., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology..)

The E2A transcription factors promote the development of thymus-seeding cells, but it remains unknown whether these proteins play a role in T lymphocyte lineage specification or commitment. Here, we showed that E2A proteins were required to promote T-lymphocyte commitment from DN2 thymocytes and to extinguish their potential for alternative fates. E2A proteins functioned in DN2 cells to limit expression of Gata3, which encodes an essential T-lymphocyte transcription factor whose ectopic expression can arrest T-cell differentiation. Genetic, or small interfering RNA-mediated, reduction of Gata3 rescued T-cell differentiation in the absence of E2A and restricted the development of alternative lineages by limiting the expanded self-renewal potential in E2A−/− DN2 cells. Our data support a novel paradigm in lymphocyte lineage commitment in which the E2A proteins are necessary to limit the expression of an essential lineage specification and commitment factor to restrain self-renewal and to prevent an arrest in differentiation.

Purpose: To report the prevalence and incidence of ophthalmic pathology from a small, rural town in Haiti and to determine the leading causes of blindness in this population., Design: Retrospective study from 2002 to 2009. Data collected include visual acuity, intraocular pressure, and ocular and family history., Method: The study was conducted in a single center--Hospital de Lascahobas, Lascahobas, Haiti. Patients were natives of Lascahobas and the surrounding areas. Treatments were dispensed as indicated or warranted., Results: A total of 3702 patients were seen and examined: 51.52% were male and 49.48% were female. Ages ranged from 6 months to 92 years (mean, 48.69 SD +/- 49.94). Uncorrected refractive error was the most common diagnosis (53.27%), followed by presbyopia (43.76%), hyperopia (34.03%), and myopia (22.21%). A total 981 patients (26.50%) were diagnosed with cataract. Three hundred twenty-three (32.93%) cataract surgeries were performed. The overall postoperative complications rate was 9.29%. A total of 706 patients (19.07%) were diagnosed with glaucoma: 23.65% were glaucoma suspect and 76.35% were diagnosed with open-angle glaucoma (POAG). Of those diagnosed with POAG, 35.06% had end-stage (absolute) glaucoma. The mean age at diagnosis was 52.56 SD +/- 8.2 years. The mean intraocular pressure was 24.07 and 25.60 mm Hg, and the mean cup to disc ratio of the right eye (OD) and the left eye (OS), respectively, was 0.67 and 0.72., Conclusions: Glaucoma was the most common cause for blindness. The most common cause of correctable vision loss was uncorrected refractive error followed by cataract. Providing constant eye care in this region will most likely decrease the incidence of correctable and permanent vision loss.

Forty beef carcasses were classified for conformation and fatness. Besides, carcass weight, fat thickness (FT), carcass dimension, marbling by computer image analysis and ultrasound readings was recorded to complement grading. For predicting intramuscular fat (IMF) content, FT, number of intramuscular flecks and conformation increased R(2)-value from 0.19 to 0.64 compared to conformation alone. For visual marbling, ultrasound readings and thoracic depth (TD) increased the R(2)-value from 0.24 to 0.57 compared to fatness score (FS). The best variables for predicting weight of fabricated subprimals were carcass weight or compactness which is a function of carcass weight (R(2) between 0.94 and 0.63). Fatness score was poorer than FT for predicting yield of subprimals cuts from round (R(2)=0.16 vs. 0.50) and ultrasound readings for less valuable subprimals (R(2)=0.31 vs. 0.39). These results showed that other variables could be used in combination with carcass fatness or conformation to achieve a more accurate estimation of fat and carcass yield.

To investigate the striping phenomenon in fresh, enhanced pork, a series of experiments were undertaken to identify possible causes of the problem. No one factor (individual brine components, brine pH, ingredient concentration, enhancement pressure, meat and brine pH, or enhancement level) was specifically identified, which could be used to reduce the severity of the striping problem. Furthermore, tumbling the product for 2h, did not reduce the amount of striping, indicating once striping has occurred, it is permanent. Evaluation of the striping pattern indicates that the stripes are formed not only at the needle injection site, but also follow the muscle fiber orientation. The use of darker pork provided more of a contrast when evaluating striping, thus exacerbating the perceived level of striping.

The Edmonston vaccine strain of measles virus has potent and selective activity against a wide range of tumors. Tumor cells infected by this virus or genetically modified strains express viral proteins that allow them to fuse with neighboring cells to form syncytia that ultimately die. Moreover, infected cells may produce new virus particles that proceed to infect additional tumor cells. We present a model of tumor and virus interactions based on established biology and with proper accounting of the free virus population. The range of model parameters is estimated by fitting to available experimental data. The stability of equilibrium states corresponding to complete tumor eradication, therapy failure and partial tumor reduction is discussed. We use numerical simulations to explore conditions for which the model predicts successful therapy and tumor eradication. The model exhibits damped, as well as stable oscillations in a range of parameter values. These oscillatory states are organized by a Hopf bifurcation.

Different raw beef quality traits from four local Spanish cattle breeds were studied using correlation, factorial, discriminant and multiple regression analysis. The following variables were studied after 0, 5, 10 and 15 days of storage under 60% O2, 30% CO2 and 10% N2 modified atmosphere packaging (MAP): colour physical variables, meat pigments, sensory degradation of odour and colour, microbial counts, thiobarbituric acid (TBA), pH, drip loss, lipid composition and volatile compounds. The degradation of raw beef quality was related to the increase in 2,3,3-trimethylpentane, 2,2,5-trimethylhexane, 3-methyl-2-heptene, 2-octene, 3-octene, 2-propanone, Enterobacteriaceae and aerobial plate counts (APC), metmyoglobin (MMb), lightness (L*), yellowness (b*), drip loss and TBA. Among these variables, TBA, b* and MMb may be useful in evaluating raw beef quality. No variables related to fat, except for TBA, including pH were limiting factors of the colour and odour shelf-life of raw beef under MAP. Each breed had some characteristics that were unique and these differences may influence the stability of meat to oxidation depending on myoglobin concentration and the polyunsaturated fatty acid (PUFA)/saturated fatty acid (SFA) ratio.

Meat quality traits and palatability characteristics were evaluated on 240 barrows and gilts subjected to one of eight dietary regimens: (1) control (no supplement), (2) vitamin D(3)(D(3)), (3) vitamin E (E), (4) magnesium (Mg), (5) vitamins D(3) and E (D(3)/E), (6) vitamin D(3) and magnesium (D(3)/Mg), (7) vitamin E and magnesium (E/Mg), and (8) vitamins D(3) and E, and magnesium (D(3)/E/Mg). Barrows supplemented with D(3)/E/Mg had the highest (P>0.05) ultimate pH. Those supplemented with E had a higher ultimate pH than those supplemented with D(3)/Mg or the control. Gilts supplemented with Mg had the highest ultimate pH of all of the gilts while those supplemented with D(3) had the lowest. Barrows supplemented with Mg or E had more marbling than those supplemented with D(3) or D/E. Gilts supplemented with Mg had the most marbling when compared to other gilts. At 48 h postmortem, no differences due to dietary treatment were observed in L (∗), a (∗) or b (∗) value, drip loss or purge loss. At 14 days postmortem, no differences due to diet existed in sensory characteristics. Results suggest that supplementation of swine diets with some dietary supplement combinations of containing Mg may have some potential benefit for increasing ultimate pH.

The lipid composition of intramuscular fat from 30 young bulls of 5 Spanish cattle breeds (Asturiana de los Valles, Morucha, Parda Alpina, Pirenaica and Retinta) was studied. Steaks from each shortloin were packaged in 60% O(2), 30% CO(2) and 10% N(2) and aged for 0, 5, 10 and 15 days. Lipid classes obtained by thin layer chromatography and total fatty acids obtained by gas chromatography were evaluated. Meat from Asturiana de los Valles had high PL and C contents, and low TG contents that reflected its low intramuscular percentage content. This breed showed high FFA content that likely originated from lipolysis of PL. The main breed effect was due to the low intramuscular fat content observed in the Asturiana de los Valles. After 5 days, FFA decreased because they were probably transformed into other compounds. The Morucha breed may have a genetic predisposition for depositing MUFA, and the high MUFA and C14:0 values observed in the Morucha breed were likely due to its high intramuscular fat percentage. Regarding fatty acid composition, no "days of storage" effect was observed for any of the studied fatty acids, except for C18:3ω6 that increased during the first 5 days of storage in Asturiana de los Valles. Concerning the fatty acid composition, Asturiana de los Valles had the highest PUFA/SFA ratio, while Parda Alpina and Morucha possessed low ω6/ω3 ratios but high C22:6ω3 contents. Finally, the presence of C22:6ω3 and 15-CH(3)-C16:0 may be related to higher intramuscular fat contents.

Objective: Lack of or no prenatal care (NPC) is associated with preterm birth (PTB) and low birth weight (LBW). Our purpose was to determine whether LBW infants delivered after NPC have worse outcomes than LBW infants with prenatal care (PC)., Study Design: Eight thousand sixty-five consecutive women delivered at six hospitals in Shelby County, Tenn, were evaluated regarding clinical characteristics and perinatal outcomes depending on the occurrence of PC. Infant and LBW infant outcomes were evaluated on the basis of the occurrence of PC. Multivariate analysis was performed for neonatal outcomes adjusting for race, plurality, antenatal steroids, amnionitis, and ponderal index. A P value less than .05 was considered significant., Results: NPC women were more likely multiparous (80% vs 65%), African American (70% vs 61%), and uninsured (25% vs 4%), P<.0001 for each. PTB (36% vs 15%) and LBW (22% vs 12%) were more common with NPC, P<.0001 for each. Women with NPC had more advanced cervical dilation (ACD) greater than 4 cm (ACD: 63% vs 39%) and more amnionitis on admission (2% vs 1%), P

Background: Soy consumption is known to reduce plasma total cholesterol and LDL cholesterol in hypercholesterolemic subjects, but the responsible soy components and the effects in normocholesterolemic subjects remain unclear., Objective: The effects of soy isoflavone consumption on plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerol, apolipoprotein A-I, apolipoprotein B, and lipoprotein(a) concentrations and on LDL peak particle diameter were examined in normocholesterolemic, premenopausal women., Design: Thirteen healthy, normocholesterolemic, free-living, premenopausal female volunteers took part in this randomized, crossover-controlled trial. Each subject acted as her own control. Three soy isoflavone intakes (control: 10.0 +/- 1.1; low: 64.7 +/- 9.4; and high: 128.7 +/- 15.7 mg/d), provided as soy protein isolate, were consumed for 3 menstrual cycles each. Total cholesterol, HDL cholesterol, LDL cholesterol, and triacylglycerol were measured over the menstrual cycle. Apolipoprotein A-I, apolipoprotein B, lipoprotein(a), and LDL peak particle diameter were evaluated in the midluteal phase., Results: Total cholesterol, HDL-cholesterol, and LDL-cholesterol concentrations changed significantly across menstrual cycle phases (P < 0.005). During specific phases of the cycle, the high-isoflavone diet lowered LDL cholesterol by 7.6-10.0% (P < 0.05), the ratio of total cholesterol to HDL cholesterol by 10.2% (P < 0.005), and the ratio of LDL to HDL cholesterol by 13.8% (P < 0.002)., Conclusions: Isoflavones significantly improved the lipid profile across the menstrual cycle in normocholesterolemic, premenopausal women. Although of small magnitude, these effects could contribute to a lower risk of developing coronary heart disease in healthy people who consume soy over many years.

The observation that dietary stearic acid does not raise plasma cholesterol concentration is well documented, although the regulating mechanisms are not completely understood. Therefore, we examined the effect of dietary stearic acid on cholesterol absorption and sterol balance using male Syrian hamsters fed modified NIH-07 cereal-based diets selectively enriched in palmitic acid (16:0), stearic acid (18:0), trans fatty acid (18:1t), cis oleic acid (18:1c) or linoleic acid (18:2). All diets contained 17 g/100 g total fat and 0.05 g/100 g cholesterol; the five fat blends were enriched 30% with the fatty acid of interest above a constant fatty acid background. Cholesterol absorption efficiency was 50-55% in all treatment groups except for the 18:0 group, in which cholesterol absorption was significantly reduced to 21%. Plasma total cholesterol concentration was significantly lower in the 18:0 group compared to the 16:0 group. Fecal neutral steroid excretion was significantly greater in hamsters fed the high 18:0 diet compared to the other treatment groups. After accounting for unabsorbed dietary cholesterol, endogenous cholesterol excretion was about 100% higher in the 18:0 group. Consequently, the calculated rate of whole body cholesterol synthesis was significantly increased by dietary 18:0. Bile acid excretion accounted for only 12-20% of total sterol output by the hamsters in this study. Thus, the data suggest that reduced plasma cholesterol concentration in hamsters fed high 18:0 diets may be influenced by reduced cholesterol absorption and increased excretion of endogenous cholesterol.

Objective: We sought to evaluate the effect of antepartum and intrapartum antibiotic use on antimicrobial-resistant neonatal sepsis., Study Design: We analyzed perinatal outcomes for 8474 pregnancies (8593 live births) delivered at 6 hospitals. Data were collected regarding maternal antibiotic use and perinatal course, neonatal cultures, and outcomes. The diagnosis of confirmed neonatal sepsis required at least one positive blood or cerebrospinal fluid culture. Neonatal cultures were evaluated on the basis of the occurrence and timing of maternal antibiotic exposure., Results: There were 96 neonates with confirmed sepsis (11.2/1000 live births). Sepsis was 19.3-fold more common after preterm birth (57 vs 3. 1/1000; P <.001), with 76% of septic infants being delivered preterm. Forty-five percent of pathogens were ampicillin resistant. Ampicillin resistance increased with preterm birth (50% vs 26%; P =. 04), antepartum antibiotics (57% vs 34%; P =.03), intrapartum antibiotics (55% vs 28%; P <.01), and any prenatal antibiotic exposure (52% vs 22%; P =.01). Infection with an organism resistant to at least one maternal antibiotic was more common with intrapartum antibiotic exposure than with antepartum exposure only (57% vs 17%; P =.01). Regarding early-onset sepsis (n = 55), ampicillin resistance was more common with intrapartum antibiotics (50% vs 16%; P <.01), and resistance to at least one maternally administered antibiotic was more frequent with intrapartum exposure (56.7% vs 0%; P <.01)., Conclusions: Maternal antibiotic treatment is associated with neonatal sepsis by organisms resistant to ampicillin and to maternally administered antibiotics.

Background: Past 1H magnetic resonance spectroscopy (MRS) studies of the temporal lobe in schizophrenic patients have shown decreased levels of N-acetylaspartate (NAA) suggesting reduced neuronal density in this region. However, the measured volumes have been large and included contributions from mostly white matter., Methods: Short echo 1H MRS was used to measure levels of NAA and other metabolites (i.e., glutamate and glutamine) from a 6 cm3 volume in the left mesial-temporal lobe of 11 first-episode schizophrenic patients and 11 healthy control subjects of comparable age, gender, handedness, education, and parental education levels. Spectra were quantified without operator interaction using automated software developed in our laboratory. Metabolite levels were normalized to the internal water concentration of each volume studied. Images were also obtained to determine temporal lobe gray and white matter volumes., Results: No significant differences were found between levels of NAA or other metabolites, or gray and white matter volumes, in first-episode schizophrenic patients and comparison subjects., Conclusions: Since the volume studied was small compared to previous studies and contained mostly gray matter, this result suggests consequential NAA decreases may be restricted to regions of white matter.

Background: Current 31P spectroscopy research in schizophrenia has examined phospholipid metabolism by measuring the sum of phosphomonoesters and the sum of phosphodiester-containing molecules. Proton decoupling was implemented to measure the individual phosphomonoester and phosphodiester components. This is the first study employing this technique to examine schizophrenic patients., Methods: Multivoxel two-dimensional chemical shift in vivo phosphorous-31 magnetic resonance spectroscopy with proton decoupling was used to examine a 50-cm3 volume in prefrontal, motor, and parieto-occipital regions in the brain. Eleven chronic medicated schizophrenic patients were compared to 11 healthy controls of comparable gender, education, parental education, and handedness., Results: A significant increase in the mobile phospholipid peak area and its full width at half maximum was observed in the medicated schizophrenic patients compared to the healthy controls in the prefrontal region. Inorganic orthophosphate and phosphocholine were lower in the schizophrenic group in the prefrontal region., Conclusions: The increased sum of phosphodiester [mobile phospholipid + glycerol-3-phosphoethanolamine (GPEth) + glycerol-3-phosphocholine (GPCh)] in schizophrenic patients, measured in earlier studies, arises from the phospholipid peak (MP) and not the more mobile phosphodiesters (GPEth, GPCh) as was originally suspected. A decrease in the phosphocholine component of the phosphomonoesters was also observed in the schizophrenic patients. These findings are consistent with an abnormality in membrane metabolism in the prefrontal region in schizophrenics.

The study investigated the relationships among children's self-report of anticipatory pain and fear, physiological measures of distress, and previous medical experience in 62 outpatients during allergy skin testing. Younger (aged 3-7 years) and older (aged 8-12 years) children reported similar amounts of pain and fear. Girls reported more pain than boys. Older children and boys provided differential pain and fear ratings compared with younger children and girls. Younger children's self-report of distress was not related to any physiological measures, but older children's report of fear was significantly related to blood pressure. In girls, positive medical experience was correlated with less pain. The implications of these findings for the clinical measurement and intervention of children's distress during painful medical procedures are discussed.

This study was conducted to test the hypothesis that increased intestinal contents viscosity lowers plasma cholesterol concentrations by decreasing cholesterol absorption. Male Golden Syrian hamsters were fed for 4 wk diets containing 0.12% cholesterol, and either 4% cellulose or four different viscosity grades of hydroxypropyl methylcellulose (HPMC). Dietary HPMC confers viscosity in the small intestine but is resistant to fermentation. Cholesterol absorption efficiency was measured using the dual isotope ratio method, and plasma and liver cholesterol concentrations were determined enzymatically. Ex vivo viscosity of intestinal contents supernatants was measured using a Wells-Brookfield cone/plate viscometer, and the means of treatment groups ranged from 6 to 6532 mPa.s. Relative to dietary cellulose, all viscosity grades of HPMC resulted in significantly lower cholesterol absorption efficiency, lower plasma cholesterol concentration, and lower liver cholesteryl ester content. The logarithm of intestinal contents ex vivo viscosity was inversely correlated with dietary cholesterol absorption (r2 = 0.84, P = 0.028). Furthermore, dietary cholesterol absorption was positively correlated with plasma cholesterol concentration (r2 = 0.89, P = 0.017) and liver cholesteryl ester content (r2 = 0.96, P = 0.0031). Thus, the data suggest an independent role of intestinal contents viscosity in lowering plasma cholesterol concentration and liver cholesteryl ester content by reducing cholesterol absorption efficiency.

Posttransplantation lymphoproliferative disease (PTLD) is virtually always associated with Epstein-Barr virus (EBV) infection. BCL-2 and other proteins that confer resistance to apoptosis have been implicated in the pathogenesis of a variety of malignancies including lymphomas. One EBV protein, BHRF1, is a homologue of BCL-2, whereas another, the latency membrane protein 1 (LMP-1), upregulates BCL-2 expression in vitro. In the present study, we used immunohistochemistry to study the expression of these viral and cellular proteins as well as a variety of other EBV-encoded proteins in PTLD. BHRF1 was not detected in any PTLD specimen, whereas BCL-2 was shown in 12 of 17 lesions examined. With one exception, all LMP1-positive cases also expressed BCL-2 and the absence of LMP1 was always associated with a lack of BCL-2 expression. The results do not support a role for the EBV homologue of BCL-2 in PTLD, but they do support a role for viral induction of BCL-2 expression.

Posttransplant lymphoproliferative disorder (PTLD) is a frequently fatal complication of organ transplantation, occurring in 2% to 6% of cardiac recipients. Treatment remains poorly defined. Reduction in immunosuppression is effective in a proportion of cases, but mortality on the order of 80% is reported for patients requiring chemotherapy. The reason for such poor outcomes is unclear, but may be partly caused by the concomitant use of immunosuppressives. Nineteen consecutive cardiac recipients with PTLD were studied retrospectively in terms of clinical features and outcome. Patients were managed according to a uniform treatment approach. Initial therapy was a trial of reduced immunosuppression with concomitant acyclovir followed, if unsuccessful, by aggressive combination chemotherapy. The regimen used was predominantly ProMACE-CytaBOM. Six patients with phenotypically polyclonal PTLD presented less than 6 months after transplantation (median 6 weeks). Only 1 of 4 (25%) treated patients responded to reduced immunosuppression; the remainder died of multiorgan failure. Thirteen patients presented with phenotypically monoclonal disease > or = 6 months after transplantation. In 8 of 12 (75%) treated patients initial therapy was reduction in immunosuppression. None achieved complete remission (CR) and 2 experienced fatal rejection. Two patients achieved durable surgical CR. The remaining 8 patients received chemotherapy; 2 of 8 (25%) died during treatment, 6 of 8 (75%) achieved CR. None have relapsed, at a median duration of follow-up of 38 months. Neutropenic sepsis and subclinical doxorubicin cardiotoxicity at a mean cumulative dose of 63 mg/m2 were the principal toxicities. Our data indicate that aggressive chemotherapy is both feasible and effective in phenotypically monoclonal PTLD refractory to reduced immunosuppression. ProMACE-CytaBOM is well suited to cardiac recipients, minimizing doxorubicin exposure and obviating the need for concurrent immunosuppressives.

To test the hypothesis that newly synthesized cholesteryl esters are required for hepatic lipoprotein assembly and secretion, isolated livers of African green monkeys were perfused with medium containing an ACAT inhibitor. Three ACAT inhibitors with different structural and chemical properties were used: CI-976 (Parke-Davis), CP-113818 (Pfizer), or PD-138142-15 (Parke-Davis). Each compound produced variable effects on secretion of lipids and apolipoproteins. A significant decrease in the secretion rates of cholesteryl ester and apoB was common to all three inhibitors, indicating that fewer lipoprotein particles were secreted during ACAT inhibition. Triacylglycerol secretion was decreased in the presence of CP-113818 and PD-138142-15 but no decrease in triacylglycerol secretion was observed with CI-976. Particles secreted in the presence of CI-976 were enriched in triacylglycerol relative to apoB. Effects on secretion of other apolipoproteins (apoA-I, apoA-II, and apoE) were variable. When all data were combined, the percent inhibition of cholesteryl ester secretion and apoB secretion in the presence of ACAT inhibitors was positively correlated (r = 0.84), whereas a similar relationship was not observed between triacylglycerol and apoB. While the results demonstrate some lack of specificity for these ACAT inhibitors, the complimentary results using the three different ACAT inhibitors suggest that secretion of cholesteryl ester and apoB are coordinately regulated. The data suggest that newly synthesized cholesteryl esters may participate in and promote the assembly and secretion of hepatic apoB-containing lipoproteins. The availability of triacylglycerol during lipoprotein assembly, while also important, would appear to serve a role separate from that of cholesteryl ester.

A 72-year-old man presented with a posterior left ventricular aneurysm 5 years after undergoing quadruple coronary artery bypass grafting. An angiogram demonstrated patent saphenous vein grafts, but also showed incidental asymptomatic aortic aneurysms. Left ventricular endoaneurysmorrhaphy was performed through a left thoracotomy. This approach affords excellent exposure of a posterior left ventricular aneurysm, averts many of the risks associated with reoperation, and should be considered in patients who have undergone a median sternotomy and who do not require myocardial revascularization.

A 78-year-old woman underwent mitral reconstruction, consisting of a quadrangular posterior leaflet resection without a concomitant annular ring, for symptomatic mitral regurgitation. Postoperatively she became hypotensive while being treated with dopamine. Transesophageal echocardiography revealed systolic anterior motion of the mitral valve with significant mitral regurgitation. With discontinuation of the dopamine regimen, institution of phenylephrine administration, and volume loading of the ventricle the systolic anterior motion disappeared as did the mitral regurgitation. The patient recovered uneventfully.

A 48-year-old patient had a lucent right hemithorax and marked mediastinal shift of unknown duration that appeared on a chest radiograph. He was unchanged symptomatically from his baseline status. Video-assisted thoracoscopy was used to distinguish between tension from a giant bulla and a chronic tension pneumothorax.

The distributions of plasma lipoprotein alpha-tocopherol and lipids were studied in African green monkeys consuming diets enriched in saturated, monounsaturated, or polyunsaturated fatty acids. Plasma total alpha-tocopherol concentrations were not different among the animals fed the three diets, whereas plasma total cholesterol concentrations were significantly different among the diet groups. The alpha-tocopherol: total lipid molar ratio in plasma high density lipoproteins (HDL) was significantly higher compared to low density lipoproteins (LDL) and very low plus intermediate-sized low density lipoprotein (VLDL + ILDL) of each diet group, suggesting that HDL may exhibit a greater affinity for alpha-tocopherol. The presence of a positive correlation between HDL alpha-tocopherol and plasma apoA-I concentration and the absence of a correlation between HDL alpha-tocopherol and total lipid in HDL suggested that alpha-tocopherol associates with the protein moiety of HDL on the surface of the particle. A direct relationship between the plasma apoA-I: apoB molar ratio and the percentage of alpha-tocopherol found in the HDL fraction indicated that a greater proportion of alpha-tocopherol associates with HDL as the number of HDL particles in plasma increases relative to LDL particles. LDL from monkeys fed diets high in saturated fat contained 40% and 33% fewer alpha-tocopherol molecules per particle than LDL from monkeys fed polyunsaturated and monounsaturated fats, respectively. The phase transition temperature of LDL cholesteryl esters, indicative of the physical state of the lipids in the particle core, was well above body temperature in LDL from saturated fat-fed monkeys and was significantly higher compared to the other diet groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnetic resonance imaging of the thorax was performed on ten occasions in eight HIV-positive patients with a clinical picture suggestive of Pneumocystis carinii pneumonia. The diagnosis of PCP was subsequently confirmed on six occasions. Patients without PCP had low MRI profusion scores, while four of six patients with PCP had MRI profusion scores greater than 6/21. Neither the chest roentgenogram appearance nor computer-generated T1 and T2 relaxation times could reliably distinguish between these two groups. Magnetic resonance imaging may be useful in the early and noninvasive diagnosis of PCP in HIV-positive patients.

Confirmation of the diagnosis of intralobar pulmonary sequestration has usually required angiographic demonstration of the systemic arterial supply. We report a young man who presented with non-resolving pneumonia where magnetic resonance imaging (MRI) suggested the correct diagnosis by demonstrating two arteries arising from the aorta supplying the sequestrum. MRI appears to offer a safe, noninvasive alternative for the diagnosis of sequestration.

Four reading-related, information-processing tasks were administered to right-handed blind readers of braille who differed in level of reading skill and in preference for using the right hand or the left hand when required to read text with just one hand. The tasks were letter identification, same-different matching of letters that differed in tactual similarity, short-term memory for lists of words that varied in tactual and phonological similarity, and paragraph reading with and without a concurrent memory load of digits. The results showed interactions between hand preference and the hand that was actually used to read the stimulus materials, such that left preferrers were significantly faster and more accurate with their left hands than with their right hands whereas right preferrers were slightly but usually not significantly faster with their right hands than with their left hands. In all cases, the absolute magnitude of the left-hand advantage among left preferrers was substantially larger than the right-hand advantage among right preferrers. The results suggest that encoding strategies for dealing with braille are reflected in hand preference and that such strategies operate to modify an underlying but somewhat plastic superiority of the right hemisphere for dealing with the perceptual requirements of tactual reading. These requirements are not the same as those of visual reading, leading to some differences in patterns of hemispheric specialization between readers of braille and readers of print.

5 of 8 infarcted human myocardial tissues were shown to contain an angiogenesis factor which resembles that obtained from solid tumours. The concentration of angiogenesis factor, measured by radioimmunoassay, was similar to that in tumours. It is suggested that the myocardial-infarct angiogenesis factor modulates collateral enlargement or ingrowth of new blood vessels in the infarcted tissues.

Patients with active interstitial lung disease (ILD) are often treated with high-dose corticosteroids, although such therapy is not universally effective and has significant risks. Clinicians have utilized various ancillary diagnostic techniques to help with difficult treatment decisions. Since magnetic resonance imaging (MRI) has the theoretic and experimental potential of differentiating various stages of ILD, we prospectively studied 34 adult patients in a 0.15 Tesla resistive magnet body imager. The most severely affected patients, who were thought to warrant a steroid trial, had the greatest MRI image intensity, and dramatic improvement was seen following successful treatment. Qualitative MRI data were as useful as any other ancillary diagnostic technique (radiographic, physiologic, scintigraphic) in predicting clinical course. Computer-generated relaxation times were not sufficiently precise to differentiate active from inactive disease. Although limited by availability and cost, MRI appears to be a useful ancillary diagnostic technique in ILD patients facing immunomodulating therapy.

A rare case of a primary early T-cell non-Hodgkin's lymphoma (NHL) in the bronchus of a 10 year old boy is presented. Although histological examination of the biopsied material was compatible with the diagnosis of NHL or carcinoma, the use of monoclonal antibodies showed it to be an early T-cell NHL and not carcinoma. Accordingly the child was treated using a chemotherapy protocol of the UKCCG for NHL. The patient responded so well to his treatment regime that within 2 weeks of the initiation of chemotherapy there was re-expansion of the collapsed lobe. Six weeks later bronchoscopy was entirely normal with no evidence of residual tumour and now 15 months after the time of diagnosis he remains very well with normal chest X-ray.

Precooked beef slices from top round roasts were used in replicate trials to determine the effects of packaging treatment upon shelf-life characteristics (microbial growth and color attributes) during retail storage. Roasts were dry-roasted to an internal temperature of 60°C, cooled for 1 h, then sliced (3-4 mm). Slices were packaged in: (a) vacuum; (b) 15% CO 2 , 40% O 2 , 45% N 2 ; (c) 15% CO 2 , 20% O 2 , 65% N 2 ; or (d) 15% CO 2 , 10% O 2 , 75% N 2 and held at 4°C for up to 18 d. Enumeration of microorganisms and determination of color attributes were done at 0, 3, 6, 9, 12, 15, and 18 d of storage. Psychrotrophic counts were higher (P<.05) on slices stored 9-18 d in atmospheres containing ambient (20%) oxygen level as compared to the other packaging treatments. Vacuum packaging exhibited a greater lag phase for psychrotrophs. Vacuum packaged slices maintained a superior cooked beef color for 18 d and had greater (P<.05) chroma readings, indicating a greater color intensity.

One of the major tenets of current non-Hodgkin's lymphoma classifications is the relationship of morphologic subtypes to stages in the sequence of normal B-lymphocyte transformation occurring in the germinal follicle. To test this hypothesis, quantitative morphometric image analysis was carried out on in vivo and in vitro samples of mouse splenic lymphocytes in which transformation was induced by bacterial lipopolysaccharide (LPS), a specific B-cell mitogen. The results were compared with a similar analysis of germinal center lymphocyte populations of normal human spleen. In the in vivo mouse model, initial stages of B-cell transformation were detectable as early as 4 hours after LPS injection, and the process was essentially fully developed by 48-72 hours. Quantitative evaluation revealed that the majority of nuclear profiles were nearly spherical or only slightly eccentric and that no major alteration in nuclear contour occurred during any phase of the progressive increase in nuclear size following mitogen-induced lymphocyte transformation. In fact, in this system, B lymphocytes with a nuclear profile cleft of greater than or equal to 0.4 mu accounted for only 3% of the combined unstimulated and LPS-activated population assessed (N = 9936). This compared with normal human spleen, in which 16% of germinal center lymphocyte populations had similarly cleft nuclear profiles. Sequential alterations in the organization of condensed chromatin occurred concomitant with gradual nuclear enlargement during mitogen-induced mouse spleen lymphocyte transformation. A comparative morphologic and morphometric assessment of nuclear profiles of lymphocyte populations in germinal centers of normal human spleen provides indirect evidence for a similar pattern of nuclear alterations in human B lymphocytes. Autoradiographic data obtained from LPS-activated mouse splenic lymphocytes indicate that nuclear morphologic aspects of the transformation process can occur entirely within the G1 phase of the cell cycle. The results of this study suggest that subtypes of non-Hodgkin's lymphoma largely composed of neoplastic lymphocytes with extensively convoluted or cleft nuclei do not reflect a morphologic stage in the transformation of normal lymphocytes. In addition, the heterogeneous nuclear forms of follicular center cell lymphocytes would appear to result from parallel transformation processes involving cleaved and noncleaved nucleated lymphocytes and not the sequential pathway proposed by Lukes and Collins.