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Jesse Lopes da Silva,1 Giselle de Souza Carvalho,1 Lucas Zanetti de Albuquerque,1 Fabiana Resende Rodrigues,2 Priscila Valverde Fernandes,2 Daniel Kischinhevsky,1 Andreia Cristina de Melo1 1Division of Clinical Research and Technological Development, Brazilian National Cancer Institute, Rio de Janeiro, Brazil; 2Division of Pathology, Brazilian National Cancer Institute, Rio de Janeiro, BrazilCorrespondence: Jesse Lopes da Silva, Brazilian National Cancer Institute (INCA), Clinical Research Division, 37 André Cavalcanti Street, 5th Floor, Annex Building, Rio de Janeiro, 20231-050, Brazil, Tel/Fax +55 21 32076585, Email jesse.silva@inca.gov.brPurpose: This study aimed to compare the clinical behavior, clinicopathological and sociodemographic characteristics of patients with early-stage triple-negative breast cancer (TNBC) who belong to the HER2-low and HER2-zero subgroups.Patients and Methods: This study involved a thorough search in the internal database of a single Brazilian institution to identify women with TNBC who underwent neoadjuvant chemotherapy (NACT) followed by curative surgery within the period from January 2010 to December 2014. HER2 analysis through immunohistochemistry (IHC) and, if required, amplification by in situ hybridization, was conducted using core biopsy samples. The study assesses outcomes of residual cancer burden (RCB), event-free survival (EFS), and overall survival (OS).Results: A total of 170 cases were analyzed, with a mean age of 51.4 years (standard deviation, SD 11.2). The HER2 status was categorized as IHC 0, 1+, or 2+ in 80 (47.1%), 73 (42.9%), and 17 (10%) patients, respectively. No significant differences were observed in the prevalence of clinical pathological characteristics among the subgroups. The absence of significant results for clinicopathological and demographic features hindered the multivariate analysis of HER2 subgroups. Similarly, no significant differences were found in the RCB, EFS, and OS outcomes between HER2 subgroups.Conclusion: The findings of this study suggest that, in early-stage TNBC, the clinical behavior and survival outcomes of the HER2-low subgroup may not differ significantly from those of the HER2-zero subgroup.Keywords: HER2 status, HER2-low, biomarker, triple-negative breast cancer

Summary: Gene–gene interactions cause hidden genetic variation in natural populations and could be responsible for the lack of replication that is typically observed in complex traits studies. This study aimed to identify gene–gene interactions using the empirical Hilbert–Schmidt Independence Criterion method to test for epistasis in beef fatty acid profile traits of Nellore cattle. The dataset contained records from 963 bulls, genotyped using a 777 962k SNP chip. Meat samples of Longissimus muscle, were taken to measure fatty acid composition, which was quantified by gas chromatography. We chose to work with the sums of saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA), omega‐3 (OM3), omega‐6 (OM6), SFA:PUFA and OM3:OM6 fatty acid ratios. The SNPs in the interactions where P<10‐8 were mapped individually and used to search for candidate genes. Totals of 602, 3, 13, 23, 13, 215 and 169 candidate genes for SFAs, MUFAs, PUFAs, OM3s, OM6s and SFA:PUFA and OM3:OM6 ratios were identified respectively. The candidate genes found were associated with cholesterol, lipid regulation, low‐density lipoprotein receptors, feed efficiency and inflammatory response. Enrichment analysis revealed 57 significant GO and 18 KEGG terms (P < 0.05), most of them related to meat quality and complementary terms. Our results showed substantial genetic interactions associated with lipid profile, meat quality, carcass and feed efficiency traits for the first time in Nellore cattle. The knowledge of these SNP–SNP interactions could improve understanding of the genetic and physiological mechanisms that contribute to lipid‐related traits and improve human health by the selection of healthier meat products. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the association of single nucleotide polymorphisms (SNPs) with birth weight, weight gain from birth to weaning and from weaning to yearling, yearling height and cow weight in Nelore cattle. Data from 5064 animals participating in the DeltaGen and PAINT breeding programs were used. The animals were genotyped with a panel of 777 962 SNPs (Illumina BovineHD BeadChip) and 412 993 SNPs remained after quality control analysis of the genomic data. A genome-wide association study was performed using a single-step methodology. The analyses were processed with the BLUPF90 family of programs. When applied to a genome-wide association studies, the single-step GBLUP methodology is an iterative process that estimates weights for the SNPs. The weights of SNPs were included in all analyses by iteratively applying the single-step GBLUP methodology and repeated twice so that the effect of the SNP and the effect of the animal were recalculated in order to increase the weight of SNPs with large effects and to reduce the weight of those with small effects. The genome-wide association results are reported based on the proportion of variance explained by windows of 50 adjacent SNPs. Considering the two iterations, only windows with an additive genetic variance >1.5% were presented in the results. Associations were observed with birth weight on BTA 14, with weight gain from birth to weaning on BTA 5 and 29, with weight gain from weaning to yearling on BTA 11, and with yearling height on BTA 8, showing the genes TMEM68 (transmembrane protein 8B) associated with birth weight and yearling height, XKR4 (XK, Kell blood group complex subunit-related family, member 4) associated with birth weight, NPR2 (natriuretic peptide receptor B) associated with yearling height, and REG3G (regenerating islet-derived 3-gamma) associated with weight gain from weaning to yearling. These genes play an important role in feed intake, weight gain and the regulation of skeletal growth. [ABSTRACT FROM AUTHOR]

Carcass traits measured after slaughter are economically relevant traits in beef cattle. In general, the slaughter house payment system is based on HCW. Ribeye area (REA) is associated with the amount of the meat in the carcass, and a minimum of backfat thickness (BFT) is necessary to protect the carcass during cooling. The aim of this study was to identify potential genomic regions harboring candidate genes affecting those traits in Nellore cattle. The data set used in the present study consisted of 1,756 Nellore males with phenotype records. A subset of 1,604 animals had both genotypic and phenotypic information. Genotypes were generated based on a panel with 777,962 SNPs from the Illumina Bovine HD chip. The SNP effects were calculated based on the genomic breeding values obtained by using the single-step GBLUP approach and a genomic matrix re-weighting procedure. The proportion of the variance explained by moving windows of 100 consecutive SNPs was used to assess potential genomic regions harboring genes with major effects on each trait. The top 10 non-overlapping SNP-windows explained 8.72%, 11.38%, and 9.31% of the genetic variance for REA, BFT, and HCW, respectively. These windows are located on chromosomes 5, 7, 8, 10, 12, 20, and 29 for REA; chromosomes 6, 8, 10, 13, 16, 17, 18, and 24 for BFT; and chromosomes 4, 6, 7, 8, 14, 16, 17, and 21 for HCW. For REA, there were identified genes (CDKN2A and CDKN2B) involved in the cell cycle biological process which affects many aspects of animal growth and development. The SLC38A1 and SLC38A2 genes, both from SLC38 AA transporter family, was also associated with REA. The AA transporters are essential for cell growth and proliferation, acting as carriers of tissue nutrient supplies. Various genes identified for BFT (SORCS2, AQP3, AQP7, CDC42BPA, ASIP, and ACSS2) have been associated with lipid metabolism in different mammal species. One of the most promising genes identified for HCW was the PLAG1. There is evidence, in the literature, that this gene is located in putative QTL affecting carcass weight in beef cattle. Our results showed several genomic regions containing plausible candidate genes that may be associated with carcass traits in Nellore cattle. Besides contributing to a better understanding of the genetic control of carcass traits, the identified genes can also be helpful for further functional genomic studies. [ABSTRACT FROM AUTHOR]

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In order to contribute to the genetic breeding programs of buffaloes, this study aimed to determine the influence of environmental effects on the stayability (ST) of dairy female Murrah buffalo in the herd. Data from 1016 buffaloes were used. ST was defined as the ability of the female to remain in the herd for 1, 2, 3, 4, 5 or 6 years after the first calving. Environmental effects were studied by survival analysis, adjusted to the fixed effects of farm, year and season of birth, class of first-lactation milk yield and age at first calving. The data were analyzed using the LIFEREG procedure of the SAS program that fits parametric models to failure time data (culling or ST50), and estimates parameters by maximum likelihood estimation. Breeding farm, year of birth and first-lactation milk yield significantly influenced (P<0.0001) the ST to the specific ages (1 to 6 years after the first calving). Buffaloes that were older at first calving presented higher probabilities of being culled 1 year after the first calving, without any effect on culling at older ages. Buffaloes with a higher milk yield at first calving presented a lower culling probability and remained for a longer period of time in the herd. The effects of breeding farm, year of birth and first-lactation milk yield should be included in models used for the analysis of ST in buffaloes. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify genomic regions associated with the total amount of saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids in the beef of Nellore cattle. The investigated dataset contained records from 963 Nellore bulls, about two years old, finished in feedlot (90 days). Meat samples of Longissimus dorsi muscle, between the 12th and 13th ribs of the left half-carcasses, were taken to measure the fatty acids (FAs). FAs were quantified by gas chromatography (GC-2010 Plus - Shimadzu AOC 20i autoinjector) using SP-2560 capillary column (100 m × 0.25 mm diameter with 0.02 mm thickness; Supelco, Bellefonte, PA). The animals were genotyped using the high-density SNP panel (BovineHD BeadChip assay 777k, Illumina Inc., San Diego, CA). Those SNP markers with minor allele frequency less than 0.05, call rate less than 90%, monomorphic, located on sex chromosomes, and those with unknown position were removed from the analysis. After genomic quality control, 470,007 SNPs and 868 animals were available for the analyses. Missing genotypes were imputed using FImpute software. Genotypes were phased to haplotypes using fastPHASE software and then haplotype blocks were defined based on linkage disequilibrium using HaploView software. Genome-wide association analyses were performed considering one haplotype at a time. The model included fixed effects of contemporary group (92 levels), haplotype (linear regression on number of copies), and age at slaughter as a linear covariate. Bonferroni correction was applied at 5% significance to adjust for multiple tests. A total of 83,883 haplotypes were included in the genome-wide association analyses. From those haplotypes, 292, 17, and 31 were significantly associated (P < 0.05) with SFA, MUFA, and PUFA, respectively. Most associations were found on BTA17, BTA3, BTA1, BTA8, BTA25, and BTA2. These significant regions harbor genes such as GALNT12, SLC6A7, CAMK2A, SYTL3, EPAS1, PRKCB, EPHA6, MPZL1, UHMK1, KIRREL, FYN, LTBP1, PRKCE, SIK2, TOM1L1, NF1, DNAJA3, SH2B2, AFAP1L2, and AGAP1. These genes are involved in lipid metabolism, reproductive hormone receptors, transport and use of fatty acids and cholesterol, phospholipid and membrane hydrolysis and biosynthesis, energy metabolism, and protein kinase synthesis. Thus, the identification of these associated haplotypes may contribute to further studies to validate these regions and prospect candidate genes that would be useful for breeding programs to improve the beef quality of Nellore cattle. [ABSTRACT FROM AUTHOR]

Background: The place of death profoundly affects end-of-life care quality, particularly in cancer. Assisting individuals at home enhances support, privacy, and control, reducing healthcare costs. This study seeks to elucidate factors associated and trends in place of death by cancer in Brazil., Methods: Using data obtained from the National Mortality Information System, this study extracted tumour topography, sociodemographic characteristics, and the place of death (outcome classified into hospital or home death) by cancer in Brazil from 2002 to 2021., Findings: The analysis included 3,677,415 cases, with 82.3% of deaths occurring in hospitals and 17.7% at home. Most participants were male (53.1%), had gastrointestinal tumours (32.2%), and resided in the Southeastern region (48.7%). Home deaths were more frequent in the Northeastern (30.2%) and Northern (24.8%) regions compared to the Southern (17.1%) and Southeastern (12.2%) regions. A strong inverse correlation was found between home deaths and the Human Development Index of the region. Over the years, there was a reduction in home deaths, followed by a recent increase. Individuals with no formal education, indigenous individuals, and patients from the North, Northeast, and Central-West regions had higher rates of home deaths, while patients with haematological malignancies had lower rates compared to those with gastrointestinal tumours., Interpretation: The minority of deaths by cancer in Brazil occur at home, with distinct trends over time. Home death was associated with regional, racial and educational level differences., Funding: No funding., Competing Interests: Andréia Cristina de Melo has grants or contracts from Amgen, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, GSK, MSD, Novartis, Regeneron, and Roche, with payments made to the institution. Additionally, she has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Bristol Myers Squibb, GSK, MSD, Novartis, and Roche. Lívia Machado Moura has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Pfizer and Novartis. The remaining authors declare that they have no conflicts of interest., (© 2024 The Author(s).)

Objective: To present strategies for managing tumor mass formation and their corresponding postoperative outcomes., Methods: We conducted a systematic literature review following the guidelines and protocol of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched the PubMed and EMBASE databases, screened titles and abstracts, and further evaluated full-text publications to select relevant studies. Additionally, a narrative review of other pertinent articles on PubMed was performed. Case reports, cohort studies, and clinical trials were included. Animal studies were excluded., Results: Of 6 patients enrolled in this study, most had American Spinal Injury Association Impairment Scale grade A (66.7%) following intramedullary injury, and 1 patient had American Spinal Injury Association Impairment Scale grade D (16.65%). The discovery time of the intramedullary mass formation ranged from approximately 5 to 14 years. Surgical intervention was performed in most cases (66.7%), with improvement reported in 3 of the surgical cases (75%). The majority of cases (83.3%) involved cervical lesions, while only 1 case (16.7%) involved a thoracic lesion., Conclusions: Due to the scarcity of described cases, there is no specific treatment for this tumor. Although our patient remained stable after conservative treatment, other studies have shown improvement in symptoms after mass resection. It is essential that the management of this complication be researched further due to the variety of clinical characteristics presented., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Transcranial direct current stimulation of the cerebellum (c-tDCS) improves motor performance in young and old adults. Based on the cerebellar involvement in Parkinson's disease (PD), c-tDCS could have potential to improve motor function in PD. The purpose was to determine the effects of c-tDCS on motor performance in PD while participants were on medications. The study was a randomized, double-blind, SHAM-controlled, between-subjects design. Twenty-two participants with PD were allocated to either a c-tDCS group or a SHAM group. All participants completed one experimental session and performed two motor tasks with their most affected hand in a Baseline condition (no stimulation) and an Experimental condition. The motor tasks were a visuomotor isometric precision grip task (PGT) and a rapid arm movement task (AMT). The primary dependent variables were force error and endpoint error in the PGT and AMT, respectively. There were no significant differences in force error or endpoint error in the Experimental condition between the c-tDCS and SHAM groups. These results indicate that an acute application of c-tDCS does not enhance motor performance in hand and arm tasks in PD. Longer-term c-tDCS application over multiple days may be needed to enhance motor function in PD.

The aim of this study was to analyze the genomic homology between cattle ( Bos taurus ) and buffaloes ( Bubalus bubalis ) and to propose a rearrangement of the buffalo genome through linkage disequilibrium analyses of buffalo SNP markers referenced in the cattle genome assembly and also compare it to the buffalo genome assembly. A panel of bovine SNPs (single nucleotide polymorphisms) was used for hierarchical, non-hierarchical and admixture cluster analyses. Thus, the linkage disequilibrium information between markers of a specific panel of buffalo was used to infer chromosomal rearrangement. Haplotype diversity and imputation accuracy of the submetacentric chromosomes were also analyzed. The genomic homology between the species enabled us to use the bovine genome assembly to recreate a buffalo genomic reference by rearranging the submetacentric chromosomes. The centromere of the submetacentric chromosomes exhibited high linkage disequilibrium and low haplotype diversity. It allowed hypothesizing about chromosome evolution. It indicated that buffalo submetacentric chromosomes are a centric fusion of ancestral acrocentric chromosomes. The chronology of fusions was also suggested. Moreover, a linear regression between buffalo and cattle rearranged assembly and the imputation accuracy indicated that the rearrangement of the chromosomes was adequate. When using the bovine reference genome assembly, the rearrangement of the buffalo submetacentric chromosomes could be done by SNP BTA (chromosome of Bos taurus ) calculations: shorter BTA (shorter arm of buffalo chromosome) was given as [(shorter BTA length - SNP position in shorter BTA)] and larger BTA length as [shorter BTA length + (larger BTA length - SNP position in larger BTA)]. Finally, the proposed linkage disequilibrium-based method can be applied to elucidate other chromosomal rearrangement events in other species with the possibility of better understanding the evolutionary relationship between their genomes., (Copyright © 2020 Jordan de Abreu Santos et al.)

This research aimed to estimate genetic parameters for milk yield and type traits [withers height (WH), croup height (CH), body length (BL), croup length (CL), iliac width (ILW), ischial width (ISW), and thoracic circumference] in Murrah buffaloes and to identify genomic regions related to type traits by applying a single-step genome-wide association study. Data used to estimate the genetic parameters consisted of 601 records of milk yield in the first lactation and the aforementioned type traits. For the single-step genome-wide association study, 322 samples genotyped with a 90K Axiom Buffalo Genotyping array (Thermo Fisher Scientific, Santa Clara, CA) were used. Bivariate analysis revealed that heritability for milk yield (kg) at 305 d was 0.31 ± 0.11, whereas it ranged from 0.22 ± 0.07 to 0.34 ± 0.09 for the studied conformation traits. Based on the percentages of genetic variance explained by windows of 10 markers, there were 16 genomic regions explaining more than 0.5% of the variance for WH, CH, BL, CL, ILW, ISW, and thoracic circumference. Between those regions, 4 were associated with more than 1 trait, suggesting pleiotropic roles for some genes of Bos taurus autosome (BTA) 12 on CL and WH, BTA13 on ISW and ILW, BTA23 on CH and BL, and BTA28 on ISW and BL. Most of these regions coincide with known quantitative trait loci for milk traits. Thus, further studies based on sequence data will help to validate the association of this region with type traits and likely identify the causal mutations., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Stayability, which can be defined as the probability of a cow calving at a certain age when given the opportunity, is an important reproductive trait in beef cattle because it is directly related to herd profitability. The objective of this study was to estimate genetic parameters and to identify possible genomic regions associated with the phenotypic expression of stayability in Nellore cows. The variance components were estimated by Bayesian inference using a threshold animal model that included the systematic effects of contemporary group and sexual precocity and the random effects of animal and residual. The SNP effects were estimated by the single-step genomic BLUP method using information of 2,838 animals (2,020 females and 930 sires) genotyped with the Illumina High-Density BeadChip Array (San Diego, CA, USA). The variance explained by windows formed by 200 consecutive SNPs was used to identify genomic regions of largest effect on the expression of stayability. The heritability was 0.11 ± 0.01 when A matrix (pedigree) was used and 0.14 ± 0.01 when H matrix (relationship matrix that combines pedigree information and SNP data) was used. A total of 147 candidate genes for stayability were identified on chromosomes 1, 2, 5, 6, 9 and 20 and on the X chromosome. New candidate regions for stayability were detected, most of them related to reproductive, immunological and central nervous system functions.

The purpose of this study was to identify genomic regions associated with carcass traits in an experimental Nelore cattle population. The studied data set contained 2,306 ultrasound records for longissimus muscle area (LMA), 1,832 for backfat thickness (BF), and 1,830 for rump fat thickness (RF). A high-density SNP panel (BovineHD BeadChip assay 700k, Illumina Inc., San Diego, CA) was used for genotyping. After genomic data quality control, 437,197 SNPs from 761 animals were available, of which 721 had phenotypes for LMA, 669 for BF, and 718 for RF. The SNP solutions were estimated using a single-step genomic BLUP approach (ssGWAS), which calculated the variance for windows of 50 consecutive SNPs and the regions that accounted for more than 0.5% of the additive genetic variance were used to search for candidate genes. The results indicated that 12, 18, and 15 different windows were associated to LMA, BF, and RF, respectively. Confirming the polygenic nature of the studied traits, 43, 65, and 53 genes were found in those associated windows, respectively for LMA, BF, and RF. Among the candidate genes, some of them, which already had their functions associated with the expression of energy metabolism, were found associated with fat deposition in this study. In addition, ALKBH3 and HSD17B12 genes, which are related in fibroblast death and metabolism of steroids, were found associated with LMA. The results presented here should help to better understand the genetic and physiologic mechanism regulating the muscle tissue deposition and subcutaneous fat cover expression of Zebu animals. The identification of candidate genes should contribute for Zebu breeding programs in order to consider carcass traits as selection criteria in their genetic evaluation., Competing Interests: The authors have declared that no competing interests exist.

We reviewed the history, volume, outcomes, uniqueness, and challenges of living donor liver transplantation (LDLT) in Latin America. We used the data from the Latin American and Caribbean Transplant Society, local transplant societies, and opinions from local transplant experts. There are more than 160 active liver transplant teams in Latin America, but only 30 centers have used LDLT in the past 2 years. In 2014, 226 LDLTs were done in the region (8.5% of liver transplant activities). Living donor liver transplantation is mainly restricted to pediatric patients. Adult-to-adult LDLT activities decreased after the implementation of the model for end-stage liver disease score and a concomitant increase on the rate of deceased donors per million population. Posttransplant outcome analysis is not mandatory, transparent or regulated in most countries. More experienced teams have outcomes comparable to international expert centers, but donor and recipient morbidity might be underreported. Latin America lags behind in terms of the number of adult LDLT and the rate of living donor utilization in comparison with other continents with similar donation rates. Local alliances and collaborations with major transplant centers in the developed world will contribute to the development of LDLT in Latin America.

The aim of this study was to estimate genetic and phenotypic associations of growth traits with carcass and meat traits in Nellore cattle. Data from male and female animals were used for weaning weight (WW; N = 241,416), yearling weight (YW, N = 126,596), weight gain from weaning to yearling (GWY, N = 78,687), and yearling hip height (YHH, N = 90,720), respectively; 877 male animals were used for hot carcass weight (HCW) and 884 for longissimus muscle area (LMA), backfat thickness (BT), marbling score (MS), and shear force (SF). The variance components were estimated by the restricted maximum likelihood method using three-trait animal models that included WW. The model for WW included direct and maternal additive genetic, maternal permanent environmental, and residual effects as random effects; contemporary group as fixed effects; and age of dam at calving and age of animal as covariates (linear and quadratic effects). For the other traits, maternal effects and the effect of age of dam at calving were excluded from the model. Heritability ranged from 0.10 ± 0.12 (LMA) to 0.44 ± 0.007 (YW). Genetic correlations ranged from -0.40 ± 0.38 (WW x LMA) to 0.55 ± 0.10 (HCW x YW). Growth, carcass, and meat traits have sufficient genetic variability to be included as selection criteria in animal breeding programs.

Buffalo milk has excellent physical and chemical qualities as a consequence of the high percentage of constituents. This milk property is desirable for the dairy industry because it facilitates manufacture of mozzarella cheese. We estimated genetic parameters for milk yield, milk fat and protein and their effects on mozzarella cheese production using Bayesian inference. Using information from 4907 lactation records of buffaloes, genetic and non-genetic parameters were estimated for accumulated 305-day milk yield (MY), milk fat (%F) and protein (%P) percentages and mozzarella production per lactation (MP). The (co)variance components were obtained by Bayesian inference using a multiple trait model, which included as fixed effects contemporary group, milking number and buffalo age at calving as covariables (linear and quadratic), along with the additive genetic, permanent environmental and residual random effects. Mean a posteriori heritability distributions for MY, %F, %P, and MP were 0.25, 0.30, 0.38, and 0.23, respectively. The genetic correlation estimates between MY with %P and %F were negative and moderate. Positive genetic correlation estimates varying from 0.19 (%P/MP) to 0.95 (MY/MP) were obtained among the traits. Milk yield, milk components, and mozzarella production in Murrah buffaloes have enough genetic variation for selection purposes. We conclude that selection to increase milk yield would be effective in improving mozzarella production.

With the improved control of acute diarrheal illness mortality with oral rehydration therapy, persistent diarrhea is now emerging as a major cause of childhood mortality in tropical developing areas like the impoverished populations in Brazil's Northeast. "Graveyard surveillance" in the rural community of Guaiuba in northeastern Brazil revealed fully half of the 70% diarrhea mortality was due to persistent diarrheal illnesses. Furthermore, 11% of 14 or more diarrheal illnesses per child per year in an urban slum in Fortaleza persisted beyond 14 days, a definition that clearly identified the high risk children for heavy diarrhea burdens. Not only did heavy diarrhea burdens ablate the key "catch-up" growth seen in severely malnourished children and in children following previous diarrheal illnesses, but malnutrition significantly predisposed children to a greater incidence and duration of diarrhea as well as a greater incidence of persistent diarrhea. Etiologic studies of 37 children presenting with persistent diarrhea to Hospital das Clinicas in Fortaleza revealed that Cryptosporidium (in 13%) and enteroadherent E. coli (36% with aggregative, 29% with diffuse and 13% with localized adherence to HEp-2 cells) were the predominant potential pathogens found in the stool or upper small bowel. These findings suggest that persistent diarrhea is emerging as an important health problem in Brazil's Northeast, that it identifies a high risk child for heavy diarrhea burdens, that important interactions occur with malnutrition and that Cryptosporidium and enteroadherent E. coli warrant further study as potential etiologies of this major cause of morbidity and mortality.