Hepatocellular Carcinoma in Ceará: Epidemiology and Treatment in a Reference Liver Transplant Center in Northeast Brazil.

Hepatocellular carcinoma remains a significant worldwide malignancy and an important cause of cancer-related death. The incidence is increasing globally. In Latin America, there is no consistent data on the epidemiology of hepatocellular carcinoma. However, Brazil is considered a country with an intermediate incidence of this liver neoplasm. In the state of Ceará, situated in the northeast region of Brazil, there are no consistent clinical and epidemiologic data on the actual incidence and the treatment of hepatocellular carcinoma. The purpose of this article is to describe epidemiologic characteristics and treatment forms of patients with hepatocellular carcinoma who were treated in a Liver Transplant Center. A retrospective observational study was conducted using the database from the register of 299 patients with hepatocellular carcinoma between June 2004 and February 2022. Only patients born in Ceará were included. Therefore, most patients were eligible, based on the Milan Criteria, to undergo liver transplantation with a Model End Stage Liver Disease score of 12.48 ± 4.66 points, and the waiting list time was approximately 7 months with 8.7% hepatocellular carcinoma recurrence after liver transplant. A total of 38.5 % of cases were outside the Milan criteria at the time of cancer diagnosis, and transarterial chemoembolization was the main treatment choice. In conclusion, the diagnosis of hepatocellular carcinoma in Ceará mainly occurs in male patients with hepatitis C or alcoholism, with a mean age of 61.55 years and a previous diagnosis of liver disease. Liver transplantation was the best curative therapeutic form in patients with cirrhosis and hepatocellular carcinoma in Ceará, where a significant number of patients were diagnosed with intermediate and advanced-stage hepatocellular carcinoma, so public health policies are important for the screening and monitoring of liver disease.

Optimization of GATE simulations for whole-body planar scintigraphic acquisitions using the XCAT male phantom with 177Lu-DOTATATE biokinetics in a Siemens Symbia T2.

Simulations of planar whole body acquisitions in therapeutic procedures are often extensively time-consuming and therefore rarely used. However, optimising tools and variance reduction techniques can be employed to overcome this problem. In this paper, a variety of features available in GATE are explored and their capabilities to reduce simulation time are evaluated. For this purpose, the male XCAT phantom was used as a virtual patient with 177Lu-DOTATATE pharmacokinetic for whole body planar acquisition simulations in a Siemens Symbia T2 model. Activity distribution was divided into 8 compartments that were simulated separately. GATE optimization techniques included reducing the amount of time spent in both voxel and detector tracking. Some acceleration techniques led to a decrease of CPU-time by a factor of 167, while image statistics were kept constant. In that context, the simulation of therapeutic procedure imaging would still require 46days on a single CPU, but this could be reduced to hours on a dedicated cluster.

Presence of Mycobacterium leprae DNA and PGL-1 antigen in household contacts of leprosy patients from a hyperendemic area in Brazil.

Leprosy is a highly infectious disease endemic to underdeveloped countries. In Maranhão State, Northeastern Brazil, the hyperendemic rate of 56.11 cases/100,000 inhabitants increased the necessity of better understanding the epidemiological profile of this population, particularly regarding efficient methods for evaluating individuals residing with diagnosed patients to understand disease transmission and the risk of infection. In this study, we examined the percentage of contacts with positive indices for Mycobacterium leprae DNA and phenol-glycolipid-1 antigen (PGL-1). PGL-1 was analyzed by an enzyme-linked immunosorbent assay, the ML-Flow test, and polymerase chain reaction of oral and nasal secretions of 808 leprosy contacts from Maranhão. PGL-1 was detected in 14.0% of patients and differed by operational classification of the index case (P < 0.05). Seropositive results of ML-Flow were 15.0% and identified individuals with and without Bacillus Calmette-Guérin vaccine scars. Molecular diagnosis detected M. leprae DNA in 5.6% of oral samples and 4.6% of nasal tissues, and 87% of subjects resided with high bacillary load patients. This study reinforces the efficacy of combining molecular and serological techniques to identify potential bacillus carriers in the asymptomatic stage of infection, such as in household contacts, highlighting the importance of these meth-ods for monitoring hyperendemic populations.

Levels of mannose-binding lectin in individuals with visceral leishmaniasis in the northeast region of Brazil.

Visceral leishmaniasis (VL) is one of the seven priority endemic diseases in the world. The clinical outcome of many infections is not only dependent on the pathogenic organism, but also on the genetic variability of the host susceptibility to infection. Mannose-binding lectin (MBL) is a protein that plays an important role in the innate immune system. The aim of this study was to compare the serum levels of MBL between healthy controls and carriers of VL. The VL cases were recruited randomly from the main hospitals and referral outpatient clinics for VL in São Luís, and from home visits. Determination of MBL protein levels was performed by enzyme-linked immunosorbent assay. Of the 161 patients with VL and the 161 healthy controls, 60.9 and 67.1% had high levels of MBL, respectively. There was no significant difference in MBL levels between cases and controls. Low socioeconomic status and living conditions are conducive to the occurrence of VL. Owing to the small number of existing studies, it is extremely important to conduct further studies on MBL levels and susceptibility to VL, especially in regions where the disease is endemic, such as Maranhão, Brazil.

Association of CD28 and CTLA-4 gene polymorphisms with aggressive periodontitis in Brazilians.

OBJECTIVE: Susceptibility to and severity of periodontal disease is influenced by gene polymorphisms related to the immune response. Co-stimulatory molecules, such as CD28 and CTLA-4, are critical in the development of such responses. Our hypothesis is that polymorphisms in genes that code for these molecules may be associated with periodontitis. The aim of the study was to investigate the association between +17 (T/C) CD28 and +49 (A/G) CTLA-4 gene polymorphisms and periodontitis in Brazilians. MATERIALS AND METHODS: Genomic DNA was obtained from oral swabs of 424 individuals categorized into three groups (control group, aggressive, and chronic periodontitis) considering clinical parameters such as probing depth and clinical attachment loss. The genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: There was an association between the T(-) genotype of the CD28 polymorphism and aggressive periodontitis (P = 0.04). Moreover, the A(+) genotype for CTLA-4 was associated with greater clinical attachment loss in non-smokers with aggressive periodontitis (P = 0.006, OR = 16.25, CI = 2.25-117.11). CONCLUSIONS: These findings show that T(-) in CD28 + 17 (T/C) and the A(+) in CTLA-4 +49 (A/G) genotypes are associated with susceptibility to aggressive periodontal disease. Thus, our study highlights these polymorphisms as potential genetic susceptibility markers of periodontitis in Brazilians.

The association between osteoporosis and static balance in elderly women.

SUMMARY: This study aimed at answering the question: do people with high bone loss have greater postural instability? Groups were separated into group 1: women with normal bone mineral density, group 2: women with osteopenia, and group 3: women with osteoporosis. The balance was evaluated in four upright postural situations. Osteoporosis group had greater oscillation in the anteroposterior displacement in all situations compared to control group and the greatest mediolateral displacement in all situations compared to other groups. INTRODUCTION: It is not known whether the presence of osteoporosis can be considered a factor aggravating the postural control. This study aimed at answering the question: do people with high bone loss have greater postural instability? METHODS: This study was divided into three groups: group 1 (n = 20) consisting of women with normal bone mineral density, group 2 (n = 20) women with osteopenia, and group 3 (n = 20) women with osteoporosis. All the participants were submitted to evaluation of the balance using the Polhemus system in four upright postural situations. RESULTS: Osteoporosis group had greater oscillation in the anteroposterior displacement in all situations compared to control group. The osteoporosis group also showed the greatest mediolateral displacement in all situations compared to other groups. CONCLUSION: The results suggest that osteoporotic women had the worst balance, possibly due to the more pronounced body changes compared to non-osteoporotic women.

Frequency distribution of XbaIG > T and HaeIIIT > C GLUT1 polymorphisms among different Brazilian ethnic groups.

GLUT is the major glucose transporter in mammalian cells. Single nucleotide polymorphisms (SNP) at GLUT1 promoter and regulatory regions have been associated to the risk of developing nephropathy in different type 1 and type 2 diabetic populations. It has been demonstrated that differences in allelic and genotypic frequencies of GLUT1 gene (SLC2A1) polymorphisms occur among different populations. Therefore, ethnic differences in distribution of GLUT1 gene polymorphisms may be an important factor in determining gene-disease association. In this study, we investigated the XbaIG > T and HaeIIIT > C polymorphisms in six different Brazilian populations: 102 individuals from Salvador population (Northern Brazil), 56 European descendants from Joinville (South Brazil), 85 Indians from Tiryió tribe (North Brazil) and 127 samples from Southern Brazil: 44 from European descendants, 42 from African descendants and 41 from Japanese descendants. Genotype frequencies from both sites did not differ significantly from those expected under the Hardy-Weinberg equilibrium. We verified that the allele frequencies of both polymorphisms were heterogeneous in these six Brazilian ethnic groups.

TNF-alpha gene polymorphism (-308G/A) and toxoplasmic retinochoroiditis.

AIM: To investigate the possible association between TNF-alpha (-308G/A) polymorphism and toxoplasmic retinochoroiditis (TR) in humans. METHODS: A cross-sectional study was performed which included 100 Brazilian patients with diagnosis of TR and 100 matched control subjects with positive serology to toxoplasmosis and no sign of uveitis. Genomic DNA was obtained from oral swabs of all subjects and amplified using the polymerase chain reaction (PCR) with specific primers flanking the locus -308 of TNF-alpha. PCR products were submitted to restriction endonuclease digestion and analysed by polyacrylamide gel electrophoresis to distinguish alleles, allowing the determination of the genotypes. RESULTS: There was no significant difference in the genotype (chi(2) = 0.79, p = 0.67), allele (chi(2) = 0.095, p = 0.75) and allele carriage (chi(2) = 0.70, p = 0.40) frequencies in TR patients compared with control subjects. Frequencies of the genotype (chi(2) = 2.05, p = 0.35) and allele (chi(2) = 0.13, p = 0.71) did not differ significantly between TR patients with and without recurrent episodes. CONCLUSION: This is the first study to investigate the association between TNF-alpha polymorphism and the occurrence of TR in humans. TNF-alpha gene polymorphism (-308G/A) does not seem to be associated with the occurrence or recurrence of TR.

Ethnic differences in the distribution of interleukin-6 polymorphisms among three Brazilian ethnic groups.

Polymorphisms in the interleukin-6 promoter region have been associated with diseases. In this study we investigated the -634G/C and -174G/C IL-6 promoter polymorphisms in three Brazilian ethnic groups. We verified that the allele frequencies of the two polymorphisms and haplotype frequencies varied significantly between the populations.

Closure of rRNA related gaps in the Chromobacterium violaceum genome with the PCR-assisted contig extension (PACE) protocol

In the finishing phase of the Chromobacterium violaceum genome project, the shotgun sequences were assembled into 57 contigs that were then organized into 19 scaffolds, using the information from shotgun and cosmid clones. Among the 38 ends resulting from the 19 scaffolds, 10 ended with sequences corresponding to rRNA genes (seven ended with the 5S rRNA gene and three ended with the 16S rRNA gene). The 28 non-ribosomal ends were extended using the PCR-assisted contig extension (PACE) methodology, which immediately closed 15 real gaps. We then applied PACE to the 16S rRNA gene containing ends, resulting in eight different sequences that were correctly assembled within the C. violaceum genome by combinatory PCR strategy, with primers derived from the non-repetitive genomic region flanking the 16S and 5S rRNA gene. An oriented combinatory PCR was used to correctly position the two versions (copy A and copy B, which differ by the presence or absence of a 100-bp insert); it revealed six copies corresponding to copy A, and two to copy B. We estimate that the use of PACE, followed by combinatory PCR, accelerated the finishing phase of the C. violaceum genome project by at least 40 per cent

A new set of bioinformatics tools for genome projects

A new tool called System for Automated Bacterial Integrated Annotation--SABIA (SABIA being a very well-known bird in Brazil) was developed for the assembly and annotation of bacterial genomes. This system performs automatic tasks of assembly analysis, ORFs identification/analysis, and extragenic region analyses. Genome assembly and contig automatic annotation data are also available in the same working environment. The system integrates several public domains and newly developed software programs capable of dealing with several types of databases, and it is portable to other operational systems. These programs interact with most of the well-known biological database/softwares, such as Glimmer, Genemark, the BLAST family programs, InterPro, COG, Kegg, PSORT, GO, tRNAScan and RBSFinder, and can also be used to identify metabolic pathways

A recombinant peptide antigen line immunoassay optimized for the confirmation of Chagas' disease.

BACKGROUND: The transfusion of contaminated blood has become the major route of transmission for Chagas' disease in Brazil. Current screening tests are insensitive and yield conflicting results, while confirmatory assays do not exist. A line immunoassay (INNO-LIA Chagas Ab [INNO-LIA]) combining relevant, immunodominant recombinant and synthetic antigens on a single nylon membrane strip was evaluated for the serologic confirmation of Chagas' disease. STUDY DESIGN AND METHODS: Sera from 1062 patients and healthy residents of four Brazilian regions endemic for Chagas' disease were used for test optimization. The established confirmation algorithm was evaluated with an independent set of positive (n = 75) and negative (n = 148) samples. RESULTS: In the optimization phase, without an established comparative gold standard, the results with the INNO-LIA were compared with those obtained in four other screening assays. In the validation phase, the INNO-LIA showed a sensitivity of 100 percent (95% CI, 95.21-100) and a specificity of 99.32 percent (95% CI, 96.29-99.98) for well-characterized sera. Moreover, its specificity reached 100 percent with a set of 40 sera obtained from patients with documented leishmaniasis. The interpretation criteria defined in this study indicated that the INNO-LIA accurately detected the presence of antibodies to various specific antigens of Trypanosoma cruzi. CONCLUSION: The INNO-LIA Chagas Ab assay may become the first commercial assay to reliably confirm the presence of antibodies to T. cruzi.

Evaluation of three commercial enzyme-linked immunosorbent assays for diagnosis of Chagas' disease.

Chagas' disease is a common cause of morbidity in Latin American countries. In Brazil, naturally occurring transmission of its etiologic agent, Trypanosoma cruzi, has been almost completely abolished through effective control programs aimed at the triatomid insect vector. Thus, transfusion of blood from infected donors has become the major route for contracting Chagas' disease due to the socioeconomically motivated migration of residents from areas where the disease is endemic to the larger urban centers. Therefore, the employment of screening tests is mandatory for all blood banks throughout the country. We compared the diagnostic performances of three commercially available screening assays used in routine testing in Brazilian blood banks: the Abbott Chagas antibody enzyme immunoassay (Abbott Laboratórios do Brasil, São Paulo), the BIOELISACRUZI kit (Biolab-Mérieux, Rio de Janeiro, Brazil), and the BIOZIMA Chagas kit (Polychaco S.A.I.C., Buenos Aires, Argentina). The evaluation was performed with sera obtained from chagasic patients and healthy residents of four different areas in Brazil where Chagas' disease is either endemic or emergent and where clinical manifestations of the disease and circulating parasite strains vary. The results obtained with each kit were compared to matched in-house enzyme-linked immunosorbent assay and immunofluorescence assay data obtained for each sample. Depending on the area under investigation, the three commercial kits produced specificity values between 93.3 and 100.0%, sensitivity values between 97.7 and 100%, and accuracies ranging from 93.6 to 100.0%.