Systematic exploration of a decade of publications on psychiatric genetics in Latin America.

Psychiatric disorders have a great impact in terms of mortality, morbidity, and disability across the lifespan. Considerable effort has been devoted to understanding their complex and heterogeneous genetic architecture, including diverse ancestry populations. Our aim was to review the psychiatric genetics research published with Latin American populations from 2010 to 2019, and classify it according to country of origin, type of analysis, source of funding, and other variables. We found that most publications came from Brazil, Mexico, and Colombia. Also, local funds are generally not large enough for genome-wide studies in Latin America, with the exception of Brazil and Mexico; larger studies are often done in collaboration with international partners, mostly funded by US agencies. In most of the larger studies, the participants are individuals of Latin American ancestry living in the United States, which limits the potential for exploring the complex gene-environment interaction. Family studies, traditionally strong in Latin America, represent about 30% of the total research publications. Scarce local resources for research in Latin America have probably been an important limitation for conducting bigger and more complex studies, contributing to the reduced representation of these populations in global psychiatric genetics studies. Increasing diversity must be a goal to improve generalizability and applicability in clinical settings.

Rotavirus antigenemia as a common event among children hospitalised for severe, acute gastroenteritis in Belém, northern Brazil.

BACKGROUND: Rotavirus antigenemia and RNAemia (the presence of rotavirus RNA in serum) have been commonly identified among paediatric patients with acute gastroenteritis. In this study we examined the association between rotavirus antigenemia and clinical features, and sought to determine the genotypes of rotaviruses detected in paired stool and serum samples. METHODS: Paired stool and serum samples were obtained from children hospitalised for acute gastroenteritis in Belém, Brazil, between June 2012 and June 2015. The 20-point Vesikari scoring system was used to assess the disease severity upon a retrospective medical record review. Stool and serum samples were primarily screened for the presence of rotavirus antigen using a commercial ELISA assay. The rotavirus isolates from stool and serum samples were genotyped by using the classical reverse-transcriptase polymerase chain reaction (RT-PCR) and/or through nucleotide sequencing of VP4 and VP7 genes. Viral load was estimated using real-time RT-PCR. RESULTS: In total rotavirus antigen was detected in 109 (24.2%) stool samples from 451 children, whereas antigenemia occurred in 38.5% (42/109) of these patients. We demonstrated that patients positive for rotavirus RNA in paired stool and serum samples were more likely to have a higher frequency of vomiting episodes in a 24-h period (p = 0.0035). Our findings also suggested that children not vaccinated against rotavirus are more likely to develop antigenemia, as compared to those given at least one vaccine dose (p = 0.0151). G12P [8] and G2P [4] genotypes were predominant throughout the study period, accounting for 52.3% (57/109) and 27.5% (30/109) of the typed isolates, respectively. Ten stool-serum pairs could be typed for VP4 and VP7 genes. Seven of these pairs showed concordant results with G2P [4] genotype being detected in stool and serum samples, whereas discrepancies between genotypes (G2P [4]/G2P[NT] and G12P [8]/G2P[NT]) were seen in three pairs. CONCLUSIONS: Rotavirus antigenemia and RNAemia occur in a significant number of children hospitalised for acute gastroenteritis in Belém, Brazil, and may contribute to a greater disease severity, particularly translated into a greater number of vomiting episodes. This study documented a high concordance of genotypes detected in a subgroup of paired stool and serum samples.

The impact of everolimus in reducing cytomegalovirus events in kidney transplant recipients on steroid-avoidance strategy: 3-year follow-up of a randomized clinical trial.

There is no evidence of whether everolimus (EVR) reduces cytomegalovirus (CMV) events in patients receiving steroid-free regimens. Besides, studies evaluating a tacrolimus (TAC) and EVR regimen are limited to 1-year follow-up. In this single-center prospective randomized trial, the incidence of CMV and 3-year efficacy and safety outcomes of EVR were compared to those of mycophenolate sodium (MPS) in a steroid-free regimen based on low-exposure TAC. Both groups received rabbit anti-thymocyte globulin (r-ATG) induction (6 mg/kg) and the steroids were withdrawn at day 7. Maintenance immunosuppression consisted of TAC (4-7 ng/ml until month 3 and 2-4 ng/ml thereafter) plus EVR (3-8 ng/ml) in the EVR group (n = 59); and TAC (4-7 ng/ml during all follow-up) plus MPS (1440 mg) in the MPS group (n = 56). The EVR group presented with a lower incidence of CMV events (18.6% vs. 50%, P = 0.001). No differences were observed in biopsy-proven acute rejection (6.8% vs. 3.6%, P = 0.680),graft loss (0.0% vs. 1.8%, P = 0.487),death (6.8% vs. 1.8%, P = 0.365), or estimated glomerular filtration rate at 36 months (61.1 ± 25.4 vs. 66.3 ± 24 ml/min/1.73 m2 , P = 0.369). A higher proportion of patients discontinued MPS treatment (8.5% vs. 26.8%, P = 0.013) for safety issues. In conclusion, EVR was associated with lower rates of CMV events in patients induced with standard dose r-ATG and a maintenance steroid-free regimen based on TAC. This regimen effectively prevented acute rejection and demonstrated a more favorable safety profile. (ClinicalTrials.gov:NCT02084446).

Donor-Specific Anti-Human Leukocyte Antigens Antibodies, Acute Rejection, Renal Function, and Histology in Kidney Transplant Recipients Receiving Tacrolimus and Everolimus.

BACKGROUND: This analysis compared efficacy, renal function, and histology in kidney transplant recipients receiving tacrolimus (TAC) combined with everolimus (EVR) or mycophenolate (MPS). METHODS: This was a retrospective analysis from a randomized trial in kidney transplant recipients who received a single 3 mg/kg dose of rabbit antithymocyte globulin (r-ATG), TAC, EVR, and prednisone (PRED; r-ATG/EVR, n = 85), basiliximab (BAS), TAC, EVR, and PRED (BAS/EVR, n = 102) or BAS, TAC, MPS, and PRED (BAS/MPS, n = 101). We evaluated the incidence of de novo donor-specific anti-human leukocyte antigens antibodies (DSA) and histology on protocol biopsies at 12 months, and the incidence of acute rejection, estimated glomerular filtration rate (eGFR) and proteinuria at 36 months. RESULTS: At 12 months, there were no differences in de novo DSA (6.4 vs. 3.4 vs. 5.5%) or in subclinical inflammation (2.0 vs. 4.8 vs. 10.2%), interstitial fibrosis/tubular atrophy (57.1 vs. 58.5 vs. 53.8%) and C4d deposition (2.0 vs. 7.3 vs. 2.6%). At 36 months, there were no differences in the incidence of treatment failure (19.0 vs. 27.7 vs. 27.7%, p = 0.186), first biopsy-proven acute rejection (9.5 vs. 21.8 vs. 16.8%, p = 0.073), and urine protein/creatinine ratios (0.53 ± 1.05 vs. 0.62 ± 0.75 vs. 0.71 ± 1.24). eGFR was lower in the BAS/EVR compared to that in the BAS/MPS group (53.4 ± 20.9 vs. 50.8 ± 19.5 vs. 60.7 ± 21.2 mL/min/1.73 m2, p = 0.017) but comparable using a sensitive analysis (49.5 ± 23 vs. 47.5 ± 22.6 vs. 53.6 ± 27.8 mL/min/1.73 m2, p = 0.207). CONCLUSION: In this cohort, the use of EVR and reduced TAC concentrations were associated with comparable efficacy, renal function, and histological parameters compared to the standard-of-care immunosuppressive regimen.

Efficacy and Safety of Elective Conversion From Sotrastaurin (STN) to Tacrolimus (TAC) or Mycophenolate (MPS) in Stable Kidney Transplant Recipients.

BACKGROUND: This study aimed to evaluate the efficacy and safety outcomes of conversion strategies in stable kidney transplant recipients after premature termination of the sotrastaurin (STN) development program. METHODS: This is an exploratory and prospective study, including 38 stable renal transplant recipients. Tacrolimus (TAC) group [STN → mycophenolate sodium (MPS)] consisted of 9 patients receiving TAC, STN, and prednisone that were converted from STN to MPS. Everolimus (EVR) group (STN → TAC) consisted of 29 patients receiving EVR, STN, and prednisone that were converted from STN to TAC. RESULTS: In TAC (STN → MPS) group, dose-adjusted TAC concentrations decreased from baseline to first week (2.3 ± 1.1 versus 1.5 ± 1.0 ng·mL·mg, P < 0.05). Two patients experienced a first acute rejection episode. Conversion to MPS was associated with a higher incidence of adverse events. In EVR (STN → TAC) group, dose-adjusted EVR concentrations decreased from baseline to first week (3.6 ± 2.3 ng·mL·mg versus 1.9 ± 0.8 ng·mL·mg, P < 0.01). The proportion of patients with donor-specific antibodies was lower in TAC (STN → MPS) (11%) compared to EVR (STN → TAC) (31%) before conversion. Conversion from STN to TAC was associated with a reduction in estimated glomerular filtration rate (69.6 ± 16.9 versus 61.0 ± 18.8 mL·min·1.73 m, P < 0.01) and a decreased proportion of patients with donor-specific antibodies (31% versus 14%) at 12 months. CONCLUSIONS: Conversion from TAC/STN to TAC/MPS or from EVR/STN to TAC/EVR was associated with significant pharmacokinetic changes in both TAC and EVR whole-blood trough concentrations due to known drug-to-drug interaction, which were associated with changes in efficacy and safety.

Compartment-specific expression of natural killer cell markers in renal transplantation: immune profile in acute rejection.

Natural killer (NK) cells have been implicated in graft dysfunction. Here, we formulated hypothesis that distinct patterns of expression NK cells markers correlated with acute rejection in kidney transplantation. Therefore, we studied the pattern of NK cell markers CD56, CD57, and CD16 in different compartments of biopsies obtained from recipients diagnosed with acute graft rejection, with or without donor-specific antibodies (DSA). DSA-negative biopsies-from patients with acute T-cell mediated rejection (aTCMR) had an increased expression of CD56+ and CD57+ cells (P = 0.004 and P = 0.001) in the interstitial compartment in comparison with DSA-positive biopsies from patients acute antibody-mediated rejection (aABMR) with (aABMR C4d+) and without C4d deposition (aABMR C4d-). CD16+ cells was increased (P = 0.03) in the glomerular compartment in DSA-positive biopsies. We assume that CD16+ expression and antibody-dependent cellular cytotoxicity (ADCC) in microvascular injury can be associated with aABMR. IFN-γ release from cytoplasmic granules of NK cell could be associated with aTCMR. Our findings suggest that NK cells need to be carefully evaluated because variations in NK cell marker expression might imply the involvement of different immune system pathways in graft rejection.

Challenges on Production of a Certified Reference Material of Ochratoxin A in Roasted Coffee: A Brazilian Experience.

Background: Coffee is an important agricultural commodity with technical barriers for exportation because of possible contamination with ochratoxin A (OTA), a mycotoxin nephrotoxic and carcinogenic. The maximum limit for OTA in roasted coffee is 5.0 µg/kg in the European Union and 10 µg/kg in Brazil, and the use of certified reference materials (CRM) is required for reliable measurements. Objective: This paper describes the development of a candidate CRM of OTA in roasted coffee following the requirements of ISO 17034 and ISO Guide 35. Methods: A primary method of isotope dilution MS was developed and validated using (13C20)-OTA as internal standard. The sample preparation was based on AOAC Official Methods of AnalysisSM using immunoaffinity column. Results: The linear working range is 2.0-15.0 µg/kg, with recoveries of 92.2-110.8% and relative SDs lower than 12.4%. The method was successfully applied to the feasibility study, which defined the procedure for preparation of a large batch around 5 µg/kg. It was produced by spiking blank roasted coffee with OTA standard, mixing and filling in amber flasks with 50 g of coffee, and storing at -80°C. The homogeneity study showed an acceptable degree of heterogeneity of 1.44%, and the short-term-stability study defined the conditions for transportation as maximum temperature of 50°C up to 28 days. Conclusions: These results show that certification is possible. Highlights: The long-term stability study at -20°C is in progress, and the characterization will be conduzed by a interlaboratory comparison. This material will be an important tool for QC in laboratories.

Heightened expression of HLA-DQB1 and HLA-DQB2 in pre-implantation biopsies predicts poor late kidney graft function.

BACKGROUND: Accurate pre-transplant prediction of late graft function remains an unmet need in kidney transplantation. The aim of this study was to evaluate HLA genes expression levels in pre-implantation biopsies (PIB) of deceased donor kidneys as markers for long-term graft outcome. METHODS: HLA genes expression analysis was initially performed using microarray data of 53 PIB, previously generated by our laboratory. The validation analysis was performed by real-time PCR in 116 PIB from an independent cohort. RESULTS: The microarray data showed association between high expression levels of HLA class II genes, especially HLA-DQB1 and -DQB2, in kidneys from young (18 to 49-year-old) donors and poor (eGFR < 45 mL/min/1.73 m2) 1- and 5-year graft function. A subsequent study in an independent cohort, in which only HLA-DQB2 expression was evaluated, validated the association between increased HLA-DQB2 expression in PIB of kidneys from young donors and poor 1-year graft function: expression levels ≥0.0025 relative units conferred an odds ratio of 22.5, with positive and negative predictive values of 71.4% and 90.0%, respectively. CONCLUSION: Heightened expression of HLA-DQB1 and -DQB2 in PIB are promising tools for pre-transplant risk assessment of poor late graft function in transplants with kidneys from 18 to 49-year-old donors.

Influence of immunosuppressive drugs on the CD30 molecule in kidney transplanted patients.

BACKGROUND: Soluble CD30 (sCD30) is a suggested marker for kidney transplantation outcomes. We investigated whether sCD30 serum levels are influenced by immunosuppression and whether they correlate with findings in protocol biopsies and with CD30 gene expression in peripheral blood mononuclear cells (PBMC). METHODS: We studied 118 kidney transplant recipients that initially received tacrolimus (TAC) and, at month-3, were converted or not to sirolimus (SRL). RESULTS: sCD30 serum levels gradually declined after transplantation, being the decline more pronounced in the SRL group. CD30 gene expression in PBMC was higher in the SRL group than in the TAC group. Patients with IF/TA ≥ I in the month-24 protocol biopsy had higher sCD30 levels than patients without IF/TA, in the SRL group (P = .03) and in the TAC group (P = .07). CD30+ cells were observed in three out of 10 biopsies with inflammatory infiltrate from the SRL group. In mixed lymphocyte cultures, SRL and TAC diminished the number of CD30+ T cells and the sCD30 levels in the supernatant, but the effect of SRL was stronger. CONCLUSIONS: Overall, sCD30 levels are lower in SRL-treated patients, but the association between increased sCD30 levels and IF/TA at month-24 post-transplantation is stronger in SRL than in TAC-treated patients.

Detection and genetic characterization of the emergent GII.17_2014 norovirus genotype among children with gastroenteritis from Northern Brazil.

Norovirus is the most important cause of viral gastroenteritis outbreaks worldwide. Recently, a novel GII.17 norovirus variant emerged and caused epidemics in Asian countries, replacing the GII.4 Sydney 2012 strain in hospitalized cases. In this study we describe the emergence of this novel NoV GII.17_2014 strain in Brazil.

Predicting delayed kidney graft function with gene expression in preimplantation biopsies and first-day posttransplant blood.

The purpose of this study was to investigate possible markers for predicting delayed graft function (DGF). To this end we analyzed, in pre-implantation biopsies (PIB) and in first-day post-Tx peripheral blood mononuclear cells (PBMC), the expression of five genes (ACSL4, CUBN, DEFB1, FABP3, GK) through real-time TaqMan PCR assays. These genes were selected from a large scale gene expression study in PIB. DEFB1, FABP3 and GK expression levels in PIB were lower in cases with DGF and, in a multivariate analysis which included these genes and clinical variables, only FABP3 expression remained independently associated with DGF. FABP3 expression lower than -1.32 units of relative expression conferred an odds ratio for DGF of 41.1. Compared to the PBMC of recipients without DGF, recipients with prolonged DGF (pDGF) had lower ACSL4 and higher DEFB1 expression levels. In a multivariate analysis, including PBMC gene expression levels of ACSL4, DEFB1 and TLR4 (data from a previous study with the same patients) and clinical variables, only TLR4 remained independently associated with pDGF. In summary, this study revealed FABP3 expression in PIB as a marker for DGF and disclosed new genes possibly involved in the pathogenesis of DGF.

Post-transplant soluble CD30 levels are associated with early subclinical rejection in kidney transplantation.

Several studies have shown association of high pre- or post-transplant levels of soluble CD30 (sCD30) with acute rejection and poor late kidney transplant outcome. Our goal was to investigate whether sCD30 levels at month-3 post-transplant are associated with subclinical rejection, presence of CD30(+) cells within the graft, and expression of immune response genes in peripheral blood mononuclear cells. The study comprised 118 adult first kidney graft recipients, transplanted at a single center, receiving tacrolimus in low concentration. All were submitted to a protocol biopsy at month-3. Subclinical rejection was identified in 10 biopsies and sCD30 levels ≥ 61.88 ng/mL (P = 0.004), younger recipient age (P = 0.030) and non-Caucasian ethnicity (P = 0.011) were independently associated with this outcome. Rare CD30(+) cells were present in only two biopsies. There was a correlation between sCD30 levels and CD30 gene expression in peripheral blood mononuclear cells (r = 0.385, P = 0.043). These results show that high sCD30 levels are independent predictors of graft dysfunction and may contribute to patient selection protocols by indicating those who could benefit from a more thorough evaluation.

Subclinical Lesions and Donor-Specific Antibodies in Kidney Transplant Recipients Receiving Tacrolimus-Based Immunosuppressive Regimen Followed by Early Conversion to Sirolimus.

BACKGROUND: There is no evidence on the incidence of subclinical inflammation and scaring lesions in patients receiving tacrolimus (TAC) minimization and elimination immunosuppressive regimens. METHODS: This study analyzed preimplantation, 3 and 24 months protocol biopsies and anti-HLA donor-specific antibodies (DSA) in 140 low immunological risk kidney transplant recipients receiving reduced TAC exposure, prednisone, and mycophenolate, randomized at 3 months to be converted or not to sirolimus (SRL). RESULTS: Mean TAC concentrations were 6.0 ± 2.4 ng/mL and 5.8 ± 2.2 ng/mL at 3 and 24 months. The incidence of subclinical inflammation lesions at 3 months was 9.3%. The incidence of (interstitial fibrosis) IF/(tubular atrophy) TA at month 24 was 57.6%, higher in SRL compared to TAC group (68.8 vs 44.4%; P = 0.022). Patients converted to SRL showed higher incidence of acute rejection (7.3% vs 0%), proteinuria (59.6% vs 25%; P = 0.001), and DSA (17.8% vs 7.3%; P = 0.201), respectively. Biopsy-proven acute rejection (odds ratio [OR] 2.32, 95% confidence interval [95% CI], 0.979-5.518, P = 0.056), subclinical inflammation lesions at 3 months (OR, 11.75; 95% CI, 1.286-107.474; P = 0.029) and conversion to SRL (OR, 2.72; 95% CI, 1.155-6.383; P = 0.022) were associated with IF/TA at month 24. Black ethnicity (OR, 0.22; 95% CI, 0.058-0.873; P = 0.031), donor age (OR, 2.74; 95% CI, 1.329-5.649; P = 0.006), and conversion to SRL (OR, 2.34; 95% CI, 1.043-5.267; P = 0.039) were associated with inferior renal function at 24 months. CONCLUSIONS: In kidney transplant recipients receiving reduced TAC exposure, subclinical inflammation lesions at 3 months were associated with IF/TA at 24 months. Conversion from TAC to SRL was associated with inferior renal function, higher incidence of IF/TA, and trends to higher incidence of DSA at 24 months.

Investigation of apoptosis-related gene expression levels in preimplantation biopsies as predictors of delayed kidney graft function.

BACKGROUND: The purpose of this study was to investigate the expression of the gene coding for the antiapoptotic molecule Bcl-2, the proapoptotic molecule Bax, and the apoptosis executor enzyme caspase-3 in preimplantation renal biopsies (PIB) as markers for delayed graft function. METHODS: In this prospective single-center study, gene expression levels were evaluated using real-time TaqMan polymerase chain reaction in PIB of kidneys from 72 deceased donors (DDs) and 18 living donors (LDs). RESULTS: CASP3 and BAX expression levels were higher, whereas those of BCL2 were lower, in DD than in LD PIB. In biopsies from DD, BCL2 levels were lower in cases with DGF, whereas no differences were observed concerning CASP3 and BAX. The BAX/BCL2 gene expression ratio greater than 2.29 associated with DGF with an odds ratio of 2.00. A multiple regression analysis including data of TLR4 expression in the first day posttransplant PB from a previous study of our group conducted in the same patients revealed a very strong association of the combination of BAX/BCL2 greater than 2.3 in PIB and TLR4 of 0.95 uRE or lesser in PB with the occurrence of DGF, with OR of 120 and positive and negative predictive values of 91% and 92%, respectively. CONCLUSIONS: The power to predict DGF of the combination of high BAX/BCL2 expression in PIB and low TLR4 expression in the first day posttransplant peripheral blood observed in the present study is extremely high, in comparison to any other marker or combinations of markers so far published in the literature.

Antibodies against denatured HLA class II molecules detected in luminex-single antigen assay.

False-positive anti-HLA reactions may occur in Luminex-single antigen (SA) beads assays, and it is important to recognize them to correctly interpret the test. The purpose of this report is to describe a peculiar pattern of reactivity, characterized by positivity with beads coated with HLA-DRB1*09:01, DRB3*01:01, DRB3*02:02, DRB3*03:01, DPB1*02:01, DPB1*20:01 and DPB1*28:01, that was observed in 141 of 8121 serum samples tested in our laboratory with three different lots of the same kit (LABScreen(®) SA, One Lambda). These 141 serum samples came from 56 different patients on the kidney transplant waiting list, corresponding to 1% of the patients. Of these, 10 males had never been transfused or transplanted. About 66% of the patients had positive reactions against self-antigen HLA-DRB3 alleles. No reactions against native HLA-DRB1*09:01 were observed in flow cytometry crossmatch and in absorption/elution experiments, leading to the conclusion that the reactivity was due to antibodies against epitopes present in denatured forms of HLA-class II antigens. The occurrence of this reactivity pattern was associated with female gender and systemic lupus erythematosus (SLE).

Association of high post-transplant soluble CD30 serum levels with chronic allograft nephropathy.

The purpose of this study was to evaluate the association of post-transplant soluble CD30 (sCD30) levels, isolated or in combination with of anti-HLA class II antibodies and of serum creatinine levels, with kidney graft loss due to chronic allograft nephropathy (CAN), and type of lesions in graft biopsies for cause. The study comprised 511 first kidney graft recipients, transplanted at a single center, with a graft functioning for at least 2.8 years. A single blood sample was collected from each patient. sCD30 levels were determined by ELISA, and HLA antibodies by Luminex assay. The minimum follow-up after testing was 9.3 years. High sCD30 levels, set at sCD30 ≥ 34.15 ng/mL, the presence of HLA class II antibodies, and serum creatinine ≥ 1.9 mg/dL were independently associated with CAN-graft loss (P values <0.0001, 0.05, <0.0001, respectively), and the combined hazard ratio for CAN-graft loss was 20.2. Analyses of 166 biopsies for cause showed that high sCD30 levels and creatinine were independently associated with interstitial lesions. Post-transplant sCD30 serum levels, especially in conjunction with information regarding HLA class II antibodies and serum creatinine levels, provide valuable information regarding graft outcome and could be useful for the management of kidney transplant recipients.

TLR4 mRNA levels as tools to estimate risk for early posttransplantation kidney graft dysfunction.

BACKGROUND: The participation of Toll-like receptor (TLR) 4, an innate immunity receptor, has been previously demonstrated in the pathogenesis of acute renal injury. We aimed to investigate whether messenger RNA (mRNA) levels of TLR4 and its adapter molecule, myeloid differentiation primary response gene (MYD) 88, are associated with delayed graft function (DGF) and could be used as biomarkers of its occurrence. METHODS: TLR4 and MYD88 gene mRNA levels were evaluated with real-time polymerase chain reaction, in preimplantation biopsies (n=89) and first day posttransplantation samples of urine (n=67) and blood (n=80) from graft recipients and analyzed according to donor type (living or deceased) and DGF occurrence. RESULTS: Expression levels of both genes were higher in biopsies from deceased donors than from living donors (P<0.001 for both) but did not differ between deceased-donor kidney transplants with and without DGF; in urine, TLR4 expression levels were higher in patients with prolonged DGF (DGF lasting >14 days) (P=0.05, compared with cases without DGF); in blood, lower mRNA levels of TLR4 and MYD88 predicted pDGF occurrence with an accuracy of 86% and 87%, respectively. CONCLUSION: The expression levels of TLR4 and MYD88 were higher in kidneys from deceased donors than from living donors. Lower levels of expression of both genes in blood were associated with DGF occurrence. The prediction of prolonged DGF by low TLR4 and MYD88 expression levels in blood with a greater the 85% accuracy was the most important finding of this study.

Anti-HLA class II antibodies and chronic allograft nephropathy.

The purpose of this study was to prospectively analyze the relationship between posttransplant IgG anti-HLA class I and/or class II antibodies and graft failure due to chronic allograft nephropathy (CAN). We studied 512 first kidney graft recipients transplanted at a single center, with a graft functioning for at least 3 years. A single blood sample was collected from each patient, and the presence of antibodies was evaluated by PRA-ELISA. The median post-transplant time after blood collection was 4.4 years and did not differ between patients with or without anti-HLA antibodies. Among the 512 recipients, 55 (10.7%)were positive for anti-HLA class II, 20 (3.9%) for anti-HLAclass I, and 16 (3.1%) for anti-HLA class I and class II antibodies. After antibody evaluation, the patients were followed for at least 34 months. Anti-HLA class II antibodies and serum creatinine levels > or = 2 mg/dl at the time of antibody testing were independently associated with graft loss due to CAN, with relative risks (RR) of 3.29 and 13.82, respectively. When both factors were present, the RR rose to 36.07. In graft biopsies with CAN, the lesions believed to be mediated by antibodies (chronic glomerulopathy, arteriosclerosis, and lamination of the peritubular capillaries basement membrane) were more prevalent in biopsies with CAN from patients with anti-HLA class II antibodies. In conclusion, our data support not only an association but also a pathogenic role of anti-HLA class II antibodies in approximately 40% of chronic allograft cases.

A primeira residência brasileira de medicina de família dentro de uma instituição privada: a experiência das residentes / La primera residencia brasileña de medicina de familia dentro de una institución privada: la experiencia de las residentes / The first brazilian residence of family medicine inside a private institution: the experience of residents

A Medicina de Família é uma especialidade médica que propõe um novo modelo de profissional médico, com enfoque de formação diferenciada, centrada no cuidado do indivíduo, em atenção continuada e abrangente, coordenando também os componentes biopsicossociais. O médico de família credencia-se para responsabilizar-se pelo paciente no contexto hospitalar e contribuir para a coordenação dos cuidados, gerando por consequência uma maior qualidade no atendimento e satisfação por parte do paciente e seus familiares pelos cuidados recebidos. Seu enfoque centrado na pessoa contribui para que mesmo no ambiente hospitalar haja maior tranquilidade para a ponderação tanto do uso de recursos diagnósticos e terapêuticos muitas vezes desnecessários ou ineficazes, quanto no cuidado na aplicação de intervenções muito distantes da realidade doméstica do paciente e que após seu retorno para a casa deverão ser mantidas, tornando sua rotina mais difícil resultando em baixa aderência ao tratamento. A partir destas reflexões iniciais, o programa de residência médica em Medicina de Família é abordado com uma análise individual das atividades realizadas e as experiências cotidianas são comentadas a partir de casos clínicos vivenciados pelas residentes. E após 6 meses dentro de jornada da residência temos segurança em afirmar que hoje fazemos a medicina que sonhamos e que na prática, esta medicina faz a diferença na vida de nossos pacientes e seus familiares e que Medicina de Família é possível, e num país com tantas desigualdades sociais como o nosso, desponta com uma alternativa viável para uma saúde mais justa e humana.

Family Medicine is a medical specialty that proposes a new model for medical professionals, with a differentiated approach to education centered in caring for individuals, in a continued and broader assistance coordinating also biopsychosocial components. Family doctors is accredited to take responsibility for the patient in hospital settings and to contribute to the co-ordination of cares, producing consequently a higher quality of service and a greater satisfaction of patients and relatives to received care. An approach centered in the person contributes, even in hospital settings, better conditions for both deciding on the use of diagnostic and therapeutic resources very often unnecessary or ineffective and also in care in the application of interventions strange to the patients’ home reality but which must be maintained after they returning to their homes, making extremely difficult their routine in a way that almost prevents adhesion top treatments. From these initial reflections, the program of medical residence in Family Medicine is approached by means of an individual analysis of daily activities and a debate about daily experiences from clinical cases assisted by female residents After 6 months in residence we can certainly say that today we practice the kind of medicine we dream about and we know that in practice this kind of medicine makes a difference in the life of our patients and his relatives and which Family Medicine is possible We may also say in a country with so many social inequalities like ours, Family Medicine emerges as a viable alternative for a more just and human health care.

La Medicina de Familia es una especialidad médica que propone un nuevo modelo de profesional médico, dotado de un enfoque de formación diferenciada, centrada en el cuidado del individuo, en atención continuada e abarcadora, coordinando también los componentes biopsicosociales. El médico de familia acreditase para responsabilizarse del paciente en el contexto hospitalario y contribuir para la coordinación de los cuidados, generando por consiguiente una mayor cualidad en el atendimiento e satisfacción por parte del paciente y sus familiares por los cuidados recibidos. Su enfoque centrado en la persona contribuye para que el propio ambiente hospitalario proporcione mayor tranquilidad para la ponderación tanto del uso de recursos diagnósticos y terapéuticos muchas veces innecesarios o ineficaces, como del cuidado en la aplicación de intervenciones muy distantes de la realidad doméstica del paciente y que, después de su retorno a la casa, deberán ser mantenidas, tornando su rutina más difícil; y el resultado de eso es una baja adherencia al tratamiento. A partir de esas reflexiones iniciales, el programa de residencia médica en medicina de familia es abordado por medio de un análisis individual de las actividades realizadas, siendo las experiencias cotidianas comentadas a partir de casos clínicos vividos por las residentes. E, después de 6 meses en la jornada de la residencia, podemos afirmar con seguridad que hoy hacemos la medicina que soñamos y que, en la práctica, esa medicina hace la diferencia en la vida de nuestros pacientes y sus familiares; podemos afirmar de igual modo que la Medicina de Familia es posible y, en un país con tantas desigualdades sociales como el nuestro, despunta como una alternativa viable para una salud más justa y humana.

Análise in vivo da adaptação de apoios em prótese parcial removível / In vivo analysis of adaptation in support of removable partial denture

A confecção das Próteses Parciais Removíveis (PPR) na Universidade tem como orientação a adequação às necessidades dospacientes, ao mesmo tempo em que proporciona aos alunos um aprendizado voltado para a qualidade do trabalho protético. O objetivo desse trabalho foi avaliar a adaptação dos apoios de PPR nos seus respectivos nichos, executados por 20 alunos da Disciplina de PPR da Faculdade de Odontologia da UFF, utilizando como método a moldagem do descanso sob o apoio. Foram selecionados na Clínica da FO-UFF, 20 pacientes num total de 36 arcos a serem reabilitados com PPR cujo planejamento incluísse descansos em pré-molares e molares. Os preparos (n=100) com dimensões de 1/3 da largura vestíbulo-lingual do dente e profundidade 1,2 mm. As armações metálicas (Co-Cr) foram confeccionadas por único laboratório. Após a prova e ajustes, seguiu-se o registro da adaptação dos apoios com moldagem do descanso com silicona de condensação de baixa densidade. Removidos os excessos e examinados quanto a integridade com lupa foram obtidas imagens em microscópio óptico de cada corpo de prova. A presença de pelo menos uma perfuração no molde do nicho foi um indicativo de que houve adaptação do apoio no nicho. Observou-se que 78% dos moldes avaliados apresentavam perfurações, sendo que 35% delas ocorreram na borda do apoio, 3% no corpo do apoio e 40% em ambos. Os apoios desadaptados em número de 22 apresentaram uma média de 0,11 e desvio padrão de 0,88 entre os alunos. Os resultados mostram prevalência de adaptados e refletem a aprendizagem dos alunos.

Fabrication of Removable Partial Dentures (RPD) at the University is guided by meeting the needs of patients and simultaneouslyproviding students with an opportunity to learn with emphasis on the quality of the prosthetic work. The aim of this study was to evaluate the fit of RPD rests in their respective niches, performed by 20 students of the RPD Course at the UFF School ofDentistry, using the method of casting beneath the RPD rest on the retentive niche. At the FO-UFF Clinic, 20 patients were selected, representing a total of 36 dental arches to be rehabilitated with RPDs, whose planning would include RPD rests inpremolars and molars. The dimensions of preparations (n=100) were 1/3 of the vestibular-lingual width of the tooth and depth of1.2 mm. Metal frameworks (Co-Cr) were fabricated by a single laboratory. Try-in and adjustments were followed by registering the fit of the RPD rests by preparing casts of the retentive niches with low density condensation silicone. After excesses were removed and integrity was examined using a loupe, images of each test specimen were obtained by optical microscope. Thepresence of at least one perforation in the cast of the niche was an indication that the RPD rest fitted into the niche. It was observed that 78% of the casts evaluated presented perforations, with 35% of these occurring at the niche margin, 3% in the bodyof the niche and 40% in both sites. The 22 misfitting niches presented a mean of 0.11 and standard deviation of 0.88 among the students. The results showed prevalence of fitting, and reflected student learning.