Search

Background: Concerns have been raised about cardiac inflammation in patients with long COVID-19, particularly those with myocardial injury during the acute phase of the disease. This study was conducted to examine myopericardial involvement, detected by cardiac magnetic resonance (CMR) imaging in patients hospitalized for COVID-19., Methods: Adult patients hospitalized with COVID-19 who presented myocardial injury or increased D-dimers were enrolled in this prospective study. All patients were invited to undergo CMR imaging examination after discharge. During follow-up, patients with nonischemic myocardial or pericardial involvement detected on the first CMR imaging examination underwent second examinations. CMR imaging findings were compared with those of a control group of healthy patients with no comorbidity., Results: Of 180 included patients, 53 underwent CMR imaging examination. The mean age was 58.4 ± 18.3 years, and 73.6 % were male. Myocardial and pericardial LGE was reported in 43.4 % and 35.8 % of patients, respectively. Nonischemic myocardial or pericardial involvement was reported in 26 (49.1 %) patients. The prevalence of pericardial LGE was associated inversely with the interval between hospital discharge and CMR. COVID-19 survivors had higher end-systolic volume indices (ESVis) and lower left-ventricular ejection fractions than did healthy controls. Seventeen patients underwent follow-up CMR imaging; the end-diastolic volume index, ESVi, and prevalence of pericardial LGE, but not that of nonischemic LGE, were reduced., Conclusion: Among COVID-19 survivors with myocardial injury during the acute phase of the disease, the incidences of nonischemic myocardial and pericardial LGE and CMR imaging-detected signs of cardiac remodeling, partially reversed during follow-up, were high., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Health literacy is crucial to adherence to medical interventions in therapeutics, prevention, and diagnosis. The basis for literacy is knowledge. To accomplish the goals for the elimination of cervical cancer, one of the most prevalent and preventable cancers, we must understand the determinants of non-adherence and address them specifically to ensure patients' active participation., Aim: To determine women's knowledge regarding the manifestations of cervical cancer and its prevention., Materials and Methods: We conducted a cross-sectional study in an urban population from northern Portugal. Women aged 18 to 30 years were randomly assigned to answer the Cervical Cancer Awareness Measure questionnaire, including questions of knowledge about the causes and symptoms of cervical cancer, prospecting for individual and social-related determinants., Results: The total number of participants was 270, with a mean age of 24.7 years. Knowledge about symptoms scored 5.4 ± 2.6, with a maximum of 12 points, and knowledge about the causes scored 5.7 ± 1.9, with a maximum of 11 points. The correlation between both was 0.334. High education, high socio-economic status, self-perception of one's capacity to recognize symptoms, and knowledge about the HPV vaccine were associated with better knowledge., Discussion: Portuguese women present low knowledge about cervical cancer, potentially affecting their health through exposure to risk situations and non-adherence to routine screening., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rodrigues, Duarte, Costa, Pimentel, Chaves, Gomes, Santos, Santos, Moreira, Lobão, Nazaré and Santos.)

Background: Comorbidities such as obesity, hypertension, and diabetes are associated with COVID-19 development and severity, probably due to immune dysregulation; however, the mechanisms underlying these associations are not clear. The immune signatures of hypertensive patients with obesity with COVID-19 may provide new insight into the mechanisms of immune dysregulation and progression to severe disease in these patients., Methods: Hypertensive patients were selected prospectively from a multicenter registry of adults hospitalized with COVID-19 and stratified according to obesity (BMI ≥ 30 kg/m²). Clinical data including baseline characteristics, complications, treatment, and 46 immune markers were compared between groups. Logistic regression was performed to identify variables associated with the risk of COVID-19 progression in each group., Results: The sample comprised 213 patients (89 with and 124 without obesity). The clinical profiles of patients with and without obesity differed, suggesting potential interactions with COVID-19 severity. Relative to patients without obesity, patients with obesity were younger and fewer had cardiac disease and myocardial injury. Patients with obesity had higher EGF, GCSF, GMCSF, interleukin (IL)-1ra, IL-5, IL-7, IL-8, IL-15, IL-1β, MCP 1, and VEGF levels, total lymphocyte counts, and CD8 + CD38 + mean fluorescence intensity (MFI), and lower NK-NKG2A MFI and percentage of CD8 + CD38 + T cells. Significant correlations between cytokine and immune cell expression were observed in both groups. Five variables best predicted progression to severe COVID-19 in patients with obesity: diabetes, the EGF, IL-10, and IL-13 levels, and the percentage of CD8 + HLA-DR + CD38 + cells. Three variables were predictive for patients without obesity: myocardial injury and the percentages of B lymphocytes and HLA-DR + CD38 + cells., Conclusion: Our findings suggest that clinical and immune variables and obesity interact synergistically to increase the COVID-19 progression risk. The immune signatures of hypertensive patients with and without obesity severe COVID-19 highlight differences in immune dysregulation mechanisms, with potential therapeutic applications., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated., Methods: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury., Results: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8 + CD38 + mean fluorescence intensity (MFI), and percentage of CD8 + human leukocyte antigen DR isotope (HLA-DR) + CD38 - cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A) + MFI, percentage of CD8 + CD38 + cells, CD8 + HLA-DR + MFI, CD8 + NKG2A + MFI, and percentage of CD8 + HLA-DR - CD38 + cells. On multivariate regression, the CD8 + HLA-DR + MFI, CD8 + CD38 + MFI, and total lymphocyte count were associated significantly with myocardial injury., Conclusion: Our findings suggest that lymphopenia, CD8 + CD38 + MFI, and CD8 + HLA-DR + MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Guidelines recommend the diagnosis of diabetes should be based on either plasma glucose or glycated hemoglobin (HbA 1C ) findings. However, lately studies have advocated glycated albumin (GA) as a useful alternative to HbA 1c . We conducted a systematic review and meta-analysis to determine the overall diagnostic accuracy of GA for the diagnosis of diabetes., Content: We searched for articles of GA diabetes diagnostic accuracy that were published up to August 2021. Studies were selected if reported an oral glucose tolerance test as a reference test, measured GA levels by enzymatic methods, and had data necessary for 2 × 2 contingency tables. A bivariate model was used to calculate the pooled estimates., Summary: This meta-analysis included nine studies, totaling 10,007 individuals. Of those, 3,106 had diabetes. The studies showed substantial heterogeneity caused by a non-threshold effect and reported different GA optimal cut-offs for diagnosing diabetes. The pooled diagnostic odds ratio (DOR) was 15.93 and the area under the curve (AUC) was 0.844, indicating a good level of overall accuracy for the diagnosis of diabetes. The effect of the GA threshold on diagnostic accuracy was reported at 15.0% and 17.1%. The optimal cut-off for diagnosing diabetes with GA was estimated as 17.1% with a pooled sensitivity of 55.1% (95% CI 36.7%-72.2%) and specificity of 94.4% (95% CI 85.3%-97.9%)., Outlook: GA has good diabetes diagnostic accuracy. A GA threshold of 17.1% may be considered optimal for diagnosing diabetes in previously undiagnosed individuals., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Suicide represents a major health concern, especially in developing countries. While many demographic risk factors have been proposed, the underlying molecular pathology of suicide remains poorly understood. A body of evidence suggests that aberrant DNA methylation and expression is involved. In this study, we examined DNA methylation profiles and concordant gene expression changes in the prefrontal cortex of Mexicans who died by suicide., Methods: In collaboration with the coroner's office in Mexico City, brain samples of males who died by suicide (n = 35) and age-matched sudden death controls (n = 13) were collected. DNA and RNA were extracted from prefrontal cortex tissue and analyzed with the Infinium Methylation480k and the HumanHT-12 v4 Expression Beadchips, respectively., Results: We report evidence of altered DNA methylation profiles at 4430 genomic regions together with 622 genes characterized by differential expression in cases vs controls. Seventy genes were found to have concordant methylation and expression changes. Metacore-enriched analysis identified 10 genes with biological relevance to psychiatric phenotypes and suicide (ADCY9, CRH, NFATC4, ABCC8, HMGA1, KAT2A, EPHA2, TRRAP, CD22, and CBLN1) and highlighted the association that ADCY9 has with various pathways, including signal transduction regulated by the cAMP-responsive element modulator, neurophysiological process regulated by the corticotrophin-releasing hormone, and synaptic plasticity. We therefore went on to validate the observed hypomethylation of ADCY9 in cases vs control through targeted bisulfite sequencing., Conclusion: Our study represents the first, to our knowledge, analysis of DNA methylation and gene expression associated with suicide in a Mexican population using postmortem brain, providing novel insights for convergent molecular alterations associated with suicide., (© The Author(s) 2021. Published by Oxford University Press on behalf of CINP.)

Background: There is no study evaluating the use of glycated albumin (GA) for the detection of post-transplantation diabetes mellitus (PTDM) in kidney transplant recipients. We evaluated the overall accuracy of GA at four months after kidney transplantation., Methods: Diagnostic test accuracy study including 134 kidney transplant recipients without pre-existing diabetes. Receiver operator characteristic (ROC) curve was used to estimate sensitivity, specificity, likelihood ratios and area under the curve (AUC) for GA, considering oral glucose tolerance test (OGTT) and/or glycated hemoglobin (HbA1c) as reference criteria., Results: Thirty-three patients were diagnosed with PTDM by OGTT and/or HbA1c ≥ 6.5%. GA showed moderate accuracy to detect PTDM [AUC 0.673 (95% CI 0.557-0.789, p < 0.01)]. The use of OGTT and/or HbA1c ≥ 6.2% increased the number of PTDM cases from 33 to 38, and AUC was 0.713 (95% CI 0.608-0.819, p < 0.01). GA ≥ 17% showed specificity close to 90% when OGTT and/or HbA1c ≥ 6.5% were used as reference tests., Conclusions: GA showed low diagnostic accuracy for the detection of PTDM at the fourth month after transplantation. The use of a single GA point is not enough for the screening and diagnosis of PTDM; however, GA ≥ 17% presented high specificity to rule in the disease after kidney transplantation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Suicide rates vary substantially by sex. Suicides committed by males significantly outnumber female suicides. Disparities in community and social factors provide a partial explanation for this phenomenon. Thus, the evaluation of sex differences at a biological level might contribute to the elucidation of the factors involved in this imbalance. The aim of the present study was to evaluate sex-specific gene expression patterns in the suicidal brain., Methods: postmortem samples from the dorsolateral prefrontal cortex (DLPFC) of 75 Latino individuals were analyzed. We considered the following groups: i) male suicides (n = 38), ii) female suicides (n = 10), iii) male controls (n = 20), and iv) female controls (n = 7). Gene expression profiles were evaluated by microarrays. Differentially expressed genes among the groups were identified with a linear model. Similarities and differences in the gene sets between the sexes were identified., Results: Differentially expressed genes were identified between suicides and controls of each sex: 1,729 genes in females and 1,997 genes in males. Female-exclusive suicide genes were related to cell proliferation and immune response. Meanwhile, male-exclusive suicide genes were associated to DNA binding and ribonucleic protein complex. Sex-independent suicide genes showed enrichment in mitochondrial and vesicular functions., Limitations: Relatively small sample size. Our diagnosis approach was limited to information found on coroner's records. The analysis was limited to a single brain area (DLPFC) and we used microarrays., Conclusion: Previously unexplored sex differences in the brain gene expression of suicide completers were identified, providing valuable foundation for the evaluation of sex-specific factors in suicide., Competing Interests: Declarations of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: Considering that exercise programmes are related with a range of benefits for end-stage renal disease patients, we evaluated the association between haemodialysis (HD) patients' involvement in intradialytic exercise training with the burden of their family caregivers., Methods: In this cross-sectional study, 60 caregivers of HD patients were recruited, 30 of them who cared for patients that regularly participated in an exercise programme during dialysis sessions and 30 caregivers who looked after patients undergoing usual HD treatment without intradialytic exercise. The caregivers were submitted to the Caregiver Burden Scale (CBS) and their quality of life (short-form-36 (SF-36)), anxiety and depression levels were assessed. Data were expressed as mean ± SD or median (interquartile range)., Results: Multiple linear regression showed that the global CBS score was significantly associated with the exercise training after adjusting for age, educational level and anxiety level of caregivers, and dependency level of patients measured by the Lawton scale (coefficient of determination = 0.53; adjusted coefficient of determination = 0.48). Additionally, the caregivers of HD patients submitted to intradialytic exercise (42.0 ± 12.9 years, 33.3% male) compared to caregivers of patients undergoing usual treatment (50.7 ± 17.5 years, 26.7% male) exhibited less caregiver burden (global CBS score = 1.2 (0.2) vs 1.9 (0.7), P < 0.001), better quality of life (physical component score = 53.7 (9.6) vs 49.7 (16.2) and mental component score = 50.6 (17.5) vs 28.2 (32.5), P < 0.05) and lower anxiety (7.2 ± 4.2 vs 10.8 ± 4.1, P = 0.001) and depression levels (3.0 (3.3) vs 6.0 (5.3), P = 0.034), respectively., Conclusions: Intradialytic exercise training in HD patients was associated with lower burden of their family caregivers., (© 2019 Asian Pacific Society of Nephrology.)

Objective: Dual diagnosis (DD) is the co-occurrence of at least one substance use disorder and one or more mental disorders in a given individual. Despite this comorbidity being highly prevalent and associated with adverse clinical outcomes, its neurobiology remains unclear. Furthermore, patients with DD are at higher risk for suicidal behavior in comparison with single disorder patients. Our objective was to evaluate brain gene expression patterns in individuals with DD who died by suicide. Methods: We compared the gene expression profile in the dorsolateral prefrontal cortex of suicides with DD ( n  = 10) to the transcriptome of suicides with substance use disorder alone ( n  = 10), suicides with mood disorders (MD) alone ( n  = 13), and suicides without mental comorbidities ( n  = 5). Gene expression profiles were assessed by microarrays. In addition, we performed a brain cell type enrichment to evaluate whether the gene expression profiles could reflect differences in cell type compositions among the groups. Results: When comparing the transcriptome of suicides with DD to suicides with substance use disorder alone and suicides with MD alone, we identified 255 and 172 differentially expressed genes (DEG), respectively. The overlap of DEG between both comparisons (112 genes) highlighted the presence of common disrupted pathways in substance use disorder and MD. When comparing suicides with DD to suicides without mental comorbidities, we identified 330 DEG, mainly enriched in neurogenesis. Cell type enrichment indicated higher levels of glial markers in suicides with DD compared to the other groups. Conclusions: Suicides with DD exhibited a gene expression profile distinct from that of suicides with a single disorder, being substance use disorder or MD, and suicides without mental disorders. Our results suggest alteration in the expression of genes involved in glial specific markers, glutamatergic and GABAergic neurotransmission in suicides with DD compared to suicides with a single disorder and suicides without mental comorbidities. Alterations in the expression of synaptic genes at different levels were found in substance use disorder and MD.

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by fungi of the genus Paracoccidioides spp., which mainly affects workers in rural regions of Latin America. Although the antifungal agents currently available for the treatment of PCM are effective in controlling the disease, many months are needed for healing, making the side effects and drug interactions relevant. In addition, conventional treatments are not able to control the sequelae left by PCM, even after the cure, justifying the search for new therapeutic options against PCM. In this context, the enzyme homoserine dehydrogenase of P. brasiliensis (PbHSD) was used to screen a library of natural products from the Zinc database using three different docking programs, i.e. Autodock, Molegro, and CLC Drugdiscovery Workbench. Three molecules (Zinc codes 2123137, 15967722, and 20611644) were better ranked than the homoserine substrate (HSE) and were used for in vitro trials of the minimum inhibitory concentration (MIC) and minimal fungicidal concentration (MCF). All three molecules presented a fungicidal profile with MICs/MCFs of 8, 32, and 128 μg mL -1 , respectively. The two most promising molecules presented satisfactory results with wide therapeutic ranges in the cytotoxicity assays. Molecular dynamics simulations of PbHSD indicated that the ligands remained bound to the protein by a common mechanism throughout the simulation. The molecule with the lowest MIC value presented the highest number of contacts with the protein. The results presented in this work suggest that the molecule Zinc2123137 may be considered as a hit in the development of new therapeutic options for PCM.

Background We conducted a systematic review and meta-analysis to establish the overall accuracy of glycated hemoglobin (HbA1c) in the diagnosis of gestational diabetes mellitus (GDM) diagnosis. Methods We searched MEDLINE, EMBASE, SCOPUS and ClinicalTrials.gov up to October 2018, using keywords related to GDM, HbA1c and diagnosis. Studies were included that were carried out with pregnant women without previous diabetes that assessed the performance of HbA1c (index test) compared to the 75 g oral glucose tolerance test (OGTT) (reference test) for the diagnosis of GDM, that measured HbA1c by standardized methods and presented data necessary for drawing 2 × 2 tables. Results This meta-analysis included eight studies, totaling 6406 pregnant women, of those 1044 had GDM. The diagnostic accuracy of HbA1c was reported at different thresholds ranging from 5.4% (36 mmol/mol) to 6.0% (42 mmol/mol), and the area under the curve (AUC) was 0.825 (95% confidence interval [CI] 0.751-0.899), indicating a good level of overall accuracy. The pooled sensitivities and specificities were 50.3% (95% CI 24.8%-75.7%) and 83.7% (67.5%-92.7%); 24.7% (10.3%-48.5%) and 95.5% (85.7%-98.7%); 10.8% (5.7%-19.41%) and 98.7% (96.2%-99.5%); 12.9% (5.5%-27.5%) and 98.7% (97.6%-99.3%), for the cut-offs of 5.4% (36 mmol/mol), 5.7% (39 mmol/mol), 5.8% (40 mmol/mol) and 6.0% (42 mmol/mol), respectively. Conclusions We observed a high heterogeneity among the studies. The effect of ethnicities, different criteria for OGTT interpretation and the individual performance of HbA1c methods may have contributed to this heterogeneity. The HbA1c test presents high specificity but low sensitivity regardless of the threshold used to diagnose GDM. These findings point to the usefulness of HbA1c as a rule-in test. HbA1c should be used in association with other standard diagnostic tests for GDM diagnosis.

Objective: To analyze sex differences in demographic and clinical characteristics of individuals who died by suicide in Mexico City. Method: Statistical analysis of residents of Mexico City whose cause of death was suicide, during two years period from January 2014 to December 2015, with a coroner's report. Suicide mortality rates were calculated by age, sex, and location within the city. The Chi-squared test was used to assess statistical differences. Results: From January 2014 to December 2015, 990 residents of Mexico City died by suicide (men: 78.28%, women: 21.72%). Among males, the highest mortality rates were among the groups of 20-24 and 75-79 years old, whereas in women, the group with the highest mortality rate was 15 to 19 years old. 74% of the sample used hanging as suicide method. However, men had higher rates of a positive result in the toxicology test (40%) ( p < 0.05). There was no concordance between male and female suicide by city jurisdictions. Conclusion: Our results provide evidence that the characteristics of Mexico City's residents who committed suicide had significant sex-related differences, including where they used to live. Understanding the contributory factors associated with completed suicide is essential for the development of effective preventive strategies.

Spermadhesins are a group of low molecular weight proteins present in seminal plasma. In Texel rams, they represent more than 70% of the seminal plasma proteins. Although their functions have not yet been fully clarified, there is much discussion about the role of these proteins in maintaining sperm viability during and after the semen freezing process. This work sought to isolate the major component of the seminal plasma from rams of the Texel breed (O. aries SPD2) and to evaluate its structural and biophysical characteristics in order to better understand its role in spermatic viability. The protein was isolated by centrifugation and ion exchange chromatography and its biophysical properties were evaluated by circular dichroism spectrometry. Molecular dynamics simulations of the modelled protein compared to the homologous bovine protein were also carried out. The results showed that O. aries SPD2 has a transition temperature (T m ) of 65 °C and a ΔH m of 322.5 kJ mol -1 , similar to the results for other spermadhesins described in the literature. The estimated composition of the secondary structure elements for the native protein is in agreement with that observed for the theoretical model. Its structural characteristics were preserved in simulations at temperatures of 27 °C and 40 °C, as was the case for bull spermadhesin. Taken together, these results suggest that the major component of the spermadhesins of Texel rams (O. aries SPD2) may play an important role in maintaining the viability of spermatozoa in fresh semen as well as after thawing., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Glycated hemoglobin (HbA1c) is an alternative test used for the diagnosis and monitoring of diabetes in kidney transplant recipients. Immunosuppressive drugs are the most important risk factors related with changes in the glucose metabolism after transplant. It is still unknown if they impact on the variability of HbA1c. We assessed the variability of HbA1c levels in a group of renal transplant recipients without diabetes during the first year after transplant., Methods: We estimated the variability of HbA1c in a group of 95 Brazilian kidney transplant recipients. Three EDTA whole blood samples were collected from each patient, one every four months for twelve months, totalizing 285 blood specimens. HbA1c values were measured by HPLC (Bio-Rad Variant™ II Turbo analyzer). Estimations were calculated according to Fraser and Harris method., Results: There was no difference in HbA1c mean levels between men and women. Within-subject and between-subject biological variations were 4.42% and 7.05%, respectively. The reference change value calculated for HbA1c was 16.15% and the index of individuality was 0.63., Conclusions: Kidney transplant patients without diabetes presented higher HbA1c within-subject variation than individuals without diabetes from the general population. This should be considered when interpreting HbA1c results in the diagnosis and management of diabetes after kidney transplantation., (Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

This work evaluated new potential inhibitors of the enzyme homoserine dehydrogenase (HSD) of Paracoccidioides brasiliensis , one of the etiological agents of paracoccidioidomycosis. The tertiary structure of the protein bonded to the analogue NAD, and l-homoserine was modeled by homology. The model with the best output was subjected to gradient minimization, redocking, and molecular dynamics simulation. Virtual screening simulations with 187,841 molecules purchasable from the Zinc database were performed. After the screenings, 14 molecules were selected and analyzed by the use of absorption, distribution, metabolism, excretion, and toxicity criteria, resulting in four compounds for in vitro assays. The molecules HS1 and HS2 were promising, exhibiting MICs of 64 and 32 μg · ml -1 , respectively, for the Pb18 isolate of P. brasilensis , 64 μg · ml -1 for two isolates of P. lutzii , and also synergy with itraconazole. The application of these molecules to human-pathogenic fungi confirmed that the HSD enzyme may be used as a target for the development of drugs with specific action against paracoccidioidomycosis; moreover, these compounds may serve as leads in the design of new antifungals., (Copyright © 2017 American Society for Microbiology.)

The current multidrug therapy for tuberculosis (TB) is based on the use of isoniazid (INH) in combination with other antibiotics such as rifampin, ethambutol and pyrazinamide. Literature reports have shown that Mycobacterium tuberculosis, the causative agent of TB, has become resistant to this treatment by means of point mutations in the target enzymes of these drugs, such as catalase-peroxidase (KatG). By means of equilibrium molecular dynamics in the presence of the ligand, this work evaluated ten point mutations described in the enzyme KatG that are related to resistance to INH . The results showed that the resistance mechanism is related to stereochemical modifications at the N-terminal domain of the protein, which restrict INH access to its catalytic site, not involving mechanisms of electrostatic nature. These results show insights that can be useful for the identification of new anti-TB drugs which may be able to circumvent this mechanism of resistance.

Background: Early detection of post-transplantation diabetes mellitus (PTDM) allows prompt clinical and pharmacological interventions, reducing the chance of adverse outcomes. We conducted a systematic review and meta-analysis to determine the overall diagnostic accuracy of glycated hemoglobin (HbA1c) for the diagnosis of renal PTDM., Methods: We searched MEDLINE, Embase and SCOPUS up to June 2016. Studies that included adults without previous diabetes were selected if they reported an oral glucose tolerance test as a reference test, HbA1c levels measured by standardized methods and data necessary for drawing 2 × 2 tables. A bivariate model was used to calculate the pooled estimates., Results: Based on 2057 kidney recipients from six studies, an HbA1c cut-off point of 6.5% in early months after transplant resulted in sensitivity of 0.48 [95% confidence interval (95% CI) 0.31-0.65], specificity of 0.96 (95% CI 0.95-0.97), positive likelihood ratio (PLR) of 12.0 (95% CI 7.4-19.5) and negative likelihood ratio (NLR) of 0.54 (95% CI 0.38-0.77). Based on 1888 kidney recipients from four studies, an HbA1c cut-off point of 6.2% early after transplant resulted in sensitivity of 0.76 (95% CI 0.49-0.91), specificity of 0.89 (95% CI 0.86-0.92), PLR of 7.18 (95% CI 5.29-9.75) and NLR of 0.27 (95% CI 0.11-0.65)., Conclusion: HbA1c cut-off points of 6.5% and 6.2% presented high specificity but low/moderate sensitivity to diagnose PTDM., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Aims/hypothesis: Disparities in HbA1c levels have been observed among ethnic groups. Most studies were performed in patients with diabetes mellitus (DM), which may interfere with results due to the high variability of glucose levels. We conducted a systematic review and meta-analysis to investigate the effect of ethnicity on HbA1c levels in individuals without DM., Methods: This is a systematic review with meta-analysis. We searched MEDLINE and EMBASE up to September 2016. Studies published after 1996, performed in adults without DM, reporting HbA1c results measured by certified/standardized methods were included. A random effects model was used and the effect size was presented as weighted HbA1c mean difference (95% CI) between different ethnicities as compared to White ethnicity., Results: Twelve studies met the inclusion criteria, totalling data from 49,238 individuals. There were significant differences between HbA1c levels in Blacks [0.26% (2.8 mmol/mol); 95% CI 0.18 to 0.33 (2.0 to 3.6), p <0.001; I2 = 90%, p <0.001], Asians [0.24% (2.6 mmol/mol); 95% CI 0.16 to 0.33 (1.7 to 3.6), p <0.001; I2 = 80%, p = 0.0006] and Latinos [0.08% (0.9 mmol/mol); IC 95% 0.06 to 0.10 (0.7 to 1.1); p <0.001; I2 = 0%; p = 0.72] when compared to Whites., Conclusions/interpretation: This meta-analysis shows that, in individuals without DM, HbA1c values are higher in Blacks, Asians, and Latinos when compared to White persons. Although small, these differences might have impact on the use of a sole HbA1c point to diagnose DM in all ethnic populations., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Studies suggest that iron deficiency anaemia (IDA) is associated with higher HbA1c levels. We conducted a control–case study to investigate the effect of IDA on HbA1c levels, measured by two commonly used methods, in non-diabetic individuals., Design and Methods: A total of 122 patients were included, 61 patients with IDA and 61 patients without anaemia. HbA1c was measured by both ion exchange HPLC Variant II Turbo BioRad and immunoturbidimetry (IT) Tina Quant II Roche Diagnostics in each sample. HbA1c results were compared between groups. For correlation analysis, patients were considered altogether., Results: There was a significant difference between the results of HbA1c in patients with IDA [HPLC 5.6 ± 0.4% (38 ± 4.4 mmol/mol) and IT 5.7 ± 0.4% (39 ± 4.4 mmol/mol)] and those measured in patients without anaemia [HPLC 5.3 ± 0.4% (34 ± 4.4 mmol/mol) and IT 5.3 ± 0.3% (34 ± 3.3 mmol/mol)], (p < 0.001). Significant negative correlations were observed between total haemoglobin (Hb), haematocrit, mean corpuscular volume (MCV) and ferritin with HbA1c values measured by IT (r = − 0.557; r = − 0.539; r = − 0.488; r = − 0.499; p < 0.01; respectively). These negative correlations were weaker with HbA1c measured by HPLC (r = − 0.272; r = − 0.250; r = − 0.273; r = − 0.229 for Hb, haematocrit, MCV and ferritin; p < 0.05; respectively). HbA1c results were higher in patients with moderate and severe anaemia. However mild anaemia did not show significant effects on HbA1c results measured by both methods., Conclusions: IDA affects HbA1c results and this effect is dependent on anaemia degree. These upward changes are statistically significant but they may be not clinically relevant when the overall variability of the HbA1c test is considered. The presence of slight anaemia is likely to have a minor effect on HbA1c levels favouring its use to diagnose diabetes in patients with mild anaemia.

We conducted a literature review about renal posttransplantation diabetes mellitus (PTDM), a glucose metabolism alteration with high incidence. Immunosuppressive therapy, by different diabetogenic mechanisms, is the major risk factor for PTDM. Although corticosteroids and calcineurin inhibitors are the drugs most related to PTDM, the mechanisms of other drugs have been also investigated. Available data in the literature show that, in renal transplant patients, the oral glucose tolerance test presents the highest diagnostic sensitivity for PTDM, although fasting plasma glucose is the most requested test. In addition, we also discussed the possible role of hemoglobin A1C in the diagnosis of PTDM. Renal PTDM is associated with patient survival reduction, increased cardiovascular mortality and has been linked to worsening graft function. As crucial as the screening, the accurate management of the disease can ameliorate graft and patient survival as well as the quality of life of this especial population. Several drugs have been studied in PTDM patients in order to achieve a better glycemic control and, in the best scenario, prevent PTDM. We present proper management approaches that should help to reduce the possible long-term consequences of PTDM., (Copyright © 2015 Elsevier B.V. All rights reserved.)

We carried out a systematic review and meta-analyses of studies that evaluated the possible effects of anemia, variant hemoglobin, and uremia on A1C levels in individuals without diabetes (DM). Medline and Embase were searched for studies that measured A1C values in groups with and without iron deficiency anemia (IDA) and/or iron deficiency (ID), variant hemoglobin and/or uremia by standardized methods. The difference between A1C levels in the groups with and without interferences was obtained by using random-effects meta-analysis and the effect size was presented as absolute difference of means (95% CI). Ten studies fulfilled the inclusion criteria, providing data from 11,176 participants without DM. There were no statistically significant differences in A1C in the presence of IDA/ID, HbS, and uremia by HPLC and uremia by immunoassay [0.79% (95% IC -0.39; 1.97), -0.13% (95% IC -0.51; 0.26), 0.15% (95% CI -0.58; 0.88) and -0.19% (95% CI -0.78; 0.40), respectively]. The effects of HbAS and uremia on A1C levels are within the expected individual variation and should not affect A1C results to diagnose DM. However, the effects of IDA/ID remain inconclusive and further studies are needed to clarify the glycation mechanisms in individuals with IDA/ID without diabetes., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The role of glycated hemoglobin (A1C) in the screening and diagnosis of posttransplantation diabetes mellitus (PTDM) is still not entirely understood. We evaluated the use of A1C test in renal transplant recipients at four months after transplantation., Methods: A total of 122 out of 274 patients without previous diabetes that underwent kidney transplantation were enrolled. ROC curve was used to analyze the performance of A1C to diagnose PTDM considering OGTT as the reference standard., Results: OGTT identified 32 (26.2%) patients with PTDM, whereas A1C≥6.5% (48 mmol/mol) identified only 16 patients. A1C showed moderate accuracy to detect PTDM in the ROC curve [AUC 0.832 (95% CI 0.740-0.924, p<0.001)]. A1C of 5.8% (40 mmol/mol) was the equilibrium point (sensitivity 75% and specificity 72.2%) and A1C≥6.2% (44 mmol/mol) showed high specificity of 93.3%., Conclusions: A1C≥6.5% (48 mmol/mol) is not enough to be used alone in the diagnosis of PTDM. The combined use of A1C cut-off points of ≤5.8% (40 mmol/mol) and ≥6.2% (44 mmol/mol) would reduce the number of OGTT by 85%. The use of an algorithm with A1C test in combination with FPG and/or 2h-PG proved to be the most efficient strategy to diagnose or rule out PTDM., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The neonatal ventral hippocampal lesion (NVHL) is an established neurodevelopmental rat model of schizophrenia. Rats with NVHL exhibit several behavioral, molecular and physiological abnormalities that are similar to those found in schizophrenics. Schizophrenia is a severe psychiatric illness characterized by profound disturbances of mental functions including neurophysiological deficits in brain information processing. These deficits can be assessed by auditory evoked potentials (AEPs), where schizophrenics exhibit abnormalities in amplitude, duration and latency of such AEPs. The aim of the present study was to compare the density of cells in the temporal cerebral cortex and the N40-AEP of adult NVHL rats versus adult sham rats. We found that rats with NVHL exhibit significant lower amplitude of the N40-AEP and a significant lower number of cells in bilateral regions of the temporal cerebral cortex compared to sham rats. Because the AEP recordings were obtained from anesthetized rats, we suggest that NVHL leads to inappropriate innervation in thalamic-cortical pathways in the adult rat, leading to altered function of cortical networks involved in processing of primary auditory information., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Dietary supplements containing bitter orange unripe fruit extract/p-synephrine are consumed worldwide for lose weight. This study were conducted to determine the concentration of p-synephrine in unripe fruits and leaves from Citrus aurantium Lin, C. sinensis Osbeck, C. deliciosa Ten, C. limon Burm and C. limonia Osbeck, collected in Southern Brazil, and to evaluate the acute toxicity of C. aurantium extract and p-synephrine. A high performance liquid chromatographic method with diode array detector (HPLC-DAD) was optimized and validated for determination of p-synephrine. The results indicate that all of analyzed samples present p-synephrine in amounts that range from 0.012% to 0.099% in the unripe fruits and 0.029 to 0.438% in the leaves. Acute oral administration of C. aurantium extracts (2.5% p-synephrine, 300-5,000 mg/kg) in mice produced reduction of locomotor activity, p-synephrine (150-2,000 mg/kg) produced piloerection, gasping, salivation, exophtalmia and reduction in locomotor activity, which was confirmed in spontaneous locomotor activity test. All the effects were reversible and persisted for 3-4h. The toxic effects observed seem to be related with adrenergic stimulation and should alert for possible side effects of p-synephrine and C. aurantium.

Population: Unrelated males from the São Paulo State, Brazil (n=617).

Mycobacterial pseudotumor (MP) is a rare pathologic presentation of both Mycobacterium tuberculosis and non-tuberculous mycobacterial disease, hitherto reported to occur only in immunosuppressed patients with or without human immunodeficiency virus infection. This lesion shares close pathologic resemblance to certain mesenchymal neoplasms, particularly Kaposi's sarcoma (KS), from which it must be properly differentiated due to distinct prognosis and therapy. We report a case of MP obliterating the lumen of the appendix vermiformis in a 34-year-old patient who died of complications of AIDS at our hospital in Rio de Janeiro. A total of 24 cases of MP (including our patient) have been described in the literature. MP has been found especially in lymph nodes, but extranodal lesions have been described in the skin, spleen, lung, bone marrow, brain and, in our patient, the appendix vermiformis. We offer a review of the other 23 published case reports of MP in both HIV-infected and uninfected patients and discuss the pathologic features that differentiate MP from KS.