Occupational Lead Exposure Ototoxicity Evaluated With Distortion-Product Otoacoustic Emissions.

OBJECTIVES: To evaluate the extent of hearing loss among pottery workers in Mexico exposed to lead. DESIGN: The authors conducted a cross-sectional study including 315 adult pottery workers. Auditory function was evaluated by air conduction pure-tone audiometry (pure-tone average) and distortion-product otoacoustic emission (DPOAE) levels (amplitude and signal-to-noise ratio). Lead exposure was assessed with a single blood sample test and classified as low, medium, and high according to blood lead tertiles. Logistic regression models were calculated for the association between blood lead levels, pure-tone average, and DPOAE records. RESULTS: Median (25th-75th) blood lead levels were 14 µg/dL (7.5-22.6 µg/dL). The audiometric pattern and DPOAE records were similar across blood lead levels groups in all frequencies, and no statistically significant differences were found. Adjusted logistic regression models showed no increase in the odds for hearing thresholds >25 dB (HL) and DPOAE absence associated with blood lead levels, and no dose-response pattern was observed ( p > 0.05). CONCLUSIONS: Given the results from this cross-sectional study, no association was found between blood lead levels and hearing loss assessed with DPOAE. Future longitudinal work should consider chronic lead exposure estimates among underrepresented populations, which can potentially inform safer work practices to minimize the risk of ototoxicity.

Establishment of reference intervals for complete blood count in times of COVID-19 and vaccination.

Introduction: COVID-19 and vaccination may affect some parameters of the complete blood count (CBC). The aim of this study was to determine reference intervals (RI) of CBC in healthy population with different COVID-19 and vaccination backgrounds and compare them with those established previously. Materials and methods: A cross-sectional study was conducted in donors who attended the Traumatology Hospital "Dr. Victorio de la Fuente Narváez" (HTVFN) from June to September 2021. Reference intervals were established using the non-parametric method on Sysmex XN-1000. For differences between groups with different COVID-19 and vaccination backgrounds, non-parametric tests were used. Results: The RI were established in 156 men and 128 women. Haemoglobin (Hb), haematocrit (Hct), red blood cells (RBC), platelets (Plt), mean platelets volume (MPV), monocytes and relative neutrophils were higher in men than women (P < 0.001). The percentiles of Hb, Hct, RBC, MPV and relative monocytes showed higher values; Plt, white blood cells (WBC), lymphocytes, monocytes, neutrophils, eosinophils and absolute basophils, the 2.5th was higher and the 97.5th was lower; for lymphocytes and relative neutrophils, both percentiles had a trend toward lower values, compared to previous RI. Differences between groups with different COVID-19 and vaccination backgrounds, in lymphocytes (P = 0.038), neutrophils (P = 0.017) and eosinophils (P = 0.018) in men; Hct (P = 0.014), RDW (P = 0.023) in women and MPV (P = 0.001) in both, were not considered pathological. Conclusions: The RI for the CBC were established in a Mestizo-Mexican population with different COVID-19 and vaccination backgrounds, so should be updated and validated in different hospitals close to the HTVFN that use the same analyser.

Relationship between urinary biomarkers of early kidney damage and exposure to inorganic toxins in a pediatric population of Apizaco, Tlaxcala, Mexico.

BACKGROUND: In recent years, chronic kidney disease has increased in the pediatric population and has been related to environmental factors. In the diagnosis of kidney damage, in addition to the traditional parameters, early kidney damage biomarkers, such as kidney injury molecule 1, cystatin C, and osteopontin, among others, have been implemented as predictors of early pathological processes. OBJECTIVE: This study aimed to evaluate the relationship between exposure to environmental pollutants and early kidney damage biomarkers. METHODS: A cross-sectional pilot study was conducted in February 2016 and involved 115 apparently healthy children aged 6-15 residing in Apizaco, Tlaxcala. Participant selection was carried out randomly from among 16,472 children from the municipality of Apizaco. A socio-demographic questionnaire included  age, sex, education, duration of residence in the area, occupation, water consumption and dietary habits, pathological history, and some non-specific symptoms. Physical examination included blood pressure, weight, and height. The urine concentrations of urinary aluminum, total arsenic, boron, calcium, chromium, copper, mercury, potassium, sodium, magnesium, manganese, molybdenum, lead, selenium, silicon, thallium, vanadium, uranium, and zinc, were measured. Four of the 115 participants selected for the study were excluded due to an incomplete questionnaire or lack of a medical examination, leaving a final sample population of 111 participants. RESULTS: The results showed a mean estimated glomerular filtration rate of 89.1 ± 9.98 mL/min/1.73m2 and a mean albumin/creatinine ratio of 12.9 ± 16.7 mg/g urinary creatinine. We observed a positive and significant correlation between estimated glomerular filtration rate with fluoride, total arsenic and lead, and a correlation of albumin/creatinine ratio with fluoride, vanadium, and total arsenic. There was also a significant correlation between the early kidney damage biomarkers and fluoride, vanadium, and total arsenic, except for cystatin C. CONCLUSION: In conclusion, our results show that four urinary biomarkers: α1-microglobulin, cystatin C, kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin are related to environmental exposure to urinary fluoride, vanadium, and total arsenic in our pediatric population.

Assessment of miR-103a-3p in leukocytes-No diagnostic benefit in combination with the blood-based biomarkers mesothelin and calretinin for malignant pleural mesothelioma diagnosis.

Malignant pleural mesothelioma (MPM) is a cancer associated with asbestos exposure and its diagnosis is challenging due to the moderate sensitivities of the available methods. In this regard, miR-103a-3p was considered to increase the sensitivity of established biomarkers to detect MPM. Its behavior and diagnostic value in the Mexican population has not been previously evaluated. In 108 confirmed MPM cases and 218 controls, almost all formerly exposed to asbestos, we quantified miR-103-3a-3p levels in leukocytes using quantitative Real-Time PCR, together with mesothelin and calretinin measured in plasma by ELISA. Sensitivity and specificity of miR-103-3a-3p alone and in combination with mesothelin and calretinin were determined. Bivariate analysis was performed using Mann-Whitney U test and Spearman correlation. Non-conditional logistic regression models were used to calculate the area under curve (AUC), sensitivity, and specificity for the combination of biomarkers. Mesothelin and calretinin levels were higher among cases, remaining as well among males and participants ≤60 years old (only mesothelin). Significant differences for miR-103a-3p were observed between male cases and controls, whereas significant differences between cases and controls for mesothelin and calretinin were observed in men and women. At 95.5% specificity the individual sensitivity of miR-103a-3p was 4.4% in men, whereas the sensitivity of mesothelin and calretinin was 72.2% and 80.9%, respectively. Positive correlations for miR-103a-3p were observed with age, environmental asbestos exposure, years with diabetes mellitus, and glucose levels, while negative correlations were observed with years of occupational asbestos exposure, creatinine, erythrocytes, direct bilirubin, and leukocytes. The addition of miR-103a-3p to mesothelin and calretinin did not increase the diagnostic performance for MPM diagnosis. However, miR-103a-3p levels were correlated with several characteristics in the Mexican population.

Neurotoxicidad en trabajadores petroquímicos con bajos índices de exposición a disolventes orgánicos.

OBJETIVO: Estimar el desempeño neuropsicológico y su asociación con la exposición a disolventes orgánicos (DO) en trabajadores petroquímicos en México. Material y méto-dos. Estudio transversal en 203 trabajadores: 102 expuestos a DO y 101 no expuestos. Se evaluó el desempeño neuropsi-cológico con Neurobehavioral Core Test Battery y la exposición a DO con la medición de metabolitos de exposición para tolueno, xilenos y benceno. RESULTADOS: Los trabajadores expuestos presentaron un peor desempeño en todas las pruebas (p<0.05), excepto en la prueba de Santa Ana. Esto se corroboró con modelos de regresión; los trabajadores expuestos a DO tuvieron un mayor número de errores y realizaron las pruebas en mayor tiempo (p<0.05), además de presentar mayores probabilidades de padecer síntomas de neurotoxicidad (OR: 2.93; IC95%: 0.96, 8.96). Conclusio-nes. La exposición ocupacional a disolventes orgánicos, aun a niveles permitidos por la normatividad mexicana vigente, se relacionó con un menor desempeño neuropsicológico.

Neurotoxicidad en trabajadores petroquímicos con bajos índices de exposición a disolventes orgánicos / Neurotoxicity among petrochemical workers with low exposure indexes to organic solvents

Resumen: Objetivo: Estimar el desempeño neuropsicológico y su asociación con la exposición a disolventes orgánicos (DO) en trabajadores petroquímicos en México. Material y métodos: Estudio transversal en 203 trabajadores: 102 expuestos a DO y 101 no expuestos. Se evaluó el desempeño neuropsicológico con Neurobehavioral Core Test Battery y la exposición a DO con la medición de metabolitos de exposición para tolueno, xilenos y benceno. Resultados: Los trabajadores expuestos presentaron un peor desempeño en todas las pruebas (p<0.05), excepto en la prueba de Santa Ana. Esto se corroboró con modelos de regresión; los trabajadores expuestos a DO tuvieron un mayor número de errores y realizaron las pruebas en mayor tiempo (p<0.05), además de presentar mayores probabilidades de padecer síntomas de neurotoxicidad (OR: 2.93; IC95%: 0.96, 8.96). Conclusiones: La exposición ocupacional a disolventes orgánicos, aun a niveles permitidos por la normatividad mexicana vigente, se relacionó con un menor desempeño neuropsicológico.

Abstract: Objective: To estimate the neuropsychological performance and its association with exposure to organic solvents (OS) among petrochemical workers in Mexico. Materials and methods: Cross-sectional study including 203 workers: 102 exposed to OS and 101 non-exposed. Neuropsychological performance was evaluated with Neurobehavioral Core Test Battery. Exposure to OS was evaluated with the metabolites from exposure to toluene, xylenes and benzene. Results: Exposed workers presented with a worse performance in all tests (p<0.05), except for Santa Ana test. This was corroborated with regression models; workers exposed to OS had a higher number of mistakes and performed the tests in longer time (p<0.05), together with having greater odds of neurotoxicity symptoms (OR: 2.93; 95%CI: 0.96, 8.96). Conclusions: Occupational exposure to organic solvents, even at levels allowed by current Mexican standards, was related to an impaired neuropsychological performance.

Prestin and otolin-1 proteins in the hearing loss of adults chronically exposed to lead.

BACKGROUND: Some studies in animal models and humans suggest that exposure to lead is associated with hearing loss. Lead can reach the inner ear through the blood circulation; evidence suggests that lead could accumulate in the inner ear, causing inner ear damage. AIM: To evaluate prestin and otolin-1 protein levels and their relationship with an increased hearing threshold in participants exposed to lead. METHODS: We conducted a cross-sectional study with 315 participants from Tlaxcala, Mexico. Blood lead levels (BPb) were evaluated by graphite furnace atomic absorption spectrometry. Serum prestin and otolin-1 were quantified using ELISA. Auditory function at frequencies of 0.125 to 8 kHz was evaluated in a soundproof chamber. RESULTS: Participants were classified according to BPb: group I (<10 µg/dL) had a median BPb of 6 µg/dL and prestin levels of 11.06 ng/mL. While participants in group II (≥10 µg/dL) had a median of BPb 20.7 µg/dL (p < 0.05) and prestin levels of 0.15 ng/mL (p < 0.001). Participants in both groups showed a normal hearing. Otolin-1 levels were higher for participants with normal hearing and lower for participants with hearing loss in both groups, p > 0.05. Multiple linear regression models predict an average decrease of 0.17 to 0.26 ng/mL in prestin levels per decibel increase for the frequencies evaluated. CONCLUSIONS: Participants with high BPb showed an increase in hearing threshold, and prestin levels decreased proportionally to the hearing threshold increase. This is the first study to evaluate prestin as a potential biomarker for hearing damage, evaluated by audiometry, in participants with lead exposure.

Commute times and audiometric findings among adult population in Mexico City.

INTRODUCTION: Long commute times are common in big cities. OBJECTIVE: To determine hearing thresholds and their association with commute time in Mexico City. METHODS: Cross-sectional study that included 177 healthy adults from 2009 to 2011. Demographic information and commute times were recorded. Hearing was assessed by audiometry. Regression models were constructed to determine the predictors of hearing thresholds. RESULTS: There were 101 men (53%) and 76 women (43%). Mean commute time was 43 minutes (1-150 minutes). A hearing threshold drop was observed at 4000 Hz, with recovery at 8000 Hz in both ears when patients were stratified by gender and age groups. A commute time > 40 min/day increased the hearing threshold at 4000 Hz (ß = 2.96 dB HL, p < 0.01). Men had higher thresholds (ß = 2.6 dB HL), as older subjects also did: 25-34 years, ß = 2.2 dB HL; 35-44 years, ß = 5.2 dB HL; and ≥ 45 years, ß = 8.3 dB HL. CONCLUSION: The hearing pattern, although normal, resembled that of noise-induced hearing loss, associated with long commute times.

INTRODUCCIÓN: Los tiempos prolongados de traslado son comunes en las ciudades grandes. OBJETIVO: Determinar los umbrales auditivos y su asociación con el tiempo de traslado al trabajo en la Ciudad de México. MÉTODOS: Estudio transversal que incluyó a 177 adultos sanos de 2009 a 2011. Se registró información demográfica y tiempo de traslado al trabajo. La audición se evaluó mediante audiometría. Se realizaron modelos de regresión para determinar los predictores de los umbrales auditivos. RESULTADOS: Se trató de 101 hombres (53 %) y 76 mujeres (43 %). El tiempo promedio de traslado fue 43 minutos (1 a 150 minutos). Se observó una caída del umbral auditivo en 4000 Hz, con recuperación en 8000 Hz en ambos oídos al estratificar por sexo y grupos de edad. Un tiempo de traslado > 40 minutos/día incrementó el umbral auditivo en 4000 Hz (b = 2.96 dB HL, p < 0.01). Los hombres presentaron umbrales mayores (b = 2.6 dB HL), al igual que los sujetos de edad más avanzada: 25 a 34 años, b = 2.2 dB HL; 35 a 44 años, b = 5.2 dB HL y ≥ 45 años, b = 8.3 dB HL. CONCLUSIÓN: El patrón auditivo, aunque normal, se asemejó a la pérdida auditiva por ruido asociada a tiempo prolongado de traslado al trabajo.

Audiometric findings of printing press workers exposed to noise and organic solvents.

OBJECTIVE: To determine if exposure to organic solvents and noise is associated with audiometric results among workers from a printing press in Mexico City. DESIGN: Cross-sectional study. STUDY SAMPLE: One hundred and seventy-six male workers at a printing press in Mexico City exposed to noise and organic solvents, including xylene, and 103 non-exposed male workers as reference group. Hearing thresholds were assessed with pure-tone audiometry. RESULTS: Poorer hearing thresholds were observed among printing workers than non-exposed controls, particularly among groups with over 5 years of exposure. Hearing thresholds differences were observed in the frequencies above 500 Hz, especially in 4000 Hz in all exposure groups compared to the reference. Adjusted models for age and previous exposure to noise and organic solvents showed worse hearing thresholds as years of seniority increased -ß coefficients (95% CI): ≤5 years: 3.06 dB (0.01, 6.10); >5-10 years: 4.51 dB (1.13, 7.89); >10 years: 4.58 dB (1.20, 7.96). Further analyses showed no interaction between noise and organic solvents on hearing thresholds, considering both current and previous occupational exposures. CONCLUSION: Exposure to noise levels that were below recommended exposure limits and organic solvents were associated with poorer hearing thresholds than those observed among non-exposed study participants. This suggests that workers exposed to solvents should be included in hearing conservation programmes, even when noise exposures are below 85 dB. If only noise levels were taken into consideration in the risk assessment of this worker population, the risk of hearing effects could have been overlooked.

Natriuretic peptides and echocardiographic parameters in Mexican children environmentally exposed to arsenic.

BACKGROUND: Arsenic exposure is associated with cardiovascular risk in adults; however, few epidemiologic studies have evaluated biomarkers of cardiovascular risk in children who are environmentally exposed to arsenic. OBJECTIVE: The aim of this study was to assess the associations between urinary arsenic, plasma natriuretic peptides and echocardiographic parameters in Mexican children exposed to arsenic through the drinking water. METHODS: We conducted a cross-sectional study with 192 children (3-8 years old) from Zimapan, Hidalgo, Mexico. B-type natriuretic peptide (BNP), NT-proBNP and atrial natriuretic peptide (ANP) were measured by ELISA, urinary arsenic concentration (UAs) were measured via by hydride generation-cryotrapping-atomic absorption spectrometry, and cardiac parameters were measured by echocardiography. RESULTS: The median plasma concentrations of ANP, BNP and NT-proBNP were 36.9 ng/mL, 49.7 pg/mL, and 226.1 pg/mL, respectively. Using multivariable models, a dose-response relationship was observed between BNP concentrations and UAs tertiles (<47 ng/mL: reference, 47-72 ng/mL: 48.7 pg/mL, >72 ng/mL: 52.2 pg/mL, P-trend = 0.020). BNP concentrations also increased with increasing U-tAs as continuous variables (0.43 pg/mL increase per 1 ng/mL increase of U-tAs; P-Value = 0.008). Additionally, BNP was positively associated with arsenic methylated metabolites (U-MAs and U-DMAs). On the other hand, BNP was inversely related to relative wall thickness (RWT). No associations were found for other cardiac parameters. Finally, neither ANP nor NT-proBNP were significantly related to arsenic exposure or echocardiographic parameters. CONCLUSIONS: In this study, we showed associations between plasma BNP and arsenic exposure. Our results support the importance of reducing childhood arsenic exposure, which may have cardiovascular effects early in life.

Identification of Factors Associated With Acute Tubular Necrosis Following Kidney Transplant in Northern Mexico: Increased Risk With Cold Ischemia After 8 Hours.

AIM: To identify potential risk factors associated with the incidence of acute tubular necrosis (ATN) following kidney transplant in a sample of patients from northern Mexico. METHODS: Secondary analysis of data extracted from clinical files of patients who underwent a kidney transplant between 2000 and 2017 at Christus Muguerza Hospital in the city of Chihuahua. The final sample with complete data included 485 patients. ATN was diagnosed in 13.2% of patients using pathologic, clinical, and laboratory criteria. Adjusted odds ratio (ORs) with 95% CIs from multivariate binary logistic regression were used to identify predictors of ATN. RESULTS: Only 4 of 21 variables analyzed remained statistically significant in the final adjusted model. Cold and warm ischemia followed time-trend patterns with higher odds with longer ischemia times. For cold ischemia, compared with 0 to 240 minutes, ORs were 1.32 (95% CI, 0.49-3.51) for 241-480 minutes, 4.87 (95% CI, 2.29-10.3) for 481-960 minutes, and 10.0 (95% CI, 2.86-35.0) for > 960 minutes; for warm ischemia, compared with 40 to 59 minutes, these were 6.27 (95% CI, 1.95-20.8) for 60-70 minutes and 10.32 (95% CI, 1.95-54.4) for 71-110 minutes. Hypotension during surgery was associated with a higher chance of ATN (OR, 15.9; 95% CI, 4.97-50.9). When the recipients' age was 30 years or older, the probability also increased significantly (OR, 2.88; 95% CI, 1.09-7.57). The final model fitted well and explained 27% of the probability to develop ATN after a kidney transplant. CONCLUSION: Shortening the duration of ischemia and avoiding hypotension during surgery is essential to prevent ATN following a kidney transplant.

Neuropsychological effects among workers exposed to organic solvents.

OBJECTIVE: To assess neuropsychological performance among workers at a paint factory in Mexico City. MATERIALS AND METHODS: During 2004 and 2005 we assessed the neuropsychological performance of 208 workers who were exposed to organic solvents at a paint factory, mainly toluene and xylene. We categorized workers into low and high exposure groups using a cumulative index for toluene, based on times spent in different tasks. We evaluated cognitive and motor functions with 13 neuropsychological tests. RESULTS: We found lower attention, longer time to complete the test ß=5.5 (R2=12.3%), and a lower score in the motor-cognitive test ß=-15.7 (R2=19.5%) in the high exposure group through multiple linear regression model analysis, with adjustment for age and education. CONCLUSIONS: Our results are similar to the ones reported in the literature, but the effects are less severe, probably due to lower exposure to organic solvents.

OBJETIVO: Evaluar el desempeño neuropsicológico de los trabajadores de una fábrica de pintura en la Ciudad de México. MATERIAL Y MÉTODOS: Se evaluó el desempeño neuropsicológico de 208 trabajadores expuestos a disolventes orgánicos, principalmente tolueno y xileno, en una fábrica de pintura en la Ciudad de México durante 2004 y 2005. Se categorizaron en grupos de baja y alta exposición con un índice acumulado de tolueno con base en el tiempo empleado por actividad. Se evaluaron funciones motoras y cognitivas con 13 pruebas neuropsicológicas. RESULTADOS: Se registró un tiempo más largo para completar la prueba ß=5.5 (R2=12.3%) y una puntuación baja en la prueba motor-cognitiva de ß=- 15.7 (R2=19.5%) en el grupo de alta exposición en los modelos de regresión lineal múltiple, ajustados por confusores. CONCLUSIONES: Los presentes resultados son similares a los reportados en la literatura, aunque los efectos son menos graves, probablemente debido a la baja exposición.

Neuropsychological effects among workers exposed to organic solvents / Efectos neuropsicológicos en trabajadores expuestos a disolventes orgánicos

Abstract: Objective: To assess neuropsychological performance among workers at a paint factory in Mexico City. Materials and methods: During 2004 and 2005 we assessed the neuropsychological performance of 208 workers who were exposed to organic solvents at a paint factory, mainly toluene and xylene. We categorized workers into low and high exposure groups using a cumulative index for toluene, based on times spent in different tasks. We evaluated cognitive and motor functions with 13 neuropsychological tests. Results: We found lower attention, longer time to complete the test β=5.5 (R2=12.3%), and a lower score in the motor-cognitive test β=-15.7 (R2=19.5%) in the high exposure group through multiple linear regression model analysis, with adjustment for age and education. Conclusion: Our results are similar to the ones reported in the literature, but the effects are less severe, probably due to lower exposure to organic solvents.

Resumen: Objetivo: Evaluar el desempeño neuropsicológico de los trabajadores de una fábrica de pintura en la Ciudad de México. Material y métodos: Se evaluó el desempeño neuropsicológico de 208 trabajadores expuestos a disolventes orgánicos, principalmente tolueno y xileno, en una fábrica de pintura en la Ciudad de México durante 2004 y 2005. Se categorizaron en grupos de baja y alta exposición con un índice acumulado de tolueno con base en el tiempo empleado por actividad. Se evaluaron funciones motoras y cognitivas con 13 pruebas neuropsicológicas. Resultados: Se registró un tiempo más largo para completar la prueba β=5.5 (R2=12.3%) y una puntuación baja en la prueba motor-cognitiva de β=-15.7 (R2=19.5%) en el grupo de alta exposición en los modelos de regresión lineal múltiple, ajustados por confusores. Conclusión: Los presentes resultados son similares a los reportados en la literatura, aunque los efectos son menos graves, probablemente debido a la baja exposición.

Chronic Kidney Disease in Children Aged 6-15 Years and Associated Risk Factors in Apizaco, Tlaxcala, Mexico, a Pilot Study.

INTRODUCTION: Tlaxcala, a small state in central Mexico, has the highest prevalence of chronic kidney disease (CKD) deaths in population aged 5-14 in Mexico, most of them with unknown etiology. OBJECTIVE: To determine the prevalence of CKD in apparently healthy pediatric population in Apizaco, Tlaxcala. METHODS: A cross-sectional pilot study was carried out in children deemed as healthy; subjects with previous diagnosis of CKD were excluded. Informed consent was obtained in all cases. A physical examination was performed, a questionnaire was applied. Blood and urine samples were obtained for serum creatinine, urinalysis, and microalbumin/creatinine ratio. A second and third evaluation was performed after 6 and 18 months in those found with urinary anomalies/CKD to confirm the diagnosis. RESULTS: One hundred and nine subjects completed physical examination, which are the biological samples. Median age was 12 years. CKD stage 2 was confirmed in 5 subjects in the sixth month confirmation visit (4.6%). One patient accepted renal biopsy and Alport Syndrome was found. In a robust multivariate analysis, the risk factors related to reduction in the glomerular filtration rate were males -5.15 mL/min/1.73 m2 (p = 0.002), older participants as by -1.58 mL/min/1.73 m2 per year (p < 0.0001), and among participants living close to a river -3.76 mL/min/1.73 m2 (p = 0.033). DISCUSSION/CONCLUSION: The prevalence of CKD in the population studied in Apizaco Tlaxcala was confirmed in 4.6 cases per 100 inhabitants between 6 and 15 years. Males, older age, and living close to a river were the risk predictive factors. More studies are needed to determine the causes of the high CKD prevalence in this population.

Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma.

PURPOSE: Malignant pleural mesothelioma (MPM) is a highly lethal cancer caused by exposure to asbestos. Currently, the diagnosis is a challenge, carried out by means of invasive methods of limited sensitivity. This is a case-control study to evaluate the individual and combined performance of minimally invasive biomarkers for the diagnosis of MPM. METHOD: A study of 166 incident cases of MPM and 378 population controls of Mestizo-Mexican ethnicity was conducted. Mesothelin, calretinin, and megakaryocyte potentiating factor (MPF) were quantified in plasma by ELISA. The samples were collected from 2011 to 2016. RESULTS: Based on ROC analysis and a preset specificity of 95%, the combination of the three biomarkers reached an AUC of 0.944 and a sensitivity of 82% in men. In women, an AUC of 0.937 and a sensitivity of 87% were reached. In nonconditional logistic regression models, the adjusted ORs in men were 7.92 (95% CI 3.02-20.78) for mesothelin, 20.44 (95% CI 8.90-46.94) for calretinin, and 4.37 (95% CI 1.60-11.94) for MPF. The ORs for women were 28.89 (95% CI 7.32-113.99), 17.89 (95% CI 3.93-81.49), and 2.77 (95% CI 0.47-16.21), respectively. CONCLUSIONS: To our knowledge, this is the first study evaluating a combination of mesothelin, calretinin, and MPF, and demonstrating a sex effect for calretinin. The biomarker panel showed a good performance in a Mestizo-Mexican population, with high sensitivity and specificity for the diagnosis of MPM.

Evaluation of vascular and kidney injury biomarkers in Mexican children exposed to inorganic fluoride.

Exposure to inorganic fluoride (F) has been implicated in cardiovascular and kidney dysfunction mainly in adult populations. However, limited epidemiological information from susceptible populations, such as children, is available. In this study we evaluated the relationship of F exposure with some vascular and kidney injury biomarkers in children. A cross-sectional study was conducted in 374 Mexican schoolchildren. Dental fluorosis and F concentrations in the water and urine were evaluated. The glomerular filtration rate (eGFR) and the urinary concentrations of kidney injury molecule 1 (KIM-1) and cystatin-C (uCys-C) were examined to assess kidney injury. The carotid intima media thickness (cIMT) and serum concentrations of vascular adhesion molecule 1 (VCAM-1), intracellular adhesion molecule 1 (ICAM-1), endothelin 1(ET-1) and cystatin-C (sCys-C) were measured to assess vascular alterations. High proportions of children exposed to F were observed (79.7% above 1.2 ppm F in urine) even in the low water F exposure regions, which suggested additional sources of F exposure. In robust multiple linear regression models, urinary F was positively associated with eGFR (ß = 1.3, p = 0.015), uCys-C (ß = -8.5, p = 0.043), VCAM-1 (ß = 111.1, p = 0.019), ICAM-1 (ß = 57, p = 0.032) and cIMT (ß = 0.01, p = 0.032). An inverse association was observed with uCys-C (ß = -8.5, p = 0.043) and sCys-C (ß = -9.6, p = 0.021), and no significant associations with ET-1 (ß = 0.069, p = 0.074) and KIM-1 (ß = 29.1, p = 0.212) were found. Our findings revealed inconclusive results regarding F exposure and kidney injury. However, these results suggest that F exposure is related to early vascular alterations, which may increase the susceptibility of cardiovascular diseases in adult life.

Determination of reference ranges for coagulation tests in Mexican-mestizo population / Determinación de límites de referencia de pruebas de coagulación en población mestizo-mexicana

Background: It is necessary to establish biological parameters for each population. Objective: To establish reference values for prothrombin time (PT), activated partial thromboplastin time (PTT) and fibrinogen in healthy population and to determine intra- and inter-assay concordance. Methods: Cross-sectional study that included 204 women and 202 men from the Blood Donor service. Coagulation tests were carried out in order to obtain reference ranges. All procedures were made according to the Clinical & Laboratory Standards Institute guidelines. Results: Mean PT, PTT and fibrinogen were 14.1 s, 28.8 s and 381 mg/dL in men, and 15.1 s, 29.0 s and 381 mg/dL in women. The proposed PT, PTT and fibrinogen reference ranges for men were 12.7 to 16.3 s, 24.2 to 36.3 s and 239 to 276 mg/dL, respectively; for women, 12.7 to 16.6 s, 23.5 to 35.4 s and 276 to 598 mg/dL. The latter was statistically significant (p ≤ 0.001). Conclusions: Reference values for blood coagulation tests were determined. This is of great importance for fast medical diagnosis and treatment. The results from this study can be adopted by other clinic laboratories after appropriate validation procedures.

Introducción: Es necesario establecer valores de referencia biológicos para cada población. Objetivo: Establecer los límites de referencia de tiempo de protrombina (TP), tiempo parcial de tromboplastina (TTP) y fibrinógeno en población mestizo-mexicana sana, así como la correlación y la concordancia en la determinación de estas pruebas con los dos equipos utilizados. Métodos: Estudio transversal en 204 mujeres y 202 hombres que acudieron al servicio de donadores y se les determinó TP, TTP y fibrinógeno para obtener los límites de referencia. Los procedimientos se realizaron de acuerdo con las guías del Instituto de Estándares de Laboratorio y Clínicos (CLSI C28-A3). Resultados: La media de TP, TTP y fibrinógeno en hombres fue de 14.1 s, 28.8 s y 381 mg/dL, y en mujeres de 15.1 s, 29.0 s y 381 mg/dL, respectivamente. Los límites de referencia para hombres en TP, TTP y fibrinógeno fueron de 12.7 a 16.3 s, de 24.2 a 36.3 s y de 239 a 276 mg/dL; para mujeres de 12.7 a 16.6 s, de 23.5 a 35.4 s y de 276 a 598 mg/dL, respectivamente. Este último fue estadísticamente significativo (p ≤ 0.001). Conclusiones: Se determinaron los límites de referencia para las pruebas de coagulación. Los resultados obtenidos en este estudio pueden ser adoptados por otros laboratorios clínicos, después de su apropiada validación.

Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population.

Background: Diagnosis of malignant pleural mesothelioma (MPM) remains a challenge, especially when resources in pathology are limited. The study aimed to evaluate cost-effective tumor markers to predict the probability of MPM in plasma samples in order to accelerate the diagnostic workup of the tissue of potential cases. Methods: We conducted a case-control study stratified by gender, which included 75 incident cases with MPM from three Mexican hospitals and 240 controls frequency-matched by age and year of blood drawing. Plasma samples were obtained to determine mesothelin, calretinin, and thrombomodulin using enzyme-linked immunosorbent assays (ELISAs). We estimated the performance of the markers based on the area under the curve (AUC) and predicted the probability of an MPM diagnosis of a potential case based on the marker concentrations. Results: Mesothelin and calretinin, but not thrombomodulin were significant predictors of a diagnosis of MPM with AUCs of 0.90 (95% CI: 0.85-0.95), 0.88 (95% CI: 0.82-0.94), and 0.51 (95% CI: 0.41-0.61) in males, respectively. For MPM diagnosis in men we estimated a true positive rate of 0.79 and a false positive rate of 0.11 for mesothelin. The corresponding figures for calretinin were 0.81 and 0.18, and for both markers combined 0.84 and 0.11, respectively. Conclusions: We developed prediction models based on plasma concentrations of mesothelin and calretinin to estimate the probability of an MPM diagnosis. Both markers showed a good performance and could be used to accelerate the diagnostic workup of tissue samples in Mexico.

Evaluation of kidney injury biomarkers in an adult Mexican population environmentally exposed to fluoride and low arsenic levels.

Fluoride (F) is a toxicant widely distributed in the environment. Experimental studies have shown kidney toxicity from F exposure. However, co-exposure to arsenic (As) has not been considered, and epidemiological information remains limited. We evaluated the association between F exposure and urinary kidney injury biomarkers and assessed As co-exposure interactions. A cross-sectional study was conducted in 239 adults (18-77 years old) from three communities in Chihuahua, Mexico. Exposure to F was assessed in urine and drinking water, and As in urine samples. We evaluated the urinary concentrations of albumin (ALB), cystatin-C (Cys-C), kidney injury molecule 1 (KIM-1), clusterin (CLU), osteopontin (OPN), and trefoil factor 3 (TFF-3). The estimated glomerular filtration rate (eGFR) was calculated using serum creatinine (Creat) levels. We observed a positive correlation between water and urine F concentrations (ρ = 0.7419, p < 0.0001), with median values of 1.5 mg/L and 2 µg/mL, respectively, suggesting that drinking water was the main source of F exposure. The geometric mean of urinary As was 18.55 ng/mL, approximately 39% of the urine samples had As concentrations above the human biomonitoring value (15 ng/mL). Multiple linear regression models demonstrated a positive association between urinary F and ALB (ß = 0.56, p < 0.001), Cys-C (ß = 0.022, p = 0.001), KIM-1 (ß = 0.048, p = 0.008), OPN (ß = 0.38, p = 0.041), and eGFR (ß = 0.49, p = 0.03); however, CLU (ß = 0.07, p = 0.100) and TFF-3 (ß = 1.14, p = 0.115) did not show significant associations. No interaction with As exposure was observed. In conclusion, F exposure was related to the urinary excretion of early kidney injury biomarkers, supporting the hypothesis of the nephrotoxic role of F exposure.

[Chronic kidney disease in Mexico and its relation with heavy metals]. / Enfermedad renal crónica en México y su relación con los metales pesados.

Chronic kidney disease (CKD) is a public health problem in Mexico, causing 25% of deaths related to diabetes mellitus (DM) and 28% related to hypertensive heart disease. In 2008 CKD reached the highest incidence of end-stage renal disease in the world. Diabetes mellitus is the main risk factor associated with CKD in Mexican population; however, heavy metals such as lead, arsenic, cadmium and mercury have been associated to nephropathies. In Mexico there are still high levels of these compounds in occupational and environmental settings; therefore, chronic exposures to these metals persist. In this review we approach to the main mechanisms of action of these metals in the body and its renal effects, as well as information about the sources of exposure to these chemical risks, the relationship between exposure to heavy metals and CKD, coupled with the economic and social consequences of this disease.

La enfermedad renal crónica (ERC) constituye un problema de salud pública en México, pues ocasiona el 25% de las muertes en pacientes con diabetes mellitus (DM) y 28% de las muertes relacionadas con cardiopatía hipertensiva. En 2008 la ERC alcanzó la tasa de incidencia más alta de enfermedad renal terminal en el mundo. La DM es el principal factor de riesgo asociado a la ERC en la población mexicana; sin embargo, los metales pesados como el plomo, el arsénico, el cadmio y el mercurio se han relacionado con las nefropatías. En México aún persisten niveles elevados de estos compuestos en diversos trabajos y en el ambiente, lo que condiciona una exposición crónica en la población. En esta revisión se describen los principales mecanismos de acción de estos metales en el organismo, así como sus efectos a nivel renal, además de información acerca de las fuentes de exposición a estos riesgos químicos, la relación entre la exposición a metales pesados y ERC, y, por último, las consecuencias económicas y sociales de esta enfermedad.