Factors driving the inter-individual variability in the metabolism and bioavailability of (poly)phenolic metabolites: A systematic review of human studies.

This systematic review provides an overview of the available evidence on the inter-individual variability (IIV) in the absorption, distribution, metabolism, and excretion (ADME) of phenolic metabolites and its determinants. Human studies were included investigating the metabolism and bioavailability of (poly)phenols and reporting IIV. One hundred fifty-three studies met the inclusion criteria. Inter-individual differences were mainly related to gut microbiota composition and activity but also to genetic polymorphisms, age, sex, ethnicity, BMI, (patho)physiological status, and physical activity, depending on the (poly)phenol sub-class considered. Most of the IIV has been poorly characterised. Two major types of IIV were observed. One resulted in metabolite gradients that can be further classified into high and low excretors, as seen for all flavonoids, phenolic acids, prenylflavonoids, alkylresorcinols, and hydroxytyrosol. The other type of IIV is based on clusters of individuals defined by qualitative differences (producers vs. non-producers), as for ellagitannins (urolithins), isoflavones (equol and O-DMA), resveratrol (lunularin), and preliminarily for avenanthramides (dihydro-avenanthramides), or by quali-quantitative metabotypes characterized by different proportions of specific metabolites, as for flavan-3-ols, flavanones, and even isoflavones. Future works are needed to shed light on current open issues limiting our understanding of this phenomenon that likely conditions the health effects of dietary (poly)phenols.

Evaluation of the presence of gingivitis as confounding factor in assessing inflammatory status in serum and saliva of dogs with diabetes mellitus.

The aim of this study was to evaluate the changes in the serum and salivary inflammatory markers induced by Diabetes mellitus (DM) in dogs and to assess the possible confounding effect of gingivitis. A panel of 13 cytokines was measured in the serum and saliva of dogs diagnosed with DM and compared with healthy dogs without gingivitis (control group 1; CG1) and dogs with gingivitis but otherwise healthy (control group 2; CG2). The results of the present study showed statistically significantly higher levels of IL-8, KC-like and MCP1 in the serum of dogs with DM compared to CG1 dogs. In the case of saliva, the DM group presented statistically higher GM-CSF, IL6, IL15, and MCP1 levels compared to CG1, and lower KC-like chemokine compared to CG2. Finally, gingivitis produced changes in saliva, with salivary levels of GM-CSF, IL-6, IL-7, IL-15, IP-10, KC-like, IL-10, IL-18, MCP1, TNFα being statistically significantly higher in the saliva of CG2 dogs compared to CG1. The results of the present study indicate that dogs with DM have altered cytokine levels in serum and saliva compared to healthy dogs. In addition, this study highlights the importance of taking oral health into account when determining cytokines in dogs, as gingivitis can significantly alter their concentrations. .

Assessment of anti-malondialdehyde-acetaldehyde antibody frequencies in rheumatoid arthritis with new data from two independent cohorts, meta-analysis, and meta-regression.

BACKGROUND: Autoantibodies are critical elements in RA pathogenesis and clinical assessment. The anti-malondialdehyde-acetaldehyde (anti-MAA) antibodies are potentially useful because of their claimed high sensitivity for all RA patients, including those lacking RF and anti-CCP antibodies. Therefore, we aimed to replicate these findings. METHODS: We independently attempted replication in Santiago and Barcelona using sera from 517 and 178 RA patients and 272 and 120 healthy controls, respectively. ELISA protocols for anti-MAA antibodies included five antigens (human serum albumin in three formulations, fibrinogen, and a synthetic peptide) and assays for the IgG, IgM, and IgA isotypes. We integrated our results with information found by searching the Web of Science for reports of anti-MAA antibodies in RA. The available patients (4989 in 11 sets) were included in a meta-analysis aimed at heterogeneity between studies. Factors accounting for heterogeneity were assessed with meta-regression. RESULTS: The sensitivity of anti-MAA antibodies in our RA patients was low, even in seropositive patients, with the percentage of positives below 23% for all ELISA conditions. Our results and bibliographic research showed IgG anti-MAA positive patients ranging from 6 to 92%. The extreme between-studies heterogeneity could be explained (up to 43%) in univariate analysis by sex, African ethnicity, the site of study, or recruitment from the military. The best model, including African ancestry and smoking, explained a high heterogeneity fraction (74%). CONCLUSION: Anti-MAA antibody sensitivity is extremely variable between RA patient collections. A substantial fraction of this variability cannot be attributed to ELISA protocols. On the contrary, heterogeneity is determined by complex factors that include African ethnicity, smoking, and sex.

Incidence of Anal Cancer and Related Risk Factors in HIV-Infected Patients Enrolled in the National Prospective Spanish Cohort CoRIS.

BACKGROUND: People living with HIV have an increased risk of anal cancer. OBJECTIVE: To estimate anal cancer incidence and related risk factors in a national cohort of HIV-infected patients. DESIGN: Prospective multicenter cohort study. SETTINGS: Multicenter study including patients from the Spanish HIV Research Network. PATIENTS: We collected data from 16,274 HIV-infected treatment-naive adults recruited from January 2004 to November 2020. MAIN OUTCOMES MEASURES: The primary outcome measures of this study were the incidence and prevalence of anal carcinoma. The secondary outcome measures included the associations between baseline and time-dependent covariables and the primary end point. RESULTS: Twenty-six cases of anal cancer were diagnosed, 22 of which were incident cases resulting in a cumulative incidence of 22.29 of 100,000 person-years, which was stable during the study period. At the end of the study, 20 of the 43 centers had screening programs for high-grade anal dysplasia. Patients with anal cancer were males (26/26; 100% vs 13,833/16,248; 85.1%), were mostly men who have sex with men (23/26; 88.5% vs 10,017/16,248; 61.6%), had a median age of 43 years (interquartile range, 35-51), were more frequently previously diagnosed with an AIDS-defining illness (9/26; 34.6% vs 2429/16,248; 15%), and had lower nadir CD4 cell counts (115 vs 303 µL). About a third (34.6%, 9/26) were younger than 35 years. In multivariable analysis, men who have sex with men and patients with previous AIDS-defining illness had an 8.3-fold (95% CI, 1.9-36.3) and 2.7-fold (95% CI, 1.1-6.6) increased HR for developing anal cancer, respectively. Patients with higher CD4 cell counts during the follow-up showed a 28% lower risk per each additional 100 CD4 cell/µL (95% CI, 41%-22%). LIMITATIONS: Lack of information on some potential risk factors, screening, and treatment of high-grade anal dysplasia were not uniformly initiated across centers during the study period. CONCLUSIONS: Although the overall incidence in our study was low, there was a significant number of patients younger than 35 years with anal cancer. In addition to age, other factors, such as men who have sex with men and patients with severe immunosuppression (current or past), should be prioritized for anal cancer screening. INCIDENCIA DEL CNCER DE ANO Y LOS FACTORES DE RIESGO RELACIONADOS CON PACIENTES INFECTADOS POR VIH INCLUIDOS EN LA COHORTE PROSPECTIVA NACIONAL ESPAOLA CORIS: ANTECEDENTES:Las personas portadoras del virus de la inmunodeficiencia humana tienen un mayor riesgo de cáncer anal.OBJETIVO:Nosotros queremos estimar la incidencia de cáncer anal y los factores de riesgo relacionados en una cohorte nacional española de pacientes infectados por VIH.DISEÑO:Estudio de cohortes de tipo multicéntrico y prospectivo.ÁMBITO:Se incluyeron pacientes de la Red Española de Investigación en VIH.PACIENTES:Recolectamos los datos de 16,274 adultos infectados por el VIH que nunca habían recibido tratamiento, reclutados desde enero de 2004 hasta noviembre de 2020.MEDIDAS DE RESULTADO PRINCIPALES:Las medidas de resultado primarias de este estudio fueron la incidencia y la prevalencia del carcinoma anal. Las medidas de resultado secundarias incluyeron las asociaciones entre las covariables basales y dependientes del tiempo y el criterio principal de valoración.RESULTADOS:Se diagnosticaron 26 casos de cáncer anal, de los cuales 22 fueron casos incidentales resultando con una incidencia acumulada de 22,29/100.000 personas-año que se mantuvo estable durante el período de estudio.Al final de nuestro estudio, 20 de los 43 centros referentes tenían programas de detección de displasia anal de alto grado. Los pacientes con cáncer anal eran hombres (26/26; 100% vs 13 833/16 248; 85,1%), en su mayoría hombres que mantenían sexo con otros hombres (23/26; 88,5% vs 10 017/16 248; 61,6%), la mediana de edad fue de 43 años (IQR: 3 -51), 34,6% (9/26) < 35 años, previa y frecuentemente diagnosticados con una enfermedad definitoria de SIDA (9/26; 34,6% vs 2429/16248; 15%) y que tenían un punto opuesto mucho más bajo en el recuentos de células CD4 (115 µL frente a 303 µL).En el análisis multivariable, los hombres que tenían relaciones sexuales con otros hombres y los pacientes con enfermedades definitorias de sida anteriores, tenían un aumento de 8,3 veces (IC del 95%: 1,9 a 36,3) y de 2,7 veces (IC del 95%: 1,1 a 6,6) en el cociente de riesgos instantáneos para desarrollar cáncer anal, respectivamente. Los pacientes con recuentos de células CD4 más altos durante el seguimiento mostraron un riesgo 28 % menor por cada 100 células CD4/µl adicionales (95% IC: 41%- 22%).LIMITACIONES:La falta de información sobre algunos factores potenciales de riesgo, la detección y el tratamiento de la displasia anal de alto grado no se iniciaron uniformemente en todos los centros durante el período de estudio.CONCLUSIONES:Si bien la incidencia general en nuestro estudio fue baja, hubo un número significativo de pacientes de <35 años con cáncer anal. Además de la edad, otros factores como los hombres que tienen sexo con hombres y los pacientes con inmunosupresión severa (actual o pasada) deben priorizarse para la detección del cáncer anal. ( Traducción-Dr. Xavier Delgadillo ).

Analysing biomarkers in oral fluid from pigs: influence of collection strategy and age of the pig.

BACKGROUND AND OBJECTIVES: Oral fluid (OF) is an easy-to-collect, inexpensive, fast and non-invasive sample to characterize health and welfare status of the pig. However, further standardisation of the collection methods is needed in order to use it regularly in veterinary practice. Cotton ropes are routinely used to collect OF for pathogen detection but they may not be optimal for biomarker analysis due to sample contamination. This study compared two methods (cotton ropes and sponges) to collect porcine OF for biomarker analysis. A panel of 11 biomarkers of stress, inflammation, sepsis, immunity, redox status and general homeostasis was studied. MATERIALS AND METHODS: Eighteen farrow-to-finish pig farms were included in the study. In each farm, three (for sponges) or four pens of pigs (for ropes) were sampled at four age categories: the week after weaning (5 weeks), before (11-12 weeks) and after (12-13 weeks) moving to finisher facility and the week before slaughter (22-25 weeks). In total, 288 OF samples were collected with cotton ropes and 216 with sponges and analysed for the biomarkers: cortisol, alpha-amylase, oxytocin (stress), haptoglobin (inflammation), procalcitonin (sepsis), adenosine deaminase, immunoglobulin G (immune system), ferric reducing antioxidant power (redox status), and creatine kinase, lactate dehydrogenase and total protein (general homeostasis). Samples were also scored visually for dirtiness using a score from 1 (clean) to 5 (very dirty). RESULTS: Rope-collected OF had higher levels of dirtiness (3.7 ± 0.04) compared to sponge-collected OF (2.7 ± 0.15) and had higher values than sponges for cortisol, procalcitonin, oxytocin, haptoglobin, total protein, lactate dehydrogenase and ferric reducing antioxidant power. All biomarkers decreased in value with age. Immunoglobulin G did not perform well for any of the two collection methods. DISCUSSION AND CONCLUSION: The results showed a clear effect of age on the biomarkers in OF collected with both, sponges or ropes. Sponges provided a cleaner sample than cotton ropes for biomarker analysis. Both methods are easy to apply under the commercial conditions in pig farms although sponges may take more time in early weaner stages. From a practical point of view, sampling with sponges achieved the best combination of reduced sampling time and low contamination.

Serum Ferritin in Obese Dogs: Changes and Comparison with Other Analytes.

Canine obesity is the most common nutritional disorder and is associated with decreased quality of life and longevity as well as comorbidities including cardiorespiratory, endocrine, oncologic, or orthopaedic disorders. Ferritin is a major acute-phase protein in dogs, increasing during inflammation; however, it could also be affected by other conditions, including trauma, iron metabolism dysregulations, neoplasia, or hypoxia. Higher ferritin levels have been reported in obese humans, but ferritin has not been explored in canine obesity. To evaluate the possible changes in serum ferritin in canine obesity, ferritin levels from lean/normal weight (CG, n = 55) and overweight/obese dogs (OG, n = 37) were measured, together with complete hemogram and biochemical analyses. Statistically significant higher ferritin levels (1.2-fold) were found in OG (median, (interquartile range), 204 (166-227.5) µg/L) in comparison to CG animals (172 (137-210) µg/L)), with median levels of ferritin in OG dogs above the reference range for healthy animals in our laboratory (60-190 µg/L). In addition, statistically significant higher mean corpuscular volume (MCV), mean cell haemoglobin concentration (MCHC), total proteins, globulins, haptoglobin, total ferric fixation capacity (TIBC), alkaline phosphatase (ALP), butyrylcholinesterase (BChE), triglycerides, and calcium were observed in OG in comparison to CG. The higher levels in ferritin, together with higher TBIC, haematocrit, and MCV, could indicate tissue hypoxia in obese dogs.

SARS CoV-2 infection screening via the exhaled breath fingerprint obtained by FTIR spectroscopic gas-phase analysis. A proof of concept.

The COVID-19 pandemic remains a global challenge now with the long-COVID arising. Mitigation measures focused on case counting, assessment and determination of variants and their likely targets of infection and transmission, the pursuit of drug treatments, use and enhancement of masks, social distancing, vaccination, post-infection rehabilitation, and mass screening. The latter is of utmost importance given the current scenario of infections, reinfections, and long-term health effects. Research on screening platforms has been developed to provide more sensitive, specific, and reliable tests that are accessible to the entire population and can be used to assess the prognosis of the disease as well as the subsequent health follow-up of patients with sequelae of COVID-19. Therefore, the aim of the present study was the simulation of exhaled breath of COVID-19 patients by evaluation of three identified COVID-19 indicator breath biomarkers (acetone (ACE), acetaldehyde (ACH) and nitric oxide (NO)) by gas-phase infrared spectroscopy as a proof-of-concept principle for the detection of infected patients' exhaled breath fingerprint and subsequent follow-up. The specific fingerprints of each of the compounds and the overall fingerprint were obtained. The synthetic exhaled breath evaluation concept revealed a linearity of r = 0.99 for all compounds, and LODs of 6.42, 13.81, 9.22 ppm, and LOQs of 42.26, 52.57, 69.23 ppm for NO, ACE, and ACH, respectively. This study proves the fundamental feasibility of gas-phase infrared spectroscopy for fingerprinting lung damage biomarkers in exhaled breath of patients with COVID-19. This analysis would allow faster and cheaper screening and follow-up of infected individuals, which could improve mass screening in POC settings.

Study the Effect of an Innovative Educational Program Promoting Healthy Food Habits on Eating Disorders, Mediterranean Diet Adherence and Body Composition in University Students.

The university stage is a good time to promote healthy eating strategies. The sociological and cultural changes experienced by students lead them to skip meals, increase their intake of fast food and energy-dense foods, decreasing adherence to the Mediterranean diet (MD). Professionals related to food such as nutritionists and dietitians are also considered a population at risk of developing eating disorders due to the extensive knowledge they possess, which can be used for both good and bad practice. The objective was to analyze the impact of a 4-month educational program promoting the Mediterranean diet on risky eating behaviors, adherence to the Mediterranean diet, and body composition in nutrition and dietetics students, studying the differences according to the group investigated (control group and educated group). The context of the research was 196 students (49 males and 147 females) from two consecutive years. The control group did not receive any type of intervention, while with the control group (educated) an educational program was carried out. Results showed that women with greater control over energy intake, carbohydrates, and sugar had a lower percentage of fat mass, while in men, the relationship was established with weight. Regarding adherence to the Mediterranean diet, at post, it is adequate in both men (8.25 ± 2.87) and women (7.90 ± 2.89), with no significant differences between the intervention groups.

Perspectives of Therapeutic Drug Monitoring of Biological Agents in Non-Infectious Uveitis Treatment: A Review.

Biological drugs, especially those targeting anti-tumour necrosis factor α (TNFα) molecule, have revolutionized the treatment of patients with non-infectious uveitis (NIU), a sight-threatening condition characterized by ocular inflammation that can lead to severe vision threatening and blindness. Adalimumab (ADA) and infliximab (IFX), the most widely used anti-TNFα drugs, have led to greater clinical benefits, but a significant fraction of patients with NIU do not respond to these drugs. The therapeutic outcome is closely related to systemic drug levels, which are influenced by several factors such as immunogenicity, concomitant treatment with immunomodulators, and genetic factors. Therapeutic drug monitoring (TDM) of drug and anti-drug antibody (ADAbs) levels is emerging as a resource to optimise biologic therapy by personalising treatment to bring and maintain drug concentration within the therapeutic range, especially in those patients where a clinical response is less than expected. Furthermore, some studies have described different genetic polymorphisms that may act as predictors of response to treatment with anti-TNFα agents in immune-mediated diseases and could be useful in personalising biologic treatment selection. This review is a compilation of the published evidence in NIU and in other immune-mediated diseases that support the usefulness of TDM and pharmacogenetics as a tool to guide clinicians' treatment decisions leading to better clinical outcomes. In addition, findings from preclinical and clinical studies, assessing the safety and efficacy of intravitreal administration of anti-TNFα agents in NIU are discussed.

Recent Advances in Proteomics-Based Approaches to Studying Age-Related Macular Degeneration: A Systematic Review.

Age-related macular degeneration (AMD) is a common ocular disease characterized by degeneration of the central area of the retina in the elderly population. Progression and response to treatment are influenced by genetic and non-genetic factors. Proteomics is a powerful tool to study, at the molecular level, the mechanisms underlying the progression of the disease, to identify new therapeutic targets and to establish biomarkers to monitor progression and treatment effectiveness. In this work, we systematically review the use of proteomics-based approaches for the study of the molecular mechanisms underlying the development of AMD, as well as the progression of the disease and on-treatment patient monitoring. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guidelines were followed. Proteomic approaches have identified key players in the onset of the disease, such as complement components and proteins involved in lipid metabolism and oxidative stress, but also in the progression to advanced stages, including factors related to extracellular matrix integrity and angiogenesis. Although anti-vascular endothelial growth factor (anti-VEGF)-based therapy has been crucial in the treatment of neovascular AMD, it is necessary to deepen our understanding of the underlying disease mechanisms to move forward to next-generation therapies for later-stage forms of this multifactorial disease.

Caracterización y biomonitoreo de contaminantes orgánicos e inorgánicos en una zona ladrillera de San Luis Potosí / Characterization and biomonitoring of organic and inorganic contaminants in a brick-making area of San Luis Potosí

Resumen El sector ladrillero se caracteriza por la elaboración del ladrillo de forma artesanal donde utilizan técnicas rudimentarias, hornos de baja tecnología y diversos combustibles de poca calidad generando humos negros con gran cantidad de contaminantes. Por lo que el objetivo de este estudio fue caracterizar los metales en suelo, HAPs en aire y biomonitoreo de HAPs en trabajadores de la zona ladrillera "Las Terceras" San Luis Potosí, México. Con el fin de conocer la exposición laboral se determinó la concentración de HAPs en partículas PM10, se caracterizó el suelo de la zona de trabajo y se realizó un biomonitoreo de me-tabolitos hidroxilados HAPs (OH-HAPs) en orina de los trabajadores. En aire se encontraron 14 de los 16 HAPs prioritarios por la Agencia de Protección Ambiental en la fracción de PM10, con una concentración media de 5293,05 gg/m3 (3,11-10510,81). Los resultados del análisis químico de los polvos mostraron que están constituidos principalmente de cuarzo (SiO2) y arcillas (SiAlOx) con presencia de óxidos de Fe-Ti, fosfatos de tierras raras (Lantano, Cerio, Neodimio Torio), silicatos de zirconio, sulfatos de bario, óxidos de zinc. En el biomonitoreo participaron 42 trabajadores ladrilleros, los resultados de la exposición a OH-HAPs en orina demostraron la media total de los OH-HAPs de 15,7 (6,92-195) ng/ml. Estos resultados muestran que el monitoreo ocupa-cional de las zonas ladrilleras es importante debido al escenario de riesgo y a las condiciones precarias de este trabajo, además de la alta exposición a contaminantes que afectan la salud de los trabajadores y sus familias, así como la propuesta de estrategias que ayuden a minimizar los impactos ambientales y prevenir los efectos en salud de las poblaciones.

Abstract The brick-making sector is characterized by artisanal brick production using rudimentary techniques, low-tech kilns and various low-quality fuels that generate black fumes with a large amount of pollutants. Therefore, the objective of this study was to characterize metals in soil, PAHs in air and biomonitoring of PAHs in workers of the "Las Terceras" brick area in San Luis Potosí, Mexico. In order to know the occupational exposure, the concentration of PAHs in PM10 particles was determined, the soil of the work area was characterized and a biomonitoring of hydroxylated PAH metabolites (OH-HAPs) in the urine of the workers was carried out. In air, 14 of the 16 PAHs prioritized by the Environmental Protection Agency were found in the PM10 fraction, with an average concentration of 5293.05 gg/m3 (3.11-10510.81). The results of the chemical analysis of the dusts showed that they are mainly constituted of quartz (SiO2) and clays (SiAlOx) with presence of Fe-Ti oxides, rare earth phosphates (Lanthanum, Cerium, Neodymium Thorium), zirconium silicates, barium sulfates, zinc oxides. The biomonitoring involved 42 brick workers, the results of OH-HAPs exposure in urine showed the mean total OH-HAPs of 15.7 (6.92-195) ng/ml. These results show that occupational moni-toring of brick-making areas is important due to the risk scenario and the precarious conditions of this work, in addition to the high exposure to pollutants that affect the health of workers and their families, as well as the proposal of strategies that help minimize environmental impacts and prevent health effects on populations.

Evaluación de la exposición a Hidrocarburos Aromáticos Policíclicos, salud renal y respiratoria en población indígena de Tocoy, San Antonio, S. L. P, México / Evaluation of exposure to polycyclic aromatic hydrocarbons, renal and respiratory health in the indigenous population of Tocoy, San Antonio, S. L. P, México

Resumen La contaminación del aire interior es un problema de salud pública, ya que afecta a unos 2.600 millones de personas en todo el mundo que siguen cocinando con combustibles sólidos como la madera, los residuos de las cosechas, etc. Esta exposición aumenta el factor de riesgo de desarrollo de enfermedades crónicas. La población indígena es muy susceptible a estar expuesta a mezclas de contaminantes del humo de leña como los Hidrocarburos Aromáticos Policíclicos (HAPs) debido a los métodos tradicionales de cocción. El objetivo de este trabajo fue evaluar la exposición a HAPs por medio de 10 metabolitos hidroxilados en orina de la población indígena de la Huasteca Potosina, mediante cromatografía de gases acoplada a espectrometría de masas; por otro lado, la salud renal y pulmonar fueron evaluadas con una prueba general de orina y la toxina urémica Indoxil sulfato, esta fue evaluada por medio cromatografía líquida de alto rendimiento, y la función pulmonar con una espirometría. Los resultados indican la presencia de metabolitos hidroxilados en el 89,47% de las muestras de orina, los más frecuentes fueron el 1-OH-PIRENO, el 1,2-OH-NAFTALENO. El Indoxil sulfato se presentó en el 100% de las muestras y la media era de 193,4 ± 91,85 gg/L En cuanto a la salud pulmonar, los resultados indican que algunos sujetos presentan patrones respiratorios regulares e irregulares. Estos resultados indican que la población se encuentra expuesta de manera crónica a una mezcla de contaminantes en el aire que podría producir el desarrollo de daño en los pulmones y los riñones y aumentar el riesgo al desarrollo de enfermedades crónicas.

Abstract Interior air pollution is a public health concern, it affects about 2.6 billion people around the world who still cook using solid fuels such as wood, crop wastes, among others. This exposition increases the risk of the development of non-communicable diseases (NCDs). The indigenous population is very susceptible to being exposed to mixtures of pollutants from the wood smoke such as Polycyclic Aromatic Hydrocarbons (PAHs) due to traditional methods of cooking, heating and waste burning. Therefore, the objective of this work was to evaluate the exposure to PAHs through the application of 10 hydroxylated metabolites (OH-PAHs) in the urine of the indigenous population from the Huasteca Potosina, this by gas chromatography coupled to mass spectrometry and to assess renal health of the population at the time of the study, with a general test of urine and through the uremic toxin Indoxyl Sulfate (IS), this by high-performance liquid chromatography, and the and pulmonary health with spirometry. The results indicate the presence OH-PAHs in 89.47% of the urine samples, the most frequent metabolites were 1-OH-PYRENE, 2-OH-NAPTHALENE. IS was present in 100% of the samples in mean concentrations of 193.4 ± 91.85 gg/L. For pulmonary health, the results indicate some subjects have regular and irregular respiratory patterns. These results indicate that the population is highly exposed to a mixture of pollutants in the air that might damage the lungs and kidneys and increase the risk of NCDs development.

Aplicación de modelos metabolómicos para la identificación de EPOC en poblaciones expuestas a humo de leña en una comunidad indígena de México / Application of metabolomic models for the identificaron of coPD in populations exposed to wood smoke in an indigenous community in Mexico

Resumen Propósito: Para la evaluación metabólica de la fisiopatología pulmonar se utiliza principalmente el aliento exhalado, el cual ha tomado una gran relevancia como método de diagnóstico no invasivo, de bajo costo, rápido y seguro. El objetivo del presente estudio fue aplicar modelos metabolómicos para la identificación de la Enfermedad Pulmonar Obstructiva Crónica (EPOC) en población vulnerable expuesta a la quema de biomasa en una comunidad indígena de México. Métodos: El estudio se conformó por 142 participantes, 44 pacientes con EPOC asociado a la quema de biomasa, 60 controles y 38 población indígena expuesta a la quema de biomasa (PIE). Las muestras de aliento exhalado se analizaron mediante una nariz electrónica (HERACLES II, Alpha MOS). Con los datos obtenidos se realizó un Análisis Canónico de Coordenadas principales (CAP), que fue utilizado para la predicción de EPOC de la PIE y se determinó la concentración de 1-hidroxipireno (1-OHP) en muestras de orina. Resultados: Se logró identificar un total 59 COVs en las muestras de aliento exhalado de los grupos de estudio, los cuales se utilizaron para establecer un modelo de discriminación entre la huella química del grupo de pacientes con EPOC y el grupo control. El modelo CAP indicó una separación entre las huellas químicas de los pacientes con EPOC y sujetos sanos, con una correcta predicción de 91,34%, con una sensibilidad y especificidad de 93,2 y 96,7% respectivamente. Se encontraron 10 participantes de la PIE con patrón obstructivo y una alta concentración de 1-OHP, determinando que existe una concentración del 1,31 ± 0,67gg/mol de creatinina. Esta concentración se encuentra más de 5 veces arriba de los valores de referencia establecidos en el 2001, que es de 0,24 gg/mol de creatinina. Al comparar los resultados de la huella química de la PIE se posicionó en el grupo de EPOC. Conclusión: Se logró obtener un diagnóstico oportuno en población vulnerable mediante el uso de la metabolómica y se demostró la exposición y los efectos pulmonares en población indígena de San Luis Potosí.

Abstract Purpose: to evaluate metabolic disorders of the pathophysiology of the lung, the exhaled breath is mainly used, this has become highly relevant as a non-invasive, low-cost, fast and safe diagnostic method. The objective of this study is to apply metabolomic models for the identification of Chronic Obstructive Pulmonary Disease (COPD) in a vulnerable population exposed to biomass burning in an indigenous community in Mexico. Methods: The study consisted of 142 participants, 44 patients with COPD associated with biomass burning, 60 controls and 38 indigenous population exposed to biomass burning (PIE). Exhaled breath samples were analyzed using an electronic nose (HERACLES II, Alpha MOS). With the data obtained, a Canonical Analy-sis of Principal Coordinates (CAP) was performed, which was used for the prediction of COPD of IEP and the concentration of 1-hydroxypyrene (1-OHP) in urine samples was determined. Results: A total of 59 VOCs were identified in the exhaled breath samples of the study groups, which were used to establish a discrimination model between the chemical fingerprint of the COPD patient group and the control group. The CAP model indicated a separation between the chemical fingerprints of COPD patients and healthy subjects, with a correct prediction of 91,34%, with a sensitivity and specificity of 93,2 and 96,7%, respectively. 10 IEP participants with an obstructive pattern and a high concentration of 1-OHP were found, determining that there is a concentration of 1,31 ± 0,67gg/mol of creatinine. This concentration is more than 5 times above the reference values established in 2001, which is 0,24 -jg/mol of creatinine. When comparing the results of the Chemical fingerprint of the PIE, it was positioned in the COPD group. Conclusion: It was possible to obtain an opportune diagnosis in a vulnerable population using metabolomics and exposure and pulmonary effects were demonstrated in the indigenous population of San Luis Potosí.

One-Drop Serum Screening Test for Anal Cancer in Men via Infrared Attenuated Total Reflection Spectroscopy.

Rare cancers are a challenge for clinical practice, the treatment experience at major centers to which rare cancers are referred is limited and are the most difficult to diagnose. Research to identify causes or develop prevention and early detection strategies is extremely challenging. Anal cancer is an example of a rare cancer, with the human papillomavirus (HPV) infection being the most important risk factor associated. In the early stages, anal cancer does not exhibit evident symptoms. This disease is diagnosed by means of anoscopy, which diagnoses some cases of early cancer; nevertheless, sensitivity of this test ranges between 47 and 89%. Therefore, the development of new, effective, and evidence-based screening methodologies for the early detection of rare cancers is of great relevance. In this study, the potential of ATR-FTIR spectroscopy has been explored as a sensitive, nondestructive, and inexpensive analytical method for developing disease screening platforms in serum. Spectral differences were found in the regions of 1700-1100 and 1700-1400 cm-1 between the control group and the anal cancer group related to the presence of proteins and nucleic acids. The chemometric analysis presented differences in the spectral fingerprints for both spectral regions with a high sensitivity ranging from 95.2 to 99.9% and a specificity ranging from 99.2 to 100%. This is the first step that we report for a methodology that is fast, nondestructive, and easy to perform, and the high sensitivity and specificity of the method are the basis for extensive research studies to implement these technologies in the clinical field.

Cysteamine Eye Drops in Hyaluronic Acid Packaged in Innovative Single-Dose Systems: Stability and Ocular Biopermanence.

Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs causing, among other symptoms, severe ocular manifestations. Cysteamine eye drops are prepared in hospital pharmacy departments to facilitate access to treatment, for which vehicles that provide adequate biopermanence, as well as adaptable containers that maintain its stability, are required. Difficulties related to cysteamine preparation, as well as its tendency to oxidize to cystamine, show the importance of conducting rigorous galenic characterization studies. This work aims to develop and characterize an ophthalmic compounded formulation of cysteamine prepared with hyaluronic acid and packaged in innovative single-dose systems. For this task, the effect of different storage temperatures and the presence/absence of nitrogen on the physicochemical stability of the formulation and its packaging was studied in a scaled manner, until reaching the optimal storage conditions. The results showed that 0.55% cysteamine, prepared with hyaluronic acid and packaged in single-dose containers, is stable for 30 days when stored at -20 °C. In addition, opening vials every 4 h at room temperature after 30 days of freezing maintains the stability of the cysteamine formulation for up to 16 h. Moreover, ocular biopermanence studies were conducted using molecular imaging, concluding that the biopermanence offered by the vehicle is not affected by the freezing process, where a half-life of 31.11 min for a hyaluronic acid formulation stored for 30 days at -20 °C was obtained, compared with 14.63 min for 0.9% sodium chloride eye drops.

Effects of pen faeces and feed contamination in biomarkers determination in oral fluid of pigs.

The present study aims to evaluate the possible effects of the presence of pen faeces and feed on the measurement of a panel of biomarkers in porcine oral fluid. For this, clean porcine oral fluid was pooled and incubated with two different concentrations of pen faeces or feed representing a high or low level of contamination with each material. In addition, these pools were aliquoted and subjected to centrifugation, filtration or chemical clarification to evaluate if these techniques could revert the effects of those contaminants in biomarker evaluation. A panel of 21 biomarkers that assessed stress, inflammation, immune system and redox homeostasis among others, were measured for all aliquots. Changes of statistical relevance (p < 0.05) in oral fluid contaminated with pen faeces or feed versus untreated samples were observed for all methods employed with the exception of adenosine deaminase (ADA) and creatine kinase (CK) in oral fluid contaminated with pen faeces or feed. Pen faeces did not affect the measurement of haptoglobin, superoxide dismutase, CK, lactate dehydrogenase (LDH), ADA and cortisol (when the latter is measured by chemiluminescence); while uric acid, LDH, CK, ADA, and hydrogen peroxide methods were not affected by the presence of feed in oral fluid. The effects of centrifugation, filtration or chemical clarification with chitosan in these contaminated samples were modest and for most cases did not caused baseline levels on the measured biomarkers. In conclusion, the presence of pen faeces or feed in porcine oral fluid can interfere with the results obtained when analytes are measured.

Microbiome in Immune-Mediated Uveitis.

In the last decades, personalized medicine has been increasing its presence in different fields of medicine, including ophthalmology. A new factor that can help us direct medicine towards the challenge of personalized treatments is the microbiome. The gut microbiome plays an important role in controlling immune response, and dysbiosis has been associated with immune-mediated diseases such as non-infectious uveitis (NIU). In this review, we gather the published evidence, both in the pre-clinical and clinical studies, that support the possible role of intestinal dysbiosis in the pathogenesis of NIU, as well as the modulation of the gut microbiota as a new possible therapeutic target. We describe the different mechanisms that have been proposed to involve dysbiosis in the causality of NIU, as well as the potential pharmacological tools that could be used to modify the microbiome (dietary supplementation, antibiotics, fecal microbiota transplantation, immunomodulators, or biologic drugs) and, consequently, in the control of the NIU. Furthermore, there is increasing scientific evidence suggesting that the treatment with anti-TNF not only restores the composition of the gut microbiota but also that the study of the composition of the gut microbiome will help predict the response of each patient to anti-TNF treatment.

Evaluation of cytokines in exhaled breath condensate in an occupationally exposed population to pneumotoxic pollutants.

The quarrying is considered a precarious occupation with high toxicity, is an informal economic activity that employs low technology, limited protection, and poses a risk to workers and their families. In quarrying, silica dust is generated and there is also occupational exposure to significant mixtures of pneumotoxic pollutants, including mineral dust (crystalline silica, carbon or cement, polycyclic aromatic hydrocarbons (PAHs), solvents, and others, which are aggravated by the lack of use of protective equipment, causing irreversible damage to the worker's respiratory health. Thus, the objective of this work focused on the evaluation of the respiratory health of artisan stonemasons in San Luis Potosí, Mexico through the study of exhaled breath condensate (EBC) (pH, pro-inflammatory cytokines) as well as the study of the exposure to pollutants present in the work area (PAHs, toluene, and 2.5 µm particulate matter) through biomarkers of exposure (hippuric acid and hydroxylated metabolites of PAHs). The results show the presence of crystalline SiO2 in 100% of the samples analyzed; the PM2.5 concentrations were 5 to 10 times the permitted levels. Regarding exposure to PAHs, all the stonemasons presented urine concentrations of at least 5 of the OH-PAHs evaluated; 9-OH-FLU occurred at higher concentrations of 171.2 (122.7-279.4) µg L-1; hippuric acid, which was present in 100% of the workers evaluated in concentrations of 283.4 (27.72-1119) mg L-1, 100% of which were above the values established for occupational scenarios. The pH values obtained for the EBC samples were presented at an average of 7.07 (6.33-7.66). Pro-inflammatory cytokines were present in 86.1% of the study population. The cytokine that was found in higher concentrations was IL-2, with a mean of 178.01 pg mL-1 and 3124.01 pg mL-1 for the pH < 7 and pH > 7 groups, respectively. Some correlations between the cytokines and the exposure biomarkers were presented. Stonemasons are highly exposed to pneumotoxic pollutants and markers of inflammation at the pulmonary level; in addition, a high risk of developing silicosis. Quarrying should be addressed as a carcinogenic activity, which would imply the design of monitoring and control strategies for these pollutants that our country currently lacks, particularly in precarious occupations. It is necessary to develop strategies to protect the health of precarious workers.

Spontaneous Haematomas in Anticoagulated Covid-19 Patients: Diagnosis and Treatment by Embolization.

PURPOSE: To assess the safety and efficacy of embolization for spontaneous bleeding in anticoagulated patients with COVID-19. MATERIAL AND METHODS: Single center retrospective study in 9 patients with COVID-19 who experienced bleeding complications following anticoagulation. The study included 8 men and 1 woman aged from 48 to 80 years (mean 69.7 years), who had a total of 10 soft tissue haematomas: 1 in the thigh, 1 in the anterior abdominal wall, 6 retroperitoneal and 2 thoracic haematomas. All patients were referenced for vascular embolization, mostly with Onyx-18. RESULTS: A total of 10 haematomas were embolized in 9 patients. Technical success was achieved in all patients. No complications or adverse events were noted. One patient required percutaneous drainage of an infected haematoma 88 days after embolization. The mean hemoglobin level before embolization was 8,64 mg/dL and increased to 9,08 mg/dL after embolization (p = 0,3). After embolization all patients recovered haemodynamic stability and blood pressure levels improved. Seven patients resumed anticoagulation therapy after embolization. There were no recurrences or new bleedings in all treated patients. No patients required any additional invasive therapies or surgery. Mean intensive unit care and hospital stay was 6.7 and 35.2 days, respectively. All patients were discharged and were well at follow-up clinic visits 2-7 months after embolization. Seven patients performed a control CT scan 1-6 months after embolization, showing complete resolution of the haematoma. CONCLUSION: Embolization is safe and effective to treat spontaneous haematomas in anticoagulated patients with COVID-19, allowing to resume anticoagulation therapy. Level of evidence IV Level 4, case-series.

A Systematic Review of the Cardiometabolic Benefits of Plant Products Containing Mixed Phenolics and Polyphenols in Postmenopausal Women: Insufficient Evidence for Recommendations to This Specific Population.

Menopause is characterized by endocrine and physiological changes and is often accompanied by increased body weight and cholesterol, glucose intolerance, and/or hypertension. These alterations are associated with increased risk for cardiovascular diseases (CVDs) and Type II diabetes mellitus (T2DM) that may be moderate by dietary plant phenolic compounds. In this review, we examine the current evidence of the impact of a variety of plant products (foods, extracts, beverages) rich in a mixture of phenolics and polyphenols on: (i) glucose and insulin levels; (ii) lipid profile; (iii) blood pressure; and (iv) biomarkers of inflammation and oxidative stress in postmenopausal women. We critically evaluate both the results of a range of intervention studies conducted in this specific subpopulation and the level of evidence supporting the benefits of consuming those products after the menopause. Overall, the current available evidence does not allow for specific dietary recommendations of these plant products rich in phenolics and polyphenols in this high-risk subpopulation. Our data show rather variable and small effects of the different products examined on the cardiometabolic biomarkers and further support the need to: (1) improve the quality of the study designs and data reporting; and (2) understand the variability in the response of the different biomarkers and establish clear differences between healthy and cardiometabolic disease levels.