Integrative analysis of systemic lupus erythematosus biomarkers: Role of fecal hsa-mir-223-3p and gut microbiota in transkingdom dynamics.

Systemic lupus erythematosus (SLE) involves a florid set of clinical manifestations whose autoreactive origin is characterized by an overactivation of the immune system and the production of a large number of autoantibodies. Because it is a complex pathology with an inflammatory component, its pathogenesis is not yet fully understood, assuming both genetic and environmental predisposing factors. Currently, it is known that the role of the human microbiome is crucial in maintaining the transkingdom balance between commensal microorganisms and the immune system. In the present work we study the intestinal microbiota of Argentine patients with different stages of SLE receiving or not different treatments. Microbiota composition and fecal miRNAs were assessed by 16 S sequencing and qPCR. hsa-miR-223-3p, a miRNA involved in several inflammation regulation pathways, was found underexpressed in SLE patients without immunosuppressive treatment. In terms of microbiota there were clear differences in population structure (Weighted and Unweighted Unifrac distances, p-value <0.05) and core microbiome between cases and controls. In addition, Collinsella, Bifidobacterium, Streptococcus genera and aromatics degradation metabolisms were overrepresented in the SLE group. Medical treatment was also determinant as several microbial metabolic pathways were influenced by immunosuppressive therapy. Particularly, allantoin degradation metabolism was differentially expressed in the group of patients receiving immunosuppressants. Finally, we performed a logistic regression model (LASSO: least absolute shrinkage and selection operator) considering the expression levels of the fecal hsa-miR223-3p; the core microbiota; the differentially abundant bacterial taxa and the differentially abundant metabolic pathways (p<0.05). The model predicted that SLE patients could be associated with greater relative abundance of the formaldehyde oxidation pathway (RUMP_PWY). On the contrary, the preponderance of the ketodeoxyoctonate (Kdo) biosynthesis and activation route (PWY_1269) and the genera Lachnospiraceae_UCG_004, Lachnospira, Victivallis and UCG_003 (genus belonging to the family Oscillospiraceae of the class Clostridia) were associated with a control phenotype. Overall, the present work could contribute to the development of integral diagnostic tools for the comprehensive phenotyping of patients with SLE. In this sense, studying the commensal microbial profile and possible pathobionts associated with SLE in our population proposes more effective and precise strategies to explore possible treatments based on the microbiota of SLE patients.

Dermatosis en la región mamaria: estudio retrospectivo de 171 pacientes atendidas en el Hospital General Dr. Manuel Gea González / Skin diseases of the breast: A retrospective study of 171 patients at "Dr. Manuel Gea González" General Hospital

Resumen OBJETIVO: Describir las dermatosis de la región mamaria que para su diagnóstico durante la consulta dermatológica ameritaron estudio histopatológico. MATERIALES Y MÉTODOS: Estudio retrospectivo llevado a cabo con base en los expedientes electrónicos de pacientes atendidas en el servicio de Dermatopatología entre 1992 y 2021. Los términos de búsqueda fueron: "mama", "seno", "areola" y "pezón". RESULTADOS: Se reunieron 171 reportes histopatológicos. El diagnóstico clínico de envío más común en mujeres fue la infiltración cutánea por cáncer de mama y en hombres el pezón supernumerario. Las dermatosis más frecuentes pertenecieron al grupo de tumoraciones benignas (78 de 171), seguidas de las dermatosis inflamatorias no infecciosas (48 de 171), en tercer lugar las neoplasias malignas (39 de 171) y 6 de 171 correspondieron a dermatosis inflamatorias infecciosas. CONCLUSIONES: Las enfermedades cutáneas de la mama tienen diversas manifestaciones clínicas que, en ocasiones, ameritan un estudio histopatológico, sobre todo para un diagnóstico oportuno de neoplasias malignas.

Abstract OBJECTIVE: Describe dermatoses of the mammary region that warranted histopathological diagnosis in dermatologic consults. MATERIALS AND METHODS: The Hospital "Dr. Manuel Gea Gonzalez" Dermatopathology Department record database was reviewed in the 1992 to 2021 period, using the search engine terms "breast," "mammary," "nipple," and "areola." Lesions were classified as benign, malignant, infectious and noninfectious inflammatory tumors. RESULTS: 171 histopathological reports were reviewed. There was a female predominance in histopathological studies (153/171). The most frequent clinical diagnosis for referral in female patients was breast cancer with cutaneous infiltration; supernumerary nipple was the most frequent clinical diagnosis for male patients. The most frequent dermatoses belonged to the benign tumor category (78/171), followed by noninfectious inflammatory dermatoses (48/171). Malignant neoplasms were in third place (39/171), and 3.5% of dermatoses were infectious inflammatory dermatoses. CONCLUSIONS: Cutaneous mammary disease has diverse clinical presentations that might occasionally warrant histopathological studies, mainly for the early diagnosis of malignant neoplasms.

Disseminated Sporotrichosis: An Important Differential Diagnosis for Venous Ulcers.

The authors present the case of a 45-year-old immunosuppressed man with lower extremity ulcers. Initially treated as venous ulcers, the wounds were later correctly diagnosed as cutaneous disseminated sporotrichosis. After appropriate treatment with systemic antifungals was initiated, the patient healed within 4 months.

Translation, cross-cultural adaptation and validation of the "Cardiff wound impact schedule," a wound-specific quality of life instrument, to the native Spanish of Mexican patients.

The aim of this study was to translate into Mexican Spanish, cross-culturally adapt and validate the wound-specific quality of life (QoL) instrument Cardiff wound impact schedule (CWIS) for Mexican patients. This instrument went through the full linguistic translation process based on the guidelines of Beaton et al (Beaton DE, Bombardier C, Guillemin F, Ferraz MB, Guidelines for the process of cross-cultural adaptation of self-report measures, Spine Phila Pa, 1976, 2000, 318-391). We included a total of 500 patients with chronic leg ulcers. The expert committee evaluated the Face validity and they agreed unanimously that the instrument was adequate to assess the QoL of these patients, covering all relevant areas presented by them. The content validity index obtained was of 0.95. The construct validity demonstrated moderately significant correlations between related sub-scales of CWIS and SF-36 (P = .010 to P < .001). The instrument was able to discriminate between healed and unhealed ulcers. The instrument obtained an overall Cronbach's alpha of .952, corresponding to an excellent internal consistency (.903-.771 alpha range for domains). The CWIS can be appropriately used to assess the health-related QoL of Mexican patients with chronic leg ulcers.

Aging Exacerbates Neuroinflammatory Outcomes Induced by Acute Ozone Exposure.

The role of environmental stressors, particularly exposure to air pollution, in the development of neurodegenerative disease remains underappreciated. We examined the neurological effects of acute ozone (O3) exposure in aged mice, where increased blood-brain barrier (BBB) permeability may confer vulnerability to neuroinflammatory outcomes. C57BL/6 male mice, aged 8-10 weeks or 12-18 months were exposed to either filtered air or 1.0 ppm O3 for 4 h; animals received a single IP injection of sodium fluorescein (FSCN) 20 h postexposure. One-hour post-FSCN injection, animals were transcardially perfused for immunohistochemical analysis of BBB permeability. ß-amyloid protein expression was assessed via ELISA. Flow cytometric characterization of infiltrating immune cells, including neutrophils, macrophages, and microglia populations was performed 20 h post-O3 exposure. Flow cytometry analysis of brains revealed increased microglia "activation" and presentation of CD11b, F4/80, and MHCII in aged animals relative to younger ones; these age-induced differences were potentiated by acute O3 exposure. Cortical and limbic regions in aged brains had increased reactive microgliosis and ß-amyloid protein expression after O3 insult. The aged cerebellum was particularly vulnerable to acute O3 exposure with increased populations of infiltrating neutrophils, peripheral macrophages/monocytes, and Ly6C+ inflammatory monocytes after insult, which were not significantly increased in the young cerebellum. O3 exposure increased the penetration of FSCN beyond the BBB, the infiltration of peripheral immune cells, and reactive gliosis of microglia. Thus, the aged BBB is vulnerable to insult and becomes highly penetrable in response to O3 exposure, leading to greater neuroinflammatory outcomes.

Surface area-dependence of gas-particle interactions influences pulmonary and neuroinflammatory outcomes.

BACKGROUND: Deleterious consequences of exposure to traffic emissions may derive from interactions between carbonaceous particulate matter (PM) and gaseous components in a manner that is dependent on the surface area or complexity of the particles. To determine the validity of this hypothesis, we examined pulmonary and neurological inflammatory outcomes in C57BL/6 and apolipoprotein E knockout (ApoE-/-) male mice after acute and chronic exposure to vehicle engine-derived particulate matter, generated as ultrafine (UFP) and fine (FP) sizes, with additional exposures using UFP or FP combined with gaseous copollutants derived from fresh gasoline and diesel emissions, labeled as UFP + G and FP + G. RESULTS: The UFP and UFP + G exposure groups resulted in the most profound pulmonary and neuroinflammatory effects. Phagocytosis of UFP + G particles via resident alveolar macrophages was substantial in both mouse strains, particularly after chronic exposure, with concurrent increased proinflammatory cytokine expression of CXCL1 and TNFα in the bronchial lavage fluid. In the acute exposure paradigm, only UFP and UFP + G induced significant changes in pulmonary inflammation and only in the ApoE-/- animals. Similarly, acute exposure to UFP and UFP + G increased the expression of several cytokines in the hippocampus of ApoE-/- mice including Il-1ß, IL-6, Tgf-ß and Tnf-α and in the hippocampus of C57BL/6 mice including Ccl5, Cxcl1, Il-1ß, and Tnf-α. Interestingly, Il-6 and Tgf-ß expression were decreased in the C57BL/6 hippocampus after acute exposure. Chronic exposure to UFP + G increased expression of Ccl5, Cxcl1, Il-6, and Tgf-ß in the ApoE-/- hippocampus, but this effect was minimal in the C57BL/6 mice, suggesting compensatory mechanisms to manage neuroinflammation in this strain. CONCLUSIONS: Inflammatory responses the lung and brain were most substantial in ApoE-/- animals exposed to UFP + G, suggesting that the surface area-dependent interaction of gases and particles is an important determinant of toxic responses. As such, freshly generated UFP, in the presence of combustion-derived gas phase pollutants, may be a greater health hazard than would be predicted from PM concentration, alone, lending support for epidemiological findings of adverse neurological outcomes associated with roadway proximity.

Multienzymatic-rotating biosensor for total cholesterol determination in a FIA system.

Fabrication of an amperometric-rotating biosensor for the enzymatic determination of cholesterol is reported. The assay utilizes a combination of three enzymes: cholesterol esterase (ChE), cholesterol oxidase (ChOx) and peroxidase (HRP); which were co-immobilizing on a rotatory disk. The method is developed by the use of a glassy carbon electrode as detector versus Ag/AgCl/3M NaCl in conjunction with a soluble-redox mediator 4-tert-butylcatechol (TBC). ChE converts esterified cholesterol to free cholesterol, which is then oxidized by ChOx with hydrogen peroxide as product. TBC is converted to 4-tert-butylbenzoquinone (TBB) by hydrogen peroxide, catalyzed by HRP, and the glassy carbon electrode responds to the TBB concentration. The system has integrated a micro packed-column with immobilized ascorbate oxidase (AAOx) that works as prereactor to eliminate l-ascorbic acid (AA) interference. This method could be used to determine total cholesterol concentration in the range 1.2muM-1mM (r=0.999). A fast response time of 2min has been observed with this amperometric-rotating biosensor. Lifetime is up to 25 days of use. The calculated detection limits was 11.9nM. Reproducibility assays were made using repetitive standards solutions (n=5) and the percentage standard error was less than 4%.