Nor climate nor human impact factors: Chytrid infection shapes the skin bacterial communities of an endemic amphibian in a biodiversity hotspot.

The bacterial communities of the amphibian skin (i.e., the bacteriome) are critical to the host's innate immune system. However, it is unclear how different drivers can alter this function by modulating the bacteriome's structure. Our aim was to assess the extent to which different host attributes and extrinsic factors influence the structure of the bacterial communities of the skin. Skin bacterial diversity was examined in 148 individuals of the four-eyed frog (Pleurodema thaul) from 16 localities spanning almost 1800 km in latitude. The richness and beta diversity of bacterial families and the richness and abundance of Bd-inhibitory bacterial genera were used to describe their structure. Predictors associated with the host (developmental stage, genetic lineage, individual Batrachochytrium dendrobatidis [Bd] infection status) and the landscape (current climate, degree of anthropogenic disturbance) were used in the statistical modeling in an information theoretical approach. Bd infection and host developmental stage were the only predictors affecting bacteriome richness, with Bd+ individuals and postmetamorphic stages (adults and juveniles) having higher richness than Bd- ones and tadpoles. High diversity in Bd+ individuals is not driven by bacterial genera with known anti-Bd properties. Beta diversity was not affected by Bd infection and was mainly a consequence of bacterial family turnover rather than nestedness. Finally, for those bacterial genera known to have inhibitory effects on chytrid, Bd+ individuals had a slightly higher diversity than Bd- ones. Our study confirms an association between Bd infection and the host developmental stage with the bacterial communities of the skin of P. thaul. Unexpectedly, macroclimate and human impact factors do not seem to play a role in shaping the amphibian skin microbiome. Our study exemplifies that focusing on a single host-parasite system over a large geographic scale can provide essential insights into the factors driving host-parasite-bacteriome interactions.

Percutaneous Gastrostomies: Associated Complications in PUSH vs. PULL Techniques over 12 Years in a Referral Centre.

Objectives: To compare complications associated with percutaneous gastrostomies performed using PUSH and PULL techniques, whether endoscopic (PEG) or radiological (PRG), in a tertiary-level hospital. Methods: This was a prospective observational study. Adult patients who underwent percutaneous PULL or PUSH gastrostomy using PEG or PRG techniques at the Virgen del Rocio University Hospital and subsequently followed up in the Nutrition Unit between 2009-2020 were included. X2 tests or Fisher's test were used for the comparison of proportions when necessary. Univariate analysis was conducted to study risk factors for PRG-associated complications. Results: n = 423 (PULL = 181; PUSH = 242). The PULL technique was associated with a higher percentage of total complications (37.6% vs. 23.8%; p = 0.005), exudate (18.2% vs. 11.2%; p = 0.039), and irritation (3.3% vs. 0%; p = 0.006). In the total sample, there were 5 (1.1%) cases of peritonitis, 3 (0.7%) gastrocolic fistulas, and 1 (0.2%) death due to complications associated with gastrostomy. Gender, age, and different indications were not risk factors for a higher number of complications. The most common indications were neurological diseases (35.9%), head and neck cancer (29%), and amyotrophic lateral sclerosis (17.2%). Conclusions: The PULL technique was associated with more total complications than the PUSH technique, but both were shown to be safe techniques, as the majority of complications were minor.

[In silico analysis of molecular mimicry between human aquaporin 3, Aspergillus fumigatus aquaporin and aquaporins from allergic sources]. / Análisis en silico del mimetismo molecular entre acuaporina 3 humana y Aspergillus fumigatus: implicaciones para el potencial de reactividad cruzada.

OBJECTIVE: Conduct an in-silico assessment of potential molecular mimicry between human aquaporins, A. fumigatus, and diverse allergenic sources. METHODS: Amino acid sequences of human AQP3 and A. fumigatus aquaporin were compared through multiple alignments with 25 aquaporins from diverse allergenic sources. Phylogenetic analysis and homology-based modeling were executed, and the ElliPro server predicted conserved antigenic regions on 3D structures. RESULTS: Global identity among studied aquaporins was 32.6%, with a specific conserved local region at 71.4%. Five monophyletic clades (A-E) were formed, and Group B displayed the highest identity (95%), including 6 mammalian aquaporins, notably AQP3. A. fumigatus aquaporin exhibited the highest identity with Malassezia sympodialis (35%). Three linear and three discontinuous epitopes were identified in both human and A. fumigatus aquaporins. The Root Mean Square Deviation (RMSD) from overlapping aquaporin structures was 1.006. CONCLUSION: Identification of potential linear and conformational epitopes on human AQP3 suggests likely molecular mimicry with A. fumigatus aquaporins. High identity in a specific antigenic region indicates potential autoreactivity and a probable antigenic site involved in cross-reactivity. Validation through in vitro and in vivo studies is essential for further understanding and confirmation.

OBJETIVO: Realizar una evaluación in silico del posible mimetismo molecular entre las acuaporinas humanas, A. fumigatus y diversas fuentes alergénicas. MÉTODOS: Se compararon secuencias de aminoácidos de AQP3 humana y acuaporina de A. fumigatus mediante alineamientos múltiples con 25 acuaporinas de diversas fuentes alergénicas. Se ejecutaron análisis filogenéticos y modelos basados en homología, y el servidor ElliPro predijo regiones antigénicas preservadas en estructuras 3D. RESULTADOS: La identidad global entre las acuaporinas estudiadas fue del 32.6%, con una región local específica preservada en el 71.4%. Se formaron cinco clados monofiléticos (A-E), y el grupo B mostró la identidad más alta (95%), incluidas 6 acuaporinas de mamíferos, en particular AQP3. A. fumigatus aquaporin exhibió la mayor identidad con Malassezia sympodialis (35%). Se identificaron tres epítopos lineales y tres discontinuos en acuaporinas tanto humanas como de A. fumigatus. La desviación cuadrática media (RMSD) de las estructuras de acuaporinas superpuestas fue de 1,006. CONCLUSIÓN: La identificación de posibles epítopos lineales y conformacionales en AQP3 humano sugiere un probable mimetismo molecular con acuaporinas de A. fumigatus. La identidad alta en una región antigénica específica indica autorreactividad potencial y un sitio antigénico probable implicado en la reactividad cruzada. La validación mediante estudios in vitro e in vivo es desicivo para una mayor comprensión y confirmación.

[Molecular mimicry between Plasmodium sp and Guillain-Barre syndrome antigens]. / Mimetismo molecular entre el Plasmodium sp y los antígenos del síndrome de Guillain-Barre.

OBJECTIVE: Analyze the molecular mimicry between Plasmodium spp. and autoantigens associated with GBS, identifying possible antigenic epitopes. METHODS: PSI-Blast, Praline, Emboss, Protein Data Bank, Swiss Model Server, AlphaFold 2, Ellipro and PyMol 2.3 were used to search for homologies, perform alignments, obtain protein structures, and predict epitopes. RESULTS: 17 autoantigens and seven immunological targets of the peripheral nervous system were included, identifying 72 possible epitopes associated with GBS. From the proteome of Plasmodium spp. (298 proteins), only two showed similarities close to 30% with TRIM21 and BACE1, generating seven possible epitopes. CONCLUSION: No significant homologies were observed between the proteome of GBS and Plasmodium spp. The exploration of other mechanisms such as immune-mediated capillary damage, Epitope Spreading or Bystander Activation is suggested to explain the mentioned association. These findings underscore the need to clarify the etiology of autoimmune diseases and the role of pathogens. The need for experimental studies to validate these results is emphasized.

OBJETIVO: Analizar el mimetismo molecular entre Plasmodium spp. y autoantígenos asociados al SGB, identificando posibles epítopos antigénicos. MÉTODOS: Se emplearon PSI-Blast, Praline, Emboss, Protein Data Bank, Swiss Model Server, AlphaFold 2, Ellipro y PyMol 2.3 para buscar homologías, realizar alineamientos, obtener estructuras proteicas y predecir epítopos. RESULTADOS: Se incluyeron 17 autoantígenos y siete objetivos inmunológicos del sistema nervioso periférico, identificándose 72 posibles epítopos asociados al SGB. Del proteoma de Plasmodium spp. (298 proteínas), solo dos mostraron similitud cercana al 30% con TRIM21 y BACE1, generando siete posibles epítopos. CONCLUSIÓN: No se observaron homologías significativas entre el proteoma de SGB y Plasmodium spp. Se sugiere la exploración de otros mecanismos como el daño capilar inmunomediado, Epitope Spreading o Bystander Activation para explicar la asociación mencionada. Estos hallazgos subrayan la necesidad de aclarar la etiología de las enfermedades autoinmunes y el papel de los patógenos. Se enfatiza la necesidad de estudios experimentales para validar estos resultados.

[Molecular mimicry between human thyroid peroxidase, thyroglobulin, cosinophil peroxidase, IL-24 and microorganisms antigens]. / Mimetismo molecular entre peroxidasa tiroidea humana, tiroglobulina, peroxidasa de eosinófilos, IL-24 y antígenos de microorganismos.

OBJECTIVE: Identify molecular mimicry between TPO, eosinophil peroxidase (EPX), thyroglobulin and IL24 and microorganism antigens. METHODS: Through in silico analysis, we performed local alignments between human and microorganism antigens with PSI-BLAST. Proteins that did not present a 3D structure were modeled by homology through the Swiss Modeller server and epitope prediction was performed through Ellipro. Epitopes were located in the 3D models using PYMOL software. RESULTS: A total of 38 microorganism antigens (parasites, bacteria) had identities between 30% and 45%, being the highest with Anisakis simplex. The alignment between 2 candidate proteins from A. simplex and EPX presented significant values, with identities of 43 and 44%. In bacteria, Campylobacter jejuni presented the highest identity with thyroglobulin (35%). 220 linear and conformational epitopes of microorganism antigens were predicted. Peroxidasin-like proteins from Toxocara canis and Trichinella pseudospiralis presented 10 epitopes similar to TPO and EPX, as possible molecules triggering cross-reactivity. No virus presented identity with the human proteins studied. CONCLUSION: TPO and EPX antigens shared potential cross-reactive epitopes with bacterial and nematode proteins, suggesting that molecular mimicry could be a mechanism that explains the relationship between infections and urticaria/hypothyroidism. In vitro work is needed to demonstrate the results obtained in the in silico analysis.

OBJETIVO: Identificar mimetismo molecular entre TPO, eosinofil peroxidasa (EPX), tiroglobulina e IL24 y antígenos de microorganismos. MÉTODOS: A través de análisis in silico, realizamos los alineamientos locales entre los antígenos humanos y de microorganismos con PSI-BLAST. Las proteínas que no presentaban estructura 3D, fueron modeladas por homología a través del servidor Swiss Modeller y se realizó una predicción de epítopes a través de Ellipro. Los epítopes se localizaron en los modelos 3D utilizando el software PYMOL. RESULTADOS: Un total de 38 antígenos de microorganismos (parásitos y bacterias), tuvieron identidades entre 30 y 45%, siendo los más altos con Anisakis simplex. El alineamiento entre dos proteínas candidatas de A. simplex y EPX presentaron valores importantes, con identidades de 43 y 44%. En las bacterias, Campylobacter jejuni presentó la mayor identidad con tiroglobulina (35%). Se predijeron 220 epítopes lineales y conformacionales de antígenos de microorganismos. Las proteínas similares a la peroxidasina de Toxocara canis y Trichinella pseudospiralis presentaron diez epítopes similares a TPO y EPX, como posibles moléculas desencadenantes de una reactividad cruzada. Ningún virus presentó identidad con las proteínas humanas estudiadas. CONCLUSIÓN: Los antígenos TPO y EPX compartieron potenciales epítopes de reacción cruzada con proteínas bacterianas y nematodos, lo que sugiere que el mimetismo molecular podría ser un mecanismo que explique la relación entre infecciones y la urticaria/hipotiroidismo. Se necesitan trabajos in vitro que demuestren los resultados obtenidos en el análisis in silico.

Locus coeruleus features are linked to vagus nerve stimulation response in drug-resistant epilepsy.

The locus coeruleus-norepinephrine system is thought to be involved in the clinical effects of vagus nerve stimulation. This system is known to prevent seizure development and induce long-term plastic changes, particularly with the release of norepinephrine in the hippocampus. However, the requisites to become responder to the therapy and the mechanisms of action are still under investigation. Using MRI, we assessed the structural and functional characteristics of the locus coeruleus and microstructural properties of locus coeruleus-hippocampus white matter tracts in patients with drug-resistant epilepsy responding or not to the therapy. Twenty-three drug-resistant epileptic patients with cervical vagus nerve stimulation were recruited for this pilot study, including 13 responders or partial responders and 10 non-responders. A dedicated structural MRI acquisition allowed in vivo localization of the locus coeruleus and computation of its contrast (an accepted marker of LC integrity). Locus coeruleus activity was estimated using functional MRI during an auditory oddball task. Finally, multi-shell diffusion MRI was used to estimate the structural properties of locus coeruleus-hippocampus tracts. These characteristics were compared between responders/partial responders and non-responders and their association with therapy duration was also explored. In patients with a better response to the therapy, trends toward a lower activity and a higher contrast were found in the left medial and right caudal portions of the locus coeruleus, respectively. An increased locus coeruleus contrast, bilaterally over its medial portions, correlated with duration of the treatment. Finally, a higher integrity of locus coeruleus-hippocampus connections was found in patients with a better response to the treatment. These new insights into the neurobiology of vagus nerve stimulation may provide novel markers of the response to the treatment and may reflect neuroplasticity effects occurring in the brain following the implantation.

Clinical evaluation of posterior restorations over wet and dry dentin using an etch-and-rinse adhesive: A 36-month randomized clinical trial.

OBJECTIVES: To evaluate the clinical performance of posterior restorations over wet and dry dentin with an etch-and-rinse adhesive after 36 months of clinical service. METHODS: Forty-five participants were recruited, each one had at least two posterior teeth that needed restoration. Ninety restorations were placed on Class I or Class II cavities. For the restoration protocol, a simplified etch-and-rinse adhesive (Adper Single Bond 2) was applied over wet (WD) or dry dentin (DD) and later restored with a bulk-fill composite (Filtek Bulk Fill) under rubber dam isolation. Each restoration was evaluated using the World Dental Federation (FDI) criteria after 6, 12, and 36 months of clinical service, regarding the following principal restoration characteristics: postoperative sensitivity, marginal discoloration, marginal adaptation, fracture of material and retention, and recurrence of caries. Kruskal Wallis analysis of variance rank (α = 0.05) and Kaplan-Meier survival analysis were used for statistical analysis. RESULTS: After 36 months of clinical evaluation, no significant difference between groups was observed in each FDI criterion (p > 0.05). Twenty restorations (WD=10, DD=10) showed minor marginal staining, and twenty-two restorations (WD=11, DD=11) presented small marginal adaptation defects (p > 0.05). Four restorations were lost (WD = 2, DD = 2) and the fracture rates (95% confidence interval) were 94.9% for each one, without significant difference between wet and dry dentin (p > 0.05). SIGNIFICANCE: The degree of dentin moisture does not seem to affect the clinical performance of a simplified etch-and-rinse adhesive in posterior restorations when the adhesive is applied vigorously over the dentine surface.

Consulta de preanestesia no presencial en niños: experiencias y recomendaciones / Telemedicine pre-anesthesia evaluation in children: Experiences and recommendations

Desde hace años se realizan consultas y seguimiento de pacientes de forma no presencial. Durante la pandemia de COVID-19 diferentes sociedades han recomendado potenciar las consultas telemáticas. La consulta preanestésica no presencial es un acto médico que debe incluir los objetivos básicos de evaluación, preparación, información y obtención del consentimiento. Se debe disponer de medios y tiempo para realizarla. Al comienzo de la consulta debe identificarse el médico y el o los progenitores. La consulta preoperatoria no presencial es especialmente útil en niños ASA I y II que van a someterse a cirugías de bajo riesgo, a una reintervención o a procedimientos diagnósticos. Aquellos pacientes que requieran una exploración física, más allá de la posible de manera telemática, deberán citarse en la consulta presencial. El personal de enfermería puede participar de forma activa en este proceso siempre y cuando el anestesiólogo supervise todo el proceso, tome todas las decisiones sobre el procedimiento y sea el responsable de la información que se da a los padres y al niño, aclarando personalmente cualquier duda. El anestesiólogo debe informar del procedimiento, sus riesgos, incluidos los personalizados, y alternativas. Se registrará en la historia clínica que se ha informado, cuándo y a quién. EL anestesiólogo firmará el Consentimiento Informado haciendo figurar la fecha que da la información y los padres deberán firmarlo antes de la intervención.(AU)

Medical consult and follow-up of patients have been carried out remotely for years. During the COVID-19 pandemic, different societies have recommended promoting online consultations. The remote pre-anesthetic consultation is a medical act that must include the basic objectives of evaluation, preparation, information and obtaining consent. You must have the resources and time to do it. At the beginning of the consultation, the doctor and the parent(s) must be identified. Non-face-to-face preoperative consultation is especially useful in ASA I and II children evaluated for low-risk surgeries, reintervention, or diagnostic procedures. Those patients who require a physical examination, beyond that possible electronically, should make an appointment in the face-to-face consultation. The nursing staff can actively participate in this process as long as the anesthesiologist supervises the entire process, makes all decisions about the procedure and is responsible for the information given to the parents and the child, personally clarifying any doubts. The anesthesiologist must inform about the procedure, its risks, including personalized ones, and alternatives. It will be recorded in the medical history the information given, when and to whom. The anesthesiologist will sign the Informed Consent stating the date that the information is given, and the parents must sign it before the intervention.(AU)

Intrageneric cross-reactivity of monospecific rabbit antisera against venoms of mamba (Elapidae: Dendroaspis spp.) snakes.

Snakebite envenomation is a neglected tropical disease posing a high toll of mortality and morbidity in sub-Saharan Africa. Polyspecific antivenoms of broad effectiveness and specially designed for this region require a detailed understanding of the immunological features of the mamba snake (Dendroaspis spp.) venoms for the selection of the most appropriate antigen combination to produce antivenoms of wide neutralizing scope. Monospecific antisera were generated in rabbits against the venoms of the four species of mambas. The toxic effects of the immunization scheme in the animals were evaluated, antibody titers were estimated using immunochemical assays, and neutralization of lethal activity was assessed. By the end of the immunization schedule, rabbits showed normal values of the majority of hematological parameters tested. No muscle tissue damage was noticed, and no alterations in most serum chemical parameters were observed. Immunological analyses revealed a variable extent of cross-reactivity of the monospecific antisera against the heterologous venoms. The venoms of D. jamesoni and D. viridis generated the antisera with broader cross-reactivity by immunochemical parameters. The venoms of D. polylepis and D. viridis generated the antisera with better cross-neutralization of lethality, although the neutralizing ability of all antisera was lower than 0.16 mg venom/mL antiserum against either homologous or heterologous venoms. These experimental results must be scaled to large animal models used in antivenom manufacture at industrial level to assess whether these predictions are reproducible.

Covariation between the shape and mineralized tissues of the rib cross section in Homo sapiens, Pan troglodytes and Sts 14.

OBJECTIVES: Studying rib torsion is crucial for understanding the evolution of the hominid ribcage. Interestingly, there are variables of the rib cross section that could be associated with rib torsion and, consequently, with the morphology of the thorax. The aim of this research is to conduct a comparative study of the shape and mineralized tissues of the rib cross section in different hominids to test for significant differences and, if possible, associate them to different thoracic morphotypes. MATERIALS AND METHODS: The sample consists of the rib cross sections at the midshaft taken from 10 Homo sapiens and 10 Pan troglodytes adult individuals, as well as from A. africanus Sts 14. The shape of these rib cross sections was quantified using geometric morphometrics, while the mineralized tissues were evaluated using the compartmentalization index. Subsequently, covariation between both parameters was tested by a Spearman's ρ test, a permutation test and a linear regression. RESULTS: Generally, P. troglodytes individuals exhibit rib cross sections that are rounder and more mineralized compared to those of H. sapiens. However, the covariation between both parameters was only observed in typical ribs (levels 3-10). Although covariation was not found in the rib cross sections of Sts 14, their parameters are closer to P. troglodytes. DISCUSSION: On the one hand, the differences observed in the rib cross sections between H. sapiens and P. troglodytes might be related to different degrees of rib torsion and, consequently, to different thoracic 3D configurations. These findings can be functionally explained by considering their distinct modes of breathing and locomotion. On the other hand, although the rib cross sections belonging to Sts 14 are more similar to those of P. troglodytes, previous publications determined that their overall morphology is closer to modern humans. This discrepancy could reflect a diversity of post-cranial adaptations in Australopithecus.

Review Article White Piedra: Review of 131 cases.

This study analyzes the clinical characteristics of patients diagnosed with White Piedra through a systematic review of cases in the literature. A sample of 131 subjects was considered, of which 91.6% were female and most were 18 years of age or younger. Most studies were conducted in Brazil, followed by India, and Mexico. The most common etiologic agent found was Trichosporon spp (34.3%). Most affected patients were asymptomatic (94.6%) and predisposing factors included long hair, use of a hair band or hair accessories, and wet hair. The most common clinical feature was the presence of nodules. The evaluation of treatment effectiveness was hindered by the scarcity of follow-up information in the majority of the studies. It is concluded that White Piedra infection is more common in young women and is associated with hair-related factors.

The Inflammatory and Oxidative Status of Newly Diagnosed Class III and Class IV Lupus Nephritis, with Six-Month Follow-Up.

Lupus nephritis (LN) is the most frequent and severe complication of systemic lupus erythematosus (SLE). A prospective cohort with a six-month follow-up was performed. Twelve SLE patients diagnosed with LN Class III, twelve NL Class IV patients, and twelve healthy control subjects (HC) were included. SLE data, renal function, oxidants, antioxidants, and inflammation were determined at baseline and six-month follow-up. During the six-month follow-up, the SLE Disease Activity Index (SLEDAI-2K) decreased in both LN Class III (20.08 ± 6.92 vs. 11.92 ± 5.87, p < 0.001) and LN Class IV (25.33 ± 6.01 vs. 13.83 ± 5.52, p < 0.001) patients. Furthermore, the values of the C4 component also increased during follow-up for LN Class III (25.36 ± 6.34 vs. 30.91 ± 9.22, p = 0.027) and LN Class IV (12.18 ± 3.90 vs. 20.33 ± 8.95, p = 0.008) groups. Regarding inflammation markers, both groups presented decreased C-reactive protein (CRP), but this was only significant for patients with LN class III (7.93 ± 1.77 vs. 4.72 ± 3.23, p = 0.006). Renal function remained stable in both groups, with no changes in eGFR. Patients with LN Class III and Class IV showed higher baseline levels for lipoperoxides (Class III p < 0.01, Class IV p < 0.1) and carbonyl groups in proteins (Class III p < 0.01, Class IV p < 0.1) compared to HC. Moreover, both groups presented lower baseline values of total antioxidant capacity (Class III p < 0.01, Class IV p < 0.1) and catalase (Class III p < 0.01, Class IV p < 0.1) compared to HCs. However, antioxidant and oxidant markers did not show significant differences between baseline values and at six months for either of the two study groups. In conclusion, patients show an imbalance in the oxidative state characterized by the increase in the oxidants LPO and protein carbonyl groups and the decrease in the activity of the antioxidant enzymes TAC and CAT compared to HC. However, the patients did not present an increase in disease activity and renal function improvement. The glomerular filtration rate did not change during the length of the study, and SLEDAI -2K, C3, and C4 improved. The early co-management between Rheumatologists and Nephrologists is essential to prevent the rapid progression of LN. It would be interesting to administer antioxidant supplements to patients with a recent diagnosis of LN and evaluate its effect in a follow-up study.

Factors Associated with Candidiasis in Pemphigus Vulgaris Patients: Results from a Retrospective Study in Two Second-Care Level Hospitals in Mexico.

BACKGROUND: Infections are a major cause of morbidity and mortality in patients with pemphigus vulgaris (PV). One of the most common infections in these patients is candidiasis. This is probably due to the use of systemic immunosuppressants, including oral and intravenous corticosteroids, mainly in megadoses (pulse therapy), although it is unknown if there are other associated factors, in addition to immunosuppressive treatment. We determine the factors associated with candidiasis in PV patients in two second-care level hospitals in Mexico. METHODS: We reviewed 100 cases with PV. Cases were randomly selected from the databases of two second-care level hospitals between January 2010 and December 2019 (10 years). The primary endpoint was the incidence of candidiasis in patients with PV. RESULTS: One hundred patients with PV were enrolled in this retrospective study. Candidiasis was observed in 79 patients (79%). A maximum corticosteroid dose of 55 mg/day during the last year (p = 0.001) and a higher neutrophil/lymphocyte ratio were associated with candidiasis in patients with PV (p = 0.001). CONCLUSION: Risk factors favoring candidiasis in patients with PV are not only related to the use of corticosteroids, but also to demographic factors, the activity of the disease, and the systemic inflammation associated with autoimmunity.

Bioavailability and systemic transport of oleanolic acid in humans, formulated as a functional olive oil.

Evidence of the pharmacological activity of oleanolic acid (OA) suggests its potential therapeutic application. However, its use in functional foods, dietary supplements, or nutraceuticals is hindered by limited human bioavailability studies. The BIO-OLTRAD trial is a double-blind, randomized controlled study with 22 participants that received a single dose of 30 mg OA formulated as a functional olive oil. The study revealed that the maximum serum concentration of OA ranged from 500 to 600 ng mL-1, with an AUC0-∞ value of 2862.50 ± 174.50 ng h mL-1. Furthermore, we discovered a physiological association of OA with serum albumin and triglyceride-rich lipoproteins (TRL). UV absorption spectra showed conformational changes in serum albumin due to the formation of an adduct with OA. Additionally, we demonstrated that TRL incorporate OA, reaching a maximum concentration of 140 ng mL-1 after 2-4 hours. We conjecture that both are efficient carriers to reach target tissues and to yield high bioavailability.

The Role of the Oxidative State and Innate Immunity Mediated by TLR7 and TLR9 in Lupus Nephritis.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) and is considered one of the leading causes of mortality. Multiple immunological pathways are involved in the pathogenesis of SLE, which makes it imperative to deepen our knowledge about this disease's immune-pathological complexity and explore new therapeutic targets. Since an altered redox state contributes to immune system dysregulation, this document briefly addresses the roles of oxidative stress (OS), oxidative DNA damage, antioxidant enzymes, mitochondrial function, and mitophagy in SLE and LN. Although adaptive immunity's participation in the development of autoimmunity is undeniable, increasing data emphasize the importance of innate immunity elements, particularly the Toll-like receptors (TLRs) that recognize nucleic acid ligands, in inflammatory and autoimmune diseases. Here, we discuss the intriguing roles of TLR7 and TLR9 in developing SLE and LN. Also included are the essential characteristics of conventional treatments and some other novel and little-explored alternatives that offer options to improve renal function in LN.

Recalcitrant primary cutaneous Rosai-Dorfman disease. Efficacy of sirolimus and intralesional methylprednisolone.

Sinus histiocytosis or Rosai-Dorfman disease (RDD) is a rare disorder with severe lymphadenopathy and a limited clinical course, the aetiology of which is still controversial. The disease usually affects cervical nodes, with fever, polyclonal gammopathy, and leucocytosis with neutrophilia. Pure cutaneous involvement occurs as the only manifestation in only 3% of cases. Cutaneous RDD is often associated with infections, immunodeficiency, and autoimmune disorders. A 52-year-old patient presented with disseminated, recurrent, and relapsed pure cutaneous RDD that responded well to treatment with sirolimus and local infiltrations of methylprednisolone. The patient had multiple nonpainful nodular and tumour-like lesions, histiocytic infiltrates with emperipolesis were observed on histologic examination, and positive immunohistochemistry for CD68, and S100. There is no standardised treatment, then the patient was treated with various therapies, including systemic steroids, chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone), radiotherapy, and other immunosuppressive treatments. Some lesions were treated surgically, resulting in recurrence. Sirolimus and local infiltration with methylprednisolone were tried as salvage treatments, the patient responded well, reducing the incidence of new lesions during follow-up, and the size of the preexisting lesions.