Measurement of IFN-γ and IL-2 for the assessment of the cellular immunity against SARS-CoV-2.

The study of specific T-cell responses against SARS-CoV-2 is important for understanding long-term immunity and infection management. The aim of this study was to assess the dual IFN-γ and IL-2 detection, using a SARS-CoV-2 specific fluorescence ELISPOT, in patients undergoing acute disease, during convalescence, and after vaccination. We also evaluated humoral response and compared with T-cells with the aim of correlating both types of responses, and increase the number of specific response detection. Blood samples were drawn from acute COVID-19 patients and convalescent individuals classified according to disease severity; and from unvaccinated and vaccinated uninfected individuals. IgGs against Spike and nucleocapsid, IgMs against nucleocapsid, and neutralizing antibodies were also analyzed. Our results show that IFN-γ in combination with IL-2 increases response detection in acute and convalescent individuals (p = 0.023). In addition, IFN-γ detection can be a useful biomarker for monitoring severe acute patients, as our results indicate that those individuals with a poor outcome have lower levels of this cytokine. In some cases, the lack of cellular immunity is compensated by antibodies, confirming the role of both types of immune responses in infection, and confirming that their dual detection can increase the number of specific response detections. In summary, IFN-γ/IL-2 dual detection is promising for characterizing and assessing the immunization status, and helping in the patient management.

Accuracy of sentinel node mapping in patients with biopsy-proven metastatic axillary lymph nodes and upfront surgery: preliminary results of the Multimodal Targeted Axillary Surgery (MUTAS) trial.

Background: Some studies suggested that the patients included in the Z0011 trial may represent patients with ultrasound-negative axillary nodes and axillary invasion diagnosed by sentinel node (SN) biopsy. Nevertheless, the National Comprehensive Cancer Network (NCCN) guidelines recommend SN mapping if 1 or 2 suspicious lymph nodes are identified on axillary ultrasound (AU). The aim of this preliminary phase of the Multimodal Targeted Axillary Surgery (MUTAS) trial was to establish the accuracy of SN mapping in patients with axillary involvement undergoing upfront surgery. Methods: Between September 2019 and March 2022, we recruited patients with biopsy-proven metastatic axillary nodes and upfront surgery from a single center. We performed SN mapping in these patients before the surgical intervention, which included axillary lymph node dissection. The biopsy-proven metastatic node, SNs and the remaining axillary nodes were excised separately. SN status was considered representative of the status of the remaining axillary nodes. We calculated the sensitivity, specificity, negative predictive value and positive predictive value of the SN, overall and in patients with palpable nodes, in those with non-palpable nodes and an AU leading to diagnosis of axillary involvement, in those with 1 or 2 suspicious nodes on AU, and in patients with a single suspicious node on AU. We evaluated clinical, imaging and pathology features as predictors of the status of the remaining axillary nodes, false-negatives, and false-positives. Results: We included 25 patients in this phase. The false-negative rate of SN mapping was 28% overall, 21.42% for patients with palpable nodes, 36.36% for patients with non-palpable nodes and an AU diagnosis of axillary involvement, 28.75% for those with 1 or 2 suspicious nodes on AU, and 15.38% in patients with a single suspicious node on AU. The negative predictive value was highest in patients with a single suspicious node on AU (75%). The only significant predictive factor was that FN showed a higher Ki67 index score. Conclusions: In this study, SN mapping was not reliable in patients with biopsy-proven metastatic axillary nodes and upfront surgery for any of the subgroups studied. Further research should elucidate the best staging pathways in these patients to avoid premature de-escalation.

Autoimmune/inflammatory syndrome induced by mineral oil: a health problem.

Autoimmune/inflammatory syndrome induced by adjuvant (ASIA) includes the following conditions: siliconosis, Gulf War syndrome, macrophagic myofasciitis syndrome, and post-vaccination phenomena. Afterward, other syndromes have been recognized, such as in ASIA by mineral oil (ASIA-MO). These conditions are triggered by adjuvants and they are the result of the interplay of genetic and environmental factors. ASIA-MO is defined as the infiltration of oily type modeling substances for cosmetic purposes. It has been reported in many countries and used surreptitiously. Pathogenesis of ASIA-MO is not clear, but is characterized by chronic granulomatous inflammation, like the pristane model in mice, with increase of proinflammatory cytokines: type I interferons (IFNα and IFNß), systemic lupus erythematosus (SLE), and erosive arthritis. In humans, an increase of interleukin 1 (IL-1) has been found. Clinical spectrum of ASIA-MO is heterogeneous, varying from mild to severe and being local and systemic. The systemic manifestations can be non-specific and specific, meeting criteria for any autoimmune disease (AID), i.e., SLE, rheumatoid arthritis, and systemic sclerosis, among others. The areas of the body where the mineral oil is mostly applied include the following: buttocks (38-72%), breasts (12-16%), lower extremities (18-22%), and face (6-10%). The penis augmentation is also common. Treatment is focused on local and systemic manifestations and requires medical and surgical management representing a challenge for the physician.

Identification of the molecular sex-differentiation period in the Siberian sturgeon.

Sexual development prior to gonadal sex differentiation is regulated by various molecular mechanisms. In fish, a "molecular sex-differentiation period" has been identified in species for which sex can be ascertained prior to gonadal sex differentiation. The present study was designed to identify such a period in a species for which no genetic sex markers or monosex populations are available. Siberian sturgeons undergo a slow sex-differentiation process over several months, so gonad morphology and gene expression was tracked in fish from ages 3-27 months to identify the sex-differentiation period. The genes amh, sox9, and dmrt1 were selected as male gonad markers; cyp19a1a and foxl2a as female gonad markers; and cyp17a1 and ar as markers of steroid synthesis and steroid receptivity. Sex differentiation occurred at 8 months, and was preceded by a molecular sex-differentiation period at 3-4 months, at which time all of the genes except ar showed clear expression peaks. amh and sox9 expression seemed to be involved in male sexual development whereas dmrt1, a gene involved in testis development in metazoans, unexpectedly showed a pattern similar to those of the genes known to be involved in female gonadal sex differentiation (cyp19a1 and foxl2a). In conclusion, the timing of and gene candidates involved with molecular sex differentiation in the Siberian sturgeon were identified.

Expression of aquaporins early in human pregnancy.

BACKGROUND: Aquaporins (AQPs) constitute a family of channel proteins implicated in transmembrane water transport. Thirteen different AQPs (AQP0-12) have been described but their precise biologic function still remains unclear. AQPs 1, 3, 4, 8, and 9 expression has been described in human chorion, amnion and placenta; however, AQP4 is the only that has been identified in the first trimester of human pregnancy. OBJECTIVE: To assess multiplicity of AQPs expression from 10th to 14th week gestation. POPULATION AND METHODS: Chorionic villi samples (CVS) collected in pregnant women for prenatal diagnosis were analysed by real time-PCR to assess cDNA expression of AQPs 1, 2, 3, 4, 5, 6, 7, 8, 9, and 11, and compared with AQPs expression in placentas from normal term pregnancies. RESULTS: 26 CVS corresponding to 26 pregnant women (age: 32.7±4.5 years; gestational age: 12.4±0.9 weeks) and 10 placental samples corresponding to normal term pregnancies were analysed. In CVS karyotype was normal in 16 cases, trisomy in 6 cases, mosaicism in 1 and unknown in 1. We found high mRNA expression for AQPs 1, 3, 9 and 11, low for AQPs 4, 5, and 8, and non-detectable for AQPs 2, 6, and 7 in chorionic villi. CONCLUSIONS: This is the first study systematically assessing the expression of a multiplicity of AQPs in chorionic villi samples between 10th and 14th weeks of gestation. High expression of AQP11 has been identified for the first time in early stages of human pregnancy. Chromosomal abnormalities did not alter AQPs' expression.

Análisis de las cifras de ácido lactico en el líquido cefalorraquideo en pacientes con síndrome neurológico infeccioso / Analysis of lactic acid figures in the cerebrospinal fluid of patients with infectious neurologic syndrome

Se realizó la determinación de lactato en todos los líquidos cefalorraquídeos (LCR) que se obtuvieron por punción lumbar a los pacientes que acudieron al Cuerpo Guardia con síntomas sospechosos de infección del sistema nervioso central (SNC) en el período comprendido entre el 15 de febrero al 30 de abril de 1985; se analizaron un total de 177 LCR. Los resultados obtenidos fueron los siguientes: en pacientes sin infección del SNC los valores del lactato fluctuaron de 1,0 a 2,44 mmol/L y en los pacientes con meningoencefalitis viral de 1,1 a 2,77 mmol/L. Estas cifras contrastan con las encontradas en pacientes con infección del SNC bacteriana, donde encontramos valores de 2,2 a 5,11 mmol/L, por lo que se concluye que no se constatan prácticamente diferencias entre las cifras de ácido láctico en el LCR de pacientes sin infección del SNC y en los que tienen infección viral del SNC; se observa que las cifras de lactato en el LCR son más elevadas en las meningoencefalitis bacterianas que en las virales; por tanto, se considera que dicha investigación resulta de utilidad para establecer el diagnóstico diferencial entre las infecciones bacteriana y virales del SNC. Se sugiere la posibilidad de que esta investigación pueda ser útil para establecer criterios de pronóstico (AU)

Análisis de las cofras de ácido lactico en el líquido cefalorraquideo en pacientes con síndrome neurológico infeccioso / Analysis of lactic acid figures in the cerebrospinal fluid of patients with infectious neurologic syndrome

Se realizó la determinación de lactato en todos los líquidos cefalorraquídeos (LCR) que se obtuvieron por punción lumbar a los pacientes que acudieron al Cuerpo Guardia con síntomas sospechosos de infección del sistema nervioso central (SNC) en el período comprendido entre el 15 de febrero al 30 de abril de 1985; se analizaron un total de 177 LCR. Los resultados obtenidos fueron los siguientes: en pacientes sin infección del SNC los valores del lactato fluctuaron de 1,0 a 2,44 mmol/L y en los pacientes con meningoencefalitis viral de 1,1 a 2,77 mmol/L. Estas cifras contrastan con las encontradas en pacientes con infección del SNC bacteriana, donde encontramos valores de 2,2 a 5,11 mmol/L, por lo que se concluye que no se constatan prácticamente diferencias entre las cifras de ácido láctico en el LCR de pacientes sin infección del SNC y en los que tienen infección viral del SNC; se observa que las cifras de lactato en el LCR son más elevadas en las meningoencefalitis bacterianas que en las virales; por tanto, se considera que dicha investigación resulta de utilidad para establecer el diagnóstico diferencial entre las infecciones bacteriana y virales del SNC. Se sugiere la posibilidad de que esta investigación pueda ser útil para establecer criterios de pronóstico