Adenosine increases PD-L1 expression in mesenchymal stromal cells derived from cervical cancer through its interaction with A2AR/A2BR and the production of TGF-ß1.

Mesenchymal stromal cells (MSCs) together with malignant cells present in the tumor microenvironment (TME), participate in the suppression of the antitumor immune response through the production of immunosuppressive factors, such as transforming growth factor beta 1 (TGF-ß1). In previous studies, we reported that adenosine (Ado), generated by the adenosinergic activity of cervical cancer (CeCa) cells, induces the production of TGF-ß1 by interacting with A2AR/A2BR. In the present study, we provide evidence that Ado induces the production of TGF-ß1 in MSCs derived from CeCa tumors (CeCa-MSCs) by interacting with both receptors and that TGF-ß1 acts in an autocrine manner to induce the expression of programmed death ligand 1 (PD-L1) in CeCa-MSCs, resulting in an increase in their immunosuppressive capacity on activated CD8+ T lymphocytes. The addition of the antagonists ZM241385 and MRS1754, specific for A2AR and A2BR, respectively, or SB-505124, a selective TGF-ß1 receptor inhibitor, in CeCa-MSC cultures significantly inhibited the expression of PD-L1. Compared with CeCa-MSCs, MSCs derived from normal cervical tissue (NCx-MSCs), used as a control and induced with Ado to express PD-L1, showed a lower response to TGF-ß1 to increase PD-L1 expression. Those results strongly suggest the presence of a feedback mechanism among the adenosinergic pathway, the production of TGF-ß1, and the induction of PD-L1 in CeCa-MSCs to suppress the antitumor response of CD8+ T lymphocytes. The findings of this study suggest that this pathway may have clinical importance as a therapeutic target.

Adenosine Increases the Immunosuppressive Capacity of Cervical Cancer Cells by Increasing PD-L1 Expression and TGF-ß Production through Its Interaction with A2AR/A2BR.

The present study provides evidence showing that adenosine (Ado) increases the expression of programmed death ligand 1 (PD-L1) in cervical cancer (CeCa) cells by interacting with A2AR/A2BR and that TGF-ß1 acts in an autocrine manner to induce PD-L1 expression, enhancing the immunosuppressive effects of CeCa cells on activated T lymphocytes (ATLs) and CD8+ cytotoxic T lymphocytes (CTLs) specific for antigenic peptides derived from E6 and E7 proteins of HPV-16. Interestingly, the addition of the antagonists ZM241385 and MRS1754, which are specific for A2AR and A2BR, respectively, or SB-505124, which is a selective TGF-ß1 receptor inhibitor, to CeCa cell cultures significantly inhibited PD-L1 expression. In addition, supernatants from CeCa cells that were treated with Ado (CeCa-Ado Sup) increased the expression of PD-1, TGF-ß1, and IL-10 and decreased the expression of IFN-γ in ATLs. Interestingly, the addition of an anti-TGF-ß neutralizing antibody strongly reversed the effect of CeCa-Ado Sup on PD-1 expression in ATLs. These results strongly suggest the presence of a feedback mechanism that involves the adenosinergic pathway, the production of TGF-ß1, and the upregulation of PD-L1 expression in CeCa cells that suppresses the antitumor response of CTLs. The findings of this study suggest that this pathway may be clinically important and may be a therapeutic target.

Evidence that cervical cancer cells cultured as tumorspheres maintain high CD73 expression and increase their protumor characteristics through TGF-ß production.

Recently, a link between the biological activity of CD73 and tumorigenicity in solid tumors has been proposed. We previously reported that the generation of adenosine (Ado) by the activity of CD73 in cervical cancer (CC) cells induces transforming growth factor-beta 1 (TGF-ß1) production to maintain CD73 expression. In the present study, we analyzed the participation of TGF-ß1 in CD73 expression and the development of protumoral characteristics in CaSki CC cells cultured as tumorspheres (CaSki-T) and in monolayers (CaSki-M). Compared with those in CaSki-M cells, CD73 expression and Ado generation ability were significantly increased in CaSki-T cells. CaSki-T cells exhibited enrichment in the CSC-like phenotype due to increases in the expression levels of stem cell markers (CD49f, CK17, and P63; OCT4 and SOX2), greater sphere formation efficiency (SFE), and an increase in the percentage of side population (SP) cells. Interestingly, compared with CaSki-M cells, CaSki-T cells produced a greater amount of TGF-ß1 and presented a marked protumor phenotype characterized by a significant decrease in the expression of major histocompatibility complex class-I (MHC-I) molecules, an increase in the expression of multidrug resistance protein-I (MRP-I) and vimentin, and an increase in the protein expression levels of Snail-1 and Twist, which was strongly reversed with TGF-ß1 inhibition. These results suggest that the presence of TGF-ß1-CD73-Ado feedback loop can promote protumoral characteristics in the CC tumor microenvironment.

Satisfacción laboral y compromiso organizacional: un análisis de percepción en el sector sanitario / Job satisfaction and organizational commitment: an analysis of perception in the healthcare sector

Es importante el estudio de variables del comportamiento organizacional, ya que ayudan a la empresa a tener una mejor gestión de los recursos humanos, debido a que la satisfacción laboral tiene relaciones positivas y estadísticamente significativas con el desempeño laboral. El objetivo de este estudio fue medir los niveles de percepción laboral de empleados del sector sanitario del área pública y privada, con respecto a las variables satisfacción laboral y compromiso organizacional. El estudio es de tipo transversal y descriptivo, el instrumento de medición es una encuesta que consta de 3 partes y la muestra estuvo conformada por 271 administrativos. Se presentaron análisis univariados principales, luego un análisis de conglomerados para segmentar a los participantes, y finalmente se efectúan modelos de regresión. Se determinó que existen tres segmentos de trabajadores que son claramente definidos, compuestos por aquellos administrativos con una baja percepción en general (21% y 42%, respectivamente), aquellos con una percepción media (54% y 38%, respectivamente) y aquellos con una percepción alta (25% y 20%, respectivamente). Se confirma que el compromiso organizacional afecta significativamente y de forma positiva a la satisfacción laboral(AU)

The study of variables of organizational behavior is important, since they help the company better manage its human resources, as job satisfaction has been positively and significantly correlated with job performance. The objective of this study was to measure the levels of job perception of employees in the public and private healthcare sector, with respect to job satisfaction and organizational commitment. The study was cross-sectional and descriptive, and the measurement instrument was a survey consisting of three sections. The study sample consisted of 271 administrative staff. We present the main univariate analysis results, followed by a cluster analysis to segment the participants, and then regression analysis. We identified three clearly defined segments of workers, consisting of administrative staff with a low overall perception of hob satisfaction and organizational commitment (21% and 42%, respectively), those with a medium perception (54% and 38%, respectively) and those with a high perception (25% and 20%, respectively). The results confirm that organizational commitment significantly and positively affects job satisfaction(AU)

Mycobacterial Growth Inhibition Assay (MGIA) as a Host Directed Diagnostic Tool for the Evaluation of the Immune Response in Subjects Living With Type 2 Diabetes Mellitus.

The lack of efficient and cost-effective diagnostic tools contributes to poor control of tuberculosis in endemic countries. Moreover, host biological processes influence susceptibility, and infection resolution. It is well known that comorbidities such as type 2 diabetes mellitus (DM2) affect the host immune response, making individuals more susceptible to Mycobacterium tuberculosis infection. Currently, there are no laboratory tools that can identify those subjects who have a higher risk of developing the disease. In this study, we used a whole blood mycobacterial growth inhibition assay to assess the immune response capacity to inhibit mycobacterial growth between healthy subjects and those living with DM2 with optimal and poor glycemic control. We also measured cytokine levels in the culture supernatant by cytokine bead arrays. We included 89 patients with DM2: 54 patients with optimal control (mean age 56.2 ± 11.75 years) and 35 patients with poor control (mean age 52.05 ± 9.94 years). We also included 44 healthy subjects as controls (mean age 42.12 ± 11.75 years). We compared the Δlog UFC (a value that represents the difference between mycobacterial growth in the control tube versus the subject's blood) between each group. Our results demonstrate that patients with DM2 had a lower capacity to inhibit M. tuberculosis growth (Δlog UFC DM2 subjects 0.9581 (-0.3897 to 2.495) vs Δlog UFC healthy subjects 0.7190 (-0.2678 to 2.098); p=0.013). Comparing subjects living with DM2 (optimal and poor glycemic control) vs healthy subjects, we found only significant differences between healthy subjects and patients poorly controlled (Δlog UFC optimal control group 0.876 (-0.3897 to 2.495); Δlog UFC poor control group 1.078 (0.068 to 2.33); Δlog UFC healthy subjects 0.7190 (-0.2678 to 2.098); p= 0.022). Therefore, glycemic control assessed by glycosylated hemoglobin values influences the capacity of the host to control the infection. Our results confirm that the whole blood mycobacterial growth inhibition assay has potential utility as an in vitro marker of M. tuberculosis immunological control in vivo in subjects living with DM2. This assay can be used to evaluate the immune response of each individual against M. tuberculosis, allowing clinicians to choose a more specific host-directed therapy.

Inhibitors of Chemoresistance Pathways in Combination with Ara-C to Overcome Multidrug Resistance in AML. A Mini Review.

Acute myeloid leukemia (AML), the most common type of leukemia in older adults, is a heterogeneous disease that originates from the clonal expansion of undifferentiated hematopoietic progenitor cells. These cells present a remarkable variety of genes and proteins with altered expression and function. Despite significant advances in understanding the molecular panorama of AML and the development of therapies that target mutations, survival has not improved significantly, and the therapy standard is still based on highly toxic chemotherapy, which includes cytarabine (Ara-C) and allogeneic hematopoietic cell transplantation. Approximately 60% of AML patients respond favorably to these treatments and go into complete remission; however, most eventually relapse, develop refractory disease or chemoresistance, and do not survive for more than five years. Therefore, drug resistance that initially occurs in leukemic cells (primary resistance) or that develops during or after treatment (acquired resistance) has become the main obstacle to AML treatment. In this work, the main molecules responsible for generating chemoresistance to Ara-C in AML are discussed, as well as some of the newer strategies to overcome it, such as the inclusion of molecules that can induce synergistic cytotoxicity with Ara-C (MNKI-8e, emodin, metformin and niclosamide), subtoxic concentrations of chemotherapy (PD0332991), and potently antineoplastic treatments that do not damage nonmalignant cells (heteronemin or hydroxyurea + azidothymidine).

Nosocomial pathogen biofilms on biomaterials: Different growth medium conditions and components of biofilms produced in vitro.

BACKGROUND/PURPOSE (S): Nosocomial pathogens can develop biofilms on hospital surfaces and medical devices; however, few studies have focused on the evaluation of mono-and dual-species biofilms developed by nosocomial pathogens under different growth conditions. METHODS: This study investigated biofilm development by nosocomial pathogens (Acinetobacter baumannii, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) on biomaterials in different culture media and their components of the extracellular matrix biofilm. RESULTS: The mono-species biofilms showed cell densities from 7.50 to 9.27 Log10 CFU/cm2 on natural rubber latex type I (NLTI) and from 7.58 to 8.79 Log10 CFU/cm2 on stainless steel (SS). Dual-species biofilms consisted of S. aureus + P. aeruginosa (7.87-8.27 Log10 CFU/cm2 in TSBP and TSBME onto SS; p < 0.05), E. coli + P. aeruginosa (8.32-8.86 Log10 CFU/cm2 in TSBME onto SS and TSBP onto NLTI; p < 0.05), and S. aureus + E. coli (7.82 Log10 CFU/cm2 in TSBME onto SS; p < 0.05). Furthermore, biofilm detachment after proteinase K treatment was 5.54-32.81% compared to 7.95-24.15% after DNase I treatment in the mono-dual species biofilm matrix. Epifluorescence microscopy and scanning electron microscopy (SEM) enabled visualizing the bacteria and extracellular polymeric substances of biofilms on SS and NLTI. CONCLUSION: Nosocomial pathogens can develop biofilms on biomaterials. Mono-species biofilms of Gram-negative bacteria showed lower densities than dual-species biofilms in TSBME and TSBP. Additionally, dual-species biofilms showed a higher concentration of proteins and eDNA in the extracellular matrix.

Co-infection of Dengue, Zika and Chikungunya in a group of pregnant women from Tuxtla Gutiérrez, Chiapas: Preliminary data. 2019.

INTRODUCTION: Dengue, Zika and Chikungunya are RNA Arboviruses present in some areas of Mexico, mainly in the endemic state of Chiapas that is characterized by presence of the vector that transmit them and an ecology that favors high transmission. According to the national epidemiological surveillance system, Dengue has intensified since 2018 and outbreaks continue in various states while for Zika and Chikungunya a decrease in cases has been reported in recent years. The main objective of this study was to determine the incidence of Dengue, Zika and Chikungunya infections during pregnancy in the state of Chiapas. PRINCIPAL FINDINGS: The presence of previous and current infections and coinfections diagnosed by molecular (RT-PCR) and immunological (ELISA for IgG determination) techniques indicates a wide circulation of viruses in asymptomatic people, specifically in pregnant women showing that silent infections in dry season contributes to the preservation of viruses. CONCLUSIONS: From 136 studied samples, 27.7% tested positive for DENV, 8% for ZIKV and 24.1% for CHIKV by RTPCR and the values of IgG in sera show that 83.9% were positive for IgG antibodies against DENV, 65% against ZIKV and 59.1% against CHIKV. Results demonstrated presence of ZIKV and CHIKV, not detected by the epidemiological surveillance system, so the importance of establishing proactive epidemiological systems more strict, especially because these infections in pregnant women can cause severe health problems for newborn children.

Echocardiographic Findings in Canine Model of Chagas Disease Immunized with DNA Trypanosoma cruzi Genes.

Chagas disease (ChD) is considered an emerging disease in the USA and Europe. Trypanosoma cruzi genes encoding a trans-sialidase protein and an amastigote-specific glycoprotein were tested as vaccines in canine model. The aim for this study was determining the prophylactic effect of these genes in experimentally infected dogs by echocardiography evaluation to compare with our findings obtained by other techniques published previously. Low fractional-shortening values of non-vaccinated dogs suggested an impairment in general cardiac function. Low left ventricular ejection fraction values found in infected dogs suggested myocardial injury regardless of whether they were vaccinated. Low left ventricular diastolic/systolic diameters suggested that progressive heart damage or heart dilation could be prevented by DNA vaccination. Systolic peak time was higher in non-vaccinated groups, increasing vulnerability to malignant arrhythmias and sudden death. High left ventricular volume suggested a decrease in wall thickness that might lead to increased size of the heart cavity, except in the pBCSP plasmid-vaccinated dogs. There was an echocardiographic evidence of left ventricular dilation and reduction in systolic function in experimental chagasic dogs. Echocardiography allowed a more complete follow-up of the pathological process in the living patient than with other techniques like electrocardiography, anatomopathology, and histopathology, being the method of choice for characterizing the clinical stages of ChD.

Adenosine augments the production of IL-10 in cervical cancer cells through interaction with the A2B adenosine receptor, resulting in protection against the activity of cytotoxic T cells.

Cervical cancer (CeCa) produces large amounts of IL-10, which downregulates the major histocompatibility complex class I molecules (HLA-I) in cancer cells and inhibits the immune response mediated by cytotoxic T lymphocytes (CTLs). In this study, we analyzed the ability of CeCa cells to produce IL-10 through the CD73-adenosine pathway and its effect on the downregulation of HLA-I molecules to evade CTL-mediated immune recognition. CeCa cells cultured in the presence of ≥10 µM AMP or adenosine produced 4.5-6 times as much IL-10 as unstimulated cells. The silencing of CD73 or the blocking of A2BR with the specific antagonist MRS1754 reversed this effect. In addition, IL-10 decreased the expression of HLA-I molecules, resulting in the protection of CeCa cells against the cytotoxic activity of CTLs. The addition of MRS1754 or anti-IL-10 reversed the decrease in HLA-I molecules and favored the cytotoxic activity of CTLs. These results strongly suggest the presence of a feedback loop encompassing the adenosinergic pathway, the production of IL-10, and the downregulation of HLA-I molecules in CeCa cells that favors immune evasion and thus tumor progression. This pathway may have clinical importance as a therapeutic target.

IL-2 Induces Transient Arrest in the G1 Phase to Protect Cervical Cancer Cells from Entering Apoptosis.

Interleukin 2 (IL-2) has been used for the treatment of different types of cancer that express the IL-2 receptor (IL-2R). However, the effect of IL-2 on cervical cancer cells is unknown. IL-2R is present in normal cells of the immune system but not in the healthy cervix. We report that IL-2R is expressed in cervical cancer cells. IL-2 decreases cervical cancer cell proliferation via transient arrest of the G1 phase, which does not result in apoptosis or senescence. IL-2 upregulates the expression of p53 and p21 and downregulates cyclin D. In addition, we report the resistance of cervical cancer cells to treatments that induce apoptosis in HeLa and INBL cells. When arrested cells were treated with cisplatin, the cytokine protected cells from apoptosis induced by cisplatin. The effects of IL-2 on the cell cycle do not induce cellular senescence or activate the proapoptotic protein Bax. The cell arrest induced by IL-2 is conferring protection to cells against apoptosis.

Mesenchymal Stromal Cells Derived from Normal Cervix and Cervical Cancer Tumors Increase CD73 Expression in Cervical Cancer Cells Through TGF-ß1 Production.

Mesenchymal stromal cells (MSCs) in the tumor microenvironment (TME) participate together with tumor cells to suppress antitumor effector cells through the production of immunosuppressive factors, such as transforming growth factor-beta 1 (TGF-ß1). Furthermore, TGF-ß1 can induce 5'-nucleotidase (CD73) expression in various cell types; this functional activity is associated with the production of adenosine (Ado), which is an immunosuppressive nucleoside. In this study, we provide evidence that coculture of MSCs derived from cervical tumors (CeCa-MSC) with CeCa tumor cells increases CD73 expression in tumor cells and the capacity of these cells to generate Ado in a MSC ratio-dependent manner. Interestingly, the increase in CD73 in the CeCa cell membrane corresponded to an increase in the TGF-ß1 expression level in the tumor cells and the TGF-ß1 content in the supernatants of the CeCa/CeCa-MSC cocultures. The addition of anti-hTGF-ß neutralizing antibodies strongly reversed CD73 expression in the tumor cells. This phenomenon was not exclusive to CeCa-MSCs; coculture of MSCs derived from the normal cervix with CeCa cells produced similar results. These results suggest that the interaction of MSCs with CeCa tumor cells in the TME may condition higher TGF-ß1 production to maintain an immunosuppressive status not only through the activity of this cytokine per se but also through its ability to induce CD73 expression in tumor cells and generate an immunosuppressive microenvironment rich in Ado.

Cobertura de vacunación y proporción de esquema incompleto en niños menores de siete años en México / Vaccination coverage and proportion of incomplete vaccination schedule in children under seven years of age in Mexico

Resumen: Objetivo: Evaluar la cobertura de vacunación en menores de siete años. Material y métodos: Estudio basado en la Encuesta Nacional de Salud y Nutrición de Medio Camino 2016. Resultados: La cobertura de esquema completo en los niños menores de un año fue de 51.7% [rango: de 67.6%, para la vacuna pentavalente (PV), a 93.9%, para la vacuna Bacillus Calmette-Guerin (BCG)]; en los de 12-23 meses fue de 53.9% [rango: de 68.5%, para la vacuna triple viral (SRP), a 98.3%, para la BCG], y en los de 24-35 meses, de 63.2% [rango: de 85.3%, para la vacuna contra neumococo, a 98.6%, para la BCG]. En niños de seis años, la cobertura de una dosis de SRP fue de 97.8%, y para dos dosis, de 50.7%. Sólo 2.2% de los niños de seis años no estaban vacunados. Las variables asociadas con esquema incompleto fueron edad de 2-5 meses, madre menor de 20 años o hablante de lengua indígena. Conclusiones: Debe mejorarse el reclutamiento de recién nacidos al programa de vacunación, así como su seguimiento, hasta completar el esquema, aprovechando los contactos con los servicios de salud para vacunarlos.

Abstract: Objective: To assess vaccination coverage in children under seven years of age. Materials and methods: Study based on the Halfway National Health and Nutrition Survey (Ensanut MC 2016). Results: Full vaccination coverage in children <1 year was 51.7%, (range: 67.6% [pentavalent (PV)] to 93.9% [BCG]), in those aged 12-23 months was 53.9% (range: 68.5% [MMR] to 98.3% [BCG]) and in those 24-35 months was 63.2% (range: 85.3% [pneumococcal]) to 98.6% [BCG]). In children aged six years, the coverage of 1 MMR dose was 97.8% and 50.7% for two doses. Only 2.2% of six year olds were not vaccinated. Variables associated with incomplete schedule were age of 2-5 months, mother being under 20 years of age or maternal language indigenous. Conclusions: The vaccination program needs to improve recruitment of newborns and their follow-up until they complete their immunization schedule, taking advantage of the local contacts with health services to vaccinate them.

GLMEEMSAL epitope common in different isoforms of hMena elicits in vitro activation of cytotoxic T cells and stimulates specific antitumor immunity in BALB/c mice.

BACKGROUND: Alternative expression of human ortholog of murine Mena (hMena) hMena/hMena11a and hMena/hMenaΔv6 isoforms regulate the invasiveness and metastatic potential of tumor cells. It is then important to identify epitopes of these proteins that can elicit antitumor immune response to contribute to the elimination of cells with metastatic potential. METHODS: We assayed the capacity of the peptide GLMEEMSAL, common in hMena/hMena11a and hMena/hMenaΔv6 isoforms, to generate an antitumor immune response through an in vitro vaccination system with mature dendritic cells (MDC) loaded with this peptide and in vivo immunization using a tumor model with the mammary adenocarcinoma JC cell line to induce tumors in BALBc mice. RESULTS: MDC loaded with the peptide GLMEEMSAL elicited strong proliferation and activation of CD8+ T lymphocytes. The CTLs generated with this system were capable to lyse specifically BrCa and CeCa cell lines expressing either hMena/hMena11a or hMena/hMenaΔv6. Immunization with GLMEEMSAL provided protective and therapeutic antitumor activity as well as increased survival in BALB/c mice. CONCLUSION: These results are highly relevant for the use of common peptides among the different isoforms of hMena to develop immunotherapy protocols to counteract the growth and metastatic potential of tumors with over-expression of hMena.

Absence of Measles Virus Detection from Stapes of Patients with Otosclerosis.

Objective To determine molecularly the presence of measles virus genetic material in the stapes of patients with otosclerosis. Study Design A cross-sectional study. Setting A tertiary referral hospital. Subjects and Methods Genetic material was extracted from the stapes of patients with otosclerosis (n = 93) during the period from March 2011 to April 2012. The presence of viral measles sequences was evaluated by the real-time reverse transcriptase polymerase chain reaction (RT-PCR). The expression of the CD46 gene was determined. Results Ninety-three patients were included in the study. No sample was positive for any of 3 measles virus genes (H, N, and F). Measles virus RNA was not detected in any sample by real-time RT-PCR. CD46 levels were positive in 3.3% (n = 3) and negative in 96.7% (n = 90). Conclusion This study does not support the theory of measles virus as the cause of otosclerosis. It is necessary to do more research about other causal theories to clarify its etiology and prevention.

Endolymphatic Sac Surgery for Ménière's Disease - Current Opinion and Literature Review

Abstract Introduction The endolymphatic sac is thought to maintain the hydrostatic pressure and endolymph homeostasis for the inner ear, and its dysfunction may contribute to the pathophysiology of Ménière's disease. Throughout the years, different surgical procedures for intractable vertigo secondary to Ménière's disease have been described, and though many authors consider these procedures as effective, there are some who question its long-term efficacy and even those who think that vertigo control is achieved more due to a placebo effect than because of the procedure itself. Objective To review the different surgical procedures performed in the endolymphatic sac for the treatment of Ménière's disease. Data Sources PubMed, MD consult and Ovid-SP databases. Data Synthesis We focus on describing the different surgical procedures performed in the endolymphatic sac, such as endolymphatic sac decompression, endolymphatic sac enhancement, endolymphatic sac shunting and endolymphatic duct blockage, their pitfalls and advantages, their results in vertigo control and the complication rates. The senior author also describes his experience after 30 years of performing endolymphatic sac surgery. Conclusions The endolymphatic sac surgery, with all its variants, is a good option for patients with incapacitating endolymphatic hydrops, providing a high percentage of vertigo control and hearing preservation.

Endolymphatic Sac Surgery for Ménière's Disease - Current Opinion and Literature Review.

Introduction The endolymphatic sac is thought to maintain the hydrostatic pressure and endolymph homeostasis for the inner ear, and its dysfunction may contribute to the pathophysiology of Ménière's disease. Throughout the years, different surgical procedures for intractable vertigo secondary to Ménière's disease have been described, and though many authors consider these procedures as effective, there are some who question its long-term efficacy and even those who think that vertigo control is achieved more due to a placebo effect than because of the procedure itself. Objective To review the different surgical procedures performed in the endolymphatic sac for the treatment of Ménière's disease. Data Sources PubMed, MD consult and Ovid-SP databases. Data Synthesis We focus on describing the different surgical procedures performed in the endolymphatic sac, such as endolymphatic sac decompression, endolymphatic sac enhancement, endolymphatic sac shunting and endolymphatic duct blockage, their pitfalls and advantages, their results in vertigo control and the complication rates. The senior author also describes his experience after 30 years of performing endolymphatic sac surgery. Conclusions The endolymphatic sac surgery, with all its variants, is a good option for patients with incapacitating endolymphatic hydrops, providing a high percentage of vertigo control and hearing preservation.

Sodium Caseinate (CasNa) Induces Mobilization of Hematopoietic Stem Cells in a BALB/c Mouse Model.

BACKGROUND Hematopoietic stem cells transplantation has high clinical potential against a wide variety of hematologic, metabolic, and autoimmune diseases and solid tumors. Clinically, hematopoietic stem cells derived from peripheral blood are currently used more than those obtained from sources such as bone marrow. However, mobilizing agents used in the clinic tend to fail in high rates, making the number of mobilized cells insufficient for transplantation. We investigated whether sodium caseinate induces functional mobilization of hematopoietic stem cells into peripheral blood of Balb/c mice. MATERIAL AND METHODS Using a mouse model, we administrated sodium caseinate or Plerixafor, a commercial mobilizing agent, and analyzed counts of hematopoietic stem cells in peripheral blood, and then cells were transplanted into lethally irradiated mice to restore hematopoiesis. All assays were performed at least twice. RESULTS We found that sodium caseinate increases the number of mononuclear cells in peripheral blood with the immunophenotype of hematopoietic stem cells (0.2 to 0.5% LSK cells), allowing them to form colonies of various cell lineages in semisolid medium (p<0.05). This effect is similar to that of Plerixafor, and cells transplanted into lethally irradiated mice can restore hematopoiesis at higher percentages than mononuclear cells mobilized by Plerixafor (40% vs. 20%, respectively). Further, a secondary transplant rescued a separate group of irradiated mice from death, proving definitive evidence of hematopoietic reconstitution after hematopoietic stem cells transplantation. Data are presented as mean ± standard deviation. To determine significant differences between the data, one-way ANOVA and the Tukey test were used. CONCLUSIONS Collectively these results show the utility of sodium caseinate as a mobilizer of hematopoietic stem cells and its potential clinical application in transplantation settings.

Immunization with an HPV-16 L1-based chimeric virus-like particle containing HPV-16 E6 and E7 epitopes elicits long-lasting prophylactic and therapeutic efficacy in an HPV-16 tumor mice model.

HPV L1-based virus-like particles vaccines (VLPs) efficiently induce temporary prophylactic activity through the induction of neutralizing antibodies; however, VLPs that can provide prophylactic as well as therapeutic properties for longer periods of time are needed. For this purpose, we generated a novel HPV 16 L1-based chimeric virus-like particle (cVLP) produced in plants that contains a string of T-cell epitopes from HPV 16 E6 and E7 fused to its C-terminus. In the present study, we analyzed the persistence of specific IgG antibodies with neutralizing activity induced by immunization with these cVLPs, as well as their therapeutic potential in a tumor model of C57BL/6 mice. We observed that these cVLPs induced persistent IgG antibodies for over 12 months, with reactivity and neutralizing activity for VLPs composed of only the HPV-16 L1 protein. Efficient protection for long periods of time and inhibition of tumor growth induced by TC-1 tumor cells expressing HPV-16 E6/E7 oncoproteins, as well as significant tumor reduction (57 %), were observed in mice immunized with these cVLPs. Finally, we discuss the possibility that chimeric particles of the type described in this work may be the basis for developing HPV prophylactic and therapeutic vaccines with high efficacy.