Levels of biomarkers associated with subconcussive head hits in mixed martial arts fighters.

Background: Concussion and the damage resulting from this event related to brain function have been widely studied; however, little is known about subconcussive impacts, especially in Mixed Martial Arts (MMA) fighters, which is a combat and full contact sport in which most blows are aimed at the head. Objective: This study aims to evaluate the biomarker levels associated with subconcussive hits to the head in MMA fighters. Methods: This is an exploratory study in which 30 male subjects (10 MMA fighters, 10 healthy individuals who practice muscle training, and 10 healthy sedentary individuals) aged between 18 and 32 years (25.4 ± 3.8) were evaluated. These individuals underwent blood collection to assess their Ubiquitin C-terminal hydrolase (UCH-L1), Glial Fibrillary Acidic Protein (GFAP) and Brain Derived Neurotrophic Factor (BDNF) levels before, immediately after and 72 hours after the sparring session (for the fighters) and were compared between groups. Results: Significant differences were found at baseline between active and healthy fighters in BDNF levels (p = 0.03). A significant reduction of BDNF levels were also observed between the post-immediate and 72h after the sparring session (p = 0.03). No differences were observed in the number or severity of symptoms reported by the fighters. Conclusion: Despite the exploratory approach, the findings of this study may help to understand the influence of repeated subconcussive hits to the head in MMA fighters, as well as to propose preventive interventions which can minimize the effects of the impact of hits, preserving fighters' neuronal integrity and function.

Enhanced Tumor Targeting of Radiolabeled Mouse/Human Chimeric Anti-Tn Antibody in Losartan-Treated Mice Bearing Tn-Expressing Lung Tumors.

Aim: ChiTn, a mouse/human chimeric anti-Tn monoclonal antibody, was radiolabeled with iodine-131 (131I) and technetium-99m (99mTc) to assess its biodistribution and internalization in Tn-expressing (Tn+) and wild-type (Tn-) LL/2 lung cancer cells. Results: Selective accumulation and gradual internalization of ChiTn were observed in Tn+ cells. Biodistribution in mice with both Tn+ or Tn- lung tumors indicated that the uptake of radiolabeled ChiTn within tumors increased over time. Dual-labeling experiments with 99mTc and 131I showed different biodistribution patterns, with 99mTc exhibiting higher values in the liver, spleen, and kidneys, while 131I showed higher uptake in the thyroid and stomach. However, tumor uptake did not significantly differ between Tn+ and Tn- tumors. To improve tumor targeting, Losartan, an antihypertensive drug known to enhance tumor perfusion and drug delivery, was investigated. Biodistribution studies in Losartan-treated mice revealed significantly higher radiolabeled ChiTn uptake in Tn+ tumors. No significant changes were observed in the uptake of the control molecule IgG-HYNIC™99mTc. Conclusions: These findings demonstrate the enhanced tumor targeting of radiolabeled ChiTn in Losartan-treated mice with Tn-expressing lung tumors. They highlight the potential of ChiTn as a theranostic agent for cancer treatment and emphasize the importance of Losartan as an adjunctive treatment to improve tumor perfusion and drug delivery.

Human papillomavirus prevalence and frequency of sexually transmitted diseases in encarcered women by self-sampling approach.

OBJECTIVE: This study aimed to assess the sociodemographic and clinical profile of women deprived of their liberty and to identify the prevalence of sexually transmitted diseases and human papillomavirus through self-sampling samples. METHODS: This is an epidemiological, cross-sectional, observational, and descriptive study of the prevalence and correlation of the diagnosis of human papillomavirus infection in 268 encarcered women in Amazonas submitted to self-sampling from June 2019 to September 2020 using the genotyping analysis. Patients with positive and inconclusive results were evaluated by commercialized PCR to detect pathogens causing sexually transmitted diseases. The sample size used was based on a convenience sample. RESULTS: In 268 women, human papillomavirus DNA was detected in 87 (32.5%) of them. Sexually transmitted diseases were detected in 30 (34.48%) of the 87 women with a positive or inconclusive result for human papillomavirus. Women with more than three pregnancies had a higher risk of human papillomavirus detection (p=0.004). CONCLUSION: The prevalence of human papillomavirus and other sexually transmitted diseases in encarcered women in Amazonas is 32.5 and 34.48%, respectively. Most women were single (60.4%) and reported having had more than 15 partners (90.8%).

Face-to-face interviews versus Internet surveys: Comparison of two data collection methods in the Rome foundation global epidemiology study: Implications for population-based research.

BACKGROUND AND AIMS: The Rome Foundation Global Epidemiology Study (RFGES) assessed the prevalence, burden, and associated factors of Disorders of Gut-Brain Interaction (DGBI) in 33 countries around the world. Achieving worldwide sampling necessitated use of two different surveying methods: In-person household interviews (9 countries) and Internet surveys (26 countries). Two countries, China and Turkey, were surveyed with both methods. This paper examines the differences in the survey results with the two methods, as well as likely reasons for those differences. METHODS: The two RFGES survey methods are described in detail, and differences in DGBI findings summarized for household versus Internet surveys globally, and in more detail for China and Turkey. Logistic regression analysis was used to elucidate factors contributing to these differences. RESULTS: Overall, DGBI were only half as prevalent when assessed with household vs Internet surveys. Similar patterns of methodology-related DGBI differences were seen within both China and Turkey, but prevalence differences between the survey methods were dramatically larger in Turkey. No clear reasons for outcome differences by survey method were identified, although greater relative reduction in bowel and anorectal versus upper gastrointestinal disorders when household versus Internet surveying was used suggests an inhibiting influence of social sensitivity. CONCLUSIONS: The findings strongly indicate that besides affecting data quality, manpower needs and data collection time and costs, the choice of survey method is a substantial determinant of symptom reporting and DGBI prevalence outcomes. This has important implications for future DGBI research and epidemiological research more broadly.

Human papillomavirus prevalence and frequency of sexually transmitted diseases in encarcered women by self-sampling approach

SUMMARY OBJECTIVE: This study aimed to assess the sociodemographic and clinical profile of women deprived of their liberty and to identify the prevalence of sexually transmitted diseases and human papillomavirus through self-sampling samples. METHODS: This is an epidemiological, cross-sectional, observational, and descriptive study of the prevalence and correlation of the diagnosis of human papillomavirus infection in 268 encarcered women in Amazonas submitted to self-sampling from June 2019 to September 2020 using the genotyping analysis. Patients with positive and inconclusive results were evaluated by commercialized PCR to detect pathogens causing sexually transmitted diseases. The sample size used was based on a convenience sample. RESULTS: In 268 women, human papillomavirus DNA was detected in 87 (32.5%) of them. Sexually transmitted diseases were detected in 30 (34.48%) of the 87 women with a positive or inconclusive result for human papillomavirus. Women with more than three pregnancies had a higher risk of human papillomavirus detection (p=0.004). CONCLUSION: The prevalence of human papillomavirus and other sexually transmitted diseases in encarcered women in Amazonas is 32.5 and 34.48%, respectively. Most women were single (60.4%) and reported having had more than 15 partners (90.8%).

Pregnancy and Inflammatory Bowel Disease: A Special Combination.

Inflammatory bowel disease (IBD) comprises a spectrum of chronic immune-mediated diseases that affect the gastrointestinal tract. Onset typically occurs in early adulthood. The incidence of this disease has increased worldwide. Its prevalence has increased in Colombia and occurs predominantly in women. Considering that this disease is not curable, the main objective of management is to achieve remission. Many women are affected by IBD during different stages of their lives, including their reproductive life, pregnancy, and menopause. Because of this, the way the disease is managed in women of reproductive age can affect the course of IBD. Treatment and health maintenance strategies are very relevant; for patients with a desire to conceive, remission of the disease is very important at the time of conception and throughout the pregnancy to ensure adequate outcomes for both mother and fetus. Also, remission is necessary at least 3 months prior to conception. It is well known that active disease during conception and pregnancy is associated with adverse outcomes. In addition, active perianal disease is an indication of cesarean delivery, resulting in an increased risk of intestinal surgery and post-operative complications.

Trypanosoma cruzi-Derived Molecules Induce Anti-Tumour Protection by Favouring Both Innate and Adaptive Immune Responses.

Lung cancer remains the leading cause of cancer mortality worldwide. Thus, the development of strategies against this type of cancer is of high value. Parasite infections can correlate with lower cancer incidence in humans and their use as vaccines has been recently explored in preclinical models. In this study, we investigated whether immunisations with a Trypanosoma cruzi lysate from epimastigotes protect from lung tumour growth in mice. We also explore the role of parasite glycans in the induction of the protective immune response. A pre-clinical murine cancer model using the lung tumour cell line LL/2 was used to evaluate the anti-tumour potential, both in preventive and therapeutic settings, of a T. cruzi epimastigote-derived protein lysate. Immunisation with the parasite lysate prevents tumour growth and induces both humoral and cellular anti-tumour immune responses to LL-2 cancer cells. The induced immunity and tumour protection were associated with the activation of natural killer (NK) cells, the production of interferon-γ (IFN-γ) and tumour cell cytotoxicity. We also show that mannose residues in the T. cruzi lysate induce Toll-like receptor (TLR) signalling. The evaluated T. cruzi lysate possesses anti-tumour properties likely by activating innate and adaptive immunity in a process where carbohydrates seem to be essential.

Lung Tumor Cells with Different Tn Antigen Expression Present Distinctive Immunomodulatory Properties.

Lung cancer is the first leading cause of cancer-related deaths in the world. Aberrant glycosylation in lung tumors leads to the expression of tumor-associated carbohydrate structures, such as the Tn antigen, consisting of N-acetyl-galactosamine (GalNAc) linked to a serine or threonine residue in proteins (α-GalNAc-O-Ser/Thr). The Tn antigen can be recognized by the Macrophage Galactose/GalNAc lectin (MGL), which mediates various immune regulatory and tolerogenic functions, mainly by reprogramming the maturation of function of dendritic cells (DCs). In this work, we generated two different Tn-expressing variants from the Lewis-type lung murine cancer cell line LL/2, which showed different alterations in the O-glycosylation pathways that influenced the interaction with mouse MGL2 and the immunomodulatory properties of DCs. Thus, the identification of the biological programs triggered by Tn+ cancer cells might contribute to an improved understanding of the molecular mechanisms elicited by MGL-dependent immune regulatory circuits.

Macrophage Gal/GalNAc lectin 2 (MGL2)+ peritoneal antigen presenting cells during Fasciola hepatica infection are essential for regulatory T cell induction.

Fasciola hepatica, one of the agents that causes fasciolosis, modulates the host immune system to allow parasite survival in the host. F. hepatica expresses carbohydrate-containing glycoconjugates that are decoded by C-type lectin receptors, such as Dectin-1, mannose receptor, DC-SIGN and MGL, that are mainly present on myeloid antigen presenting cells (APCs) and can mediate immunoregulatory properties on T cells. In particular, Macrophage Gal/GalNAc lectin 2 (MGL2) expands modified Th2 immune responses, while suppressing Th1 polarization, upon recognition of GalNAc-glycosylated parasite components. In this study, by using MGL2-DTR transgenic mice that encode human diphtheria toxin receptor in MGL2+ cells, we demonstrate the role of peritoneal APCs during F. hepatica infection in favoring parasite survival. This process might be mediated by the induction of splenic Tregs in vivo, since the depletion of MGL2+ cells conferred mice with partial resistance to the infection and abrogated the increase of CD4+/CD25+ FoxP3+ Tregs induced by the parasite. Therefore, MGL2+ cells are critical determinants of F. hepatica infection and could constitute immune checkpoints to control parasite infection.

Chiropterans as a potential hosts of Leishmania spp. in endemic areas for leishmaniasis in northeastern Brazil.

The species of the genus Leishmania are protozoa that are widely distributed from Asia to the Americas, affecting humans and wild and domestic animals. Little is known about infection by Leishmania in bats in the state of Maranhão, Brazil. The objective of this study was to investigate the presence of Leishmania in bats in Maranhão. Blood samples were collected from bat species for parasitological diagnosis. Samples of spleen and liver were collected for molecular analysis. All the blood cultures were negative. In two blood smears, organisms similar to amastigotes of Leishmania sp. were detected. Of the 116 samples, two spleen samples were positive and showed similarity to Leishmania infantum. Therefore, further studies are needed to elucidate whether bats take part in the epidemiological chain of leishmaniasis.

Liver function markers and haematological dynamics during acute and chronic phases of experimental Fasciola hepatica infection in cattle treated with triclabendazole.

Fasciola hepatica, a worldwide-distributed liver fluke, is one of the causative agents of fasciolosis, a zoonotic disease that affects livestock and humans. In livestock, fasciolosis causes huge economic losses worldwide, reducing animal fertility, milk production, weight gain and condemnation of livers. In spite of the availability of drugs, such as triclabendazole (TCZ), for the treatment of fasciolosis, they do not necessarily prevent liver damage or parasite reinfection and can eventually increase parasite resistance. The aim of this research was to relate the hepatic function, haematological parameters, leukocyte counts in circulation and parasite egg shedding during F. hepatica acute and chronic phases of infection in cattle as well as to determine how these parameters change with TCZ-treatment of chronically infected cattle. Our results show that increased levels of serum aspartate aminotransferase (AST) and gamma glutamyltransferase (GGT) were detected in early stages of the experimental infection. Moreover, high circulating eosinophil count and plateletcrit levels were correlated with fluke number in livers from infected cattle. On the other hand, although TCZ-treatment in the chronic phase of infection reduced parasite burden and damage in the liver, it was not able to completely avoid them. In conclusion, our work sheds light into the physiopathological mechanisms induced during fluke infection in cattle, revealing the complexity of the host response to the infection, together with the effects of TCZ-treatment in chronically infected animals.

Advances in the Immunomodulatory Properties of Glycoantigens in Cancer.

Aberrant glycosylation in tumour progression is currently a topic of main interest. Tumour-associated carbohydrate antigens (TACAs) are expressed in a wide variety of epithelial cancers, being both a diagnostic tool and a potential treatment target, as they have impact on patient outcome and disease progression. Glycans affect both tumour-cell biology properties as well as the antitumor immune response. It has been ascertained that TACAs affect cell migration, invasion and metastatic properties both when expressed by cancer cells or by their extracellular vesicles. On the other hand, tumour-associated glycans recognized by C-type lectin receptors in immune cells possess immunomodulatory properties which enable tumour growth and immune response evasion. Yet, much remains unknown, concerning mechanisms involved in deregulation of glycan synthesis and how this affects cell biology on a major level. This review summarises the main findings to date concerning how aberrant glycans influence tumour growth and immunity, their application in cancer treatment and spotlights of unanswered challenges remaining to be solved.

Experience in the Use of Video Capsule Endoscopy in Patients with Unexplained Iron Deficiency Anemia / Experiencia con el uso de la videocápsula endoscópica en pacientes con anemia ferropénica inexplicada

Abstract Introduction: The prevalence of iron deficiency anemia in developed countries has been estimated between 2-5 %, associated with high morbidity and mortality. Etiological identification is sometimes difficult and requires diagnostic methods, such as video capsule endoscopy (VCE). Aim: This study intends to characterize the findings of this technique in patients with unexplained iron deficiency anemia. Materials and methods: Descriptive observational retrospective study. We describe the VCE findings (PillCamSB2-SB3) in all patients seen between 2011 and 2019. The findings were interpreted according to the Saurin classification: normal (P0), uncertain potential (P1), and high bleeding potential (P2). Results: Of the 490 VCEs performed during the study period, 155 indicated iron deficiency anemia; 106 were women (68.4 %), and the mean age was 57.1 ± 16.6 years. The main comorbidities were cardiovascular in 23 (18.3 %) and arterial hypertension in 16 (12.6 %). Antiplatelets were present in 18 (15.4 %) and anticoagulants in six (5.1 %). Small bowel lesions were vascular in 44 studies (28.4 %), inflammatory in 33 (21.2 %), and neoplastic in seven (4.5 %). Angiectasias were the most frequent lesions in 33 cases (21.3 %). P2 lesions were present in 53 VCEs (34.2 %). Conclusions: VCE is helpful in the study of iron deficiency anemia and helps detect positive findings in the midgut in three out of four patients for which it is indicated. The most frequent significant P2 lesions were vascular. These findings allow providing adequate treatment.

Resumen Introducción: la prevalencia de la anemia ferropénica en países desarrollados se ha estimado entre 2 %-5 %, asociada con una alta morbimortalidad. La identificación etiológica a veces es difícil, y requiere de métodos diagnósticos, como la videocápsula endoscópica (VCE). Objetivo: el objeto del presente estudio fue caracterizar los hallazgos de esta técnica en pacientes con anemia ferropénica inexplicada. Materiales y métodos: estudio descriptivo, observacional y retrospectivo. Se describen los hallazgos de VCE (PillCamSB2-SB3) en todos los pacientes atendidos entre 2011 y 2019. Los hallazgos se interpretaron según la clasificación de Saurin: normal (P0), potencial incierto (P1) y alto potencial de sangrado (P2). Resultados: del total de 490 VCE realizadas durante el período del estudio, 155 se efectuaron con indicación de anemia ferropénica; 106 fueron mujeres (68,4 %) y la edad media fue de 57,1 ± 16,6 años. Las comorbilidades principales fueron cardiovasculares en 23 (18,3 %) e hipertensión arterial en 16 (12,6 %). La ingesta de antiplaquetarios se presentó en 18 (15,4 %) y anticoagulantes en 6 (5,1 %). Las lesiones en el intestino delgado fueron vasculares en 44 estudios (28,4 %), inflamatorias en 33 (21,2 %) y neoplásicas en 7 (4,5 %). Las angiectasias fueron las lesiones más frecuentes en 33 casos (21,3 %). En 53 VCE se presentaron lesiones P2 (34,2 %). Conclusiones: la VCE es útil en el estudio de la anemia ferropénica, y ayuda a detectar hallazgos positivos en el intestino medio en 3 de cada 4 pacientes en los cuales se indica su uso. Las lesiones P2 significativas más frecuentes fueron las vasculares. Estos hallazgos permiten enfocar un tratamiento adecuado.

The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer.

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths. Among breast cancers (BC) subtypes, triple-negative (TN) BC is characterized by metastatic progression and poor patient prognosis. Although, TNBC is initially sensitive to chemotherapy, many TNBC patients rapidly develop resistance, at which point metastatic disease is highly lethal. Cancer cells present phenotypic changes or molecular signatures that distinguish them from healthy cells. The Tn antigen (GalNAc-O-Thr/Ser), which constitutes a powerful tool as tumor marker, was recently reported to contribute to tumor growth. However, its role in BC-derived metastasis has not yet been addressed. In this work, we generated a pre-clinical orthotopic Tn+ model of metastatic TNBC, which mimics the patient surgical treatment and is useful to study the role of Tn in metastasis and immunoregulation. We obtained two different cell clones, which differed in their Tn antigen expression: a high Tn-expressing and a non-expressing clone. Interestingly, the Tn-positive cell line generated significantly larger tumors and higher degree of lung metastases associated with a lower survival rate than the Tn-negative and parental cell line. Furthermore, we also found that both tumors and draining-lymph nodes from Tn+-tumor-bearing mice presented a higher frequency of CD4+ FoxP3+ T cells, while their splenocytes expressed higher levels of IL-10. In conclusion, this work suggests that the Tn antigen participates in breast tumor growth and spreading, favoring metastases to the lungs that are associated with an immunoregulatory state, suggesting that Tn-based immunotherapy could be a strategy of choice to treat these tumors.

Heme-Oxygenase-1 Attenuates Oxidative Functions of Antigen Presenting Cells and Promotes Regulatory T Cell Differentiation during Fasciola hepatica Infection.

Fasciola hepatica is a fluke that infects livestock and humans causing fasciolosis, a zoonotic disease of increasing importance due to its worldwide distribution and high economic losses. The parasite regulates the host immune system by inducing a strong Th2 and regulatory T (Treg) cell immune response through mechanisms that might involve the expression or activity of heme-oxygenase-1 (HO-1), the rate-limiting enzyme in the catabolism of free heme that also has immunoregulatory and antioxidant properties. In this paper, we show that F. hepatica-infected mice upregulate HO-1 on peritoneal antigen-presenting cells (APC), which produce decreased levels of both reactive oxygen and nitrogen species (ROS/RNS). The presence of these cells was associated with increased levels of regulatory T cells (Tregs). Blocking the IL-10 receptor (IL-10R) during parasite infection demonstrated that the presence of splenic Tregs and peritoneal APC expressing HO-1 were both dependent on IL-10 activity. Furthermore, IL-10R neutralization as well as pharmacological treatment with the HO-1 inhibitor SnPP protected mice from parasite infection and allowed peritoneal APC to produce significantly higher ROS/RNS levels than those detected in cells from infected control mice. Finally, parasite infection carried out in gp91phox knockout mice with inactive NADPH oxidase was associated with decreased levels of peritoneal HO-1+ cells and splenic Tregs, and partially protected mice from the hepatic damage induced by the parasite, revealing the complexity of the molecular mechanisms involving ROS production that participate in the complex pathology induced by this helminth. Altogether, these results contribute to the elucidation of the immunoregulatory and antioxidant role of HO-1 induced by F. hepatica in the host, providing alternative checkpoints that might control fasciolosis.

Stents metálicos autoexpandibles para el manejo endoscópico de las fístulas esofagogástricas / Self-expanding metal stents for endoscopic management of esophageal and gastric fistulas

Resumen Objetivos: mostrar la eficacia y seguridad de los stents metálicos autoexpandibles para el manejo endoscópico de las fístulas esofágicas. Materiales y métodos: se evalúo una serie de casos de manera retrospectiva entre el 2007 y el 2017, en los que se manejaron a 11 pacientes con un stent metálico autoexpandible para el manejo de fístula esofágica, en quienes se realizó el diagnóstico por clínica, endoscopia digestiva alta o estudios radiológicos en la unidad de gastroenterología del Hospital Universitario San Ignacio (HUSI) de Bogotá D. C., Colombia. Resultados: el principal síntoma inicial fue la disnea en 27,3 % de los casos, seguido por tos en un 18,2 %. El hallazgo más frecuentemente encontrado durante el seguimiento fue el derrame pleural en el 36,4 %, se realizó el diagnóstico de fístula en el 45,5 % con esofagograma y el tipo de lesión más reportada fue la fuga en la anastomosis esofagoentérica, con un 45,5 %, seguida de la esofagopleural, con un 36,4 %; y estos pacientes fueron manejados con un stent metálico autoexpandible. En el 100 % hubo éxito técnico y la resolución del defecto se evidenció en el 72,7 % de los casos. La única complicación reportada fue el desplazamiento del stent en el 27,3 %, y en un paciente se requirió el cambio del stent en 3 oportunidades. El promedio de estancia hospitalaria fue de 41,5 días. Conclusiones: el manejo endoscópico de las fístulas esofagogástricas con stents metálicos autoexpandibles es efectivo y seguro, con una baja tasa de complicaciones.

Abstract Objective: To demonstrate the efficacy and safety of self-expanding metal stents for endoscopic management of esophageal fistulas. Materials and methods: Retrospective case series between 2007 and 2017. A total of 11 patients were treated with self-expanding metal stents for esophageal fistula management, after being diagnosed based on symptoms, upper endoscopy, and/or radiological studies in the gastroenterology unit of the Hospital Universitario San Ignacio (HUSI) in Bogotá D.C, Colombia. Results: The most common initial symptom was dyspnea in 27.3% of cases, followed by cough in 18.2%. The most frequent finding during follow-up was pleural effusion in 36.4% of the cases, of which 45.5% received a diagnosis of fistula through esophagogram. The most reported lesion was esophagoenteric anastomotic leak with 45.5%, followed by esophagopleural injury with 36.4%; these patients were those who received self-expanding metal stent management. Technical success was achieved in 100% of the cases, and the defect was resolved in in 72.7% of them. The only complication reported was stent migration in 27.3%, requiring 3 changes in 1 patient. The average hospital stay was 41.5 days. Conclusions: Endoscopic management of esophagogastric fistulas with self-expanding metal stents is effective and safe, with a low complication rate.

The Tn antigen promotes lung tumor growth by fostering immunosuppression and angiogenesis via interaction with Macrophage Galactose-type lectin 2 (MGL2).

Tn is a tumor-associated carbohydrate antigen that constitutes both a diagnostic tool and an immunotherapeutic target. It originates from interruption of the mucin O-glycosylation pathway through defects involving, at least in part, alterations in core-1 synthase activity, which is highly dependent on Cosmc, a folding chaperone. Tn antigen is recognized by the Macrophage Galactose-type Lectin (MGL), a C-type lectin receptor present on dendritic cells and macrophages. Specific interactions between Tn and MGL shape anti-tumoral immune responses by regulating several innate and adaptive immune cell programs. In this work, we generated and characterized a variant of the lung cancer murine cell line LL/2 that expresses Tn by mutation of the Cosmc chaperone gene (Tn+ LL/2). We confirmed Tn expression by lectin glycophenotyping and specific anti-Tn antibodies, verified abrogation of T-synthase activity in these cells, and confirmed its recognition by the murine MGL2 receptor. Interestingly, Tn+ LL/2 cells were more aggressive in vivo, resulting in larger and highly vascularized tumors than those generated from wild type Tn- LL/2 cells. In addition, Tn+ tumors exhibited an increase in CD11c+ F4/80+ cells with high expression of MGL2, together with an augmented expression of IL-10 in infiltrating CD4+ and CD8+ T cells. Importantly, this immunosuppressive microenvironment was dependent on the presence of MGL2+ cells, since depletion of these cells abrogated tumor growth, vascularization and recruitment of IL-10+ T cells. Altogether, our results suggest that expression of Tn in tumor cells and its interaction with MGL2-expressing CD11c+F4/80+ cells promote immunosuppression and angiogenesis, thus favoring tumor progression.

Caracterización de los trastornos manométricos esofágicos en pacientes con enfermedad por reflujo gastroesofágico refractario con síntomas esofágicos / Characterization of esophageal motility disorders in refractory gastroesophageal reflux disease patients with esophageal symptoms

Resumen Introducción: La enfermedad por reflujo gastroesofágico (ERGE) refractaria puede conducir a complicaciones potenciales como la esofagitis persistente, estenosis esofágica, anillo de Schatzki y esófago de Barrett. Este estudio describe la motilidad en pacientes con ERGE refractaria y su relación con síntomas esofágicos. Método: Se realizó un estudio observacional analítico a partir de una cohorte retrospectiva en pacientes con diagnóstico de ERGE refractaria y síntomas esofágicos a quienes se les realizó manometría esofágica de alta resolución más impedanciometría. Se describen las características clínicas y demográficas, y la asociación entre los trastornos manométricos y los síntomas esofágicos. Resultados: Se incluyeron 133 pacientes (edad promedio: 54,1 ± 12,5 años). La pirosis y regurgitación (69,2 %) y la disfagia esofágica (13,5 %) fueron los síntomas más comunes. La motilidad normal (75,2 %), el aclaramiento completo del bolo (75,2 %) y la motilidad esofágica inefectiva (MEI) (18 %) fueron los hallazgos manométricos más frecuentes. La unión gastroesofágica tipos II y IIIb estuvieron presentes en el 35,3% y 33,8 % de los casos, respectivamente. La aperistalsis (3,8 %) y el esófago en martillo neumático (Jackhammer; 0,8 %) fueron infrecuentes. El aclaramiento incompleto del bolo se asoció con disfagia esofágica (p = 0,038) y a MEI (p = 0,008). Ningún síntoma esofágico se relacionó significativamente con trastornos de motilidad. Conclusiones: Los resultados de nuestro estudio sugieren que los trastornos de motilidad son infrecuentes en los pacientes con ERGE refractaria. Adicionalmente, sugieren que la presencia de alteraciones de motilidad esofágica no se relaciona con la presencia de síntomas esofágicos y, por tanto, que el tipo de síntoma presentado no permite predecir la existencia de dichos trastornos.

Abstract Introduction: Refractory gastroesophageal reflux disease (GERD) can lead to potential complications such as persistent esophagitis, esophageal stricture, Schatzki ring, and Barrett's esophagus. This study describes motility in patients with refractory GERD, and its association with esophageal symptoms. Materials and methods: An analytical observational study was carried out in a retrospective cohort of patients diagnosed with refractory GERD and esophageal symptoms who underwent high-resolution esophageal manometry and impedance testing. Clinical characteristics, demographics, and the association between motility disorders and esophageal symptoms are described. Results: 133 patients were included (mean age 54.1 ± 12.5 years). Heartburn and regurgitation (69.2%), and esophageal dysphagia (13.5%) were the most common symptoms. Normal motility (75.2%), complete bolus clearance (75.2%), and ineffective esophageal motility (IEM) (18%) were the most frequent manometric findings. Type II and IIIb gastroesophageal junction were observed in 35.3% and 33.8% of the cases, respectively. Esophageal aperistalsis (3.8%) and Jackhammer esophagus (0.8%) were rare findings. Incomplete bolus clearance was associated with esophageal dysphagia (p=0.038) and IEM (p=0.008). No esophageal symptoms were significantly related to motility disorders. Conclusions: The results of the present study suggest that motility disorders are rare in patients with refractory GERD. They also suggest that esophageal motility disorders are not associated with the presence of esophageal symptoms and, therefore, the type of symptom experienced does not allow predicting the existence of such disorders.

Actualización en la interpretación de la medición del pH e impedanciometría / Updated interpretation of Impedance-pH monitoring

Resumen La enfermedad por reflujo gastroesofágico (ERGE) se define como el tránsito anormal del contenido gástrico hacia el esófago, que se da por una alteración de la barrera antirreflujo, causando síntomas o complicaciones. Para su correcto diagnóstico y abordaje terapéutico, se requiere de la integración de hallazgos clínicos, endoscópicos y monitorización del pH esofágico en 24 horas con o sin impedanciometría, la cual debe ser realizada con especificaciones técnicas, y su interpretación debe basarse en la mejor evidencia clínica disponible, con el objetivo de tener diagnósticos precisos que permitan tomar las mejores decisiones con los pacientes. Recientemente, en el Consenso de Lyon se han incorporado nuevas directrices para el diagnóstico de ERGE por monitorización de pH esofágico, las cuales se revisan en este artículo.

Abstract Gastroesophageal reflux disease (GERD) is defined as the abnormal transit of gastric contents into the esophagus. It is caused by an alteration of the anti-reflux barrier, causing multiple symptoms or complications. In order to achieve accurate diagnosis and proper therapeutic approach, integration of clinical findings, endoscopic findings and 24-hour esophageal pH monitoring, with or without impedancometry, is required. These tests must be performed following technical specifications and their interpretation must be based on the best clinical evidence available to obtain accurate diagnoses that allow making the best decisions to the benefit of patients. Recently, the Lyon Consensus incorporated new guidelines for the diagnosis of GERD by esophageal pH monitoring, which are reviewed in this paper.