Immunization with a Mu-class glutathione transferase from Echinococcus granulosus induces efficient antibody responses and confers long-term protection against secondary cystic echinococcosis.

Cystic echinococcosis, a zoonosis caused by cestodes belonging to the Echinococcus granulosus sensu lato (s.l.) genetic complex, affects humans and diverse livestock species. Although a veterinary vaccine exhibiting high levels of antibody-mediated protection has successfully reached the market, the large genetic diversity among parasite isolates and their particular host preferences, makes still necessary the search for novel vaccine candidates. Glutathione transferases (GSTs) constitute attractive targets for immunoprophylaxis due to their outstanding relevance in helminth detoxification processes, against both exogenous and endogenous stressors. Among the six GSTs known to be expressed in E. granulosus s.l., EgGST1 (Mu-class), EgGST2 (Sigma-class), and EgGST3 (a still non-classifiable isoenzyme), show the highest proteomic expression. Therefore, their recombinant forms -rEgGST1, rEgGST2 and rEgGST3- were herein analyzed regarding their potential to induce long-term antiparasite protection in mice. Only immunization with rEgGST1 induced long-lasting protection; and accordingly, rEgGST1-specific antibodies enhanced the parasite killing through both the classical activation of the host complement system and the antibody-dependent cellular cytotoxicity by macrophages. These results support further testing of rEgGST1 as a vaccine candidate in diverse hosts due to the broad expression of EgGST1 in different parasite stages and tissues.

A New Face of Fibrin-Associated Large B-Cell Lymphoma: Epstein-Barr Virus-Positive Breast Implant-Associated Diffuse Large B-Cell Lymphoma.

Recently, there have been reports of what could be a new lymphoproliferative entity: breast implant-associated Epstein-Barr virus positive (EBV+) diffuse large B-cell lymphoma (EBV+ BIA-DLBCL). The new World Health Organization classification has categorized it as fibrin-associated large B-cell lymphomas (FA-LBCLs); therefore, it could be referred to as breast implant-associated fibrin-associated large B-cell lymphomas (BIA-FA-LBCLs). Although the association between breast implants and lymphomas has been known since the mid-1990s, it has been almost exclusively breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). Here, we describe the first case of BIA-FA-LBCL at our center, with a literature review of the clinical features, diagnosis and treatment approach of this lymphoma. We also explore the differential diagnosis of BIA-FA-LBCL, highlighting the diagnostic challenges and the reasons that have led these lymphomas to being labeled as a new face of FA-LBCL.

Automatic detection of health misinformation: a systematic review.

The spread of health misinformation has the potential to cause serious harm to public health, from leading to vaccine hesitancy to adoption of unproven disease treatments. In addition, it could have other effects on society such as an increase in hate speech towards ethnic groups or medical experts. To counteract the sheer amount of misinformation, there is a need to use automatic detection methods. In this paper we conduct a systematic review of the computer science literature exploring text mining techniques and machine learning methods to detect health misinformation. To organize the reviewed papers, we propose a taxonomy, examine publicly available datasets, and conduct a content-based analysis to investigate analogies and differences among Covid-19 datasets and datasets related to other health domains. Finally, we describe open challenges and conclude with future directions.

Decoding the molecular heterogeneity of pediatric monomorphic post-solid organ transplant lymphoproliferative disorders.

Posttransplant lymphoproliferative disorders (PTLDs) represent a broad spectrum of lymphoid proliferations, frequently associated with Epstein-Barr virus (EBV) infection. The molecular profile of pediatric monomorphic PTLDs (mPTLDs) has not been elucidated, and it is unknown whether they display similar genetic features as their counterpart in adult and immunocompetent (IMC) pediatric patients. In this study, we investigated 31 cases of pediatric mPTLD after solid organ transplantation, including 24 diffuse large B-cell lymphomas (DLBCLs), mostly classified as activated B cell, and 7 cases of Burkitt lymphoma (BL), 93% of which were EBV positive. We performed an integrated molecular approach, including fluorescence in situ hybridization, targeted gene sequencing, and copy number (CN) arrays. Overall, PTLD-BL carried mutations in MYC, ID3, DDX3X, ARID1A, or CCND3 resembling IMC-BL, higher mutational burden than PTLD-DLBCL, and lesser CN alterations than IMC-BL. PTLD-DLBCL showed a very heterogeneous genomic profile with fewer mutations and CN alterations than IMC-DLBCL. Epigenetic modifiers and genes of the Notch pathway were the most recurrently mutated in PTLD-DLBCL (both 28%). Mutations in cell cycle and Notch pathways correlated with a worse outcome. All 7 patients with PTLD-BL were alive after treatment with pediatric B-cell non-Hodgkin lymphoma protocols, whereas 54% of patients with DLBCL were cured with immunosuppression reduction, rituximab, and/or low-dose chemotherapy. These findings highlight the low complexity of pediatric PTLD-DLBCL, their good response to low-intensity treatment, and the shared pathogenesis between PTLD-BL and EBV-positive IMC-BL. We also suggest new potential parameters that could help in the diagnosis and the design of better therapeutic strategies for these patients.

Proteomics Characterization of Clear Cell Renal Cell Carcinoma.

PURPOSE: To explore the tumor proteome of patients diagnosed with localized clear cell renal cancer (ccRCC) and treated with surgery. MATERIAL AND METHODS: A total of 165 FFPE tumor samples from patients diagnosed with ccRCC were analyzed using DIA-proteomics. Proteomics ccRCC subtypes were defined using a consensus cluster algorithm (CCA) and characterized by a functional approach using probabilistic graphical models and survival analyses. RESULTS: We identified and quantified 3091 proteins, including 2026 high-confidence proteins. Two proteomics subtypes of ccRCC (CC1 and CC2) were identified by CC using the high-confidence proteins only. Characterization of molecular differences between CC1 and CC2 was performed in two steps. First, we defined 514 proteins showing differential expression between the two subtypes using a significance analysis of microarrays analysis. Proteins overexpressed in CC1 were mainly related to translation and ribosome, while proteins overexpressed in CC2 were mainly related to focal adhesion and membrane. Second, a functional analysis using probabilistic graphical models was performed. CC1 subtype is characterized by an increased expression of proteins related to glycolysis, mitochondria, translation, adhesion proteins related to cytoskeleton and actin, nucleosome, and spliceosome, while CC2 subtype showed higher expression of proteins involved in focal adhesion, extracellular matrix, and collagen organization. CONCLUSIONS: ccRCC tumors can be classified in two different proteomics subtypes. CC1 and CC2 present specific proteomics profiles, reflecting alterations of different molecular pathways in each subtype. The knowledge generated in this type of studies could help in the development of new drugs targeting subtype-specific deregulated pathways.

Estudio transversal: Prevalencia de arritmias cardiacas supraventriculares y factores asociados en pacientes adultos atendidos en consulta cardiológica. Hospital José Carrasco Arteaga, Cuenca, 2018 / Cross sectional Study: Prevalence of supraventricular cardiac arrhythmias and associated factors in adult patients seen at the outpatient cardiology service. Hospital José Carrasco Arteaga, Cuenca, 2018.

INTRODUCCIÓN: Las arritmias cardiacas son enfermedades cardiovasculares, causadas por alteraciones en la conducción o formación de estímulos eléctricos. La detección oportuna de estas alteraciones es crucial, pues a largo plazo mejora la calidad de vida de las personas que padecen estas patologías. El objetivo del presente estudio fue determinar la prevalencia de arritmias cardiacas supraventriculares y sus factores asociados en paciente adultos atendidos en la consulta externa de la unidad de cardiología del Hospital José Carrasco Arteaga, Cuenca, 2018. MATERIALES Y MÉTODOS: Se realizó un estudio observacional, transversal, descriptivo y de correlación con una muestra de 608 pacientes mayores de 18 años atendidos en la Institución mencionada que se realizaron electrocardiograma durante el año 2018. Se estudiaron las variables: estado nutricional, hipertensión arterial, diabetes, tabaquismo, medicamentos utilizados; edad y sexo; presencia de arritmia supraventricular. Se utilizó la prueba Chi cuadrado para buscar asociación entre las variables cualitativas; considerando diferencias estadísticamente significativas una p < 0.05. RESULTADOS: De 608 pacientes, el 57.1% fueron mujeres; 61.84% fueron menores de 65 años. El 43.9% tuvo sobrepeso, el 27.6% presentó IMC normal. Las enfermedades crónicas como HTA y Diabetes tuvieron una frecuencia de 44.4% y 16% respectivamente. La prevalencia de las arritmias supraventriculares fue del 3.8%. La fibrilación auricular fue la arritmia supraventricular más frecuente con el 47.8%, seguida de la arritmia sinusal con el 26.08%. Hubo mayor prevalencia de arritmias supraventriculares en el sexo femenino que en el masculino (4.6% vs 2.7%), en los pacientes con sobrepeso u obesidad que en los que tenían IMC normal ( 4.4% vs 2.3%), en los pacientes hipertensos en relación a los que no padecían de hipertensión (5.2% vs 2.7%), en los pacientes usuarios de medicamentos antitiroideos en relación a los que los consumían (50% vs 3.6%); sin embargo no se encontró asociación estadísticamente significativa con ninguna de estas variables. CONCLUSIÓN: La prevalencia de las arritmias supraventriculares fue del 3.8%. La principal de arritmia cardiaca diagnosticada fue la fibrilación auricular seguida de la arritmia sinusal. No se encontró asociación estadísticamente significativa entre la frecuencia de las arritmias supraventriculares y las variables estudiadas.(AU)

BACKGROUND: Cardiac arrhythmias are cardiovascular diseases, caused by disturbances in the initiation or conduction of electrical stimuli. The timely detection of these alterations is crucial, since in the long term it improves the quality of life of people suffering from these pathologies. The aim of this study was to determine the prevalence of supraventricular cardiac arrhythmias and their associated factors in adult patients treated in the outpatient clinic of the cardiology unit of Hospital José Carrasco Arteaga, Cuenca, 2018. METHODS: An observational, cross-sectional, descriptive and correlation study was carried out with a sample of 608 patients older than 18 years, at the mentioned Institution, who underwent electrocardiography during 2018. We studied the variables: nutritional status, arterial hypertension, diabetes, smoking, used drugs; age and sex; presence of supraventricular arrhythmia. We used Chi Square test to search for an association between the qualitative variables; considering statistical significance a p <0.05. RESULTS: of 608 patients, 57.1% were women; 61.84% were under 65 years of age. 43.9% were overweight, 27.6% had normal body mass index (BMI). Chronic diseases such as hypertension and diabetes had a frequency of 44.4% and 16% respectively. The prevalence of supraventricular arrhythmias was 3.8%. Atrial fibrillation was the most frequent supraventricular arrhythmia with 47.8%, followed by sinus arrhythmia with 26.08%. There was a higher prevalence of supraventricular arrhythmias in females than males (4.6% vs 2.7%), in overweight or obese patients than in those with normal BMI (4.4% vs 2.3%), in hypertensive patients than in those who didn't suffer from hypertension ( 5.2% vs 2.7%), in patients who used antithyroid drugs than in those who didn't use them (50% vs 3.6%); however, no statistically significant association was found with any of these variables. CONCLUSION: The prevalence of supraventricular arrhythmias was 3.8%. The most common cardiac arrhythmia was atrial fibrillation followed by sinus arrhythmia. No statistically significant association was found between the frequency of supraventricular arrhythmias and the variables studied.(au)

Case Report: Combined Liver-Kidney Transplantation to Correct a Mutation in Complement Factor B in an Atypical Hemolytic Uremic Syndrome Patient.

Pathogenic gain-of-function variants in complement Factor B were identified as causative of atypical Hemolytic Uremic syndrome (aHUS) in 2007. These mutations generate a reduction on the plasma levels of complement C3. A four-month-old boy was diagnosed with hypocomplementemic aHUS in May 2000, and he suffered seven recurrences during the following three years. He developed a severe hypertension which required 6 anti-hypertensive drugs and presented acrocyanosis and several confusional episodes. Plasma infusion or exchange, and immunosuppressive treatments did not improve the clinical evolution, and the patient developed end-stage renal disease at the age of 3 years. Hypertension and vascular symptoms persisted while he was on peritoneal dialysis or hemodialysis, as well as after bilateral nephrectomy. C3 levels remained low, while C4 levels were normal. In 2005, a heterozygous gain-of-function mutation in Factor B (K323E) was found. A combined liver and kidney transplantation (CLKT) was performed in March 2009, since there was not any therapy for complement inhibition in these patients. Kidney and liver functions normalized in the first two weeks, and the C3/C4 ratio immediately after transplantation, indicating that the C3 activation has been corrected. After remaining stable for 4 years, the patient suffered a B-cell non-Hodgkin lymphoma that was cured by chemotherapy and reduction of immunosuppressive drugs. Signs of liver rejection with cholangitis were observed a few months later, and a second liver graft was done 11 years after the CLKT. One year later, the patient maintains normal kidney and liver functions, also C3 and C4 levels are within the normal range. The 12-year follow-up of the patient reveals that, in spite of severe complications, CLKT was an acceptable therapeutic option for this aHUS patient.

Polypeptide-GalNAc-Transferase-13 Shows Prognostic Impact in Breast Cancer.

Breast cancer is a public health concern and is currently the fifth cause of mortality worldwide. Identification of different biological subtypes is essential for clinical management; therefore, the role of pathologists is essential and useful tools for immunohistochemistry diagnosis are needed. Polypeptide-GalNAc-transferases are emerging novel biomarkers related to cancer behavior and GalNAc-T13, correlated with aggressiveness in some tumors, is an interesting candidate. Few monoclonal antibodies reacting with native proteins, and not affected by fixation and paraffin embedding, have been reported. The aim of this work was to develop a useful monoclonal antibody anti-GalNAc-T13 and to assess its potential significance in breast cancer diagnosis. We evaluated 6 human breast cancer cell lines, 338 primary breast tumors and 48 metastatic lymph nodes and looked for clinical significance correlating GalNAc-T13 expression with patients' clinical features and survival. We found high GalNAc-T13 expression in 43.8% of the cases and observed a significant higher expression in metastatic lymph nodes, correlating with worse overall survival. We hypothesized several possible molecular mechanisms and their implications. We conclude that GalNAc-T13 may be a novel biomarker in breast cancer, useful for routine pathological diagnosis. Elucidation of molecular mechanisms related to aggressiveness should contribute to understand the role of GalNAc-T13 in breast cancer biology.

Histopathological Subtypes and PD-L1 Expression in Primary Urethral Adenocarcinoma: A Series of 5 Cases.

BACKGROUND AND OBJECTIVES: Urethral adenocarcinoma is a rare disease with poor prognosis that can display multiple histologic patterns and has an unclear histogenesis. Radical surgery with extensive periurethral resection is the preferred therapeutic approach. Both chemotherapy and radiotherapy have been used as complementary treatment options. Due to the tendency of these tumors to recur, treatment-associated complications, and the limited choice of therapeutic options, patient management can be difficult. Given the lack of literature regarding immunotherapy in urethral adenocarcinoma, our objective was to explore the expression of programmed death receptor-ligand 1 (PD-L1) throughout the different histological subtypes of primary urethral adenocarcinoma. METHODS: We reviewed all primary urethral adenocarcinomas diagnosed at our hospital between 1965 and 2019, performed immunohistochemical assays on the tissue blocks, classified them according to their histology and origin, and performed PD-L1 (22C3) immunohistochemistry assays in all cases. RESULTS: We found a total of 5 cases of primary urethral adenocarcinoma. All of the patients were women. One of the cases was a cribriform adenocarcinoma, 2 were columnar-mucinous adenocarcinomas, and 2 were clear cell adenocarcinomas. One of the clear cell adenocarcinomas strongly expressed PD-L1. In addition, a profuse inflammatory infiltration constituted by CD3-positive and CD8-positive T lymphocytes within tumor cells was observed in this case. None of the other cases showed PD-L1 expression. CONCLUSIONS: In conclusion, some urethral adenocarcinomas may strongly express PD-L1 and thus could potentially allow the use of immunotherapy in selected cases of advanced or recurrent adenocarcinoma.

A case-control study to assess the role of polyomavirus in transplant complications: Where do we stand?

PURPOSE: The study's aim was to assess whether polyomavirus DNAemia screening was associated with different outcomes in patients with positive viremia compared with negative viremia. METHODS: Case-control retrospective study of patients with polyomavirus DNAemia (viremia > 1000 copies/mL) matched 1:1 with controls. Control group consists of the patient who received a transplant immediately before or after each identified case and did have nil viremia. FINDING: Ultimately, 120 cases of BK polyomavirus (BKPyV) were detected and matched with 130 controls. Of these, 54 were adult kidney transplant recipients (KTRs), 43 were pediatric KTRs, and 23 were undergoing hemato-oncologic therapy, of which 20 were undergoing hematopoietic stem cell transplantation. The odds ratio (OR) for overall risk of poorer outcomes in cases versus controls was 16.07 (95% CI: 5.55-46.54). The unfavorable outcome of switching the immunosuppressive drug (ISD) (14/40,35%) was no different from that of those treated with reduced ISD doses (31/71, 43.6%, P = .250). Acute rejection or graft-versus-host disease, previous transplant, and intensity of immunosuppression (4 ISDs plus induction or conditioning) were risk factors for BKPyV-DNAemia (OR: 13.96, 95% CI: 11.25-15.18, P < .001; OR: 6.14, 95% CI: 3.91-8.80, P < .001; OR: 5.53, 95% CI: 3.37-7.30, P < .001, respectively). CONCLUSIONS: Despite viremia screening, dose reduction, and change in therapeutic protocol, patients with positive BKPyV-DNAemia present poorer outcomes and unfavorable results.

Molecular and clinicopathologic characterization of intravenous leiomyomatosis.

Intravenous leiomyomatosis (IVL) is an unusual uterine smooth muscle proliferation that can be associated with aggressive clinical behavior despite a histologically benign appearance. It has some overlapping molecular characteristics with both uterine leiomyoma and leiomyosarcoma based on limited genetic data. In this study, we assessed the clinical and morphological characteristics of 28 IVL and their correlation with molecular features and protein expression, using array comparative genomic hybridization (aCGH) and Cyclin D1, p16, phosphorylated-Rb, SMARCB1, SOX10, CAIX, SDHB and FH immunohistochemistry. The most common morphologies were cellular (n = 15), usual (n = 11), and vascular (n = 5; including 3 cellular IVL showing both vascular and cellular features). Among the immunohistochemical findings, the most striking was that all IVL showed differential expression of either p16 or Cyclin D1 in comparison to surrounding nonneoplastic tissue. Cytoplasmic phosphorylated-Rb was present in all but one IVL with hyalinization. SMARCB1, FH, and SDHB were retained; S0X10 and CAIX were not expressed. The most common genetic alterations involved 1p (39%), 22q (36%), 2q (29%), 1q (25%), 13q (21%), and 14q (21%). Hierarchical clustering analysis of recurrent aberrations revealed three molecular groups: Groups 1 (29%) and 2 (18%) with associated del(22q), and Group 3 (18%) with del(10q). The remaining IVL had nonspecific or no alterations by aCGH. Genomic index scores were calculated for all cases and showed no significant difference between the 14 IVL associated with aggressive clinical behavior (extrauterine extension or recurrence) and those without (median scores 5.15 vs 3.5). Among the 5 IVL associated with recurrence, 4 had a vascular morphology and 3 had alterations of 8q. Recurrent chromosome alterations detected herein overlap with those observed in the spectrum of uterine smooth muscle tumors and involve genes implicated in mesenchymal tumors at different sites with distinct morphological features.

Challenging Diagnosis of a Solitary Retroperitoneal Mass: A Case Report of Castleman's Disease and Review of the Literature.

Castleman's disease (CD) is an uncommon type of lymphoproliferative disorder. Its etiology and prevalence are unclear. The retroperitoneum is a very rare site for presentation of the unicentric variant, where it mimics malignant tumors. A 59-year-old man is referred to the urology outpatient clinic for the study of microhematuria found in a routine analysis. CT scan of the abdomen identified a solid, circumscribed mass, measuring 28 × 30 × 31 mm in the left para-aortic zone, with homogeneous contrast enhancement. Excisional surgery and regional lymphadenectomy were performed via laparoscopy. Postoperative course concurred without incidences. Histological diagnosis confirmed unicentric CD, hyaline-vascular type. CD is a rare entity, and the unicentric type presents as an asymptomatic mass. Retroperitoneum is a rare localization, where initial imaging diagnosis is unclear and surgical resection is the preferred treatment.

Selenium fortification of infant formulas: does selenium form matter?

Selenium is a trace element essential for the health and development of the growing infant. It is a necessary component of proteins and enzymes required for a variety of functions, including antioxidant defense, modulation of the inflammatory response, and production of thyroid hormones. In breast-fed infants, selenium stores depend on the selenium content of the mother's diet. In formula-fed infants, selenium levels are correlated to the residual selenium stores accumulated in utero and the level and type of selenium fortification used in the formula. Today, the United States Food and Drug Administration (FDA) recommends that infant formulas contain selenium at levels between 2.0 and 7.0 µg per 100 kcal. While the US FDA does not recommend a particular selenium form for fortification, evidence indicates that organically bound selenium forms (e.g., selenomethionine and selenium-enriched yeast) are better absorbed and retained than inorganic forms (e.g., selenite and selenate). Preliminary data from studies in adults do suggest that fortification with standardized selenium-enriched yeast may offer benefits compared to fortification with other organically bound selenium forms. However, because most studies evaluating the impact of selenium fortification of infant formula have assessed inorganic selenium supplements, additional research into the bioavailability and outcomes associated with the use of selenium-enriched yeast in infants is needed.

[Massive cardiac lipomatosis, an autopsy finding in a patient with sudden death]. / Lipomatosis cardiaca masiva, hallazgo en la autopsia de un paciente con muerte súbita.

The fat replacement of myocardial cells is a degenerative process that usually affects the right ventricle and is found in 50% of the elderly. The problem arises when this degeneration occurs to a massive degree, a differential diagnosis with other pathologies being necessary. We present the case of a patient who died suddenly and a massive cardiac lipomatosis was found on autopsy, as the only explanation of the outcome.

Apoptosis-related proteins are potential markers of neonatal hypoxic-ischemic encephalopathy (HIE) injury.

Neonatal hypoxic-ischemic encephalopathy (HIE) causes high mortality and long-term morbidity rates. The magnitude of the neuronal damage depends on the duration and severity of the initial insult combined with the deleterious effects of reperfusion and apoptosis. Currently, a diagnosis of HIE is based largely on the neurological and histological findings. Therefore, the aim of this study was to identify apoptosis-related proteins that might serve as potential markers of HIE injury. As an initial step toward reaching this objective, we analyzed changes in protein levels in an in vitro model of hypoxia using antibody arrays, and we have identified changes in the expression level of two proteins involved in apoptosis, Smac-DIABLO and cathepsin D. We obtained brain sections from eight neonatal HIE patients and performed histological staining, TUNEL assays and Smac-DIABLO and cathepsin D immunolocalization. Our results revealed a high number of TUNEL-positive cells, including neurons, astrocytes and ependymal cells, in the various regions that were analyzed. Interestingly, many of the areas that were positive for TUNEL staining did not appear to be damaged in the histological evaluation. In addition, using immunostaining, we found that Smac-DIABLO and cathepsin D had the same regional distribution pattern. Taken together, these findings indicate that these two proteins could serve as markers to identify injured regions that might not to be detectable using histological observations alone.