Modulation of Dendritic Cell Maturation by Fasciola hepatica: Implications of Glycans and Mucins for Vaccine Development

Fasciola hepatica is a worldwide distributed helminth pathogen that causes great economic losses in sheep andcattle. This parasite is able to regulate the host immune response, producing high levels of IL-5 and low levels ofIFNγ, as well as modulating the function of dendritic cells (DCs), mast cells or macrophages, among others.Moreover, TLR-mediated maturation of DCs can be suppressed by F. hepatica derived components. Here, weinvestigated the role of glycans in the modulation of LPS-induced maturation of DCs, as well as in the production ofIL-5 and IFNγ by splenocytes from infected mice. We show that F. hepatica induces the recruitment to theperitoneum of semi-matured DCs, as judged by a down-regulation of MHC class II molecule expression and anincrease of CD80 and CD86 expression of DCs in the peritoneum of infected animals. Furthermore, we provideevidence indicating that glycan structures from F. hepatica are responsible, at least in part, for inhibiting LPS-induced DC maturation and production of IFNγ by splenocytes from infected animals. On the other hand, we showthat a mucin-like non-glycosylated peptide highly expressed in NEJ (Fhmuc) is able to synergize with LPS ininducing DC-maturation, and that it induces a T cell response specific for F. hepatica, both alone or in combinationwith DCs. Our data highlight the role of F. hepatica glycans in modulating the host immune response and mightcontribute to the design of vaccines against fasciolosis.Fil: Noya, Veronica. Universidad de la República; UruguayFil: Rodriguez, Ernesto. Universidad de la República; UruguayFil: Cervi, Laura Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Giacomini, Cecilia. Universidad de la República; UruguayFil: Brossard, Natalie. Universidad de la República; UruguayFil: Chiale, Carolina. Universidad de la República; UruguayFil: Carmona, Carlos. Universidad de la República; UruguayFil: Freire, Teresa. Universidad de la República; Urugua

Emergence and spread of a B.1.1.28-derived P.6 lineage with Q675H and Q677H spike mutations in Uruguay

Uruguay controlled the viral dissemination during the first nine months of the SARS-CoV-2 pandemic. Unfortunately, towards the end of 2020, the number of daily new cases exponentially increased. Herein, we analyzed the country-wide genetic diversity of SARS-CoV-2 between November 2020 and April 2021. We identified that the most prevalent viral variant during the first epidemic wave in Uruguay (December 2020–February 2021) was a B.1.1.28 sublineage carrying Spike mutations Q675H + Q677H, now designated as P.6, followed by lineages P.2 and P.7. P.6 probably arose around November 2020, in Montevideo, Uruguay’s capital department, and rapidly spread to other departments, with evidence of further local transmission clusters; it also spread sporadically to the USA and Spain. The more efficient dissemination of lineage P.6 with respect to P.2 and P.7 and the presence of mutations (Q675H and Q677H) in the proximity of the key cleavage site at the S1/S2 boundary suggest that P.6 may be more transmissible than other lineages co-circulating in Uruguay. Although P.6 was replaced by the variant of concern (VOC) P.1 as the predominant lineage in Uruguay since April 2021, the monitoring of the concurrent emergence of Q675H + Q677H in VOCs should be of worldwide interest

Il linfonodo sentinella nei tumori del colon

Introduzione. I tumori maligni possono dare metastasi seguendo il sistema linfatico in modo sequenziale. In ogni catena linfatica al primo linfonodo che drena la regione dove si è sviluppato il tumore viene dato il nome di “linfonodo sentinella’’ (LS). Obiettivo dello studio. L’obiettivo principale del presente studio è la determinazione del valore predittivo della metodica del linfonodo sentinella nella stadiazione del cancro colico non metastatico. Pazienti e metodi. Abbiamo effettuato uno studio prospettico arruolando pazienti con adenocarcinoma del colon che soddisfacessero i seguenti criteri: - età minima di 18 anni; - stadiazione con colonoscopia, Rx torace, ecografia o TC addome completo per selezionare pazienti con adenocarcinoma del colon T2-T3 senza metastasi linfonodali ed epatiche; - rischio anestesiologico ASA 1-3; - consenso informato. A seguito della resezione colica con linfadenectomia è stata eseguita un’iniezione sottomucosa di colorante vitale (patent blue) che ha permesso di identificare il linfonodo sentinella. I linfonodi sono stati sottoposti ad esame istologico con ematossilina-eosina e successivamente con tecnica immunoistochimica. Risultati. Dal gennaio a dicembre 2008, 26 pazienti sono stati arruolati in questo studio prospettico. Di questi sono stati considerati elegibili per il nostro studio solamente 14 pazienti. L’esame con ematossilina - eosina dei linfonodi ha evidenziato: a) in 4 casi su 14 (28,57%) erano presenti metastasi sui linfonodi contenuti nel mesocolon, b) in 10 casi su 14 (71,42%) erano assenti metastasi sui linfonodi contenuti nel mesocolon. Nei casi in cui non erano presenti metastasi, all’esame con ematossilina-eosina, nei linfonodi del mesocolon è stato eseguito l’esame istologico dei linfonodi sentinella con tecnica immunoistochimica; in 2 casi è stata evidenziata la presenza di micrometastasi. In un caso sono state identificate linee aberranti di drenaggio mesenterico (skip metastasis); il linfonodo sentinella (negativo all’esame con ematossilina eosina) è stato studiato con tecnica immunoistochimica che non ha evidenziato la presenza di micrometastasi. Conclusioni. È possibile affermare che l’esame del linfonodo sentinella è fattibile con la metodica ex vivo. Nel 20% dei casi da noi studiati a livello dei LS sono presenti micrometastasi non evidenziate al classico esame con ematossilina-eosina. Lo studio dei linfonodi sentinella con sezioni multiseriate e tecniche immunoistochimiche consente un miglioramento della stadiazione patologica

La sindrome compartimentale addominale ed il ruolo della re-laparotomia decompressiva

Premessa. La Sindrome Compartimentale Addominale (ACS) è una complicanza la cui insorgenza è sempre più riconosciuta sia nei pazienti medici che in quelli chirurgici. La World Society of the Abdominal Compartment Syndrome definisce Ipertensione Intra-Addominale (IAH) la presenza di una Pressione Intra-Addominale (IAP) ≥ 12mmHg e definisce la ACS una condizione caratterizzata da una IAP ≥ 20mmHg (con o senza una pressione di perfusione addominale < 60 mmHg) associata alla disfunzione o al danneggiamento di uno o più organi non presenti precedentemente. La IAH contribuisce alla disfunzione d'organo nei pazienti con trauma addominale e sepsi e porta alla formazione di ACS. Obiettivo. In questo studio si è cercato di valutare la reale incidenza della sindrome compartimentale addominale nei pazienti sottoposti a laparotomie d’urgenza e si è valutato il ruolo della re-laparotomia decompressiva. Pazienti e metodi. Lo studio include 10 pazienti, 4 uomini e 6 donne con un'età media di 68 anni (range, 38-86), sottoposti a laparotomia dal gennaio 2007 al settembre 2008. In accordo alle indicazioni dettate dalla WSACS (World Society of the Abdominal Compartment Syndrome) abbiamo misurato la IAP in maniera indiretta attraverso l'uso di un catetere vescicale di Foley. Risultati. Dei 10 pazienti , in 8 la pressione intraaddominale rientrava nei valori compresi tra 8 mmHg e 20 mmHg e, non essendo stati riscontrati sintomi clinici significativi correlati all’aumento della IAP, non è stato necessario eseguire una re-laparotomia decompressiva. Nei 2 pazienti in cui la pressione intra-addominale era superiore ai 20 mmHg la sintomatologia era caratterizzata da tensione della parete addominale, instabilità emodinamica, oligo/anuria, modificazioni respiratorie e squilibrio acido-base per cui sono sati sottoposti a re-laparotomia decompressiva d’urgenza. Conclusioni. In base alla nostra esperienza ed ai risultati della letteratura riteniamo indispensabile il monitoraggio della pressione intraaddominale nei pazienti sottoposti a re-laparotomia addominale. Nelle re-laparotomie decompressive eseguite d’urgenza la sutura solo cutanea ha permesso una rapida chiusura dell’addome in pazienti instabili ed a rischio

Associations between Ocular Biometry, Refractive Error, and Body Characteristics

Myopia is a refractive error widely spread throughout the world, usually related to excessive axial length (AL) of the eye. This elongation could have severe consequences, even leading to blindness. However, AL varies among subjects, and it may be correlated with other anthropometric parameters. The aim of this study was to evaluate the relationships between AL, body height, refractive error, and sex. A total of 72 eyes of 36 myopic participants with a mean age of 11.1 ± 1.42 years (ranging from 8 to 14 years) were included in the study. Participants underwent objective refraction by NVision-K5001, AL measurement by Topcon MYAH biometer, and body height measurement. Significant correlations were observed between AL, body height, and spherical equivalent (SE) (Spearman’s correlation, all p ≤ 0.016). When participants were grouped by AL, significant differences were observed for body height and SE, and when grouped by height percentile, significant differences were observed for AL and SE (Kruskal–Wallis test, all p ≤ 0.006). There was a significant difference in SE, AL, and body height between genders (Mann–Whitney U test, all p ≤ 0.038). AL relates to the refractive state of the eye and is also influenced by individual anatomical characteristics

Biliopancreatic diversion: long-term effects on gonadal function in severely obese men

Background This study investigated hormonal parameters of gonadal function in severely obese men before and 1 year after undergoing biliopancreatic diversion (BPD). Methods This observational 1-year postoperative study conducted at medical and surgical clinics at an academic medical center in Italy followed 20 severely obese men age 21 to 63 years, with a mean (± standard deviation) body mass index (BMI) of 47.3 ± 13.1. The following parameters were evaluated: body composition, using body impedance analysis (BIA), and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, estradiol 17β, and leptin. Results At a mean 12 ± 1 months after surgery, the patients showed a significant decrease in weight, from 132.1 ± 36.9 before surgery to 93.5 ± 20 kg (P &lt; .0001), and BMI, from 47.3 ± 13.1 before surgery to 33.5 ± 7 (P &lt; .0001). LH increased from 2.42 ± 1.59 to 4.97 ± 2.6 mIU/ml (P &lt; .0001), FSH increased from 2.85 ± 1.85 to 4.9 ± 4.2 mIU/mL (P = .021), and total testosterone increased from subnormal presurgical values to within normal range (2.81 ± 1.08 to 9.12 ± 1.37 ng/mL; P &lt; .0001), whereas estradiol 17β decreased from elevated basal levels of 44.0 ± 29 to 16.7 ± 6.9 pg/mL (P &lt; .0001). The basal leptin level dropped from 33.0 ± 9.23 to 16.6 ± 5.12 ng/mL (P &lt; .0001), reflecting the decrease in body fat. Subjective improvement in sexual performance was reported by 80% of patients. Conclusions Severe obesity is coupled with some significant alterations of the gonadotropin-testicular axis and estradiol 17β and leptin blood levels. These derangements were substantially corrected by 1 year after BPD

Bone turnover markers in severely obese eumenorrhoic women undergoing bariatric surgery

Background and aims: a) To evaluate alterations in the circulating levels of osteocalcin (OC, a marker of osteoblastic activity) and carboxy terminal cross-linked telopeptide (ICTP, an indicator of osteoclastic function) in severely obese women under baseline conditions and after bariatric malabsorptive surgery (biliopancreatic diversion, BPD); b) To define any correlation between these parameters and some of the hormones involved in regulating bone metabolism: parathyroid hormone (PTH), gonadal and adrenal steroids, and leptin. Methods: Design: Observational, 2-year postoperative study. Participants: Fifteen severely obese, eumenorrhoic women aged 25-43 years. Measurements: Determination of body composition using body impedance analysis (BIA), and serum levels of OC, ICTP, PTH, leptin (L), estradiol 17β (E2), progesterone (P) and dehydroepiandrosterone sulfate (DHEAS). Results: The results are expressed as mean values ±SEM. Twenty-four months (±3 months) post-surgery, all of the patients showed a significant reduction in the BMI (from 46.5±2.5 to 36.2±1.6) and fat mass (from 44.1±0.8 to 37.1±0.9) (p&lt;0.001). OC increased from 12±3.2 to 37.5± 5.2 ng/ml (p&lt;0.0001) and ICTP from 6.2±0.7 to 14.9±1.9 μg/l (p&lt;0.0001), and the high baseline leptin levels of 48.7±6.4 decreased to 19.9± 3.0 ng/ml (p&lt;0.0001). There were no statistically significant changes in PTH, E2, P or DHEAS. Conclusions: Two years after bariatric surgery, the weight loss in our patients was accompanied by an increase in the serum levels of two circulating bone turnover markers OC and ICTP. As there were no significant changes in PTH or steroid status, these findings may be related to the reduction in circulating L, which may play a direct role in regulating skeletal metabolism.</br

A Branched and Double Alpha-Gal-Bearing Synthetic Neoglycoprotein as a Biomarker for Chagas Disease

Chagas disease (CD) is caused by the parasite Trypanosoma cruzi and affects 6–7 million people worldwide. The diagnosis is still challenging, due to extensive parasite diversity encompassing seven genotypes (TcI-VI and Tcbat) with diverse ecoepidemiological, biological, and pathological traits. Chemotherapeutic intervention is usually effective but associated with severe adverse events. The development of safer, more effective therapies is hampered by the lack of biomarker(s) (BMKs) for the early assessment of therapeutic outcomes. The mammal-dwelling trypomastigote parasite stage expresses glycosylphosphatidylinositol-anchored mucins (tGPI-MUC), whose O-glycans are mostly branched with terminal, nonreducing α-galactopyranosyl (α-Gal) glycotopes. These are absent in humans, and thus highly immunogenic and inducers of specific CD anti-α-Gal antibodies. In search for α-Gal-based BMKs, here we describe the synthesis of neoglycoprotein NGP11b, comprised of a carrier protein decorated with the branched trisaccharide Galα(1,2)[Galα(1,6)]Galβ. By chemiluminescent immunoassay using sera/plasma from chronic CD (CCD) patients from Venezuela and Mexico and healthy controls, NGP11b exhibited sensitivity and specificity similar to that of tGPI-MUC from genotype TcI, predominant in those countries. Preliminary evaluation of CCD patients subjected to chemotherapy showed a significant reduction in anti-α-Gal antibody reactivity to NGP11b. Our data indicated that NGP11b is a potential BMK for diagnosis and treatment assessment in CCD patients