Occurrence of Fatal and Nonfatal Adverse Outcomes after Heart Transplantation in Patients with Pretransplant Noncytotoxic HLA Antibodies

HLA antibodies (HLA ab) in transplant candidates have been associated with poor outcome. However, clinical relevance of noncytotoxic antibodies after heart transplant (HT) is controversial. By using a Luminex-based HLA screening, we retested pretransplant sera from HT recipients testing negative for cytotoxic HLA ab and for prospective crossmatch. Out of the 173 consecutive patients assayed (52±13y; 16% females; 47% ischemic etiology), 32 (18%) showed pretransplant HLA ab, and 12 (7%) tested positive against both class I and class II HLA. Recipients with any HLA ab had poorer survival than those without (65±9 versus 82±3%; P=0.02), accounting for a doubled independent mortality risk (P=0.04). In addition, HLA-ab detection was associated with increased prevalence of early graft failure (35 versus 15%; P=0.05) and late cellular rejection (29 versus 11%; P=0.03). Of the subgroup of 37 patients suspected for antibody mediated rejection (AMR), the 9 with pretransplant HLA ab were more likely to display pathological AMR grade 2 (P=0.04). By an inexpensive, luminex-based, HLA-screening assay, we were able to detect non-cytotoxic HLA ab predicting fatal and nonfatal adverse outcomes after heart transplant. Allocation strategies and desensitization protocols need to be developed and prospectively tested in these patients

Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters

IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20

X-ray microtomography for studying 3D-textures of speleothems developed inside historic walls

En este artículo se muestra una aplicación de la microtomografía computerizada de Rayos X (microCT-RX) como técnica no destructiva útil para la caracterización del interior de estructuras sin necesidad de perder la muestra. Gracias a la sensibilidad de la técnica ha sido posible distinguir diferentes tipos de crecimiento espeleotémico dentro de una estalactita localizada en las bóvedas interiores de la muralla histórica de la isla de Nueva Tabarca

Tephrochronology and chronostratigraphy of the Miocene Chilcatay and Pisco formations (East Pisco Basin, Peru)

Strata of Chilcatay and Pisco formations exposed in the Ica Desert (East Pisco Basin, southern Peru) preserve one of the most complete and rich records of Miocene marine vertebrates of the world. Despite its exceptional importance, the chronostratigraphy of these fossil-bearing deposits has been only sporadically studied in the literature until recently. This work presents a detailed reconstruction of the chronostratigraphic framework, achieved by mapping and logging of seven sections of the Miocene Chilcatay and Pisco formations along the western side of the Ica River. The Chilcatay Formation consists of two allomembers, namely Ct1 and Ct2, bounded at the base by unconformities CE0.1 and CE0.2, respectively. Similarly, the immediately overlying Pisco Formation is divided into allomembers P0, P1, and P2, bounded at the base by unconformities PE0.0, PE0.1 and PE0.2, respectively. The new 39Ar–40Ar results presented here, combined with ages of previous work, provide precise constraints on the age of several stratigraphically referenced volcanic ash layers intercalated in the studied fossil-bearing succession, placing its vertebrate fossil fauna within a refined temporal framework and laying the solid ground for its detailed regional and global comparison. The ages of the allomembers, and thus their associated faunas, can be reliably estimated by the combination of 39Ar–40Ar dating on tephra layers with diatom biostratigraphy. In the study area, the two methods are mutually consistent and constrain the deposition of the Chilcatay Formation between 19.2 and 18.0 Ma, that of P1 between 9.5 and 8.6 Ma, and that of P2 between 8.4 and 6.7 Ma. In the absence of direct dating of the P0 allomember, which lacks both preserved tephra suitable for 39Ar–40Ar dating and microfossils, its age can be constrained to the temporal gap between the youngest age available from the underlying Chilcatay strata (18.0 Ma) and the oldest age available from the overlying P1 strata (9.5 Ma)

Dietary Polyphenols Effects on Focal Adhesion Plaques and Metalloproteinases in Cancer Invasiveness

Focal adhesion plaques (FAPs) play an important role in the communication between cells and the extracellular matrix (ECM) and in cells’ migration. FAPs are macromolecular complexes made by different proteins which also interact with matrix metalloproteinases (MMPs). Because of these fundamental properties, FAPs and MMPs are also involved in cancer cells’ invasion and in the metastatic cascade. The most important proteins involved in FAP formation and activity are (i) integrins, (ii) a complex of intracellular proteins and (iii) cytoskeleton proteins. The latter, together with MMPs, are involved in the formation of filopodia and invadopodia needed for cell movement and ECM degradation. Due to their key role in cancer cell migration and invasion, MMPs and components of FAPs are often upregulated in cancer and are thus potential targets for cancer therapy. Polyphenols, a large group of organic compounds found in plant-based food and beverages, are reported to have many beneficial healthy effects, including anticancer and anti-inflammatory effects. In this review, we discuss the growing evidence which demonstrates that polyphenols can interact with the different components of FAPs and MMPs, inhibit various pathways like PI3K/Akt, lower focal adhesion kinase (FAK) phosphorylation and decrease cancer cells’ invasiveness, leading to an overall antitumoral effect. Finally, here we highlight that polyphenols could hold potential as adjunctive therapies to conventional cancer treatments due to their ability to target key mechanisms involved in cancer progression