Matching an Old Marine Paradigm: Limitless Connectivity in a Deep-Water Fish over a Large Distance.

Investigations of population structuring in wild species are fundamental to complete the bigger picture defining their ecological and biological roles in the marine realm, to estimate their recovery capacity triggered by human disturbance and implement more efficient management strategies for fishery resources. The Blackspot Seabream (Pagellus bogaraveo, Brünnich 1768) is a commercially valuable deep-water fish highly exploited over past decades. Considering its exploitation status, deepening the knowledge of intraspecific variability, genetic diversity, and differentiation using high-performing molecular markers is considered an important step for a more effective stock assessment and fishery management. With one of the largest efforts conceived of and completed by countries overlooking the Atlantic and Mediterranean coasts in recent years, a total of 320 individuals were collected from different fishing grounds in the Mediterranean Sea and Atlantic Ocean and analysed using 29 microsatellite loci. We applied multiple statistical approaches to investigate the species' connectivity and population structure across most of its described distribution area. Considering the incomplete knowledge regarding the migratory behaviour of adults, here we suggest the importance of egg and larval dispersal in sustaining the observed genetic connectivity on such a large geographical scale.

Revealing and harnessing CD39 for the treatment of colorectal cancer and liver metastases by engineered T cells.

OBJECTIVE: Colorectal tumours are often densely infiltrated by immune cells that have a role in surveillance and modulation of tumour progression but are burdened by immunosuppressive signals, which might vary from primary to metastatic stages. Here, we deployed a multidimensional approach to unravel the T-cell functional landscape in primary colorectal cancers (CRC) and liver metastases, and genome editing tools to develop CRC-specific engineered T cells. DESIGN: We paired high-dimensional flow cytometry, RNA sequencing and immunohistochemistry to describe the functional phenotype of T cells from healthy and neoplastic tissue of patients with primary and metastatic CRC and we applied lentiviral vectors (LV) and CRISPR/Cas9 genome editing technologies to develop CRC-specific cellular products. RESULTS: We found that T cells are mainly localised at the front edge and that tumor-infiltrating T cells co-express multiple inhibitory receptors, which largely differ from primary to metastatic sites. Our data highlighted CD39 as the major driver of exhaustion in both primary and metastatic colorectal tumours. We thus simultaneously redirected T-cell specificity employing a novel T-cell receptor targeting HER-2 and disrupted the endogenous TCR genes (TCR editing (TCRED)) and the CD39 encoding gene (ENTPD1), thus generating TCREDENTPD1KOHER-2-redirected lymphocytes. We showed that the absence of CD39 confers to HER-2-specific T cells a functional advantage in eliminating HER-2+ patient-derived organoids in vitro and in vivo. CONCLUSION: HER-2-specific CD39 disrupted engineered T cells are promising advanced medicinal products for primary and metastatic CRC.

cDCD organ donation pathway of Romagna Local Health Authority: strategic planning, organizational management, and results.

The introduction of pathways to enrol deceased donors after cardio-circulatory confirmation of death (donation after circulatory death, DCD) is expanding in many countries to face the shortage of organs for transplantation. The implementation of normothermic regional reperfusion (NRP) with warm oxygenated blood is a strategy to manage in-situ the organs of DCD donors. This approach, an alternative to in-situ cold preservation, and followed by prompt retrieval and cold static storage and/or ex-vivo machine perfusion (EVMP), could be limited to abdominal organs (A-NRP) or extended to the thorax (thoraco-abdominal, TA-NRP. NRP is also referred to as extracorporeal interval support for organ retrieval (EISOR). The use of EISOR is increasing in Europe, even if variably regulated. A-NRP has been demonstrated to be effective in decreasing the risk associated with transplantation of abdominal organs from DCD donors, and was recommended by the European Society for Organ Transplantation (ESOT) in a recent consensus document. We aim to explain how we select the candidates for DCD, to describe our regionalized model for implementing EISOR provision, and to introduce the health care professionals involved in this complex process, with their strictly defined roles, responsibilities, and boundaries. Finally, we report the results of our program, recruiting cDCD donors over a large network of hospitals, all pertaining to a Local Health Authority (Azienda Unità Sanitaria Locale, AUSL) in Romagna, Italy.

EISOR Delivery: Regional experience with sharing equipe, equipment & expertise to increase cDCD donor pool in time of pandemic.

Donation after circulatory death (DCD) programs are expanding in Europe, in the attempt to expand donors pool. Even in controlled DCD donors, however, a protracted warm ischemia time occurring in the perimortem period might damage organs, making these unsuitable for transplantation. Implementing a strategy of extracorporeal interval support for organ retrieval (EISOR), a regional reperfusion with normothermic, oxygenated blood provides a physiologic environment allowing extensive assessment of potential grafts, and potentially promotes recovery of native function. Here we report the results of a multi-center retrospective cohort study including 29 Maastricht Category III controlled DCD donors undergoing extracorporeal support in a regional DCD/EISOR Training Center, and in the network of referring In-Training Centers, under the liaison of the regional Transplant Coordination Center during COVID-19 pandemic, between March 2020 and November 2021. The study aims to understand whether a mobile, experienced EISOR team implementing a consistent technique and sharing its equipe, expertise and equipment in a regional network of hospitals, might be effective and efficient in implementing the regional DCD program activity even in a highly stressed healthcare system.

Description of an Integrated and Dynamic System to Efficiently Deal With a Raging COVID-19 Pandemic Peak.

Background: This study aimed to describe an innovative and functional method to deal with the increased COVID-19 pandemic-related intensive care unit bed requirements. Methods: We described the emergency creation of an integrated system of internistic ward, step-down unit, and intensive care unit, physically located in reciprocal vicinity on the same floor. The run was carried out under the control of single intensive care staff, through sharing clinical protocols and informatics systems, and following single director supervision. The intention was to create a dynamic and flexible system, allowing for rapid and fluid patient admission/discharge, depending on the requirements due to the third Italian peak of the COVID-19 pandemic in March 2021. Results: This study involved 142 COVID-19 patients and 66 non-COVID-19 patients who were admitted; no critical patient was left unadmitted and no COVID-19 severe patients referring to our center had to be redirected to other hospitals due to bed saturation. This system allowed shorter hospital length-of-stay in general wards (5.9 ± 4 days) than in other internistic COVID-19 wards and overall mortality in line with those reported in literature despite the peak raging. Conclusion: This case report showed the feasibility and the efficiency of this dynamic model of hospital rearrangement to deal with COVID-19 pandemic peaks.

Massive aspiration syndrome: a possible indication for "emergent" veno-venous extracorporeal membrane oxygenation?: a case report.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is usually performed in cases of severe respiratory failure in which conventional and advanced mechanical ventilation strategies are ineffective in achieving true lung-protective ventilation, thus triggering ventilatory-induced lung injury. If circulatory failure coexists, veno-arterial ECMO (VA-ECMO) may be preferred over VV-ECMO because of its potential for circulatory support. In VA-ECMO, the respiratory contribution is less effective and the complication rate is higher than in the VV configuration. CASE PRESENTATION: The authors present a case in which VV-ECMO was performed in an emergency setting to treat a 68-year-old White male patient who experienced acute respiratory failure after massive aspiration. Despite intubation and intensive care unit admission, multiple organ failure occurred suddenly, thus prompting referral to a level-1 trauma center with an ECMO facility. The patient's condition slowly improved with VV-ECMO support along with standard treatment for hemodynamic impairment. VV-ECMO was discontinued on day 8. The patient was extubated on day 14 and discharged home fully recovered 34 days after the event. CONCLUSIONS: Attention was focused on the decision to initiate VV-ECMO support even in the presence of severe hemodynamic derangement, although VA-ECMO could have provided better hemodynamic support but less effective respiratory support.

Machine-Learning Based Determination of Gait Events from Foot-Mounted Inertial Units.

A promising but still scarcely explored strategy for the estimation of gait parameters based on inertial sensors involves the adoption of machine learning techniques. However, existing approaches are reliable only for specific conditions, inertial measurements unit (IMU) placement on the body, protocols, or when combined with additional devices. In this paper, we tested an alternative gait-events estimation approach which is fully data-driven and does not rely on a priori models or assumptions. High-frequency (512 Hz) data from a commercial inertial unit were recorded during 500 steps performed by 40 healthy participants. Sensors' readings were synchronized with a reference ground reaction force system to determine initial/terminal contacts. Then, we extracted a set of features from windowed data labeled according to the reference. Two gray-box approaches were evaluated: (1) classifiers (decision trees) returning the presence of a gait event in each time window and (2) a classifier discriminating between stance and swing phases. Both outputs were submitted to a deterministic algorithm correcting spurious clusters of predictions. The stance vs. swing approach estimated the stride time duration with an average error lower than 20 ms and confidence bounds between ±50 ms. These figures are suitable to detect clinically meaningful differences across different populations.