Humoral and T-Cell Mediated Response after the Third Dose of mRNA Vaccines in Patients with Systemic Lupus Erythematosus on Belimumab

Objective: To evaluate humoral and T-cell cellular-mediated immune response after three doses of SARS-CoV-2 mRNA vaccines in patients with systemic lupus erythematosus (SLE) under Belimumab. Patients and methods: 12 patients on Belimumab and 13 age-matched healthy volunteers were recruited. Patients were in remission or in low disease activity, and they were taking no corticosteroids or only low doses. None of the patients and controls had detectable anti-SARS-CoV-2 antibodies due to previous exposure to the virus. All the patients received three doses of mRNA anti-SARS-CoV-2 vaccines and the humoral and cellular-mediated response were tested 4 weeks after the second dose (T0), 6 months after the second dose (T1) and 4 weeks after the third dose (T2). Comparison with the control group was performed at time T0 (i.e., 4 weeks after the second dose). Total anti-SARS-CoV-2 RBD antibodies were analyzed using a diagnostic assay, while cellular-mediated response was evaluated using the interferon-gamma release assay (IGRA). Results: A humoral response was documented in all the patients at T0 (median 459; IQR 225.25–758.5), but the antibody titer significantly declined from T0 to T1 (median 44.7; IQR: 30.3–202; p = 0.0066). At T2, the antibody titer significantly increased from T1 (median 2500; IQR: 2500–2500), and it was not different from T0 (respectively p < 0.0001, p = 0.66). Cellular-mediated response significantly declined from T0 to T1 (p = 0.003) but not from T0 to T2 (p = 0.3). No differences were found between patients and controls at T0 as regards both humoral and cellular responses (p = 1.0 and p = 0.09 for humoral and cellular responses, respectively). Conclusion: The third dose of mRNA COVID-19 vaccine can restore both humoral and cellular immune response in SLE patients on Belimumab

Nodavirus colonizes and replicates in the testis of gilthead seabream and European sea bass modulating its immune and reproductive functions

Viruses are threatening pathogens for fish aquaculture. Some of them are transmitted through gonad fluids or gametes as occurs with nervous necrosis virus (NNV). In order to be transmitted through the gonad, the virus should colonize and replicate inside some cell types of this tissue and avoid the subsequent immune response locally. However, whether NNV colonizes the gonad, the cell types that are infected, and how the immune response in the gonad is regulated has never been studied. We have demonstrated for the first time the presence and localization of NNV into the testis after an experimental infection in the European sea bass (Dicentrarchus labrax), and in the gilthead seabream (Sparus aurata), a very susceptible and an asymptomatic host fish species, respectively. Thus, we localized in the testis viral RNA in both species using in situ PCR and viral proteins in gilthead seabream by immunohistochemistry, suggesting that males might also transmit the virus. In addition, we were able to isolate infective particles from the testis of both species demonstrating that NNV colonizes and replicates into the testis of both species. Blood contamination of the tissues sampled was discarded by completely fish bleeding, furthermore the in situ PCR and immunocytochemistry techniques never showed staining in blood vessels or cells. Moreover, we also determined how the immune and reproductive functions are affected comparing the effects in the testis with those found in the brain, the main target tissue of the virus. Interestingly, NNV triggered the immune response in the European sea bass but not in the gilthead seabream testis. Regarding reproductive functions, NNV infection alters 17β-estradiol and 11-ketotestosterone production and the potential sensitivity of brain and testis to these hormones, whereas there is no disruption of testicular functions according to several reproductive parameters. Moreover, we have also studied the NNV infection of the testis in vitro to assess local responses. Our in vitro results show that the changes observed on the expression of immune and reproductive genes in the testis of both species are different to those observed upon in vivo infections in most of the casesMINECO and FEDER (AGL2010-20801-C02-01; AGL2010-20801-C02-02; AGL2013-43588-P); Fundación Séneca (04538/GERM/06)Versión del editor4,411

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Needle tract seeding after percutaneous cryoablation of small renal masses; a case series and literature review

Neoplastic cell seeding due to needle tumor manipulation during renal mass biopsy (RMB) or thermal ablative treatment is a rare but potentially serious event that can turn an organ-confined and curable tumor in a nonorgan-confined and non-curable disease. Despite the widespread use of percutaneous thermal ablative treatment for small renal masses (SRMs), this complication has been described in few case reports and small case series and has never been reported after ablative treatment alone. We report a series of two patients that underwent cryoablation for SRMs and developed recurrence along the needle tract. Available knowledge on the controversial topic of tumor seeding following needle manipulation are poor. So far, reporting cases of tumor cell seeding due to needle manipulation is useful to permit a better understanding of this complication

Energy consumption and water-soluble protein release by cell wall disruption of Nannochloropsis gaditana

Several cell disruption methods were tested on Nannochloropsis gaditana, to evaluate their efficiency in terms of cell disintegration, energy input and release of soluble proteins. High-pressure homogenization (HPH) and bead milling were the most efficient with >95% cell disintegration, ±50% (w/w) release of total proteins and low energy input (<0.5 kWh.kg−1 biomass). Enzymatic treatment required low energy input (<0.34 kWh.kg−1 biomass), but it only released ±35% protein (w/w). Pulsed Electric Field (PEF) was neither energy-efficient (10.44 kWh.kg−1 biomass) nor successful for protein release (only 10% proteins w/w) and cell disintegration. The release of proteins after applying HPH and bead milling always required less intensive operating conditions for cell disruption. The energy cost per unit of released protein ranged from 0.15–0.25 €.kgProtein −1 in case of HPH, and up to 2–20 €.kgProtein −1 in case of PEF

A case series of neoplastic seeding after cryoablative treatment for renal masses

Aim of the study: To report incidence of tumor cell seeding in patients with small renal masses who underwent percutaneous cryoablative treatment. Materials and methods: We retrospectively reviewed data stored in a prospectively maintained database of patients who underwent CT- guided percutaneous cryoablative treatment of SRMs in our tertiary referral center between June 2011 and February 2018. The resulting imagings were reviewed by our institutional multidisciplinary team with particular interest in cases of recurrences along the needle tract of the cryoprobe. Results: During the study period, 110 patients were treated using Perc- 17 probes (Galil Medical). 56 masses were histologically-proven malign RCC, 36 were benign lesions, in 8 cases biopsies were non- diagnostic and in 10 cases biopsy was avoided. Mean follow-up of the entire cohort was 31,04 months (IQR:12,5\u201339,8). 2 cases of needle tract seeding were identified during the follow-up. Case1: A 47-yo male presenting asymptomatic haematuria. CT scan revealed a 35 mm right complex cystic mass. Open NSS was performed without cystic rupture and a diagnosis of pT1a R0 Fuhrman G1 ccRCC was given. 2 years later the patient developed a 18 mm contrast-enhanced cyst, and under- went cryoablation treatment. No biopsy was performed to prevent the risk of cystic rupture. After 12 months, MRI revealed an intramuscular recurrence along the needle tract, which was surgical removed. A diagnosis of undifferentiated RCC was given. Patient developed metastatic disease in 3 months and despite additional treatment, the tumour induced death 6 months later. Case 2: A 72-yo male with solitary kidney for previous right RN (pRCC, type 1, 2002), diagnosed with left renal recurrence and treated with open NSS (2007, pRCC). In October 2017 the patient underwent cryoablative treatment for an inferior polar 14 mm mass. At 3 months follow-up CEUS and MRI demonstrated 3 solid lesions into perinephric fat, and lumbar muscle consistent with recurrences. Biopsy was obtained with a 20-gauge needle and sample was consistent with pRCC. Patient refused further surgical treatment. In January 2018, he underwent a percutaneous cryoablative treatment of the recurrences in an effort to preserve renal function. To date, no recurrence was detected. Discussion: Over the recent years, use of cryoablation for the treatment of small renal tumor is increasing and it is likely that this will rise further. This article\u2019s objective is absolutely not to deter clinicians from using cryoablation to treat SRMs. Cryoablation is helping patients and surgeons to avoid the concrete risks produced by surgery and anesthesia for unnecessary intervention. Nevertheless, unfortunately, tumor seeding seem not anecdotal as previously stated. Finally, we emphasize the importance of careful inspection of the perinephric fat, the posterior abdominal wall, the subcutaneous fat and other tissues along the ablation probe tract during oncological surveillance in order to treat possible cases of tumor seeding as early as possible

Synaptic transistors with aluminum oxide dielectrics enabling full audio frequency range signal processing

The rapid evolution of the neuromorphic computing stimulates the search for novel brain-inspired electronic devices. Synaptic transistors are three-terminal devices that can mimic the chemical synapses while consuming low power, whereby an insulating dielectric layer physically separates output and input signals from each other. Appropriate choice of the dielectric is crucial in achieving a wide range of operation frequencies in these devices. Here we report synaptic transistors with printed aluminum oxide dielectrics, improving the operation frequency of solution-processed synaptic transistors by almost two orders of magnitude to 50 kHz. Fabricated devices, yielding synaptic response for all audio frequencies (20 Hz to 20 kHz), are employed in an acoustic response system to show the potential for future research in neuro-acoustic signal processing with printed oxide electronics