Sequential administration of anti-complement component C5 eculizumab and type-2 anti-CD20 obinutuzumab for the treatment of early antibody-mediated rejection after kidney transplantation: A proof of concept.

Kidney transplant (KT) candidates with donor-specific antibodies (DSA) exhibit exceedingly high antibody-mediated rejection (ABMR) and allograft loss rates. Currently, treatment of ABMR remains an unmet clinical need. We report the use of the anti-C5 eculizumab and the type-2 anti-CD20 obinutuzumab in two patients with early ABMR.

Proposal of set-up standardization for general surgery procedures with the CMR Versius system, a new robotic platform: our initial experience.

Background: The article describes our initial experience using CMR Versius platform for several procedures in general surgery.

Methods: Between September 2022 and April 2023, seventy patients underwent robotic surgery in a multi-robotic referral center (San Paolo University Hospital, Milan, Italy). Three surgeons with only laparoscopic experience performed 24 cholecystectomies, 13 inguinal hernia repairs, 9 ventral hernia repairs, 7 right hemicolectomies, 11 left hemicolectomies, 1 sigmoidectomy, 1 ileocecal resection, 1 ventral rectopexy, 1 Nissen fundoplication, 1 total splenectomy, and 1 exploration with multiple biopsies.

Tunable quantum interferometer for correlated moiré electrons.

Magic-angle twisted bilayer graphene can host a variety of gate-tunable correlated states - including superconducting and correlated insulator states. Recently, junction-based superconducting moiré devices have been introduced, enabling the study of the charge, spin and orbital nature of superconductivity, as well as the coherence of moiré electrons in magic-angle twisted bilayer graphene. Complementary fundamental coherence effects-in particular, the Little-Parks effect in a superconducting ring and the Aharonov-Bohm effect in a normally conducting ring - have not yet been reported in moiré devices.

Hesitancy toward the Full COVID-19 Vaccination among Kidney, Liver and Lung Transplant Recipients in Italy.

Background: Coronavirus disease 2019 (COVID-19) vaccination hesitancy is a threat as COVID-19 vaccines have reduced both viral transmission and virus-associated mortality rates, particularly in high-risk subgroups. Solid organ transplant recipients (SOTRs) are particularly vulnerable, as the underlying causes of their organ failure and the chronic immunosuppression are associated with a lower immune response to COVID-19 vaccines, and with an excessive risk of death due to SARS-CoV-2 infection. We aimed to evaluate COVID-19 vaccination hesitancy and its reasons in a population of SOTRs.

Outcomes of Patients Receiving a Kidney Transplant or Remaining on the Transplant Waiting List at the Epicentre of the COVID-19 Pandemic in Europe: An Observational Comparative Study.

Since the declaration of the COVID-19 pandemic, the number of kidney transplants (KT) performed worldwide has plummeted. Besides the generalised healthcare crisis, this unprecedented drop has multiple explanations such as the risk of viral transmission through the allograft, the perceived increase in SARS-CoV-2-related morbidity and mortality in immunocompromised hosts, and the virtual "safety" of dialysis while awaiting effective antiviral prophylaxis or treatment. Our institution, operating at the epicentre of the COVID-19 pandemic in Italy, has continued the KT programme without pre-set limitations.

Allograft Vesicoureteral Reflux after Kidney Transplantation.

Allograft vesicoureteral reflux (VUR) is a leading urological complication of kidney transplantation. Despite the relatively high incidence, there is a lack of consensus regarding VUR risk factors, impact on renal function, and management. Dialysis vintage and atrophic bladder have been recognized as the most relevant recipient-related determinants of post-transplant VUR, whilst possible relationships with sex, age, and ureteral implantation technique remain debated.

COVID-19 Infection in Kidney Transplant Patients: An Italian One Year Single Centre Experience.

COVID-19 is a life-threatening infection among elderly patients, comorbid patients, or transplanted patients. Lombardy (region of Italy), accounts for 786,324 cases as of 21 April 2021. We retrospectively describe our single Centre experience in 82 adult kidney-transplant patients with COVID-19 infection during two pandemic outbreaks: 27 (first outbreak) and 65 (second outbreak).

The atypical small GTPase GEM/Kir is a negative regulator of the NADPH oxidase and NETs production through macroautophagy.

Despite the important function of neutrophils in the eradication of infections and induction of inflammation, the molecular mechanisms regulating the activation and termination of the neutrophil immune response is not well understood. Here, the function of the small GTPase from the RGK family, Gem, is characterized as a negative regulator of the NADPH oxidase through autophagy regulation. Gem knockout (Gem KO) neutrophils show increased NADPH oxidase activation and increased production of extracellular and intracellular reactive oxygen species (ROS).

Treatment options for localised renal cell carcinoma of the transplanted kidney.

Currently, there is no consensus among the transplant community about the treatment of renal cell carcinoma (RCC) of the transplanted kidney. Until recently, graftectomy was universally considered the golden standard, regardless of the characteristics of the neoplasm. Due to the encouraging results observed in native kidneys, conservative options such as nephron-sparing surgery (NSS) (enucleation and partial nephrectomy) and ablative therapy (radiofrequency ablation, cryoablation, microwave ablation, high-intensity focused ultrasound, and irreversible electroporation) have been progressively used in carefully selected recipients with early-stage allograft RCC.

Allograft artery mycotic aneurysm after kidney transplantation: A case report and review of literature.

Background: Allograft artery mycotic aneurysm (MA) represents a rare but life-threatening complication of kidney transplantation. Graftectomy is widely considered the safest option. Due to the rarity of the disease and the substantial risk of fatal consequences, experience with conservative strategies is limited.

Forty years in the making: understanding the molecular mechanism of peptide regulation in bacterial development.

Signal transduction systems are influenced by positive and negative forces resulting in an output reflecting the sum of the opposing forces. The Rap family of regulatory protein modules control the output of two-component signal transduction systems through protein∶protein and protein∶peptide interactions. These modules and their peptide regulators are found in complex signaling pathways, including the bacterial developmental pathway to sporulation, competence, and protease secretion.

Bacillus subtilis RapA phosphatase domain interaction with its substrate, phosphorylated Spo0F, and its inhibitor, the PhrA peptide.

Rap proteins in Bacillus subtilis regulate the phosphorylation level or the DNA-binding activity of response regulators such as Spo0F, involved in sporulation initiation, or ComA, regulating competence development. Rap proteins can be inhibited by specific peptides generated by the export-import processing pathway of the Phr proteins. Rap proteins have a modular organization comprising an amino-terminal alpha-helical domain connected to a domain formed by six tetratricopeptide repeats (TPR).

Role of net charge on catalytic domain and influence of cell wall binding domain on bactericidal activity, specificity, and host range of phage lysins.

The recombinant lysins of lytic phages, when applied externally to Gram-positive bacteria, can be efficient bactericidal agents, typically retaining high specificity. Their development as novel antibacterial agents offers many potential advantages over conventional antibiotics. Protein engineering could exploit this potential further by generating novel lysins fit for distinct target populations and environments.

Transcription antitermination by a phosphorylated response regulator and cobalamin-dependent termination at a B₁₂ riboswitch contribute to ethanolamine utilization in Enterococcus faecalis.

The ability of bacteria to utilize ethanolamine (EA) as a carbon and nitrogen source may confer an advantage for survival, colonization, and pathogenicity in the human intestinal tract. Enterococcus faecalis, a Gram-positive human commensal organism, depends on a two-component signaling system (TCS-17) for sensing EA and regulating the expression of the ethanolamine utilization genes. Multiple promoters participate in eut gene expression in the presence of EA as the sole carbon source and cobalamin (CoB12), an essential cofactor in the enzymatic degradation process.

Enterococcus faecalis virulence regulator FsrA binding to target promoters.

The FsrABDC signal transduction system is a major virulence regulator in Enterococcus faecalis. The FsrC sensor histidine kinase, upon activation by the gelatinase biosynthesis-activating pheromone (GBAP) peptide encoded by the fsrBD genes, phosphorylates the FsrA response regulator required for the transcription of the fsrBDC and the gelE-sprE genes from the fsrB promoter and the gelE promoter, respectively. FsrA belongs to the LytTR family of proteins, which includes other virulence regulators, such as AgrA of Staphylococcus aureus, AlgR of Pseudomonas aeruginosa, and VirR of Clostridium perfringens.

Structural insights into inhibition of Bacillus anthracis sporulation by a novel class of non-heme globin sensor domains.

Pathogenesis by Bacillus anthracis requires coordination between two distinct activities: plasmid-encoded virulence factor expression (which protects vegetative cells from immune surveillance during outgrowth and replication) and chromosomally encoded sporulation (required only during the final stages of infection). Sporulation is regulated by at least five sensor histidine kinases that are activated in response to various environmental cues. One of these kinases, BA2291, harbors a sensor domain that has ∼35% sequence identity with two plasmid proteins, pXO1-118 and pXO2-61.

Glucose-dependent activation of Bacillus anthracis toxin gene expression and virulence requires the carbon catabolite protein CcpA.

Sensing environmental conditions is an essential aspect of bacterial physiology and virulence. In Bacillus anthracis, the causative agent of anthrax, transcription of the two major virulence factors, toxin and capsule, is triggered by bicarbonate, a major compound in the mammalian body. Here it is shown that glucose is an additional signaling molecule recognized by B.

NMR solution structure and DNA-binding model of the DNA-binding domain of competence protein A.

Competence protein A (ComA) is a response regulator protein involved in the development of genetic competence in the Gram-positive spore-forming bacterium Bacillus subtilis, as well as the regulation of the production of degradative enzymes and antibiotic synthesis. ComA belongs to the NarL family of proteins, which are characterized by a C-terminal transcriptional activator domain that consists of a bundle of four helices, where the second and third helices (alpha 8 and alpha 9) form a helix-turn-helix DNA-binding domain. Using NMR spectroscopy, the high-resolution 3D solution structure of the C-terminal DNA-binding domain of ComA (ComAC) has been determined.

Lung epithelial injury by B. anthracis lethal toxin is caused by MKK-dependent loss of cytoskeletal integrity.

Bacillus anthracis lethal toxin (LT) is a key virulence factor of anthrax and contributes significantly to the in vivo pathology. The enzymatically active component is a Zn(2+)-dependent metalloprotease that cleaves most isoforms of mitogen-activated protein kinase kinases (MKKs). Using ex vivo differentiated human lung epithelium we report that LT destroys lung epithelial barrier function and wound healing responses by immobilizing the actin and microtubule network.

Two small c-type cytochromes affect virulence gene expression in Bacillus anthracis.

Regulated expression of the genes for anthrax toxin proteins is essential for the virulence of the pathogenic bacterium Bacillus anthracis. Induction of toxin gene expression depends on several factors, including temperature, bicarbonate levels, and metabolic state of the cell. To identify factors that regulate toxin expression, transposon mutagenesis was performed under non-inducing conditions and mutants were isolated that untimely expressed high levels of toxin.

The bicarbonate transporter is essential for Bacillus anthracis lethality.

In the pathogenic bacterium Bacillus anthracis, virulence requires induced expression of the anthrax toxin and capsule genes. Elevated CO2/bicarbonate levels, an indicator of the host environment, provide a signal ex vivo to increase expression of virulence factors, but the mechanism underlying induction and its relevance in vivo are unknown. We identified a previously uncharacterized ABC transporter (BAS2714-12) similar to bicarbonate transporters in photosynthetic cyanobacteria, which is essential to the bicarbonate induction of virulence gene expression.

A unique GTP-dependent sporulation sensor histidine kinase in Bacillus anthracis.

The Bacillus anthracis BA2291 gene codes for a sensor histidine kinase involved in the induction of sporulation. Genes for orthologs of the sensor domain of the BA2291 kinase exist in virulence plasmids in this organism, and these proteins, when expressed, inhibit sporulation by converting BA2291 to an apparent phosphatase of the sporulation phosphorelay. Evidence suggests that the sensor domains inhibit BA2291 by titrating its activating signal ligand.