Towards a new WHO classification of renal cell tumor: what the clinician needs to know—a narrative review

In 1952, renal cell carcinomas had been divided into 2 categories—clear cell or granular cell—depending upon their cytoplasmic staining characteristics. In the following years, the inventory of renal epithelial tumors has expanded by the addition of tumors named by their architectural pattern (i.e., papillary RCC, tubulocystic RCC), anatomic location (i.e., collecting duct carcinoma, renal medullary carcinoma), associated diseases (i.e., acquired cystic disease-associated RCCs). With the extensive application of molecular diagnostic techniques, it becomes possible to detect genetic distinctions between various types of renal neoplasm and discover new entities, otherwise misdiagnosed or diagnosed as unclassified RCC. Some tumors such as ALK rearrangement-associated RCC, MiT family translocation renal carcinomas, SDH-deficient renal cancer or FH-deficient RCC, are defined by their molecular characteristics. The most recent World Health Organization (WHO) classification of renal neoplasms account for more than 50 entities and provisional entities. New entities might be included in the upcoming WHO classification. The aim of this review is to summarise and discuss the newly acquired data and evidence on the clinical, pathological, molecular features and on the prognosis of new RCC entities, which will hopefully increase the awareness and the acceptance of these entities among clinicians and improve prognostication for individual patients.     

Validation of a screening test for alcohol use,the Russian Federation

ObjectiveTo validate a Russian-language version of the World Health Organization’s Alcohol Use Disorders Identification Test (AUDIT).MethodsWe invited 2173 patients from 21 rural and urban primary health-care centres in nine Russian regions to participate in the study (143 declined and eight were excluded). In a standardized interview, patients who had consumed alcohol in the past 12 months provided information on their sociodemographic characteristics and completed the Russian AUDIT, the Kessler Psychological Distress Scale and the Composite International Diagnostic Interview to identify problem drinking and alcohol use disorders. We assessed the feasibility of administering the test, its internal consistency and its ability to predict hazardous drinking and alcohol use disorders in primary health care in the Russian Federation.FindingsOf the 2022 patients included in the study, 1497 were current drinkers with Russian AUDIT scores. The test was internally consistent with good psychometric properties (Cronbach’s α : 0.842) and accurately predicted alcohol use disorders and other outcomes (area under the curve > 75%). A three-item short form of the test correlated well with the full instrument and had similar predictive power (area under the curve > 80%). We determined sex-specific thresholds for all outcomes, as non-specific thresholds resulted in few women being identified.ConclusionWith the validated Russian AUDIT, there is no longer a barrier to introducing screening and brief interventions into primary health care in the Russian Federation to supplement successful alcohol control policies.     

COVID-19 pandemic reduces the negative perception of oral health-related quality of life in adolescents

Quality of Life Research - As people around the world are facing the Covid-19 outbreak, their perception of oral health problems could be changed. This study aimed to evaluate the immediate effects...     

An image-based modeling framework for patient-specific computational hemodynamics

We present a modeling framework designed for patient-specific computational hemodynamics to be performed in the context of large-scale studies. The framework takes advantage of the integration of image processing, geometric analysis and mesh generation techniques, with an accent on full automation and high-level interaction. Image segmentation is performed using implicit deformable models taking advantage of a novel approach for selective initialization of vascular branches, as well as of a strategy for the segmentation of small vessels. A robust definition of centerlines provides objective geometric criteria for the automation of surface editing and mesh generation. The framework is available as part of an open-source effort, the Vascular Modeling Toolkit, a first step towards the sharing of tools and data which will be necessary for computational hemodynamics to play a role in evidence-based medicine.     

Assembly of targeting complexes driven by a single-chain antibody

Rapid development in design and production of recombinant antibodies and antibody fragments specific for cell surface markers opens new opportunities for targeted delivery of therapeutic or imaging agents. However, the progress in this field is slowed by inactivation of many antibodies by chemical conjugation of payloads and by lack of internalization of complexes formed on the cell surface. Here, we describe conversion of a non-internalizing single chain Fv (scFv) antibody P4G7 specific for vascular endothelial growth factor receptor 2 (VEGFR-2) into a targeting protein (Hu-P4G7) for assembly of a novel type of targeting complexes. Hu-P4G7 contains an N-terminal "docking" Hu-tag, a 15-aa fragment of human RNase I, capable of high affinity binding of S-protein fragment of human RNase I or bovine RNase A. Purified Hu-P4G7 and complexes of Hu-P4G7 with S-protein bind both soluble and full-length cellular VEGFR-2. To assemble targeted DNA delivery complexes, S-protein modified with a DNA condensing agent was "docked" to Hu-P4G7, and then loaded with luciferase plasmid DNA. As expected for a non-internalizing targeting protein, Hu-P4G7-based complexes did not deliver DNA in VEGFR-2 expressing cells. However, in the presence of vascular endothelial growth factor (VEGF), these complexes selectively delivered DNA into the cells overexpressing VEGFR-2 suggesting that even a non-internalizing scFv antibody can be used for targeted intracellular drug delivery.     

Technical basis for magnetic resonance images

The spin-echo procedure is the basic technique in a magnetic resonance (MR) study (the magnetization vector is flipped by 90° onto the ortogonal plane to the main magnetic field). Very soon after the MR procedure was developed, it was pointed out how important it is to achieve the needed contrast with shorter repetition times (TRs) to reduce the imaging time. Recently, fast imaging techniques have been introduced (partial flip angles, short TRs, and the lack of 180° radiofrequency pulses to refocus the spins are their main characteristics; the spins are refocused by the application of a gradient reversal technique). These techniques are particularly needed in pediatric neuroradiology, where the examination time must be as short as possible. At present, partial flip-angle techniques are almost completely replacing the conventional spin-echo procedure, but the variations in flip angle could result in a change in contrast. For these reasons, conventional spin-echo techniques may still be useful in a routine MR study.Presented at the 11th Meeting of the European Society for Paediatric Neurosurgery, Naples 1988     

Pharmacokinetics of the antitumor antibiotic n-pentyl-sparsomycin in beagle dogs

Summary N-pentyl-sparsomycin (PSm) is a lipophilic analogue of sparsomycin (Sm), which is a well known inhibitor of protein synthesis. This compound was selected for preclinical pharmacokinetic studies because of its high in vitro and in vivo antitumor activity. In this study in which the drug was evaluated in beagle dogs under anaesthesia, the drug concentrations in plasma, urine and bile samples were determined using high performance liquid chromatography (HPLC). Plasma protein binding was approximately 54%. The mean t1/2 was 0.2 hours (12 minutes) and t1/2 was 0.75 ± 0.1 hours (45 ± 6 minutes). During continuous infusions up to 5.25 hours, the steady state was reached in 3 out of 6 experiments, suggesting that in some cases the real t1/2 was longer than measured. PSm was actively reabsorbed from the renal tubuli. This process was saturable at the higher doses. Tubular reabsorption played only a minor role in pharmacokinetics as most of the drug (67%) was eliminated by the non-renal clearance. The non-renal clearance was saturable at higher doses of PSm and was the reason for non-linearity of pharmacokinetics.     

Chlorhexidine susceptibility and Eagle effect in planktonic cells and biofilm of nosocomial isolates

European Journal of Clinical Microbiology & Infectious Diseases - The aim of this study is to evaluate the chlorhexidine gluconate (CHG) susceptibility in both planktonic cells and biofilm of...     

Mechanism underlying superantigen-induced clonal deletion of mature T lymphocytes

We observed that peripheral T cells activated in vivo or invitro by superantigens are susceptible to cell death when theirantigen receptor is cross-linked with the appropriate anti-ßTCR mAb. TCR ligation by mAbs specifically drove the T cellclonal deletion in both CD4⁺ and CD8⁺ cell subsets. An IL-2/1L-2Rinteraction seems to be a critical step In predisposing superantigenactivated cells to death; In fact, in vivo IL-2R bockade reversedT cell deletion In superantlgen plus anti-ß TCR mAbtreated mice. TCR ligatlon by mAbs also produced cell deathof the relevant targets in in vitro IL-2 activated T cells.Surprisingly, no T cell deletion was demonstrable in IL-2 activatedcells following staphylococcal enterotoxin B - TCR Interaction,ruling out the possibility that superantigen in Itself can inducecell death. Thus, while superantigen activation opens the celldeath program, a subsequent TCR-antigen (self) Interaction appearsnecessary to produce clonal deletion in mature T lymphocytes.