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Recently published near full-length KSHV genomes from a Cameroon Kaposi sarcoma case-control study showed strong evidence of viral recombination and mixed infections, but no sequence variations associated with disease. Using the same methodology, an additional 102 KSHV genomes from 76 individuals with KSHV-associated diseases have been sequenced. Diagnoses comprise all KSHV-associated diseases (KAD): Kaposi sarcoma (KS), primary effusion lymphoma (PEL), KSHV-associated large cell lymphoma (KSHV-LCL), a type of multicentric Castleman disease (KSHV-MCD), and KSHV inflammatory cytokine syndrome (KICS). Participants originated from 22 different countries, providing the opportunity to obtain new near full-length sequences of a wide diversity of KSHV genomes. These include near full-length sequence of genomes with KSHV K1 subtypes A, B, C, and F as well as subtype E, for which no full sequence was previously available. High levels of recombination were observed. Fourteen individuals (18%) showed evidence of infection with multiple KSHV variants (from two to four unique genomes). Twenty-six comparisons of sequences, obtained from various sampling sites including PBMC, tissue biopsies, oral fluids, and effusions in the same participants, identified near complete genome conservation between different biological compartments. Polymorphisms were identified in coding and non-coding regions, including indels in the K3 and K15 genes and sequence inversions here reported for the first time. One such polymorphism in KSHV ORF46, specific to the KSHV K1 subtype E2, encoded a mutation in the leucine loop extension of the uracil DNA glycosylase that results in alteration of biochemical functions of this protein. This confirms that KSHV sequence variations can have functional consequences warranting further investigation. This study represents the largest and most diverse analysis of KSHV genome sequences to date among individuals with KAD and provides important new information on global KSHV genomics. Author summary: The prevalence of KSHV infection, one of eight viruses associated with human cancer, differs geographically as does the incidence of Kaposi sarcoma and other KSHV-associated diseases. Distribution of KSHV subtypes, defined solely by the sequence of the K1 gene, also differs by region. One hundred and two near full-length KSHV genomes from people with associated diseases from a wide variety of countries were sequenced, substantially increasing the number and diversity of KSHV genomes publicly available, thereby allowing the analysis of variance across geographical regions, potential contributions of viral genetics to the risk of disease, and viral evolution. Our data demonstrate that viral recombination is common, as previously published, and that infections with multiple KSHV genomes may also be frequent, which has not been widely reported. We did not find evidence of an association between viral subtypes and disease nor indications that different sampling sites from the same individual, including tumor specimens, harbored substantially different KSHV genomes. Our data significantly inform the current efforts to study epidemiology and the prevention of KSHV infection, including vaccine development, as well as the pathogenesis of associated diseases. [ABSTRACT FROM AUTHOR]

Background: Radial height is a radiographic parameter used to guide the treatment of distal radius fractures. However, it is often used synonymously with other terms, and there are substantial discrepancies in its measurement/definition. These discrepancies can alter the measurement of radial height and affect treatment decisions. The purpose of this review is to identify the different definitions of radial height in the literature relevant to distal radius fractures. Methods: A literature review was conducted in the PubMed/MEDLINE database from inception to 2022. Full-length, English-language studies that pertained to distal radius fractures and reported radial height as a recorded measurement were included. The method of radial height measurement (definition) was extracted from included studies. Level of evidence was determined by the Oxford Centre for Evidence-based Medicine Levels of Evidence tool. Results: A total of 385 studies were identified. Of these, 183 (47.5%) did not provide a definition for radial height. Of the studies that defined radial height, 50.9% (103/202) measured radial height from the radial styloid to the distal ulna, 10.9% (22/202) measured from the radial styloid to the distal radius, and 29.2% (59/202) were "other" definitions. Conclusions: There is substantial discrepancy in the way that radial height is measured and reported. We advocate for a standardized measurement of radial height (synonymous with radial length) from the radial styloid to the distal ulnar articular surface. Radial shortening is a different measurement and requires comparison with a reference value. [ABSTRACT FROM AUTHOR]

Resident memory T cells (TRMs), which are memory T cells that are retained locally within tissues, have recently been described as antigen-specific frontline defenders against pathogens in barrier and nonbarrier epithelial tissues. They have also been noted for perpetuating chronic inflammation. The conditions responsible for TRM differentiation are still poorly understood, and their contributions, if any, to sterile models of chronic kidney disease (CKD) remain a mystery. In this study, we subjected male C57BL/6J mice and OT-1 transgenic mice to five consecutive days of 2 mg/kg aristolochic acid (AA) injections intraperitoneally to induce CKD or saline injections as a control. We evaluated their kidney immune profiles at 2 wk, 6 wk, and 6 mo after treatment. We identified a substantial population of TRMs in the kidneys of mice with AA-induced CKD. Flow cytometry of injured kidneys showed T cells bearing TRM surface markers and single-cell (sc) RNA sequencing revealed these cells as expressing well-known TRM transcription factors and receptors responsible for TRM differentiation and maintenance. Although kidney TRMs expressed Cd44, a marker of antigen experience and T cell activation, their derivation was independent of cognate antigen-T cell receptor interactions, as the kidneys of transgenic OT-1 mice still harbored considerable proportions of TRMs after injury. Our results suggest a nonantigen-specific or antigen-independent mechanism capable of generating TRMs in the kidney and highlight the need to better understand TRMs and their involvement in CKD. [ABSTRACT FROM AUTHOR]

Adult learning, critical thinking, and decision-making are fields that receive attention individually, although they are interspersed with elements of each other's theories and philosophies. In addressing adult learning precepts, it is essential to include critical thinking and decision-making. One without the other creates weakness; all must be present if learning is to be effective and rewarding. This composition provides subject matter expert definitions of adult learning, critical thinking, and decision-making and then identifies the related elements. The piece also accentuates how those responsible for teaching adults must facilitate the union of adult learning, critical thinking, and decision-making.

Summary: A biopsy of lymphoid tissue is currently required to diagnose Kaposi sarcoma‐associated herpesvirus (KSHV)‐associated multicentric Castleman disease (KSHV–MCD). Patients showing clinical manifestations of KSHV–MCD but no pathological changes of KSHV–MCD are diagnosed as KSHV inflammatory cytokine syndrome. However, a lymph node biopsy is not always feasible to make the distinction. A pathognomonic feature of lymph nodes in KSHV–MCD is the expansion of KSHV‐infected, lambda‐restricted but polyclonal plasmablasts. To investigate whether these cells also reside in extra‐nodal sites, effusion from 11 patients with KSHV–MCD and 19 with KSHV inflammatory cytokine syndrome was analysed by multiparametric flow cytometry. A distinct, lambda‐restricted plasmablastic population (LRP) with highly consistent immunophenotype was detected in effusions in 8/11 patients with KSHV–MCD. The same population was also observed in 7/19 patients with KSHV inflammatory cytokine syndrome. The detection of LRP stratified KSHV inflammatory cytokine syndrome into two clinically distinct subgroups; those with detectable LRP closely resembled KSHV–MCD, showing similar KSHV viral load, comparable severity of thrombocytopenia and hypoalbuminaemia, and similar incidences of hepatosplenomegaly. Collectively, the detection of LRP by flow cytometry can serve as a valuable tool in diagnosing KSHV–MCD. KSHV inflammatory cytokine syndrome with LRP in effusions may represent a liquid‐form of KSHV–MCD. [ABSTRACT FROM AUTHOR]