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Transplant patients, including solid-organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, are exposed to various types of complications, particularly rejection. To prevent these outcomes, transplant recipients commonly receive long-term immunosuppressive regimens that in turn make them more susceptible to a wide array of infectious diseases, notably those caused by opportunistic pathogens. Among these, invasive fungal infections (IFIs) remain a major cause of mortality and morbidity in both SOT and HSCT recipients. Despite the continuing improvement in early diagnostics and treatments of IFIs, the management of these infections in transplant patients is still complicated. Here, we provide an overview concerning the most recent trends in the epidemiology of IFIs in SOT and HSCT recipients by describing the prominent yeast and mold species involved, the timing of post-transplant IFIs and the risk factors associated with their occurrence in these particularly weak populations. We also give special emphasis into basic research advances in the field that recently suggested a role of the global and long-term prophylactic regimen in orchestrating various biological disturbances in the organism and conditioning the emergence of the most adapted fungal strains to the particular physiological profiles of transplant patients.

Rheumatoid arthritis (RA) is a systemic autoimmune disease during which fibroblast-like synoviocytes (FLS) contribute to both joint inflammation and destruction. FLS represent the core component of the synovial membrane. Following inflammation of this membrane, an effusion of cell-rich synovial fluid (SF) fills the joint cavity. Unlikely, SF has been shown to contain fibroblasts with some shared phenotypic traits with the synovial membrane FLS. These cells are called SF-FLS and their origin is still unclear. They are either brought into the synovium via migration through blood vessels, or they could originate within the synovium and exist in projections of the synovial membrane. SF-FLS function and phenotype are poorly documented compared to recently well-characterized synovial membrane FLS subsets. Furthermore, no study has yet reported a SF-FLS single-cell profiling analysis. This review will discuss the origin and cellular characteristics of SF-FLS in patients with RA. In addition, recent advances on the involvement of SF-FLS in the pathogenesis of RA will be summarized. Current knowledge on possible relationships between SF-FLS and other types of fibroblasts, including synovial membrane FLS, circulating fibrocytes, and pre- inflammatory mesenchymal (PRIME) cells will also be addressed. Finally, recent therapeutic strategies employed to specifically target SF-FLS in RA will be discussed.

Tissue derived fibroblast-like synoviocytes (td-FLS) are key actors in pannus formation and contribute to joint destruction and inflammation during rheumatoid arthritis (RA). Several members of the Wnt family, including Wnt5a, may contribute to RA td-FLS activation and can potentially serve as therapeutic targets. The present work aimed to investigate the expression of Wnt5a signaling elements in RA td-FLS and their potential precursors (fluid derived (fd) FLS and fibrocytes). We also studied the role of Wnt5a in RA td-FLS pro-inflammatory activity and whether the inhibitor SFRP5 could restore Wnt5a-induced synovial dysfunction . The levels of Wnt5a, SFRP5, Wnt5a receptors/coreceptors and Wnt5a pro-inflammatory targets were determined in cultured RA td-FLS, fd-FLS and fibrocytes using qPCR under basal conditions. The expression of pro-inflammatory molecules was assessed after RA td-FLS stimulation with Wnt5a and SFRP5 at different time points. Our data showed that td-FLS, fd-FLS and fibrocytes from patients with RA expressed similar levels of Wnt5a and a set of Wnt5a receptors/coreceptors. We also demonstrated that Wnt5a stimulated the expression of the pro-inflammatory targets, especially IL1β, IL8 and IL6 in RA td-FLS. Wnt5a-induced inflammation was enhanced in the presence of SFRP5. Furthermore, Wnt5a alone and in conjunction with SFRP5 inhibited the gene expression of TCF4 and the protein levels of the canonical coreceptor LRP5. Wnt5a pro-inflammatory effect is not inhibited but enhanced by SFRP5 in RA td-FLS. This research highlights the importance of carefully evaluating changes in Wnt5a response in the presence of SFRP5.

Transplant patients, including solid-organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, are exposed to various types of complications, particularly rejection. To prevent these outcomes, transplant recipients commonly receive long-term immunosuppressive regimens that in turn make them more susceptible to a wide array of infectious diseases, notably those caused by opportunistic pathogens. Among these, invasive fungal infections (IFIs) remain a major cause of mortality and morbidity in both SOT and HSCT recipients. Despite the continuing improvement in early diagnostics and treatments of IFIs, the management of these infections in transplant patients is still complicated. Here, we provide an overview concerning the most recent trends in the epidemiology of IFIs in SOT and HSCT recipients by describing the prominent yeasts and molds species involved, the timing of post-transplant IFIs and the risk factors associated with their occurrence in these particularly weak populations. We also give special emphasis into basic research advances in the field that recently suggested a role of the global and long-term prophylactic regimen in orchestrating various biological disturbances in the organism and conditioning the emergence of the most adapted fungal strains to the particular physiological profiles of transplant patients.

Chondrocyte hypertrophic differentiation, a key process in endochondral ossification (EO), is also a feature of osteoarthritis leading to articular cartilage destruction. ShcA (Src homology and Collagen A) is an adaptor protein that binds to the cytoplasmic tail of receptor tyrosine kinases. We found that deletion of ShcA in chondrocytes of mice inhibits hypertrophic differentiation, alters the EO process, and leads to dwarfism. ShcA promotes ERK1/2 activation, nuclear translocation of the master transcription factor for chondrocyte hypertrophy, RunX2, while maintaining the Runx2 inhibitor YAP1 in its cytosolic inactive form. This leads to hypertrophic commitment and expression of markers of hypertrophy, such as Collagen X. In addition, ShcA deletion in chondrocytes protects from age-related osteoarthritis development in mice. Our results reveal that ShcA integrates multiple stimuli which affect the intracellular signaling processes leading to the hypertrophic commitment of chondrocytes and osteoarthritis. Competing Interest Statement The authors have declared no competing interest.

A systematic review and meta-analysis were carried out involving studies that compared the nutritional complications of Roux-en-Y gastric bypass (RYGB) and one-anastomosis gastric bypass (OAGB); these included the incidence of malnutrition as well as deficiencies of other nutritional elements, such as total protein, albumin, calcium and iron. A comprehensive search strategy was implemented in PubMed, Embase, and the Cochrane Library. Effect sizes included the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs), as well as mean differences (MDs) and 95% CIs of the percentage total weight loss (%TWL) and excess weight loss percentage (%EWL). Thirteen studies were included (12,964 patients, 66.27% females, 53.82% underwent OAGB). At the longest follow-up period (≥3 years), OAGB was associated with significantly higher %TWL (MD=5.41%, 95%CI, 1.52 to 9.29) and %EWL (MD=13.81%, 95%CI, 9.60 to 18.02) compared to RYGB. However, OAGB procedures were associated with malnutrition (OR=3.00, 95%CI, 1.68 to 5.36, p<0.0001), hypoalbuminemia (OR=2.38, 95%CI, 1.65 to 3.43, p<0.0001), hypoproteinemia (OR=1.85, 95%CI, 1.09 to 3.14, p=0.022), anemia (OR=1.38, 95%CI, 1.08 to 1.77, p=0.011), and hypocalcemia (OR=1.78, 95%CI, 1.01 to 3.12, p=0.046). On subgroup analyses, the proportions of anemia and hypoalbuminemia remained significantly higher at longer follow-up periods and in studies published in Asia. Despite the favorable weight loss profile, the unfavorable nutritional consequences of OAGB merits further investigations to explore the malabsorptive element, ethnic variation, and the role of biliopancreatic limb length.