Fulminant Cardiotoxicity in a Patient With Cardiac Lymphoma Treated With CAR-T Cells

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Sexually transmissible infections among young adolescents in Milan areas: a multicentre study

Objective: Sexually transmitted infections (STIs) are a major health problem affecting mostly young people, the exact magnitude of STIs is frequently unknown due to lack of country surveillance systems. Aim of this study was to determine the prevalence of STIs and relative risk factors among and adolescents in Milan areas, Italy. Methods: From May to October 2011, 117 adolescents (63 female, 54%), median age 15 years, attending hospitals from the north-western areas of Milan, Italy, were enrolled. All subjects completed a questionnaire and provided a urine sample, which was tested for Neisseria gonorrhea, Chlamidia trachomatis, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum/parvum, Trichomonas vaginalis, Treponema pallidum, Streptococcus agalatiae, Haemophylus ducrey, Citomegalovirus (CMV), Herpes Simplex Virus 1(HSV1) and Lymphogranuloma venereum by a multiplex PCR assay: Seeplex\uae STI Master ACE Detection (Seegene, Seoul, Korea). Forty tree out of 117 adolescents (36%) were HIV-1 positive, 63% (74/117) were without any underlying infectious disease. Results: Fifty seven (48,7%) out of 117 adolescent were sexually active (SA), 20 out of 57 (35%) had STIs as follow: 24.5% (14 cases) U.urealyticum/parvum, 7% (4cases) C.trachomatis, 1.7% (one case each) M. genitalium and N.gonorrhoea. Thirty-two (56%) out of 57 SA adolescents were HIV-1 positive and infected with U. urealyticum/parvum (37.5%, 12 cases) and C.trachomatis (6.2% 2 cases). A single case (3.1%) of mixed infection due to C.trachomatis, N.gonorrhoea and U.urealyticum/parvum was observed. Six out of 60 (10%) sexually inactive (SI) adolescents resulted positive for U.urealyticum/parvum (3 cases), C.trachomatis (2 cases) and N.gonorrhoea (1 case). Eleven out of 60 were HIV-1 positive and among this group one case of C.trachomatis and U.urealyticum/parvum infection was reported. For T.vaginalis, T. pallidum, S. agalatiae, H.ducrey, CMV, HSV1 and Lymphogranuloma venereum any infection was reported. Conclusion: STIs as expected were higher in SA adolescent than in SI and in HIV-1 positive patients (P <0.025).Twenty-two percent of SA adolescents resulted positive for at least one STIs. A prevalence of 14.5% (17/117) for U. urealyticum/parvum, was detected in the adolescents studied, even if its clinical significance has yet to be assessed. Findings suggest that surveillance and screening programs should be implemented to prevent sequels on this vulnerable population

Retrospective investigation on the prevalence of pulmonary hypertension in dogs with bronchial and upper respiratory diseases

Bronchial and upper respiratory diseases have been associated with hypoxia and subsequent development of pulmonary arterial hypertension (PAH). However, there are no known studies assessing the prevalence of PAH in dogs with these conditions. The aim of this study was to assess the frequency of PAH in dogs with bronchial and upper respiratory diseases. Medical records of dogs with confirmed diagnosis (by endoscopic examination) of bronchial and/or upper respiratory diseases referred for cardiovascular investigation (January 2009 - May 2013) were retrospectively reviewed. Diagnosis of PAH was made by echocardiography (tricuspid regurgitation >2.8 m/s and/or pulmonic regurgitation >2.2 m/s); possible PAH was diagnosed when two or more specific echocardiographic findings were present. 52 dogs (30 with upper respiratory diseases, 17 with bronchial disease and 5 with both) were included. Diagnosis of PAH was performed in 3 dogs (5.7%). Two dogs were considered as probably affected by PAH; a total of 5 dogs (9.4%) resulted in being affected or probably affected by PAH. Our study shows that the prevalence of PAH in dogs with bronchial and/or upper respiratory diseases is low; PAH seems to occur mostly in older dogs and/or with very advanced disease: echocardiography may therefore be a useful tool in this category of patients

Effects of the pulsed electromagnetic field PST&#174; on human tendon stem cells : A controlled laboratory study

Background: Current clinical procedures for rotator cuff tears need to be improved, as a high rate of failure is still observed. Therefore, new approaches have been attempted to stimulate self-regeneration, including biophysical stimulation modalities, such as low-frequency pulsed electromagnetic fields, which are alternative and non-invasive methods that seem to produce satisfying therapeutic effects. While little is known about their mechanism of action, it has been speculated that they may act on resident stem cells. Thus, the purpose of this study was to evaluate the effects of a pulsed electromagnetic field (PST\uae) on human tendon stem cells (hTSCs) in order to elucidate the possible mechanism of the observed therapeutic effects. Methods: hTSCs from the rotator cuff were isolated from tendon biopsies and cultured in vitro. Then, cells were exposed to a 1-h PST\uae treatment and compared to control untreated cells in terms of cell morphology, proliferation, viability, migration, and stem cell marker expression. Results: Exposure of hTSCs to PST\uae did not cause any significant changes in proliferation, viability, migration, and morphology. Instead, while stem cell marker expression significantly decreased in control cells during cell culturing, PST\uae-treated cells did not have a significant reduction of the same markers. Conclusions: While PST\uae did not have significant effects on hTSCs proliferation, the treatment had beneficial effects on stem cell marker expression, as treated cells maintained a higher expression of these markers during culturing. These results support the notion that PST\uae treatment may increase the patient stem cell regenerative potential

Lipogems product treatment increases the proliferation rate of human tendon stem cells without affecting their stemness and differentiation capability

Increasing the success rate of rotator cuff healing remains tremendous challenge. Among many approaches, the possibility of activating resident stem cells in situ, without the need to isolate them from biopsies, could represent valuable therapeutic strategy. Along this line, it has been recently demonstrated that lipoaspirate product, Lipogems, contains and produces growth-factors that may activate resident stem cells. In this study, human tendon stem cells (hTSCs) from the rotator cuff were cocultured in a transwell system with the Lipogems lipoaspirate product and compared to control untreated cells in terms of cell proliferation, morphology, stem cell marker and VEGF expression, and differentiation and migration capabilities. Results showed that the Lipogems product significantly increases the proliferation rate of hTSCs without altering their stemness and differentiation capability. Moreover, treated cells increase the expression of VEGF, which is crucial for the neovascularization of the tissue during the healing process. Overall, this study supports that directly activating hTSCs with the Lipogems lipoaspirate could represent a new practical therapeutic approach. In fact, obtaining a lipoaspirate is easier, safer, and more cost-effective than harvesting cells from tendon or bone marrow biopsies, expanding them in GMP facility and then reinjecting them in the patient

Epidemiological and clinical features of rotavirus among children younger than 5 years of age hospitalized with acute gastroenteritis in Northern Italy

BACKGROUND: Rotavirus is the major cause of acute gastroenteritis and severe dehydrating diarrhea in young children. METHODS: To estimate the proportion of hospital admissions for rotavirus acute gastroenteritis and identify the circulating G and P genotypes among children under five years of age, we conducted a prospective observational study from January to December 2008, recruiting children consecutively admitted to six hospitals in Milan and nearby towns in northern Italy. Typing was done on stool samples by reverse transcriptase polymerase chain reaction amplification. RESULTS: Of the 521 stool samples from children with acute gastroenteritis, 34.9% (95%CI, 30.8 to 39.2%) were rotavirus-positive. Two thirds (67.6%) were under two years of age, and 13.2% were under six months. The predominant G type was G1 (40.7%), followed by G9 (22.5%), G2 (13.2%), G3 (5.5%), G4 (3.8%) and G10 (1.6%). Twenty-one (11.7%) mixed-G infections were identified: G1+G10 (8.8%); G1+G9 (1.6%); and G2+G10 (1.2%). Only P[8] (67.6%) and P[4] (12.6%) types were P genotyped. The predominant single G/P combination was G1P[8] (39.7%), followed by G9P[8] (25.3%), G2P[4] (14.3%), and G3P[8] (4.1%). All G-mixed types combined with P[8]. CONCLUSIONS: These findings show an high prevalence of rotavirus infections among children admitted to hospital for acute gastroenteritis caused by different rotavirus strains circulating in the area studied

Follicular Dendritic Cell-Specific Prion Protein (PrPc) Expression Alone Is Sufficient to Sustain Prion Infection in the Spleen

Prion diseases are characterised by the accumulation of PrPSc, an abnormally folded isoform of the cellular prion protein (PrPC), in affected tissues. Following peripheral exposure high levels of prion-specific PrPSc accumulate first upon follicular dendritic cells (FDC) in lymphoid tissues before spreading to the CNS. Expression of PrPC is mandatory for cells to sustain prion infection and FDC appear to express high levels. However, whether FDC actively replicate prions or simply acquire them from other infected cells is uncertain. In the attempts to-date to establish the role of FDC in prion pathogenesis it was not possible to dissociate the Prnp expression of FDC from that of the nervous system and all other non-haematopoietic lineages. This is important as FDC may simply acquire prions after synthesis by other infected cells. To establish the role of FDC in prion pathogenesis transgenic mice were created in which PrPC expression was specifically “switched on” or “off” only on FDC. We show that PrPC-expression only on FDC is sufficient to sustain prion replication in the spleen. Furthermore, prion replication is blocked in the spleen when PrPC-expression is specifically ablated only on FDC. These data definitively demonstrate that FDC are the essential sites of prion replication in lymphoid tissues. The demonstration that Prnp-ablation only on FDC blocked splenic prion accumulation without apparent consequences for FDC status represents a novel opportunity to prevent neuroinvasion by modulation of PrPC expression on FDC

Plasmacytoid Dendritic Cells Sequester High Prion Titres at Early Stages of Prion Infection

In most transmissible spongiform encephalopathies prions accumulate in the lymphoreticular system (LRS) long before they are detectable in the central nervous system. While a considerable body of evidence showed that B lymphocytes and follicular dendritic cells play a major role in prion colonization of lymphoid organs, the contribution of various other cell types, including antigen-presenting cells, to the accumulation and the spread of prions in the LRS are not well understood. A comprehensive study to compare prion titers of candidate cell types has not been performed to date, mainly due to limitations in the scope of animal bioassays where prohibitively large numbers of mice would be required to obtain sufficiently accurate data. By taking advantage of quantitative in vitro prion determination and magnetic-activated cell sorting, we studied the kinetics of prion accumulation in various splenic cell types at early stages of prion infection. Robust estimates for infectious titers were obtained by statistical modelling using a generalized linear model. Whilst prions were detectable in B and T lymphocytes and in antigen-presenting cells like dendritic cells and macrophages, highest infectious titers were determined in two cell types that have previously not been associated with prion pathogenesis, plasmacytoid dendritic (pDC) and natural killer (NK) cells. At 30 days after infection, NK cells were more than twice, and pDCs about seven-fold, as infectious as lymphocytes respectively. This result was unexpected since, in accordance to previous reports prion protein, an obligate requirement for prion replication, was undetectable in pDCs. This underscores the importance of prion sequestration and dissemination by antigen-presenting cells which are among the first cells of the immune system to encounter pathogens. We furthermore report the first evidence for a release of prions from lymphocytes and DCs of scrapie-infected mice ex vivo, a process that is associated with a release of exosome-like membrane vesicles