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Borderline personality disorder (BPD) is a severe mental health condition marked by impairments in self and interpersonal functioning. Stigma from health staff may often result in a reluctance to diagnose, impacting recovery trajectories. Qualitative interviews were conducted with participants (N = 15; M Age = 36.4 years, SD = 7.5; 93.3% female) with lived experience of BPD exploring topics of illness onset, insight, experience of diagnosis and treatment. Qualitative responses were analysed within a co‐design framework with a member of the research team who identifies as having a lived experience of BPD. On average, participant symptoms emerged at 12.1 years of age (SD = 6.6 years, range 1.5–27), but diagnoses of BPD were delayed until 30.2 years (SD = 7.8 years, range 18–44) resulting in a 'diagnosis gap' of 18.1 years (SD = 9.6 years, range 3–30). Participant explanations for BPD emergence varied from biological, psychological and social factors. Benefits of diagnosis (e.g., fostering insight, aiding treatment planning and reducing isolation) were contrasted with challenges (e.g., stigma and treatment unavailability). Delay in diagnosis was common, and no participants reported receiving a diagnosis of BPD during their adolescence yet 85% felt they would have benefited from a diagnosis in adolescence. Only a quarter (27%) felt highly supported in the diagnostic process. An ideal four‐step diagnosis procedure was outlined based on recommendations from participants with a lived experience; this involved the following: (1) explain the process, (2) assess thoroughly, (3) explore how the features are active in everyday life and (4) link diagnosis to evidence‐based treatment planning. [ABSTRACT FROM AUTHOR]

The current SARS‐CoV‐2 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID‐19 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS‐CoV‐2 infections may, at least in part, be due also to differences between the viral subspecies with which individuals are infected. A more pertinent question is how we are to overcome the current pandemic. A vaccine against SARS‐CoV‐2 would offer significant relief, although vaccine developers have warned that design, testing and production of vaccines may take a year if not longer. Vaccines are based on a handful of different designs (i), but the earliest vaccines were based on the live, attenuated virus. As has been the case for other viruses during earlier pandemics, SARS‐CoV‐2 will mutate and may naturally attenuate over time (ii). What makes the current pandemic unique is that, thanks to state‐of‐the‐art nucleic acid sequencing technologies, we can follow in detail how SARS‐CoV‐2 evolves while it spreads. We argue that knowledge of naturally emerging attenuated SARS‐CoV‐2 variants across the globe should be of key interest in our fight against the pandemic. [ABSTRACT FROM AUTHOR]

Background We investigated the ability of clinical-grade enriched human regulatory T cells ( Treg) to attenuate experimental xenogeneic graft-versus-host disease ( GVHD) induced by peripheral blood mononuclear cells ( PBMNCs; autologous to Treg) infusion in NSG mice, as well as verified their inability to induce xenogeneic GVHD when infused alone. Study Design and Methods Human Treg were isolated from peripheral blood apheresis products with a cell separation system ( CliniMACS, Miltenyi Biotec GmbH) using a two-step procedure (simultaneous CD8 and CD19 depletion followed by CD25-positive selection) in six independent experiments with six different healthy volunteer donors. Sublethally (2.5 Gy) irradiated NSG mice were given 2 × 106 cytapheresis ( PBMNC) product cells intravenously ( IV) without ( PBMNC group) or with 1 × 106 Treg ( PBMNC + Treg group), while other NSG mice received 2 × 106 enriched Treg alone (also in IV; Treg group). Results The first five procedures were successful at obtaining a relatively pure Treg population (defined as >50%), while the sixth procedure, due to a technical problem, was not ( Treg purity, 42%). Treg cotransfusion significantly delayed death from xenogeneic GVHD in the first five experiments, (p < 0.0001) but not in the sixth experiment. Importantly, none of the mice given enriched Treg alone ( Treg group) experienced clinical signs of GVHD, while, interestingly, the CD4+ cells found in these mice 26 days after transplantation were mainly conventional T cells (median CD25+ Fox P3+ cells among human CD4+ total cells were only 2.1, 3.1, and 12.2% in spleen, marrow, and blood, respectively). Conclusions Infusion of clinical-grade enriched Treg delayed the occurrence of xenogeneic GVHD without inducing toxicity in this murine model. [ABSTRACT FROM AUTHOR]

The TLC- Ag dressings, a combination of technology lipido-colloid and silver salts, are used to promote healing in wounds with risks or signs of local infection, thanks to the antimicrobial properties of the silver salts. Nanocrystalline silver dressings containing nanocrystalline silver, also used to improve wound healing, present both antimicrobial and anti-inflammatory effects. The aim of this study was to investigate the anti-inflammatory effects of TLC- Ag dressings in a model of chronic skin inflammation induced by repeated application of 12- O-tetradecanoylphorbol-13-acetate to the skin of hairless mice, in comparison with TLC dressing, Silcryst nanocrystalline dressing, desonide cream 0.05%, a corticoid cream used as positive control, and gauze. Daily treatments of the mice began 7 days after the start of induction of chronic skin inflammation and lasted for 7 days. A macroscopic score was performed daily during the treatment period until the mice killing on day 15 and skin samples were taken for histopathological analysis. TLC- Ag reduced significantly the macroscopic score of chronic skin inflammation from day 10 in comparison with gauze and TLC dressing, similarly to Silcryst nanocrystalline dressing and desonide cream, which presented the best anti-inflammatory effects. No significant differences were observed between TLC dressing and gauze. TLC- Ag reduced significantly the microscopic score of chronic skin inflammation in comparison with TLC dressing and gauze, similarly to Silcryst nanocrystalline dressing but significantly less than desonide cream. These results demonstrate that TLC- Ag dressings present significant anti-inflammatory effects on chronic skin inflammation. They can improve wound healing, due to both the antimicrobial and anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

The human suppressive T cells that stably express transcription factor FOXP3, or regulatory T cells (Tregs), are thought to suppress antitumor immune responses. The most specific marker for human Tregs is the demethylation of CpG dinucleotides located in the first intron of FOXP3 ( FOXP3i1). FOXP3i1 is completely methylated in other hematopoietic cells, including nonsuppressive T cells that transiently express FOXP3 after activation. Previously, we and others reported estimations of the frequency of Tregs in the blood of melanoma patients using a FOXP3i1 methylation-specific qPCR assay. Here, we attempted to quantify Tregs inside tumor samples using this assay. However, we found demethylated FOXP3i1 sequences in the melanoma cells themselves. This demethylation was not associated with substantial FOXP3 mRNA or protein expression, even though the demethylation extended to the promoter and terminal regions of the gene in some melanoma cells. Our results imply that analyzing Treg frequencies by quantification of demethylated FOXP3i1 will require that tumor-infiltrating T cells be separated from melanoma cells. [ABSTRACT FROM AUTHOR]

Human Treg and Th clones secrete the latent form of TGF-β, in which the mature TGF-β protein is bound to the latency-associated peptide (LAP), and is thereby prevented from binding to the TGF-β receptor. We previously showed that upon TCR stimulation, human Treg clones but not Th clones produce active TGF-β and bear LAP on their surface. Here, we show that latent TGF-β, i.e. both LAP and mature TGF-β, binds to glycoprotein A repetitions predominant (GARP), a transmembrane protein containing leucine rich repeats, which is present on the surface of stimulated Treg clones but not on Th clones. Membrane localization of latent TGF-β mediated by binding to GARP may be necessary for the ability of Treg to activate TGF-β upon TCR stimulation. However, it is not sufficient as lentiviral-mediated expression of GARP in human Th cells induces binding of latent TGF-β to the cell surface, but does not result in the production of active TGF-β upon stimulation of these Th cells. [ABSTRACT FROM AUTHOR]

From cancerous and non-cancerous patients, we derived stable clones of CD4 Treg, defined as clones that expressed high CD25 at rest, were anergic in vitro, and suppressed the proliferation of co-cultured CD4 cells. A conserved region of FOXP3 intron 1 was demethylated in all Treg clones, whereas it was methylated in non-regulatory Th and CTL clones. In our panel of human clones, this stable epigenetic mark correlated better with suppressive activity than did FOXP3 mRNA or protein expression. We used expression microarrays to compare Treg and Th clones after activation, which is required for suppressive function. The transcriptional profile that is specific of activated Treg clones includes a TGF-β signature. Both activated Treg and Th clones produced the latent form of TGF-β. However, SMAD2 phosphorylation was observed after activation in the Treg but not in the Th clones, indicating that only activated Treg clones produced the bioactive form of TGF-β. A TGF-β signature was also displayed by a Th clone 'suppressed' by a Treg clone. In conclusion, the hallmark of our panel of activated human Treg clones is to produce bioactive TGF-β which has autocrine actions on Tregs and can have paracrine actions on other T cells. [ABSTRACT FROM AUTHOR]

Evaluates the responses of cancer patients vaccinated with a melanoma antigen-3 antigenic peptide or a recombinant virus coding for peptide aimed at establishing whether there is a correlation between tumoral regressions and T-cell responses against vaccine antigen. Characteristics of the normal anti-melanoma antigen-3.A1 (anti-MAGE-3.A1) repertoir; Detection of anti-MAGE-3.A1 T-cell responses; Analysis of vaccinated patients.