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We investigated blood samples from fully SARS-CoV2-vaccinated subjects and from previously positive tested patients up to one year after infection with SARS-CoV2, and compared short- and long-term T cell and antibody responses, with a special focus on the recently emerged delta variant (B.1.617.2). In 23 vaccinated subjects, we documented high anti-SARS-CoV2 spike protein receptor binding domain (RBD) antibody titers. Average virus neutralization by antibodies, assessed as inhibition of ACE2 binding to RBD, was 2.2-fold reduced for delta mutant vs. wild type (wt) RBD. The mean specific antibody titers were lower one year after natural infection than after vaccination; ACE2 binding to delta mutant vs. wt RBD was 1.65-fold reduced. In an additional group, omicron RBD binding was reduced compared to delta. Specific CD4+ T cell responses were measured after stimulation with peptides pools from wt, alpha, beta, gamma, or delta variant SARS-CoV2 spike proteins by flow cytometric intracellular cytokine staining. There was no significant difference in cytokine production of IFN-γ, TNF-α, or IL-2 between vaccinated subjects. T cell responses to wt or mutant SARS-CoV2 spike were significantly weaker after natural occurring infections compared to those in vaccinated individuals. Antibody neutralisation of the delta mutant was reduced compared to wt, as assessed in a novel inhibition assay with a finger prick blood drop. Strong CD4 T cell responses were present against wt and mutant SARS-CoV2 variants, including the delta (B.1.617.2) strain, in fully vaccinated individuals, whereas they were partly weaker 1 year after natural infection. Hence, immune responses after vaccination are stronger compared to those after naturally occurring infection, pointing out the need of the vaccine to overcome the pandemic.

Cancer immunotherapy activates the immune system to specifically target malignant cells. Research has often focused on CD8+ cytotoxic T cells, as those have the capacity to eliminate tumor cells after specific recognition upon TCR-MHC class I interaction. However, CD4+ T cells have gained attention in the field, as they are not only essential to promote help to CD8+ T cells, but are also able to kill tumor cells directly (via MHC-class II dependent recognition) or indirectly (e.g., via the activation of other immune cells like macrophages). Therefore, immunotherapy approaches have shifted from only stimulating CD8+ T cells to targeting and assessing both, CD4+ and CD8+ T cell subsets. Here, we discuss the various subsets of CD4+ T cells, their plasticity and functionality, their relevance in the antitumor immune response in patients affected by cancer, and their ever-growing role in therapeutic approaches for human cancer.

“Unchecked, the failed PA experiment could lead to an extinction level event for the medical profession in the NHS,” he told a busy hall at the start of business on the second day of the conference. Chris Morris of the GP registrars committee, also speaking against, said, “PAs working in general practice and seeing undifferentiated patients makes a mockery of our extensive training.” Other news from the annual conference of UK local medical committees Call to review maternity record keeping systems Delegates at the conference voted in favour of a motion that called for a review of standalone maternity clinical record keeping systems and for maternity clinical records to be interoperable with GP systems. Representatives urged the BMA’s GP committees across the four nations to “ensure there are no contractual restrictions on practices seeing private patients, subject to appropriate fair systems in place” and that practices are “not unfairly penalised financially by seeing private patients in NHS facilities.”

West Nile virus (WNV) is a mosquito-borne virus that causes severe neurological disease in humans. Despite substantial advances, our knowledge of the mechanisms involved in damaging the human brain is still limited. To address this gap, we developed a physiologically relevant in vitro model using human neuronal/glial cells and aimed to determine WNV tropism, assess whether the virus induces innate immune and inflammatory responses, and elucidate the resulting pathophysiological consequences. We found that WNV productively infected glial cells, whereas neurons exhibited a remarkable and unexpected resistance to infection. Despite the induction of a robust innate immune response mediated by IFN signalling and a rapid control of WNV replication in glial cells, we observed substantial death of astrocytes, oligodendrocytes, and neurons. Analysis of cytokine and chemokine expression further revealed that infection triggered an inflammatory response, potentially contributing to bystander cell death. We also showed that IFN signaling did not contribute to the resistance of neurons and identified IFI6 as an effector of the antiviral response in human glial cells. Together, our results underscore the importance of human neural models for confirming previous findings obtained in less physiologically relevant models and for unravelling novel cellular and molecular mechanisms.

Students’ goal-setting skills are highly related to their academic learning performance and level of motivation. A review of the literature demonstrated limited research on both applicable goal-setting strategies in higher education and the support of technology in facilitating goal-setting processes. Addressing these two gaps, this study explored the use of digital badges as an innovative approach to facilitate student goal-setting. The digital badge is a digital technology that serves as both a micro-credential and a micro-learning platform. A digital badge is a clickable badge image that represents an accomplished skill or knowledge and includes a variety of metadata such as learning requirements, instructional materials, endorsement information, issue data and institution, which allows the badges to be created, acquired and shared in an online space. In higher education, digital badges have the potential for assisting students by promoting strategic management of the learning process, encouraging persistence and devoted behavior to learning tasks, and improving learning performance. A qualitative multiple case study design (n = 4) was used to answer the research question: how did the undergraduate student participants in this study use digital badges to facilitate their goal-setting process throughout a 16-week hybrid course? Results from this study contribute to understanding how to effectively integrate digital badges to meaningfully improve self-regulated learning in higher education.

Standards slip Jack Parry-Jones, an intensive care consultant at the University Hospital of Wales in Cardiff and vice dean of the Faculty of Intensive Care, said that his department was working at or above capacity (36 ventilated patients) on his most recent shift. Raja Biswas, a consultant in care of the elderly and general medicine and clinical director at Royal Glamorgan Hospital, railed against Welsh government advice to discharge patients without care packages.1 Two years ago, his service for the care of elderly people was responsible for 70 patients across two teams. Bodey and Ryell also cited the damaging effects of negative headlines about GP availability in recent months and said that some supportive messages from the government would help morale.

The Purdue Repository for Online Teaching and Learning (PoRTAL) was developed as an Open Educational Resource (OER) for graduate students and faculty in higher education settings to enhance their online teaching skills and strategies. The PoRTAL team used a design-based research approach (DBR; Wang & Hannafin, Educational Technology Research and Development, 53(4), 5–23, 2005). In this study context, we used Van Tiem et al.’s (2012) model to identify problems faced by instructors who struggled with or were new to online teaching from a Human Performance Technology (HPT) standpoint. To address the identified needs, we created resources for online teaching and embedded our research within practical activities to further study our design process. Our efforts resulted in an HPT-OER Model for Designing Digital Repositories. The purpose of this paper is to share the DBR process that we used to develop an OER repository within an HPT model.

In this article, I utilize an indisciplinary theoretical framework through the work of Jacques Rancière to examine the artwork of artists with mental disabilities experiencing confinement in asylums in the late 19th to early 20th centuries. I further examine preexisting ways in which this artwork, focusing particularly on the Prinzhorn Collection, has been positioned within art history and psychiatric medical models in the 19th and early 20th centuries that situate these artists as geniuses, as examples of Expressionism, or as pathological. In contrast, I suggest that these artists' work can be a form of politics and dissensus. The indisciplinarity of Rancière's work and Disability Studies offer art educators new possibilities for understanding the artwork of people experiencing mental disabilities by disrupting the disciplinary logic that can inform thinking about these artists.

To evaluate the prevalence of off-label and unlicensed prescribing in inpatients at a major paediatric teaching hospital in Western Australia and to identify which drugs are commonly prescribed off-label or unlicensed, including factors influencing such prescribing. A retrospective cross-sectional study was conducted in June, 2013. Patient and prescribing data were collected from 190 inpatient medication chart records which had been randomly selected from all admissions during the second week of February 2013. Drugs were categorised as licensed, off-label or unlicensed, according to their approved Australian registration product information (PI). All drugs were classified according to the Anatomical Therapeutic Chemical (ATC) code. There were 120 male and 70 female inpatients. The average age was 6.0 years (± 4.7). The study included 1160 prescribed drugs suitable for analysis. The number of drugs prescribed per patient ranged from 1 to 25 with an average of 6.1 (± 4.3). More than half (54%) were prescribed off-label. Oxycodone, clonidine, parecoxib and midazolam were always prescribed off-label. The most common off-label drugs were ondansetron (18.5%), fentanyl (12.9%), oxycodone (8.8%) and paracetamol (6.1%). Many ATC classifications included high off-label proportions especially the genitourinary system and sex hormones, respiratory system drugs, systemic hormonal preparations and alimentary tract and metabolism drugs. This study highlights that prescribing of paediatric drugs needs to be better supported by existing and new evidence. Incentives should be established to foster the conduct of evidence-based studies in the paediatric population. The current level of off-label prescribing raises issues of unexpected toxicity and adverse drug effects in children that are in some cases severely ill.

(Sa), as one of the major human pathogens, has very effective strategies to subvert the human immune system. Virulence of the emerging community-associated methicillin-resistant Sa (CA-MRSA) depends on the secretion of phenol-soluble modulin (PSM) peptide toxins e.g., by binding to and modulation of innate immune cells. Previously, by using mouse bone marrow-derived dendritic cells we demonstrated that PSMs in combination with various Toll-like receptor (TLR) ligands induce a tolerogenic DC phenotype (tDC) characterized by the production of IL-10 and impaired secretion of pro-inflammatory cytokines. Consequently, PSM-induced tDCs favored priming of CD4 CD25 FoxP3 T with suppressor function while impairing the Th1 response. However, the relevance of these findings for the human system remained elusive. Here, we analyzed the impact of PSMα3 on the maturation, cytokine production, antigen uptake, and T cell stimulatory capacity of human monocyte-derived DCs (moDCs) treated simultaneously with either LPS (TLR4 ligand) or Sa cell lysate (TLR2 ligand). Herein, we demonstrate that PSMs indeed modulate human moDCs upon treatment with TLR2/4 ligands via multiple mechanisms, such as transient pore formation, impaired DC maturation, inhibited pro- and anti-inflammatory cytokine secretion, as well as reduced antigen uptake. As a result, the adaptive immune response was altered shown by an increased differentiation of naïve and even CD4 T cells from patients with Th1/Th17-induced diseases (spondyloarthritis and rheumatoid arthritis) into CD4 CD127 CD25 CD45RA FoxP3 regulatory T cells (T ) with suppressor function. This T induction was mediated most predominantly by direct DC-T-cell interaction. Thus, PSMs from highly virulent Sa strains affect DC functions not only in the mouse, but also in the human system, thereby modulating the adaptive immune response and probably increasing the tolerance toward the bacteria. Moreover, PSMα3 might be a novel peptide for tolerogenic DC induction that may be used for DC vaccination strategies.