NKT cells inhibit antigen-specific effector CD8 T cell induction to skin viral proteins

Type 1 diabetes (T1D) results from autoimmune destruction of insulin-producing pancreatic β cells. Therapies need to incorporate strategies to overcome the genetic defects that impair induction or maintenance of peripheral T-cell tolerance and contribute to disease development. We tested whether the enforced expression of an islet autoantigen in antigen-presenting cells (APC) counteracted peripheral T-cell tolerance defects in autoimmune-prone NOD mice. We observed that insulin-specific CD8(+) T cells transferred to mice in which proinsulin was transgenically expressed in APCs underwent several rounds of division and the majority were deleted. Residual insulin-specific CD8(+) T cells were rendered unresponsive and this was associated with TCR downregulation, loss of tetramer binding and expression of a range of co-inhibitory molecules. Notably, accumulation and effector differentiation of insulin-specific CD8(+) T cells in pancreatic lymph nodes was prominent in non-transgenic recipients but blocked by transgenic proinsulin expression. This shift from T-cell priming to T-cell tolerance exemplifies the tolerogenic capacity of autoantigen expression by APC and the capacity to overcome genetic tolerance defects

Pityriasis rubra pilaris presenting with an abnormal autoimmune profile: two case reports

<p>Abstract</p> <p>Introduction</p> <p>Pityriasis rubra pilaris is an uncommon inflammatory and hyperproliferative dermatosis of juvenile or adult onset. The etiology of the disease is still unknown.</p> <p>Case presentation</p> <p>We present the cases of two Caucasian men aged 53 and 48 who presented with pityriasis rubra pillaris type 1; both patients also exhibited an abnormal immunological profile.</p> <p>Conclusion</p> <p>Pityriasis rubra pillaris is currently classified as a keratinization disorder. The abnormal immunological profile reported in our patients along with the comorbidity of pityriasis rubra pilaris with autoimmune disorders reported in the literature poses the question of a possible pathogenetic role for the immune response in this disorder.</p

Relationship between resident workload and self-perceived learning on inpatient medicine wards: a longitudinal study

BACKGROUND: Despite recent residency workload and hour limitations, little research on the relationship between workload and learning has been done. We sought to define residents' perceptions of the optimal patient workload for learning, and to determine how certain variables contribute to those perceptions. Our hypothesis was that the relationship between perceived workload and learning has a maximum point (forming a parabolic curve): that either too many or too few patients results in sub-optimal learning. METHODS: Residents on inpatient services at two academic teaching hospitals reported their team and individual patient censuses, and rated their perception of their learning; the patient acuity; case variety; and how challenged they felt. To estimate maximum learning scores, linear regression models with quadratic terms were fit on learning score. RESULTS: Resident self-perceived learning correlated with higher acuity and greater heterogeneity of case variety. The equation of census versus learning score, adjusted for perception of acuity and case mix scores, showed a parabolic curve in some cases but not in others. CONCLUSION: These data suggest that perceived resident workload is complex, and impacted by additional variables including patient acuity and heterogeneity of case variety. Parabolic curves exist for interns with regard to overall census and for senior residents with regard to new admissions on long call days

Emetic risk classification and evaluation of the emetogenicity of antineoplastic agents—updated MASCC/ESMO consensus recommendation

PURPOSE : Our goal was to identify new anticancer agents approved by the US Food and Drug Administration (FDA) and the European Medical Agency (EMA) since the 2016 MASCC/ESMO antiemetic update and classify their emetic potential. METHODS : The MASCC/ESMO Expert Panel classified the emetogenicity of the identified new antineoplastic agents based on nonsystematic reviews of randomized controlled trials, analysis of product labeling, and evaluation of emetic classification in other international guidelines and informal consensus. The emetogenic classification system for oral anticancer agents was revised into two emetic risk categories (minimal–low; moderate–high) to be consistent with the system reported by ASCO (American Society of Clinical Oncology) in their 2017 guideline update. The previously employed four emetic risk classification categories for intravenously administered antineoplastic agents were retained for this update. RESULTS : From June 2015 to January 2023, 107 new antineoplastic agents (44 intravenously administered and 63 orally administered agents) were identified. The reported incidence of vomiting varied significantly across studies for many agents, especially for oral anticancer agents. CONCLUSION : The MASCC/ESMO Expert Panel acknowledges the limitations of our efforts to classify the emetic potential of anticancer agents, especially the imprecision associated with oral agents. However, we have attempted to provide a reasonable approximation of the emetic risk associated with new antineoplastic agents by searching the available literature and reviewing other available international antiemetic guidelines.Open Access funding enabled and organized by Projekt DEAL.https://www.springer.com/journal/520hj2024ImmunologySDG-03:Good heatlh and well-bein

Pamidronic acid and cabergoline as effective long-term therapy in a 12-year-old girl with extended facial polyostotic fibrous dysplasia, prolactinoma and acromegaly in McCune-Albright syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>McCune-Albright syndrome is a complex inborn disorder due to early embryonal postzygotic somatic activating mutations in the <it>GNAS</it>1 gene. The phenotype is very heterogeneous and includes polyostotic fibrous dysplasia, typically involving the facial skull, numerous café-au-lait spots and autonomous hyperfunctions of several endocrine systems, leading to hyperthyroidism, hypercortisolism, precocious puberty and acromegaly.</p> <p>Case presentation</p> <p>Here, we describe a 12-year-old Caucasian girl with severe facial involvement of fibrous dysplasia, along with massive acromegaly due to growth hormone excess and precocious puberty, with a prolactinoma. Our patient was treated with a bisphosphonate and the prolactin antagonist, cabergoline, resulting in the inhibition of fibrous dysplasia and involution of both the prolactinoma and growth hormone excess. During a follow-up of more than two years, no severe side effects were noted.</p> <p>Conclusion</p> <p>Treatment with bisphosphonates in combination with cabergoline is a suitable option in patients with McCune-Albright syndrome, especially in order to circumvent surgical interventions in patients suffering from polyostotic fibrous dysplasia involving the skull base.</p

Author Correction: Symptoms and syndromes associated with SARS-CoV-2 infection and severity in pregnant women from two community cohorts

Correction to: Scientific Reports https://doi.org/10.1038/s41598-021-86452-3, published online 25 March 2021 The Funding section in the original version of this Article was incomplete