Historical micronutrient psychiatry: descriptive analysis of patients with pellagra admitted to the “San Lazzaro” asylum in Reggio Emilia (Italy) in the decade 1901-1910

This study aims at describing the socio-demographic and clinical characteristics of the patients affected by pellagra and admitted to the “San Lazzaro” psychiatric asylum (Reggio Emilia, Italy) from 1901 to 1910 besides exploring possible gender differences for the collected information. Data were collected from the admission register and clinical records of those patients who were admitted to the San Lazzaro Psychiatric Hospital receiving a diagnosis of pellagra at their first admission. The pellagrous patient population was characterised by a higher rate of hospitalisation for women (64.3%) and the number of hospitalised patients suffering from pellagra gradually decreased from 1901 (78; 8.3%) to 1910 (8;0.7%). The most common profession for men admitted with pellagra was farmer/agricultural labourer, while most of the women were housewives. A characteristic shared by both the male and female population of inpatients was very high rate of illiteracy: only one patient was recorded as being able to read and write. The generic diagnosis of “mental illness from pellagra” was predominant (70%), while “dementia from pellagra” accounts for 17.85% of the admission diagnoses: no statistically significant differences between men and women were found in the frequency of diagnosis. Half of the patients, both men and women, died while being inpatients. This study confirms previous findings about the case mix of pellagra patients admitted to psychiatric hospital at the beginning of the last century in northern Italy and highlights the significance of the relationship of psychiatry with other medical disciplines and the sociocultural milieu

Blocking T cell co-stimulation in primary Sjögren's syndrome:rationale, clinical efficacy and modulation of peripheral and salivary gland biomarkers

There is accumulating evidence that patients with primary Sjögren's syndrome (pSS) display aberrant CD4+ T cell responses, both in the peripheral compartment and in the inflamed salivary glands. CD4+ T cell abnormalities are also critically associated with B cell hyper activation, one of the hallmarks of disease, which is linked with disease severity and evolution to lymphoma. T cell activation and the cross-talk between T and B cells are tightly regulated by the balance between co-stimulatory pathways, such as the interactions between CD80/CD86:CD28, CD40:CD40L and ICOS:ICOSL, and co-inhibitory signals, including the immunoregulatory CTLA-4 protein. Evidence from patients with pSS as well as data from animal models of the disease suggests that these pathways play a critical role in pSS pathogenesis and their targeting could be exploited for therapeutic purposes. In this review, we first summarise the evidence implicating aberrant T cell co-stimulation and co-inhibition in driving the disease before focusing on the results of recent randomised controlled trials (RCTs) with compounds able to block T cell co-stimulation and enhance T cell co-inhibition. Despite a clear biological effect on downstream B cell activation has been observed in patients treated with CTLA-4-Ig (abatacept) and with monoclonal antibodies targeting CD40 and ICOSL, the clinical efficacy of this approach has so far yielded mixed results; while the anti-CD40 monoclonal antibody iscalimab showed significant improvement in systemic disease activity compared to placebo, two large RCTs with abatacept and a phase IIa RCT with an anti-ICOSL monoclonal antibody (prezalumab) failed to reach their primary endpoints. Although the discrepancies between biological and clinical efficacy of targeting T cell co-stimulation on pSS remain unresolved, several factors including drug bioavailability and receptor occupancy, patient stratification based on T-cell related biomarkers and the choice of study outcome are likely to play an important role and form the basis for further work towards the quest for a disease-modifying biologic therapy in pSS

Blocking T cell co-stimulation in primary Sjögren's syndrome:rationale, clinical efficacy and modulation of peripheral and salivary gland biomarkers

There is accumulating evidence that patients with primary Sjögren's syndrome (pSS) display aberrant CD4+ T cell responses, both in the peripheral compartment and in the inflamed salivary glands. CD4+ T cell abnormalities are also critically associated with B cell hyper activation, one of the hallmarks of disease, which is linked with disease severity and evolution to lymphoma. T cell activation and the cross-talk between T and B cells are tightly regulated by the balance between co-stimulatory pathways, such as the interactions between CD80/CD86:CD28, CD40:CD40L and ICOS:ICOSL, and co-inhibitory signals, including the immunoregulatory CTLA-4 protein. Evidence from patients with pSS as well as data from animal models of the disease suggests that these pathways play a critical role in pSS pathogenesis and their targeting could be exploited for therapeutic purposes. In this review, we first summarise the evidence implicating aberrant T cell co-stimulation and co-inhibition in driving the disease before focusing on the results of recent randomised controlled trials (RCTs) with compounds able to block T cell co-stimulation and enhance T cell co-inhibition. Despite a clear biological effect on downstream B cell activation has been observed in patients treated with CTLA-4-Ig (abatacept) and with monoclonal antibodies targeting CD40 and ICOSL, the clinical efficacy of this approach has so far yielded mixed results; while the anti-CD40 monoclonal antibody iscalimab showed significant improvement in systemic disease activity compared to placebo, two large RCTs with abatacept and a phase IIa RCT with an anti-ICOSL monoclonal antibody (prezalumab) failed to reach their primary endpoints. Although the discrepancies between biological and clinical efficacy of targeting T cell co-stimulation on pSS remain unresolved, several factors including drug bioavailability and receptor occupancy, patient stratification based on T-cell related biomarkers and the choice of study outcome are likely to play an important role and form the basis for further work towards the quest for a disease-modifying biologic therapy in pSS

Soluble P-selectin levels in synovial fluid and serum from patients with psoriatic arthritis

Objective: P-selectin is an adhesion molecule expressed by activated endothelial cells and platelets favouring the leukocyte adherence to microvascular endothelium. A soluble form of this molecule has been described, whose serum levels were found to be elevated and correlate with disease activity in rheumatoid arthritis (RA) patients. Aim of this study was to determine soluble P-selectin levels in synovial fluid (SF) and serum from patients with psoriatic arthritis (PsA), where it has never been investigated, to define its involvement in PsA synovial damage. Methods: we analysed, by ELISA, soluble P-selectin serum and SF levels in 100 patients presenting a knee joint effusion: 38 of them presented PsA, 40 RA and 22 osteoarthritis (OA). We examined the main clinical and laboratory parameters of these patients. Soluble P-selectin serum levels were also detected in 15 healthy subjects. Results: soluble P-selectin SF levels were significantly higher in PsA and RA patients respect to OA subjects. Soluble P-selectin SF levels were lower than those found in serum and the SF/serum ratio was higher in PsA and RA patients respect to OA. Soluble P-selectin serum levels were not significantly different among patients and controls. No correlation was found between SF and serum levels of soluble P-selectin and the main clinical parameters. Conclusions: our study of soluble P-selectin in PsA reveals a prominent local role of this molecule, with no differences respect to RA. Histological findings may be of help in understanding the role of this adhesion molecule in PsA

Relativistic Proton Production During the 14 July 2000 Solar Event: The Case for Multiple Source Mechanisms

Protons accelerated to relativistic energies by transient solar and interplanetary phenomena caused a ground-level cosmic ray enhancement on 14 July 2000, Bastille Day. Near-Earth spacecraft measured the proton flux directly and ground-based observatories measured the secondary responses to higher energy protons. We have modelled the arrival of these relativistic protons at Earth using a technique which deduces the spectrum, arrival direction and anisotropy of the high-energy protons that produce increased responses in neutron monitors. To investigate the acceleration processes involved we have employed theoretical shock and stochastic acceleration spectral forms in our fits to spacecraft and neutron monitor data. During the rising phase of the event (10:45 UT and 10:50 UT) we find that the spectrum between 140 MeV and 4 GeV is best fitted by a shock acceleration spectrum. In contrast, the spectrum at the peak (10:55 UT and 11:00 UT) and in the declining phase (11:40 UT) is best fitted with a stochastic acceleration spectrum. We propose that at least two acceleration processes were responsible for the production of relativistic protons during the Bastille Day solar event: (1) protons were accelerated to relativistic energies by a shock, presumably a coronal mass ejection (CME). (2) protons were also accelerated to relativistic energies by stochastic processes initiated by magnetohydrodynamic (MHD) turbulence.Comment: 38 pages, 9 figures, accepted for publication in the Astrophysical Journal, January, 200