Ankylosing Spondylitis: a trade Off of HLA-B27, ERAP, and pathogen interconnections? Focus on Sardinia

The frequency of HLA-B27 in patients with Ankylosing Spondylitis (AS) is over 85%. There are more than 170 recognized HLA-B27 alleles but the majority of them is not sufficiently represented for genetic association studies. So far only two alleles, the HLA-B*2706 in Asia and the HLA-B*2709 in Sardinia, have not been found to be associated with AS. The highly homogenous genetic structure of the Sardinian population has favored the search of relevant variants for disease-association studies. Moreover, malaria, once endemic in the island, has been shown to have contributed to shape the native population genome affecting the relative allele frequency of relevant genes. In Sardinia, the prevalence of HLA-B*2709, which differs from the strongly AS-associated B*2705 prototype for one amino acid (His/Asp116) in the F pocket of the peptide binding groove, is around 20% of all HLA-B27 alleles. We have previously hypothesized that malaria could have contributed to the establishment of this allele in Sardinia. Based on our recent findings, in this perspective article we speculate that the Endoplasmic Reticulum Amino Peptidases, ERAP1 and 2, associated with AS and involved in antigen presentation, underwent co-selection by malaria. These genes, besides shaping the immunopeptidome of HLA-class I molecules, have other biological functions that could also be involved in the immunosurveillance against malaria

Cranial neuralgias: from physiopathology to pharmacological treatment

Cranial neuralgias are paroxysmal painful disorders of the head characterised by some shared features such as unilaterality of symptoms, transience and recurrence of attacks, superficial and "shock-like" quality of pain and the presence of triggering factors. Although rare, these disorders must be promptly recognised as they harbour a relatively high risk for underlying compressive or inflammatory disease. Nevertheless, misdiagnosis is frequent. Trigeminal and glossopharyngeal neuralgias are sustained in most cases by a neurovascular conflict in the posterior fossa resulting in a hyperexcitability state of the trigeminal circuitry. If the aetiology of trigeminal neuralgia (TN) and other typical neuralgias must be brought back to the peripheral injury, their pathogenesis could involve central allodynic mechanisms, which, in patients with inter-critical pain, also engage the nociceptive neurons at the thalamic-cortical level. Currently available medical treatments for TN and other cranial neuralgias are reviewed

Friends and Symptom Dimensions in Patients with Psychosis: A Pooled Analysis

PMCID: PMC3503760This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Modelling the length of hospital stay in medicine and surgical departments

Healthcare Associated Infections are among the world's leading public health problems and the most serious complications for hospitalized patients that can impact length of stay (LOS). In this work, medical record data of 24365 patients admitted to general surgery and clinical medicine wards were used collectively with the aim of creating models capable of predicting overall LOS, measured in days, considering clinical information. Multiple linear regression analysis was performed with IBM SPSS, the coefficient of determination (R2) was equal to 0,288. A regression analysis with ML algorithms was performed with the Knime Analysis Platform. The R2 were quite low for both multiple linear regression and ML regression analyses. The use of these techniques showed that there is a relationship between clinical variables and overall LOS. The results constitute a valid support tool for decision makers to provide the turnover index for the benefit of health policy in the management of departments

AIF-1 gene does not confer susceptibility to Behçet's disease: Analysis of extended haplotypes in Sardinian population

Background BehcEet's disease (BD) is a polygenic immune-mediated disorder characterized by a close association with the HLA-B∗51 allele. The HLA region has a strong linkage disequilibrium (LD) and carries several genetic variants (e.g. MIC-A, TNF-α genes) identified as associated to BD because of their LD with HLA-B∗51. In fact, the HLA-B∗51 is inherited as part of extended HLA haplotypes which are well preserved in patients with BD. Sardinian population is highly differentiated from other Mediterranean populations because of a distinctive genetic structure with very highly preserved HLA haplotypes. Patients and methods In order to identify other genes of susceptibility to BD within the HLA region we investigated the distribution of human Allograft Inflammatory Factor-1 (AIF-1) gene variants among BD patients and healthy controls from Sardinia. Six (rs2736182; rs2259571; rs2269475; rs2857597; rs13195276; rs4711274) AIF-1 single nucleotide polymorphisms (SNPs) and related extended haplotypes have been investigated as well as their LD within the HLA region and with HLA-B∗51. Overall, 64 BD patients, 43 HLA-B∗51 positive healthy controls (HC) and 70 random HC were enrolled in the study. Results HLA-B∗51 was the only allele with significantly higher frequency (pc = 0.0021) in BD patients (40.6%) than in HC (9.8%). The rs2259571TAIF-1 variant had a significantly reduced phenotypic, but not allelic frequency in BD patients (72.1%; pc = 0.014) compared to healthy population (91.3%). That was likely due to the LD between HLA-B∗51 and rs2259571G(pc= 9E-5), even though the rs2259571Gdistribution did not significantly differ between BD patients and HC. Conclusion No significant difference in distribution of AIF-1 SNPs haplotypes was observed between BD patients and HC and between HLA-B∗51 positive BD patients and HLA-B∗51 positive HC. Taken together, these results suggest that AIF-1 gene is not associated with susceptibility to BD in Sardinia

Epitaxial thin films of multiferroic Bi2FeCrO6 with B-site cationic order

Epitaxial thin films of Bi2FeCrO6 have been synthesized by pulsed laser deposition on SrRuO3 on (100)- and (111)-oriented SrTiO3 substrates. Detailed X-ray diffraction and cross-section transmission electron microscopy analysis revealed a double perovskite crystal structure of the Bi2FeCrO6 epitaxial films very similar to that of BiFeO3 along with a particularly noteworthy Fe3+/Cr3+ cation ordering along the [111] direction. The films contain no detectable magnetic iron oxide impurities and have the correct cationic average stoichiometry throughout their thickness. They however exhibit a slight modulation in the Fe and Cr compositions forming complementary stripe patterns, suggesting minor local excess or depletion of Fe and Cr. The epitaxial BFCO films exhibit good ferroelectric and piezoelectric properties, in addition to magnetic properties at room temperature, as well as an unexpected crystallographic orientation dependence of their room temperature magnetic properties. Our results qualitatively confirm the predictions made using the ab-initio calculations: the double-perovskite structure of Bi2FeCrO6 films exhibit a Fe3+/Cr3+ cation ordering and good multiferroic properties, along with the unpredicted existence of magnetic ordering at room temperature.Comment: Accepted for publication in Journal of Materials Researc

Expression analysis of HLA-E and NKG2A and NKG2C receptors points at a role for natural killer function in ankylosing spondylitis

Background. Ankylosing Spondylitis (AS) is a complex chronic inflammatory disease strongly associated with the majority of HLA-B27 alleles. HLA-E are non-classical MHC class I molecules that specifically interact with the natural killer receptors NKG2A (inhibitory) and NKG2C (activating), and have been recently proposed to be involved in AS pathogenesis. Objectives: To analyze the expression of HLA-E and the CD94/NKG2 pair of receptors in HLA-B27 positive AS patients and healthy controls (HC) bearing the AS-associated, B*2705 and the non-AS-associated, B*2709 allele. Methods: The level of surface expression of HLA-E molecules on CD14 positive peripheral blood mononuclear cell was evaluated in 21 HLA-B*2705 patients with AS, 12 HLA-B*2705 HC, 12 HLA-B*2709 HC and 6 HLA-B27 negative HC, using the monoclonal antibody MEM-E/08 by quantitative cytofluorimetric analysis. The percentage and density of expression of HLA-E ligands NKG2A and NKG2C were also measured on CD3-CD56+ NK cells. Results. HLA-E expression in CD14 positive cells was significantly higher in AS patients (587.0 IQR 424-830) compared to B*2705 HC (389 IQR 251.3-440.5, p=0.0007), B*2709 HC (294.5 IQR 209.5-422, p=0.0004) and HLA-B27 negative HC (380 IQR 197.3-515.0, p=0.01). A higher number of NK cells expressing NKG2A compared to NKG2C was found in all cohort analysed as well as a higher cell surface density. Conclusion: The higher surface level of HLA-E molecules in AS patients compared to HC, concurrently with a prevalent expression of NKG2A, suggests that the crosstalk between these two molecules might play a role in AS pathogenesis accounting for the previously reported association between HLA-E and AS

Improving performance of the hospitalization process by applying the principles of Lean Thinking

Purpose: The goal was to improve the quality of the hospitalization process and the management of patients, allowing the reduction of costs and the minimization of the preoperative Length of Hospital Stay (LOS). Design/methodology/approach: The methodology used to improve the quality of the hospitalization process and patient management was Lean Thinking. Therefore, the Lean tools (Value stream map and Ishikawa diagram) were used to identify waste and inefficiencies, improving the process with the implementation of corrective actions. The data was collected through personal observations, patient interviews, brainstorming and from printed medical records of 151 patients undergoing oral cancer surgery in the period from 2006 to 2018. Findings: The authors identified, through Value Stream Map, waste and inefficiencies during preoperative activities, consequently influencing preoperative LOS, considered the best performance indicator. The main causes were identified through the Ishikawa diagram, allowing reflection on possible solutions. The main corrective action was the introduction of the pre-hospitalization service. A comparative statistical analysis showed the significance of the solutions implemented. The average preoperative LOS decreased from 4.90 to 3.80 days (−22.40%) with a p-value of 0.001. Originality/value: The methodology allowed to highlight the improvement of the patient hospitalization process with the introduction of the pre-hospitalization service. Therefore, by adopting the culture of continuous improvement, the flow of hospitalization was redrawn. The benefits of the solutions implemented are addressed to the patient in terms of lower LOS and greater service satisfaction and to the hospital for lower patient management costs and improved process quality. This article will be useful for those who need examples on how to apply Lean tools in healthcare