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Dedicated studies evaluating the impact of COVID-19 on outcomes of pancreatobiliary IgG4 related disease (IgG4-RD) patients are scarce. Whether COVID-19 infection or vaccination would trigger IgG4-RD exacerbation remains unknown.Pancreatobiliary IgG4-RD patients ≥ 18 years old with active follow-up since January 2020 from nine referral centers in Asia, Europe, and North America were included in this multicenter retrospective study. Outcome measures include incidence and severity of COVID-19 infection, IgG4-RD disease activity and treatment status, interruption of indicated IgG4-RD treatment. Prospective data on COVID-19 vaccination status and new COVID-19 infection during the Omicron outbreak were also retrieved in the Hong Kong cohort.Of the 124 pancreatobiliary IgG4-RD patients, 25.0% had active IgG4-RD, 71.0% were on immunosuppressive therapies and 80.6% had ≥ 1 risk factor for severe COVID. In 2020 (pre-vaccination period), two patients (1.6%) had COVID-19 infection (one requiring ICU admission), and 7.2% of patients had interruptions in indicated immunosuppressive treatment for IgG4-RD. Despite a high vaccination rate (85.0%), COVID-19 infection rate has increased to 20.0% during Omicron outbreak in the Hong Kong cohort. A trend towards higher COVID-19 infection rate was noted in the non-fully vaccinated/unvaccinated group (17.6% vs 33.3%, P = 0.376). No IgG4-RD exacerbation following COVID-19 vaccination or infection was observed.While a low COVID-19 infection rate with no mortality was observed in pancreatobiliary IgG4-RD patients in the pre-vaccination period of COVID-19, infection rate has increased during the Omicron outbreak despite a high vaccination rate. No IgG4-RD exacerbation after COVID-19 infection or vaccination was observed.

Severe acute respiratory syndrome coronavirus 2 is associated with a severe respiratory disease in China, that rapidly spread across continents. Since the beginning of the pandemic, available data suggested the asymptomatic transmission and patients were treated with specific drugs with efficacy and safety data not always satisfactory. The aim of this review is to describe the vaccines developed by three companies, Pfizer‐BioNTech, Moderna, and University of Oxford/AstraZeneca, in terms of both technological and pharmaceutical formulation, safety, efficacy, and immunogenicity. A critical analysis of Phases 1, 2, and 3 clinical trial results available was conducted, comparing the three vaccine candidates, underlining their similarities and differences. All candidates showed consistent efficacy and tolerability; although some differences can be noted, such as their technological formulation, temperature storage, which will be related to logistics and costs. Further studies will be necessary to evaluate long‐term effects and to assess the vaccine safety and efficacy in the general population., Highlights The rapid development of SARS‐CoV‐2 vaccines has been possible because in the last 20 years there have been rapid improvements in vaccine development in different scientific areas, such as molecular biology, genetic engineering, nano‐materials and lipid nanotechnology.The first three SARS‐CoV‐2 vaccines developed by Pfizer–BioNTech, Moderna and the University of Oxford/AstraZeneca are described, in terms of technology, pharmaceutical formulation, safety, efficacy and immunogenicity.The main detectable difference concerns the technological formulation, influencing logistics: two of these are mRNA‐based vaccines encapsulated in LNPs, whereas one is a DNA‐based vaccine encapsulated in viral vector.mRNA‐based vaccines have an advantage over DNA ones, because mRNA is directly translated in the cytoplasm form ribosomes once inside the cell.Technological and scientific advances allowed the encapsulation of mRNA into custom‐designed LNPs that mimic the structural features of a viral vector.Efficacy and safety studies of Pfizer–BioNTech, Moderna and the University of Oxford/AstraZeneca vaccines are reported, to report the massive pharmaceutical innovation brought.

Made available in DSpace on 2022-04-28T19:46:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-02-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The study aimed to identify and quantify the metabolites profile and metabolic pathways in human muscle tissue engaged during exhaustive high-intensity cycling exercise. Seven healthy physically active men performed a graded exercise test and an exhaustive supramaximal effort at 115% of maximal aerobic power with muscles biopsies performed in rest and immediately after exhaustion for quantifying of muscle metabolites changes by 1H-NMR spectroscopy. The time until exhaustion (tlim) recorded was 224.7 ± 35.5 s whereas the muscle pH at exhaustion was 6.48 ± 0.05. A total of 54 metabolites were identified and quantified. The most enriched and impacted pathways included: beta oxidation of very long chain fatty acids, mitochondrial electron transport chain, alanine aspartate, and glutamate metabolism, citric acid cycle, arginine biosynthesis, propanoate metabolism, threonine and 2-oxobutanoate degradation and pyruvate metabolism. In addition, the muscle concentrations in Post exercise, compared to Pre increased significantly (p

BACKGROUND: Autoimmune pancreatitis (AIP) is a rare, and relatively new, form of chronic pancreatitis. The management of AIP can vary considerably among different centres in daily clinical practice. OBJECTIVES: The aim of this study is to present a picture of epidemiological, clinical characteristics, outcomes, and the real-life practice in terms of management in several academic and non-academic centres in Italy. METHODS: Data on the clinical presentation, diagnostic work-up, treatments, frequency of relapses, and long-term outcomes were retrospectively collected in a cohort of AIP patients diagnosed at 14 centres in Italy. RESULTS: One hundred and six patients were classified as type 1 AIP, 48 as type 2 AIP, and 19 as not otherwise specified. Epidemiological, clinical, radiological, and serological characteristics, and relapses were similar to those previously reported for different types of AIP. Endoscopic cytohistology was available in 46.2% of cases, and diagnostic for AIP in only 35.2%. Steroid trial to aid diagnosis was administered in 43.3% cases, and effective in 93.3%. Steroid therapy was used in 70.5% of cases, and effective in 92.6% of patients. Maintenance therapy with low dose of steroid (MST) was prescribed in 25.4% of cases at a mean dose of 5 (±1.4) mg/die, and median time of MST was 60 days. Immunosuppressive drugs were rarely used (10.9%), and rituximab in 1.7%. Faecal elastase-1 was evaluated in only 31.2% of patients, and was pathological in 59.2%. CONCLUSIONS: In this cohort of AIP patients, diagnosis and classification for subtype was frequently possible, confirming the different characteristics of AIP1 and AIP2 previously reported. Nevertheless, we observed a low use of histology and steroid trial for a diagnosis of AIP. Steroid treatment was the most used therapy in our cohort. Immunosuppressants and rituximab were rarely used. The evaluation of exocrine pancreatic insufficiency is underemployed considering its high prevalence.

Background Asymptomatic patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) can develop hypercoagulable conditions and acute vascular events. The objective of this study is to determine whether SARS‐CoV‐2 was present in resected specimens from patients with acute bowel ischemia, but asymptomatic for Coronavirus Disease 2019 (COVID‐19) and with persistently real‐time polymerase chain reaction negative pharyngeal swab. Methods Three consecutive patients presented severe abdominal symptoms due to extensive ischemia and necrosis of the bowel, with co‐existent thrombosis of abdominal blood vessels. None had the usual manifestations of COVID‐19, and repeated pharyngeal swabs tested negative. They underwent emergency surgery with intestinal resection. Immunohistochemical testing for SARS‐CoV‐2 on resected tissue was performed. Results All tested samples were strongly positive for SARS‐CoV‐2. Conclusions This is the first case report in which patients with severe intestinal symptoms presented a marked SARS‐CoV‐2 positivity in the resected tissues, without any usual clinical manifestations of COVID‐19. These results suggest that the patients might be infected with SARS‐CoV‐2 presenting acute abdominal distress but without respiratory or constitutional symptoms.

Suture materials are the most common bioimplants in surgical and clinical practice, playing a crucial role in wound healing and tendon and ligament repair. Despite the assortment available on the market, sutures are still affected by significant disadvantages, including failure in mimicking the mechanical properties of the tissue, excessive fibrosis, and inflammation. This study introduces a mandrel-less electrodeposition apparatus to fabricate continuous microfiber wires of indefinite length. The mandrel-less biofabrication produces wires, potentially used as medical fibers, with different microfiber bundles, that imitate the hierarchical organization of native tissues, and tailored mechanical properties. Microfiber wire morphology and mechanical properties are characterized by scanning electron microscopy, digital image processing, and uniaxial tensile test. Wires are tested in vitro on monocyte/macrophage stimulation and in vivo on a rat surgical wound model. The wires produced by mandrel-less deposition show an increased M2 macrophage phenotype in vitro. The in vivo assessment demonstrates that microfiber wires, compared to the medical fibers currently used, reduce pro-inflammatory macrophage response and preserve their mechanical properties after 30 days of use. These results make this microfiber wire an ideal candidate as a suture material for soft tissue surgery, suggesting a crucial role of microarchitecture in more favorable host response.

The main cause of failure of the hip acetabular component is aseptic loosen- ing. Preclinical test methods currently used to assess the stability of hip acetabular implants rely on crude simplifications. Normally, either one com- ponent of motion or bone strains are measured. We developed a test method to measure implant 3D translations and rotations and bone strains using digital image correlation. Hemipelvises were aligned and potted to allow consistent testing. A force was applied in the direction of the load peak during level walking. The force was applied in 100‐cycle packages, each load package being 20% larger than the previous one. A digital image correlation system allowed measuring the cup‐bone relative 3D displacements (permanent migra- tions and inducible micromotions) and the strain distribution in the periacetabular bone. To assess the test repeatability, the protocol was applied to six composite hemipelvises implanted with very stable cups. To assess the suitability of the method to detect mobilisation, six loose implants were tested. The method was repeatable: the interspecimen variability was 16 μm for the bone/cup relative translations, 0.04° for the rotations. The method was capa- ble of tracking extremely loose implants (translations up to 4.5 mm; rotations up to 30°). The strain distribution in the bone was measured, showing the areas of highest strain. We have shown that it is possible to measure the 3D relative translations and rotations of an acetabular cup inside the pelvis and simultaneously to measure the full‐field strain distribution in the bone sur- face. This will allow better preclinical testing of the stability of acetabular implants.

Needleless injection systems are nowadays widespread and are mainly used to overcome the common problems of needle injection systems, such as pain, hematoma, scar tissue formation, infection or abscess, possibility of accidentally injecting into a venous vessel, and transmission of infectious diseases. All these problems are independent of the type of drug injected and are exclusively related to the needle devices. Current needleless injection systems are a valuable tool, which is especially available for the administration of vaccines to large numbers of patients. Our experience focused in particular on the so-called "jet injectors," of which one of the most valid representatives is Injex®. Our patent essentially concerns a medical needleless device, suitable to inject a subcutaneous AIT (allergy immunotherapy). The mechanism at the base of our device works with compressed air by means of a spring: It is very simple and similar to that of compressed air guns. Once the syringe has been filled, it is placed perpendicular to the skin, and then, the device is activated. The pressure vaporizes the drug, without changing or altering its chemical structure; it makes it pass through the epidermis, until it quickly reaches the subcutaneous layer, at a depth between 3.2 and 9.1 mm, without the patient feeling any pain. The entrance hole made by the needleless device in the epidermis is 0.17 mm rather than 0.39 mm of a normal needle. This type of administration also allows a uniform and spray diffusion of the drug, without causing localized inflammation, as it sometimes happens with normal syringe.

Although in vitro biomechanical tests are regularly performed, the definition of a suitable reference frame for hemipelvic specimens is still a challenge. The aims of the present study were to: (i) define a reference frame for the human hemipelvis suitable for in vitro applications, based on robust anatomical landmarks; (ii) identify the alignment of a hemipelvis based on the alignment of a whole pelvis (including right/left and male/female differences); (iii) identify the relative alignment of the proposed in vitro reference frame with respect to a reference frame commonly used in gait analysis; (iv) create an in vitro alignment procedure easy, robust and inexpensive; (v) quantify the intra-operator repeatability and inter-operator reproducibility of the procedure. A procedure to univocally identify the anatomical landmarks was created, exploiting the in vitro accessibility of the specimen's surface. Through the analysis on 53 CT scans (106 hemipelvises), the alignment of the hemipelvis based on the alignment of a whole pelvis was analyzed: differences between male/female and right/left hemipelvises were not statistically significant To overcome the uncertainty in the identification of the acetabular rim, a standard acetabular plane was defined. An alignment procedure was developed to implement such anatomical reference frame. The intra-operator repeatability and the inter-operator reproducibility were quantified with four operators, on male and female hemipelvises. The intra-operator repeatability was better than 1.5°. The inter-operator reproducibility was better than 2.0°. Alignment in the transverse plane was the most repeatable. The presented procedure to align hemipelvic specimens is sufficiently robust, standardized, and accessible. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1645-1652, 2018.

Insulin-like growth factor 1 (IGF1) and its receptor IGF1R regulate normal cell growth and contribute to cell transformation through activation of downstream signaling pathways. In fibroblast cells, insulin receptor substrate 1 (IRS1), through IGF1 signaling, was found to be the key protein for nuclear translocation of β-catenin and MYC transcription activation. We herein investigated the IRS1/β-catenin axis in acute lymphoblastic leukemia (ALL) cells. Samples were obtained from 45 patients with ALL and 13 healthy donors. ALL cell lines were used. Gene expression was measured by quantitative PCR. Protein expression, associations, and cellular localization were evaluated by immunoprecipitation, subcellular fractionation, and confocal microscopy. Cells were submitted to IGF1 stimulation and/or IGF1R pharmacological inhibition (OSI-906). IRS1, β-catenin, and MYC mRNA expression were significantly elevated in ALL patients, compared to normal controls. MYC mRNA expression positively correlated with β-catenin and IRS1. Increased age and MYC expression negatively affected overall survival by univariate analysis. Total and phospho-IGF1R and IRS1, MYC and β-catenin protein expression were higher in ALL cells, compared to normal peripheral blood mononuclear cells (PBMC). IRS1 and β-catenin were found to be colocalized in the nuclei and the cytoplasm of ALL cell lines, whereas both proteins were only slightly detected in the cytoplasm of normal PBMC. In Jurkat cells, a constitutive IRS1 and β-catenin protein interaction were observed; OSI-906 treatment decreased IGF1R tyrosine phosphorylation, IRS1 expression and phosphorylation, nuclear translocation of β-catenin, IRS1 and β-catenin association, and MYC protein expression. In conclusion, the IRS1/β-catenin axis is activated in ALL cells. J. Cell. Biochem. 118: 1774-1781, 2017. © 2016 Wiley Periodicals, Inc.