Exploring Factors Influencing Changes in Incidence and Severity of Multisystem Inflammatory Syndrome in Children

Multisystem inflammatory syndrome (MIS-C) is a rare condition associated with COVID-19 affecting children, characterized by severe and aberrant systemic inflammation leading to nonspecific symptoms, such as gastrointestinal, cardiac, respiratory, hematological, and neurological disorders. In the last year, we have experienced a progressive reduction in the incidence and severity of MIS-C, reflecting the worldwide trend. Thus, starting from the overall trend in the disease in different continents, we reviewed the literature, hypothesizing the potential influencing factors contributing to the reduction in cases and the severity of MIS-C, particularly the vaccination campaign, the spread of different SARS-CoV-2 variants (VOCs), and the changes in human immunological response. The decrease in the severity of MIS-C and its incidence seem to be related to a combination of different factors rather than a single cause. Maturation of an immunological memory to SARS-CoV-2 over time, the implication of mutations of key amino acids of S protein in VOCs, and the overall immune response elicited by vaccination over the loss of neutralization of vaccines to VOCs seem to play an important role in this change

Feasibility and effectiveness assessment of sars-cov-2 antigenic tests in mass screening of a pediatric population and correlation with the kinetics of viral loads

The gold standard for diagnosis of SARS-CoV-2 infection has been nucleic acid amplification tests (NAAT). However, rapid antigen detection kits (Ag-RDTs), may offer advantages over NAAT in mass screening, generating results in minutes, both as laboratory-based test or point-of-care (POC) use for clinicians, at a lower cost. We assessed two different POC Ag-RDTs in mass screening versus NAAT for SARS-CoV-2 in a cohort of pediatric patients admitted to the Pediatric Emergency Unit of IRCCS—Polyclinic of Sant’Orsola, Bologna (from November 2020 to April 2021). All patients were screened with nasopharyngeal swabs for the detection of SARS-CoV-2-RNA and for antigen tests. Results were obtained from 1146 patients. The COVID-19 Ag FIA kit showed a baseline sensitivity of 53.8% (CI 35.4–71.4%), baseline specificity 99.7% (CI 98.4–100%) and overall accuracy of 80% (95% CI 0.68–0.91); the AFIAS COVID-19 Ag kit, baseline sensitivity of 86.4% (CI 75.0–93.9%), baseline specificity 98.3% (CI 97.1–99.1%) and overall accuracy of 95.3% (95% CI 0.92– 0.99). In both tests, some samples showed very low viral load and negative Ag-RDT. This disagreement may reflect the positive inability of Ag-RDTs of detecting antigen in late phase of infection. Among all cases with positive molecular test and negative antigen test, none showed viral loads > 106 copies/mL. Finally, we found one false Ag-RDTs negative result (low cycle thresholds; 9 × 105 copies/mL). Our results suggest that both Ag-RDTs showed good performances in detection of high viral load samples, making it a feasible and effective tool for mass screening in actively infected children

Post-Traumatic Headache in Children after Minor Head Trauma: Incidence, Phenotypes, and Risk Factors

Minor head trauma (MHT) is very frequent in children and post-traumatic headache (PTH) is one of its most common complications; however, its management is still a challenge. We aimed to assess the incidence and clinical characteristics of, and risk factors for, PTH among children referred to our pediatric emergency department (PED) for MHT. A total of 193 patients aged 3–14 years evaluated for MTH were enrolled and followed up for 6 months through phone calls and/or visits. PTH occurred in 25/193 patients (13%). PTH prevalence was significantly higher in school-aged (≥6 years) than in pre-school-aged children (21.6% vs. 4.9%, respectively, p < 0.009). Females were found to be more affected. The median time of onset was 4.6 days after MHT; resolution occurred in a median of 7 weeks. In 83.3% of patients, PTH subsided in <3 months, while in 16.7% it persisted longer. A total of 25% of children exhibited the migraine and 75% the tension-type variant. Our analysis indicates the presence of headache upon arrival in PED, isolated or associated with nausea and dizziness, as a factor predisposing the patient to the development of PTH. Our findings could be useful to identify children at risk for PTH for specific follow-up, family counseling, and treatment

Immune response against adenovirus in acute upper respiratory tract infections in immunocompetent children

During acute upper respiratory tract infections (AURTIs) caused by Adenoviruses, the mix of severe clinical presentation, together with elevation of white blood cells (WBCs) and C-reactive protein (CRP), often mimicking bacterial infection, leads to an inappropriate use of antibiotics. We studied 23 immunocompetent children admitted to our Pediatric Emergency Unit with signs of acute Adenoviral AURTIs, aiming at better clarifying the biological background sustaining this clinical presentation. Infection etiology was tested with nasopharyngeal swabs, serology, and DNA-PCR. During fever peaks and subsequent recovery, we assessed WBC count with differential, CRP, procalcitonin, serum concentration of six inflammatory cytokines, and lymphocyte subset populations. Results: IL-6 and IL-8 were found elevated in the acute phase, whereas a significant decrease during recovery was found for IL-6 and IL-10. We highlighted an increase of B lymphocytes in the acute phase; conversely, during recovery, an increase in T regulatory cells was noted. Monocytes and leukocytes were found markedly elevated during fever peaks compared to convalescence. All patients recovered uneventfully. The composition of lymphocyte population subsets and serum alterations are the main drivers of an overprescribed antibiotic. Examination of hospital admissions and performance is needed in further investigations to rule out bacterial infections or inflammatory syndromes

Foreword to Special Issue on Advances in Optimization Methods in Heat and Mass Transfer

none4sinoneGiulio, Lorenzini; Bengt, Sunden; Cesare, Biserni; Gongnan, XieGiulio, Lorenzini; Bengt, Sunden; Cesare, Biserni; Gongnan, Xi

Multimodality imaging : novel pharmacological applications of reporter systems

The development of novel drugs is a lengthy process requiring years of preclinical research and many steps indispensable to ensure that the molecule of interest can be administered to humans with a minimal risk of toxic effects. Even a minimal reduction in the initial stages of drug development would result in a tremendous saving in time; therefore, pharmaceutical companies are eager to apply novel methodologies that shorten the time required for pharmacodynamic, pharmacokinetic and toxicological studies to be carried out in vitro and in animal systems. Currently, quantitative analysis of molecular events in living organisms is done with the combined application of imaging and genetic engineering technologies. In vivo imaging provides surrogate endpoints that can improve the identification of new drug candidates and speed up their research at preclinical stages. The integration of reporter systems in animal models of human diseases represents a reachable frontier that will dramatically advance drug development in terms of costs, time and efficacy. The present review outlines the applicability of imaging technologies for drug development and presents a panorama on the state of the art of currently available imaging technologies suitable for preclinical studies, with particular focus on bioluminescence and fluorescence as the methodologies of election

NEUROTROPIC T-CELL LYMPHOMA AND NEUROLYMPHOMATOSIS IN A CAT

A 5 years old Domestic Short Hair spayed female cat living in a shelter was referred to the Veterinary Teaching Hospital of the Bologna University for a history of sudden onset of monoplegia of the left forelimb associated to jaw paralysis, not responsive to antibiotics and corticosteroid treatment. On physical examination, performed four days after the onset of the signs, the cat showed poor body condition score, dull hair and scales, inspiratory stridor, hypothermia and moderate dehydration state. On neurological examination, the cat showed a severely depressed mental status, ambulatory tetraparesis with monoplegia of the left forelimb and plantigrade stance of the pelvic limbs. Other findings included decreased conscious proprioception in pelvic limbs and severely decreased withdrawal reflex in all four limbs. Multiple cranial nerves deficits included bilateral absence of palpebral reflex and menace response, decreased reaction to cotton ball test, reduction of facial sensation and of the gag reflex, paresis of the tongue and jaw paralysis. Horizontal nystagmus with a left fast phase and left partial Horner syndrome were also present. Neuroanatomical localization was consistent with a multifocal syndrome. Ante-mortem clinicopathologic evaluation included CBC, serum biochemistry panel, FIV/FeLV serology and cerebrospinal fluid (CSF) analysis. CBC was normal. Biochemical panel showed a severe increase in CK (10256 U/L, reference interval 91 \u2013 326 U/L) and a slight increase in transaminase and bile acids. Serologic test for FeLV was positive. CSF examination, despite corticosteroids ongoing treatment, was markedly abnormal, showing severe mononuclear pleocytosis (526 cells/μl, reference interval 0 \u2013 5 cell/μl) and elevated protein concentration (97,5 mg/dl, reference interval 0 - 30 mg/dl). On cytology the CSF specimens were highly cellular and almost exclusively composed by large (36 \u2013 40 μm) monomorphic lymphocytes with high N:C ratio, diffuse chromatin pattern and prominent nucleoli; mitoses were also readily evident (one to two mitotic figures per high power field). Due to poor prognosis, the cat was euthanized for human reasons. At necropsy, whitish soft 3-5 mm multilobulated masses were evident at the skull base, surrounding oculomotor nerves and semilunar ganglia, and around ganglia and roots of thoracic spinal nerves. No other changes were grossly apparent. Histology revealed the monotonous proliferation of medium-to-large lymphocytes, with scarce cytoplasm, round to oval nuclei and prominent central nucleoli. The lymphomatous tissue aggressively infiltrated and extended to the nervous tissue, with multifocal leptomeningeal involvement, occasional perivascular cuffings, focal neuropilar infiltration of the brain stem and spinal cord, and massive endoneurium infiltration. As a direct effect of the lymphoid infiltration, there were marked degeneration and atrophy of ganglionic perikaria, which showed severe pyknosis, chromatolysis and reactive satellite cells hyperplasia, and of axons, which showed distinct formation of digestion chambers. The lymphomatous infiltration extended also to cervical muscles; no lymphoid infiltrates were evident in other histologically examined tissues (lymph nodes, liver, kidney, spleen, lungs, heart, stomach, gut). Immunohistochemistry revealed strong and diffuse CD3 immunopositivity and CD79a negativity, thereby demonstrating T-cell phenotype (peripheral T-cell lymphoma). Fragment analysis (GeneScanning) of feline TCR gene rearrangements evidenced an oligoclonal pattern with few peaks of similar height. Integrated Feline Leukemia provirus was detected by PCR in isolated snap-frozen samples. Tumors of the peripheral nervous system (PNS) are very rare in cats, and lymphomas extending to PNS have been reported occasionally. Primary lymphomas of the nervous system are also rare and have been associated in human, feline and avian species wi..

Cancer modeling: modern imaging applications in the generation of novel animal model systems to study cancer progression and therapy

Cancer is the result of a series of genetic and epigenetic mutations that evolve over years even decades and lead to the transformed phenotype. Paradoxically, most methods developed to study these changes are static and do not provide insights on the dynamics of the sequela of steps involved in tumorigenesis. This major shortcoming now can be overcome with the application of reporter genes and imaging technologies, which are providing tools to examine specific molecular events and their role in the carcinogenic process in single cells. In the last decade reporter-based biosensors were created to study gene transcription, protein/protein interactions, sub-cellular trafficking and protease activities; this wealth of systems enable to monitor intracellular signaling pathways at several key check points specifically involved in cancer cell development. The challenge is now to extend cell-based models to the generation of reporter mice, where non-invasive in vivo imaging technologies allow to follow single molecular events. When combined with murine models of cancer, these technologies will give an unprecedented opportunity to spatio-temporally investigate the molecular events resulting in neoplasia. The aim of the present review is to highlight the major changes occurring in this rapidly evolving field and their potential for increasing our knowledge in cancer biology and for the research of novel and more efficacious therapies