CLINICAL FEATURES AND TREATMENT OF MEDITERRANEAN SPOTTED FEVER IN CHILDREN: A PRACTICAL UPDATE FOR THE CLINICIAN

Mediterranean spotted fever (MSF) is a tick-borne disease caused by Rickettsia conorii. It is characterized by the symptomatologic triad of fever, exanthema and «tache noire» – the typical eschar at the site of the tick bite. Oral or parenteral administration of tetracyclines or chloramphenicol represent the standard treatment; however, both these drugs may cause significant adverse effects in children. Recent studies indicate that oral clarithromycin and azithromycin may represent an acceptable alternative for the treatment of children with MSF. There are no data to indicate that antimicrobial prophylaxis is beneficial for tick-bitten patients to prevent MSF. However, in the presence of a lesion ascribed to «tache noire», antibiotic treatment should be started even in the absence of fever or exanthema

Systematic review: macrophage activation syndrome in inflammatory bowel disease

BACKGROUND: Recently, there have been increasingly frequent reports on the occurrence of macrophage activation syndrome (MAS) in patients with inflammatory bowel disease (IBD). Clinically, MAS is characterized mainly by fever, hepatosplenomegaly, cytopenia, and elevated circulating ferritin and CD25. Mortality, even if diagnosed rapidly, is high. AIM: To identify all reports on MAS in IBD and to establish data on triggering agents, immunosuppression leading to MAS, and mortality. METHODS: A language unrestricted search on Pubmed and Scopus relating to the past 30 years was carried out by matching the following search-terms: h(a)emophagocytic lymphohistiocytosis OR h(a)emophagocytic lymphohistiocytic syndrome OR macrophage activation syndrome OR opportunistic infections OR cytomegalovirus OR Epstein-Barr virus AND Crohn's disease OR ulcerative colitis OR inflammatory bowel disease(s). RESULTS: Fifty cases were identified with an overall mortality of 30%. Virus-related MAS associated with cytomegalovirus or Epstein-Barr virus infections represents the main type of MAS, but in isolated cases bacterial infections precipitated the syndrome. In four cases (8%), a lymphoma was present at the time of MAS diagnosis or developed shortly thereafter. Thiopurine monotherapy was given before MAS onset in 56% of the patients, whereas multiple immunosuppression, including biologics, was administered to 24%. CONCLUSIONS: In IBD patients, the syndrome appears to be triggered by infections, but genetic susceptibility may contribute to its development. Since immunosuppressive therapy represents the backbone of therapeutic interventions in IBD, with the risk of new, or the reactivation of latent infections, even more frequent cases of macrophage activation syndrome may be expected

STAT1 and Its Crucial Role in the Control of Viral Infections

The signal transducer and activator of transcription (STAT) 1 protein plays a key role in the immune response against viruses and other pathogens by transducing, in the nucleus, the signal from type I, type II and type III IFNs. STAT1 activates the transcription of hundreds of genes, some of which have been well characterized for their antiviral properties. STAT1 gene deletion in mice and complete STAT1 deficiency in humans both cause rapid death from severe infections. STAT1 plays a key role in the immunoglobulin class-switch recombination through the upregulation of T-bet; it also plays a key role in the production of T-bet+ memory B cells that contribute to tissue-resident humoral memory by mounting an IgG response during re-infection. Considering the key role of STAT1 in the antiviral immune response, many viruses, including dangerous viruses such as Ebola and SARS-CoV-2, have developed different mechanisms to inhibit this transcription factor. The search for drugs capable of targeting the viral proteins implicated in both viral replication and IFN/STAT1 inhibition is important for the treatment of the most dangerous viral infections and for future viral pandemics, as shown by the clinical results obtained with Paxlovid in patients infected with SARS-CoV-2

Toxic Tau Oligomers Modulated by Novel Curcumin Derivatives

The pathological aggregation and accumulation of tau, a microtubule-associated protein, is a common feature amongst more than 18 different neurodegenerative diseases that are collectively known as tauopathies. Recently, it has been demonstrated that the soluble and hydrophobic tau oligomers are highly toxic in vitro due to their capacity towards seeding tau misfolding, thereby propagating the tau pathology seen across different neurodegenerative diseases. Modulating the aggregation state of tau oligomers through the use of small molecules could be a useful therapeutic strategy to target their toxicity, regardless of other factors involved in their formation. In this study, we screened and tested a small library of newly synthesized curcumin derivatives against preformed recombinant tau oligomers. Our results show that the curcumin derivatives affect and modulate the tau oligomer aggregation pathways, converting to a more aggregated non-toxic state as assessed in the human neuroblastoma SH-SY5Y cell line and primary cortical neuron cultures. These results provide insight into tau aggregation and may become a basis for the discovery of new therapeutic agents, as well as advance the diagnostic field for the detection of toxic tau oligomers

Analysis and Acoustic Correction of a Contemporary Italian Church

Abstract Nowadays, architects and designers build new churches primarily considering the architectural shape to emphasize the iconographic message without sufficiently investigating the acoustic climate. In many cases, designers propose elliptical or irregular geometries for the shapes of these buildings and, in addition, the furniture of indoor surfaces have unsuitable absorption and diffusivity coefficients. Thereby, it can be observed the arise of serious acoustical problems such as standing waves, flutter echo, sound focusing and intensive late reflections (greater than 100 ms) which seriously decrease speech intelligibility and diminish the effectiveness of the early sound energy. This paper presents the results of an acoustic survey on the Catholic Church "Invaluable Blood of Jesus", situated in Ragusa (Italy), which is characterized by many problems mentioned above. During last years, some refurbishment interventions have attempted to reduce the acoustic discomfort, but an uncorrected approach has completely compromised the speech intelligibility, especially during liturgical functions. Recently, the authors have been involved to propose suitable interventions for improving the acoustic quality of this environment. Preliminarily, a measurement survey was conducted to evaluate the main acoustic indices (RT60, STI, EDT, C80, D50) and portray the current acoustic climate. After that, it was developed an acoustic computer simulation on a 3D model of the church, in order to calibrate the model comparing measured and simulated data. This procedure allowed testing the reliability and accuracy of the model. Finally, We propose two different interventions of acoustic correction. Globally it is possible to obtain an improvement of RT60 from 7.3 to 2.5 s at 1 kHz and STI increases from 33% to 40%, at 1000 Hz

Please, do not forget secondary hemophagocytic lymphohistiocytosis in HIV-infected patients.

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