Transmission mode associated with coronavirus disease 2019: a review.

OBJECTIVE: In late December 2019 in Wuhan (China), Health Commission reported a cluster of pneumonia cases of unknown etiology, subsequently isolated and named Severe Acute Respiratory Syndrome (SARS) Coronavirus 2 (CoV-2). In this review, the main transmission routes and causes of mortality associated with COVID-19 were investigated. MATERIAL AND METHODS: A review was carried out to recognize relevant research available until 10 April 2020. RESULTS: The main transmission routes of COVID-19 have been the following: animal to human and human-to-human pathways, namely: respiratory transmission; oro-fecal transmission; air, surface-human transmission. Transmission from asymptomatic persons, healthcare transmission, and interfamily transmission have been well documented. CONCLUSIONS: SARS-CoV-2 possesses powerful pathogenicity and transmissibility. It is presumed to spread primarily via respiratory droplets and close contact. The most probable transmission pathway is definitely the inter-human one. Asymptomatic patients seem to play a crucial role in spreading the infection. Because of COVID-19 infection pandemic potential, careful surveillance is essential to monitor its future host adaptation, viral evolution, infectivity, transmissibility, and pathogenicity in order to gain an effective vaccine and flock immunity and reduce mortality as soon and as much as it is possible.

Analysis of oral mucosa erosive-ulcerative lesions by reflectance confocal microscopy.

In vivo Reflectance Confocal Microscopy (RCM) allows to optically biopsy vital tissues, non-invasively and in real time. It results in horizontal virtual slices at a microscopic resolution and correlating with conventional histopathology. The aim of the present work is to describe RCM cellular and architectural findings in oral mucosae affected by erosive-ulcerative diseases, thus highlighting in vivo the wellknown histological peculiarities. A series of conventionally diagnosed Recurrent Aphthous stomatitis (RAS) and Pemphigus Vulgaris (PV) erosive and/or ulcerative oral lesions underwent RCM imaging to establish the application of RCM imaging to this kind of inflammatory non-tumoral lesions. A total of 12 RAS-related lesions and 8 PV-related lesions were considered. RCM imaging was capable to visualize their microscopic peculiarities, mainly inflammatory infiltrate, vessel dilation (RAS) and acantholytic cells, intraepithelial clefts and inflammatory cell carpets (PV). Despite RCM may result unnecessary to diagnose oral lesions referred to RAS and PV, its capability to highlight their main microscopic features could be advantageously used to monitor the healing or worsening of the clinical situation as well as the responsiveness/refractoriness to therapy.

Association between denture stomatitis, candida species and diabetic status.

Candida species are commensal yeasts of the oral cavity, which, under predisposing systemic and/or local circumstances, are responsible for a wide variety of clinical manifestations, globally known as oral candidiasis. Candida-associated denture stomatitis is an oral candidiasis particularly affecting the oral mucosa covered by a dental prosthesis, with several degree of severity. Diabetics suffer oral candidiasis more frequently than healthy individuals do and if they are denture wearers, the risk increases. Since various controversies still remain regarding the interrelationship among diabetes, oral Candida spp. strains involved in denture stomatitis and the presence of dentures, the present review aims to investigate the differences in Candida species frequencies and degree of denture stomatitis severity existing among diabetic and non- diabetic individuals, with and without dentures.

Topical toluidine blue-mediated photodynamic therapy for the treatment of oral lichen planus.

Photodynamic Therapy (PDT) is a minimally invasive approach that has shown promising results in management of oral, head and neck lesions. PDT can be used alone or in combination with other conventional treatments (surgery, chemotherapy, radiotherapy). Oral Lichen Planus (OLP) is a mucosal and cutaneous chronic disease characterized by an autoimmune insult of basal keratinocytes. We aim to evaluate the feasibility of topical toluidine blue-mediated PDT for the treatment of oral cavity multifocal homogeneous white lesions by oral lichen planus without dysplastic features.

Distinct regulators control the expression of the mid-hindbrain organizer signal FGF8.

Local expression of FGF8 at the mid/hindbrain boundary (MHB) governs the development of multiple neurons and support cells. Here we show that the paired-domain protein Pax2 is necessary and sufficient for the induction of FGF8 in part by regulating the expression of Pax5&8. A network of transcription and secreted factors, including En1, Otx2, Gbx2, Grg4 and Wnt1&4, that is established independently of Pax2, further refines the expression domain and level of FGF8 at the MHB through opposing effects on Pax2 activity. Our results indicate that the expression of local organizing factors is controlled by combinatorial interaction between inductive and modulatory factors.

Relationship between T lymphocyte responsiveness and T-helper1/T-helper2 type cytokine release in chronic hepatitis C: a critical reappraisal.

Recruitment of virus-specific T lymphocyte subpopulations to liver sites in chronic hepatitis C virus (HCV) infection implies a key role for the immune response in host-virus interaction. In spite of a multispecific and polyclonal cytotoxic function exerted by CD8+ lymphocytes, CD4-mediated activity is weak. This allows the infection to persist which in turn is responsible for the development of chronic hepatitis C (CH-C). Such a finding outlines the occurrence of a possible relationship between cytokine (CK) production by CD4 subsets, i.e. T helper (Th)1 or Th2 cells, and the clinical outcome. A prevalence of Th1-derived CK occurs in infected liver, while increased amounts of Th2-related CK are usually found in peripheral blood. Moreover, peripheral blood mononuclear cell (PBMC) cultures from CH-C subjects exhibit an impaired interferon (IFN)-gamma production and an increase of interleukin (IL)-12 p70 release after stimulation. The latter pattern seems to be due to the enhanced release of IL-12 p40 homodimers, which antagonize IL-12 p70 bioactivity and favour IL-10-induced effects. These results suggest that further extensive studies on the imbalance of the CK network at a molecular level are required to improve the therapeutical approach in CH-C subjects.

[Autoantibodies in chronic hepatitis C. Markers of autoimmunity or non-specific events?]. / Autoanticorpi nell'epatite cronica da virus C. Marcatori di autoimmunità o eventi aspecifici?

In the light of the high prevalence of non organ-specific autoantibodies in chronic hepatitis C, the possibility that such a finding may represent the consequence of a viral, autoimmune or overlapping disease should be considered, which may in turn require a different therapeutical approach. It is known, anyway, that the diagnosis of autoimmune hepatitis is based on a set of epidemiological, clinical, biochemical, histological criteria and autoantibody pattern. In 113 cases of chronic hepatitis with HCV infection, we determined the presence of non organ-specific autoantibodies [anti-nuclear (ANA), anti-smooth muscle (SMA), anti-liver-kidney microsomal antibodies (LKM), anti-mithocondrial antibodies (AMA)] and described the epidemiological, clinical, biochemical, histological characteristics and therapeutic response to interferon. 40 patients (35%) exhibited non organ-specific autoantibodies: 25 patients were SMA positive (Vasal pattern), 4 ANA positive (Speckled pattern), 7 ANA (Speckled pattern) + SMA (Vasal pattern) positive and 4 LKM positive. All subjects with HCV infection and autoantibodies did not display additional criterias of autoimmunity, including the same outcome to interferon therapy when compared to HCV positive patients without autoantibodies. The failure to determine clinical features, associated to autoimmunity in HCV positive patients with autoantibodies, suggests that autoantibody occurrence may represent a fortuitous event during the course of HCV infection.

Regulatory role of extracellular matrix proteins in neutrophil respiratory burst during aging.

Neutrophil respiratory burst was assessed on plates coated with fibronectin (FN) or laminin (LM), both used at dosages inhibiting polystyrene-triggered cell activation in young healthy volunteers. Under these conditions, a low, yet significant, spontaneous superoxide anion (O(2)(-)) production, matching with enhanced levels of basal adherence, was detected in FN-plated neutrophils of elderly donors. In contrast, although neutrophil stimulation with tumor necrosis factor (TNF)-alpha, granulocyte macrophage-colony stimulating factor (GM-CSF), fMLP or phorbol myristate acetate (PMA) gave rise to a massive and prolonged FN-primed O(2)(-) release, a significant impairment of oxidative response occurred in the aged group as a result of GM-CSF or fMLP cell challenge. Such an effect was not associated to an age-related imbalance of stimulant-triggered neutrophil adhesiveness to FN, even though a larger contribution of CD18-dependent versus CD18-independent pathways was observed in old as compared to young individuals. Notably, within the aged group, anti-CD18 monoclonal antibody cell pretreatment resulted in a higher suppression of FN-primed O(2)(-) release following TNF-alpha with respect to GM-CSF stimulation, thus implying that an agonist-related defect of the coupling between beta2 integrin-dependent adhesive and oxidative events is likely to occur as a feature of age. All physiological mediators failed to activate the respiratory burst of neutrophils plated on LM-coated wells in both young and aged donors. This effect appears to be the result of an active process, since neutrophils from either group of subjects adhered to LM-coated surfaces and LM inhibited in a dose-dependent manner the FN-priming effect on neutrophil O(2)(-) production. All together the findings provide additional evidence for an imbalance of neutrophil-mediated functions in the elderly.

[Acute disseminated encephalomyelitis as initial clinical manifestation of common variable immunodeficiency. A case report]. / Encefalomielite acuta disseminata come manifestazione clinica iniziale nel deficit immunologico comune variabile. Descrizione di un caso.

Common variable immunodeficiency (CVID) is a primary immunodeficiency disease characterized by severe and recurrent infections which affect both lung and gastrointestinal systems. On the contrary, central nervous system involvement, related to virus infections, is an important, rare and usually fatal complication occurring in a later phase of the disease. Furthermore, CVID may predispose to a variety of autoimmune diseases. Here, we report the case of a 20 years old girl who developed acute disseminated encephalomyelitis as the first clinical feature in CVID. The infective agent was not determined and there was no history of recent vaccinations. CVID was diagnosed on the basis of the significant reduction of serum immunoglobulin concentration, in the absence of either diseases responsible for secondary immunodeficiency or functional and/or quantitative abnormalities of lymphocyte subsets, phagocytes and complement fractions. The treatment with high doses of native intravenous immunoglobulins (IVIG) combined with corticosteroids in the early phase led to a complete recovery with restitutio ad integrum. This case outlines the possible relationship between autoimmune diseases and infections in CVID, as suggested by the finding of either viral encephalitis in CVID patients and the well-known autoimmune pathogenesis of acute disseminated encephalomyelitis. In such a condition, the combination of IVIG and corticosteroids may offer considerable advantages in terms of therapeutical efficacy.

IUBMB updates Ph.D. standards.

The Education Committee of the International Union of Biochemistry (IUB, but IUBMB since 1991) published its report on "Standards for the Ph.D. Degree in Biochemistry and Molecular Biology" in 1989. Developments since then have led to the disappearance of the traditional demarcations between many of the biological disciplines, while information technology and bioinformatics have revolutionized the analysis, storage, and communication of scientific data. To meet these challenges, that report has now been revised through a broad interdisciplinary and international consultation. This has led to the recent publication, on behalf of the same Committee, of "Standards for the PhD Degree in the Molecular Biosciences". Like its predecessor this revised report not only defines in behavioural terms the qualities and skills expected of doctoral graduates by the international community of molecular bioscientists but also offers useful suggestions and advice as to how those skills can be developed and maximized. In addition, it discusses various topics related to doctoral education.

Grafting an RGD motif onto an epidermal growth factor-like module: chemical synthesis and functional characterization of the chimeric molecule.

A novel protein was engineered by inserting the GRGDS motif of fibronectin within the 14-residue loop of the EGF-like module from human complement protease C1r. The resulting chimeric EGF-RGD module (52 residues, three disulfide bridges) was assembled by automated solid-phase synthesis using the t-Boc strategy. Using reduced/oxidized glutathione, the EGF-RGD module was folded as efficiently as the natural C1r-EGF module, resulting in formation of the appropriate disulfide bridge pattern as shown by mass spectrometry and N-terminal sequence analyses of thermolytic fragments. Circular dichroism and NMR measurements provided further indication that introduction of the GRGDS motif had no significant effect on the folding. Using Chinese Hamster Ovary (CHO) cells bearing the integrin receptors specific for fibronectin and vitronectin, EGF-RGD was shown to induce cell adhesion via the introduced GRGDS motif. Cell binding was inhibited specifically and efficiently by the synthetic peptide GRGDSP and by fibronectin, and to a much lesser extent by vitronectin, whereas the monoclonal antibody PB1 directed to the alpha5 subunit of alpha5beta1 integrin had no effect. The ability of EGF-RGD to trigger significant cell spreading and intracellular signaling was also demonstrated using immunofluorescence and confocal microscopy.

[Pericardial involvement as initial manifestation of multiple myeloma]. / Interessamento pericardico come manifestazione iniziale di mieloma multiplo.

Pericardial involvement is a rare complication of multiple myeloma, caused by amyloidosis, infections, or plasmacell infiltration, usually at late or terminal disease stage. We report a patient with pericarditis coming from a department of Cardiology where a preceding (15 years before) diagnosis of breast cancer and present bloody pericardial effusion with probably malignant cells permitted at first to orientate towards metastatic pericardial involvement in breast cancer. Laboratory findings (pancytopenia, hypogammaglobulinemia, proteinuria) suggested to perform bone marrow aspirate, serum and concentrated urine immunoelectrophoresis, measurement of 24-h urine protein excretion, and further cytologic and immunocytochemical assay of pericardial fluid. Acquired data allowed to diagnose light chain multiple myeloma with pericardial involvement caused by plasmacell infiltration. We diagnosed this complication, representing first and main clinical feature of multiple myeloma, owing to a complete clinical and laboratory evaluation and repetition of cytologic and immunocytochemical assay of pericardial fluid.