A novel methodology for epidemic risk assessment of COVID-19 outbreak.

We propose a novel data-driven framework for assessing the a-priori epidemic risk of a geographical area and for identifying high-risk areas within a country. Our risk index is evaluated as a function of three different components: the hazard of the disease, the exposure of the area and the vulnerability of its inhabitants. As an application, we discuss the case of COVID-19 outbreak in Italy. We characterize each of the twenty Italian regions by using available historical data on air pollution, human mobility, winter temperature, housing concentration, health care density, population size and age. We find that the epidemic risk is higher in some of the Northern regions with respect to Central and Southern Italy. The corresponding risk index shows correlations with the available official data on the number of infected individuals, patients in intensive care and deceased patients, and can help explaining why regions such as Lombardia, Emilia-Romagna, Piemonte and Veneto have suffered much more than the rest of the country. Although the COVID-19 outbreak started in both North (Lombardia) and Central Italy (Lazio) almost at the same time, when the first cases were officially certified at the beginning of 2020, the disease has spread faster and with heavier consequences in regions with higher epidemic risk. Our framework can be extended and tested on other epidemic data, such as those on seasonal flu, and applied to other countries. We also present a policy model connected with our methodology, which might help policy-makers to take informed decisions.

Significance of connective tissue disease features in idiopathic interstitial pneumonia.

In idiopathic interstitial pneumonia (IIP), the significance of connective tissue disease (CTD) features in the absence of a specific CTD diagnosis remains unclear. We studied the clinical and prognostic utility of a diagnosis of undifferentiated CTD (UCTD) in patients with biopsy-proven IIP. IIP patients undergoing surgical lung biopsy (1979-2005) were studied (nonspecific interstitial pneumonia (NSIP), n = 45; idiopathic pulmonary fibrosis, n = 56). UCTD was considered present when serum autoantibodies were present and symptoms or signs suggested CTD. The relationship between UCTD and NSIP histology was evaluated. A clinical algorithm that best predicted NSIP histology was constructed using a priori variables. The prognostic utility of UCTD, and of this algorithm, was evaluated. UCTD was present in 14 (31%) NSIP and seven (13%) IPF patients. UCTD was not associated with a survival benefit. The algorithm predictive of NSIP (OR 10.4, 95% CI 3.21-33.67; p<0.0001) consisted of the absence of typical high-resolution computed tomography (HRCT) features for IPF and 1) a compatible demographic profile (females aged <50 yrs) or 2) Raynaud's phenomenon. In patients with an HRCT scan not typical for IPF, this algorithm predicted improved survival (hazard ratio 0.35, 95% CI 0.14-0.85; p = 0.02) independent of IIP severity. UCTD is associated with NSIP histology. However, the diagnostic and prognostic significance of UCTD in IIP patients remains unclear.

Optimal scoring of serial change on chest radiography in sarcoidosis.

BACKGROUND: The optimal means of quantifying change on chest radiography in sarcoidosis is uncertain. In current guidelines, the role of serial measurement of carbon-monoxide diffusing capacity (DLco) remains undefined and the prevalence of discordance between serial chest radiographic change and pulmonary function tends is unknown. OBJECTIVE: To identify and explore key uncertainties in the monitoring of sarcoidosis by serial pulmonary function tests and chest radiography. DESIGN: 354 patients with sarcoidosis and concurrent tests (chest radiography and PFTs within three months at baseline, two years and/or four years) were studied. Chest radiographs were assessed by two radiologists for changes in stage and disease extent. Radiographic change and pulmonary function trends were quantified and compared. RESULTS: Change in radiographic extent of lung disease was always more frequent than change in stage (p < 0.0001) and there was poor agreement between change in stage and change in radiographic extent (Kw = 0.21 at two years; Kw = 0.23 at four years). Change in disease extent on chest radiography was linked to PFT trends on analysis of variance (p < 0.0005 for FEV1, FVC, DLco), whereas change in radiographic stage was not. Changes in gas transfer were often isolated or discordant with other serial data. Discordance between pulmonary function data and chest radiographic data was observed in 50% of cases. CONCLUSIONS: Change in radiographic extent is more applicable to routine monitoring in sarcoidosis than change in radiographic stage. In future guidelines, the role of serial gas transfer estimation and reconciliation of divergent chest radiographic and functional trends might usefully be addressed.

Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis.

In therapeutic studies in idiopathic pulmonary fibrosis (IPF), the low prevalence of significant change in pulmonary functional tests (PFTs) has been a major constraint. The prognostic value of "marginal" changes in PFTs in IPF and fibrotic non-specific interstitial pneumonia (NSIP) was evaluated. In patients with biopsy-proven IPF (n = 84) and NSIP (n = 72), forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (D( L,CO)) trends at 6 months were categorised as "significant" (FVC >10%; D(L,CO) >15%) or "marginal" (FVC 5-10%; D(L,CO) 7.5-15%). Proportional hazards analysis and time-dependent receiver operating characteristic methodology were used to examine PFT trends against mortality. In IPF, reductions in FVC were significant in 22 cases (26%) and marginal in 19 cases (23%). Mortality was higher in patients with a significant decline in FVC (hazard ratio (HR) 2.80, 95% CI 1.54-5.06; p<0.001) and those with a marginal decline in FVC (HR 2.31, 95% CI 1.19-4.50; p = 0.01) than in those with stable disease. Progression-free survival was lower when the decline in FVC was marginal than in stable disease (HR 2.34, 95% CI 1.19-4.60; p = 0.01). Marginal changes in D(L,CO) in IPF and marginal changes in FVC and D (L,CO) in fibrotic NSIP did not provide useful prognostic information. Marginal change in FVC in IPF denotes a poor outcome. These findings are applicable to clinical practice and to the selection of patients with more progressive disease for therapeutic studies.

Eosinophilic ileocolitis by Enterobius vermicularis: a description of two rare cases.

BACKGROUND: Human enterobiasis is usually mild. Occasionally, however, an "ectopic" disease may occur with a more severe course. Two rare cases of eosinophilic ileocolitis due to Enterobius vermicularis infection are reported here. CASE REPORTS: Case n degree 1 was 46 years old, presenting with fever and bloody diarrhoea. Blood eosinophilia was present. Stool microscopy demonstrated red blood cells and leukocytes. A 2 mm long worm with bilateral cervical wings was found in wet-mount preparations of faecal samples. The Scotch tape test was positive for Enterobius vermicularis eggs. Colon biopsy specimens showed massive eosinophilic infiltration and a typical pinworm section overlying the infiltrated mucosa. Case n degree 2 was a 24-year-old, anti-HIV negative homosexual, presenting with watery diarrhoea. Tests for malabsorption were negative. Three mm long adult male E. vermicularis were found on stool microscopy. Biopsy specimens from the colon showed eosinophilic infiltration. In both cases a 200 mg/day course of oral mebendazole eliminated the symptoms within 3 days. CONCLUSIONS: In these two cases the clinical presentation of enterobiasis was atypical. A common finding was the eosinophilic infiltration of bowel mucosa, although it is still uncertain whether the worm per se may induce mast cell degranulation and eosinophil activation. Nevertheless, the possibility of Enterobius vermicularis infection should be considered in the presence of eosinophilic ileocolitis.

Hemophagocytic syndrome in a case of splenic large B-cell lymphoma.

A case of splenic large B-cell lymphoma with hemophagocytic syndrome is reported. The difficulties of diagnosis are emphasized especially when peripheral lymph nodes or bone marrow lymphomatous infiltration are not present. Diagnostic criteria for hemophagocytic syndrome and their relationship with the pathogenesis of the disease are also stressed.

2-(4-Pyridyl)-delta 2-1,3,4-oxadiazolines from isonicotinoylhydrazones and diazomethane as potential antimycobacterial and anti-HIV agents. V.

The 5-aryl-4-methyl-2-(4-pyridyl)-delta 2-1,3,4-oxadiazolines 3, previously synthesized along with isomer 4-aryl-1-methoxy-1-(4-pyridyl)-2,3-diaza-1,3-butadienes 2 from benzaldehyde isonicotinoylhydrazones and diazomethane, were tested for in vitro activity against both M. tuberculosis and some atypical mycobacterial strains as well as against human immunodeficiency virus (HIV-1). Some halophenyl derivatives, 3e, 3g, 3i, 3j, were found to display MIC ranges from 1 to 10 (micrograms/ml against H 37 Rv and a clinical isolate tubercular strain, whereas against M. avium (MAC) the MICs were higher than 20 micrograms/ml. When the combinations of oxadiazolines with ethambutol, acting as inhibitor of cell wall synthesis, were assayed on MAC strain a synergistic effect was demonstrated for 3g and 3h trifluoromethyl derivatives. The antimycobacterial profiles of 2 and 3 analogues are compared and discussed. As shown by compounds 2, no substantial anti-HIV in vitro activity was found in selected delta 2-oxadiazolines; a moderate cytotoxicity, however, appears to be a common property.

Halogenated isoniazid derivatives as possible antimycobacterial and anti-HIV agents--III.

As part of a research directed to the synthesis of novel isoniazid derivatives with potential activity on mycobacteria and HIV virus, the acetophenone-isonicotinoylhydrazones 3 and the 4-aryl-1-methoxy-1-(4-pyridyl)- 2,3-diaza-1,3-butadienes 5, obtained by reaction between isonicotinoylhydrazones and diazomethane, have been prepared and tested for such activities. Both classes of derivatives showed interesting growth inhibitory activity on non-tubercular mycobacteria, including the emerging M. avium. Such activity appears to be linked to fluorine and/or chlorine presence on benzene rings. In contrast, none of the compounds submitted to the anti-AIDS in vitro screening, displayed any protection against HIV-1 virus-induced cytopathic effect in T4-lymphocyte cell lines.

Options in aesthetic restorations: discoloration and malformation--problems and solutions.

This article is a review of the current options for treatment of discolored and malformed dentition--laminate veneers, all-ceramic crowns, and metal-ceramic crowns. It emphasizes the importance of close cooperation between the restorative dentist and the laboratory technician and a thorough knowledge of the dental materials science. The objective of this article is to provide diverse solutions for severe tooth discolorations and malformations. Four cases illustrate the procedures, the materials utilized, and the results achieved.

3,3'-Bi-[1,3-thiazolidine-4-one] system. VII. Synthesis and SARS of some 2-heteroaryl derivatives with antiinflammatory and related activities.

In pursuing the research on the SARs of chiral 3,3'-Bi-[1,3-thiazolidine-4-one] system derivatives, two new structural modifications were explored, both having on chiral C atoms thienyl or 2/3 pyridyl groups which have been found to improve antiinflammatory and related activities in the previously studied 3,3'-(1,2-ethanediyl)bisthiazolidinones. In particular a trimetylene chain was introduced between N-3 and N-3' thus obtaining the 3,3'-(1,3-propanediyl) derivatives [type Ic compounds], whereas by elimination of a thiazolidinone ring the 2-heteroaryl-3-[2'(heteroarylidenamino) ethyl]-1,3-thiazolidine-4-one derivatives (type II compounds) were prepared. The new compounds were explored in vivo for their antiinflammatory, analgesic, antipyretic activities, as well as for acute toxicity and ulcerogenic effects. The results obtained don't allow us to draw any reliable SAR except that, by increasing the distance between thiazolidinonic rings, in Ic compounds, the pharmacological profile is not improved with respect to (1,2-ethanediyl) inferior homologs. Among compounds II, only the thienyl derivative 5 appears to have antiinflammatory and analgesic activities.

Halogenated isoniazid derivatives as possible antitubercular and antineoplastic agents. Note 1.

Halogenated arylhydrazones, 2-aryl-4-thiazolidinones and their 1,1-dioxides containing isoniazid (INI) moieties were prepared and explored for antimicrobial (against bacteria, Candida and mycobacteria) and antitumor activities. None of the tested compounds showed any marked antimicrobial effect. Furthermore, among the compounds submitted to NCI in vitro primary antitumor screening, those bearing 3-fluoro or -chlorophenyl substituents were found to possess selective inhibitory effects on the growth of non small cell lung cancer, whereas those with para-phenyl substituents displayed selective effects, sometimes statistically significant, against leukemias.

N-trifluoroacetyl derivatives as pharmacological agents. V. Evaluation of antiinflammatory and antimicrobial activities of some N-heterocyclic trifluoroacetamides.

Following the investigation on pharmacological aspects of N-trifluoroacetyl compounds some heterocyclic trifluoroacetamides were prepared and explored as potential antiinflammatory-analgesic and antimicrobial agents. The trifluoroacetamides 3, 4, 5, and 6 reached significant activity in the hot plate analgesic test; the same 4 and 5, along with 7 and 8 showed inhibitory properties in the adjuvant arthritis test; only 7 however, displayed a significant dose-dependent activity in the carrageenin edema test. In addition the parent heterocyclic amines were similarly explored for comparison. Test for antimicrobial activity were carried out in parallel. Among the examined compounds, only 4-aminomorpholine and 2-aminobenzimidazole were found active when assayed against gram+ and gram- bacteria and mycetes.

Alterations due to ampicillin and rifampicin in S. sanguis and S. aureus isolated from dental plaque. An electron microscopic study.

In this work we analysed the ultrastructural changes in S. aureus and S. sanguis after exposure to rifampicin and ampicillin respectively. S. aureus grown in the presence of rifampicin showed ultrastructural changes that can be summarized as follows: the peripheral cell-wall increased to three to five times the normal thickness; the cross-walls were considerably (two to ten times) thicker than normal; after 8 h of exposure a complete lysis occurred. S. sanguis grown in the presence of ampicillin showed ultrastructural changes that can be summarized as follows: aggregation and condensation of ribosomes; alterations of division with the presence of asynchronous septa; in some bacterial cells a prominent bulge was observed at one pole of the cell; after 8 h of exposure a complete lysis occurred.

Lymphocyte populations and T cell subpopulations in blood of patients with non-Hodgkin lymphomas.

Lymphocytic populations and T cell subsets were studied in the blood of patients with nonleukemic non-Hodgkin lymphoma. A statistically significant decrease of both the T lymphocytes and the OKT4-, OKT8-binding cells was detected in low-grade malignant lymphomas (LGML). A significant decrease of the T cell population and of the OKT4-binding cells was also found in high-grade malignant lymphomas (HGML); in these, the OKT8-binding cells were not lowered. The amount of the circulating B lymphocytes was not found to be altered both in HGML and in LGML.