Large community-acquired Legionnaires’ disease outbreak caused by Legionella pneumophila serogroup 1, Italy, July to August 2018

In July 2018, a large outbreak of Legionnaires\u2019 disease (LD) caused by Legionella pneumophila serogroup 1 (Lp1) occurred in Bresso, Italy. Fifty-two cases were diagnosed, including five deaths. We performed an epidemiological investigation and prepared a map of the places cases visited during the incubation period. All sites identified as potential sources were investigated and sampled. Association between heavy rainfall and LD cases was evaluated in a case-crossover study. We also performed a case\u2013control study and an aerosol dispersion investigation model. Lp1 was isolated from 22 of 598 analysed water samples; four clinical isolates were typed using monoclonal antibodies and sequence-based typing. Four Lp1 human strains were ST23, of which two were Philadelphia and two were France-Allentown subgroup. Lp1 ST23 France-Allentown was isolated only from a public fountain. In the case-crossover study, extreme precipitation 5\u20136 days before symptom onset was associated with increased LD risk. The aerosol dispersion model showed that the fountain matched the case distribution best. The case\u2013control study demonstrated a significant eightfold increase in risk for cases residing near the public fountain. The three studies and the matching of clinical and environmental Lp1 strains identified the fountain as the source responsible for the epidemic

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Two procedures for the syntheses of labeled sialic acids and their 1,7-lactones

The synthesis of four deuterated sialic acids and their 1,7-lactones has been performed in two ways, one based on sialic acid classical chemistry, and the other involving a direct exchange of the unlabeled acyl group of N-acetylneuraminic acid with a labeled one mediated by a perfluorinated amide. The final lactonization is promoted by benzyloxycarbonyl chloride

Synthesis of unnatural homologues of deoxypyridinoline as possible internal standards in analytical detection of pyridinolinic cross links of collagen

Three homologues of the collagen cross-links deoxypyridinoline, differing for the length of the side chain at the aromatic nitrogen, have been efficiently synthesized as possible internal standards in the quantitative analyses of pyridinolines. The first has a one carbon shorter N-chain, while other two have a one carbon and a two carbon longer N-chains. The stereogenic centers are introduced stereoselectively using Williams\u2019 glycine template methodology and oxazinones to generate chirality and to suitably protect the aminoacid functionality during assembly of the pyridinoline nucleus

General and Chemoselective N-Transacylation of Secondary Amides by Means of Perfluorinated Anhydrides

Zahlreiche funktionelle Gruppen, die unter den Bedingungen der klassischen N-Transacylierung hydrolysiert werden, werden toleriert, wenn die N-Transacylierung \ufcber perfluorierte Analoga verluft, die anschlie fend zu einem normalen Amid umgesetzt werden k\uf6nne

Spaying-related urinary incontinence and oestrogen therapy in the bitch

Some aspects of spaying-related urinary incontinence in the bitch still remain incompletely clarified. Therefore, the aims of the present study were to evaluate the prevalence of the disease among spayed dogs, to detect differences in risk related to the type of surgery, to describe the characteristics of incontinent bitches, to assess the influence of age at surgery on the onset of incontinence occurrence, and to assess the effectiveness and long-term side effects of oestrogen therapy in affected bitches. Among 750 bitches submitted to ovariectomy or ovariohysterectomy, those showing spaying-related urinary incontinence were evaluated. Oestrogen replacement therapy consisted of administering an effective dose followed by an individual maintenance dose. The results showed that the disease occurred in 5% of neutered bitches, the type of surgery did not affect the disease occurrence, affected bitches frequently represented large or giant breeds or large-size mongrels, the body weight of the affected bitches at surgery was often >= 20 kg, the disease seems to be associated with tail docking, the age at surgery influences the onset of incontinence, with earlier occurrence in older bitches, and that a strong co-operation between owners and veterinarians is necessary to achieve successful response to oestrogen replacement therapy. Long-term administration seems to be unrelated to oestrogenic side effects

Simultaneous free and glycosylated pyridinium crosslink determination in urine : Validation of an HPLC-fluorescence method using a deoxypyridinoline homologue as internal standard

Pyridinoline (Pyr), deoxypyridinoline (D-Pyr), galactosyl-pyridinoline (Gal-Pyr) and glucosyl\u2013galactosyl pyridinoline (GluGal-Pyr) are enzymatic mature pyridinium crosslinks. Generally, only total Pyr and DPyr urinary amounts (free + bound forms) are evaluated by HPLC as indices of bone resorption. This report describes the validation of an HPLC-fluorescence method for the simultaneous evaluation of free Pyr and D-Pyr, together with GluGal-Pyr and Gal-Pyr, in urine of healthy women (n = 20, aged 27\u201341) and girls (n = 20, aged 5\u201310). The use of an unnatural D-Pyr homologue, here proposed for the first time as internal standard, and of pure Pyr, D-Pyr, GluGal-Pyr and Gal-Pyr synthesized to be used as primary calibrators,guarantees method specificity and correct crosslink quantification. Urine, spiked with IS, was solid-phase extracted prior to HPLC analysis. Total Pyr and D-Pyr amounts were also evaluated after urine hydrolysis. The HPLC method was validated for selectivity, sensitivity, linearity, precision, accuracy, recovery and stability for all measured crosslinks. Both free and total Pyr and D-Pyr as well as GluGal-Pyr and Gal-Pyr amounts were significantly higher in girls than in women (p < 0.0001), indicating an increased collagen turnover rather than only bone turnover. Gal-Pyr, for the first time evaluated in girls, was under its lower quantification limit (<LLOQ, <21.20 pmol/mL) in women. The measurement of free and glycosylated pyridinium crosslinks might provide more information on the degradation of various types of collagen than only that of total Pyr and D-Pyr. Moreover, this validated method could be a useful non-invasive technique for studying pathological conditions characterized by modified glycosylation enzyme activity and for more clinical investigation on bone fragility

Measles serological survey in the Italian population: interpretation of results using mixture model.

In 2003-2004, a national measles seroprevalence study was conducted in Italy and data were analysed by using both commercial ELISA cut-off, and by applying a mixture model. Results of the two methods were compared and interpreted in the light of measles incidence, vaccination coverage and previous seroprevalence data. Seroprevalence rates observed in 2004 were similar to those observed in a previous study conducted in 1996 for children up to 9 years of age, while they were significantly lower in individuals aged 10-19 years. Mixture model approach allowed to better understand these results, suggesting that in these latter age groups there was a waning of vaccine-induced immunity mainly in Northern-Central regions which historically had the highest vaccination coverage