MicroRNA-551b expression profile in low and high-grade cervical intraepithelial neoplasia

OBJECTIVE: To evaluate the expression of microRNA (miR)-551b in patients with low and high grade cervical intraepithelial neoplasia (CIN) and to find an association with high-risk Human Papillomavirus (HR-HPV) infection-related prognostic biomarkers. PATIENTS AND METHODS: The expression level of miR-551b was determined in 50 paraffin-embedded cervical specimens (10 normal squamous epithelium, 18 condylomas, 8 CIN1, and 14 CIN2-3) using quantitative Real-time polymerase chain reaction (qRT-PCR). χ2-test compared miR-551b expression in different diagnosis groups. An Ordered Logistic Regression and a Probit correlation were made to correlate miR-551b expression levels with the cervical tissue histological findings. The immunohistochemical distribution of p16 and Ki-67 according to histopathological findings was also assessed. RESULTS: The distribution of the miR-551b expression profile was significantly lower in CIN1-3 samples compared to other histological diagnosis groups (condyloma and negative). The expression levels were inversely correlated to the cervical pathological grade, from negative to CIN2-3. A 1% increase in miR-551b expression level produced an increase of 19% to the probability of a minor histological grade diagnosis in a range from negative to CIN2-3 and an increase of 13% to the probability of a negative histological grade diagnosis. Among the cases with miR-551b expression < 0.02 (considered as cut-off value) a significant statistical correlation was found between p16 and Ki-67 expression and the diagnosis of CIN2-3. CONCLUSIONS: O ur d ata s howed a s ignificant inverse correlation between miR-551b expression and the histological grading of the lesions, suggesting a tumor suppressive function in the different stages of cervical dysplasia

Age is not the only risk factor in COVID-19: the role of comorbidities and of long staying in residential care homes

Background: The actual SARS-CoV-2 outbreak caused a highly transmissible disease with a tremendous impact on elderly people. So far, few studies focused on very elderly patients (over 80 years old). In this study we examined the clinical presentation and the outcome of the disease in this group of patients, admitted to our Hospital in Rome. Methods: This is a single-center, retrospective study performed in the Sant’Andrea University Hospital of Rome. We included patients older than 65 years of age with a diagnosis of COVID-19, from March 2020 to May 2020, divided in two groups according to their age (Elderly: 65–80 years old; Very Elderly &gt; 80 years old). Data extracted from the each patient record included age, sex, comorbidities, symptoms at onset, the Pneumonia Severity Index (PSI), the ratio of the partial pressure of oxygen in arterial blood (PaO2) to the inspired oxygen fraction (FiO2) (P/F) on admission, laboratory tests, radiological findings on computer tomography (CT), length of hospital stay (LOS), mortality rate and the viral shedding. The differences between the two groups were analyzed by the Fisher’s exact test or the Wilcoxon signed-rank test for categorical variables and the Mann-Whitney U test for continuous variables. To assess significance among multiple groups of factors, we used the Bonferroni correction. The survival time was estimated by Kaplan-Meier method and Log Rank Test. Univariate and Multivariate logistic regression were performed to estimate associations between age, comorbidities, provenance from long-stay residential care homes (LSRCH) s and clinical outcomes. Results: We found that Very Elderly patients had an increased mortality rate, also due to the frequent occurrence of multiple comorbidities. Moreover, we found that patients coming from LSRCHs appeared to be highly susceptible and vulnerable to develop severe manifestations of the disease. Conclusion: We demonstrate that there were considerable differences between Elderly and Very Elderly patients in terms of inflammatory activity, severity of disease, adverse clinical outcomes. To establish a correct risk stratification, comorbidities and information about provenience from LSRCHs should be considered

Chemoenzymatic synthesis in flow reactors: a rapid and convenient preparation of Captopril

The chemoenzymatic flow synthesis of enantiomerically pure captopril, a widely used antihypertensive drug, is accomplished starting from simple, inexpensive, and readily available reagents. The first step is a heterogeneous biocatalyzed regio- and stereoselective oxidation of cheap prochiral 2-methyl-1,3-propandiol, performed in flow using immobilized whole cells of Acetobacter aceti MIM 2000/28, thus avoiding the use of aggressive and environmentally harmful chemical oxidants. The isolation of the highly hydrophilic intermediate (R)-3-hydroxy-2-methylpropanoic acid is achieved in-line by using a catch and-release strategy. Then, three sequential high-throughput chemical steps lead to the isolation of captopril in only 75 min. In-line quenching and liquid-liquid separation enable breaks in the workflow and other manipulations to be avoided

Safety of mRNA COVID-19 Vaccines in Patients with Inborn Errors of Immunity: an Italian Multicentric Study

Purpose: Little is known about vaccine safety in inborn errors of immunity (IEI) patients during the current vaccination campaign for COVID-19. To better investigate the reactogenicity and adverse event profile after two, three, and four doses of mRNA vaccines, we conducted an observational, multicentric study on 342 PID patients from four Italian Referral Centres. Methods: We conducted a survey on self-reported adverse reactions in IEI patients who received mRNA vaccine by administering a questionnaire after each dose. Results: Over the whole study period, none of the patients needed hospitalization or had hypersensitivity reactions, including anaphylaxis and delayed injection site reaction. After two vaccination doses, 35.4% of patients showed only local reactogenicity-related symptoms (RrS), 44.4% reported both systemic and local RrS, and 5% reported only systemic RrS. In more than 60% of cases, local or systemic RrS were mild. After the first and second booster doses, patients showed fewer adverse events (AEs) than after the first vaccination course. Patients aged 50&nbsp;years and older reported adverse events and RrS less frequently. Among AEs requiring treatment, one common variable immune deficiency patient affected by T cell large granular lymphocytic leukemia developed neutropenia and one patient had Bell’s paralysis perhaps during herpes zoster reactivation. Conclusion: Although our follow-up period is relatively short, the safety data we reported are reassuring. This data would help to contrast the vaccine hesitancy often manifested by patients with IEI and to better inform their healthcare providers

Bioprocess intensification using flow reactors: stereoselective oxidation of achiral 1,3-diols with immobilized Acetobacter Aceti

Enantiomerically enriched 2-hydroxymethylalkanoic acids were prepared by oxidative desymmetrisation of achiral 1,3-diols using immobilized cells of Acetobacter aceti in water at 28 C. The biotransformations were first performed in batch mode with cells immobilized in dry alginate, furnishing the desired products with high molar conversion and reaction times ranging from 2 to 6 h. The biocatalytic process was intensified using a multiphasic flow reactor, where a segmented gas–liquid flow regime was applied for achieving an efficient O2-liquid transfer; the continuous flow systems allowed for high yields and high biocatalyst productivity

Marine microorganisms as source of stereoselective esterases and ketoreductases : kinetic resolution of a prostaglandin intermediate

A screening among bacterial strains isolated from water-brine interface of the deep hypersaline anoxic basins (DHABs) of the Eastern Mediterranean was carried out for the biocatalytical resolution of racemic propyl ester of anti-2-oxotricyclo[2.2.1.0]heptan-7-carboxylic acid (R,S)-1, a key intermediate for the synthesis of d-cloprostenol. Bacillus horneckiae 15A gave highly stereoselective reduction of (R,S)-1, whereas Halomonas aquamarina 9B enantioselectively hydrolysed (R,S)-1; in both cases, enantiomerically pure unreacted (R)-1 could be easily recovered and purified at molar conversion below 57\u201358 %, showing the potential of DHAB extremophile microbiome and marine-derived enzymes in stereoselective biocatalysis

From Cheese Whey Permeate To An Anti-Listeria Food Packaging Device: Bacterial Cellulose Nanocrystals/Sakacin-A Conjugates (Nanosak)

In the present project cheese whey permeate (CWP), the residual by-product obtained by extraction of whey proteins from cheese whey, was used as substrate for the growth of bacterial species that produce two appealing molecules: the anti-listerial bacteriocin sakacin-A and bacterial cellulose (BC). BC is then turned into nanocrystals (BCNCs) that are finally conjugated with sakacin-A to obtain an innovative antimicrobial device for food which could support Listeria monocytogenes growth. Sakacin-A was produced by Lactobacillus sakei DSMZ 6333 in liquid cultures. The highest bacteriocin production (around 300 AU/mL) was achieved after 9 h at 26\ub0C; a food-grade, salt-free enriched sakacin-A extract was obtained by using a gravity reverse phase chromatography. BC was produced by Komagataeibacter xylinus DSMZ 2325 by static fermentation of CWP in presence of 0.5 U/mL of \u3b2-galactosidase at 30\ub0C; after 7 days, BC yield was around 7 g/L. BCNCs were then obtained by acid hydrolysis mediated by sulfuric acid, with the goal of removing the amorphous regions of BC and introduce a net negative charge by esterification on the hydroxyl group on C6. BCNCs/sakacin-A conjugates were prepared by exploiting their opposite charge: enriched sakacin-A extract was mixed with BCNCs and, after incubation, conjugates collected by centrifugation have a specific activity of 100 AU/mg BCNCs. Among all peptides present in the enriched sample, sakacin-A appears to preferentially absorb onto BCNCs, thus allowing its further purification. Sakacin-A as well its BCNCs conjugates were then included in a hydroxypropil-cellulose coating spread onto paper sheets at a concentration of 5 and 25 AU/cm2. The addition of the coating did not bring any significant change in the oxygen barrier properties of the cellulosic substrate. In a similar way, the static contact angle of both uncoated and coated substrate was of approximately 130\ub0. However, the presence of BCNCs seemed to increase the swelling phenomenon of the coating. Sakacin A was also included in whey, caseine and cellulose derived matrices to prepare films and coatings with diverse results. The kinetics of Sakacin-A released from active films to aqueous food was analyzed by immersion of samples in water (as simulant) and measuring the anti-Listeria activity of the simulant after increasing times of exposure. In vitro and in vivo antimicrobial trials were carried out on real food products demonstrated their anti-listerial effectiveness, proving that the developed devices can contribute to increase shelf life, quality and safety of perishable foods

Delayed diagnosis of coeliac disease increases cancer risk

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