Pre-exposure prophylaxis (PrEP) is effective for HIV prevention and is mostly used by men who have sex with men (MSM). The aim of this study was to describe the characteristics of a cohort of PrEP ...users at first PrEP counselling visits (baseline, BL).
Cross-sectional study of a cohort of MSM receiving PrEP (Centro San Luigi, CSL-PrEP Cohort).
Secondary-level sexually transmitted infections (STI) centre in Milan, Italy, from May 2017 to May 2022.
Overall, 624 MSM PrEP users were included; most users were Caucasian (97%), attended university (64%), with a median BL age of 34.5 years.
Overall, 45% choose the daily-based PrEP regimen, 55% the event-based one. An increasing trend in PrEP counselling visits was observed (p=0.024). The majority had between 10 and 19 partners in the 3 months before BL and 41% were chemsex users. All had a HIV Incidence Risk Index for MSM (HIRI-MSM)>10, 54% between 20 and 29. Overall, 50% had ≥1 previous STI and 22% ≥1 BL STI. BL chlamydia (10%) was often more frequent than in the past (7%). The number of sexual partners was associated with BL chlamydia (p<0.001), gonorrhoea (p=0.002) and syphilis (p=<0.001), HIRI-MSM with chlamydia (p=0.001) and gonorrhoea (p=0.008), chemsex use with chlamydia (p=0.003) and gonorrhoea (p=0.030).
We observed an unbalanced access to PrEP in respect to all key populations which might benefit from PrEP, with a similar choice for event-based or daily-based regimens. High-risk behaviours and STIs were frequently observed. History of chlamydia was very frequently high in asymptomatic MSM at BL, compared with what observed before access to PrEP. High-risk behaviours and HIRI-MSM were associated with most of STIs.
West Nile Virus infections has become endemic in various locations around the world. Symptomatic cases manifest as an acute febrile illness and in less than 1% with neuroinvasive manifestations. We ...report one of the very few cases of probable WNV-mediated isolated hepatitis to shed light on a possibly underestimated clinical picture.
To evaluate the virological outcome of darunavir-cobicistat (DRVc)-based regimens in adults living with HIV who had experienced virological failure (VF) on any previous drug combination.
This was a ...retrospective cohort study (CSLHIV Cohort) of adults living with HIV who started a DRVc-based regimen with HIV-RNA >50 copies/mL after VF on any previous drug combination. Data on demographics, antiretroviral treatment since HIV diagnosis, and immunological and metabolic parameters from baseline (start of DRVc) to 48 weeks were analyzed in order to assess the cumulative proportion of those who achieved virological success (VS), defined as at least one instance of HIV-RNA <50 copies/mL within 12 months from baseline. Follow-up lasted from the start of the DRVc-based regimen (baseline) to the first instance of HIV-RNA <50 copies/mL, last available visit, or loss to follow-up or death, whichever occurred first. Univariate and multivariate Cox proportional-hazard regression models were used to identify baseline factors associated with VS.
A total of 176 individuals were included, and 120 (68.2%) achieved <50 HIV-RNA copies/mL within 12 months since baseline. On multivariate analysis, baseline HDL cholesterol was independently associated with the occurrence of VS (adjusted HR 1.021, 95% CI 1.004-1.038;
=0.014). Among the 120 subjects with VS, 27 (22.5%) had had VF during a median follow-up of 20.8 months since the first undetectable HIV-RNA. Resistance testing after VF was available in two cases, which harboured the HIV variant-bearing protease inhibitor-resistance mutations D30N, I50V, and N88D. During a median follow-up of 38.4 months, 65 of 176 (36.9%) individuals discontinued DRVc for any reason (37 of 120, 30.8%) and achieved VS vs. 28 of 56 (50%) without VS (
=0.019). Time to discontinuation was longer in people with VS (41.5 vs. 23.0 months,
=0.0007). No statistically significant changes were observed in immunological or lipid profiles during follow-up.
Most individuals in this study achieved VS within 12 months from the beginning of a DRVc-based regimen; therefore, this treatment represent a viable option for people who have experienced VF on other regimens.
Prostate cancer (PC) is a male common neoplasm and is the second leading cause of cancer death in American men. PC is traditionally diagnosed by the evaluation of prostate secreted antigen (PSA) in ...the blood. Due to the high levels of false positives, digital rectal examination and transrectal ultrasound guided biopsy are necessary in uncertain cases with elevated PSA levels. Nevertheless, the high mortality rate suggests that new PC biomarkers are urgently needed to help clinical diagnosis. In a previous study, we have identified a network of genes, altered in high Gleason Score (GS) PC (GS ≥ 7), being regulated by miR-153. Until now, no publication has explained the mechanism of action of miR-153 in PC. By in vitro studies, we found that the overexpression of miR-153 in high GS cell lines is required to control cell proliferation, migration and invasion rates, targeting Kruppel-like factor 5 (
). Moreover, miR-153 could be secreted by exosomes and microvesicles in the microenvironment and, once entered into the surrounding tissue, could influence cellular growth. Being upregulated in high GS human PC, miR-153 could be proposed as a circulating biomarker for PC diagnosis.
This study aims to analyze the clinical characteristics, demographic features, and injury circumstances of patients admitted to the Emergency Department (ED) at Fondazione Policlinico Universitario ...A. Gemelli (IRCCS) in Rome, Italy, due to bicycle accidents.
Data on clinical characteristics, accident timing, injury circumstances, and helmet use were collected for ED patients involved in bicycle accidents from January 2019 to December 2022. Subsequently, Abbreviated Injury Scale codes of all diagnoses were recorded and the Injury Severity Score was calculated.
Over the study period, 763 patients were admitted to the ED following bicycle accidents, with a 0.3 % fatality rate and a 30.4 % frequency of multitrauma. Multivariate analysis revealed that collisions with other vehicles increased trauma severity and the risk of ICU admission. Conversely, helmet use was associated with reduced severity of head trauma and a lower likelihood of ICU admission. Notably, toxicological investigations were not conducted for any ED-admitted patients.
Although a low mortality rate and a low incidence of multi-trauma have been shown in comparison to other nations, it is necessary to adopt prevention strategies like safety devices, more cycle paths, and better infrastructures on the one hand, and stricter laws on the other. It is essential to require toxicological testing in Italy for all accidents involving this means of transport, and to make helmet use compulsory for all ages.
Approximately 20-50% of patients presenting with localized colorectal cancer progress to stage IV metastatic disease (mCRC) following initial treatment and this is a major prognostic determinant. ...Here, we have interrogated a heterogeneous set of primary colorectal cancer (CRC), liver CRC metastases and adjacent liver tissue to identify molecular determinants of the colon to liver spreading. Screening Food and Drug Administration (FDA) approved drugs for their ability to interfere with an identified colon to liver metastasis signature may help filling an unmet therapeutic need.
RNA sequencing of primary colorectal cancer specimens vs adjacent liver tissue vs synchronous and asynchronous liver metastases. Pathways enrichment analyses. The Library of Integrated Network-based Cellular Signatures (LINCS)-based and Connectivity Map (CMAP)-mediated identification of FDA-approved compounds capable to interfere with a 22 gene signature from primary CRC and liver metastases. Testing the identified compounds on CRC-Patient Derived Organoid (PDO) cultures. Microscopy and Fluorescence Activated Cell Sorting (FACS) based analysis of the treated PDOs.
We have found that liver metastases acquire features of the adjacent liver tissue while partially losing those of the primary tumors they derived from. We have identified a 22-gene signature differentially expressed among primary tumors and metastases and validated in public databases. A pharmacogenomic screening for FDA-approved compounds capable of interfering with this signature has been performed. We have validated some of the identified representative compounds in CRC-Patient Derived Organoid cultures (PDOs) and found that pentoxyfilline and, to a minor extent, dexketoprofen and desloratadine, can variably interfere with number, size and viability of the CRC -PDOs in a patient-specific way. We explored the pentoxifylline mechanism of action and found that pentoxifylline treatment attenuated the 5-FU elicited increase of ALDHhigh cells by attenuating the IL-6 mediated STAT3 (tyr705) phosphorylation.
Pentoxifylline synergizes with 5-Fluorouracil (5-FU) in attenuating organoid formation. It does so by interfering with an IL-6-STAT3 axis leading to the emergence of chemoresistant ALDHhigh cell subpopulations in 5-FU treated PDOs. A larger cohort of CRC-PDOs will be required to validate and expand on the findings of this proof-of-concept study.
The popularity of adding pulse flours to baked goods is growing rapidly due to their recognised health benefits. In this study, increasing amounts (3, 7, 10, and 15%) of white lupin flour (
L.) and ...of protein concentrate from narrow-leaved lupin (
L.) were used as replacements for durum wheat semolina to prepare bread, and their effects on the physicochemical properties of the flour blends, as well as the technological and sensory qualities of bread, were evaluated. The addition of protein concentrate from narrow-leaved lupin and white lupin flour increased the water binding capacity and the leavening rate compared to pure semolina. A farinograph test indicated that the dough development time had a slight but significant tendency to increase with the addition of lupin flour and protein concentrate of narrow-leaved lupin, while had a negative effect on the stability of dough. The alveograph strength decreased (225, 108, and 76 × 10
J for dough made with semolina, 15% of protein concentrate from narrow-leaved lupin, and 15% of white lupin flour, respectively), whereas there was an upward trend in the P/L ratio. Compared to re-milled semolina, the samples with lupin flour and protein concentrate from narrow-leaved lupin had low amylase activity, with falling number values ranging from 439 s to 566 s. The addition of the two different lupin flours lowered the specific volumes of the breads (2.85, 2.39, and 1.93 cm
/g for bread made from semolina, from 15% of protein concentrate from narrow-leaved lupin, and from 15% of white lupin flour, respectively) and increased their hardness values (up to 21.34 N in the bread with 15% of protein concentrate from narrow-leaved lupin). The porosity of the loaves was diminished with the addition of the two lupin flours (range of 5-8). The sensory analysis showed that the addition of white lupin flour or protein concentrate from narrow-leaved lupin did not impart any unpleasant flavours or odours to the bread. To conclude, the use of lupin in breadmaking requires adjustments to strengthen the gluten network but does not require a deflavouring process.
‘Violetto di Ramacca’ is a local variety of artichoke grown in Sicily (Southern Italy), known for its purple color with green streaks. In this study, the effects of two different preparation and ...drying methods (method A, fresh sample oven-dried at 40 °C for 48 h then mixed and ground into flour; and B, minced and frozen sample oven-dried at 40 °C for 24 h then blended and ground into flour) for flours from different parts of the artichoke (bracts, stems, and mix), used at different percentages of integration (5, 7.5, and 10%), in combination with re-milled semolina, have been evaluated. The polyphenol contents of the flours produced with the two methods were measured. The results showed significant differences between the methods and samples, with a range from 9.09 mg GAE/g d.m. (bracts 100%, method A) to 2.62 mg/g (mix 100%, method B). The values were then lowered in the flour products with supplements ranging from 0.96 mg GAE/g (bract flour 10%, method A) to 0.11 mg GAE/g (mixed flour 7.5%, method B). As the amounts of polyphenols increased, the antioxidant activity increased, with a range that varied in the pure flour from 8.59 mg trolox eq/g d.m. (bract flour, method A) to 3.83 mg trolox eq/g d.m. (mixed flour, method B). These flours were also analyzed for color, highlighting a clear difference between methods A (greener) and B (browner). The flours thus obtained were used to produce breads, which were evaluated for their physicochemical characteristics during 4 days of storage. The results showed a reduction in volumes and heights, an increase in the percentage of integration of the artichoke flours, a greater quantity of moisture in the integrated breads, and a lower reduction in the structural characteristics during storage compared to the control breads. The TPA was conducted on the breads from T0 to T4, highlighting that, although initially more compact, the integrated breads offered less alteration of the values during storage. The aw ranged from 0.63 (mix flour 5%, method B) to 0.90 (bract flour 5%, method B). The amounts of polyphenols (from 0.57 mg GAE/g in bread with bracts at 10% (method A) to 0.13 mg GAE/g in bread with mix 5% (method B)) and the antioxidant activity (from 0.55 mg trolox eq/g d.m. in bread with bract flour 10% (method A) to 0.14% mg trolox eq/g d.m. in bread with mix flour) were also evaluated, showing a trend similar to the values obtained in the flours. Colorimetric tests highlighted a color more similar to wholemeal bread in the loaves produced with method B. Statistical factor analysis and cluster analysis were conducted for all trials.
Over the last year, NPSs have been steadily on the rise in the illicit drug market. Among these, synthetic cathinones seem to become increasingly popular among young adults, mainly because of their ...ability to replicate the effects of traditional psychostimulant drugs, such as cocaine, MDMA and amphetamines. However, scarce data are available about the in vivo pharmaco-toxicology of these new substances. To this end, this study focused on evaluation of effects induced by repeated administration of mephtetramine (MTTA 0.1-30 mg/kg i.p.) in mice. This atypical cathinone highlighted a sensorial (inhibition of visual and acoustic reflexes) and transient physiological parameter (decrease in breath rate and temperature) change in mice. Regarding motor activity, both a dose-dependent increase (accelerod test) and biphasic effect (drag and mobility time test) have been shown. In addition, blood and urine samples have been analysed to enrich the experimental featuring of the present study with reference to evaluation of potential toxicity related to consumption of MTTA. The latter analysis has particularly revealed important changes in blood cells count and blood and urine physicochemical profile after repeated treatment with this atypical cathinone. Moreover, MTTA induced histological changes in heart, kidney and liver samples, emphasizing its potential toxicity.
