Benzimidazole-2-Phenyl-Carboxamides as Dual-Target Inhibitors of BVDV Entry and Replication

Bovine viral diarrhea virus (BVDV), also known as Pestivirus A, causes severe infection mostly in cattle, but also in pigs, sheep and goats, causing huge economical losses on agricultural farms every year. The infections are actually controlled by isolation of persistently infected animals and vaccination, but no antivirals are currently available to control the spread of BVDV on farms. BVDV binds the host cell using envelope protein E2, which has only recently been targeted in the research of a potent and efficient antiviral. In contrast, RdRp has been successfully inhibited by several classes of compounds in the last few decades. As a part of an enduring antiviral research agenda, we designed a new series of derivatives that emerged from an isosteric substitution of the main scaffold in previously reported anti-BVDV compounds. Here, the new compounds were characterized and tested, where several turned out to be potent and selectively active against BVDV. The mechanism of action was thoroughly studied using a time-of-drug-addition assay and the results were validated using docking simulations

Experiences, Emotions, and Health Consequences among COVID-19 Survivors after Intensive Care Unit Hospitalization

Literature suggested that COVID-19 patients experienced hospitalization as a physically and psychologically stressful event, with the risk to develop post-traumatic stress symptoms. The study aimed to understand psychological experiences of COVID-19 survivors with severe complications during and after ICU hospitalization, and any relevant health consequences. From October 2020 to January 2021, a qualitative study was conducted in Italy via semi-structured interviews by phone or video call addressed to COVID-19 survivors, randomly enrolled among people who released their stories publicly on newspapers, television, or social media. Fifteen individuals (three women and twelve men with average age of 56.4 years) were interviewed. Four main themes emerged: (i) emotion of fear; (ii) isolation and loneliness; (iii) unawareness about the gravity of the situation as a protective factor; (iv) "Long COVID" as consequences of the disease on physical and psychological health. During hospitalization, 66.7% of participants had mild or moderate values of anxiety and depression. After discharge, 86.7% moved to normal values. The results suggest that long-COVID is an important problem to manage to improve patients' quality of life. It is essential to guarantee a holistic take in charge starting before the discharge and continuing care after discharge in the community where they live

A Genome-Wide Association Scan on the Levels of Markers of Inflammation in Sardinians Reveals Associations That Underpin Its Complex Regulation

Identifying the genes that influence levels of pro-inflammatory molecules can help to elucidate the mechanisms underlying this process. We first conducted a two-stage genome-wide association scan (GWAS) for the key inflammatory biomarkers Interleukin-6 (IL-6), the general measure of inflammation erythrocyte sedimentation rate (ESR), monocyte chemotactic protein-1 (MCP-1), and high-sensitivity C-reactive protein (hsCRP) in a large cohort of individuals from the founder population of Sardinia. By analysing 731,213 autosomal or X chromosome SNPs and an additional ∼1.9 million imputed variants in 4,694 individuals, we identified several SNPs associated with the selected quantitative trait loci (QTLs) and replicated all the top signals in an independent sample of 1,392 individuals from the same population. Next, to increase power to detect and resolve associations, we further genotyped the whole cohort (6,145 individuals) for 293,875 variants included on the ImmunoChip and MetaboChip custom arrays. Overall, our combined approach led to the identification of 9 genome-wide significant novel independent signals—5 of which were identified only with the custom arrays—and provided confirmatory evidence for an additional 7. Novel signals include: for IL-6, in the ABO gene (rs657152, p = 2.13×10−29); for ESR, at the HBB (rs4910472, p = 2.31×10−11) and UCN119B/SPPL3 (rs11829037, p = 8.91×10−10) loci; for MCP-1, near its receptor CCR2 (rs17141006, p = 7.53×10−13) and in CADM3 (rs3026968, p = 7.63×10−13); for hsCRP, within the CRP gene (rs3093077, p = 5.73×10−21), near DARC (rs3845624, p = 1.43×10−10), UNC119B/SPPL3 (rs11829037, p = 1.50×10−14), and ICOSLG/AIRE (rs113459440, p = 1.54×10−08) loci. Confirmatory evidence was found for IL-6 in the IL-6R gene (rs4129267); for ESR at CR1 (rs12567990) and TMEM57 (rs10903129); for MCP-1 at DARC (rs12075); and for hsCRP at CRP (rs1205), HNF1A (rs225918), and APOC-I (rs4420638). Our results improve the current knowledge of genetic variants underlying inflammation and provide novel clues for the understanding of the molecular mechanisms regulating this complex process

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Acute Intoxication with Drugs of Abuse and Psychopharmacological Medications in The Emergency Room – the Situation in Cagliari, Italy

Given the incidence and severity of acute intoxication, this issue is of considerable importance today for the Emergency Departments (ED). The objective of this study was to evaluate acute intoxications by psychopharmacological medications and abuse of drugs for patients managed in an Outpatient Emergency Department. Retrospective analyses were performed on data on admissions to the Emergency Department for the years 2012 and 2013, in Holy Trinity Hospital, Cagliari, Italy; the reference population were outpatients with intoxication reported as the main problem, taken from a total population of utpatients with every kind of medical problem admitted to the ED during the studied period. The sample included patients of all ages with acute intoxication by psychopharmacological medications and drugs of abuse (psychoactive drugs and alcohol). For the year 2012, the number of total Emergency Room (ER) visits because of intoxication amounted to 338 and 243 of these were due to the abuse of drugs (72%), representing 0.72% of the total number of ER outpatients visits (n=33823). For the year 2013, this percentage increased reporting 287 outpatients for intoxication by drugs of abuse (79% of those admitted because of intoxication, n=362), representing 0.83% of the total number of ER outpatients visits (n=34,476). If we consider jointly outpatients with intoxication because of drug abuse for the two years (n=530), the descriptive analysis shows that: 56.0% are male and 44.0% females. Yellow as priority code had been assigned in 67.7% cases and red in 9.2% cases (χ2=10.053, df=3, p=0.018). Patients with a diagnosis of psychiatric illness were 40.8%; with diagnosis of drug addiction 18.5%, 10.9% alcoholism, drug addiction and alcoholism 2.6%; psychiatric condition associated with drug addiction and/or alcoholism 4.5% (χ2=85.697, df=7, p<0.001). The drugs taken were: psychopharmacological medications 46.2%; alcohol 22.6%; mixed drugs and alcohol abuse 13.7% (χ2=104.870, df=8, p<0.001). This study showed that there is a high level of comorbidity between psychiatric disease (Bipolar Disorders: 28.7%, Unipolar Mood Disorders: 48.6%, Psychosis: 9.3%, Anxiety Disorders: 10.2%) [1] and acute intoxication in patients who are admitted to an Emergency Department; this data, which show an increase of admissions of such patients during the examined period prove the necessity to reflect on the importance of an appropriate management of this patient population

Sex Differences in the Bitterness Perception of an Aromatic Myrtle Bitter Liqueur and Bitter Compounds

We evaluated sex differences in the perception of bitter compounds and an aromatic bitter herbal liqueur (Mirtamaro) obtained by the infusion of myrtle leaves/berries together with a mixture of Mediterranean herbs/plants as flavoring/bittering ingredients. In a healthy population (n = 231 participants), using bivariate correlations and multivariate linear regression analyses, significant sex differences emerged in quinine bitterness perception, with women showing a higher bitter taste intensity rating than men. Among all participants, 40 subjects (subpopulation) were randomly selected for the evaluation of sex differences in Mirtamaro gustatory and olfactory perception using a hedonic Likert-type scale. Women showed higher ratings in Mirtamaro aroma (odor intensity) and bitterness (taste intensity) perception than men, with a superior capacity to perceive/describe its sensory attributes. 1,8-Cineole and methyl chavicol were the main contributors to the bitter liqueur aroma. A significant correlation (r = 0.564, p < 0.01) between Mirtamaro odor pleasantness/taste pleasantness was observed in women, indicating a positive contribution of aromatic herbs to bitter taste acceptability. Moreover, a higher bitter intensity rating of 6-n-propylthiouracil was evidenced in women than men. Our results highlighted sex differences in bitter taste acuity and the role of aromatic herbs/plants in modulating bitter taste acceptance, which is useful information in the field of precision nutrition and medicine

Flavoring of sea salt with Mediterranean aromatic plants affects salty taste perception

Background: Salt (sodium chloride) is an essential component of daily food, crucial for many physiological processes. Due to health risks related to salt over consumption, considerable interest is devoted to strategies to reduce dietary salt intake. In this work we evaluated the sensory dimensions of sea salts flavored with Mediterranean aromatic plants with the aim to confirm the role of herbs/spices in the enhancement of salty perception and to validate the use of flavored salts as a strategy to reduce salt intake. To this goal we compared taste dimensions (pleasantness, intensity, and familiarity) of solutions obtained with salt and sea salts flavored with Mediterranean herbs, spices, and fruits. Sensorial differences were analyzed using a 7-point hedonic Likert-type scale on 58 non-trained judges. Results: Main flavor compounds, identified by GC-FID/MS analysis, were α-pinene and 1,8-cineole in myrtle salt (FS 1), verbenone, α-pinene, 1,8-cineole, and rosifoliol in herbs/plants salt (FS 2), and limonene in orange fruits/saffron salt (SF 3). At the dose of 0.04 g mL-1 , saline solutions obtained with flavored salt (containing approximately 6-30% less of NaCl) were perceived as more intense, less familiar, but equally pleasant than pure salt solution. In particular, sea salt flavored with orange fruits/saffron emerged as the most interesting in potentiating saltiness perception. Conclusion: Our study confirmed the important role of Mediterranean aromatic plants in the enhancement of saltiness perception and qualified the use of flavored sea salt during food preparation/cooking instead of normal salt as a potential strategy to reduce the daily salt intake. This article is protected by copyright. All rights reserved

Patient Involvement in Shared Decision-Making: Do Patients Rate Physicians and Nurses Differently?

Background. Shared decision-making implies that patients and healthcare professionals make decisions together about clinical exams, available treatments, choice of options, and the benefit or downside of every choice. Patients involved in the shared decision-making process are more compliant with treatments and have a reduced risk of complications related to the pathology. In Italy, patient involvement in caring processes is still barely investigated. Aim. To investigate patients&rsquo; perceptions about shared decision-making with physicians and nurses, respectively, and to examine the relationship between shared decision-making and patient satisfaction and perceived quality of care/treatment. Methods. The study was performed between March and June 2019 in two wards of one Italian hospital. A questionnaire was administered to inpatients at the time of admission and again at discharge, including demographic information and measurement scales regarding patient involvement in shared decision-making, patient satisfaction, and perceived quality of treatment/care. Results. A total of 151 out of 301 patients completed questionnaires at both admission and discharge. Patients&rsquo; scores for shared decision-making (information, patient needs, treatment planning) were significantly different for physicians and nurses. At both admission and discharge, patients rated shared decision-making significantly higher for physicians compared to nurses, while there were no differences in their satisfaction ratings. Patient ratings of physicians did not change from admission (information: mean (M) = 3.50, standard deviation (SD) = 0.81; patient need: M = 3.05, SD = 1.05; treatment planning: M = 2.75, SD = 1.23) to discharge (information: M = 3.50, SD = 0.79; patient need: M = 3.17, SD = 1.02; treatment planning: M = 2.66, SD = 1.23) (p = 0.924, p = 0.098, p = 0.293, respectively), but patients&rsquo; ratings of nurses&rsquo; behavior increased significantly from admission (information: M = 2.44, SD = 1.23; patient need: M = 2.27, SD = 1.17; treatment planning: M = 2.12, SD = 1.19) to discharge (information: M = 2.62, SD = 1.22; patient need: M = 2.53, SD = 1.24; treatment planning: M = 2.35, SD = 1.21) (p = 0.019, p = 0.001, p = 0.003, respectively). Attention to patients&rsquo; needs was the key determinant of both satisfaction with nurses (OR = 3.65, 95% CI = 1.31&ndash;10.14, p = 0.013) and perceived quality of care (OR = 3.97, 95% CI = 1.49&ndash;10.55, p = 0.006). Providing appropriate information about disease progress and treatments was a key determinant of both satisfaction with physicians (OR = 19.75, 95% CI = 7.29&ndash;53.55, p &lt; 0.001) and perceived quality of treatment (OR = 8.03, 95% CI = 3.25&ndash;19.81, p &lt; 0.001). Discussion. Nurses should be sensitized to involving patients in the decision-making process, especially upon hospital admission. Specific training about effective communication techniques can be implemented to manage relationships with patients in different caring situations. Practical implications and future directions are discussed

Production of farmstead lactose-free Pecorino di Osilo and ricotta cheeses from sheep’s milk

The present work was aimed to define and validate farmstead production of lactose- free Pecorino di Osilo cheese, fresh ricotta cheese, and salted and smoked ricotta cheese (Ricotta mustia). The enzymatic activity of the commercial preparation containing lactase (1.1 g/mL), preliminarily tested using a spectrophotometric titration, showed activity equal to 4950±40 neutral lactase unit/g. The amount of lactase required to obtain the lactose-free milk was then established in triplicate laboratory trials, by adding the enzyme at concentrations of 0.7, 0.9 and 1.1 g/L in flasks containing 160 mL of raw sheep’s milk. Samples were incubated under conditions expected during milk storage and cheese-making. The residual lactose content in milk was determined by enzymatic method. The addition of lactase at concentration of 1.1 g/L of milk reduced the lactose concentration below the limit of detection (LOD) of 0.06 g/L. The procedure was validated at a dairy farm, using three different batches of bulk raw sheep’s lactose-free milk that were transformed into Pecorino di Osilo cheese. The resulting whey was used to produce fresh ricotta and Ricotta mustia cheese. Raw milk and whey samples were always below lactose detection limit. The residual lactose was measured in Pecorino di Osilo cheese, after 24 hours and 30 days from production; in fresh ricotta cheese, after 48 hours; in Ricotta mustia cheese after 7 days. The determination of lactose content in cheese samples was conducted by a gas chromatography- flame ionization detection method, which showed a LOD and limit of quantification respectively of 1.8 and 5.6 mg/kg for cheese, and 1.35 and 4.2 mg/kg for both ricotta cheeses. The lactose concentration was always below the relevant LOD values in all samples. The mean concentration of galactose and glucose were respectively 13,000±2000 and 11,000±2000 mg/kg in fresh Pecorino di Osilo, 1100±300 and 1200±300 mg/kg in fresh ricotta, and 950±400 and 750±250 mg/kg in Ricotta mustia. The results of the present study showed that the production of farmstead lactose-free Pecorino di Osilo cheese and ricotta cheeses from raw sheep’s milk is easily achievable. The main issue for farmstead production of artisanal lactose-free products is the implementation of permanent procedures based on hazard-analysis and critical control principles aimed at guaranteeing the effectiveness of the process and at acquiring analytical evidences to demonstrate the fulfilment of law requirements for labelling