Explore the vast range of titles available.

Coumarin is an effective treatment for primary lymphoedema, as well as lymphoedema related to breast cancer radiotherapy or surgery. However, its clinical use is limited in several countries due to the possible occurrence of hepatotoxicity, mainly in the form of mild to moderate transaminase elevation. It is worth noting that only a few cases of severe hepatotoxicity have been described in the literature, with no reported cases of liver failure. Data available on coumarin absorption, distribution, metabolism, and excretion have been reviewed, focusing on hepatotoxicity studies carried out in vitro and in vivo. Finally, safety and tolerability data from clinical trials have been thoroughly discussed. Based on these data, coumarin-induced hepatotoxicity is restricted to a small subset of patients, probably due to the activation in these individuals of alternative metabolic pathways involving specific CYP450s isoforms. The aim of this work is to stimulate research to clearly identify patients at risk of developing hepatotoxicity following coumarin treatment. Early identification of this subset of patients could open the possibility of more safely exploiting the therapeutical properties of coumarin, allowing patients suffering from lymphoedema to benefit from the anti-oedematous activity of the treatment.

Molecular data are now widely used in epidemiological studies to investigate the transmission, distribution, biology, and diversity of pathogens. Our objective was to establish recommendations to support good scientific reporting of molecular epidemiological studies to encourage authors to consider specific threats to valid inference. The statement Strengthening the Reporting of Molecular Epidemiology for Infectious Diseases (STROME-ID) builds upon the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative. The STROME-ID statement was developed by a working group of epidemiologists, statisticians, bioinformaticians, virologists, and microbiologists with expertise in control of infection and communicable diseases. The statement focuses on issues relating to the reporting of epidemiological studies of infectious diseases using molecular data that were not addressed by STROBE. STROME-ID addresses terminology, measures of genetic diversity within pathogen populations, laboratory methods, sample collection, use of molecular markers, molecular clocks, timeframe, multiple-strain infections, non-independence of infectious-disease data, missing data, ascertainment bias, consistency between molecular and epidemiological data, and ethical considerations with respect to infectious-disease research. In total, 20 items were added to the 22 item STROBE checklist. When used, the STROME-ID recommendations should advance the quality and transparency of scientific reporting, with clear benefits for evidence reviews and health-policy decision making.

A strong correlation between the occurrence of various pathological conditions and intestinal dysbiosis is supported by a range of strong evidence. Vice versa, many pathologies have been shown, in turn, to be responsible for alterations in the gut microbiota, a condition that can worsen illness outcomes and response to therapies. For these reasons, great efforts have been made, and studies are still ongoing, to elucidate the mechanisms underlying gut microbiota alterations and to search for pharmacologic or other strategies that can effectively restore the gut microbiota. In this narrative review, we examined the most significant literature on the role of some milk bioactive compounds, such as milk oligosaccharides and whey proteins, in modulating the composition of the gut microbiota and the underlying mechanisms of action, with the aim of investigating the impact of the microbiota changes mediated by these milk bioactive molecules on human health, and their potential use as therapeutics to treat or adjuvate the treatment of gut dysbiosis and associated pathologies.

Usnic acid (UA) is a dibenzofuran derivative naturally present in lichens, organisms resulting from the symbiosis between a fungus and a cyanobacterium, or an alga. UA shows antimicrobial, antitumor, antioxidant, analgesic, anti-inflammatory as well as UV-protective activities. Its use as pharmacological agent is widely described in traditional medicine, and in the past few years, the product has been marketed as a food supplement for the induction of weight loss. However, the development of severe hepatotoxicity in a limited number of subjects prompted the FDA to issue a warning letter, which led to the withdrawal of the product from the market in November 2001. Data published in literature on UA toxicology, genotoxicity, mutagenesis, and teratogenicity have been reviewed, as well as the case reports of subjects who developed hepatotoxicity following oral administration of UA as a slimming agent. Finally, we reviewed the most recent studies on the topical use of UA, as well as studies aimed at improving UA pharmacologic activity and reducing toxicity. Indeed, advancements in this field of research could open the possibility to reintroduce the use of UA as therapeutical agent.

COVID-19 is the global pandemic that affected our population in the past 2 years. Considerable research has been done to better understand the pathophysiology of this disease and to identify new therapeutic targets, especially for severe cases. Galectin-3 (Gal-3) is a receptor present at the surface of different cell types, namely epithelial and inflammatory cells, which has been described as a severity marker in COVID-19. The activation of Gal-3 through its binding protein (Gal-3BP) is directly linked to the production of pro-inflammatory cytokines that contribute for the cytokine storm (CS) observed in severe COVID-19 patients. Here, we show that D2, a recombinant fragment of the lectin-binding region of Gal-3BP was able to stimulate the expression of IL-6 in colon and lung epithelial cell lines in β-galactoside dependent manner. We further show that D2-induced IL-6 augmentation was reduced by the anti-Gal-3BP monoclonal antibody 1959. Our data confirm and extend prior findings of Gal-3BP mediated IL-6 induction, enlightening the potential of its antibody-mediated s blockage for the prevention and treatment of CS and severe disease in COVID-19 patients.

Comparison of COVID-19 trends in space and over time is essential to monitor the pandemic and to indirectly evaluate non-pharmacological policies aimed at reducing the burden of disease. Given the specific age- and sex- distribution of COVID-19 mortality, the underlying sex- and age-distribution of populations need to be accounted for. The aim of this paper is to present a method for monitoring trends of COVID-19 using adjusted mortality trend ratios (AMTRs). Age- and sex-mortality distribution of a reference European population (N = 14,086) was used to calculate age- and sex-specific mortality rates. These were applied to each country to calculate the expected deaths. Adjusted Mortality Trend Ratios (AMTRs) with 95% confidence intervals (C.I.) were calculated for selected European countries on a daily basis from 17th March 2020 to 29th April 2021 by dividing observed cumulative mortality, by expected mortality, times the crude mortality of the reference population. These estimated the sex- and age-adjusted mortality for COVID-19 per million population in each country. United Kingdom experienced the highest number of COVID-19 related death in Europe. Crude mortality rates were highest Hungary, Czech Republic, and Luxembourg. Accounting for the age-and sex-distribution of the underlying populations with AMTRs for each European country, four different patterns were identified: countries which experienced a two-wave pandemic, countries with almost undetectable first wave, but with either a fast or a slow increase of mortality during the second wave; countries with consistently low rates throughout the period. AMTRs were highest in Eastern European countries (Hungary, Czech Republic, Slovakia, and Poland). Our methods allow a fair comparison of mortality in space and over time. These might be of use to indirectly estimating the efficacy of non-pharmacological health policies. The authors urge the World Health Organisation, given the absence of age and sex-specific mortality data for direct standardisation, to adopt this method to estimate the comparative mortality from COVID-19 pandemic worldwide.

Bacterial resistance to antimicrobials is considered a major issue worldwide. This condition may account for treatment failure of urinary tract infections, which are among the most common infections both in community and healthcare settings. Therapy against uropathogens is generally administered empirically, possibly leading to unsuccessful therapy, recurrence and development of antibiotic resistance. The reduction in analytical time to obtain antimicrobial susceptibility test (AST) results could play a key role in reducing the cost of healthcare, providing information about antibiotic efficacy and thus preventing from either exploiting new and expensive antibiotics unnecessarily or using obsolete and ineffective ones. A more rational choice among treatment options would hence lead to more effective treatment and faster resolution. In this paper we evaluated the performance of a new Point Of Care Test (POCT) for the rapid prediction of antimicrobial susceptibility in urine samples performed without the need of a laboratory or specialized technicians. 349 patients were enrolled in two open-label, monocentric, non-interventional clinical trials in partnership with an Emergency Medicine ward and the Day Hospital of two large healthcare facilities in Rome. Antibiogram was carried out on 97 patients. Results from analysis of urine samples with the POCT were compared with those from routine AST performed on culture-positive samples, displaying high accuracy (>90%) for all tested antimicrobial drugs and yielding reliable results in less than 12 hours from urine collection thus reducing analytical and management costs.

Exposure to per- and polyfluorinated substances (PFAS) and hydroxylated polychlorinated biphenyls (OH-PCBs) is associated with adverse human health effects, including immunosuppression. It is unknown if these substances can affect the course of autoimmune diseases. This study was based on 907 individuals with multiple sclerosis (MS) and 907 matched controls, where the MS cases were followed longitudinally using the Swedish MS register. We demonstrate sex- and disease-specific differences in serum PFAS concentrations between individuals with MS and controls. Moreover, two OH-PCBs (4-OH-CB187 and 3-OH-CB153) are associated with an increased risk of developing multiple sclerosis, regardless of sex and immigration status. With a clinical follow-up time of up to 18 years, an increase in serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorodecanoic acid (PFDA) decreases the risk of confirmed disability worsening in both sexes, as well as perfluoroheptanesulfonic acid (PFHpS) and perfluorononanoic acid (PFNA), only in males with MS. These results show previously unknown associations between OH-PCBs and the risk of developing MS, as well as the inverse associations between PFAS exposure and the risk of disability worsening in MS. PFAS and OH-PCBs are associated with health effects. Here, the authors present an association between OH-PCB exposure and increased risk of multiple sclerosis, while increased PFAS levels were associated with reduced risk of disability worsening.

Like other steroid hormones, vitamin D elicits both transcriptional events and rapid non genomic effects. Vitamin D receptor (VDR) localization and mechanisms of VDR-triggered non genomic responses are still controversial. Although anticoagulant effects of vitamin D have been reported and VDR signalling has been characterized in monocytes and vascular cells, nothing is known about VDR expression and functions in human platelets, anucleated fragments of megakaryocytes which are known targets of other steroids. In this study we characterized the expression and cellular localization of VDR in human platelets and in a megakaryocyte lineage. Human platelets and their TPA-differentiated precursors expressed a classical 50 kDa VDR protein, which increased with megakaryocytes maturation. By biochemical fractionation studies we demonstrated the presence of the receptor in the soluble and mitochondrial compartment of human platelets, and the observation was confirmed by immunoelectron microscopy analysis. Similar localization was found in mature megakaryocytes, where besides its classical nuclear localization the receptor was evident as soluble and mitochondria resident protein. The results reported here suggest that megakaryocytopoiesis and platelet activation, which are calcium-dependent events, might be modulated by a mitochondrial non genomic activity of VDR. These data open challenging future studies on VDR physiological role in platelets and more generally in mitochondria.

The use of disinfection agents in the washing processing of ready-to-eat (RTE) vegetables, especially sodium hypochlorite, is a common industrial practice performed to enhance microbiological quality. However, some studies have reported a restart of bacterial growth and a substantial increase in bacterial load during early storage associated with the use of disinfection agents, which might represent a risk for consumers. We evaluated the effect of sodium hypochlorite on bacterial growth trends during the shelf-life in Lactuca sativa, simulating the industrial procedures for RTE vegetable packaging. Immediately after sodium hypochlorite treatment, an effective abatement of the bacterial load was observed, followed by a restart of growth throughout storage. After 5 days, the bacterial load was close to that reached by the control samples, indicating that the net increase in bacterial load was significantly higher in the treated samples. This might be ascribed to the reduction in competitive microflora and/or to the induction of adaptive responses by resting bacteria, which might select disinfectant-resistant bacteria. These findings elicit some concerns about the actual duration of the shelf-life; products might decrease their microbiological quality earlier during storage, pointing out the need to better clarify the impact of sodium hypochlorite as a sanitizer to closer consider its use in RTE vegetable processing. Furthermore, due to the importance of the rapid estimation of bacterial load and the early detection of foodborne pathogens throughout the food chain, the accuracy of the rapid bacteria detection method, the Micro Biological Survey (MBS), and its effectiveness for microbiological analyses of RTE vegetables were evaluated.