Search

Plasmatic presepsin (PSP) is a novel biomarker reported to be useful for sepsis diagnosis and prognosis. During the pandemic, only few studies highlighted a possible correlation between PSP and COVID-19 severity, but results remain inconsistent. The present study aims to establish the correlation between PSP and COVID-19 severity. English-language papers assessing a correlation between COVID-19 and PSP from MEDLINE, PubMed, Google Scholar, Cochrane Library, MeSH, LitCovid NLM, EMBASE, CINAHL Plus and the World Health Organization (WHO) website, published from January 2020 were considered with no publication date limitations. Two independent reviewers performed data abstraction and quality assessment, and one reviewer resolved inconsistencies. The protocol was registered on PROSPERO (CRD42022325971).Fifteen articles met our eligibility criteria. The aggregate study population included 1373 COVID-19 patients who had undergone a PSP assessment. The random-effect meta-analysis was performed in 7 out of 15 selected studies, considering only those reporting the mean PSP levels in low- and high-severity cases (n = 707).The results showed that the pooled mean difference of PSP levels between high- and low-severity COVID-19 patients was 441.70 pg/ml (95%CI: 150.40–732.99 pg/ml).Our data show that presepsin is a promising biomarker that can express COVID-19 severity.

Inflammatory bowel diseases show a gender bias, as reported for several other immune-mediated diseases. Female-specific differences influence disease presentation and activity, leading to a different progression between males and females. Women show a genetic predisposition to develop inflammatory bowel disease related to the X chromosome. Female hormone fluctuation influences gastrointestinal symptoms, pain perception, and the state of active disease at the time of conception could negatively affect the pregnancy. Women with inflammatory bowel disease report a worse quality of life, higher psychological distress, and reduced sexual activity than male patients. This narrative review aims to resume the current knowledge of female-related features in clinical manifestations, development, and therapy, as well as sexual and psychological implications related to inflammatory bowel disease. The final attempt is to provide gastroenterologists with a roadmap of female-specific differences, to improve patients’ diagnosis, management, and treatment.

Background: Gastrointestinal (GI) and extra-GI symptoms/manifestations represent key clinical features of patients with non-celiac gluten/wheat sensitivity (NCG/WS). This study aimed to investigate neuro-immune (focusing on mast cells, MCs) interactions in the duodenal submucosa of patients with NCG/WS. Methods: Submucosal whole mounts from duodenal biopsies of 34 patients with self-reported NCG/WS, 28 with celiac disease (CD), 13 with functional dyspepsia (FD), and 24 healthy controls (HC) were analyzed by immunohistochemistry. Quantitative data on neuronal and MCs density and the percentage of MCs in close vicinity to nerves were obtained, and correlations among neurons, MC density and MC-nerve distance (D), and symptoms were assessed in the three groups. Key Results: The number of submucosal neurons was not different among groups. In NCG/WS, MC density was not different from HC, while it was slightly increased vs. CD (P=.07) and significantly decreased vs. FD (P&nbsp

Opioids such as morphine—acting at the mu opioid receptor—are the mainstay for treatment of moderate to severe pain and have good efficacy in these indications. However, these drugs produce a plethora of unwanted adverse effects including respiratory depression, constipation, immune suppression and with prolonged treatment, tolerance, dependence and abuse liability. Studies in β-arrestin 2 gene knockout (βarr2(−/−)) animals indicate that morphine analgesia is potentiated while side effects are reduced, suggesting that drugs biased away from arrestin may manifest with a reduced-side-effect profile. However, there is controversy in this area with improvement of morphine-induced constipation and reduced respiratory effects in βarr2(−/−) mice. Moreover, studies performed with mice genetically engineered with G-protein-biased mu receptors suggested increased sensitivity of these animals to both analgesic actions and side effects of opioid drugs. Several new molecules have been identified as mu receptor G-protein-biased agonists, including oliceridine (TRV130), PZM21 and SR–17018. These compounds have provided preclinical data with apparent support for bias toward G proteins and the genetic premise of effective and safer analgesics. There are clinical data for oliceridine that have been very recently approved for short term intravenous use in hospitals and other controlled settings. While these data are compelling and provide a potential new pathway-based target for drug discovery, a simpler explanation for the behavior of these biased agonists revolves around differences in intrinsic activity. A highly detailed study comparing oliceridine, PZM21 and SR–17018 (among others) in a range of assays showed that these molecules behave as partial agonists. Moreover, there was a correlation between their therapeutic indices and their efficacies, but not their bias factors. If there is amplification of G-protein, but not arrestin pathways, then agonists with reduced efficacy would show high levels of activity at G-protein and low or absent activity at arrestin; offering analgesia with reduced side effects or ‘apparent bias’. Overall, the current data suggests—and we support—caution in ascribing biased agonism to reduced-side-effect profiles for mu-agonist analgesics.

Epidemiological studies highlighted the possibility that exposure to cyanotoxins leads to the development of the neurodegenerative disease amyotrophic lateral sclerosis (ALS).We devised a population-based case-control study in two Italian populations. We used residential proximity of the residence to water bodies as a measure of possible exposure to cyanotoxins.Based on 703 newly-diagnosed ALS cases and 2737 controls, we calculated an ALS odds ratio (OR) of 1.41 (95% CI: 0.72-2.74) for current residence in the vicinity of water bodies, and a slightly lower estimate for historical residence (OR: 1.31; 95% CI: 0.57-2.99). Subjects65 years and people living in the Northern Italy province of Modena had higher ORs, especially when historical residence was considered.Overall, despite some risk of bias due to exposure misclassification and unmeasured confounding, our results appear to support the hypothesis that cyanotoxin exposure may increase ALS risk.

The physiological role of the mitochondrial ATP synthase complex is to generate ATP through oxidative phosphorylation. Indeed, the enzyme can reverse its activity and hydrolyze ATP under ischemic conditions, as shown in isolated mitochondria and in mammalian heart and liver. However, what occurs when cancer cells experience hypoxia or anoxia has not been well explored. In the present study, we investigated the bioenergetics of cancer cells under hypoxic/anoxic conditions with particular emphasis on ATP synthase, and the conditions driving it to work in reverse. In this context, we further examined the role exerted by its endogenous inhibitor factor, IF1, that it is overexpressed in cancer cells. Metabolic and bioenergetic analysis of cancer cells exposed to severe hypoxia (down to 0.1% O2) unexpectedly showed that Δψm is preserved independently of the presence of IF1 and that ATP synthase still phosphorylates ADP though at a much lower rate than in normoxia. However, when we induced an anoxia-mimicking condition by collapsing ΔμΗ+ with the FCCP uncoupler, the IF1-silenced clones only reversed the ATP synthase activity hydrolyzing ATP in order to reconstitute the electrochemical proton gradient. Notably, in cancer cells IF1 overexpression fully prevents ATP synthase hydrolytic activity activation under uncoupling conditions. Therefore, our results suggest that IF1 overexpression promotes cancer cells survival under temporary anoxic conditions by preserving cellular ATP despite mitochondria dysfunction.

Gaussian dispersion models are widely used to simulate the concentrations and deposition fluxes of pollutants emitted by source areas. Very often, the calculation time limits the number of sources and receptors and the geometry of the sources must be simple and without holes. This paper presents CAREA, a new GIS-based Gaussian model for complex source areas. CAREA was coded in the Python language, and is largely based on a simplified formulation of the very popular and recognized AERMOD model. The model allows users to define in a GIS environment thousands of gridded or scattered receptors and thousands of complex sources with hundreds of vertices and holes. CAREA computes ground level, or near ground level, concentrations and dry deposition fluxes of pollutants. The input/output and the runs of the model can be completely managed in GIS environment (e.g. inside a GIS project). The paper presents the CAREA formulation and its applications to very complex test cases. The tests shows that the processing time are satisfactory and that the definition of sources and receptors and the output retrieval are quite easy in a GIS environment. CAREA and AERMOD are compared using simple and reproducible test cases. The comparison shows that CAREA satisfactorily reproduces AERMOD simulations and is considerably faster than AERMOD.

Tumours are characterized by a metabolic rewiring that helps transformed cells to survive in harsh conditions. The endogenous inhibitor of the ATP-synthase IF1 is overexpressed in several tumours and it has been proposed to drive metabolic adaptation. In ischemic normal-cells, IF1 acts limiting the ATP consumption by the reverse activity of the ATP-synthase, activated by ΔΨm collapse. Conversely, IF1 role in cancer cells is still unclear. It has been proposed that IF1 favours cancer survival by preventing energy dissipation in low oxygen availability, a frequent condition in solid tumours. Our previous data proved that in cancer cells hypoxia does not abolish ΔΨm, avoiding the ATP-synthase reversal and IF1 activation. In this study, we investigated the bioenergetics of cancer cells in conditions mimicking anoxia to evaluate the possible role of IF1. Data obtained indicate that also in cancer cells the ΔΨm collapse induces the ATP-synthase reversal and its inhibition by IF1. Moreover, we demonstrated that upon uncoupling conditions, IF1 favours cancer cells growth preserving ATP levels and energy charge. We also showed that in these conditions IF1 favours the mitochondrial mass renewal, a mechanism we proposed driving apoptosis-resistance. Cancer adaptability is also associated with the onset of therapy resistance, the major challenge for melanoma treatment. Recent studies demonstrated that miRNAs dysregulation drive melanoma progression and drug-resistance by regulating tumour-suppressor and oncogenes. In this context, we attempted to identify and characterize miRNAs driving resistance to vemurafenib in patient-derived metastatic melanoma cells BRAFV600E-mutated. Our results highlighted that several oncogenic pathways are altered in resistant cells, indicating the complexity of both drug-resistance phenomena and miRNAs action. Profiling analysis identified a group of dysregulated miRNAs conserved in vemurafenib-resistance cells from distinct patients, suggesting that they ubiquitously drive drug-resistance. Functional studies performed with a first miRNA confirmed its pivotal role in resistance towards vemurafenib.

Background/aim Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with still unknown aetiology. Among environmental factors, pesticides have been investigated due to their potential neurotoxic effects. Within a population-based case-control study conducted in two Italian regions, we aimed to investigate ALS risk due to passive residential exposure to pesticides using two methodologies. Methods The exposure assessment was carried with an individual questionnaire, which collected information of the entire residential history of subjects, focusing on rural residence or in the vicinity of agricultural areas. It was compared with assessment based on geographical information system (GIS), avoiding direct contact with study subjects. To do that, we computed the percentage (≥50%) of rural land use within the 100 m round buffer around each subjects’ residence, according to cover maps of two periods available from the Department of Agriculture, recent (2003–2009) and historical (1978–1989) ones. Risk for passive residential exposure to pesticides was computed using a sex and age adjusted logistic regression model for both methods, and their agreement was assessed using Cohen’s kappa (k). Results The odds ratio (OR) with their 95% confidence intervals (CI) for passive residential exposure to pesticides was 1.67 (95% CI 0.87 to 3.20) from the questionnaire-based assessment, while ORs from the GIS-based assessment were 1.05 (0.40 to 2.73) and 1.13 (0.49 to 2.63) for the recent and historical period, respectively. The agreement between two methods considering all participants was generally moderate to high, with k of 0.564 (95% CI: 0.361 to 0.767) and 0.648 (0.494–0.802) for recent and historical periods, respectively. Analyses divided between cases and controls yielded similar results, with k of 0.468 (0.133–0.803) in cases and 0.630 (0.382–0.879) in controls for recent period, and 0.642 (0.380–0.904) in cases and 0.652 (0.464–0.840) in controls for historical one. Conclusion Our results showed a slight increased risk of passive exposure to pesticides using the questionnaire-based assessment, with less conclusive results from the GIS-based one. The similar agreement either between periods and case/control status, suggested also that no substantial information bias and differential exposure misclassification occurred when assessing pesticides exposure in our population.

Coronal shear fractures of the distal humerus are uncommon injuries and are not exempt from complications. The aim of this research is to evaluate the possible advantages and drawbacks using cannulated compression headless screws. We performed a prospective study including all the consecutive patients who were treated with cannulated screws for coronal shear fractures of the distal humerus between 2010 and 2013. Following the Dubberley’s classification, three patients were type 1A, one patient was 1B, three patients were 2B, and one patient was 3B. The mean follow-up was 30 months. The clinical and radiological evaluation included analysis of passive range of motion, functional outcome, radiological evaluation of fracture healing and reduction maintenance, and the occurrence of possible adverse events. All fractures healed, and radiographic union was observed at an average of 3 months. The average elbow range of motion was 125°, with 125° of flexion and 20 of extension. According to the Broberg and Morrey score, there were four excellent and four good results. Using the Mayo Elbow Performance Index, five cases achieved excellent scores and three reported good results. Adverse events reported in three cases were as follows: heterotopic ossification, complex regional pain syndrome and delayed lateral collateral ligament disruption. The use of cannulated compression headless screws has given satisfactory results, allowing a strong inter-fragmentary compression, early mobilization, with high union rates and good elbow function. However, patients should be counseled about the high proportion of adverse events following these injuries.

We have previously demonstrated that cells adapt to hypoxia using different metabolic reprogramming mechanisms depending on metabolism. We now investigate how the different adapting mechanisms affect reactive oxygen species (ROS) levels, and how ROS levels and cellular metabolism are linked. We show that when skin fibroblasts grew under short-term hypoxia (1% oxygen tension) ROS level markedly decreased (-50%) whatever substrate was available to the cells. Indeed, cellular ROS level linearly and directly decreased with oxygen tension. However, these relationships cannot explain the progressive ROS level decrease observed after prolonged cells hypoxia exposure. In glucose-enriched medium reduced mitochondrial mass and greater fragmentation are observed, both clear-cut indications of mitophagy suggesting that this is responsible for cellular ROS level decrease. Otherwise, in glucose-free medium exposure to prolonged hypoxia resulted in only minor mass reduction, but significantly enhanced expression of antioxidant enzymes. Interestingly, cellular ROS levels were lower in glucose-free compared to glucose-enriched medium under either normoxic or hypoxic conditions. Taken together, these findings reveal that in primary human fibroblasts hypoxia induces a decline in ROS and that different metabolism-dependent mechanisms contribute it, besides the major oxygen concentration decrease. In addition, the present data support the notion that metabolisms generating fewer ROS are associated with lower HIF-1α stabilization.

The physiological role of the mitochondrial ATP synthase complex is to generate ATP through oxidative phosphorylation. Indeed, the enzyme can reverse its activity and hydrolyze ATP under ischemic conditions, as shown in isolated mitochondria and in mammalian heart and liver. However, what occurs when cancer cells experience hypoxia or anoxia has not been well explored. In the present study, we investigated the bioenergetics of cancer cells under hypoxic/anoxic conditions with particular emphasis on ATP synthase, and the conditions driving it to work in reverse. In this context, we further examined the role exerted by its endogenous inhibitor factor, IF

For the last few decades, there have been a lot of studies recognising the significant roles of the urban trees as a high-quality carbon sink. This work is a preliminary study about how remote sensing and photogrammetry could be useful tools to identify urban trees for the purpose of Carbon Storage (CS) computation in urban areas. Our first study area is a typical urban park located in Sassuolo, a municipality in the northern part of Italy in the so-called “Pianura Padana”. We measured the tree Height (H) and the Diameter at Breast Height (DBH), required for the calibration of the CS, based on the tree allometry during the field data collection along with the constructing a 3D model through the photogrammetric approach. A high-resolution WorldView (WV) 3 satellite image of the same area, was classified using an object-oriented approach to count the number of trees varied with different species. This preliminary study will enhance the possibilities of the application of these approaches in case of the larger urban areas to ascertain the accuracy of the tree CS calibration.

Background Exposure to pesticides has been suggested as a risk factor for childhood leukemia, but definitive evidence on this relation and the specific pesticides involved is still not clear. Objective We carried out a population-based case-control study in a Northern Italy community to assess the possible relation between passive exposure to agricultural pesticides and risk of acute childhood leukemia. Methods We assessed passive pesticide exposure of 111 childhood leukemia cases and 444 matched controls by determining density and type of agricultural land use within a 100-m radius buffer around children’s homes. We focused on four common crop types, arable, orchard, vineyard and vegetable, characterized by the use of specific pesticides that are potentially involved in childhood induced leukemia. The use of these pesticides was validated within the present study. We computed the odds ratios (OR) of the disease and their 95% confidence intervals (CI) according to type and density of crops around the children’s homes, also taking into account traffic pollution and high-voltage power line magnetic field exposure. Results Childhood leukemia risk did not increase in relation with any of the crop types with the exception of arable crops, characterized by the use of 2.4-D, MCPA, glyphosate, dicamba, triazine and cypermethrin. The very few children (n = 11) residing close to arable crops had an OR for childhood leukemia of 2.04 (95% CI 0.50–8.35), and such excess risk was further enhanced among children aged Conclusions Despite the null association with most crop types and the statistical imprecision of the estimates, the increased leukemia risk among children residing close to arable crops indicates the need to further investigate the involvement in disease etiology of passive exposure to herbicides and pyrethroids, though such exposure is unlikely to play a role in the vast majority of cases.