Effects of a medium cut-off (Theranova®) dialyser on haemodialysis patients: a prospective, cross-over study

Background. Despite significant advances in haemodialysis (HD) in recent decades, current dialysis techniques are limited by inadequate removal of uraemic solutes such as middle molecules and protein-bound uraemic toxins. Novel medium cut-off (MCO) membrane or \u2018expanded haemodialysis\u2019 (HDx) provides diffusive removal of conventional and large middle molecular weight uraemic toxins, with marginal albumin leak. Methods. This prospective, open-label, controlled, cross-over pilot study compared HDx (novel MCO membrane TheranovaVR 400) and conventional HD in 20 prevalent HD patients. Biochemical, dialysis adequacy and safety measures (adverse events, infections and hospitalization frequency) were recorded. Ten patients underwent conventional HD high-flux dialyser and 10 patients underwent HDx for 3 months, and the patients then switched and received the other treatment for a further 3 months. Results. Treatment with HDx was associated with a significant reduction in serum albumin concentration [median (interquartile range) reduction 0.45 g/dL (0.575 to 0.05); P \ubc 0.025]. However, median albumin levels were 3.5 g/dL and no patients had clinical symptoms of hypoalbuminaemia or needed intravenous albumin administration. The number of infections was lower in patients treated with HDx (n \ubc 7/19) compared with patients treated with HD (n \ubc 14/20; P \ubc 0.03). Patients treated with HDx had reduced levels of interleukin (IL)-1b (from 0.06 6 0.02 pg/mL versus 0.28 6 0.18 pg/mL with HD) and IL-6 (6.45 6 1.57 pg/mL versus 9.48 6 2.15 pg/mL), while tumour necrosis factor-a levels remain unchanged. Conclusions. This study demonstrates that the chronic use of the novel MCO dialyser TheranovaVR appears to be safe and well-tolerated, without serious side effects or hypoalbuminaemia, as well as fewer infections. These results need to be confirmed in larger randomized clinical trials

Influence of cover crop termination on ground dwelling arthropods in organic vegetable systems

open7noA key aspect in cover crop management is termination before the cash crop is planted. The aim of this study was to assess the effects of termination methods on ground-dwelling arthropods. The conventional mechanical termination method—i.e., green manuring by means of a disc harrow—was compared to flattening using a roller crimper. Two different crop systems were investigated for two growing seasons; cauliflower was grown in autumn after the termination of a mixture of cowpea, pearl millet, and radish, and tomato was cropped in spring and summer after the termination of a mixture of barley and vetch. Ground beetles (Coleoptera: Carabidae), rove beetles (Coleoptera: Staphylinidae), and spiders (Araneae) were sampled by means of standard pitfall traps throughout the growing season of both cash crops. The roller crimper increased the overall abundance of ground beetles in the first growing season of both cash crops, whereas in the second year, no significant effect could be detected. Rove beetles were more abundant in plots where the cover crops were terminated by the roller crimper. Finally, green manuring increased the abundance of spiders, especially on the first sampling date after cover crop termination. Albeit different taxa showed different responses, the termination of cover crops by a roller crimper generally increased the abundance of ground dwelling arthropods. Given that most of the sampled species were generalist predators, their increased abundance could possibly improve biological control.openDepalo L.; Burgio G.; Magagnoli S.; Sommaggio D.; Montemurro F.; Canali S.; Masetti A.Depalo L.; Burgio G.; Magagnoli S.; Sommaggio D.; Montemurro F.; Canali S.; Masetti A

Physical exercise in major depression: Reducing the mortality gap while improving clinical outcomes

Major depression shortens life while the effectiveness of frontline treatments remains modest. Exercise has been shown to be effective both in reducing mortality and in treating symptoms of major depression, but it is still underutilized in clinical practice, possibly due to prevalent misperceptions. For instance, a common misperception is that exercise is beneficial for depression mostly because of its positive effects on the body (\u201cfrom the neck down\u201d), whereas its effectiveness in treating core features of depression (\u201cfrom the neck up\u201d) is underappreciated. Other long-held misperceptions are that patients suffering from depression will not engage in exercise even if physicians prescribe it, and that only vigorous exercise is effective. Lastly, a false assumption is that exercise may be more harmful than beneficial in old age, and therefore should only be recommended to younger patients. This narrative review summarizes relevant literature to address the aforementioned misperceptions and to provide practical recommendations for prescribing exercise to individuals with major depression

Exploring the human chorionic gonadotropin induced steroid secretion profile of mouse Leydig tumor cell line 1 by a 20 steroid LC-MS/MS panel

The canonical androgen synthesis in Leydig cells involves Delta 5 and Delta 4 steroids. Besides, the backdoor pathway, eompassing 5 alpha and 5 alpha,3 alpha steroids, is gaining interest in fetal and adult pathophysiology. Moreover, the role of androgen epimers and progesterone metabolites is still unknown. We developed a liquid chromatographytandem mass spectrometry (LC-MS/MS) method for measuring 20 steroids and used it to investigate the steroid secretion induced by human chorionic gonadotropin (hCG) in the mouse Leydig tumor cell line 1 (mLTC1). Steroids were extracted from 500 mu L supernatants from unstimulated or 100 pM hCG-exposed mLTC1 cells, separated on a Luna C8 100 x 3 mm, 3 mu m column, with 100 mu M NH4F and methanol as mobile phases, and analyzed by positive electrospray ionization and multiple reaction monitoring. Sensitivity ranged within 0.012-38.0 nmol/L. Intra-assay and inter-assay imprecision were < 9.1% and 10.0%, respectively. Trueness, recovery and matrix factor were within 93.4-122.0, 55.6-104.1 and 76.4-106.3%, respectively. Levels of 16OH-progesterone, 11-deoxycortisol, androstenedione, 11-deoxycorticosterone, testosterone, 17OH-progesterone, androstenedione, epitestosterone, dihydrotestosterone, progesterone, androsterone and 17OH-allopregnanolone were effectively measured. Traces of 17OH-dihydroprogesterone, androstanediol and dihydroprogesterone were found, whereas androstenediol, 17OH-pregnenolone, dehydroepiandrosterone, pregnenolone and allopregnanolone showed no peak. hCG induced an increase of 80.2-102.5 folds in 16OH-progesterone, androstenedione and testosterone, 16.6 in dihydrotestosterone, 12.2-27.5 in epitestosterone, progesterone and metabolites, 8.1 in 17OH-allopregnanolone and <= 3.3 in 5 alpha and 5 alpha,3 alpha steroids

The ground beetle Pseudoophonus rufipes gut microbiome is influenced by the farm management system

: Intensive conventional farm management, characterized by high agrochemicals input, could alter the composition of microbial communities with potential negative effects on both functional traits and the ecosystem services provided. In this study, we investigated the gut microbial composition of a high ecological relevance carabid Pseudoophonus rufipes, sampled in two fields subjected to conventional and organic management practices. Carabids' gut microbiota was analyzed via qPCR and NGS. Profound differences between the microbial composition of organic and conventional samples were detected: the abundance of Tenericutes and Proteobacteria was significant higher in organic and conventional samples, respectively. Spiroplasmataceae and Bifidobacteriaceae families were significantly more abundant in samples from organic management, while Enterococcaceae, Morganellaceae and Yersiniaceae were more abundant in samples from conventional management. The diverse gut microbial composition of insects between the two management systems is related to the pressure of environmental stressors and it may representing an important bioindication of ecological functions and services provided by a carabid species

PO-485 Low abundance circulating proteins in giant cell tumours of bone

Introduction Circulating low-abundance proteins/fragments generating from tumour cells and tissues, represent the most important source of cancer biomarkers useful for early diagnosis and prognosis. Giant cell tumour of bone (GCT) is a benign neoplasm occurring in the long bone and in the axial skeleton of young adults. Approximately 5% of GCT develop pulmonary metastases. Although many biomarkers have been proposed, identification of circulating low abundance molecules may be useful to predict metastasis with a non invasive method. Material and methods The hydrogel nanoparticles technique followed by mass spectrometry was used to detect low molecular weight serum proteins or protein fragments in serum of 20 GCT patients with different clinical course and in 10 healthy sera used as control. The most representative low-abundant de novo or differentially abundant proteins were submitted to String database in order to define protein-protein interaction network. Cluster analysis was performed to identify prognostic groups of patients with similar abundance of proteins that significantly discriminate between the groups. Results and discussions For the 25 low-abundant de novo or differentially abundant proteins identified, we recognised that the top interconnected pathways included protein activation cascade, wound healing, blood coagulation, cell-substrate adhesion. Proteoma cluster analysis separated metastasis-free from metastatic GCT patients in two well-defined groups where serum levels of signalling transduction mediators and regulators of kinase activity presented a high discriminatory power. Increased expression of proteins STAT5B, GRB2 and OXSR1 was related to a higher probability of metastasis. Conclusion In conclusion, using a no invasive technique, we identified differentially abundant serum biomarkers, also providing prognostic information in patients with GCT of bone. Future studies are ongoing to establish the interplay between these biomarkers in order to fully understand the mechanism involved in tumour development and to focus on the planning of tailored therapies that should be more effective and less toxic

Prognosis of follicular lymphoma: a predictive model based on a retrospective analysis of 987 cases

Patients (n-987) with a histologically confirmed diagnosis of follicular lymphoma were studied with the aim of developing a prognostic model specifically devised for this type of lymphoma. We collected information on age, sex, Ann Arbor stage, number of extranodal disease sites, bone marrow (BM) involvement, bulky disease, B symptom criteria (fever, night sweats, and weight loss), performance status (PS), serum lactate dehydrogenase (LDH) level, serum albumin level, hemoglobin level, and erythrocyte sedimentation rate (ESR). In the training sample of 429 patients with complete data, multivariate analysis showed that age, sex, number of extranodal sites, B symptoms, serum LDH level, and ESR were factors predictive for overall survival. Using these 6 variables, a prognostic model was devised to identify 3 groups at different risk. The 5- and 10-year survival rate was 90% and 65% for patients at low risk, respectively; 75% and 54% for patients at intermediate risk; and 38% and 11% for those at high risk (log-rank test, 86.62; P < .0001). The model was also predictive (P = .0001) in the validation sample of 265 patients with complete data only for the 6 variables used in the development of the model and even in the group of 210 patients from the validation sample uniformly treated with doxorubicin-containing regimens (P = .0001). The prognostic model appears to be very useful in identifying patients with follicular lymphoma at low, intermediate, or high risk

Intensive Care Unit Mortality and Length of Stay Among Critically Ill Patients With Sepsis Treated With Corticosteroids: A Retrospective Cohort Study

Objectives: Sepsis is a major cause of morbidity and mortality in critically ill patients worldwide, and corticosteroids are commonly used to treat it. However, the evidence supporting the use of corticosteroids in sepsis patients admitted to the intensive care unit (ICU) is of low certainty, with conflicting results reported in previous studies. Thus, we aimed to investigate the potential association between corticosteroid treatment and various outcomes, including 30-day ICU mortality, ICU length of stay (LOS), mechanical ventilation use, new onset of infection, and hyperglycemia in patients diagnosed with sepsis and admitted to the ICU. Materials and Methods: We conducted a cohort study utilizing data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database from 2008 to 2019. The study compared users of corticosteroids following admission to the ICU with non-users. Outcomes assessed included 30-day ICU mortality, ICU length of stay (LOS), mechanical ventilation use, new onset of infection, and hyperglycemia. Doubly robust, augmented inverse propensity weighted models were employed to control for confounders and determine the average treatment effect (ATE) of corticosteroids on study outcomes. Results: A total of 10,098 patients with a first diagnosis of sepsis were identified, of which 1,235 (12.2%) received corticosteroid treatment, and 8,863 (87.8%) did not. Corticosteroid use was associated with increased 30-day ICU mortality (ATE, 0.127; 95% CI, 0.083 to 0.171), ICU LOS (ATE, 1.773; 95% CI, 1.036 to 2.510), mechanical ventilation use (ATE, 0.181; 95% CI, 0.130 to 0.233), new onset of infection (ATE, 0.063; 95% CI, 0.032 to 0.094), and hyperglycemia (ATE, 0.024; 95% CI, 0.013 to 0.035) compared to non-use. Conclusion: The safety profile of corticosteroid therapy in sepsis patients admitted to the ICU remains a concern. Clinicians should carefully consider all available evidence and patient preferences when deciding to prescribe corticosteroids. Given the low certainty of evidence supporting the current treatment guidelines, further research is warranted to provide a more conclusive understanding of the risks and benefits associated with corticosteroid use in this patient population

Repurposing Anti-Inflammasome NRTIs for Improving Insulin Sensitivity and Reducing Type 2 Diabetes Development

Innate immune signaling through the NLRP3 inflammasome is activated by multiple diabetes-related stressors, but whether targeting the inflammasome is beneficial for diabetes is still unclear. Nucleoside reverse-transcriptase inhibitors (NRTI), drugs approved to treat HIV-1 and hepatitis B infections, also block inflammasome activation. Here, we show, by analyzing five health insurance databases, that the adjusted risk of incident diabetes is 33% lower in patients with NRTI exposure among 128,861 patients with HIV-1 or hepatitis B (adjusted hazard ratio for NRTI exposure, 0.673; 95% confidence interval, 0.638 to 0.710; P \u3c 0.0001; 95% prediction interval, 0.618 to 0.734). Meanwhile, an NRTI, lamivudine, improves insulin sensitivity and reduces inflammasome activation in diabetic and insulin resistance-induced human cells, as well as in mice fed with high-fat chow; mechanistically, inflammasome-activating short interspersed nuclear element (SINE) transcripts are elevated, whereas SINE-catabolizing DICER1 is reduced, in diabetic cells and mice. These data suggest the possibility of repurposing an approved class of drugs for prevention of diabetes