The Efficiency of Wastewater Treatment Plants for the Removal of Antibiotics

Undoubtedly domestic Wastewater Treatment Plants (WWTPs) are not designed for the removal of some pollutants such as antibiotics. This chapter summarizes the occurrence and fate of six groups of the most widely used antibiotics (β-lactams, sulfonamides, quinolones, tetracyclines, macrolides, and others) in domestic WWTPs. The literature showed that the six groups of antibiotics have been frequently detected during wastewater treatment train (influent, primary treatment, secondary treatment, tertiary treatment, effluent, and sludge treatment) of domestic WWTPs. Also, it was clear that the main removal routes of antibiotics during sewage treatment of domestic WWTPs were adsorption, biodegradation, membrane filtration, and disinfection. Domestic WWTPs cannot remove most of the antibiotics which finally enter the environment through treated effluent and sludge

Phage-Encoded Endolysins

Due to the global emergence of antibiotic resistance, there has been an increase in research surrounding endolysins as an alternative therapeutic. Endolysins are phage-encoded enzymes, utilized by mature phage virions to hydrolyze the cell wall from within. There is significant evidence that proves the ability of endolysins to degrade the peptidoglycan externally without the assistance of phage. Thus, their incorporation in therapeutic strategies has opened new options for therapeutic application against bacterial infections in the human and veterinary sectors, as well as within the agricultural and biotechnology sectors. While endolysins show promising results within the laboratory, it is important to document their resistance, safety, and immunogenicity for in-vivo application. This review aims to provide new insights into the synergy between endolysins and antibiotics, as well as the formulation of endolysins. Thus, it provides crucial information for clinical trials involving endolysins

Effects of Milling and Cooking Processes on the Deoxynivalenol Content in Wheat

Deoxynivalenol (DON, vomitoxin) is a natural-occuring mycotoxin mainly produced by Fusarium graminearum, a food-borne fungi widely distributed in crops and it is one of the most important mycotoxins in wheat and wheat-based foods and feeds. DON affects animal and human health causing diarrhea, vomiting, gastro-intestinal inflammation, and immunomodulation. Since the rate of the occurrence of DON in wheat is high, effective procedures to remove or eliminate DON from food products is essential to minimize exposures in those who consume large amounts of wheat. Cleaning prior to milling reduced to some extent the concentration of DON in final products. Since DON is distributed throughout the kernels, with higher content in the outer skin, milling is also effective in reducing the DON levels of wheat-based foods if bran and shorts are removed before thermal cooking. DON is water-soluble and cooking with larger amounts of water lowers DON content in products such as spaghetti and noodles. During baking or heating, DON is partially degraded to DON-related chemicals, whose toxicological effects are not studied well. This paper reviews the researches on the effects of milling and cooking on the DON level and discusses the perspectives of further studies

Musculoskeletal manifestations in children with Behçet's syndrome: data from the AIDA Network Behçet's Syndrome Registry

This study aims to describe musculoskeletal manifestations (MSM) in children with Behçet's syndrome (BS), their association with other disease manifestations, response to therapy, and long-term prognosis. Data were retrieved from the AIDA Network Behçet's Syndrome Registry. Out of a total of 141 patients with juvenile BS, 37 had MSM at disease onset (26.2%). The median age at onset was 10.0 years (IQR 7.7). The median follow-up duration was 21.8 years (IQR 23.3). Recurrent oral (100%) and genital ulcers (67.6%) and pseudofolliculitis (56.8%) were the most common symptoms associated with MSM. At disease onset, 31 subjects had arthritis (83.8%), 33 arthralgia (89.2%), and 14 myalgia (37.8%). Arthritis was monoarticular in 9/31 cases (29%), oligoarticular in 10 (32.3%), polyarticular in 5 (16.1%), axial in 7 (22.6%). Over time, arthritis became chronic-recurrent in 67.7% of cases and 7/31 patients had joint erosions (22.6%). The median Behçet's Syndrome Overall Damage Index was 0 (range 0-4). Colchicine was inefficacious for MSM in 4/14 cases (28.6%), independently from the type of MSM (p = 0.46) or the concomitant therapy (p = 0.30 for cDMARDs, p = 1.00 for glucocorticoids); cDMARDs and bDMARDs were inefficacious for MSM in 6/19 (31.4%) and 5/12 (41.7%) cases. The presence of myalgia was associated with bDMARDs inefficacy (p = 0.014). To conclude, MSM in children with BS are frequently associated with recurrent ulcers and pseudofolliculitis. Arthritis is mostly mono- or oligoarticular, but sacroiliitis is not unusual. Prognosis of this subset of BS is overall favorable, though the presence of myalgia negatively affects response to biologic therapies. ClinicalTrials.gov Identifier: NCT05200715 (registered on December 18, 2021)

Clinical and laboratory features associated with macrophage activation syndrome in Still's disease: data from the international AIDA Network Still's Disease Registry

: To characterize clinical and laboratory signs of patients with still's disease experiencing macrophage activation syndrome (MAS) and identify factors associated with MAS development. patients with still's disease classified according to internationally accepted criteria were enrolled in the autoInflammatory disease alliance (AIDA) still's disease registry. clinical and laboratory features observed during the inflammatory attack complicated by MAS were included in univariate and multivariate logistic regression analysis to identify factors associated to MAS development. A total of 414 patients with Still's disease were included; 39 (9.4%) of them developed MAS during clinical history. At univariate analyses, the following variables were significantly associated with MAS: classification of arthritis based on the number of joints involved (p = 0.003), liver involvement (p = 0.04), hepatomegaly (p = 0.02), hepatic failure (p = 0.01), axillary lymphadenopathy (p = 0.04), pneumonia (p = 0.03), acute respiratory distress syndrome (p < 0.001), platelet abnormalities (p < 0.001), high serum ferritin levels (p = 0.009), abnormal liver function tests (p = 0.009), hypoalbuminemia (p = 0.002), increased LDH (p = 0.001), and LDH serum levels (p < 0.001). at multivariate analysis, hepatomegaly (OR 8.7, 95% CI 1.9-52.6, p = 0.007) and monoarthritis (OR 15.8, 95% CI 2.9-97.1, p = 0.001), were directly associated with MAS, while the decade of life at Still's disease onset (OR 0.6, 95% CI 0.4-0.9, p = 0.045), a normal platelet count (OR 0.1, 95% CI 0.01-0.8, p = 0.034) or thrombocytosis (OR 0.01, 95% CI 0.0-0.2, p = 0.008) resulted to be protective. clinical and laboratory factors associated with MAS development have been identified in a large cohort of patients based on real-life data

A patient-driven registry on Behçet’s disease: the AIDA for patients pilot project

IntroductionThis paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behçet’s disease (BD).MethodsThe project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behçet), in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme. Quality of life, fatigue, socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry.ResultsRespondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%). The median value of the Behçet’s Disease Quality of Life (BDQoL) score was 14 (IQR 11, range 0–30), indicating a medium quality of life, and the median Global Fatigue Index (GFI) was 38.7 (IQR 10.9, range 1–50), expressing a significant level of fatigue. The mean Beliefs about Medicines Questionnaire (BMQ) necessity-concern differential was 0.9 ± 1.1 (range – 1.8–4), showing that the registry participants prioritized necessity belief over concerns to a limited extent. As for the socioeconomic impact of BD, in 104 out of 187 cases (55.6%), patients had to pay from their own pocket for medical exams required to reach the diagnosis. The low family socioeconomic status (p < 0.001), the presence of any major organ involvement (p < 0.031), the presence of gastro-intestinal (p < 0.001), neurological (p = 0.012) and musculoskeletal (p = 0.022) symptoms, recurrent fever (p = 0.002), and headache (p < 0.001) were associated to a higher number of accesses to the healthcare system. Multiple linear regression showed that the BDQoL score could significantly predict the global socioeconomic impact of BD (F = 14.519, OR 1.162 [CI 0.557–1.766], p < 0.001).DiscussionPreliminary results from the AIDA for Patients BD registry were consistent with data available in the literature, confirming that PROs and PREs could be easily provided by the patient remotely to integrate physician-driven registries with complementary and reliable information

Detection of Human cytomegalovirus UL55 Gene and IE/E Protein Expression in Colorectal Cancer Patients in Egypt

Abstract Background A possible relation between Human cytomegalovirus (HCMV) and colorectal cancer (CRC) has been widely explored with an unclear role yet speculated. Aim The study aimed at detecting HCMV UL55 gene, immediate early and early (IE/E) proteins in colorectal tumor tissues and adjacent non neoplastic tissues (ANNT). Also, it aimed to correlate HCMV presence with CRC clinicopathological features. Subjects and methods A prospective study of 50 HCMV seropositive patients with resectable CRC were enrolled in the study. Demographic, clinical, and radiological findings were recorded. Pathological assessment was done. Paired CRC tumorous and ANNT were examined for HCMV UL55 by PCR and for IE/ E proteins by immunohistochemistry (IHC). Results 70% of CRC patients enrolled were females and 36% were elderly (> 60y). Adenocarcinoma was the prevalent histopathological type (92%) with Grade 2, higher stages, and nodal involvement accounting for (64%, 64% and 56%) respectively. HCMV detection was significantly higher in tumoral tissue versus ANNT by PCR and IHC (P < 0.001, P < 0.008) respectively. Moderate agreement was found between the two techniques (κ = 0.572, P < 0.001). Univariate analysis identified HCMV presence to be significantly higher in elderly patients, in tumors with higher stage and with nodal involvement (P = 0.041, P = 0.008, P = 0.018 respectively). In multivariate analysis, the latter two retained significance (P = 0.010, P = 0.008). Conclusion CRC tumor tissues are more infected by HCMV than ANNT. A significant association of HCMV presence with a higher CRC tumor stage and nodal involvement in an age-dependent manner was detected. HCMV oncomodulatory and a disease progression role is suspected

Nephroprotective Effect of N-Acetyl-L-Cysteine against Diazinon-induced Nephrotoxicity in Rats via IKβ, NFκB, NLRP3 Signaling Pathway

The present study analyzes the efficacy of N-acetyl cysteine (NAC) against diazinon (DZN)-induced nephrotoxicity in male Wistar rats. Rats were divided into five groups with six animals in each group: Group 1 (G1) was maintained in typical control circumstances and given saline once daily intragastric (IG) for 4 weeks; G2 was administered 0.1 mL olive oil IG for 4 weeks; G3 was administered IG NAC 150 mg/kg daily as an aqueous solution for 4 weeks; G4 was administered IG diazinon at a dose of 15 mg/kg daily for 4 weeks; and G5 was administered IG NAC daily one hour before diazinon at the same dose in G3 and G4 for 4 weeks. Sub-chronic exposure to DZN impairs the kidney structure and function, as evidenced by the histopathology, immunohistochemistry, and gene expression of NLRP3, NFκB, IKB, BCL2, BAX mRNA. Our findings showed that NAC reduces the renal dysfunctions induced by DZN by restoring urea and creatinine levels as well as oxidative indicators. Moreover, serum inflammatory markers (IL-1β and TNF-α) concentrations were ameliorated by NAC treatment. However, NAC has shown to play a beneficial role against nephrotoxicity by reversing the cytoarchitecture and downregulation of inflammatory (NLRP3, NFκB, IKB) and apoptotic (BAX) as well as upregulated BCL2 genes and proteins in kidney tissues, bringing them to near-normal levels. Moreover, IHC examination of renal tissue revealed the attenuation of expression of TNF-α. Therefore, NAC could be potentially used to protect the kidneys from pathological changes induced by DZN

Derivation and validation of four patient clusters in Still's disease, results from GIRRCS AOSD-study group and AIDA Network Still Disease Registry

Background: Different patient clusters were preliminarily suggested to dissect the clinical heterogeneity in Still's disease. Thus, we aimed at deriving and validating disease clusters in a multicentre, observational, prospective study to stratify these patients. Methods: Patients included in GIRRCS AOSD-study group and AIDA Network Still Disease Registry were assessed if variables for cluster analysis were available (age, systemic score, erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and ferritin). K-means algorithm with Euclidean metric and Elbow plot were used to derive an adequate number of clusters. Results: K-means clustering assessment provided four clusters based on means standardised according to z-scores on 349 patients. All clusters mainly presented fever, skin rash and joint involvement. Cluster 1 was composed by 115 patients distinguished by lower values of age and characterised by skin rash myalgia, sore throat and splenomegaly. Cluster 2 included 128 patients identified by lower levels of ESR, ferritin and systemic score; multiorgan manifestations were less frequently observed. Cluster 3 comprised 31 patients categorised by higher levels of CRP and ferritin, they were characterised by fever and joint involvement. Cluster 4 contained 75 patients derived by higher values of age and systemic score. Myalgia, sore throat, liver involvement and life-threatening complications, leading to a high mortality rate, were observed in these patients. Conclusions: Four patient clusters in Still's disease may be recognised by a multidimensional characterisation ('Juvenile/Transitional', 'Uncomplicated', 'Hyperferritinemic' and 'Catastrophic'). Of interest, cluster 4 was burdened by an increased rate of life-threatening complications and mortality, suggesting a more severe patient group