Soybean Meal‐Dependent Acute Intestinal Inflammation Delays Osteogenesis in Zebrafish Larvae

Foods are known to be modulators of inflammation and skeletal development. The intestine plays an essential role in the regulation of bone health mainly through the regulation of the absorption of vitamin D and calcium; in fact, inflammatory bowel diseases are often related to bone health issues such as low bone mineral density, high fracture risk, osteoporosis and osteopenia. Considering the complexity of the pathways involved, the use of a simple animal model can be highly useful to better elucidate the pathogenic mechanisms. Soybean flour with a high saponin content has been used in many studies to induce intestinal inflammation in zebrafish larvae. Using a 50% soybean meal (SBM), we analyzed the effects of this soy-induced inflammatory bowel disease on zebrafish larval osteogenesis. Soybean meal induces intestinal functional alterations and an inflammatory state, highlighted by neutral red staining, without altering the general development of the larvae. Our data show that the chondrogenesis as well as endochondral ossification of the head of zebrafish larvae are not affected by an SBM-diet, whereas intramembranous ossification was delayed both in the head, where the length of the ethmoid plate reduced by 17%, and in the trunk with a delayed vertebral mineralization of 47% of SBM larvae. These data highlight that diet-dependent bowel inflammation can differently modulate the different mechanisms of bone development in different zones of the skeleton of zebrafish larvae

Soybean meal-dependent intestinal inflammation induces different patterns of bone-loss in adult zebrafish scale

Inflammatory bowel disease have been linked to several health issues, including high risk of low bone mineral density. Danio rerio (zebrafish) is a good model to verify the effects of intestinal inflammation, since its gastrointestinal and immune systems are closely related to that of mammalians. Zebrafish is also a powerful model to study bone metabolism using the scale as the read-out model. Food strongly impacts zebrafish gut physiology, and it is well known that soybean meal induces intestinal inflammation. Adult zebrafish fed with defatted soybean meal (SBM) exhibited an intestinal inflammation evidenced by morphological alterations, inflammatory infiltrate, and increased mRNA expression of inflammatory cytokines (IL-1\u3b2, IL-6, IL-8, IL-10, TGF\u3b2, TNF-\u3b1). The peak of acute intestinal inflammation, spanning between week 2 and 3, correlates with a transitory osteoporosis-like phenotype in the scale border. Later, a chronic inflammatory condition, associated with persistent IL-8 expression, correlates with the progression of resorption lacunae in the scale center. Both types of resorption lacunae were associated with intense osteoclastic tartrate-resistant acid phosphatase (TRAP) activity. After 3 weeks of SBM treatment, osteoclast activity decreased in the scale border but not in the center. At the same time, alkaline phosphatase (ALP) is activated in the border to repair the bone matrix. This model can contribute to elucidate in vivo the molecular mechanisms that links intestinal inflammation and bone metabolism in IBD

Danio rerio : the Janus of the bone from embryo to scale

Danio rerio (zebrafish), like the Roman god Janus, is an old animal model which is recently emerged and looks to the future with an increasing scientific success. Unlike other traditional animal models, zebrafish represents a versatile way to approach the study of the skeleton. Transparency of the larval stage, genetic manipulability and unique anatomical structures (scales) makes zebrafish a powerful and versatile instrument to investigate the bone tissue in terms of structure and function. Like Janus, zebrafish offers two different faces, or better, two models in one animal: larval and adult stage. The embryo can be used to isolate new genes involved in osteogenesis by large-scale mutagenesis screenings. The behavior of bone cells and genes in osteogenesis can be investigate by using transgenic lines, vital dyes, mutants and traditional molecular biology techniques. The adult zebrafish represents an important resource to study the pathways related to the bone metabolism and turnover. In particular, the properties of the caudal fin allow to study mechanisms of bone regeneration and reparation whereas the elasmoid scale represents an unique tool to investigate the bone metabolism under physiological or pathological conditions

Do novel European Headache Federation criteria identify differences in migraine burden?: baseline data of an international real-life study on resistant and refractory migraine (REFINE)

Question. We evaluated if EHF criteria for resistant (RES) and refractory (REF) migraine identify patients with more severe migraine burden. Methods. We performed an observational, multi center, international study to compare baseline characteristics, comorbidities, and PROMs of non-resistant and non-refractory (NRNR) migraine, RES and REF individuals in the REFINE study. Results. We included 175 individuals with NRNR migraine, 133 (39.7%) with RES and 27 (8.0%) with REF. Individuals with RES and REF migraine as compared to those with NRNR reported higher monthly migraine days (median=8, IQR=5-14 vs. median=13, IQR=10- 17 and median=15, IQR=10-20; p≤0.001), months of chronification (median=24, IQR=12-72 vs. median=40, IQR=12-108 and median=60, IQR=18-96; p=0.044), monthly days of symptomatic drugs assumption (median=8, IQR=5-15 vs. median=12, IQR=9-20 and median=15, IQR=10-20; p≤0.001), medication overuse (19.4% vs. 45.9% and 40.7%; p≤0.001). They also had more comorbidities such as depression (18.3% vs. 31.1% and 44.4%; p=0.002) and anxiety (13.7% vs. 21.1% and 37%; p=0.009). In these groups, PROMs also revealed a higher presence of anxiety (p≤0.001) and depression (p≤0.001) symptoms and poorer sleep quality (p=0.006). Regarding specific perceptions about migraine, RES and REF individuals reported higher impact of migraine on daily life (p≤0.001) and work, household work, and social life (p≤0.001), along with a lower perception of the effectiveness of their ongoing treatment for migraine (p≤0.001), when compared to NRNR subjects (Table 1). Conclusion. RES and REF migraine is associated with relevant migraine burden considering migraine features, comorbidities and scores at several scales; the severe burdensome condition of RES and REF is confirmed by the median number of monthly migraine days and PROMs.info:eu-repo/semantics/publishedVersio

One week of levofloxacin plus dexamethasone eye drops for cataract surgery: an innovative and rational therapeutic strategy

Background: Cataract surgery is the most common operation performed worldwide. A fixed topical corticosteroid-antibiotic combination is usually prescribed in clinical practice for 2 or more weeks to treat post surgical inflammation and prevent infection. However, this protracted schedule may increase the incidence of corticosteroid-related adverse events and notably promote antibiotic resistance. Methods: This International, multicentre, randomized, blinded-assessor, parallel-group clinical study evaluated the non-inferiority of 1-week levofloxacin/dexamethasone eye drops, followed by 1-week dexamethasone alone, vs. 2-week gold-standard tobramycin/dexamethasone (one drop QID for all schedules) to prevent and treat ocular inflammation and prevent infection after uncomplicated cataract surgery. Non-inferiority was defined as the lower limit of the 95% confidence interval (CI) around a treatment difference >\u201310%. The study randomized 808 patients enrolled in 53 centres (Italy, Germany, Spain and Russia). The primary endpoint was the proportion of patients without anterior chamber inflammation on day 15 defined as the end of treatment. Endophthalmitis was the key secondary endpoint. This study is registered with EudraCT code: 2018-000286-36. Results: After the end of treatment, 95.2% of the patients in the test arm vs. 94.9% of the control arm had no signs of inflammation in the anterior chamber (difference between proportions of patients = 0.028; 95% CI: 120.0275/0.0331). No case of endophthalmitis was reported. No statistically significant difference was evident in any of the other secondary endpoints. Both treatments were well tolerated. Conclusions: Non-inferiority of the new short pharmacological strategy was proven. One week of levofloxacin/dexamethasone prevents infection, ensures complete control of inflammation in almost all patients and may contain antibiotic resistance

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes