MiR-205-5p inhibition by locked nucleic acids impairs metastatic potential of breast cancer cells

Mir-205 plays an important role in epithelial biogenesis and in mammary gland development but its role in cancer still remains controversial depending on the specific cellular context and target genes. We have previously reported that miR-205-5p is upregulated in breast cancer stem cells targeting ERBB pathway and leading to targeted therapy resistance. Here we show that miR-205-5p regulates tumorigenic properties of breast cancer cells, as well as epithelial to mesenchymal transition. Silencing this miRNA in breast cancer results in reduced tumor growth and metastatic spreading in mouse models. Moreover, we show that miR-205-5p knock-down can be obtained with the use of specific locked nucleic acids oligonucleotides in vivo suggesting a future potential use of this approach in therapy

Henoch-Schönlein Purpura in children: Not only kidney but also lung

Background: Henoch-Sch\uf6nlein Purpura (HSP) is the most common vasculitis of childhood and affects the small blood vessels. Pulmonary involvement is a rare complication of HSP and diffuse alveolar hemorrhage (DAH) is the most frequent clinical presentation. Little is known about the real incidence of lung involvement during HSP in the pediatric age and about its diagnosis, management and outcome. Methods: In order to discuss the main clinical findings and the diagnosis and management of lung involvement in children with HSP, we performed a review of the literature of the last 40 years. Results: We identified 23 pediatric cases of HSP with lung involvement. DAH was the most frequent clinical presentation of the disease. Although it can be identified by chest x-ray (CXR), bronchoalveolar lavage (BAL) is the gold standard for diagnosis. Pulse methylprednisolone is the first-line of therapy in children with DAH. An immunosuppressive regimen consisting of cyclophosphamide or azathioprine plus corticosteroids is required when respiratory failure occurs. Four of the twenty-three patients died, while 18 children had a resolution of the pulmonary involvement. Conclusions: DAH is a life-threatening complication of HSP. Prompt diagnosis and adequate treatment are essential in order to achieve the best outcome

Review of Systemic Antibiotic Treatments in Children with Rhinosinusitis

Antibiotic treatment in paediatric rhinosinusitis is still a matter of debate, as the current guidelines have been drafted mainly based on clinical studies published before 2013. Recent modifications in the epidemiological basis of the disease might mean that current treatments are not completely adequate considering the evolving microbiological profile of the disease. The present paper reviews the role of systemic antibiotics in children with acute (ARS), chronic (CRS), recurrent (RARS), and complicated acute (CoARS) rhinosinusitis. A total of 14 studies (including 3 prospective non-randomised studies, 8 retrospective studies, and 3 prospective randomised studies) of the 115 initially identified papers were included in this review, corresponding to 13,425 patients. Five papers dealt with ARS, four papers with RARS or CRS, and five papers with CoARS; the remaining papers included patients with either ARS or CRS. Data about the effectiveness of antibiotic treatment in children with ARC, CRS, and CoARS is scarce, as only three randomised controlled trials have been published in the last decade, with contrasting results. There is an urgent need for dedicated controlled trials not only to test the actual clinical benefits deriving from the routine use of systemic antibiotics in different categories of patients but also to compare the effectiveness of various therapeutic protocols in terms of the type of antibacterial molecules and the duration of treatment

Impact of adenotonsillectomy on pediatric quality of life: review of the literature

Adenotonsillectomy (ADT) is one of the most widely used procedures in the treatment of paediatric recurrent acute tonsillitis (RAT) and obstructive sleep apnoea syndrome (OSAS), both of which have significant repercussions on the patients' quality of life (QoL). The purpose of our review of literature was to highlight the great variety of tools that are currently used to evaluate QoL in children, to examine data available on their efficacy and the feasibility of their use in daily clinical practice, and to determine possible limitations related to an indirect and subjective assessment of QoL in children. Although the use of different parameters makes it difficult to compare the published studies, an analysis of the evidence currently available in the literature suggests that ADT has a generally positive impact on the QoL (especially in case of OSAS). It also highlights the importance of combining tonsillectomy and adenoidectomy in the treatment of OSAS, and documents the comparability of tonsillectomy and tonsillotomy in improving obstructive symptoms. In conclusion, our findings suggest that literature supports that ADT is associated with positive changes in QOL; however further studies using comparable standardised criteria are necessary to confirm the size and duration of this benefit

Platelets induce free and phospholipid-esterified 12-hydroxyeicosatetraenoic acid generation in colon cancer cells by delivering 12-lipoxygenase

Platelets promote tumor metastasis by inducing promalignant phenotypes in cancer cells and directly contributing to cancer-related throm-botic complications. Platelet-derived extracellular vesicles (EVs) can promote epithelial-mesenchymal transition (EMT) in cancer cells, which confers high-grade malignancy. 12S-hydroxyeicosatetraenoic acid (12-HETE) generated by platelet-type 12-lipoxygenase (12-LOX) is considered a key modulator of cancer metastasis through unknown mechanisms. In plate-lets, 12-HETE can be esterified into plasma membrane phospholipids (PLs), which drive thrombosis. Using cocultures of human platelets and human colon adenocarcinoma cells (line HT29) and LC-MS/MS, we investigated the impact of platelets on cancer cell biosynthesis of 12S-HETE and its esterification into PLs and whether platelet ability to transfer its mo-lecular cargo might play a role. To this aim, we performed coculture experiments with CFSE[5-(and-6)-carboxyfluorescein diacetate, succinimidyl ester]-loaded platelets. HT29 cells did not generate 12S-HETE or express 12-LOX. However, they ac-quired the capacity to produce 12S-HETE mainly esterified in plasmalogen phospholipid forms following the uptake of platelet-derived medium-sized EVs (mEVs) expressing 12-LOX. 12-LOX was detected in plasma mEV of patients with adenomas/ adenocarcinomas, implying their potential to deliver the protein to cancer cells in vivo. In cancer cells exposed to platelets, endogenous but not exogenous 12S-HETE contributed to changes in EMT gene expression, mitigated by three structurally unrelated 12-LOX inhibitors. In conclusion, we showed that platelets induce the generation of primarily esteri-fied 12-HETE in colon cancer cells following mEV-mediated delivery of 12-LOX. The modification of cancer cell phospholipids by 12-HETE may functionally impact cancer cell biology and represent a novel target for anticancer agent development

Perception, knowledge and attitude towards childhood fever: A survey among final-year medical students

Aims: Undue concerns about the consequences of fever and its inappropriate management have been documented worldwide among physicians. However, no data exist on medical students. We investigated the perception, knowledge and attitude towards childhood fever among final-year medical students. Methods: Between June and September 2021, final-year medical students of six Italian universities were invited to complete an online survey on their conceptions and attitude towards pharmacological and non-pharmacological management of childhood fever. History of relevant personal or second-hand experience with childhood fever was also addressed. Both quantitative and qualitative approaches were used. Results: Of 1095 (69%) final-year medical students, 756 completed the survey. Many students believe that high fever might cause brain damage, would recommend physical methods and alternate two drugs for fever. Most students do not think that fever has mainly beneficial effects. In Northern Italy, students are less likely to believe that fever might lead to brain damage (OR 0.55, 95% CI 0.33-0.94), and in Southern Italy students are more likely to advise physical methods (OR 1.77, 95% CI 1.22-2.57) and less likely to believe that fever has mainly beneficial effects (OR 0.55, 95% CI 0.39-0.77). History of a relevant personal episode of fever during childhood was not associated with these outcomes. Conclusions: Misconceptions about fever are common among final-year medical students in Italy. Cultural factors rather than individually learned traits might underlie these beliefs. Medical students are a promising target for educational interventions to improve childhood fever management