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The purpose of this study was to investigate the trajectory of mothers caring for children with blood cancer.Fourteen mothers of children with blood cancer participated in in-depth interviews, from 30 min to 2 h in length, from July 1 through September 30, 2019. Grounded theory was used to investigate the trajectory for mothers of children with blood cancer. Purposive sampling and semi-structured questionnaires were employed to obtain in-depth interviews.10 categories and 28 concepts were extracted from the raw data. The core category was 'living with anxiety: from life to independence of their sick child' which consisted of three phases: feeling chaos, immersing oneself in treatment, and returning to normal life. In the trajectory of mothers of caring for children with blood cancer, some participants felt like being on an island and hope to forget, whereas others tended to thank for the support of those near and find their own life according to the dimension of anxiety, support from others, and acceptance of illness.Healthcare providers must have a better understanding of how the mothers of children with blood cancer can accept and cope with their child's illness in spite of the ongoing anxiety as well as need to explore the ways in which families can accept their child's chronic illness and reconstruct their life.

Purpose: To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant) 0.7 and 0.35 mg in the treatment of patients with diabetic macular edema (DME).Design: Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols were conducted. Data were pooled for analysis.Participants: Patients (n = 1048) with DME, best-corrected visual acuity (BCVA) of 20/50 to 20/200 Snellen equivalent, and central retinal thickness (CRT) of ≥300 μm by optical coherence tomography.Methods: Patients were randomized in a 1:1:1 ratio to study treatment with DEX implant 0.7 mg, DEX implant 0.35 mg, or sham procedure and followed for 3 years (or 39 months for patients treated at month 36) at ≤40 scheduled visits. Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months.Main Outcome Measures: The predefined primary efficacy endpoint for the United States Food and Drug Administration was achievement of ≥15-letter improvement in BCVA from baseline at study end. Safety measures included adverse events and intraocular pressure (IOP).Results: Mean number of treatments received over 3 years was 4.1, 4.4, and 3.3 with DEX implant 0.7 mg, DEX implant 0.35 mg, and sham, respectively. The percentage of patients with ≥15-letter improvement in BCVA from baseline at study end was greater with DEX implant 0.7 mg (22.2%) and DEX implant 0.35 mg (18.4%) than sham (12.0%; P ≤ 0.018). Mean average reduction in CRT from baseline was greater with DEX implant 0.7 mg (−111.6 μm) and DEX implant 0.35 mg (−107.9 μm) than sham (−41.9 μm; P < 0.001). Rates of cataract-related adverse events in phakic eyes were 67.9%, 64.1%, and 20.4% in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham groups, respectively. Increases in IOP were usually controlled with medication or no therapy; only 2 patients (0.6%) in the DEX implant 0.7 mg group and 1 (0.3%) in the DEX implant 0.35 mg group required trabeculectomy.Conclusions: The DEX implant 0.7 mg and 0.35 mg met the primary efficacy endpoint for improvement in BCVA. The safety profile was acceptable and consistent with previous reports.

Positional ranking functions, widely used in web search engines and related search systems, improve result quality by exploiting the positions of the query terms within documents. However, it is well known that positional indexes demand large amounts of extra space, typically about three times the space of a basic nonpositional index. Textual data, on the other hand, is needed to produce text snippets. In this paper, we study time–space trade-offs for search engines with positional ranking functions and text snippet generation. We consider both index-based and non-index based alternatives for positional data. We aim to answer the question of whether positional data should be indexed, and how. We show that there is a wide range of practical time–space trade-offs. Moreover, we show that using about 1.30 times the space of positional data, we can store everything needed for efficient query processing, with a minor increase in query time. This yields considerable space savings and outperforms, both in space and time, recent alternatives from literature. We also propose several efficient compressed text representations for snippet generation, which are able to use about half of the space of current state-of-the-art alternatives with little impact in query processing time.

Lactobacillus sakei K040706 is the most populous lactic acid bacteria (LAB) in over ripened Doenjang, a traditional Korean fermented soybean paste. In this study, we investigated the immunostimulating effects of L. sakei K040706 (K040706) in macrophages and in cyclophosphamide-induced immunosuppressed mice. Upon exposure to K040706, significant increases in phagocytic activity and in the productions of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were observed in rIFN-γ-primed RAW 264.7 macrophages. K040706 also increased the expressions of inducible nitric oxide synthase (iNOS) at the protein and promoter binding levels, and the expressions of iNOS, TNF-α, and IL-6, at the mRNA level. In addition, K040706 significantly increased the transcriptional activities and DNA binding of nuclear factor-κB (NF-κB), which was accompanied by parallel enhancement of the nuclear translocation of p65 via the phosphorylations inhibitory kappa B-α (IκB-α) and IκB-kinase (IKK). On the other hand, pretreatment with NF-κB inhibitors reduced K040706-induced NO production in IFN-γ-primed RAW 264.7 macrophages. Furthermore, K040706 induced-NO production was completely abolished by anti-Toll-like receptor 2 (TLR2) antibody. In our cyclophosphamide-induced immunosuppressed mouse model, administration of K040706 restored thymus and spleen indices. Taken together, our findings suggest that K040706 improves immune function by regulating immunological parameters, such as, the productions of NO, TNF-α, and IL-6 via NF-κB activation, and by activating TLR2 in rIFN-γ-primed macrophages. In parallel, K040706 restored immunological parameters in cyclophosphamide-induced immunosuppressed mice and may warrant further evaluations as potential immunomodulatory agent.

French Abstract: Depuis les premiers projets de creation d'un brevet commun aux Etats membres, le role accorde a la CJUE a ete considerablement reduit. Le systeme semble aujourd’hui avoir ete repousse a la frontiere de l’ordre juridique de l’Union europeenne. Pourtant, au regard des enjeux economiques, politiques et humains lies a la fonction sociale du droit de brevet, cette situation menacerait la construction d’un droit europeen des brevets equilibre et accepte, prenant en compte l’ensemble des interets qui composent la societe. L’etude invite donc a une lecture renouvelee des textes relatifs au brevet unitaire, qui reinsere le contentieux dans l’ordre juridique de l’Union europeenne grâce au controle de la CJUE sur l’action specialisee de la juridiction unifiee du brevet. English Abstract: Ever since EU member states started to consider the implementation of a unitary patent system, the powers granted to the CJEU in the different projects have been constantly reduced. The future system of a European patent with unitary effect seems to have been pushed back to the frontier of the EU legal system. Yet, because of the economic, political and human issues at stake, this situation is a threat to the establishment of well-balanced patent system in the EU that would not unduly favour some interests over the others and that would be accepted by all parties. The author of this study believes that a new understanding of unitary patent legislation should be considered in order to reintegrate patent litigation into the European Union legal order, by means of the CJUE supervision over the unified patent court.

International audience; Muscular dystrophies are a group of genetically distinct diseases for which no treatment exists. While gene transfer approach is being tested for several of these diseases, such strategies can be hampered when the size of the corresponding complementary DNA (cDNA) exceeds the packaging capacity of adeno-associated virus vectors. This issue concerns, in particular, dysferlinopathies and titinopathies that are due to mutations in the dysferlin (DYSF) and titin (TTN) genes. We investigated the efficacy of RNA trans-splicing as a mode of RNA therapy for these two types of diseases. Results obtained with RNA trans-splicing molecules designed to target the 3' end of mouse titin and human dysferlin pre-mRNA transcripts indicated that trans-splicing of pre-mRNA generated from minigene constructs or from the endogenous genes was achieved. Collectively, these results provide the first demonstration of DYSF and TTN trans-splicing reprogramming in vitro and in vivo. However, in addition to these positive results, we uncovered a possible issue of the technique in the form of undesirable translation of RNA pre-trans-splicing molecules, directly from open reading frames present on the molecule or associated with internal alternative cis-splicing. These events may hamper the efficiency of the trans-splicing process and/or lead to toxicity.