In-label, off-label prescription, efficacy and tolerability of dalbavancin: report from a National Registry

PurposeAlthough dalbavancin is currently approved for the treatment of ABSSIs, several studies suggest its efficacy and tolerance as long-term therapy for other off-label indications requiring prolonged intravenous antibiotic administration.MethodsWe conducted a prospective nationwide study of dalbavancin use in real-life settings for both approved and off-label indications analysing for each case the clinical and microbiological characteristics of infection the efficacy and safety of treatments.ResultsDuring the study period (from December 2018 to July 2021), the ID specialists from 14 different centres enrolled 223 patients treated with dalbavancin [141 males (63%) and 82 females (37%); male/female ratio 1.72; mean age 59 (SD 17.2) years, (range 15-96). Most patients in the study population (136/223; 61.0%) came from community rather than health care facilities and most of them were visited in Infectious Diseases wards (93/223; 41.7%) and clinics (55/223; 24.7%) even though some patients were cured in other settings, such as surgery wards (18/223; 8.1%), orthopaedic wards (11/223; 4.9%), Emergency Rooms (7/223; 3.1%) and non-surgical other than ID wards (6/223; 2.7%). The most common ID diagnoses were osteomyelitis (44 cases/223; 19.7%; of which 29 acute and 15 chronic osteomyelitis), cellulitis (28/223; 12.5%), cutaneous abscess (23/223; 10.3%), orthopaedic prosthesis-associated infection (22/223; 9.9%), surgical site infection (20/223; 9.0%) and septic arthritis (15/223; 6.7%).ConclusionIn conclusion, by virtue of its PK/PD properties, dalbavancin represents a valuable option to daily in-hospital intravenous or outpatient antimicrobial regimens also for off-label indications requiring a long-term treatment of Gram-positive infections

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists

Ultra-low-loss optical fiber nanotapers

Optical fiber tapers with a waist size larger than 1µm are commonplace in telecommunications and sensor applications. However the fabrication of low-loss optical fiber tapers with subwavelength diameters was previously thought to be impractical due to difficulties associated with control of the surface roughness and diameter uniformity. In this paper we show that very-long ultra-low-loss tapers can in fact be produced using a conventional fiber taper rig incorporating a simple burner configuration. For single-mode operation, the optical losses we achieve at 1.55µm are one order of magnitude lower than losses previously reported in the literature for tapers of a similar size. SEM images confirm excellent taper uniformity. We believe that these low-loss structures should pave the way to a whole range of fiber nanodevices

An embedded optical nanowire loop resonator refractometric sensor

A novel refractometric sensor based on an embedded optical nanowire loop resonator is presented. The device sensitivity has been studied in two typical configurations and its dependence on the nanowire diameter and coating thickness determined

Predictive maintenance for buses. Outcomes and potential from an Italian case study

The paper deals with an innovative Predictive Maintenance (PdM) system to assess the quality of the engine oil for buses, tested in Ravenna within the European Bus System of the Future - EBSF_2 project, funded by the European Union. The system relies on a PdM software linked to oil sensors and filters, installed on a test fleet, and on an IT architecture, specifically designed. The system enables a continuous assessment of the oil quality, which is highly predictive of the engine performance, thus detecting potential breakdowns and planning the replacement of spare parts ahead of regular schedules; the system also detects which substances and problems cause the poor quality of the oil. The paper describes the system, the testing scenarios, the performance assessment, and the main outcomes. Results also enable an assessment of additional, potential environmental benefits (especially mitigation of emissions toxicity and improvement of waste management). Additional features are also reported such as an algorithm to estimate the date when oil has to be changed. Such results are analysed and commented with the research objective to provide advanced knowledge for further research studies

Alternative splicing enhances transcriptome complexity in desiccating seeds

Before being dispersed in the environment, mature seeds need to be dehydrated. The survival of seeds after dispersal depends on their low hydration in combination with high desiccation tolerance. These characteristics are established during seed maturation. Some key seed maturation genes have been reported to be regulated by alternative splicing (AS). However, so far AS was described only for single genes and a comprehensive analysis of AS during seed maturation has been lacking. We investigated gene expression and AS during Arabidopsis thaliana seed development at a global level, before and after desiccation. Bioinformatics tools were developed to identify differentially spliced regions within genes. Our data suggest the importance and shows the peculiar features of AS during seed desiccation. We identified AS in 34% of genes that are expressed at both timepoints before and after desiccation. Most of these AS transcript variants had not been found before in other tissues. Among the AS genes some seed master regulators could be found. Interestingly, 6% of all expressed transcripts were not transcriptionally regulated during desiccation, but only modified by AS. We propose that AS should be more routinely taken into account in the analysis of transcriptomic data to prevent overlooking potentially important regulators

The Enhancement of Plant Disease Resistance Using CRISPR/Cas9 Technology

Genome editing technologies have progressed rapidly and become one of the most important genetic tools in the implementation of pathogen resistance in plants. Recent years have witnessed the emergence of site directed modification methods using meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindrome repeats (CRISPR)/CRISPR-associated protein 9 (Cas9). Recently, CRISPR/Cas9 has largely overtaken the other genome editing technologies due to the fact that it is easier to design and implement, has a higher success rate, and is more versatile and less expensive. This review focuses on the recent advances in plant protection using CRISPR/Cas9 technology in model plants and crops in response to viral, fungal and bacterial diseases. As regards the achievement of viral disease resistance, the main strategies employed in model species such as Arabidopsis and Nicotiana benthamiana, which include the integration of CRISPR-encoding sequences that target and interfere with the viral genome and the induction of a CRISPR-mediated targeted mutation in the host plant genome, will be discussed. Furthermore, as regards fungal and bacterial disease resistance, the strategies based on CRISPR/Cas9 targeted modification of susceptibility genes in crop species such as rice, tomato, wheat, and citrus will be reviewed. After spending years deciphering and reading genomes, researchers are now editing and rewriting them to develop crop plants resistant to specific pests and pathogens

The Conserved Splicing Factor SUA Controls Alternative Splicing of the Developmental Regulator ABI3 in Arabidopsis[W][OA]

The Arabidopsisgene ABI3 shows developmentally regulated alternative splicing. ABI3-α and ABI3-β splice variants encode full-length and truncated ABI3 proteins, respectively. The conserved splicing factor SUA reduces splicing of a cryptic ABI3 intron, which leads to the accumulation of ABI3-α. Mutations in sua suppress the frameshift mutant abi3-5 by restoring its reading frame

Transcriptional and Post-transcriptional Mechanisms Limit Heading Date 1 (Hd1) Function to Adapt Rice to High Latitudes

Rice flowering is controlled by changes in the photoperiod that promote the transition to the reproductive phase as days become shorter. Natural genetic variation for flowering time has been largely documented and has been instrumental to define the genetics of the photoperiodic pathway, as well as providing valuable material for artificial selection of varieties better adapted to local environments. We mined genetic variation in a collection of rice varieties highly adapted to European regions and isolated distinct variants of the long day repressor HEADING DATE 1 (Hd1) that perturb its expression or protein function. Specific variants allowed us to define novel features of the photoperiodic flowering pathway. We demonstrate that a histone fold domain scaffold formed by GRAIN YIELD, PLANT HEIGHT AND HEADING DATE 8 (Ghd8) and several NF-YC subunits can accommodate distinct proteins, including Hd1 and PSEUDO RESPONSE REGULATOR 37 (PRR37), and that the resulting OsNF-Y complex containing Hd1 can bind a specific sequence in the promoter of HEADING DATE 3A (Hd3a). Artificial selection has locally favored an Hd1 variant unable to assemble in such heterotrimeric complex. The causal polymorphism was defined as a single conserved lysine in the CCT domain of the Hd1 protein. Our results indicate how genetic variation can be stratified and explored at multiple levels, and how its description can contribute to the molecular understanding of basic developmental processes

Non-silica microstructured optical fibers for mid-IR supercontinuum generation from 2 µm - 5 µm

We have performed numerical simulations to investigate the optimization of compound glass microstructured optical fibers for mid IR supercontinuum generation beyond the low loss transmission window of silica, using pump wavelengths in the range 1.55-2.25 µm. Large mode area fibers for high powers, and small core fiber designs for low powers, are proposed for a variety of glasses. Modeling results showed that for Bismuth and lead oxide glasses, which have nonlinearities ~10 x that of silica, matching the dispersion profile to the pump wavelength is essential. For chalcogenide glasses, which have much higher nonlinearities, the dispersion profile is less important. The pump pulses have duration of <1 ps, and energy <30 nJ. The fiber lengths required for generating continuum were <40 mm, so the losses of the fibers were not a limiting factor. Compared to planar rib-waveguides or fiber-tapers, microstructured fiber technology has the advantages of greater flexibility for tailoring the dispersion profile over a broad wavelength span, and a much wider possible range of device lengths