Starch-based orodispersible film for diclofenac release

The form of drug administration affects the success of treatment, since it can influence adherence of the patient to the therapy. The use of orodispersible films has emerged as a way to overcome some drawbacks of conventional methods of drug delivery, especially for patients experiencing difficulty in swallowing. These films are prepared using a matrix that incorporates the drug and contains other substances that confer the properties of the system. The present work describes the use of thermoplastic starch as a carrier for the model drug diclofenac, including film preparation and testing of its orodispersible potential. Preparation of the film employed a microwave oven to gelatinize and plasticize corn starch, with incorporation of the model drug, followed by solvent-casting. The samples were characterized using mechanical tests, analyses of water uptake and water content, and Fourier transform infrared spectroscopy. The results indicated that the film presented promising properties as an alternative system for oral drug administration, with good incorporation and distribution of the drug in the matrix. The material displayed satisfactory mechanical properties, which are crucial for this type of material, due to the need for oral administration and handling before use

Sarcoma primário de leptomeninges: apresentação não usual e aspectos de neuroimagem previamente não descritos

Sem informação77967567

Unveiling the gravitational universe at mu-Hz frequencies

Funding Information: Open access funding provided by Università degli Studi di Milano - Bicocca within the CRUI-CARE Agreement. Publisher Copyright: © 2021, The Author(s).We propose a space-based interferometer surveying the gravitational wave (GW) sky in the milli-Hz to mu-Hz frequency range. By the 2040s, the mu-Hz frequency band, bracketed in between the Laser Interferometer Space Antenna (LISA) and pulsar timing arrays, will constitute the largest gap in the coverage of the astrophysically relevant GW spectrum. Yet many outstanding questions related to astrophysics and cosmology are best answered by GW observations in this band. We show that a mu-Hz GW detector will be a truly overarching observatory for the scientific community at large, greatly extending the potential of LISA. Conceived to detect massive black hole binaries from their early inspiral with high signal-to-noise ratio, and low-frequency stellar binaries in the Galaxy, this instrument will be a cornerstone for multimessenger astronomy from the solar neighbourhood to the high-redshift Universe.Peer reviewe

Astrophysics with the Laser Interferometer Space Antenna

Laser Interferometer Space Antenna (LISA) will be a transformative experiment for gravitational wave astronomy as it will offer unique opportunities to address many key astrophysical questions in a completely novel way. The synergy with ground-based and other space-based instruments in the electromagnetic domain, by enabling multi-messenger observations, will add further to the discovery potential of LISA. The next decade is crucial to prepare the astrophysical community for LISA's first observations. This review outlines the extensive landscape of astrophysical theory, numerical simulations, and astronomical observations that are instrumental for modeling and interpreting the upcoming LISA datastream. To this aim, the current knowledge in three main source classes for LISA is reviewed: ultra-compact stellar-mass binaries, massive black hole binaries, and extreme or intermediate mass ratio inspirals. The relevant astrophysical processes and the established modeling techniques are summarized. Likewise, open issues and gaps in our understanding of these sources are highlighted, along with an indication of how LISA could help make progress in the different areas. New research avenues that LISA itself, or its joint exploitation with studies in the electromagnetic domain, will enable, are also illustrated. Improvements in modeling and analysis approaches, such as the combination of numerical simulations and modern data science techniques, are discussed. This review is intended to be a starting point for using LISA as a new discovery tool for understanding our Universe

Porcine circovirus type 2 detection in in vitro produced porcine blastocysts after virus sperm exposure

This study was aimed at assessing the capability of semen experimentally infected with porcine circovirus type 2 (PCV2) to produce porcine blastocysts PCR positive for PCV2. Embryos were obtained from in vitro maturation (IVM) and in vitro fertilization (IVF) of porcine oocytes or by parthenogenesis. Sperm suspension was exposed to PCV2b and utilized for IVF. PCV2 spiked semen did not reveal any reduction in sperm viability or motility but its ability to produce infected blastocysts was irrelevant as only one out of 15 blastocysts obtained by IVF were PCV2b; however two blastocysts were PCV2a positive. Furthermore, the presence of PCV2 was demonstrated also in embryos obtained by parthenogenesis (one out of 17 was PCV2b and one PCV2a positive). Even if PCV2 firmly attaches to the surface of spermatozoa, experimentally spiked sperm were not effective in infecting oocytes during IVF and in producing PCR positive embryos. The infected blastocysts we obtained derived most probably from infected oocytes recovered at the abattoir

Concurrent validity, internal consistency and responsiveness of the portuguese version of the king's health questionnaire (KHQ) in women after stress urinary incontinence surgery

OBJECTIVE: To evaluate the concurrent validity, internal consistency and responsiveness of King's Health Questionnaire (KHQ) in patients who underwent sling procedures for the treatment of stress urinary incontinence. MATERIALS AND METHODS: We performed a prospective open label multicenter study in 4 tertiary referral centers. Sixty-eight female patients were enrolled with urodynamically diagnosed urinary stress incontinence. Patients were treated using surgical procedures, mostly (73%) with the synthetic sling procedure, which has been considered one of the gold standard methods for the treatment of urinary incontinence. The patients were assessed before and after one month of postoperative follow up, using the KHQ in its validated Portuguese version. Patients also underwent preoperative urodynamic test, Stamey incontinence grading, pad usage and the assessment of number of pads used per day. After surgery, patients underwent stress test, Stamey incontinence grading pad usage and the assessment of number of pads used per day. RESULTS: The concurrent validity showed good correlations in some domains of KHQ to clinical parameters. The internal consistency was higher after treatment compared to preoperative values. Objective parameters, such as pad usage and the assessment of number of pads used per day, had significant correlation with changes in post-treatment scores on KHQ. The responsiveness expressed in terms of standardized effect size (SES) and standardized response mean (SRM) was large. CONCLUSION: The results showed moderate concurrent validity, strong internal consistency and high responsiveness for KHQ, indicating that it is suitable for measuring outcomes in clinical trials among female patients with stress urinary incontinence

Transcriptome analyses of the cortex and white matter of focal cortical dysplasia type II: Insights into pathophysiology and tissue characterization

IntroductionFocal cortical dysplasia (FCD) is a common cause of pharmacoresistant epilepsy. According to the 2022 International League Against Epilepsy classification, FCD type II is characterized by dysmorphic neurons (IIa and IIb) and may be associated with balloon cells (IIb). We present a multicentric study to evaluate the transcriptomes of the gray and white matters of surgical FCD type II specimens. We aimed to contribute to pathophysiology and tissue characterization.MethodsWe investigated FCD II (a and b) and control samples by performing RNA-sequencing followed by immunohistochemical validation employing digital analyses.ResultsWe found 342 and 399 transcripts differentially expressed in the gray matter of IIa and IIb lesions compared to controls, respectively. Cholesterol biosynthesis was among the main enriched cellular pathways in both IIa and IIb gray matter. Particularly, the genes HMGCS1, HMGCR, and SQLE were upregulated in both type II groups. We also found 12 differentially expressed genes when comparing transcriptomes of IIa and IIb lesions. Only 1 transcript (MTRNR2L12) was significantly upregulated in FCD IIa. The white matter in IIa and IIb lesions showed 2 and 24 transcripts differentially expressed, respectively, compared to controls. No enriched cellular pathways were detected. GPNMB, not previously described in FCD samples, was upregulated in IIb compared to IIa and control groups. Upregulations of cholesterol biosynthesis enzymes and GPNMB genes in FCD groups were immunohistochemically validated. Such enzymes were mainly detected in both dysmorphic and normal neurons, whereas GPNMB was observed only in balloon cells.DiscussionOverall, our study contributed to identifying cortical enrichment of cholesterol biosynthesis in FCD type II, which may correspond to a neuroprotective response to seizures. Moreover, specific analyses in either the gray or the white matter revealed upregulations of MTRNR2L12 and GPNMB, which might be potential neuropathological biomarkers of a cortex chronically exposed to seizures and of balloon cells, respectively

Unveiling the gravitational universe at μ-Hz frequencies

We propose a space-based interferometer surveying the gravitational wave (GW) sky in the milli-Hz to μ-Hz frequency range. By the 2040s, the μ-Hz frequency band, bracketed in between the Laser Interferometer Space Antenna (LISA) and pulsar timing arrays, will constitute the largest gap in the coverage of the astrophysically relevant GW spectrum. Yet many outstanding questions related to astrophysics and cosmology are best answered by GW observations in this band. We show that a μ-Hz GW detector will be a truly overarching observatory for the scientific community at large, greatly extending the potential of LISA. Conceived to detect massive black hole binaries from their early inspiral with high signal-to-noise ratio, and low-frequency stellar binaries in the Galaxy, this instrument will be a cornerstone for multimessenger astronomy from the solar neighbourhood to the high-redshift Universe