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Introduction Nabiximols, a cannabinoid-based oromucosal spray, is indicated as add-on therapy for symptomatic relief of spasticity in persons with multiple sclerosis (MS). This review compiles tolerability and safety data from clinical trials that investigated nabiximols for spasticity and/or chronic pain.Areas covered Systematic searches identified 38 placebo-controlled randomized controlled trials (RCTs) or post-RCT open-label studies reporting safety data 15 in spasticity; 16 in neuropathic pain; six in chronic cancer pain; and one in rheumatoid arthritis pain. In RCTs, discontinuation rates due to adverse events (AEs) for nabiximols and placebo were lower in spasticity studies (5.4% and 2.8%) than in neuropathic pain (12.9% and 5.3%) or cancer pain (19.5% and 16.6%) studies. The most consistently identified AEs were dizziness, nausea and fatigue in spasticity or neuropathic pain studies; and dizziness, nausea, vomiting and somnolence in cancer pain studies. Serious AE (SAE) rates for nabiximols and placebo were higher in cancer pain (21.8% and 16.9%) than in MS spasticity (4.7% vs. 0.8%) and neuropathic pain (4.1% vs. 3.1%) studies despite similar dose ranges. Treatment-related SAEs showed no particular pattern.Expert opinion More than 15 years of investigation of nabiximols oromucosal spray in spasticity and chronic pain conditions indicates an acceptable overall safety profile.

To investigate the feasibility of providing general practitioners (GPs) direct and fast referral access to transvaginal ultrasound (TVUS).

A prospective cohort study.

A total of 232 Danish general practices in parts of the Central Denmark Region.

Women aged ≥40 years who consulted their GP for vague and non-specific symptoms (

 = 479).

The feasibility assessment included the GPs' referral rate, indications for referral, management of test results, and findings from TVUS.

A total of 479 women were referred to TVUS. The examinations revealed abnormalities in 104 (21.7%) women. Additional investigations were needed in 68 (14.2%) women of whom seven (1.5%) underwent major surgery. No case of ovarian cancer was diagnosed during the study period or the 6-month follow-up. However, three (0.6%) women with an abnormal transvaginal ultrasound were diagnosed with urogynecological cancer; this yielded a PPV of 4.4% (95% confidence interval 1.5-12.2) and an NPV of 100.0% (95% confidence interval 96.7-100.0) fo woman had a false negative TVUS result.

Direct access to TVUS could be an important pathway to ensure fast evaluation of women presenting with vague non-specific symptoms of potential ovarian cancer. Future studies should explore the patient experience, cancer outcomes, and health economics issues.KEY POINTS   Current awareness  • GPs have no fast referral option for women presenting with vague non-specific symptoms that could indicate underlying ovarian cancer.   Key findings  • We offered GPs direct and fast referral access to TVUS; 51.7% of practices used the opportunity.  • The GPs referred 479 women to TVUS; 104 had an abnormal TVUS and 68 needed additional investigations.  • Seven women underwent major surgery, leading to three cases of urogynecological cancer. No woman had a false negative TVUS result.Endophytic fungi usually establish a symbiotic relationship with the host plant and affect its growth. In order to evaluate the impact of endophytic fungi on the Chinese herbal medicinal plant Houttuynia cordata Thunb., three endophytes isolated from the rhizomes of H. cordata, namely Ilyonectria liriodendra (IL), unidentified fungal sp. (UF), and Penicillium citrinum (PC), were co-cultured individually with H. this website cordata in sterile soil for 60 days. Analysis of the results showed that the endophytes stimulated the host plant in different ways IL increased the growth of rhizomes and the accumulation of most of the phenolics and volatiles, UF promoted the accumulation of the medicinal compounds afzelin, decanal, 2-undecanone, and borneol without influencing host plant growth, and PC increased the fresh weight, total leaf area and height of the plants, as well as the growth of the rhizomes, but had only a small effect on the concentration of major secondary metabolites. Our results proved that the endophytic fungi had potential practical value in terms of the production of Chinese herbal medicines, having the ability to improve the yield and accumulation of medicinal metabolites.Leuconostoc pseudomesenteroides belongs to a group of lactic acid bacteria normally isolated from fruits, which has the capacity to produce exopolysaccharides (EPS). The present study aimed to optimize the EPS production of L. pseudomesenteroides JF17, isolated from juçara fruits (palm trees threatened with extinction in the Atlantic Forest), using the response surface methodology (RSM), besides evaluating the fermentation kinetics. The maximum production of EPS 53.77 mg/mL was obtained under ideal conditions of MRS broth supplemented with sucrose at 18%, w/v, fermentation temperature of 20 °C and initial pH of 7.30. The Luedeking-Piret model suggested that the production of EPS by the JF17 strain appeared to be associated with the cell growth of the microorganism, in addition to having high efficiency in the production of the polysaccharide from the substrate (Yp/s = 17.85 ± 0.74 mg EPS/log CFU ). Thus, the ideal optimization conditions and kinetic parameters can be useful for increasing the scale up of the fermentation process in the industrial production of EPS by L. pseudomesenteroides JF17.Ablepharon-macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are congenital ectodermal dysplasias associated with mutations in the TWIST2 gene. Among the ophthalmic anomalies that occur in these syndromes, underdevelopment of the anterior lamella of the eyelid is a defining feature. Reports of mosaic expression of TWIST2 mutations are extremely rare, with only five confirmed or suspected cases described to date. Mosaic expression of TWIST2 variants is correlated with a less severe phenotype than that reported for the typical expression of TWIST2 variants associated with BSS or AMS. Abnormal development of the anterior lamella appears to be a common feature in all cases of AMS with mosaic expression. Here, we describe the phenotype of a patient with mosaic expression of a TWIST2 mutation that is typically associated with AMS. We additionally describe the surgical approach employed in the treatment of this patient.

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