Explore the vast range of titles available.

Tzukit Zehavi-Dorin,1 Anne E Kutzscher,1,2 Mai Badr,3 Marta Mora,1 Yennie Shyu,1 Travis C Porco,1 Robert L Stamper1 1Department of Ophthalmology, University of California at San Francisco, San Francisco, CA, USA; 2Department of Ophthalmology, California Pacific Medical Center, San Francisco, CA, USA; 3Department of Internal Medicine, University of Massachusetts, Worcester, MA, USACorrespondence: Robert L Stamper, Department of Ophthalmology, University of California at San Francisco, UCSF Wayne and Gladys Valley Center of Vision, 490 Illinois Street, San Francisco, CA, USA, Email robert.stamper@ucsf.eduPurpose: To compare global peripapillary and perifoveal vessel densities between primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG) patients with the same glaucoma severity using optical coherence tomography angiography (OCTA).Methods: Subjects with POAG or NTG were recruited consecutively at the glaucoma clinic of the University of California at San Francisco. The glaucoma severity was graded as early, moderate, or severe based on the Hodapp-Parrish-Anderson Visual Field Criteria. All subjects underwent OCTA imaging (RTVue-XR Avanti; Optovue, Fremont, CA, USA) of the optic disc and macula by a trained technician. The main outcome measures were vessel density of the radial peripapillary capillary area and the perifoveal superficial layer as obtained from the disc and macula imaging respectively, using the AngioVue software.Results: The study included 156 eyes (93 POAG, 63 NTG) from 91 patients. There was no significant difference between the perifoveal and peripapillary vessel density of subjects with NTG and POAG with similar extent of glaucomatous damage. In early glaucoma, a trend toward lower peripapillary vessel density in NTG compared with POAG was observed. No such trend was seen in moderate or severe stages.Conclusion: Global vessel density parameters did not differ significantly between NTG and POAG eyes of similar severity. The observed trend toward lower peripapillary vessel density in early NTG may indicate a possible vascular contribution in early disease, but this finding is preliminary and requires confirmation in larger, prospective studies.Keywords: OCT angiography, POAG, NTG, vessel density

The aim of this study was to evaluate the efficacy of trabeculectomy for primary open angle glaucoma (POAG) with low preoperative intraocular pressure (IOP). This was a retrospective single facility, non-randomized study. We included POAG patients with preoperative IOP ≤12 mmHg who were taking maximally tolerance glaucoma medications. We enrolled 11 patients who underwent trabeculectomy and could be followed for ≥3 years. We used the value of inclination of the mean deviation (MD) slope (dB/year) as the speed of progression of visual field defects as an index of surgical efficacy. We compared the MD slope before and after trabeculectomy. The mean preoperative IOP was 11.1±1.4 mmHg and the mean postoperative IOP was 6.5±2.5, 8.6±2.8 and 8.8±2.1 mmHg at 1, 2, and 3 years respectively. The inclination value of MD slope significantly improved from -1.19±0.35 to -0.13±0.37 dB/year (p<0.001). Trabeculectomy significantly decreased IOP and slowed the progression of visual field defects. The results suggest that trabeculectomy might be effective even in patients with very low preoperative IOP.

To compare global peripapillary and perifoveal vessel densities between primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG) patients with the same glaucoma severity using optical coherence tomography angiography (OCTA). Subjects with POAG or NTG were recruited consecutively at the glaucoma clinic of the University of California at San Francisco. The glaucoma severity was graded as early, moderate, or severe based on the Hodapp-Parrish-Anderson Visual Field Criteria. All subjects underwent OCTA imaging (RTVue-XR Avanti; Optovue, Fremont, CA, USA) of the optic disc and macula by a trained technician. The main outcome measures were vessel density of the radial peripapillary capillary area and the perifoveal superficial layer as obtained from the disc and macula imaging respectively, using the AngioVue software. The study included 156 eyes (93 POAG, 63 NTG) from 91 patients. There was no significant difference between the perifoveal and peripapillary vessel density of subjects with NTG and POAG with similar extent of glaucomatous damage. In early glaucoma, a trend toward lower peripapillary vessel density in NTG compared with POAG was observed. No such trend was seen in moderate or severe stages. Global vessel density parameters did not differ significantly between NTG and POAG eyes of similar severity. The observed trend toward lower peripapillary vessel density in early NTG may indicate a possible vascular contribution in early disease, but this finding is preliminary and requires confirmation in larger, prospective studies.

Spinosad is an efficient and broad-spectrum environmentally friendly biopesticide, but its low yield in wild-type Saccharopolyspora spinosa limits its further application. ARTP/NTG compound mutagenesis was used in this study to improve the spinosad titer of S. spinosa and obtain a high-yield mutant—NT24. Compared with the wild-type strain, the fermentation cycle of NT24 was shortened by 2 days and its maximum titer of spinosad reached 858.3 ± 27.7 mg/L, which is 5.12 times more than for the same-period titer of the wild-type strain. In addition, RT-qPCR, resequencing, and targeted metabolomics showed that the upregulation of the key differential genes accD6, fadD, sdhB, oadA, and gntZ caused increased metabolic flux in the tricarboxylic acid cycle and pentose phosphate pathway, suggesting that the accumulation of pyruvate and short-chain acyl-CoA was the primary cause of spinosad accumulation in NT24. This study demonstrates the effectiveness of ARTP mutagenesis in S. spinosa, and provides new insights for the mechanism of spinosad biosynthesis and metabolic engineering in S. spinosa.

Mycoplasma (M.) hyorhinis causes substantial economic losses in swine. Currently, prevention and treatment rely on minimizing risk factors and administering antibiotics, as no vaccines are commercially available in Europe. However, antibiotics often cannot fully eliminate the bacteria. The development of an effective vaccine could lead to a potentially long-term control method. A temperature-sensitive M. hyorhinis strain was developed using 1-methyl-3-nitro-1-nitrosoguanidine (NTG) mutagenesis. The immunogenicity and efficacy of this vaccine candidate clone were evaluated in combination with an adjuvant. Three-week-old piglets were immunized with the candidate vaccine strain, and the vaccination site was monitored daily. At six weeks of age, the pigs were challenged intravenously on two subsequent days. Daily clinical examinations were conducted, with blood and nasal swabs collected weekly throughout the study for M. hyorhinis enzyme-linked immunosorbent assay (ELISA), real-time PCR analysis, and isolation. Three weeks post-challenge, the animals were euthanized for gross and histopathological examinations. Body temperature was recorded daily, and body weight was measured upon arrival, and then at six and nine weeks of age. Vaccination significantly reduced clinical signs (p = 0.03), as well as gross pathological (p = 0.01) and histopathological (p = 0.005) lesions compared with the positive control group. The vaccinated group exhibited an earlier and higher increase in M. hyorhinis-specific IgG antibody levels post-challenge than the positive control group. However, the vaccine candidate did not mitigate the impact of M. hyorhinis infection on the weight gain. After the challenge (days 21–42), both the vaccinated (p = 0.001) and the positive control (p = 0.003) groups exhibited reduced weight gain compared with the negative control group. Overall, the attenuated M. hyorhinis strain, combined with the adjuvant, provided protection against M. hyorhinis infection. These results form a basis for the development of a novel vaccine candidate that offers effective prevention.

Transient receptor potential melastatin subtype 8 (TRPM8) is a cation channel extensively expressed in sensory neurons and implicated in different painful states. However, the effectiveness of TRPM8 modulators for pain relief is still a matter of discussion, since structurally diverse modulators lead to different results, depending on the animal pain model. In this work, we described the antinociceptive activity of a β–lactam derivative, RGM8-51, showing good TRPM8 antagonist activity, and selectivity against related thermoTRP channels and other pain-mediating receptors. In primary cultures of rat dorsal root ganglion (DRG) neurons, RGM8-51 potently reduced menthol-evoked neuronal firing without affecting the major ion conductances responsible for action potential generation. This compound has in vivo antinociceptive activity in response to cold, in a mouse model of oxaliplatin-induced peripheral neuropathy. In addition, it reduces cold, mechanical and heat hypersensitivity in a rat model of neuropathic pain arising after chronic constriction of the sciatic nerve. Furthermore, RGM8-51 exhibits mechanical hypersensitivity-relieving activity, in a mouse model of NTG-induced hyperesthesia. Taken together, these preclinical results substantiate that this TRPM8 antagonist is a promising pharmacological tool to study TRPM8-related diseases.

Lipstatin, natural inhibitor of pancreatic lipase produced by Streptomyces toxytricini and used as an anti-obesity drug. Chemical mutagenesis was performed with different concentrations of N-methyl-N′-nitro-N-nitrosoguanidine (NTG) for strain improvement to obtain high yield of lipstatin. It was observed that the potential of the wild type strain to produce lipstatin (1.09 g/L) was very low. Selected mutants produced lipstatin in the range of 1.20–2.23 g/L at the flask level where maximum amount of lipstatin was produced by M5 mutant. For comparative study, both the parent and M5 mutant strain of S. toxytricini were grown at the lab scale bioreactor with suitable sources of carbon and nitrogen. Significant increase in the production of lipstatin was observed at the bioreactor level where the wild type strain produced 2.4 g/L of lipstatin, while through the NTG mutation, the production of lipstatin was 5.35 g/L. However, Dry Cell Weight (DCW) of the mutant strain was less in comparison with wild type strain and significant morphological differences were observed. Nearly 5 times increase in the production of lipstatin was achieved through NTG mutation and bioreactor-controlled conditions. It was determined that the NTG treatment might be beneficial for strain improvement to get a better candidate for lipstatin production on commercial scale.

Purpose This paper aims to identify the gap existing between the current and future needs regarding digital skills, as well as the training needs for the 2030 horizon in Spanish tourism organisations belonging to five subsectors (accommodation, food and beverage, destination management, visitor attractions and travel agents and tour operators). Design/methodology/approach A mixed research methodology, which combined qualitative and quantitative approaches, served as the basis for this research work. Qualitative research took place between April 2018 and March 2019 and went through three stages: desk research, focus groups and interviews. Quantitative research developed from January to June 2019 by means of an online administered survey (Qualtrics). In total, 139 Spanish tourism organisations participated. Findings Tourism organisations analysed consider that digital skills are still an unresolved issue. Employees are willing to operate in environments where technology has an increasingly leading role. However, organisations believe that there remains a lot to be done until employees have, both at present and by the year 2030, a suitable level of digital skills enabling them to operate in the tourism subsectors analysed. Originality/value This study is framed within the European project called Next Tourism Generation (NTG), which involves 14 partners from eight countries. The findings obtained will help to develop a Europe Blueprint Strategy for digital skills within the tourism and hospitality sector, to provide employees, employers, entrepreneurs, teachers, trainers and students with a set of core digital skills represented in a skills matrix.

Microbial exopolysaccharides (EPSs) are biopolymer materials with advantages such as biodegradability, biocompatibility, ease of mass production, and reproducibility. The EPS that was isolated from Rhizobium leguminosarum bv. viciae VF39 is an anionic polysaccharide with a backbone structure consisting of one galactose, five glucose molecules, and two glucuronic acids, along with 3-hydroxybutanoyl, acetyl, and pyruvyl functional groups. Through N-methyl-N′-nitro-N-nitrosoguanidine (NTG) mutagenesis, we isolated and purified a mutant EPS from VF39, VF39 #54, which demonstrated enhanced physicochemical and rheological properties compared to the wild-type VF39. The EPS structure of the VF39 #54 mutant strain showed a loss of glucuronic acid and 3-hydroxybutanoyl groups compared to the wild-type, as confirmed by FT-IR, NMR analysis, and uronic acid assays. The molecular weight of the VF39 #54 EPS was 250% higher than that of the wild-type. It also exhibited improved viscoelasticity and thermal stability. In the DSC and TGA analyses, VF39 #54 had a higher endothermic peak (172 °C) compared to the wild-type (142 °C), and its thermal decomposition point was 260 °C, surpassing the wild-type’s value of 222 °C. Additionally, the VF39 #54 EPS maintained a similar viscosity to the wild-type in various pH, temperature, and metal salt conditions, while also exhibiting a higher overall viscosity. The cytotoxicity test using HEK-293 cells confirmed that the VF39 #54 EPS was non-toxic. Due to its high viscoelastic properties, the VF39 #54 EPS shows potential for use in products such as thickeners, texture enhancers, and stabilizers. Furthermore, its thermal stability and biocompatibility make it a promising candidate for applications in food, pharmaceuticals, and cosmetic formulations. Additionally, its ability to maintain viscosity under varying environmental conditions highlights its suitability for industrial processes that require consistent performance.

Commercial bacterial exopolysaccharide (EPS) applications have been gaining interest; therefore, strains that provide higher yields are required for industrial-scale processes. Succinoglycan (SG) is a type of bacterial anionic exopolysaccharide produced by Rhizobium, Agrobacterium, and other soil bacterial species. SG has been widely used as a pharmaceutical, cosmetic, and food additive based on its properties as a thickener, texture enhancer, emulsifier, stabilizer, and gelling agent. An SG-overproducing mutant strain (SMC1) was developed from Sinorhizobium meliloti 1021 through N-methyl-N′-nitro-N-nitrosoguanidine (NTG) mutation, and the physicochemical and rheological properties of SMC1-SG were analyzed. SMC1 produced (22.3 g/L) 3.65-fold more SG than did the wild type. Succinoglycan (SMC1-SG) overproduced by SMC1 was structurally characterized by FT-IR and 1H NMR spectroscopy. The molecular weights of SG and SMC1-SG were 4.20 × 105 and 4.80 × 105 Da, respectively, as determined by GPC. Based on DSC and TGA, SMC1-SG exhibited a higher endothermic peak (90.9 °C) than that of SG (77.2 °C). Storage modulus (G′) and loss modulus (G″) measurements during heating and cooling showed that SMC1-SG had improved thermal behavior compared to that of SG, with intersections at 74.9 °C and 72.0 °C, respectively. The SMC1-SG′s viscosity reduction pattern was maintained even at high temperatures (65 °C). Gelation by metal cations was observed in Fe3+ and Cr3+ solutions for both SG and SMC1-SG. Antibacterial activities of SG and SMC1-SG against Escherichia coli and Staphylococcus aureus were also observed. Therefore, like SG, SMC1-SG may be a potential biomaterial for pharmaceutical, cosmetic, and food industries.