-
Walters Fulton posted an update 6 months, 3 weeks ago
Cutaneous T-cell lymphomas (CTCL) are rare non-Hodgkin lymphomas with a generally indolent course managed with topical, skin-directed therapies. A small subset, however, will progress to advanced stage disease necessitating systemic therapy for disease control. Currently approved therapies have low response rates and generally short durations of response. Novel therapies, therefore, are urgently needed to address this unmet need. In this review, the mechanisms of CTCL pathogenesis and progression, including the role of the tumor microenvironment and molecular alterations, are summarized. Based on these biologic insights, novel therapies currently under investigation and those with a strong preclinical biologic rationale including T cell and macrophage checkpoint inhibitors, epigenetic regulators, targeted antibodies, tyrosine kinase inhibitors, and apoptosis modulating therapies are discussed.Background HIV pre-exposure prophylaxis (PrEP) has been rapidly implemented in Australia, initially through restricted access in demonstration studies, and then through prescribing across sexual health clinics and general practice settings. In 2018, PrEP was publicly subsidised for people with Medicare (universal health insurance for citizens, permanent residents and those from countries with reciprocal arrangements). There is little research examining the experiences of PrEP providers in Australia, and existing research has been primarily conducted before public subsidy.
In this qualitative study, we examine the challenges that have emerged for PrEP-providing clinicians after public subsidy for PrEP was introduced. We conducted 28 semi-structured interviews in 2019-20 with PrEP providers in two Australian states, and analysed data thematically. Participants included general practitioners (GPs), sexual health nurses and sexual health physicians.
Sexual health services have been reconfigured to meet changinld ensure that PrEP is delivered more effectively and equitably. Additionally, PrEP providers require encouragement to build confidence in providing on-demand PrEP.The aim of this study was to learn from trainees separating from the Queensland Rural Generalist Pathway (QRGP) the reasons and circumstances around their decision so as to improve the efficiency of the program and experience of trainees. Forty-one QRGP trainees who separated without achieving a Rural Generalist (RG) end point to training were interviewed regarding their reasons for separation and thoughts on improving the program. The mean period of time enrolled in the QRGP was 2.87 years. Broadly, the cohort divided into those separating for specialist training, those moving into non-RG general practice and those undecided. Separation for specialist training tended to occur during prevocational years and that to general practice later in the program before trainees had completed advanced skill training. Female trainees were over-represented among trainees separating without completing training. This cohort provided their opinions on the strengths of the QRGP and possible improvements. Understanding and addressing the reasons for early separation suggested several strategies to improve the efficiency of the QRGP in selecting and retaining trainees. Lessons learned included the value of employer-provided coordinated prevocational placements and training, potential benefits of guiding rural-interested medical graduates who ultimately enter other specialist training and the need for greater liaison with external Australian General Practice Training administration organisations to coordinate transition of trainees. There is a need to further address accessibility of advanced training for all trainees.An anaerobic, Gram-stain-positive, rod-shaped, motile and spore-forming bacterium, designated strain LBM18003T, was isolated from pit clay used for making Chinese strong aroma-type liquor. Growth occurred at 20-40 °C (optimum, 30-37 °C), pH 4.5-9.5 (optimum, pH 6.5-7.0) and in the presence of 0.0-1.0 % (w/v) sodium chloride (optimum, 0 %). The predominant fatty acids were C160, C140, C140 DMA and C160 3-OH, and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, two unidentified phospholipids and nine unidentified glycolipids. click here Phylogenetic analysis revealed that strain LBM18003T is a novel member of the family Oscillospiraceae. The 16S rRNA gene sequence similarities of strain LBM18003T to its two most closely related species were less than 94.5 % for distinguishing genera, i.e. closely related to Caproiciproducens galactitolivorans JCM 30532T (94.1 %) and Caproicibacter fermentans DSM 107079T (93.2 %). The genome size of strain LBM18003T was 2 996 201 bp and its DNA G+C content was 48.4CM 33783T).Three strains (YZ01T, YZ02 and YZ03) of Gram-stain-positive, facultatively anaerobic rods were isolated from the forestomach contents collected from a captive male proboscis monkey (Nasalis larvatus) at Yokohama Zoo in Japan. Phylogenetic analysis of the 16S rRNA gene sequences revealed that these strains belonged to the genus Lactobacillus. Based on the sequence similarity of the 16S rRNA gene, Lactobacillus delbrueckii subsp. indicus JCM 15610T was the closest phylogenetic neighbour to YZ01T. Sequence analyses of two partial concatenated housekeeping genes, the RNA polymerase alpha subunit (rpoA) and phenylalanyl-tRNA synthase alpha subunit (pheS) also indicated that the novel strains belonged to the genus Lactobacillus. The average nucleotide identity and digital DNA-DNA hybridization (dDDH) between L. delbrueckii subsp. indicus and YZ01T were 85.9 and 31.4 %, respectively. The phylogenetic tree based on the whole genomic data of strains YZ01T, YZ02 and YZ03 suggested that these three strains formed a single monophyletic cluster in the genus Lactobacillus, indicating that it belonged to a new species. The DNA G+C content of strain YZ01T was 51.6 mol%. The major fatty acids were C16 0 and C18 1 ω9c. Therefore, based on phylogenetic, phenotypic and physiological evidence, strains YZ01T, YZ02 and YZ03 represent a novel species of the genus Lactobacillus, for which the name Lactobacillus nasalidis sp. nov. is proposed with the type strain YZ01T (=JCM 33769T=DSM 110539T).