Use of long-acting injectable antiretroviral agents for human immunodeficiency Virus: A review

The development of potent antiretroviral drugs has significantly reduced morbidity and mortality associated with human immunodeficiency virus infection, however, the effectiveness of these medications depends upon consistent daily oral intake. Non-adherence can lead to the emergence of resistance, treatment failure and disease progression. This has necessitated the development of long-acting antiretroviral formulations administrable via an infrequent dosing regimen. Long-acting injectable forms of cabotegravir and rilpivirine have reached various stages in clinical trials both for the treatment and prevention of HIV. Other long-acting agents are at various stages of development. This review evaluates the current research on the development of long-acting injectable antiretroviral agents for the treatment and prevention of HIV

Broad Absorption Line Quasar catalogues with Supervised Neural Networks

We have applied a Learning Vector Quantization (LVQ) algorithm to SDSS DR5 quasar spectra in order to create a large catalogue of broad absorption line quasars (BALQSOs). We first discuss the problems with BALQSO catalogues constructed using the conventional balnicity and/or absorption indices (BI and AI), and then describe the supervised LVQ network we have trained to recognise BALQSOs. The resulting BALQSO catalogue should be substantially more robust and complete than BI- or AI-based ones.Comment: 5 pages, 3 figures, to appear in the proceedings of "Classification and Discovery in Large Astronomical Surveys", Ringberg Castle, 14-17 October 200

Utilising Features of Sport Commentating to Provide a Framework for Co-Teaching the Online Lecture

Higher education teaching abruptly changed during the COVID-19 pandemic to remote, on-line learning and teaching. The use of on-line communication software to teach became the norm and remains at many institutions. This software contains features, such as the chat, that offer teaching and learning advantages; however, potential benefits can be challenging to realise for academics used to traditional modes of lecture delivery. In most cases a solo-taught lecture designed for a physical room does not transition well to the on-line space. Co-teaching, which involves two or more academics teaching the same class, is a pedagogy that can improve engagement and satisfaction for students and academics alike. However, how co-teaching can transition to the on-line space and take full benefit of the communication software features is not well known. We recognised that some aspects of sports announcing (commentating) align with desirable qualities of co-teaching on-line. In this paper we use these features to develop a practical framework for co-teaching in the on-line space and evaluate the model in a second-year university science subject. Using data from student surveys, we found that the co-teaching model helped integrate the chat functionality into the main lecture and led to improved engagement and enjoyment of on-line classes. The model also assisted students in identifying key learning outcomes. Using the framework as a practical guide for how to incorporate co-teaching into on-line classes helps realise the benefits of contemporary communication software

The 5'-3' exoribonuclease Pacman (Xrn1) regulates expression of the heat shock protein Hsp67Bc and the microRNA miR-277-3p in Drosophila wing imaginal discs

Pacman/Xrn1 is a highly conserved exoribonuclease known to play a critical role in gene regulatory events such as control of mRNA stability, RNA interference and regulation via miRNAs. Although Pacman has been well studied in Drosophila tissue culture cells, the biologically relevant cellular pathways controlled by Pacman in natural tissues are unknown. This study shows that a hypomorphic mutation in pacman (pcm5) results in smaller wing imaginal discs. These tissues, found in the larva, are known to grow and differentiate to form wing and thorax structures in the adult fly. Using microarray analysis, followed by quantitative RT-PCR, we show that eight mRNAs were increased in level by >2 fold in the pcm5 mutant wing discs compared to the control. The levels of pre mRNAs were tested for five of these mRNAs; four did not increase in the pcm5 mutant, showing that they are regulated at the post-transcriptional level and therefore could be directly affected by Pacman. These transcripts include one that encodes the heat-shock protein Hsp67Bc, which is upregulated 11.9-fold at the post-transcriptional level and 2.3-fold at the protein level. One miRNA, miR-277-3p, is 5.6-fold downregulated at the post-transcriptional level in mutant discs, suggesting that Pacman affects its processing in this tissue. Together, these data show that a relatively small number of mRNAs and miRNAs substantially change in abundance in pacman mutant wing imaginal discs. Since Hsp67Bc is known to regulate autophagy and protein synthesis, it is possible that Pacman may control the growth of wing imaginal discs by regulating these processes

A role for the extracellular calcium-sensing receptor in cell-cell communication in pancreatic islets of Langerhans

Background: The extracellular calcium-sensing receptor (CaR) is expressed in many tissues that are not associated with Ca2+ homeostasis, including the endocrine cells in pancreatic islets of Langerhans. We have demonstrated previously that pharmacological activation of the CaR stimulates insulin secretion from islet -cells and insulin-secreting MIN6 cells. Methods: In the present study we have investigated the effects of CaR activation on MIN6 cell proliferation and have used shRNA-mediated CaR knockdown to determine whether the CaR is involved in the regulation of insulin secretion via cell-cell communication. Results: CaR activation caused the phosphorylation and activation of the p42/44 MAPK signalling cascade, and this activation was prevented by the shRNA-induced down-regulation of CaR mRNA expression. CaR activation also resulted in increased proliferation of MIN6 cells, consistent with the known role of the p42/44 MAPK system in the regulation of -cell proliferation. Down-regulation of CaR expression had no detectable effects on glucose-induced insulin secretion from MIN6 cells maintained as monolayers, but blocked the increases in insulin secretion that were observed when the cells were configured as three-dimensional islet-like structures (pseudoislets), consistent with a role for the CaR in cell-cell communication in pseudoislets. Conclusion: It is well established that islet function is dependent on communication between islet cells and the results of this study suggest that the CaR is required for -cell to -cell interactions within islet-like structures

Mechanisms of pelvic floor muscle function and the effect on the urethra during a cough

Background: Current measurement tools have difficulty identifying the automaticphysiologic processes maintaining continence, and many questions still remainabout pelvic floor muscle (PFM) function during automatic events.Objective: To perform a feasibility study to characterise the displacement, velocity,and acceleration of the PFM and the urethra during a cough.Design, setting, and participants: A volunteer convenience sample of 23 continentwomen and 9 women with stress urinary incontinence (SUI) from the generalcommunity of San Francisco Bay Area was studied.Measurements: Methods included perineal ultrasound imaging, motion trackingof the urogenital structures, and digital vaginal examination. Statistical analysisused one-tailed unpaired student t tests, and Welch’s correction was applied whenvariances were unequal.Results and limitations: The cough reflex activated the PFM of continent women tocompress the urogenital structures towards the pubic symphysis, which wasabsent in women with SUI. The maximum accelerations that acted on the PFMduring a cough were generally more similar than the velocities and displacements.The urethras of women with SUI were exposed to uncontrolled transverse accelerationand were displaced more than twice as far ( p = 0.0002), with almost twicethe velocity ( p = 0.0015) of the urethras of continent women. Caution regardingthe generalisability of this study is warranted due to the small number of women inthe SUI group and the significant difference in parity between groups.Conclusions: During a cough, normal PFM function produces timely compressionof the pelvic floor and additional external support to the urethra, reducing displacement,velocity, and acceleration. In women with SUI, who have weakerurethral attachments, this shortening contraction does not occur; consequently,the urethras of women with SUI move further and faster for a longer duratio

Effects of Growing Season Fire on Northern Bobwhite Nest Site Selection and Survival

Restoration and management of longleaf pine (Pinus palustris) communities necessitates frequent prescribed fire. Prior to human colonization of the southeastern United States thousands of years ago, longleaf pine forests burned primarily during the growing-season as a result of lightning-ignited fires. Growing-season prescribed fire may suppress woody vegetation and promote herbaceous groundcover better than dormant-season fire. Despite the potential ecological benefits of growing-season fire, many land managers use only dormant-season prescribed fire to avoid destruction of ground nests, including those from northern bobwhite (Colinus virginianus). Our objective was to determine bobwhite nest survival and nest-site selection in the presence of early, growing-season prescribed fire on a 3-year return interval. We compared vegetation composition and structure at nest sites and paired random sites to identify important predictors of nest-site selection and to evaluate the effects of habitat covariates on nest survival. We captured bobwhite and attached radio transmitters. Radio-marked individuals were tracked to locate nests and determine nest survival. We documented 2 nests that burned during a growing-season prescribed fire. All 14 nests were located within units that were burned at least 2 years prior, putting these nests at a greater risk for being destroyed by prescribed fire that occurred on a 3-year return interval. We suggest that restricting early, growing-season prescribed burning to April through early June should limit an overlap between prescribed burns and the peak of northern bobwhite nesting season, which occurred mid-July at our study site. Additionally, longer fire return intervals may be needed to allow development of woody understory structure selected by bobwhites for nesting, especially on poor soils like those on our study site in the Sandhills physiographic region