Viral hijacking of cellular metabolism.

This review discusses the current state of the viral metabolism field and gaps in knowledge that will be important for future studies to investigate. We discuss metabolic rewiring caused by viruses, the influence of oncogenic viruses on host cell metabolism, and the use of viruses as guides to identify critical metabolic nodes for cancer anabolism. We also discuss the need for more mechanistic studies identifying viral proteins responsible for metabolic hijacking and for in vivo studies of viral-induced metabolic rewiring. Improved technologies for detailed metabolic measurements and genetic manipulation will lead to important discoveries over the next decade

Outcomes of Heavy Silicone Oil (Densiron) compared to Silicone Oil in primary rhegmatogenous retinal detachment:a multivariable regression model

PURPOSE: To measure the visual outcomes, proliferative vitreoretinopathy (PVR) and retinectomy rates following primary rhegmatogenous retinal detachment (RRD) repair, comparing silicone oil (SO) and heavy SO (Densiron). METHODS: Retrospective, continuous comparative study from January 2017 to May 2021 of all primary RRD. Multivariable linear (logMAR gain) and binary-logistic (PVR-C and retinectomy rate) regression models to compare tamponade were performed. Covariates included age, gender, ocular co-morbidities, high myopia, macula-status, giant-retinal-tear (GRT), pre-op vision, PVR-C, oil type, perfluorocarbon-use, combined scleral buckle/vitrectomy, combined phaco-vitrectomy, 360-degrees-endolaser and oil duration. Cases with trauma or less than six-month follow-up were excluded. RESULTS: A total of 259 primary RD were analysed. There were 179 SO patients and 80 Densiron patients that had six-month primary re-detachment in 18 (10.1%) and 8 (10.0%) respectively (p = 1.000). No difference in logMAR gain was detected between tamponade choice on multivariable linear regression. Subsequent glaucoma surgery was 5 (2.8%) and 4 (5.0%) for SO and Densiron patients respectively (p = 0.464). On multivariate binary-logistic regression we found no difference in development of PVR-C between oil tamponades. However, SO had significantly higher subsequent retinectomy rate compared to Densiron (odds ratio 15.3, 95% CI 1.9–125.5, p = 0.011). Duration of oil tamponade was not linked to differences in logMAR gain, PVR-C formation or increased retinectomy rate. CONCLUSIONS: We report no difference in primary anatomical success, number of further RRD surgeries, subsequent glaucoma surgery, visual outcomes, PVR-C between both tamponades on multivariable models. Densiron oil was found to be more retinectomy sparing relative to SO

Effect of deprivation and ethnicity on primary macula-on retinal detachment repair success rate and clinical outcomes:A study of 568 patients

Purpose Socio-economic deprivation and ethnic variation have been frequently linked to poorer health outcomes. We collected a large series of primary macula-on rhegmatogenous retinal detachment (RRD) cases and analysed the effect of socio-economic deprivation and ethnicity on both six-month retinal re-detachment rate and visual outcomes. Materials and methods Retrospective consecutive case series of 568 patients attending Birmingham and Midlands Eye Centre from January 2017–2020. Multiple Indices of Deprivation (IMD) deciles were used for deprivation status and split to two groups: IMD-A (Decile 1–5) and IMD-B (Decile 6–10). The two largest subgroups of ethnicities were compared, White and South Asians (SA). Results We report an overall retinal re-detachment rate of 8.5%. IMD-A re-detached significantly more than IMD-B (11.2% vs 6.0% respectively, p = 0.034). No statistical significance was found between White and SA re-detachment rate (9.1% and 5.6% respectively, p = 0.604). SA median age significantly lower at 49 years (IQR: 37–61) compared to White patients at 57 years (IQR: 50–65) (p = Conclusion We demonstrated an increased retinal re-detachment rate in our more deprived patients according to IMD and a younger cohort of SA compared to White ethnicity. Further prospective studies are required to demonstrate the link between socio-economic deprivation and surgical success

A whole cell pathway screen reveals seven novel chemosensitizers to combat chloroquine resistant malaria

Due to the widespread prevalence of resistant parasites, chloroquine (CQ) was removed from front-line antimalarial chemotherapy in the 1990s despite its initial promise of disease eradication. Since then, resistance-conferring mutations have been identified in transporters such as the PfCRT, that allow for the efflux of CQ from its primary site of action, the parasite digestive vacuole. Chemosensitizing/ chemoreversing compounds interfere with the function of these transporters thereby sensitizing parasites to CQ once again. However, compounds identified thus far have disappointing in vivo efficacy and screening for alternative candidates is required to revive this strategy. In this study, we propose a simple and direct means to rapidly screen for such compounds using a fluorescent-tagged CQ molecule. When this screen was applied to a small library, seven novel chemosensitizers (octoclothepin, methiothepin, metergoline, loperamide, chlorprothixene, L-703,606 and mibefradil) were quickly elucidated, including two which showed greater potency than the classical chemosensitizers verapamil and desipramine

A Randomised, Cross-Over, Placebo-Controlled Study of Aloe vera in Patients with Irritable Bowel Syndrome: Effects on Patient Quality of Life

Background. Irritable bowel syndrome (IBS) is a chronic, difficult to treat condition. The efficacy of Aloe vera in treating IBS symptoms is not yet proven. The purpose of this study was to determine if Aloe vera is effective in improving quality of life. Methods. A multicentre, randomised, double-blind, cross-over placebo controlled study design. Patients were randomised to Aloe vera, wash-out, placebo or placebo, washout, Aloe vera. Each preparation (60 mL) was taken orally twice a day. Patient quality of life was measured using the Gastrointestinal Symptoms Rating Score, Irritable Bowel Syndrome Quality of Life, EuroQol and the Short-Form-12 at baseline and treatment periods 1 and 2. Results. A total of 110 patients were randomised, but only 47 completed all questionnaires and both study arms. Statistical analysis showed no difference between the placebo and Aloe vera treatment in quality of life. Discussion. This study was unable to show that Aloe vera was superior to placebo in improving quality of life. Drop outs and other confounding factors may have impacted on the power of the study to detect a clinically important difference. Conclusion. This study failed to find Aloe vera superior to placebo in improving quality of life proven Irritable Bowel Syndrome patients

Uncovering treatment burden as a key concept for stroke care: a systematic review of qualitative research

<b>Background</b> Patients with chronic disease may experience complicated management plans requiring significant personal investment. This has been termed ‘treatment burden’ and has been associated with unfavourable outcomes. The aim of this systematic review is to examine the qualitative literature on treatment burden in stroke from the patient perspective.<p></p> <b>Methods and findings</b> The search strategy centred on: stroke, treatment burden, patient experience, and qualitative methods. We searched: Scopus, CINAHL, Embase, Medline, and PsycINFO. We tracked references, footnotes, and citations. Restrictions included: English language, date of publication January 2000 until February 2013. Two reviewers independently carried out the following: paper screening, data extraction, and data analysis. Data were analysed using framework synthesis, as informed by Normalization Process Theory. Sixty-nine papers were included. Treatment burden includes: (1) making sense of stroke management and planning care, (2) interacting with others, (3) enacting management strategies, and (4) reflecting on management. Health care is fragmented, with poor communication between patient and health care providers. Patients report inadequate information provision. Inpatient care is unsatisfactory, with a perceived lack of empathy from professionals and a shortage of stimulating activities on the ward. Discharge services are poorly coordinated, and accessing health and social care in the community is difficult. The study has potential limitations because it was restricted to studies published in English only and data from low-income countries were scarce.<p></p> <b>Conclusions</b> Stroke management is extremely demanding for patients, and treatment burden is influenced by micro and macro organisation of health services. Knowledge deficits mean patients are ill equipped to organise their care and develop coping strategies, making adherence less likely. There is a need to transform the approach to care provision so that services are configured to prioritise patient needs rather than those of health care systems

Targeting of Pseudorabies Virus Structural Proteins to Axons Requires Association of the Viral Us9 Protein with Lipid Rafts

The pseudorabies virus (PRV) Us9 protein plays a central role in targeting viral capsids and glycoproteins to axons of dissociated sympathetic neurons. As a result, Us9 null mutants are defective in anterograde transmission of infection in vivo. However, it is unclear how Us9 promotes axonal sorting of so many viral proteins. It is known that the glycoproteins gB, gC, gD and gE are associated with lipid raft microdomains on the surface of infected swine kidney cells and monocytes, and are directed into the axon in a Us9-dependent manner. In this report, we determined that Us9 is associated with lipid rafts, and that this association is critical to Us9-mediated sorting of viral structural proteins. We used infected non-polarized and polarized PC12 cells, a rat pheochromocytoma cell line that acquires many of the characteristics of sympathetic neurons in the presence of nerve growth factor (NGF). In these cells, Us9 is highly enriched in detergent-resistant membranes (DRMs). Moreover, reducing the affinity of Us9 for lipid rafts inhibited anterograde transmission of infection from sympathetic neurons to epithelial cells in vitro. We conclude that association of Us9 with lipid rafts is key for efficient targeting of structural proteins to axons and, as a consequence, for directional spread of PRV from pre-synaptic to post-synaptic neurons and cells of the mammalian nervous system