Marine alkaloid rigidins are cytotoxic compounds known to kill cancer cells at nanomolar concentrations by targeting the microtubule network. Here, a rigidin analogue containing a thioether group was “caged” by coordination of its thioether group to a photosensitive ruthenium complex. In the dark, the coordinated ruthenium fragment prevented the rigidin analogue from inhibiting tubulin polymerization and reduced its toxicity in 2D cancer cell lines monolayers, 3D lung cancer tumor spheroids (A549), and in a lung cancer tumor xenograft (A549) in nude mice. Photochemical activation of the prodrug upon green light irradiation led to the photosubstitution of the thioether ligand by water, thereby releasing the free rigidin analogue capable of inhibiting the polymerization of tubulin. In cancer cells, such photorelease was accompanied by a drastic reduction of cell growth, not only when the cells were grown in normoxia (21% O2) but also, remarkably, in hypoxic conditions (1% O2). In vivo, low toxicity was observed at a dose of 1 mg.kg-1 when the compound was injected intraperitoneally, and light activation of the compound in the tumor led to 30% tumor volume reduction, which represents the first demonstration of the safety and efficacy of a ruthenium-based PACT compounds in a tumor xenograft.
29 October 2020 in Alcohol, Clinical and Experimental Research
This is the first systematic review and meta-analysis to ascertain incidences of post-vasectomy pain following traditional scalpel, or non-scalpel vasectomy. Electronic databases PubMed, Embase and PsycINFO were searched up to 1 July 2019 for peer-reviewed articles recording post-vasectomy pain. We identified 733 publications, screened 559 after removal of duplicates and excluded 533. Of the remaining 26 full-text articles, 8 were excluded with reasons, leaving 18 for detailed analyses. Meta-analysis was performed on 25 separate datasets (11 scalpel, 11 non-scalpel, 3 other/combined). Study follow-up ranged from 2 weeks to 37 years and sample sizes from 12 to 723 patients. The overall incidence of post-vasectomy pain was 15% (95% CI 9% to 25%). The incidences of post-vasectomy pain following scalpel and non-scalpel techniques were 24% (95% CI 15% to 36%) and 7% (95% CI 4% to 13%), respectively. Post-vasectomy pain syndrome occurred in 5% (95% CI 3% to 8%) of subjects, with similar estimates for both techniques. We conclude that the overall incidence of post-vasectomy pain is greater than previously reported, with three-fold higher rates of pain following traditional scalpel, compared to non-scalpel vasectomy, whereas the incidence of post-vasectomy pain syndrome is similar.
Physical activity and obesity counselling have both been gaining increasing interest in preventive health and treatment. However, most healthcare professionals do not provide advice on these topics nearly as often as they should. There are many reasons for this. Common barriers for the provision of brief advice on physical activity and obesity in both primary and secondary care are lack of time, motivation and knowledge. Systematic reviews have been published on the barriers of physical activity and obesity counselling in the primary care setting, but there is no published work on the barriers present in secondary care. This systematic review aims to assess all published data that discuss the barriers of physical activity and obesity counselling as noted by healthcare providers in secondary care. Four databases will be searched using the same search strategy, and the findings will be compiled using the COM-B model to explore the frequency of a reported barrier. This systematic review will be beneficial not only to practicing healthcare providers, but also the educational and managerial staff of secondary care facilities, as it may highlight the need for further training to fill gaps in the provision of preventive healthcare.
Background: This study investigated the impact of COVID-19 on patients with sickle cell crisis (SCC) using National Inpatient Sample (NIS) data for the year 2020. Methods: A retrospective cohort analysis was conducted utilizing International Classification of Diseases (ICD-10) codes to identify adults who were admitted with a principal diagnosis of sickle cell crisis. The primary outcomes examined were inpatient mortality, while the secondary outcomes assessed included morbidity, hospital length of stay, and resource utilization. Analyses were conducted with STATA. Multivariate logistic and linear regression analyses were used to adjust for confounding variables. Results: Of 66,415 adult patients with a primary SCC diagnosis, 875 were identified with a secondary diagnosis of COVID-19 infection. Unadjusted mortality rate was higher for SCC patients with COVID-19 (2.28%) compared to those without (0.33%), with an adjusted odds ratio (aOR) of 8.49 (p = 0.001). They also showed increased odds of developing acute respiratory failure (aOR = 2.37, p = 0.003) and acute kidney injury requiring dialysis (aOR = 8.66, p = 0.034). Additionally, these patients had longer hospital stays by an adjusted mean of 3.30 days (p < 0.001) and incurred higher hospitalization charges by an adjusted mean of USD 35,578 (p = 0.005). Conclusions: The SCC patients with COVID-19 presented higher mortality rates, increased morbidity indicators, longer hospital stays, and substantial economic burdens.