Morphologic Changes of Apoptosis Induced in Human Chronic Myelogenous Leukemia Blast Cells by SC41661A (Searle), A Selective Inhibitor of 5-Lipoxygenase

Several inhibitors of the arachidonic acid-metabolizing enzyme, 5-lipoxygenase reduce proliferation of hematopoietic and non-hematopoietic cells and cell lines and some cells undergo limited differentiation. Cells were cultured from patients with chronic myelogenous leukemia in blast crisis with the selective inhibitor of 5-lipoxygenase,SC41661A[3-{3,5-bis(1,1-dimethyl)-4-hydroxyphenyl}hiol]-N-methyl-N-[2-(2-phridinyl-propanamide)]. Cells cultured for 3 to 5 days with 40 μM SC41661A exhibited reduced cellular numbers along with ultrastructural changes and DNA laddering characteristic of apoptosis. Similar culture conditions reduced proliferation of U937 monoblastoid cells. In U937 cells, the ultrastructural features of apoptosis were not observed at 72 hours, when DNA laddering was present and cell numbers were reduced, but was present after 144 hours of culture. Dissociation between certain morphologic and biochemical sequelae of apoptosis has been described in other systems. These observations are of interest since the induction of apoptosis in dividing chronic myelogenous leukemia (CML) cells by a noncytotoxic agent suggests paradigmatically new sites for therapeutic intervention

Inappropriate behaviours in a dental training environment: pilot of a UK-wide questionnaire

Incivility and inappropriate behaviour in the workplace are topics of growing interest due to their impact on patient care and safety. Several surveys and campaigns have emerged highlighting the existence of a problem. However, the true scale is difficult to ascertain. The aim of this study is to determine the existence of inappropriate behaviours within the UK dental training environment. An anonymous pilot questionnaire was distributed across multiple platforms reaching out to dental professionals within training environments, inviting responses between July 2022 and October 2022. A total of 215 responses were received. The vast majority (73.2%) felt that inappropriate behaviour is a problem within UK dental training. Senior colleagues were identified as perpetrators in 88% of responses. Most respondents (66%) reported feeling uncomfortable raising the issue, and when raised, 30% felt unsupported. Only 9% felt confident that action was taken after the issue was reported. Belittling was experienced and witnessed most commonly. The feedback received reveals the existence of inappropriate behaviours within dental training environments. Qualitative feedback indicates that if left unaddressed, the impact of such behaviour may persist long-term. Further research is required to address this issue, improve dental training conditions and job satisfaction

Obstructive sleep apnea, myocardial perfusion and myocardial blood flow: A study of older male twins.

BackgroundObstructive sleep apnea (OSA) has been associated with incidence of cardiovascular disease and with nocturnal angina, but evidence of a link with coronary atherosclerosis and myocardial ischemia is limited and previous studies may have been affected by selection bias or unmeasured confounding factors.MethodsWe performed overnight polysomnography in 178 older male twins. The Apnea/Hypopnea Index (AHI) was calculated to assess OSA from the overnight sleep evaluation. AHI ≥15 was used as indicator of moderate/severe OSA. The following day, twins underwent myocardial perfusion imaging with [82Rb]-chloride positron emission tomography. Quantitative and semiquantitative measures of myocardial perfusion and absolute myocardial blood flow were obtained.ResultsThe mean age was 68 years and 40% of the sample had an AHI≥15, which indicates moderate to severe OSA. Abnormal myocardial perfusion, both with stress and at rest, was more common in twins with elevated AHI. After adjusting for clinical, lifestyle and behavioral factors, and previous history of cardiovascular disease, twins with AHI ≥15 had 3.6 higher odds (95% CI, 1.5-8.9) of an abnormal total severity score, defined as a score ≥100, and for each 5-point increment in AHI, the odds of abnormality increased by 20% (95% CI, 7%-34%). Twin pairs where both twins had OSA exhibited the greatest risk. There were no differences in measures of ischemia and absolute myocardial blood flow and flow reserve by AHI status.ConclusionsOSA is associated with myocardial perfusion abnormalities that suggest prior subclinical myocardial scarring or infarction. Early environmental factors that affect both twins equally may play a role and should be further explored