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Call number: LD2668 .R4 1966 H87

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Inactivation of human MAD2B in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agents

Rev7p has been suggested to play an important role in regulating DNA damage response in yeast, and recently, the human homologue (i.e., MAD2B) has been identified, which shares significant homology to the mitotic checkpoint protein MAD2. In this study, we investigated whether MAD2B played a key role in cellular sensitivity to DNA-damaging anticancer drugs by suppressing its expression using RNA interference in nasopharyngeal carcinoma cells. Using colony formation assay, we found that suppression of MAD2B conferred hypersensitivity to a range of DNA-damaging agents, especially DNA cross-linkers, such as cisplatin, and γ-irradiation. This effect was associated with reduced frequencies of spontaneous and drug-induced mutations, elevated phosphorylation of histone H2AX, and markedly increased chromosomal aberrations in response to DNA damage. In addition, there was also a significant decrease in cisplatin-induced sister chromatid exchange rate, a marker for homologous recombination-mediated post-replication repair in MAD2B-depleted cells. These results indicate that MAD2B may be a key factor in regulating cellular response to DNA damage in cancer cells. Our findings reveal a novel strategy for cancer therapy, in which cancer cells are sensitized to DNA-damaging anticancer drugs through inactivation of the MAD2B gene. ©2006 American Association for Cancer Research.link_to_OA_fulltex

Dimensional Regulation from 1D/3D to 2D/3D of Perovskite Interfaces for Stable Inverted Perovskite Solar Cells

Constructing low-dimensional/three-dimensional (LD/3D) perovskite solar cells can improve efficiency and stability. However, the design and selection of LD perovskite capping materials are incredibly scarce for inverted perovskite solar cells (PSCs) because LD perovskite capping layers often favor hole extraction and impede electron extraction. Here, we develop a facile and effective strategy to modify the perovskite surface by passivating the surface defects and modulating surface electrical properties by incorporating morpholine hydriodide (MORI) and thiomorpholine hydriodide (SMORI) on the perovskite surface. Compared with the PI treatment that we previously developed, the one-dimensional (1D) perovskite capping layer derived from PI is transformed into a two-dimensional (2D) perovskite capping layer (with MORI or SMORI), achieving dimension regulation. It is shown that the 2D SMORI perovskite capping layer induces more robust surface passivation and stronger n–N homotype 2D/3D heterojunctions, achieving a p–i–n inverted solar cell with an efficiency of 24.55%, which retains 87.6% of its initial efficiency after 1500 h of operation at the maximum power point (MPP). Furthermore, 5 × 5 cm2 perovskite mini-modules are presented, achieving an active-area efficiency of 22.28%. In addition, the quantum well structure in the 2D perovskite capping layer increases the moisture resistance, suppresses ion migration, and improves PSCs’ structural and environmental stability

Exercise mediated protection of diabetic heart through modulation of microRNA mediated molecular pathways

Abstract Hyperglycaemia, hypertension, dyslipidemia and insulin resistance collectively impact on the myocardium of people with diabetes, triggering molecular, structural and myocardial abnormalities. These have been suggested to aggravate oxidative stress, systemic inflammation, myocardial lipotoxicity and impaired myocardial substrate utilization. As a consequence, this leads to the development of a spectrum of cardiovascular diseases, which may include but not limited to coronary endothelial dysfunction, and left ventricular remodelling and dysfunction. Diabetic heart disease (DHD) is the term used to describe the presence of heart disease specifically in diabetic patients. Despite significant advances in medical research and long clinical history of anti-diabetic medications, the risk of heart failure in people with diabetes never declines. Interestingly, sustainable and long-term exercise regimen has emerged as an effective synergistic therapy to combat the cardiovascular complications in people with diabetes, although the precise molecular mechanism(s) underlying this protection remain unclear. This review provides an overview of the underlying mechanisms of hyperglycaemia- and insulin resistance-mediated DHD with a detailed discussion on the role of different intensities of exercise in mitigating these molecular alterations in diabetic heart. In particular, we provide the possible role of exercise on microRNAs, the key molecular regulators of several pathophysiological processes