Medicinal Properties of Clinacanthus nutans: A review

To date, medicinal plants are the most important resources in the discovery of new drugs. Clinacanthus nutans has been used traditionally in Thailand folk medicine to promote overall well-being. A few biological constituents of C. nutans and their physiological functions have been evaluated in previous studies. However, the mechanisms of action, potency and efficacy of the plant are still not well understood. In this review, the pharmacological properties of C. nutans such as anti-inflammatory effects, anti-proliferation, anti-venom and anti-bacterial activities, and their underlying mechanisms of action are presented and discussed.Keywords:  Clinacanthus nutans: Anti-inflammatory, Anti-proliferation, Anti-venom, Anti-bacterial propertie

Nonvirally Modified Autologous Primary Hepatocytes Correct Diabetes and Prevent Target Organ Injury in a Large Preclinical Model

BACKGROUND: Current gene- and cell-based therapies have significant limitations which impede widespread clinical application. Taking diabetes mellitus as a paradigm, we have sought to overcome these limitations by ex vivo electrotransfer of a nonviral insulin expression vector into primary hepatocytes followed by immediate autologous reimplantation in a preclinical model of diabetes. METHODS AND RESULTS: In a single 3-hour procedure, hepatocytes were isolated from a surgically resected liver wedge, electroporated with an insulin expression plasmid ex vivo and reimplanted intraparenchymally under ultrasonic guidance into the liver in each of 10 streptozotocin-induced diabetic Yorkshire pigs. The vector was comprised of a bifunctional, glucose-responsive promoter linked to human insulin cDNA. Ambient glucose concentrations appropriately altered human insulin mRNA expression and C-peptide secretion within minutes in vitro and in vivo. Treated swine showed correction of hyperglycemia, glucose intolerance, dyslipidemia and other metabolic abnormalities for > or = 47 weeks. Metabolic correction correlated significantly with the number of hepatocytes implanted. Importantly, we observed no hypoglycemia even under fasting conditions. Direct intrahepatic implantation of hepatocytes did not alter biochemical indices of liver function or induce abnormal hepatic lobular architecture. About 70% of implanted hepatocytes functionally engrafted, appeared histologically normal, retained vector DNA and expressed human insulin for > or = 47 weeks. Based on structural tissue analyses and transcriptome data, we showed that early correction of diabetes attenuated and even prevented pathological changes in the eye, kidney, liver and aorta. CONCLUSIONS: We demonstrate that autologous hepatocytes can be efficiently, simply and safely modified by electroporation of a nonviral vector to express, process and secrete insulin durably. This strategy, which achieved significant and sustained therapeutic efficacy in a large preclinical model without adverse effects, warrants consideration for clinical development especially as it could have broader future applications for the treatment of other acquired and inherited diseases for which systemic reconstitution of a specific protein deficiency is critical

Awareness and preparedness of healthcare workers against the first wave of the COVID-19 pandemic: A cross-sectional survey across 57 countries.

BACKGROUND: Since the COVID-19 pandemic began, there have been concerns related to the preparedness of healthcare workers (HCWs). This study aimed to describe the level of awareness and preparedness of hospital HCWs at the time of the first wave. METHODS: This multinational, multicenter, cross-sectional survey was conducted among hospital HCWs from February to May 2020. We used a hierarchical logistic regression multivariate analysis to adjust the influence of variables based on awareness and preparedness. We then used association rule mining to identify relationships between HCW confidence in handling suspected COVID-19 patients and prior COVID-19 case-management training. RESULTS: We surveyed 24,653 HCWs from 371 hospitals across 57 countries and received 17,302 responses from 70.2% HCWs overall. The median COVID-19 preparedness score was 11.0 (interquartile range [IQR] = 6.0-14.0) and the median awareness score was 29.6 (IQR = 26.6-32.6). HCWs at COVID-19 designated facilities with previous outbreak experience, or HCWs who were trained for dealing with the SARS-CoV-2 outbreak, had significantly higher levels of preparedness and awareness (p<0.001). Association rule mining suggests that nurses and doctors who had a 'great-extent-of-confidence' in handling suspected COVID-19 patients had participated in COVID-19 training courses. Male participants (mean difference = 0.34; 95% CI = 0.22, 0.46; p<0.001) and nurses (mean difference = 0.67; 95% CI = 0.53, 0.81; p<0.001) had higher preparedness scores compared to women participants and doctors. INTERPRETATION: There was an unsurprising high level of awareness and preparedness among HCWs who participated in COVID-19 training courses. However, disparity existed along the lines of gender and type of HCW. It is unknown whether the difference in COVID-19 preparedness that we detected early in the pandemic may have translated into disproportionate SARS-CoV-2 burden of disease by gender or HCW type

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 &lt; 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

Retirement : should you be worried?

The Central Provident Fund (CPF) is Singapore’s national saving system and contributions to CPF accounts are as high as 36% of a person’s wage. Previous studies on adequacy of CPF for retirement spending focused on the Income Replacement Rate (IRR) as the metric for measuring adequacy, but among them there is little agreement on the final IRR achievable by CPF. Furthermore, the inception of the new CPF Life scheme has rendered previous studies outdated. In this report, we propose a different quantitative approach to the question of adequacy, which is to model an individual’s savings and retirement expenditure using publicly available data, and determine if the accumulated wealth is sufficient to cover retirement spending. We find out that the CPF Life income can adequately cover retirement expenses for the 30th percentile of income earners. Therefore, CPF Life serves its purpose as a source of post-retirement funds for the lower-income group. However, adverse changes in wage growth rate or inflation rate can lead to the 30th percentile not being able to cover their retirement expenses even with personal savings. Meanwhile, the statutory Minimum Sum level may need to be reviewed as it is more than enough to sustain basic expenses after retirement.BUSINES

Analysis of Singapore Airlines' advertising campaign : 1996 to 1999

The objective of this study is to analyze the changes in SIA's advertising campaign from 1996 to 1999. We are interested to know whether the SilkAir crash and the economic crisis, which both occurred in 1997, have had any influence on SIA’s advertising strategy. Our main research method is a content and analysis in four print media –The Straits Times, TIME, Fortune and SilverKris

Creating high fidelity 360° virtual reality with high dynamic range spherical panorama images

This research explores the development of a novel method and apparatus for creating spherical panoramas enhanced with high dynamic range (HDR) for high fidelity Virtual Reality 360 degree (VR360) user experiences. A VR360 interactive panorama presentation using spherical panoramas can provide virtual interactivity and wider viewing coverage; with three degrees of freedom, users can look around in multiple directions within the VR360 experiences, gaining the sense of being in control of their own engagement. This degree of freedom is facilitated by the use of mobile displays or head-mount-devices. However, in terms of image reproduction, the exposure range can be a major difficulty in reproducing a high contrast real-world scene. Imaging variables caused by difficulties and obstacles can occur during the production process of spherical panorama facilitated with HDR. This may result in inaccurate image reproduction for location-based subjects, which will in turn result in a poor VR360 user experience. In this article we describe a HDR spherical panorama reproduction approach (workflow and best practice) which can shorten the production processes, and reduce imaging variables, and technical obstacles and issues to a minimum. This leads to improved photographic image reproduction with fewer visual abnormalities for VR360 experiences, which can be adaptable into a wide range of interactive design applications. We describe the process in detail and also report on a user study that shows the proposed approach creates images which viewers prefer, on the whole, to those created using more complicated HDR methods, or to those created without the use of HDR at all

Quantifying systematic RBE-weighted dose uncertainty arising from multiple variable RBE models in organ at risk

Purpose: Relative biological effectiveness (RBE) uncertainties have been a concern for treatment planning in proton therapy, particularly for treatment sites that are near organs at risk (OARs). In such a clinical situation, the utilization of variable RBE models is preferred over constant RBE model of 1.1. The problem, however, lies in the exact choice of RBE model, especially when current RBE models are plagued with a host of uncertainties. This paper aims to determine the influence of RBE models on treatment planning, specifically to improve the understanding of the influence of the RBE models with regard to the passing and failing of treatment plans. This can be achieved by studying the RBE-weighted dose uncertainties across RBE models for OARs in cases where the target volume overlaps the OARs. Multi-field optimization (MFO) and single-field optimization (SFO) plans were compared in order to recommend which technique was more effective in eliminating the variations between RBE models. Methods: Fifteen brain tumor patients were selected based on their profile where their target volume overlaps with both the brain stem and the optic chiasm. In this study, 6 RBE models were analyzed to determine the RBE-weighted dose uncertainties. Both MFO and SFO planning techniques were adopted for the treatment planning of each patient. RBE-weighted dose uncertainties in the OARs are calculated assuming [Formula presented] of 3 Gy and 8 Gy. Statistical analysis was used to ascertain the differences in RBE-weighted dose uncertainties between MFO and SFO planning. Additionally, further investigation of the linear energy transfer (LET) distribution was conducted to determine the relationship between LET distribution and RBE-weighted dose uncertainties. Results: The results showed no strong indication on which planning technique would be the best for achieving treatment planning constraints. MFO and SFO showed significant differences (P <.05) in the RBE-weighted dose uncertainties in the OAR. In both clinical target volume (CTV)-brain stem and CTV-chiasm overlap region, 10 of 15 patients showed a lower median RBE-weighted dose uncertainty in MFO planning compared with SFO planning. In the LET analysis, 8 patients (optic chiasm) and 13 patients (brain stem) showed a lower mean LET in MFO planning compared with SFO planning. It was also observed that lesser RBE-weighted dose uncertainties were present with MFO planning compared with SFO planning technique. Conclusions: Calculations of the RBE-weighted dose uncertainties based on 6 RBE models and 2 different [Formula presented] revealed that MFO planning is a better option as opposed to SFO planning for cases of overlapping brain tumor with OARs in eliminating RBE-weighted dose uncertainties. Incorporation of RBE models failed to dictate the passing or failing of a treatment plan. To eliminate RBE-weighted dose uncertainties in OARs, the MFO planning technique is recommended for brain tumor when CTV and OARs overlap.Published versionThis work is partially supported by the Duke- NUS Oncology Academic Clinical Programme Proton Research fund (08/FY2019/EX(SL)/65-A111) and Duke-NUS Oncology Academic Clinical Programme Proton Research fund (08/FY2020/EX(SL)/76-A152)