Purification of plant derived molecules that modulate sphingolipid enzymes in cancer and inflammation

There is a constant need to discover new anticancer and anti-inflammatory compounds that can be developed as medicines. Sphingosine kinase 1 (SK1) and dihydroceramide desaturase (Des1) have been demonstrated to have a key role in sphingolipid metabolism and are potential targets for anticancer/anti-inflammatory therapeutics. This study aims to screen a plant library collected during field work in Egypt and then to isolate new anticancer and anti-inflammatory compounds with activity against SK1 and/ or Des1. This aim was achieved using plant extracts tested on breast cancer cell viability, proliferation and SK1 and/or Des1 protein expression. Bio-assay guided fractionation and isolation of compounds using flash column, silica gel column chromatography and preparative TLC techniques, followed by structure elucidation using 1D and 2D spectroscopic analysis enabled identification of compounds that met the criteria above. Cell proliferation was determined using [3H]-thymidine incorporation assay. Western blotting technique was used to determine the effect of isolated compounds on the targeted enzymes SK1/Des1 as well as the apoptotic pathway (PARP). There were three major findings. First, three plant species Gomphocarpus sinaicus, Urginea maritima and Pancratium tortuosum exhibited anticancer activity. Second, narciclasine was isolated for the first time from P. tortuosum and was demonstrated to inhibit cell proliferation (p<0.05) and to reduce SK1 and Des1 expression in MDA-MB-231 and MCF7-7L breast cancer cells. Narciclasine also induced PARP cleavage (a marker for apoptosis) and reduced expression of Ki67 and phosphorylated AKT levels (a marker for cell survival). The reduced expression of SK1 and Des1 in response to narciclasine was independent of the ubiquitin-proteasomal pathway, suggesting that this compound might affect the transcriptional/translational regulation of SK1 and Des1. Finally, narciclasine also exhibited ant-inflammatory activity as evidenced by its ability to prevent TNFα-stimulated degradation of IκB and to inhibit NFkB- and AP1-dependent transcriptional activity in keratinocytes. Third, a mixture of cardenolide glycosides were isolated from G. sinaicus and shown to inhibit cell proliferation (p<0.05), reduce expression of SK1 and Des1 and induce modest PARP cleavage in MDA-MB-231 and MCF-7L cells. This mixture contained humistratin and calactin and/or calotropin. These compounds reduced SK1 expression by inducing its proteasomal degradation, while the reduction in Des1 expression may be via a transcriptional/translational mechanism and is independent of ubiquitin-proteasomal degradation pathway. The mixture also exhibited anti-inflammatory activity in inhibiting NFkB- and AP-1-dependent transcriptional activity in keratinocytes. Narciclasine and the cardenolide glycoside mixture are potential anticancer/anti-inflammatory compounds require further studies in order to establish whether these compounds might be usefully exploited to treat cancer and inflammatory disease.There is a constant need to discover new anticancer and anti-inflammatory compounds that can be developed as medicines. Sphingosine kinase 1 (SK1) and dihydroceramide desaturase (Des1) have been demonstrated to have a key role in sphingolipid metabolism and are potential targets for anticancer/anti-inflammatory therapeutics. This study aims to screen a plant library collected during field work in Egypt and then to isolate new anticancer and anti-inflammatory compounds with activity against SK1 and/ or Des1. This aim was achieved using plant extracts tested on breast cancer cell viability, proliferation and SK1 and/or Des1 protein expression. Bio-assay guided fractionation and isolation of compounds using flash column, silica gel column chromatography and preparative TLC techniques, followed by structure elucidation using 1D and 2D spectroscopic analysis enabled identification of compounds that met the criteria above. Cell proliferation was determined using [3H]-thymidine incorporation assay. Western blotting technique was used to determine the effect of isolated compounds on the targeted enzymes SK1/Des1 as well as the apoptotic pathway (PARP). There were three major findings. First, three plant species Gomphocarpus sinaicus, Urginea maritima and Pancratium tortuosum exhibited anticancer activity. Second, narciclasine was isolated for the first time from P. tortuosum and was demonstrated to inhibit cell proliferation (p<0.05) and to reduce SK1 and Des1 expression in MDA-MB-231 and MCF7-7L breast cancer cells. Narciclasine also induced PARP cleavage (a marker for apoptosis) and reduced expression of Ki67 and phosphorylated AKT levels (a marker for cell survival). The reduced expression of SK1 and Des1 in response to narciclasine was independent of the ubiquitin-proteasomal pathway, suggesting that this compound might affect the transcriptional/translational regulation of SK1 and Des1. Finally, narciclasine also exhibited ant-inflammatory activity as evidenced by its ability to prevent TNFα-stimulated degradation of IκB and to inhibit NFkB- and AP1-dependent transcriptional activity in keratinocytes. Third, a mixture of cardenolide glycosides were isolated from G. sinaicus and shown to inhibit cell proliferation (p<0.05), reduce expression of SK1 and Des1 and induce modest PARP cleavage in MDA-MB-231 and MCF-7L cells. This mixture contained humistratin and calactin and/or calotropin. These compounds reduced SK1 expression by inducing its proteasomal degradation, while the reduction in Des1 expression may be via a transcriptional/translational mechanism and is independent of ubiquitin-proteasomal degradation pathway. The mixture also exhibited anti-inflammatory activity in inhibiting NFkB- and AP-1-dependent transcriptional activity in keratinocytes. Narciclasine and the cardenolide glycoside mixture are potential anticancer/anti-inflammatory compounds require further studies in order to establish whether these compounds might be usefully exploited to treat cancer and inflammatory disease

E-data Utilization on National-Health Service Performance Assessment during Covid-19 in Bangladesh: New Evidence Using Data Envelopment Analysis (DEA) Technique

Making the entire world extremely nervous, more than the quarter of a year has gone past since the global breakout of deadly respiratory illness, named Coronavirus Disease-2019 (CoViD-19), over nine million people across the globe have already been infected with more than five percent death rate, and the number is still ascending at a tremendously frightening rate. This study has been driven to identify the adequacy and quality of responses from national health facilities in Bangladesh during this epidemic and discern the stimulates that influence the entire system. With an in-depth exercise of a nonparametric statistical method for proficiency weighting, namely the Data Envelopment Analysis (DEA) technique, the objective of this study of evaluating the thorough response and performance of the Bangladeshi National Health Service has been placed in efforts to be achieved. With the outcome, the method and operation of assessing the effective responsiveness, capability, and appropriate organization of the national health services (NHS) in Bangladesh during the ongoing COVID-19 pandemic have been revealed. It has also been specifically identified that this country’s health system does not possess material mastery on input variables; neither do they have strong dominance over output variables. With a view to minimizing the expenditure, they should have decreased input variables alongside enhancing input resources thoroughly to deal with this pandemic with stringent governance. Direction and limitation of future research endeavors in this area may be indicated by this study. National responses across the globe can also be benchmarked

Quick Handover in 5G for High Speed Railways and Highways Using Forward Handover and PN Sequence Detection

The cellular users, on high speed railways andhighways, travel at a very high speed and follow a nearly straightpath, in general. Thus, they typically undergo a maximumfrequency of handovers in the cellular environment. This requiresa very fast triggering of the handover. In the existing method ofhandover in 5G cellular communication, for high speed users,neither the decision-making of handover nor the triggering ofhandover is sufficiently fast. This can lead to poor signal qualityand packet losses and in the worst case, radio link failure (RLF)during a handover. This paper proposes a forward handover basedmethod, combined with PN sequence detections, to facilitate aquicker handover for high speed users on railways and highways.The proposed method adds some complexity but can offer asignificant improvement in the overall handover delay. A simplisticsimulation is used to demonstrate the improvement of the proposedmethod

Nanotechnology for high-performance textiles: A promising frontier for innovation

Nanotechnology embodies a groundbreaking innovation for the textile and apparel industry, facilitating enhancements to the functionality and performance of textiles, including durability, resistance to water, odor, flame, stain, UV-protection, and antimicrobial properties. Nanotechnology also enables biosensing, drug delivery, energy generation, and storage in textiles. Here, we present a comprehensive overview of the possibilities offered by nanotechnology in the context of high-performance textiles providing a roadmap for future research and development in this exciting field. We scrutinize the current research on nanotechnology in textiles, exploring various types of nanomaterials and their properties, the methods of incorporating nanomaterials into textiles, and the numerous applications of high-performance textiles across critical industries such as healthcare, military, sports, fashion, and wearable electronics. We conclude the review with an analysis of the potential health and environmental concerns arising from the use of nanotechnology in textiles, emphasizing the importance of further research in these areas

Patient attitudes towards medical students at Damascus University teaching hospitals

Background: The cooperation of patients and their consent to involve medical students in their care is vital to clinical education, but large numbers of students and lack of experience as well as loss of privacy may evoke negative attitudes of patients, which may sometimes adversely affect the clinical teaching environment. This study aimed to explore the attitudes of patients towards medical students at Damascus University hospitals, and to explore the determinants of those attitudes thus discussing possible implications applicable to clinical teaching. Methods: This cross-sectional study was conducted at three teaching hospitals affiliated to the Faculty of Medicine at Damascus University. Four hundred patients were interviewed between March and April 2011 by a trained sociologist using a structured questionnaire. Results: Of the patients interviewed, 67.8 % approved the presence of medical students during the medical consultation and 58.2 % of them felt comfortable with the presence of students, especially among patients with better socio-economic characteristics. 81.5 % of the patients agreed to be examined by students in the presence of the supervisor, while 40.2 % gave agreement even in the absence of the supervisor. Privacy was the most important factor in the patients ’ reticence towards examination by the students, whilst the relative safety and comfort if a supervisor was available determined patients ’ agreement

Prediction of Preterm Deliveries from EHG Signals Using Machine Learning

There has been some improvement in the treatment of preterm infants, which has helped to increase their chance of survival. However, the rate of premature births is still globally increasing. As a result, this group of infants are most at risk of developing severe medical conditions that can affect the respiratory, gastrointestinal, immune, central nervous, auditory and visual systems. In extreme cases, this can also lead to long-term conditions, such as cerebral palsy, mental retardation, learning difficulties, including poor health and growth. In the US alone, the societal and economic cost of preterm births, in 2005, was estimated to be $26.2 billion, per annum. In the UK, this value was close to £2.95 billion, in 2009. Many believe that a better understanding of why preterm births occur, and a strategic focus on prevention, will help to improve the health of children and reduce healthcare costs. At present, most methods of preterm birth prediction are subjective. However, a strong body of evidence suggests the analysis of uterine electrical signals (Electrohysterography), could provide a viable way of diagnosing true labour and predict preterm deliveries. Most Electrohysterography studies focus on true labour detection during the final seven days, before labour. The challenge is to utilise Electrohysterography techniques to predict preterm delivery earlier in the pregnancy. This paper explores this idea further and presents a supervised machine learning approach that classifies term and preterm records, using an open source dataset containing 300 records (38 preterm and 262 term). The synthetic minority oversampling technique is used to oversample the minority preterm class, and cross validation techniques, are used to evaluate the dataset against other similar studies. Our approach shows an improvement on existing studies with 96% sensitivity, 90% specificity, and a 95% area under the curve value with 8% global error using the polynomial classifier

Middle Eastern Cities in a Time of Climate Crisis

The climate crisis is hitting around the world, including in the Middle East and its cities. Urban regions are exposed to increasingly frequent heat waves and floods that leave decision makers without immediate answers. In the context of this global crisis, this book addresses the need for a better understanding of the current model of urban expansion. Cities are major sources of greenhouse gas (GHG) emissions but they are also celebrated for their contribution to economic growth. The current moment is one of a large paradigm shift as climate change is now recognized as a legitimate public problem. This is especially true for city dwellers, who are increasingly exposed to climate change, the loss of biodiversity and heavy pollution while natural breathing spaces continue to shrink around them. The sixteen chapters of this book do not offer any off-the-rack or technical solutions, but they analyze the urban conundrum and the contribution of cities to the climate crisis. Some chapters focus on individual car ownership, land privatization, waste management and land use changes under the guise of development. Others explore local and contextual answers to urban governance issues. With the support of CEDEJ and the Friedrich-Ebert-Stiftung, researchers, experts and civil society actors explore the ongoing transformations of Middle Eastern urban environments and mobilities and question them in relation to the climate crisis. The contributions are based on empirical knowledge gathered in the Nile Delta, the Greater Cairo Region, Riyadh and Beirut. Without concessions to mainstream thinking, this book contributes to a better understanding of urban challenges, climate threats and policy responses in contexts marked by growing environmental inequalities

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

Violence Against Women (VAW) as Gendered Hate Crimes

Violence against women (VAW) is a deeply rooted form of misogyny that has always been universally predominant. It targets women and girls from all socio-cultural backgrounds and impacts their self-fulfillment at the personal and professional levels. The utmost manifestation of gendered hatred and sexism, VAW has evolved into a pandemic phenomenon. This paper is based on two main premises. Gender is a risk factor in crimes that women are exposed to, such as rape, femicide or even domestic violence. For this reason, violence against women in all its forms should be legally dealt with under the scope of hate crimes. This article aims at defining the various types of VAW and studying their in-depth impact on the victims. It analyses some statistics based on the United Nations and the World Health Organization reports. It historicizes the concept of hate crimes scrutinizing its relationship with VAW. It argues for the legal relabeling of violence against women (more particularly, femicide and rape) as subcategories of hate crimes, hence the urgency to a legal reform that would protect women worldwide from such a social plight