Exploration in Using Algae to Enhance Indoor Environment in the Tropical Climate

This paper discusses an exploration in algae application as a sun shading device for buildings. Four basic algae photobioreactors were constructed to investigate the effectiveness of Chlorella species to reduce direct sunlight transmission and solar heat gain in the Tropical climate of Kuala Lumpur. From the experiment, algae flat panel photobioreactor with direct carbon dioxide supply manage to reduce up to 44.9% of heat gain due to solar radiation on average. The overall solar transmission was also reduced to only 25% on average. These indicate that algae have the potential to be used as sun shading material for buildings

Deciphering the role of 27-hydroxycholesterol in neurodegeneration

Cholesterol is constantly attributed to neurodegenerative diseases including Alzheimer’s disease (AD). This is due to the association of high blood cholesterol and the consequences of cholesterol metabolism in these conditions. However the brain isolates itself from the peripheral cholesterol with the use of its impervious barrier, therefore how does cholesterol influence the brain? Converted into the oxidized form known as 27-hydroxycholesterol (27-OH), extracerebral cholesterol is able to circumvent this blood brain barrier and enter the brain’s refuge. Some studies point to the effect of this oxysterol on brain cells, indicating that this metabolite is more than a cholesterol intermediate. Herein, we dissect the role this cholesterol metabolite undertakes in the brain both in vitro and in vivo , while probing its influence on neurodegenerative diseases. In Paper I we elucidated the levels of 27-OH in both the cerebrospinal fluid (CSF) and plasma of mild cognitively impaired (MCI) and AD patients. In addition to correlating it to AD markers, we further investigated its relationship with the angiotensin-converting enzyme (ACE), which was increased in AD as previously described. Delving deeper uncovered 27-OH had more of a causal link than a mere correlation with the renin-angiotensin system (RAS) in the brain highlighted in Paper I and Paper II. This system, apart from being independent from the renal system, is involved in many processes in the brain including learning and memory. The repercussions of 27-OH on the brain RAS was further investigated in vivo in Paper II, in mice lacking the ability to produce 27-OH, and in humans. Furthermore, the effects of 27-OH were also observed in mice fed a high-fat diet, a connection that is further investigated in all the papers within this thesis. These results draw to attention the relationship between plasma cholesterol, hypert ension and neurodegeneration. In addition to affecting the spatial memory of mice, 27-OH reduced the levels of glucose uptake in their brains. Emphasized in Paper III, the mechanistic link between 27-OH and glucose metabolism was examined, explicating several therapeutic targets. The biomarker suitability of 27-OH was tested in a small proof of concept study utilizing 18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG PET). Results illustrated a negative correlation, thus having higher levels of 27-OH in the CSF is associated with lower glucose uptake levels in the brain of individuals with ramifications on memory. Inflammation is an important part of AD and is thought to occur very early in the disease progression. Moreover, peripherally 27-OH plays a part in mediating atherosclerosis via its proinflammatory actions. To this end, we hypothesized that 27-OH may have similar actions in the brain and the resulting data is presented in Paper IV. 27-OH increased the levels of the inflammatory mediat or S100A8 in addition to its receptor, Receptor for Advanced Glycation Endproduct (RAGE) and the downstream β-secretase 1 (BACE1) observed in several mice models. S100A8 was previously described by us to be increased in the brains of AD mice models and may accumulate even before amyloid plaque formation. This study therefore accentuates the function of 27-OH in propagating inflammation in the brain, a function recognized peripherally. Neurodegenerative diseases such as AD are debilitating conditions affecting the lives of millions; however to this date the causes of these overwhelming disorders remains unclear. While the levels of CSF 27-OH are likely to be increased in many AD patients, little is known as to the ramifications of this increase. Herein, we try to bridge this gap and propose several mechanistic links between blood cholesterol and neurodegenerative diseases while underscoring several plausible therapeutic targets, in an attempt to further empower our fight against AD

Is it possible to improve memory function by upregulation of the cholesterol 24S-hydroxylase (CYP46A1) in the brain? PLoS One

Abstract We previously described a heterozygous mouse model overexpressing human HA-tagged 24S-hydroxylase (CYP46A1) utilizing a ubiquitous expression vector. In this study, we generated homozygotes of these mice with circulating levels of 24OH 30-60% higher than the heterozygotes. Female homozygous CYP46A1 transgenic mice, aged 15 months, showed an improvement in spatial memory in the Morris water maze test as compared to the wild type mice. The levels of N-Methyl-DAspartate receptor 1, phosphorylated-N-Methyl-D-Aspartate receptor 2A, postsynaptic density 95, synapsin-1 and synapthophysin were significantly increased in the hippocampus of the CYP46A1 transgenic mice as compared to the controls. The levels of lanosterol in the brain of the CYP46A1 transgenic mice were significantly increased, consistent with a higher synthesis of cholesterol. Our results are discussed in relation to the hypothesis that the flux in the mevalonate pathway in the brain is of importance in cognitive functions

Mechanism of angiotensin converting enzyme (ACE) inhibition by Syzygium polyanthum wight (WALP.) leaves

Syzygium polyanthum is an ethnomedicinal plant used for the treatment of hypertension. This study investigates its antihypertensive property using angiotensin-converting enzyme (ACE) enzyme inhibition assay. This study aims to determine the ACE inhibitory activity of S. polyanthum leaves aqueous extract (ASP), its inhibition specificity and mechanism and the possible bioactive compound. ACE inhibition activity of ASP (1-1000 µg/ml) was tested and compared with standard drug, captopril (2.06 ng/ml). The inhibition mechanism was tested using zinc chloride and bovine serum albumin (BSA). The phytochemical composition in ASP was analyzed using Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry. In silico docking analysis was then performed between the major identified compounds in ASP with ACE. ASP at 100 μg/ml exhibited the highest inhibition activity (69.43 ± 0.60%) compared to MSP (41.63 ± 0.15%), EASP (9.62 ± 1.60%) and also HSP (45.40 ± 0.15%). From the dose-response curve for ACE inhibition activity of ASP, the inhibitory concentration of ASP that causes 50% of ACE inhibition activity (IC50) was 41 μg/ml. ACE inhibition activity by ASP was significantly reduced by the presence of BSA, indicative of interaction of ASP with albumin. ACE inhibition activity by ASP was not significantly affected with the presence of zinc chloride, indicating that its inhibitory activity on ACE was non-dependent of zinc at the ACE active site. There were 26 compounds identified in ASP with 1-galloyl-glucose identified as the major compound. Molecular docking analysis showed that 1-galloyl-glucose has lower binding energy (-7.7 kcal/mol) with ACE, as compared to standard drug, captopril (-5.6 kcal/mol); indicative of good interaction between 1-galloyl-glucose and ACE. In conclusion, this study showed that ACE inhibition activity by S. polyanthum leaves possibly occurs via protein precipitation and was non-dependent to the chelation with zinc at ACE active site, with 1-galloyl-glucose suggested as the potential bioactive compound

Angiotensin Converting Enzyme (ACE) inhibitionactivity by Syzygium polyanthum Wight (Walp.) leaves: mechanism and specificity

Introduction: One of the potential antihypertensive mechanisms include angiotensin converting enzyme (ACE) inhibition. So far, there is no in-depth study on the ACE inhibition activity of S. polyanthum, an ethnomedicinal plant used in treating hypertension. Thus, we aimed to study the ACE inhibition activity of S. polyanthum leaves by evaluating its potency, mechanism, and specificity. Methods: S. polyanthum leaves were macerated in a bath-sonicator with either water, methanol, ethyl acetate, and hexane producing aqueous (ASP), methanolic (MSP), ethyl acetate (EASP) and hexane (HSP) extracts. Each extract (100 μg/mL) were initially screened for ACE inhibition activity and then compared with standard drug, captopril (2.06 ng/mL), then the most active extract was further tested at 1 to 1000μg/ml. Inhibition mechanism was studied using zinc chloride and bovine serum albumin (BSA), while inhibition specificity was determined upon screening for α-chymotrypsin and trypsin inhibition activity. Results: ASP at 100 μg/ mL exhibited the highest inhibition activity (69.43 ± 0.60 %) compared to MSP (41.63 ± 0.15 %), EASP (9.62 ± 1.60 %), and HSP (45.40 ± 0.15 %). ASP showed dose-dependent ACE inhibition activity with IC50 of 41 μg/mL. ASP’s ACE inhibition activity was significantly reduced in the presence of BSA, but not upon the presence of zinc chloride. ASP did not significantly inhibit α-chymotrypsin and trypsin. Conclusion: This study showed that the enzyme inhibition activity by S. polyanthum leaves was specific towards ACE. The ACE inhibition possibly occurs via protein precipitation and was non-dependent to the chelation with zinc at ACE active site

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

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

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe