Medicinska gljiva Lignosus rhinocerus svojim imunomodulacijskim učinkom i reguliranjem signalnog puta posredovanog faktorom nekroze tumora uzrokuje apoptozu i zaustavlja stanični ciklus stanica karcinoma usne šupljine ORL-204

Research background. Tiger milk mushroom (Lignosus rhinocerus) is a medicinal mushroom that is geographically distributed in the region of South China, Thailand, Malaysia, Indonesia, Philippines and Papua New Guinea. Consumption of its sclerotium has been reported to treat various ailments. However, its anticancer potential towards oral cancer cell lines is yet to be determined considering the traditional method of its consumption by biting/chewing of the sclerotium. Experimental approach. Mushroom sclerotial powder of cultivar TM02® was extracted and fractionated in a chromatographic column prior to cytotoxicity testing against a panel of human oral cancer cell lines. The capability of the identified bioactive fraction in regulating several molecules associated with its tumour necrosis factor (TNF) pathway was investigated. Results and conclusions. 2,5-Diphenyl-2H-tetrazolium bromide (MTT) proliferation assay indicated that cell lines ORL-48 (derived from gingiva), ORL-188 (derived from the tongue) and ORL-204 (derived from buccal mucosa) were inhibited by cold water extract of L. rhinocerus sclerotia and its high-molecular-mass fraction (HMM) in varying degrees with ORL-204 being most affected. Hence, the treatment of ORL-204 with HMM mushroom extract was further investigated. HMM mushroom extract induced apoptosis and G0/G1 phase cell cycle arrest through caspase-3/7 cleavage. Activities of MIP2 and COX-2 were downregulated by 0.2- and 4.6-fold respectively in the HMM mushroom extract-treated ORL-204 cells. Novelty and scientific contribution. Using ORL-204, we showed that HMM mushroom extract may act via the TNF pathway at various network sites as a potential dietary compound for cancer prevention and natural adjunct therapeutic to conventional cancer treatment.Pozadina istraživanja. Medicinska gljiva Lignosus rhinocerus rasprostranjena je na području južne Kine, Tajlanda, Malezije, Indonezije, Filipina i Papua Nove Gvineje. Sklerocij gljive koristi se za liječenje različitih oboljenja. Međutim, dosad još nije ispitan antikacerogeni učinak sklerocija ove medicinske gljive, koja se tradicionalno konzumira tako da se grize odnosno žvače, na stanice karcinoma usne šupljine. Eksperimentalni pristup. Ekstrakt praha sklerocija kultivara gljive TM02® frakcioniran je pomoću kromatografske kolone, te je zatim ispitan njegov citokosični učinak na različite stanične linije humanih karcinoma usne šupljine. Ispitana je sposobnost bioaktivne frakcije da regulira molekule koje sudjeluju u sintezi faktora nekroze tumora (TNF). Rezultati i zaključci. Ispitivanjem proliferacije stanica pomoću testa redukcije 2,5-difenil-2H-tetrazolijeva bromida (MTT) utvrđeno je da ekstrakt sklerocija L. rhinocerus dobiven hladnom vodom, i to frakcija velike molekulske mase, u različitoj mjeri inhibira rast staničnih linija ORL-48 (izoliranih iz desni), ORL-188 (izoliranih ih jezika), a ponajviše onih linije ORL-204 (izoliranih iz sluznice obraza). Stoga smo dodatno istražili učinak ekstrakta gljive velike molekulske mase na staničnu liniju ORL-204. Ektrakt je potaknuo apoptozu i zaustavio stanični ciklus u fazi G0/G1 cijepanjem kaspaze 3/7. U stanicama ORL-204 tretiranim ekstraktom gljive velike molekulske mase smanjila se aktivnost enzima MIP2 za 0,2 puta, a enzima COX-2 za 4,6 puta. Novina i znanstveni doprinos. Pomoću stanične linije ORL-204 pokazali smo da ekstrakt medicinske gljive velike molekulske mase može djelovati na sintezu faktora nekroze tumora, te se upotrijebiti kao prirodni dodatak prehrani za prevenciju razvoja karcinoma ili kao dodatak konvencionalnom liječenju karcinoma

Mindful gratitude journaling: psychological distress, quality of life and suffering in advanced cancer: a randomised controlled trial

Context Numerous studies have shown that gratitude can reduce stress and improve quality of life. Objective Our study aimed to examine the effect of mindful gratitude journaling on suffering, psychological distress and quality of life of patients with advanced cancer. Methods We conducted a parallel-group, blinded, randomised controlled trial at the University of Malaya Medical Centre, Malaysia. Ninety-two adult patients with advanced cancer, and an overall suffering score ≥4/10 based on the Suffering Pictogram were recruited and randomly assigned to either a mindful gratitude journaling group (N=49) or a routine journaling group (N=43). Results After 1 week, there were significant reductions in the overall suffering score from the baseline in both the intervention group (mean difference in overall suffering score=−2.0, 95% CI=−2.7 to −1.4, t=−6.125, p=0.000) and the control group (mean difference in overall suffering score=−1.6, 95% CI=−2.3 to −0.8, t=−4.106, p=0.037). There were also significant improvements in the total Hospital Anxiety and Depression Scale score (mean difference=−3.4, 95% CI=−5.3 to −1.5, t=−3.525, p=0.000) and the total Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being score (mean difference=7.3, 95% CI=1.5 to 13.1, t=2.460, p=0.014) in the intervention group after 7 days, but not in the control group. Conclusion The results provide evidence that 7 days of mindful gratitude journaling could positively affect the state of suffering, psychological distress and quality of life of patients with advanced cancer

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

RET Mutational Spectrum in Hirschsprung Disease: Evaluation of 601 Chinese Patients

Rare (RVs) and common variants of the RET gene contribute to Hirschsprung disease (HSCR; congenital aganglionosis). While RET common variants are strongly associated with the commonest manifestation of the disease (males; short-segment aganglionosis; sporadic), rare coding sequence (CDS) variants are more frequently found in the lesser common and more severe forms of the disease (females; long/total colonic aganglionosis; familial)

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

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Assessment of Brackish Shrimp Farming in Sarawak and its impacts to the environment

Water discharges from shrimp farms have been known to contain high loads of nutrients and suspended solids. Although the receiving water bodies have a capacity to dilute and assimilate the pollutant to a certain extent, eutrophication and other environmental problems could occur if that capacity is exceeded. The aim of this study was to assess the effects of different management practices in two brakish shrimp farms in Sarawak and input of nutrients into the surrounding environment. Water quality (physical and chemical) was monitored in two commercial shrimp farms, which practised open system and semi-closed system, and in estuaries adjacent to the farm. Nutrients flushed from the shrimp ponds into the receiving waters during water exchange were also quantified. Results showed that in both farms, pond water have relatively higher concentrations of ammonia nitrogen, total suspended solids and excessive growth of phytoplankton as the shrimp culture progressed. Water exchange rate of 15% of pond water volume in semi-closed system was sufficient in improving water quality of the pond, instead of 30% of water pond volume. The results of this study also indicated that semi-closed system of shrimp farming is more environmental friendly compared to the open-system based on water exchange practice and the contributions of nutrients to the adjacent water bodies. Farms practising daily water exchange is more destructive to the environmental because they discharge more pollutants into the receiving waters

A two-stage optimization method for Vehicle to Grid coordination considering building and Electric Vehicle user expectations

The formulation of the Vehicle to Grid (V2G) scheme should ideally consider both Electric Vehicle (EV) and building owners’ viewpoints. From the building owner’s viewpoint, the EVs should be present in the building and participate consistently to deliver the required power. From the EV owners’ viewpoint, participating in the V2G scheme should provide economic incentives while not compromising their travel needs. However, those proposed V2G algorithms up to this point in time had not considered any corrections required in response to unplanned changes in the EV travel plan. In this paper, a Two-stage optimization technique is proposed to determine the charging and discharging schedule for EVs participating in a vehicle-to-grid (V2G) programme at an office building. The EV owners’ travel convenience is focused with more attention in the proposed model by giving them two V2G options. Firstly, day-ahead optimization (DAO) is applied, based on the expected building load profile and EV behaviour, the optimal charging or discharging control of the EVs is obtained in order to save electricity bills by minimizing the maximum demand of the building. Subsequently, a real-time optimization (RTO) is performed to adjust the V2G operation based on actual vehicle behaviours which usually deviate from their estimations. Simulations are conducted and the preliminary results show that the proposed technique is able to adjust the EV charging or discharging in real-time with the aid of the day-ahead stage. The proposed model manages to capture a new ideal optimal maximum demand point and maintain the EV SOC profile as planned from the DAO stage in real-time when prediction deviation occurs. In addition, a comprehensive cost–benefit analysis in utilizing V2G in peak load reduction is also performed to gain insight into the potential savings and discharging rewards attributable to the building and EV owner respectively