Three novel molecular rectangles of tetranuclear Cu(ii) with a variation in the flexible methylene chain length on the two opposite sides have been synthesized from a one pot self-assembly reaction in a methanol-water mixture under ambient conditions. Their solid state molecular structures are determined by single crystal X-ray diffractometry, while their structural integrity in the solution state is confirmed by electrospray mass spectrometry. With such a subtle variation, modulation of hydrophilicity inside the cavity of these molecular rectangles is achieved as evident from the water and methanol vapor sorption studies.Mechanochemical grinding of polycrystalline powders of the Prussian blue analogue (PBA) Mn[Co(CN)6]2/3□1/3·xH2O and K3Co(CN)6 consumes the latter and chemically modifies the former. A combination of inductively-coupled plasma and X-ray powder diffraction measurements suggests the hexacyanometallate vacancy fraction in this modified PBA is reduced by approximately one third under the specific conditions we explore. We infer the mechanochemically-driven incorporation of [Co(CN)6]3- ions onto the initially-vacant sites, coupled with intercalation of charge-balancing K+ ions within the PBA framework cavities. Our results offer a new methodology for the synthesis of low-vacancy PBAs.BACKGROUND Oral squamous cell carcinoma (OSCC) is the sixth most prevalent cancer worldwide, with low 5-year survival rate. To identify novel prognostic markers for OSCC and determine the immune and stromal landscape of OSCC, a risk signature for OSCC patients was constructed in this study. MATERIAL AND METHODS Immune and stromal scores for OSCC samples from the Genomic Data Commons Data Portal were computed to delineate the tumor microenvironment landscape of oral cancer based on the Estimation of STromal and Immune cells in MAlignant Tumours using Expression data algorithm. An immune score-based risk signature was constructed by combining random forest and support vector machine methods. Correlation analysis of risk signature gene expression and immune cell infiltration was conducted, and the distinguishing power of individual signature genes was evaluated by analyzing receiver operating characteristics (ROC) curves. Differentially enriched pathways between high and low risk groups were investigated via gene set variation analysis. ROC curves were plotted for signature genes to examine their ability to distinguish the recurrence and survival status of OSCC patients from GSE84846. RESULTS An immune score-related risk signature composed of ARMH1, F2RL2, AC004687.1, COL6A5, AC008750.1, RAB19, CRLF2, GRIP2, and FAM162B performed well in the prognostic stratification of OSCC patients and could effectively distinguish their survival status. Lists of pathways, including cytokine-cytokine receptor interaction and cell adhesion molecules displayed remarkable differential enrichment between high and low risk OSCC patients. CONCLUSIONS An immune score-based risk signature constructed presently may be useful to decide appropriate treatment options for individual OSCC patients.IQSEC2 is an X-linked gene highly expressed at the excitatory synapses where it plays a crucial role in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking and synaptic plasticity. To date, several males and females with severe to profound intellectual disability have been reported harbouring frameshift and nonsense variants in this gene, whereas a milder phenotype has been recognized in females carrying missense pathogenic variants. Here, we report two novel IQSEC2 variants in four females with psychiatric features and otherwise variable cognitive impairment. A female (case 1) with severe verbal language learning disorder and a psychotic episode (precipitated by exposure to anti-contraceptive pill) harboured a de novo pathogenic frameshift variant (c.1170dupG,p.Gln391Alafs*5), whereas the female proband of family 2, displaying severe psychomotor regression and complex psychiatric features carried a missense variant of uncertain significance (c.770G[A,p.Ser257Asn) that was maternally inherited. Skewed X-inactivation was noted in the carrier mother. The maternal aunt, affected by schizophrenia, was found to bear the same IQSEC2 variant. We discuss the variable clinical presentation of IQSEC2 spectrum disorders and the challenging genotype-phenotype correlation, including the possible role of environmental factors as triggers for decompensation. Our report highlights how psychiatric features may be the main clinical presentation in subtle IQSEC2 phenotype, suggesting that the prevalence of IQSEC2 mutations in patients with psychiatric disorders may be underestimated.Diabetes mellitus and its complications are major international health problems in which there are many limitations to the orthodox approaches in the treatment. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of diabetic medications, with a different mechanism of action that may reduce risk of cardiovascular complications. To evaluate the effect of SGLT2 inhibitor monotherapy on cardiovascular complications in patients with type-2 diabetes and to compare its effect with the first-line therapy, metformin. Eighty rats divided into four groups were used nondiabetic, diabetic nontreated, diabetic + met and diabetic + dapa. At the end, the arterial blood pressure and cardiac performance were assessed. Glycemic index, lipid profile, total antioxidant capacity, malondialdehyde, tumour necrosis factor a were measured. DNA changes were assessed from the hearts and aortae. Aortic tissue changes recorded using haematoxylin and eosin, Masson trichrome and iNOS immune stain. Glycemic index, lipid profile, oxidative stress and inflammatory parameters were significantly improved in both metformin and dapagliflozin treated groups with significant improvement in blood pressure and cardiac performance. Also, there were noticeable significant reduction in DNA fragmentation in aortic and cardiac tissues and reduction in collagen deposition and iNOS expression in aortic tissue. Dapagliflozin treatment results’ significantly surpassed improvement of metformin treatment nearly in all parameters. Total genomic DNA extraction proved that SGL2 inhibitor (dapagliflozin) has superior glycemic control and cardiovascular protective effect over metformin especially in type-2 diabetes with high fat intake.Rice blast disease, caused by Magnaporthe oryzae, is one of the most importance diseases of rice production worldwide. The keyrole of defense mechanism to combat this fungus in rice follows the gene-for-gene concept, which a plant resistant (R) gene product recognizes a fungal avirulent (AVR) effector and triggers the hypersensitive response. However, the AVR genes have been shown to be rapidly evolving resulting in high level of genetic diversity. The aims of this study were to examine the nucleotide sequence variation of AVR-Pita1 gene in Thai rice blast isolates and to identify the severity of blast disease using isogenic line of Pita gene. Seventy-six rice blast isolates collected from different parts of Thailand were used. Gene specific primers for AVR-Pita1 gene coding sequence were designed and used for identifying the genetic diversity of AVR-Pita1 gene by PCR amplification and sequencing. The obtained sequences were analysed for genetic variation and genetic relationship. Our results revealed the association between the sequence variations of AVR-Pita1 and selective forces from Pita gene. This phenomenon demonstrated the coevolution between rice blast resistant gene in rice and avirulent gene in blast fungus. The information about variation and evolutionary mechanisms of AVR gene obtained from this study can be used in rice blast resistant breeding programme.Powdery mildew (Blumeria graminis f. sp. Tritici, (Bgt)) is an important worldwide fungal foliar disease of wheat (Triticum aestivum) responsible for severe yield losses. The development of resistance genes and dissection of the resistance mechanism will therefore be beneficial in wheat breeding. The Bgt resistance gene PmAS846 was transferred to the hexaploid wheat lines N9134 from Triticum dicoccoides, and it is still one of the most effective resistance genes. Here, by RNA sequencing, we identified three co-expressed gene modules using pairwise comparisons and weighted gene co-expression network analysis during wheat-Bgt interactions compared with mock-infected plants. Hub genes of stress-specific modules were significantly enriched in spliceosomes, phagosomes, the mRNA surveillance pathway, protein processing in the endoplasmic reticulum, and endocytosis. Induced module genes located on chromosome 5BL were selected to construct a protein-protein interaction network. Several proteins were predicted as the key hub node, including Hsp70, DEAD/DEAH box RNA helicase PRH75, elongation factor EF-2, cell division cycle 5, ARF guanine-nucleotide exchange factor GNOM-like, and protein phosphatase 2C 70 protein, which interacted with several disease resistance proteins such as RLP37, RPP13 and RPS2 analogues. Gene ontology enrichment results showed that wheat could activate binding functional genes via an mRNA transcription mechanism in response to Bgt stress. Of these node genes, GNOM-like, PP2C isoform X1 and transmembrane 9 superfamily member 9 were mapped onto the genetic fragment of PmAS846 with a distance of 4.8 Mb. This work provides the foundations for understanding the resistance mechanism and cloning the resistance gene PmAS846.The relationship between the long noncoding RNA (lncRNA) expression and oesophageal cancer prognosis has been widely studied, but less consensus has been reached. We conducted this study to evaluate the relationship between the expression of lncRNAs and the prognosis and clinical pathology of oesophageal cancer. We conducted a systematic search of PubMed, EMBASE and Cochrane Library until 25 January 2019. Studies that evaluated the associations of a specific lncRNA with survival and/or clinicopathology of oesophageal cancer were included. Pooled hazard ratios (HRs), odds ratios (ORs), and corresponding 95% confidence intervals (CIs) were calculated using fixed or random-effect models. Sensitivity analysis was used to verify the stability of results. Publication bias was detected usingBegg tests and adjusted utilizing the trim-and-fill method if a bias existed. A total of 51 studies comprising 6510 patients and regarding 41 lncRNAs were included in the present systematic review and meta-analysis. The results showed that dysregulation of lncRNAs was associated with overall survival, disease-free survival, and progression-free survival. The expression of lncRNAs was related to some certain clinicopathological parameters of oesophageal cancer, including tumour size, T classification, lymph node metastasis, tumour node metastasis (TNM) stage and differentiation. Among these findings, lncRNA AK001796, CASC9, HOTAIR, MALAT1 and UCA1 were identified and were expected to be ideal biomarkers for the prognosis and clinicopathology of oesophageal cancer. Although significant publication bias was observed in some studies, the results were not changed after adjustment using the trim-and-fill method. Abnormal lncRNA-expression profiles could serve as a promising indicator for prognostic evaluation of patients with oesophageal cancer. The combination of these lncRNAs will contribute to clinical decision-making in the future.Tay-Sachs disease (TSD), a deficiency of b-hexosaminidase A (Hex A), is a rare but debilitating hereditary metabolic disorder. Symptoms include extensive neurodegeneration and often result in death in infancy. We report an in silico study of 42 Hex A variants associated with the disease. Variants were separated into three groups according to the age of onset infantile (n=28), juvenile (n=9) and adult (n=5). Protein stability, aggregation potential and the degree of conservation of residues were predicted using a range of in silico tools. We explored the relationship between these properties and the age of onset of TSD. There was no significant relationship between proteinstability and disease severity or between protein aggregation and disease severity. Infantile TSD had a significantly higher mean conservation score than nondisease associated variants. This was not seen in either juvenile or adult TSD. This study has established that the degree of residue conservation may be predictive of infantile TSD. It is possible that these more highly conserved residues are involved in trafficking of the protein to the lysosome. In addition, we developed and validated software tools to automate the process of in silico analysis of proteins involved in inherited metabolic diseases. Further work is required to identify the function of well-conserved residues to establish an in silico predictive model of TSD severity.CmFT homologous gene in muskmelon was obtained by homologous cloning, introducing CmFT gene by Agrobacterium mediated transformation. The results of subcellular localization showed that CmFT protein was expressed in cytoplasm and nucleus. qRTPCR results showed that the expression levels of AtLFY, AtFT, AtCO, AtFLC, AtSOC1 and AtAP1 were upregulated in the 35SMeFT Arabidopsis line. The CmFT gene was introduced into wild-type Arabidopsis by Agrobacterium-mediated transformation, and the growth status of T2 transgenic Arabidopsis thaliana and wild-type A. thaliana was observed. The results showed that wild-type Arabidopsis began to bolt on the 25th day after sowing, we can initially confirm that the FT gene of melon can promote the early flowering of melon in the growth and development of melon.Chromosomal behaviour during megasporogenesis and microsporogenesis has been studied in ornamental Delphinium ajacis L. Meiosis in female sex cell initiates later than male. The floral buds which carry egg mother cell (EMC) at diplotene stage has pollen mother cells (PMCs) at tetrad stage of meiosis suggesting protandry. Although the 16 chromosomes formed regular eight bivalents in both the sex cells, they differed in overall chiasma frequency which was 32.95% higher in EMCs and found to be 18.52 ± 2.12 per cell. In PMCs, the average chiasma frequency recorded was 13.93 ± 1.40 per cell. Interestingly, this variation in chiasma frequency was largely confined to the two large bivalents which shared 42.61% chiasma per EMC. The use of Q-Q plot, Box plot and Whisker plot showed departure in the chiasma frequency distributions in EMCs and PMCs from the normal distribution pattern. The difference in chiasma frequency in the two sex cells was significant at all levels as indicated by the low P values of 3.094 × 10-11 obtained from nonparametric test, i.e. Wilcoxon rank-sum test. It is suggested that the two different mechanisms of recombination are operational in the two sex cells, and the sex differences of chiasma frequency could have arisen due to differential epigenetic modifications of the chromatin which pattern the double-strand breaks, and the position and frequency of crossing over visible as chiasmata.Chimpanzees (Pan troglodytes), with a dwindling population size, are distributed across sub-Saharan Africa. They are classified into two biogeographical clusters comprising of four subspecies a western African cluster that includes P. t. verus and P. t. ellioti and a central/eastern African cluster that includes P. t. troglodytes and P. t. schweinfurthii. While the genetic distinctness of Nigeria-Cameroonian chimpanzees (P. t. ellioti) from western chimpanzees has been known for a while, the fine structures within P. t. ellioti population has remained under-studied. In this study, we developed the first ever ancestry informative marker (AIMs) panel that can detect the fine population structure within Nigeria-Cameroonian chimpanzees with high resolution. We compared four commonly used AIMs determining strategies, namely Infocalc algorithm, Wright’s FST, smart principal component analysis (SmartPCA) and ADMIXTURE to first identify the best approach and then developed an AIMs panel of 435 SNPs employing the consensus of the four approaches (n = 129),with additional supplements from the best two approaches (Infocalc and ADMIXTURE). To the best of our knowledge, we have developed the first-ever AIMs panel for chimpanzees, which can greatly aid in their planned reintroduction to the natural habitat, maintaining their genetic integrity through planned captive breeding, and in tracking illegal trading across the globe.Aim Pancreatic fistula (PF) and anastomotic leakage are significant complications of the pancreaticoduodenectomy (PD). The PF is considered as the root cause of other major complications of PD. The aim of the study was to investigate the risk factors underlying PF that occurred after PD and the effects of the PF on postoperative morbidity. Material and methods In this study, fifty patients who underwent classic PD were evaluated, retrospectively. Patients were divided into two groups as patients with PF and patients without PF. The following demographical, clinical and operative parameters were collected to evaluate the PF; age, gender, preoperative biochemical parameters, resection type, duration of the operation, patient’s comorbidities, amount of perioperative transfusion, localization of the tumour, texture of the residual pancreas, type of the anastomosis and the diameter of the pancreatic duct. Results A statistically significant relation was found between the texture of the remnant pancreatic parenchyma and PF (p less then 0.001). A significant relation was determined between PF and preoperative ALP, GGT, AST, ALT, hemoglobin levels and length of the hospitalization (p less then 0.05). In this study, we found that mortality, abdominal bleeding, bile leakage, intra-abdominal abscess were associated with reoperation and prolonged hospitalization. Conclusion The lack of internationally accepted definition of a fistula is an important issue. Preoperative high ALP, ALT, AST, GGT values, low hemoglobin values and soft texture of remnant pancreatic tissue were found to be related with PF that occurs after PD. Residual pancreatic tissue has been shown as an independent risk factor. Key words ISPGF, Pancreaticoduodenectomy, Pancreatic fistula, Risk factors.Introduction There has been increasing attention on preventing problematic youth substance use in light of concerns about rates of use and policy changes in Canada. Strengths-based approaches that emphasize protective factors, including positive mental health, are at the forefront of current prevention recommendations. However, there is a dearth of research on the association between positive mental health and substance use among youth. This study examines the associations between cannabis and alcohol use among youth and positive mental health as measured through the lens of self-determination theory. Methods Secondary analyses of the 2014/2015 Canadian Student Tobacco, Alcohol and Drugs Survey (CSTADS) were conducted. Participating Grade 7 to 12 students residing in Canada completed the Children’s Intrinsic Needs Satisfaction Scale (CINSS), which measures autonomy, competence and relatedness, and answered questions that measure past 30-day and more frequent cannabis use, alcohol use and binge-drinking. The associations between autonomy, competence and relatedness and substance use, stratified by sex, were examined using logistic regression. Results Fully adjusted models revealed that relatedness and competence were associated with lower odds of 30-day and more frequent cannabis use, alcohol use and binge-drinking. Higher autonomy was associated with higher odds of these behaviours. All associations were significant with the exception of competence and more frequent cannabis use among boys, and autonomy and more frequent alcohol use among girls. Conclusion The findings offer new evidence on the associations between positive mental health and substance use among youth, specifically how autonomy, competence and relatedness are associated with cannabis use, alcohol use and binge-drinking. This evidence can be used to inform health promotion and substance use prevention programs.Introduction This study describes the events and circumstances preceding children aged 16 years or younger being treated for cannabis poisoining in the emergency department (ED) of a Canadian pediatric hospital. Methods We extracted cannabis poisoning treated in the ED at British Columbia Children’s Hospital (BCCH) between 1 January, 2016 and 31 December, 2018, from the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) database. The poisonings were distinguished by the inadvertent or intentional ingestion of cannabis. We reviewed the hospital’s electronic health information system and the patients’ health records to obtain additional information on the context, including spatial and temporal characteristics. Results Of the 911 poisonings treated at BCCH, 114 were related to intentional cannabis use (12.5%). Fewer than 10 poisonings resulted from inadvertent ingestions by children and the median age for these was 3 years. All inadvertent ingestion occurred at home and involved cannabis belonging to the patient’s family. The vast majority of poisonings resulted from the intentional use of cannabis only (28.9%) or cannabis use with other psychoactive substances (co-ingestions; 71.1%). The median patient age was 15 years. Most patients reported consuming cannabis through inhalation with peers. Cannabis and co-ingestion poisonings were more often reported on weekdays than weekends. The consumption of cannabis leading to poisoning more often occurred in private residences. Patients with cannabis poisoning more often sought medical treatment themselves or were helped by their family. Conclusion The characteristics of cannabis poisonings among children are described for the three-year period prior to recreational cannabis legalization in Canada in order to set a baseline for future comparisons. Implications for improving injury prevention initiatives and policies are discussed.Introduction In October 2018, Canada legalized the nonmedical use of cannabis for adults. The aim of our study was to present a more recent temporal pattern of cannabis-related injuries and poisonings found in the electronic Canadian Hospitals Injury Reporting and Prevention Program (eCHIRPP) database and provide a descriptive summary of the injury characteristics of cannabis-related cases captured in a nine-year period. Methods We conducted a search for cannabis-related cases in the eCHIRPP database reported between April 2011 and August 2019. The study population consisted of patients between the ages of 0 and 79 years presenting to the 19 selected emergency departments across Canada participating in the eCHIRPP program. We calculated descriptive estimates examining the intentionality, external cause, type and severity of cannabis-related cases to better understand the contextual factors of such cases. We also conducted time trend analyses using Joinpoint software establishing the directionality of cannabisrally captured in this surveillance system and the limited number of sites found across Canada. With Canada’s recent amendments to cannabis regulations, ongoing surveillance of the health impacts of cannabis will be imperative to help advance evidence to protect the health of Canadians.Introduction Given the recent and impending changes to the legal status of nonmedical cannabis use in Canada, understanding the effects of cannabis use on the health care system is important for evaluating the impact of policy change. The aim of this study was to examine pre-legalization trends in hospitalizations for mental and behavioural disorders due to the use of cannabis, according to demographics factors and clinical conditions. Methods We assessed the total number of inpatient hospitalizations for psychiatric conditions with a primary diagnosis of a mental or behavioural disorder due to cannabis use (ICD-10-CA code F12) from the Hospital Mental Health Database for ten years spanning 2006 to 2015, inclusive. We included hospitalizations from all provinces and territories except Quebec. Rates (per 100 000 persons) and relative proportions of hospitalizations by clinical condition, age group, sex and year are reported. Results Between 2006 and 2015, the rate of cannabis-related hospitalizations in Canada doubled. Of special note, however, is that hospitalizations during this time period for those with the clinical condition code „mental and behavioural disorders due to use of cannabinoids, psychotic disorder” (F12.5) tripled, accounting for almost half (48%) of all cannabis-related hospitalizations in 2015. Conclusion Further research is required to investigate the reasons for the increase in hospitalizations for cannabis-related psychotic disorder. The introduction of high-potency cannabinoid products and synthetic cannabinoids into the illicit market are considered as possible factors.Introduction We conducted a pilot assessment of the feasibility of implementing the International Alcohol Control (IAC) Study in Ontario, Canada, to allow for future comparisons on the impacts of alcohol control policies with a number of countries. Methods The IAC Study questionnaire was adapted for use in the province of Ontario, and a split-sample approach was used to collect data. Data were collected by computer-assisted telephone interviewing of 500 participants, with half the sample each answering a subset of the adapted IAC Study survey. Results Just over half of the sample (53.6%) reported high frequency drinking (once a week or more frequently), while 6.5% reported heavy typical occasion drinking (8 drinks or more per session). Self-reported rates of alcohol-related harms from one’s own and others’ drinking were relatively low. Attitudes towards alcohol control varied. A substantial majority supported more police spot checks to detect drinking and driving, while restrictions on the number of alcohol outlets and increases in the price of alcohol were generally opposed. Conclusion This pilot study demonstrated that the IAC Study survey can be implemented in Canada with some modifications. Future research should assess how to improve participation rates and the feasibility of implementing the longitudinal aspect of the IAC Study. This survey provides additional insight into alcohol-related behaviours and attitudes towards alcohol control policies, which can be used to develop appropriate public health responses in the Canadian context.Introduction In 2017, Canada increased alcohol excise taxes for the first time in over three decades. In this article, we describe a model to estimate various effects of additional tax and price policies that are predicted to improve health outcomes. Methods We obtained alcohol sales and taxation data for 2016/17 for all Canadian jurisdictions from Statistics Canada and product-level sales data for British Columbia. We modelled effects of alternative price and tax policies – revenue-neutral taxes, inflation-adjusted taxes and minimum unit prices (MUPs) – on consumption, revenues and harms. We used published price elasticities to estimate impacts on consumption and revenue and the International Model for Alcohol Harms and Policies (InterMAHP) to estimate impacts on alcohol-attributable mortality and morbidity. Results Other things being equal, revenue-neutral alcohol volumetric taxes (AVT) would have minimal influence on overall alcohol consumption and related harms. Inflation-adjusted AVT would result in 3.83% less consumption, 329 fewer deaths and 3762 fewer hospital admissions. A MUP of $1.75 per standard drink (equal to 17.05mL ethanol) would have reduced consumption by 8.68% in 2016, which in turn would have reduced the number of deaths by 732 and the number of hospitalizations by 8329 that year. Indexing alcohol excise taxes between 1991/92 and 2016/17 would have resulted in the federal government gaining approximately $10.97 billion. We estimated this could have prevented 4000-5400 deaths and 43 000-56 000 hospitalizations. Conclusion Improved public health outcomes would be made possible by (1) increasing alcohol excise tax rates across all beverages to compensate for past failures to index rates, and (2) setting a MUP of at least $1.75 per standard drink. While reducing alcohol-caused harms, these tax policies would have the added benefit of increasing federal government revenues.Introduction The aim of this study was to document the scope of violations of the Canadian Radio-television and Telecommunications Commission (CRTC) „Code for Broadcast Advertising of Alcoholic Beverages” (CRTC Code) by drinking venues posting alcohol-related content on social media platforms, and to assess whether CRTC Code violations by drinking venues relate to their popularity among university students and to students’ drinking behaviours. Methods In phase 1 of the study, a probability sample of 477 students from four Canadian university responded to a questionnaire about their drinking and preferred drinking venues. In phase 2, a probability sample of 78 students assessed the compliance of drinking venues’ social media posts with the 17 CRTC Code guidelines. We pooled both datasets and linked them by drinking venues. Results Popular drinking venues were overwhelming posting alcohol-related content that contravenes the CRTC Code. Adjusted effect estimates show that a decrease in the mean level of compliance with the CRTC Code was significantly associated with a 1% increase in popularity score of drinking venues (t-test, p less then .001). With regard to drinking behaviours, a 1% increase in the overall mean level of compliance with the CRTC Code was associated with 0.458 fewer drinking days per week during a semester (t-test, p = .01), 0.294 fewer drinks per occasion (t-test, p = .048) and a lesser likelihood of consuming alcohol when attending a drinking venue (t-test, p = .001). Conclusion The results of this study serve as a reminder to territorial and provincial regulatory agencies to review their practices to ensure that alcohol advertising guidelines are applied and enforced consistently. More importantly, these results call for the adoption of federal legislation with a public health mandate that would apply to all media, including print, television and radio, digital and social.This summary article compares government revenue from the sale and distribution of alcohol to the societal costs caused by alcohol use for the year 2014. Statistics Canada data reported government revenue of $10.9 billion; however, this was offset by net societal costs of $14.6 billion, as reported by Canada’s national substance use surveillance system, the Canadian Substance Use Costs and Harms project. The societal costs include health care, economic loss of production, criminal justice and other direct costs. Though revenue from alcohol sales has been described as a benefit to public coffers, accounting that includes costs incurred shows that all provinces and territories in Canada are running an alcohol deficit, totalling $3.7 billion nationally.This special issue on substance use issues comes at a critical time for Canadian health policy makers and researchers. Most attention is currently focussed on the opioid crisis and the potential impacts of cannabis legalization. However, our most widely used and harmful substances continue to be alcohol and nicotine. Our policies to reduce harms from these substances are failing. While alcohol control policies are being gradually abandoned, opportunities to maximize the harm reduction potential of new, alternative and safer nicotine delivery devices are not being grasped. More generally, a greater focus is needed on harm reduction strategies that are informed by the experience of marginalized people with severe substance use-related problems so as to not exacerbate health inequities. In order to better inform policy responses, we recommend innovative approaches to monitoring and surveillance that maximize the use of multiple data sources, such as those used in the Canadian Substance Use Costs and Harms (CSUCH) project. Greater attention to precision in defining patterns of risky use and harms is also needed to support policies that more accurately reflect and respond to actual levels of substance use-related harm in Canadian society.In 2009 the EU Regulation 386/2009 established a new functional group of feed additives called „substances for reduction of the contamination of feed by mycotoxin”. Later, di-octahedral bentonite (1 m558) was authorised, as an anti-aflatoxin additive, being the only additive of this group authorised to date. This work aims to demonstrate the effectiveness of other bentonites, such as tri-octahedral bentonites, versus Fusarium-mycotoxins, since very few adsorbents have proved their effectiveness in relation to this group of mycotoxins. For this purpose, 7 bentonites (six of them tri-octahedral) and 7 commercial adsorbents, added at 0.02% (w/v), were assayed in an in vitro adsorption experiment using two simulated gastro-intestinal (GI) juices (pH 1.3 and 6.8) versus zearalenone (ZEN 0.1-5 mg/L), fumonisin B1 (FB1 1-10 mg/L) and deoxynivalenol (DON 2-10 mg/L). Mycotoxin adsorption data were fitted to Langmuir and Freundlich isotherms. In vitro adsorption experiments showed that ZEN and FB1 (in the latter case only in acid medium) were partially adsorbed, while the adsorption of DON was negligible. Moreover, the increase of adsorbent dose (up to 0.20%, w/v) significantly improved the in vitro adsorption of ZEN and FB1, reaching >90% of adsorption. The present work proposes the use of some tri-octahedral bentonites as feed additives for Fusarium-mycotoxin reduction.Objectives We aimed to investigate the protective effects of cyclosporin A (CsA) against ischemia-reperfusion (I/R) damage in a mouse ischemia model and the possible underlying mechanism. Methods Mice were divided equally into five groups Sham, I/R, Vehicle, I/R plus CsA (10 mg/kg), and I/R plus CsA (20 mg/kg). Nerve function scores, infarct volume, brain water content, and Evans blue (EB) leakage were evaluated, and western blotting was performed to analyze the changes in CypA, p-Akt, NF-κB, MMP-9, and Claudin-5 expression. Results CsA can attenuate I/R damage in a mouse ischemic stroke model, as indicated by improved neurological function scores and decreased infarct volume, brain water content, and EB leakage. Additionally, high-dose CsA showed better protective effects than low-dose. The molecular mechanisms underlying the effects of CsA were explored, and it was found that CsA could inhibit the increase in CypA, p-Akt, NF-κB, and MMP-9 protein expression after middle cerebral artery occlusion, while Claudin-5 expression was decreased. Discussion CsA showed potential as a neuroprotective drug for the treatment of ischemic stroke patients; besides interfering with the typical NF-κB signaling pathway, the Akt pathway may also be involved in the effects of CsA.Aims The purpose of our study was to analyze utilization trends and physician specialty distribution in spinal catheter angiography and magnetic resonance angiography in the Medicare fee-for-service population. Methods Data from the CMS Physician/Supplier Procedure Summary Master Files for 2004 to 2016 were used for this study. The Current Procedural Terminology version 4 codes for spinal magnetic resonance angiography (72159) and spinal catheter angiography (75705) were used to analyze the volumes of these procedures. Using Medicare’s 108 specialty code, we compared procedure volumes among physician specialties. Data analysis was performed using SAS version 9.3 for Windows. Results The volume of spinal catheter angiography performed was 4758 in 2004, peaked at 6869 in 2012, and dropped to 6656 in 2016. Overall, the volume of spinal catheter angiography increased by 40% from 2004 to 2016. Radiologists performed the majority of these procedures (3736 or 56.1%) in 2016, followed by neurosurgeons (2456 or 36.9%), and neurologists (346 or 5.2%). The spinal magnetic resonance angiography volume fluctuated between 0 and 1 from 2004 to 2009, then precipitously increased to 40 in 2010, peaked at 133 in 2011, and declined to 81 in 2016. The volume of spinal magnetic resonance angiography procedures increased by 8000% from 2004 to 2016, with radiologists performing the majority of them. Conclusion Our results show that spinal catheter angiography volumes continue to rise in the Medicare fee-for-service population, and are largely performed by radiologists, neurosurgeons, and neurologists. Although spinal magnetic resonance angiography volumes have started to increase, they comprise only a small fraction of studies performed for vascular evaluation of the spine.After a two-decade hiatus in which research on psychedelics was essentially halted, placebo-controlled clinical trials of psychedelic-assisted therapy for mental health conditions have begun to be published. We identified nine randomized, placebo-controlled clinical trials of psychedelic-assisted therapy published since 1994. Studies examined psilocybin, LSD (lysergic acid diethylamide), ayahuasca (which contains a combination of N,N-dimethyltryptamine and harmala monoamine oxidase inhibitor alkaloids), and MDMA (3,4-methylenedioxymethamphetamine). We compared the standardized mean difference between the experimental and placebo control group at the primary endpoint. Results indicated a significant mean between-groups effect size of 1.21 (Hedges g), which is larger than the typical effect size found in trials of psychopharmacological or psychotherapy interventions. For the three studies that maintained a placebo control through a follow-up assessment, effects were generally maintained at follow-up. Overall, analyses support the efficacy of psychedelic-assisted therapy across four mental health conditions – post-traumatic stress disorder, anxiety/depression associated with a life-threatening illness, unipolar depression, and social anxiety among autistic adults. While study quality was high, we identify several areas for improvement regarding the conduct and reporting of trials. Larger trials with more diverse samples are needed to examine possible moderators and mediators of effects, and to establish whether effects are maintained over time.Objective College students may not view sexual consent communication while under the influence of substances (i.e., alcohol and drugs) as problematic if media models the co-occurrence of these behaviors. The purpose of this study was to assess the types of consent cues used by characters who are and are not under the influence of substances in mainstream films. Method Four researchers inductively analyzed popular mainstream films (N = 50). Films were assessed for substance use and consent communication cues. Results Characters using substances were depicted using implicit verbal and explicit nonverbal consent cues more than characters who had not used substances. Conclusion Films may perpetuate cultural narratives that substance use can be part of the consent process and that consent is communicated differently when people have used substances. Prevention programs could include media literacy to address misleading messages college students may internalize about substance use and sexual consent communication.Although semantic system is composed of two distinctive processes (i.e., semantic knowledge and semantic control), it remains unknown in which way these two processes dissociate from each other. Investigating the white matter neuroanatomy underlying these processes helps improve understanding of this question. To address this issue, we recruited brain-damaged patients with semantic dementia (SD) and semantic aphasia (SA), who had selective predominant deficits in semantic knowledge and semantic control, respectively. We built regression models to identify the white matter network associated with the semantic performance of each patient group. Semantic knowledge deficits in the SD patients were associated with damage to the left medial temporal network, while semantic control deficits in the SA patients were associated with damage to the other two networks (left frontal-temporal/occipital and frontal-subcortical networks). The further voxel-based analysis revealed additional semantic-relevant white matter tracts. These findings specify different processing principles of the components in semantic system.Introduction Although many reports have analyzed the outcomes of central venous catheters (CVCs) in oncologic and oncohematologic patients, current guidelines do not routinely recommend a specific type of CVC over the other. Methods We retrospectively evaluated the outcomes of 178 patients with CVCs referred to an Italian specialized cancer center between January 2016 and December 2018. The analysis compares midterm peripherally inserted central venous catheters (PICCs) with long-term centrally inserted catheters, including totally implanted ports and tunneled catheters with central insertion (tCVCs). Results A total of 130 PICCs (73%) and 48 tCVCs (27%) were analyzed. The overall complication rate was significantly increased in the PICC cohort compared to the tCVC cohort (43.1% vs 25%, respectively; p = 0.037), leading to complication-related device removal in 30.8% of PICCs vs 12.5% of tCVCs (p = 0.013). No significant differences in terms of catheter-related thromboses (p = 0.676) or catheter-related infections (p = 0.140) were detected. Nonthrombotic obstructions were significantly higher in the PICC group compared to the tCVC cohort (p = 0.006). Overall complication-free survival was significantly longer for tCVCs compared to PICCs (hazard ratio [HR], 0.262; 95% confidence interval [CI], 0.128-0.536; p less then 0.0001), as well as obstruction-free survival (HR, 0.082; 95% CI, 0.018-0.372; p less then 0.0001). In multivariable analysis, the type of CVC was independently correlated with the occurrence of any complication (HR, 0.273; 95% CI, 0.135-0.553; p less then 0.0001). Conclusions This Italian real-world experience suggests that PICCs are associated with a higher risk of overall complications compared with tCVCs. Catheter choice in oncologic patients should be guided by treatment type and duration, risk-benefit assessment, patient preferences, and compliance.Purpose Urine dipstick analysis (UDA) is a useful tool in clinical practices. Abnormalities in UDA parameters have been observed as a result of extreme exercise. The exact incidence of UDA abnormalities, particularly proteinuria, as the result of running ultramarathons is unknown. The purpose of this study was to estimate the incidence of proteinuria and to identify the characteristics of those with proteinuria. Methods We conducted a prospective observational study using urine samples from volunteer athletes before and immediately after the Leadville Trail 100 Run in August 2014. There were 33 runners with both pre-race and post-race samples and a total of 70 provided post-race samples. Demographic information was collected as a part of a larger study. Results At least one abnormality was demonstrated in 89% of post-race urine samples. Twenty-one (30%) runners had post-race proteinuria (≥1+). Serum creatine kinase concentration (CK) was the only variable that was significantly correlated with the incidence of proteinuria in a multiple logistic regression model. Conclusion A majority of runners developed abnormalities in their UDA. Proteinuria was common and found to be associated with serum CK concentration.The purpose of this study was to use routine morphologic-based staining techniques to examine the histology of commercially labeled rawhide and rawhide-free dog chew products and compare the results to the product labeling. Ten dog chew products were examined by light microscopy using hematoxylin and eosin and Masson’s trichrome stains. The products were labeled by the manufacturer as rawhide, beef hide, beef chew/rawhide free, and rawhide free. Four of the products were composed of two separate materials, a main chew roll and a second substance (filler) which was coated on or between the layers of the main chew roll. These materials were processed independently. Microscopically, a variety of tissues and materials were identified including collagen, skeletal muscle, fat, plant material, and starch. The products and their fillers were separated into four distinct groups based on microscopic appearance. The components identified in eight of the products appeared consistent with the product labeling. Two products labeled as rawhide free appeared similar to the dermis and this was inconsistent with product labeling. Masson’s trichrome stain was not helpful in distinguishing tissue types in the tested products and this may have been due to the heat processing the products underwent during manufacturing. Bacteria and/or fungi were identified by microscopy in the H&E stained sections in four rawhide-free products.Objective To determine levels of Electronic Health Record (EHR) satisfaction in order to add to the body of knowledge and assist professionals in the college/university health field with system/vendor selection. Methods Nine health centers, all within highly selective colleges and universities, participated in this benchmarking study. Multidisciplinary staff (n = 316) received an anonymous 32-item survey to assess levels of agreement/satisfaction on statements pertaining to their EHR’s functionality. Results The EHRs most commonly used were Point and Click, Medicat, Allscripts, and EPIC. There was considerable variation on levels of user satisfaction/agreement within features among the EHR systems, but differences were not statistically significant. Conclusion No systems emerged as clear „winners” in terms of user satisfaction. Features were identified within systems that can be leveraged to meet specific care delivery and quality reporting needs among college/university health professionals, and could be considered in the use of EHRs by health services.Aims To compare the duration of anaesthesia, surgery, and postoperative hospitalisation, the proportion of tumours excised with complete histologic margins and immediate postoperative surgical site complications in dogs undergoing removal of cutaneous or subcutaneous soft tissue sarcomas (STS) by either carbon dioxide (CO2) laser or non-laser surgical excision methods. Methods Medical records of dogs that underwent surgical excision of cutaneous and subcutaneous STS at the University of Missouri between December 2004 and May 2018 were evaluated. The study population consisted of client-owned dogs that underwent CO2 laser (n=4) or non-laser (n=20) excision of a single STS. Data recorded included signalment, duration of anaesthesia, surgery and postoperative hospitalisation, tumour characteristics, completeness of histologic margins, postoperative complications, adjunctive therapy, and other procedures at the time of surgery. Results . There was no evidence of a difference in mean age, body weight or tumour size between groups. Similarly there was no evidence of a difference in the duration of anaesthesia or surgery, or in the proportion of dogs whose STS were removed with complete histologic margins between dogs whose STS was removed using laser or non-laser surgical excision methods. However, the duration of postoperative hospitalisation trended towards being longer for the laser excision group (p =0.061). Conclusions These data provide preliminary evidence that excision of cutaneous or subcutaneous STS with CO2 surgical laser is comparable to non-laser methods for the measured outcomes.Bordering the wealthy town of Apex, North Carolina, is a majority African-American neighborhood, Irongate Drive, without town water service, relying on private wells. Residents have long sought access to town water as their wells are running dry, but problems have not been systematically documented. Using a comprehensive survey and qualitative interviews, this study assesses the frequency of water shortages, uncovers the effects on daily lives, and reports on water source preferences. Surveys showed 80 percent of households experience water scarcity. Respondents reported not having enough water to flush toilets, shower, wash hands, or do laundry. Annual well maintenance costs averaged $1405; additional costs included dealing with water shortage and buying additional items to cope. More than 75 percent actively seek municipal water, and none oppose it. These results could inform assessments of impacts of water access disparities in similar peri-urban minority communities nationwide that remain excluded from nearby municipal services.Under solvothermal conditions, two new coordination polymers (CPs), namely [Cu(HL)]·2CH3CNn (1) and [Cu(HL)(bimb)]·4H2On (2) (H3L = tris(p-carboxyphenyl)phosphane oxide, bimb = 1,4-bis(imidazol-1-ylmethyl)benzene) were prepared. Their treatment activity on the human prostate cancer was evaluated through series of biological experiments. Firstly, the human prostate cancer cells proliferation was determined with Cell Counting Kit-8 (CCK-8) detection kit. The influence of compounds 1 and 2 on the cancer cells migration and invasion ability was measured with trans-well assay. Next, the important role of the EGF-R human prostate cancer cells was determined with western blotting. In the end, the activation of the HIPPO signaling pathway was detected with real-time reverse transcription polymerase chain reaction (RT-PCR).Cancer information seeking and scanning predict a variety of preventive health behaviors. However, previous work has rarely gauged seeking and scanning of specific cancer screening information. Moreover, colorectal cancer prevalence and mortality rates are higher among black than white Americans and it remains unclear if these groups differ in their cancer screening information acquisition patterns. We surveyed black and white Americans between 45 and 74 years of age to investigate rates, sources, and correlates of colorectal cancer screening (CRCS) information seeking and scanning. Black and white Americans had similar likelihoods of engaging in information seeking and scanning regarding CRCS. However, black Americans reported using significantly more sources for CRCS information seeking and scanning than did white Americans. Both screening test-specific information seeking and scanning are associated with stool-based tests, but only information seeking is associated with flexible sigmoidoscopy or colonoscopy. We discuss study implications for reaching out to different racial groups to promote colorectal cancer screening behavior.Objectives The present study was undertaken to investigate the effects and related mechanisms of hypothermia on oxidative stress and apoptosis caused by cardiac arrest (CA)-induced brain damage in rats. Methods The CA/CPR model was initiated by asphyxia. Body temperature in the normothermia and hypothermia groups was maintained at 37°C ± 0.2°C and 34°C ± 0.2°C, respectively, by surface cooling with an ice pack. First, neurological deficit scores (NDSs) were assessed, and then hippocampus samples were collected at 24 and 72 h after return of spontaneous circulation (ROSC). Results The NDSs of rats were significantly reduced after CA, and hypothermia ameliorated neurological deficits. Varying degrees of changes in cellular nuclei and mitochondria were observed in the hippocampus following CA; however, morphological changes became less apparent after therapeutic hypothermia. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were higher in the hippocampus at 24 h after ROSC. In contrast, hypothermia did not alter MDA content, while SOD activity further increased.