Liquid Glycan Array.

The M13 phage platform is a stable and monodisperse nanoscale carrier, which can be modified with different molecules by chemical conjugation strategies. Here, we describe M13 phage acylated on pVIII protein with a dibenzocyclooctyne reacting with azido glycan to yield 30-1500 copy numbers of glycan per phage and monitored by MALDI-TOF spectrometry to generate multivalent glycoconjugates that contain desired densities of glycans. We prepared the liquid glycan arrays (LiGA) such that both the structure and density of glycans were encoded in the DNA of the bacteriophage. The LiGA can be used to validate the binding properties of glycans to purified lectins and explore the effect of glycan density on such binding. From a mixture of multivalent glycan probes, LiGAs can also identify the glycoconjugates with optimal avidity necessary for binding to lectins on living cells in vitro and live animals in vivo.

Saccharomyces cerevisiae Δ9-desaturase Ole1 forms a supercomplex with Slc1 and Dga1.

Biosynthesis of the various lipid species that compose cellular membranes and lipid droplets depends on the activity of multiple enzymes functioning in coordinated pathways. The flux of intermediates through lipid biosynthetic pathways is regulated to respond to nutritional and environmental demands placed on the cell necessitating that there be flexibility in pathway activity and organization. This flexibility can in part be achieved through the organization of enzymes into metabolon supercomplexes. However, the composition and organization of such supercomplexes remain unclear. Here, we identified protein-protein interactions between acyltransferases Sct1, Gpt2, Slc1, Dga1, and the Δ9 acyl-CoA desaturase Ole1 in Saccharomyces cerevisiae. We further determined that a subset of these acyltransferases interact with each other independent of Ole1. We show that truncated versions of Dga1 lacking the carboxyl-terminal 20 amino acid residues are nonfunctional and unable to bind Ole1. Furthermore, charged-to-alanine scanning mutagenesis revealed that a cluster of charged residues near the carboxyl terminus was required for the interaction with Ole1. Mutation of these charged residues disrupted the interaction between Dga1 and Ole1 but allowed Dga1 to retain catalytic activity and to induce lipid droplet formation. These data support the formation of a complex of acyltransferases involved in lipid biosynthesis that interacts with Ole1, the sole acyl-CoA desaturase in S. cerevisiae, that can channel unsaturated acyl chains toward phospholipid or triacylglycerol synthesis. This desaturasome complex may provide the architecture that allows for the necessary flux of de novo-synthesized unsaturated acyl-CoA to phospholipid or triacylglycerol synthesis as demanded by cellular requirements.

Occurrences, sources, fate and impacts of plastic on aquatic organisms and human health in global perspectives: What Bangladesh can do in future?

Bangladesh is not an exception to the growing global environmental problem of plastic pollution. Plastics have been deemed a blessing for today's world thanks to their inexpensive production costs, low weight, toughness, and flexibility, but poor biodegradability and massive misuse of plastics are to blame for widespread contamination of the environmental components. Plastic as well as microplastic pollution and its adverse consequences have attracted significant investigative attention all over the world. Plastic pollution is a rising concern in Bangladesh, but scientific studies, data, and related information are very scarce in numerous areas of the plastic pollution problem. The current study examined the effects of plastic and microplastic pollution on the environment and human health, and it examined Bangladesh's existing knowledge of plastic pollution in aquatic ecosystems in light of the rapidly expanding international research in this field. We also made an effort to investigate the current shortcomings in Bangladesh's assessment of plastic pollution. This study proposed several management approaches to the persistent plastic pollution problem by analyzing studies from industrialized and emerging countries. Finally, this work pushed investigators to investigate Bangladesh's plastic contamination thoroughly and develop guidelines and policies to address the issue.

Antibiotic resistance pattern of microorganisms causing urinary tract infection: a 10-year comparative analysis in a tertiary care hospital of Bangladesh.

BACKGROUND: Antimicrobial resistance is an emerging concern globally in recent years. Management of common infectious diseases like urinary tract infection (UTI) has become challenging. In this context, the purpose of this study is to compare the shifting trends in bacteriology and antibiotic resistance pattern among uropathogens to similar studies conducted at various times in Bangladesh. METHODS: It was a cross-sectional study conducted at the CUMILLA MEDICAL COLLEGE HOSPITAL'S MEDICINE DEPARTMENT in three phases (2011, 2016, 2021. Patients who visited the outpatient and inpatient departments of the study center with symptoms suggestive of a urinary tract infection were undergone urine culture. Those who yielded positive growth in urne culture were finally included in the study. RESULTS: Escherichia coli (62% in 2021, 86% in 2016 and 76% in 2011) and Klebsiella species (11% in 2021, 10% in 2016 and 11% in 2011) were the most frequently isolated bacteria. Overall, in Gram-negative organisms, resistance was almost > 50% to all the tested antibiotics. Very high frequency of resistance ranging from 66.67 to 93.75% to cotrimoxazole, ciprofloxacin, cefuroxime, cephradine, amoxicillin and nalidixic acid, moderately high resistance to ceftriaxone (64.52%) and gentamicin (53.13%) and low resistance to nitrofurantoin (25.38%) were shown by the most commonly isolated organisms. Resistance to common antibiotics has been significantly increased over time in the isolated orgnaisms, especially in carbapenem and aminoglycoside group. CONCLUSION: Resistance of uropathogens against conventional antibiotics used to treat UTI is high and the proportion has been increased over time. The situation might be grave in upcoming years if rational consumption of antibiotics is not warranted.

Development of Acute Myocardial Infarction Mortality and Readmission Models for Public Reporting on Hospital Performance in Canada.

BACKGROUND: Given changes in the care and outcomes of acute myocardial infarction (AMI) patients over the past several decades, we sought to develop prediction models that could be used to generate accurate risk-adjusted mortality and readmission outcomes for hospitals in current practice across Canada. METHODS: A Canadian national expert panel was convened to define appropriate AMI patients for reporting and develop prediction models. Preliminary candidate variable evaluation was conducted using Ontario patients hospitalized with a most responsible diagnosis of AMI from April 1, 2015 to March 31, 2018. National data from the Canadian Institute for Health Information was used to develop AMI prediction models. The main outcomes were 30-day all-cause in-hospital mortality and 30-day urgent all-cause readmission. Discrimination of these models (measured by c-statistics) was compared with that of existing Canadian Institute for Health Information models in the same study cohort. RESULTS: The AMI mortality model was assessed in 54,240 Ontario AMI patients and 153,523 AMI patients across Canada. We observed a 30-day in-hospital mortality rate of 6.3%, and a 30-day all-cause urgent readmission rate of 10.7% in Canada. The final Canadian AMI mortality model included 12 variables and had a c-statistic of 0.834. For readmission, the model had 13 variables and a c-statistic of 0.679. Discrimination of the new AMI models had higher c-statistics compared with existing models (c-statistic 0.814 for mortality; 0.673 for readmission). CONCLUSIONS: In this national collaboration, we developed mortality and readmission models that are suitable for profiling performance of hospitals treating AMI patients in Canada.

CONTEXTE: Compte tenu des changements apportés au cours des dernières décennies aux soins des patients ayant subi un infarctus aigu du myocarde (IAM) et aux issues d'un tel événement, nous avons voulu élaborer des modèles prédictifs pouvant servir à calculer de façon précise les résultats relatifs à la mortalité et aux réadmissions, ajustés selon les risques, pour les hôpitaux dans la pratique actuelle au Canada. MÉTHODOLOGIE: Un groupe national d'experts canadiens a été mis sur pied et a reçu le mandat de définir les critères appropriés applicables aux patients ayant subi un IAM aux fins de déclaration des cas et d'élaborer des modèles prédictifs. L'évaluation préliminaire des variables proposées a été effectuée à partir de patients hospitalisés en Ontario entre le 1er avril 2015 et le 31 mars 2018 chez lesquels l'IAM était le diagnostic principal à l'origine de l'hospitalisation. Les données à l'échelle nationale de l'Institut canadien d'information sur la santé (ICIS) ont été utilisées pour élaborer des modèles prédictifs d'IAM. Les deux principales issues évaluées étaient la mortalité hospitalière toutes causes confondues à 30 jours et la réadmission urgente toutes causes confondues à 30 jours. Le pouvoir discriminant de ces modèles (mesuré par la statistique C) a été comparé à celui des modèles existants de l'ICIS dans la même cohorte de l'étude. RÉSULTATS: Le modèle de mortalité par IAM a été évalué auprès de patients ayant subi un IAM, dont 54 240 en Ontario et 153 523 dans l'ensemble du Canada. Nous avons observé un taux de mortalité hospitalière à 30 jours de 6,3 % et un taux de réadmission urgente à 30 jours toutes causes confondues de 10,7 % au Canada. Le modèle canadien final de prédiction de la mortalité par IAM était constitué de 12 variables et avait une statistique C de 0,834. Pour la réadmission, le modèle comportait 13 variables et présentait une statistique C de 0,679. Le pouvoir discriminant des nouveaux modèles d'IAM présentait une statistique C supérieure à celle des modèles existants (statistique C de 0,814 pour la mortalité et de 0,673 pour la réadmission). CONCLUSIONS: Dans le cadre de cette collaboration nationale, nous avons élaboré des modèles prédictifs de la mortalité et de la réadmission hospitalière qui permettent d'établir un profil des résultats obtenus par les hôpitaux traitant des patients ayant subi un IAM au Canada.

Correction to: Factors Associated with Mood Disorder Diagnosis Among a Population Based Cohort of Men and Women Living With and Without HIV in British Columbia Between 1998 and 2012.

Using data from the Comparison of Outcomes and Service Utilization Trends (COAST) study we examined factors associated with mood disorder diagnosis (MDD) among people living with HIV (PLHIV) and HIV-negative individuals in British Columbia, Canada. MDD cases were identified between 1998 and 2012 using International Classification of Disease 9 and 10 codes. A total of 491,796 individuals were included and 1552 (23.7%) and 60,097 (12.4%) cases of MDD were identified among the HIV-positive and HIV-negative populations, respectively. Results showed HIV status was associated with greater odds of MDD among men and lower odds among women. Among PLHIV, MDD was significantly associated with: identifying as gay, bisexual or other men who have sex with men compared to heterosexuals; higher viral load; history of injection drug use; and concurrent anxiety, dysthymia, and substance use disorders. Findings highlight the need for comprehensive and holistic HIV and mental health care.

Factors Associated with Mood Disorder Diagnosis Among a Population Based Cohort of Men and Women Living With and Without HIV in British Columbia Between 1998 and 2012.

Using data from the Comparison of Outcomes and Service Utilization Trends (COAST) study we examined factors associated with mood disorder diagnosis (MDD) among people living with HIV (PLHIV) and HIV-negative individuals in British Columbia, Canada. MDD cases were identified between 1998 and 2012 using International Classification of Disease 9 and 10 codes. A total of 491,796 individuals were included and 1552 (23.7%) and 60,097 (12.4%) cases of MDD were identified among the HIV-positive and HIV-negative populations, respectively. Results showed HIV status was associated with greater odds of MDD among men and lower odds among women. Among PLHIV, MDD was significantly associated with: identifying as gay, bisexual or other men who have sex with men compared to heterosexuals; higher viral load; history of injection drug use; and concurrent anxiety, dysthymia, and substance use disorders. Findings highlight the need for comprehensive and holistic HIV and mental health care.

Health-adjusted life expectancy in HIV-positive and HIV-negative men and women in British Columbia, Canada: a population-based observational cohort study.

BACKGROUND: We sought to understand whether people living with HIV (PLHIV) ever on highly active antiretroviral therapy (ART) follow a pattern where morbidity is compressed into the last years of life or lessened as people age. We aimed to estimate health-adjusted life expectancy (HALE) among adults living with and without HIV, and examine dependency between causes of comorbidities. METHODS: The Comparative Outcomes and Service Utilization Trends (COAST) study is a retrospective cohort of adults (≥20 years) including all known PLHIV and a 10% random sample of the general population of British Columbia, and with longitudinal data spanning from April 1, 1996, to Dec 31, 2012. We determined the prevalence of select comorbidities (cardiovascular, respiratory, liver, and renal diseases, and non-AIDS defining cancers because of their high prevalence among PLHIV) by age and sex by use of case-finding algorithms. Deaths were obtained from a vital event registry from British Columbia, Canada. Comorbid-specific HALE was estimated from 20 years of age by HIV status and sex. For each comorbidity, a healthy state was defined as the proportion of life expectancy comorbid-free, and was adjusted on the probability of occurrence of other different comorbidities. The sensitivity of HALE estimates was assessed to the sequencing of select comorbidities for the dependent comorbidity adjustments. FINDINGS: Our sample consisted of electronic health records from 9310 HIV-infected and 510 313 uninfected adults over the period April 1, 1996, to Dec 31, 2012. These individuals contributed 49 605 deaths and 5 576 841 person-years over the study period. At exactly age 20 years, HALE was about 31 years (SD 0·16) among men living with HIV and 27 years (0·16) among women living with HIV. In the HIV-negative population, HALE was around 58 years (SD 0·02) for men and 63 years (0·02) for women. These results seem independent of ordering. However, PLHIV, particularly women living with HIV, had much shorter overall life expectancies than did their HIV-negative counterparts in the general population [29·1 years (SD 0·1) vs 65·4 years (0·1)], and thus spent less time in a healthy state. INTERPRETATION: Although we noted little differences in the levels of morbidity compression by HIV status, PLHIV-especially women living with HIV-spent less time in a healthy state. Expanded service delivery interventions to address complex care needs of ageing PLHIV are crucial to address shorter life expectancies, and improve their healthy states. FUNDING: Canadian Institutes of Health Research.

First Occurrence of Diabetes, Chronic Kidney Disease, and Hypertension Among North American HIV-Infected Adults, 2000-2013.

Background: There remains concern regarding the occurrence of noncommunicable diseases (NCDs) among individuals aging with human immunodeficiency virus (HIV), but few studies have described whether disparities between demographic subgroups are present among individuals on antiretroviral therapy (ART) with access to care. Methods: We assessed the first documented occurrence of type 2 diabetes mellitus (DM), chronic kidney disease (CKD), and treated hypertension (HTN) by age, sex, and race within the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). HIV-infected adults (≥18 years) who initiated ART were observed for first NCD occurrence between 1 January 2000 and 31 December 2013. Cumulative incidences as of age 70 were estimated accounting for the competing risk of death; Poisson regression was used to compare rates of NCD occurrence by demographic subgroup. Results: We included >50000 persons with >250000 person-years of follow-up. Median follow-up was 4.7 (interquartile range, 2.4­8.1) years. Rates of first occurrence (per 100 person-years) were 1.2 for DM, 0.6 for CKD, and 2.6 for HTN. Relative to non-black women, the cumulative incidences were increased in black women (68% vs 51% for HTN, 52% vs 41% for DM, and 38% vs 35% for CKD; all P < .001); this disparity was also found among men (73% vs 60% for HTN, 44% vs 34% for DM, and 30% vs 25% for CKD; all P < .001). Conclusions: Racial disparities in the occurrence of DM, CKD, and HTN emphasize the need for prevention and treatment options for these HIV populations receiving care in North America.

Postmarket safety of drugs approved by Health Canada on the basis of clinical and surrogate outcomes: a cohort study.

BACKGROUND: Health Canada approves drugs on the basis of evidence from clinical trials using clinical or surrogate outcomes. This study compares the postmarket safety of these 2 groups of drugs. METHODS: Information about whether clinical or surrogate outcomes were used and the date of market approval were obtained from Health Canada's Summary Basis of Decision documents issued from Jan. 1, 2005, to Dec. 31, 2014. Safety warnings and the dates they were issued were identified through advisories on the MedEffect Canada website. Kaplan-Meier survival curves were calculated to determine the likelihood that drugs in the clinical and surrogate outcome groups would receive a serious safety warning. The time from market authorization to first serious safety warning was compared for the 2 groups of drugs. RESULTS: A total of 124 drugs were approved by Health Canada using clinical outcomes and 114 using surrogate outcomes. Kaplan-Meier curves did not differ between the 2 groups (p < 0.9). The median time from market authorization to first serious safety warning was 722 days in the clinical outcome group and 818 days in the surrogate outcome group (difference 96 days, 95% confidence interval -295 to 425). INTERPRETATION: We found no statistically significant difference in postmarket safety between drugs approved using clinical outcomes and those approved using surrogate outcomes. Because drugs in the surrogate outcome group are approved before their benefit:harm ratio is fully established, these drugs should be used with caution until their clinical benefits are better understood.

Assessing the accuracy of death records and pre-mortem clinical diagnoses in children diagnosed with brain tumors: A retrospective chart review of children in British Columbia, Canada.

The advantages of autopsy have been demonstrated in pediatric oncology; however, it is unknown to what extent the utility of autopsy is in deceased children diagnosed with a pediatric brain tumor (PBT). The purpose of this study was to describe the frequency of autopsy, prevalence of clinical discrepancies, and accuracy of cancer registry death records for deceased children diagnosed with a PBT in British Columbia, Canada. A retrospective chart review was performed of medical records and autopsy reports of pediatric patients diagnosed with a PBT that died between 1982 and 2012 in British Columbia. Clinical discrepancies between pre- and post-mortem findings were classified based on a modified classification system of the Goldman Criteria. The overall autopsy rate was 15.5% (32 of 206) during 1982-2012, with a significant (P=0.001) decrease of 22.4% observed between decade 1 (32.8%) and decade 2 (10.4%) and a further slight decrease (4.5%) between decade 2 (10.4%) and decade 3 (5.9%) (P=0.379). A third of patients had discrepancies between pre-mortem and post-mortem clinical diagnoses, with slightly over 10% of these cases revealing information that would have altered the probability of survival had it been known prior to death. More than half (59.3%) of cases had discordant cause of death as recorded in the cancer registry when compared to autopsy findings. Autopsy for children diagnosed with a PBT can provide health care professionals with important information about the accuracy of their diagnoses and evaluate the efficacy of therapy.