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"Khalili, Kevin"
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Influence of water stress on biomass production by isolates of an ericoid mycorrhizal endophyte of Woollsia pungens and Epacris microphylla (Ericaceae)
The influence of water stress on growth of six isolates of an anamorphic ericoid mycorrhizal fungal endophyte from two Australian Ericaceae hosts was investigated. Biomass production was determined in liquid media amended with NaCl or polyethylene glycol to give osmotic potentials of -0.05 to -2.24 MPa. Regardless of the osmoticum, biomass yields of all isolates at the highest level of imposed water stress (-2.24 MPa) did not differ significantly from, or were significantly higher than, those at the lowest level of water stress. The data suggest that the endophyte isolates possess considerable resistance to water stress and may be of functional importance to their plant hosts under water-stress conditions.
Journal Article
Real-life use of tolvaptan in ADPKD: a retrospective analysis of a large Canadian cohort
Tolvaptan is the first disease-modifying drug proven to slow eGFR decline in high-risk patients with ADPKD. However, barriers from the patient perspective to its use in real-life settings have not been systemically examined in a large cohort. This was a single-center, retrospective study of 523 existing or new patients with ADPKD followed at the Center for Innovative Management of PKD in Toronto, Ontario, between January 1, 2016 to December 31, 2018. All patients underwent clinical assessment including total kidney volume measurements and Mayo Clinic Imaging Class (MCIC). Those who were deemed to be at high risk were offered tolvaptan with their preference (yes or no) and reasons for their choices recorded. Overall, 315/523 (60%) patients had MCIC 1C-1E; however, only 96 (30%) of them were treated with tolvaptan at their last follow-up. Among these high-risk patients, those not treated versus treated with tolvaptan were more likely to have a higher eGFR (82 ± 26 vs. 61 ± 27 ml/min/1.73 m
2
), CKD stages 1–2 (79% vs. 41%), and MCIC 1C (63% vs. 31%). The most common reasons provided for not taking tolvaptan were lifestyle preference related to the aquaretic effect (51%), older age ≥ 60 (12%), and pregnancy/family planning (6%). In this real-world experience, at least 60% of patients with ADPKD considered to be at high risk for progression to ESKD by imaging were not treated with tolvaptan; most of them had early stages of CKD with well-preserved eGFR and as such, were prime targets for tolvaptan therapy to slow disease progression. Given that the most common reason for tolvaptan refusal was the concern for intolerability of the aquaretic side-effect, strategies to mitigate this may help to reduce this barrier to tolvaptan therapy.
Journal Article
Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice
A novel internal ribosomal entry site in the 5' end of the dystrophin gene allows for expression of a form of the protein that could be therapeutic for certain forms of Duchenne muscular dystrophy.
Most mutations that truncate the reading frame of the
DMD
gene cause loss of dystrophin expression and lead to Duchenne muscular dystrophy. However, amelioration of disease severity has been shown to result from alternative translation initiation beginning in
DMD
exon 6 that leads to expression of a highly functional N-truncated dystrophin. Here we demonstrate that this isoform results from usage of an internal ribosome entry site (IRES) within exon 5 that is glucocorticoid inducible. We confirmed IRES activity by both peptide sequencing and ribosome profiling in muscle from individuals with minimal symptoms despite the presence of truncating mutations. We generated a truncated reading frame upstream of the IRES by exon skipping, which led to synthesis of a functional N-truncated isoform in both human subject–derived cell lines and in a new DMD mouse model, where expression of the truncated isoform protected muscle from contraction-induced injury and corrected muscle force to the same level as that observed in control mice. These results support a potential therapeutic approach for patients with mutations within the 5′ exons of
DMD
.
Journal Article
Coverage, inequity and predictors of hepatitis B birth vaccination in Myanmar from 2011–2016: results from a national survey
Background
Hepatitis B virus birth dose (HepB-BD) vaccination is recommended to reduce mother to infant transmission. We evaluated the HepB-BD status of women who gave birth between 2011 and 2016 (
N
= 3,583) using the 2015–2016 Myanmar Demographic and Health Survey.
Methods
Frequency distributions of HepB-BD vaccination across maternal and health system factors, concentration indices, and logistic regression models were used to estimate coverage, inequity, and factors associated with vaccination.
Results
The majority of participants were younger than 30 years of age, lived in rural areas, and were multiparous. Almost all received antenatal care (ANC), but only 43% received recommended ANC services, and 60% gave birth at home. The overall HepB-BD coverage rate was 26%. Vaccination coverage was higher in urban areas and was inequitably concentrated among children of more educated and wealthier women. HepB-BD coverage was also positively associated with receipt of ANC at non-governmental facilities, and delivery at a facility, skilled provider at birth and Cesarean delivery. After adjusting for sociodemographic and health system factors, receipt of the HepB-BD was positively associated with weekly media exposure, receipt of recommended ANC, and Cesarean delivery, and inversely associated with home delivery.
Conclusions
Both socioeconomic and health systems factors influenced suboptimal and inequitable vaccination coverage. Improved access to quality ANC and delivery services may increase HepB-BD coverage although targeted approaches to reach home births are likely required to achieve national goals.
Journal Article
Alcohol Consumption is Associated With An Increased Risk of Microscopic Colitis: Results From 2 Prospective US Cohort Studies
Abstract
Background
No dietary factors have yet been shown to conclusively impact the incidence of microscopic colitis (MC). Here, we sought to examine the relationship between alcohol intake and the risk of MC.
Methods
We conducted a prospective cohort study of 209,902 participants (age range, 28.5–66.7 years) enrolled in the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII). Validated data on alcohol consumption were collected at baseline in 1986 in the NHS and 1991 in the NHSII and updated every 4 years. Diagnoses of MC were confirmed via review of histopathology data. We used Cox proportional hazards modeling to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).
Results
Through 2016 in the NHS and 2017 in the NHSII, we confirmed 352 incident cases of MC over 4,994,324 person-years. Higher alcohol consumption was associated with an increased risk of MC (Ptrend < .001). Compared to non-users, the aHRs of MC were 1.20 (95% CI, 0.86–1.67) for consumers of 0.1–4.9 g/day of alcohol, 1.90 (95% CI, 1.34–2.71) for consumers of 5–14.9 g/day, and 2.31 (95% CI, 1.54–3.46) for consumers of ≥15 g/day. The associations were consistent across the histologic subtypes of collagenous and lymphocytic colitis (Pheterogeneity = .523). When stratified by alcohol type, the risk according to every 2 servings/week appeared to be strongest with consumption of wine (aHR, 1.08; 95% CI, 1.04–1.12) as compared to beer (aHR, 1.01; 95% CI, 0.91–1.12) or liquor (aHR, 1.00; 95% CI, 0.92–1.09).
Conclusions
Alcohol consumption was associated with an increased risk of MC. Further studies are needed to determine the mechanism underlying these associations, as well as the impact of reducing alcohol intake in patients with MC.
Journal Article
Pan-Canadian consensus recommendations for GIST management in high- and low-throughput centres across Canada
Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours that originate from the interstitial cells of Cajal. GISTs are mainly driven by gain-of-function mutations in receptor tyrosine kinase or platelet-derived growth factor receptor alpha. Surgical resection is the only curative treatment for localized tumours and all currently approved medical GIST treatments are based on orally available tyrosine kinase inhibitors. Recent discoveries in the molecular and clinical features of GISTs have greatly impacted GIST management. Due to the provincially rather than nationally administered Canadian healthcare system, there have been inconsistencies in the treatment of GISTs across the country. Therefore, guidance on the latest knowledge, clinical management and treatment of GIST is needed to standardize the approach to GIST management nationwide. To establish pan-Canadian guidance, provide up-to-date data and harmonize the clinical practice of GIST management in high- and low-throughput centres across Canada; a panel of 20 physicians with extensive clinical experience in GIST management reviewed relevant literature. This included radiologists, pathologists, interventional radiologists, surgeons and medical oncologists across Canada. The structured literature focused on seven key domains: molecular profiling, radiological techniques/reporting, targeted localized therapy, intricacies of systemic treatments, emerging tests, multidisciplinary care and patient advocacy. This literature review, along with clinical expertise and opinion, was used to develop this concise and clinically relevant consensus paper to harmonize the knowledge and clinical practice on GIST management across Canada. The content presented here will help guide healthcare providers, especially in Canada, in terms of approaching and managing GIST.
Journal Article
A Randomized Trial of a Hepatitis Care Coordination Model in Methadone Maintenance Treatment
Objectives. We evaluated the efficacy of a hepatitis care coordination intervention to improve linkage to hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccination and clinical evaluation of hepatitis C virus (HCV) infection among methadone maintenance patients. Methods. We conducted a randomized controlled trial of 489 participants from methadone maintenance treatment programs in San Francisco, California, and New York City from February 2008 through June 2011. We randomized participants to a control arm (n = 245) and an intervention arm (n = 244), which included on-site screening, motivational-enhanced education and counseling, on-site vaccination, and case management services. Results. Compared with the control group, intervention group participants were significantly more likely (odds ratio [OR] = 41.8; 95% confidence interval [CI] = 19.4, 90.0) to receive their first vaccine dose within 30 days and to receive an HCV evaluation within 6 months (OR = 4.10; 95% CI = 2.35, 7.17). A combined intervention adherence outcome that measured adherence to HAV–HBV vaccination, HCV evaluation, or both strongly favored the intervention group (OR = 8.70; 95% CI = 5.56, 13.61). Conclusions. Hepatitis care coordination was efficacious in increasing adherence to HAV–HBV vaccination and HCV clinical evaluation among methadone patients.
Journal Article
Dietary Nut and Legume Intake and Risk of Crohn’s Disease and Ulcerative Colitis
Abstract
Background
We investigated the relationship between nut and legume intake and risk of Crohn’s disease (CD) and ulcerative colitis (UC).
Methods
We conducted a prospective cohort study of 223 283 adults from the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (1986-2017), excluding those with inflammatory bowel disease (IBD) at baseline. Food frequency questionnaires were used to calculate nut and legume intake. Inflammatory bowel disease was self-reported on questionnaires and confirmed via blinded record review. Using Cox proportional hazards models, we calculated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CD and UC according to categories of nut and legume intake.
Results
In over 5 460 315 person-years of follow-up (CD = 371, UC = 481), neither nut nor legume intake was associated with CD or UC risk. Compared to those who never consumed nuts, those who consumed nuts ≥2 times/week had an aHR = 0.96 (95% CI, 0.63-1.47; Ptrend = 0.57) for CD and 1.30 (95% CI, 0.92-1.84; Ptrend = 0.36) for UC. Compared to those who consumed legumes 0-3 times/month, those who consumed legumes ≥4 times/week had an aHR of 1.26 (95% CI, 0.78-2.04; Ptrend = 0.59) for CD and 0.72 (95% CI, 0.44-1.18; Ptrend = 0.20) for UC. Baseline BMI modified the relationship between nut intake and CD risk (Pint = 0.03). In those with BMI ≥25, the aHR for CD was 0.14 (95% CI, 0.03-0.56; P = .006) per additional serving/day of nuts compared with 0.88 (95% CI, 0.45-1.74; P = .72) for those with BMI <25.
Conclusions
Nut and legume intake were not associated with CD or UC risk. However, higher nut intake decreased CD risk in overweight or obese individuals. Thus, personalized-risk stratification, rather than generalized dietary recommendations, may be important for IBD prevention strategies.
Lay Summary
Here, we show that overall nut and legume intake was not associated with risk for development of IBD; however, higher nut intake decreased Crohn’s disease risk in those with elevated body mass index.
Journal Article
Association of Childhood Abuse With Incident Inflammatory Bowel Disease
INTRODUCTION:A link between inflammatory bowel disease (IBD), stressful life events, and psychological factors has previously been reported. Our objective was to examine the relationship between emotional, physical, and sexual abuse of childhood and risk of IBD using a large cohort of female health professionals.METHODS:We included participants in the Nurses' Health Study II who completed the Physical and Emotional Abuse Subscale of the Childhood Trauma Questionnaire and the Sexual Maltreatment Scale of the Parent-Child Conflict Tactics Scale in 2001. Diagnosis of IBD was determined by self-report and confirmed independently by 2 physicians through review of medical records. We used Cox proportional hazard modeling to estimate the risk of Crohn's disease (CD) and ulcerative colitis (UC) while adjusting for covariates.RESULTS:Among 68,167 women followed from 1989 until 2017, there were 146 incident cases of CD and 215 incident cases of UC. Compared with women with no history of abuse, the adjusted hazard ratios of CD were 1.16 (95% confidence interval [CI] 0.67-2.02) for mild, 1.58 (95% CI 0.92-2.69) for moderate, and 1.95 (95% CI 1.22-3.10) for severe abuse (Ptrend = 0.002). We did not observe an association between childhood abuse and risk of UC.DISCUSSION:Women who reported early life severe abuse had an increased risk of CD. These data add to the growing body of evidence on the critical role of early life stressors in development of CD.
Journal Article