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In experimental and clinical studies, green or black tea consumption has been shown to reduce oxidative stress. However, these studies involved high levels of tea consumption and may not reflect patterns in the general population. Here, we examined the association between black or green tea consumption and oxidative stress in a cross-sectional study of 889 premenopausal US women aged 35–54 years. Tea consumption was measured using the Block-98 FFQ. Urinary 8-iso-PGF2α (F2-IsoP) and 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (15-F2t-IsoP-M) were used as biomarkers of oxidative stress. These compounds were measured by MS and normalised to creatinine. Linear regression was used to calculate the geometric mean differences (GMD) and 95% CI for log-transformed urinary F2-IsoP or 15-F2t-IsoP-M in relation to black or green tea consumption. We further examined whether adjusting for caffeine impacted associations between tea and oxidative stress. Geometric means of urinary F2-IsoP and 15-F2t-IsoP-M were 1·44 (95% CI 1·39, 1·49) and 0·71 (95% CI 0·69, 0·73) ng/mg creatinine, respectively. Overall, green tea consumption was not associated with urinary F2-IsoP or 15-F2t-IsoP-M. High-level black tea consumption (≥5 cups/week compared with 0) was associated with higher 15-F2t-IsoP-M concentrations (adjusted GMD=0·10, 95 % CI 0·02–0.19) but not F2-IsoP. Adjusting for caffeine nullified the association between black tea and 15-F2t-IsoP-M. Our findings do not support the hypothesis that dietary tea consumption is inversely associated with oxidative stress.
Psychotropic medications are frequently co-prescribed with antiretroviral therapy (ART), owing to a high prevalence of psychiatric illness within the population living with HIV, as well as a 7-fold increased risk of HIV infection among patients with psychiatric illness. While ART has been notoriously associated with a multitude of pharmacokinetic drug interactions involving the cytochrome P450 enzyme system, the magnitude and clinical impact of these interactions with psychotropics may range from negligible effects on plasma concentrations to life-threatening torsades de pointes or respiratory depression. This comprehensive review summarizes the currently available information regarding drug–drug interactions between antiretrovirals and pharmacologic agents utilized in the treatment of psychiatric disorders—antidepressants, stimulants, antipsychotics, anxiolytics, mood stabilizers, and treatments for opioid use disorder and alcohol use disorder—and provides recommendations for their management. Additionally, overlapping toxicities between antiretrovirals and the psychotropic classes are highlighted. Knowledge of the interaction and adverse effect potential of specific antiretrovirals and psychotropics will allow clinicians to make informed prescribing decisions to better promote the health and wellness of this high-risk population.
This study examined the effectiveness of a formal postdoctoral education program designed to teach skills in clinical and translational science, using scholar publication rates as a measure of research productivity.
Participants included 70 clinical fellows who were admitted to a master’s or certificate training program in clinical and translational science from 1999 to 2015 and 70 matched control peers. The primary outcomes were the number of publications 5 years post-fellowship matriculation and time to publishing 15 peer-reviewed manuscripts post-matriculation.
Clinical and translational science program graduates published significantly more peer-reviewed manuscripts at 5 years post-matriculation (median 8 vs 5, p=0.041) and had a faster time to publication of 15 peer-reviewed manuscripts (matched hazard ratio = 2.91, p=0.002). Additionally, program graduates’ publications yielded a significantly higher average H-index (11 vs. 7, p=0.013).
These findings support the effectiveness of formal training programs in clinical and translational science by increasing academic productivity.
Objectives: Down syndrome (DS) is a population with known hippocampal impairment, with studies showing that individuals with DS display difficulties in spatial navigation and remembering arbitrary bindings. Recent research has also demonstrated the importance of the hippocampus for novel word-learning. Based on these data, we aimed to determine whether individuals with DS show deficits in learning new labels and if they may benefit from encoding conditions thought to be less reliant on hippocampal function (i.e., through fast mapping). Methods: In the current study, we examined immediate, 5-min, and 1-week delayed word-learning across two learning conditions (e.g., explicit encoding vs. fast mapping). These conditions were examined across groups (twenty-six 3- to 5-year-old typically developing children and twenty-six 11- to 28-year-old individuals with DS with comparable verbal and nonverbal scores on the Kaufman Brief Intelligence Test – second edition) and in reference to sleep quality. Results: Both individuals with and without DS showed retention after a 1-week delay, and the current study found no benefit of the fast mapping condition in either group contrary to our expectations. Eye tracking data showed that preferential eye movements to target words were not present immediately but emerged after 1-week in both groups. Furthermore, sleep measures collected via actigraphy did not relate to retention in either group. Conclusions: This study presents novel data on long-term knowledge retention in reference to sleep patterns in DS and adds to a body of knowledge helping us to understand the processes of word-learning in typical and atypically developing populations. (JINS, 2018, 24, 955–965)
Bowel cancer risk is strongly influenced by lifestyle factors including diet and physical activity. Several studies have investigated the effects of adherence to the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) cancer prevention recommendations on outcomes such as all-cause and cancer-specific mortality, but the relationships with molecular mechanisms that underlie the effects on bowel cancer risk are unknown. This study aimed to investigate the relationships between adherence to the WCRF/AICR cancer prevention recommendations and wingless/integrated (WNT)-pathway-related markers of bowel cancer risk, including the expression of WNT pathway genes and regulatory microRNA (miRNA), secreted frizzled-related protein 1 (SFRP1) methylation and colonic crypt proliferative state in colorectal mucosal biopsies. Dietary and lifestyle data from seventy-five healthy participants recruited as part of the DISC Study were used. A scoring system was devised including seven of the cancer prevention recommendations and smoking status. The effects of total adherence score and scores for individual recommendations on the measured outcomes were assessed using Spearman’s rank correlation analysis and unpaired t tests, respectively. Total adherence score correlated negatively with expression of Myc proto-oncogene (c-MYC) (P=0·039) and WNT11 (P=0·025), and high adherers had significantly reduced expression of cyclin D1 (CCND1) (P=0·042), WNT11 (P=0·012) and c-MYC (P=0·048). Expression of axis inhibition protein 2 (AXIN2), glycogen synthase kinase (GSK3β), catenin β1 (CTNNB1) and WNT11 and of the oncogenic miRNA miR-17 and colonic crypt kinetics correlated significantly with scores for individual recommendations, including body fatness, red meat intake, plant food intake and smoking status. The findings from this study provide evidence for positive effects of adherence to the WCRF/AICR cancer prevention recommendations on WNT-pathway-related markers of bowel cancer risk.
Ischemic stroke treatment is time-sensitive, and barriers to providing prehospital care encountered by Emergency Medical Services (EMS) providers have been under-studied.
This study described barriers to providing prehospital care, identified predictors of these barriers, and assessed the impact of these barriers on EMS on-scene time and administration of tissue plasminogen activator (tPA) in the emergency department (ED).
A retrospective cohort study was performed using the Get With The Guidelines-Stroke (GWTG-S; American Heart Association [AHA]; Dallas, Texas USA) registry at two hospitals to identify ischemic stroke patients arriving by EMS. Variables were abstracted from prehospital and hospital medical records and merged with registry data. Barriers to care were grouped into themes. Logistic regression was used to identify predictors of barriers to care, and bi-variate tests were used to assess differences in EMS on-scene time and the proportion of patients receiving tPA between patients with and without barriers.
Barriers to providing prehospital care were documented for 15.5% of patients: 29.6% related to access, 26.7% communication, 23.0% extrication and transportation, 20.0% refusal, and 14.1% assessment/management. Non-white and non-black race (OR: 3.69; 95% CI, 1.63-8.36) and living alone (OR: 1.53; 95% CI, 1.05-2.23) were associated with greater odds of barriers to providing care. The EMS on-scene time was ≥15 minutes for 70.4% of patients who had a barrier to care, compared with 49.0% of patients who did not (P<.001). There was no significant difference in the proportion of patients who were administered tPA between those with and without barriers to care (14.1% vs 19.2%; P=.159).
Barriers to providing prehospital care were documented for a sizable proportion of ischemic stroke patients, with the majority related to patient access and communication, and occurred more frequently among non-white and non-black patients and those living alone. Although EMS on-scene time was longer for patients with barriers to care, the proportion of patients receiving tPA in the ED did not differ.
LiT, CushmanJT, ShahMN, KellyAG, RichDQ, JonesCMC. Barriers to Providing Prehospital Care to Ischemic Stroke Patients: Predictors and Impact on Care. Prehosp Disaster Med.2018;33(5):501–507.
Foodborne non-typhoidal salmonellosis causes approximately 1 million illnesses annually in the USA. In April 2015, we investigated a multistate outbreak of 65 Salmonella Paratyphi B variant L(+) tartrate(+) infections associated with frozen raw tuna imported from Indonesia, which was consumed raw in sushi. Forty-six (92%) of 50 case-patients interviewed ate sushi during the week before illness onset, and 44 (98%) of 45 who specified ate sushi containing raw tuna. Two outbreak strains were isolated from the samples of frozen raw tuna. Traceback identified a single importer as a common source of tuna consumed by case-patients; this importer issued three voluntary recalls of tuna sourced from one Indonesian processor. Four Salmonella Weltevreden infections were also linked to this outbreak. Whole-genome sequencing was useful in establishing a link between Salmonella isolated from ill people and tuna. This outbreak highlights the continuing foodborne illness risk associated with raw seafood consumption, the importance of processing seafood in a manner that minimises contamination with pathogenic microorganisms and the continuing need to ensure imported foods are safe to eat. People at higher risk for foodborne illness should not consume undercooked animal products, such as raw seafood.
Background: Language mapping is a key goal in neurosurgical planning. With the discontinuation of the Wada test in Canada, neurosurgeons often rely on fMRI and intraoperative techniques for determining language lateralization. Recent studies have also evaluated the utility of diffusion tensor imaging (DTI) for preoperative language lateralization, but further research is needed to confirm its efficacy. We report a patient with a left frontal AVM. fMRI and DTI was used to localize language and motor functioning. Methods: The tasks included word reading, picture naming, pseudohomophones (e.g., dawg) and semantic questions. All fMRI analyses were performed using BrainVoyager. Tensors were tracked from 30-direction diffusion MR images using DSI-Studio. Results: The fMRI results revealed consistent Broca’s and Wernicke’s areas, confirming left hemisphere dominance. There was also a region of activation in the precentral gyrus near the surgical resection. The results were loaded onto the neuronavigation system to help determine safe surgical margins. The DTI results revealed that the left arcuate and uncinate -fasciculus had three times more tracts than the right hemisphere, further supporting left hemisphere dominance. Conclusions: This case highlights the value of a combined, multimodal approach for preoperative language localization, which will further enhance surgical safety by helping preserve regions for essential brain functions.
The patient portal may be an effective method for administering surveys regarding participant research experiences but has not been systematically studied.
We evaluated 4 methods of delivering a research participant perception survey: mailing, phone, email, and patient portal. Participants of research studies were identified (n=4013) and 800 were randomly selected to receive a survey, 200 for each method. Outcomes included response rate, survey completeness, and cost.
Among those aged <65 years, response rates did not differ between mail, phone, and patient portal (22%, 29%, 30%, p>0.07). Among these methods, the patient portal was the lowest-cost option. Response rates were significantly lower using email (10%, p<0.01), the lowest-cost option. In contrast, among those aged 65+ years, mail was superior to the electronic methods (p<0.02).
The patient portal was among the most effective ways to reach research participants, and was less expensive than surveys administered by mail or telephone.
Background: CNS innate immune cells, microglia and macrophages (MMs), are the largest component of the inflammatory infiltrate in glioblastoma (GBM). They initially participate in tumor surveillance, but are co-opted by GBM to further angiogenesis and invasion. There are no effective immunotherapies against GBM in part because GBM-associated MMs are not well understood. We hypothesized that the extent and inflammatory phenotype of MM infiltration into GBM is variable between patients. This variability could have important implications on immunotherapy selection and treatment outcomes. Methods: Using automated quantitation of fluorescently labeled human GBMs, flow cytometry/live cell sorting, collection of conditioned GBM-associated MM media, and corroboration with TCGA and previously published scRNA-seq data, we have uncovered there is surprisingly marked variation in the amount of MM infiltration between tumors. Results: MM infiltration can range from almost non-existent, to comprising ~70% of GBM cells. By detecting cell surface markers and secreted cytokines, we determined that a mixture of pro- and anti-inflammatory MMs are found in each tumor. The overall inflammatory phenotype did not depend on the amount of infiltration. Interestingly, IDH-mutant GBM-associated MMs are more pro-inflammatory and less heterogeneous than IDH-wildtype GBMs. Conclusions: Taken together, the highly variable immunologic status of GBMs suggests the success of immunotherapies hinges on selecting appropriately vulnerable tumors.
Early postnatal intestinal development involves the preparation of the intestinal epithelium for extrauterine life when maternal secretions provide the sole nutrient source. A further shift in the digestive capability of the epithelium occurs later in development with the introduction of complex solid foods. Ontogenesis involves extensive epithelial cell proliferation and cytodifferentiation including changes in the expression of enzymes, receptors and transport systems and is regulated through the interaction of endogenous and exogenous factors. The mucosal epithelium plays a key rôle in the reception and transmisson of these trophic signals. In particular, the interplay between dietary constituents and microvillar membranes exerts profound influence on intestinal development and adaptation during the postnatal period.