Aluminum and ABC transporter activity.

Aluminum is the third most common element on Earth´s crust and despite its wide use in our workaday life it has been associated with several health risks after overexposure. In the present study the impact of aluminum salts upon ABC transporter activity was studied in the P-GP-expressing human blood-brain barrier cell line hCMEC/D3, in MDCKII cells overexpressing BCRP and MRP2, respectively, and in freshly isolated, functionally intact kidney tubules from Atlantic killifish (Fundulus heteroclitus), which express the analog ABC transporters, P-gp, Bcrp and Mrp2. In contrast to previous findings with heavy metals salts (cadmium(II) chloride or mercury(II) chloride), which have a strong inhibitory effect on ABC transporter activity, or zinc(II) chloride and sodium arsenite, which have a stimulatory effect upon ABC transport function, the results indicate no modulatory effect of aluminum salts on the efflux activity of the human ABC transporters P-GP, BCRP and MRP2 nor on the analog transporters P-gp, Bcrp and Mrp2.

Evaluation of a single-use gastroscope in patients presenting with suspected upper gastrointestinal hemorrhage: a pilot feasibility study (One-Scope I).

BACKGROUND : Outbreaks of multidrug-resistant bacteria due to contaminated duodenoscopes and infection risks during the COVID-19 pandemic have driven the development of single-use endoscopes. The first single-use gastroscope is now available in Europe. Besides waste disposal and cost issues, the infection risk and performance remain unclear. We aimed to evaluate a single-use gastroscope in patients with signs of upper gastrointestinal bleeding. METHODS : 20 consecutive patients presenting with clinical signs of upper gastrointestinal bleeding between October and November 2022 were included in this case series. The primary aim was technical success, defined as access to the descending duodenum and adequate assessment of the upper gastrointestinal tract for the presence of a bleeding site. RESULTS : The primary aim was achieved in 19/20 patients (95 %). The bleeding site was identified in 18 patients. A therapeutic intervention was performed in six patients (two cap-mounted clips, one standard hemostatic clip, two variceal band ligations, one hemostatic powder, two adrenaline injections); technical and clinical success were achieved in all six patients. Two crossovers to a standard gastroscope occurred. CONCLUSIONS : Use of single-use gastroscopes may be feasible for patients presenting for urgent endoscopic evaluation and treatment of upper gastrointestinal bleeding.

Nephrotoxicity of iopamidol is associated with mitochondrial impairment in human cell and teleost models.

Iopamidol is a nonionic, low-osmolar iodinated contrast agent used for angiography. Its clinical use is associated with renal dysfunction. Patients suffering from preexisting kidney disease have an increased risk of renal failure upon iopamidol administration. Studies in animals confirmed renal toxicity, but the involved mechanisms remain unclear. Therefore, the aim of the present study was to use human embryonic kidney cells (HEK293T) as a general cell model of mitochondrial damage, as well as, zebrafish larvae, and isolated proximal tubules of killifish to investigate factors promoting renal tubular toxicity of iopamidol with a focus on mitochondrial damage. Results from in vitro HEK293T cell-based assays indicate that iopamidol affects mitochondrial function Treatment with iopamidol induces ATP depletion, reduces the mitochondrial membrane potential, and elevates mitochondrial superoxide and reactive oxygen species accumulation. Similar results were obtained with gentamicin sulfate and cadmium chloride, two well-known model compounds associated with renal tubular toxicity. Confocal microscopy confirms changes in mitochondrial morphology, such as mitochondrial fission. Importantly, these results were confirmed in proximal renal tubular epithelial cells using ex vivo and in vivo teleost models. In conclusion, this study provides evidence for iopamidol-induced mitochondrial damage in proximal renal epithelial cells. Teleost models allow studying proximal tubular toxicity with translational relevance for humans.

An artificial intelligence algorithm is highly accurate for detecting endoscopic features of eosinophilic esophagitis.

The endoscopic features associated with eosinophilic esophagitis (EoE) may be missed during routine endoscopy. We aimed to develop and evaluate an Artificial Intelligence (AI) algorithm for detecting and quantifying the endoscopic features of EoE in white light images, supplemented by the EoE Endoscopic Reference Score (EREFS). An AI algorithm (AI-EoE) was constructed and trained to differentiate between EoE and normal esophagus using endoscopic white light images extracted from the database of the University Hospital Augsburg. In addition to binary classification, a second algorithm was trained with specific auxiliary branches for each EREFS feature (AI-EoE-EREFS). The AI algorithms were evaluated on an external data set from the University of North Carolina, Chapel Hill (UNC), and compared with the performance of human endoscopists with varying levels of experience. The overall sensitivity, specificity, and accuracy of AI-EoE were 0.93 for all measures, while the AUC was 0.986. With additional auxiliary branches for the EREFS categories, the AI algorithm (AI-EoE-EREFS) performance improved to 0.96, 0.94, 0.95, and 0.992 for sensitivity, specificity, accuracy, and AUC, respectively. AI-EoE and AI-EoE-EREFS performed significantly better than endoscopy beginners and senior fellows on the same set of images. An AI algorithm can be trained to detect and quantify endoscopic features of EoE with excellent performance scores. The addition of the EREFS criteria improved the performance of the AI algorithm, which performed significantly better than endoscopists with a lower or medium experience level.

Methotrexate does not increase the risk of liver fibrosis in patients with rheumatoid arthritis: assessment by ultrasound elastography (ARFI-MetRA study).

OBJECTIVES: Only limited data are available on the risk of liver fibrosis in patients with rheumatoid arthritis on long-term methotrexate treatment. To assess the risk of liver fibrosis in patients with rheumatoid arthritis treated with methotrexate, non-invasive, ultrasound-based elastography [acoustic radiation force impulse (ARFI) imaging] was applied. METHODS: In total, 119 patients were assessed using acoustic radiation force impulse (ARFI) imaging between July 2018 and April 2019. In a cross-sectional, single-centre study design, ARFI scores were compared between patient subgroups with (n = 65) and without (n = 54) methotrexate exposure. The main outcome variable was the mean fibrosis score as measured by the ARFI method. The mean shear wave velocity was calculated from 10 valid ARFI measurements for each patient. Inferential statistical analyses (between group) were performed using ANOVA for independent samples in the case of continuous outcome variables. RESULTS: Sixty-five patients with and fifty-four patients without MTX exposure were assessed using the ARFI elastography method. Participating patients on MTX medication (1.113 m/s) showed ARFI scores that were comparable to those of participants without MTX exposure (1.062 m/s); P = 0.228. The mean cumulative dose in the group of MTX-exposed patients was 3602 mg. CONCLUSION: The mean value of the repeated determination of liver density using ARFI imaging did not differ significantly between the MTX-exposed and MTX-naive patients with RA. No increased rate of liver fibrosis was found among RA patients treated with MTX.

Examining Associations Between Licensed and Unlicensed Outlet Density and Cannabis Outcomes From Preopening to Postopening of Recreational Cannabis Outlets.

BACKGROUND AND OBJECTIVES: To expand on epidemiologic studies examining associations between the legalization of recreational cannabis and use among young adults, we examined the associations between licensed and unlicensed cannabis outlet density and cannabis outcomes. METHODS: A total of 1097 young adults aged 21 and older living in Los Angeles County were surveyed before licensed recreational cannabis outlets opened (Time 1: July to December 2017) and after (Time 2: July 2018 to June 2019). Using a database of open licensed and unlicensed cannabis retailers to calculate individual-level cannabis outlet density measures, we examined associations between outlet density within a 4-mile radius of participants' residences with Time 2 outcomes of any past-month use, daily use, intentions to use, quantity used, consequences, and cannabis use disorder (CUD) symptoms. RESULTS: After controlling for demographic factors and cannabis outcomes at a time point prior to their opening (Time 1), licensed cannabis outlets were associated with young adults' cannabis use, heavy use, and intentions, and unlicensed outlets were associated with young adults' heavy cannabis use and CUD symptoms. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: This study expands beyond studies of outlet prevalence to find that, after controlling for outcomes 1 year prior, licensed and unlicensed outlets were associated with young adults' cannabis outcomes. The current study is among the first to find associations between cannabis use outcomes and density of cannabis outlets among young adults using data from two time points: preopening and postopening of recreational cannabis retailers. Findings can inform policies around the density and placement of cannabis outlets. (Am J Addict 2020;00:00-00).

Locating Medical and Recreational Cannabis Outlets for Research Purposes: Online Methods and Observational Study.

BACKGROUND: An increasing number of states have laws for the legal sale of recreational and medical cannabis out of brick-and-mortar storefront locations. Given the proliferation of cannabis outlets and their potential for impact on local economies, neighborhood structures, and individual patterns of cannabis use, it is essential to create practical and thorough methods to capture the location of such outlets for research purposes. However, methods used by researchers vary greatly between studies and often do not include important information about the retailer's license status and storefront signage. OBJECTIVE: The aim of this study was to find methods for locating and observing cannabis outlets in Los Angeles County after the period when recreational cannabis retailers were granted licenses and allowed to be open for business. METHODS: The procedures included searches of online cannabis outlet databases, followed by methods to verify each outlet's name, address, license information, and open status. These procedures, conducted solely online, resulted in a database of 531 outlets. To further verify each outlet's information and collect signage data, we conducted direct observations of the 531 identified outlets. RESULTS: We found that 80.9% (430/531) of these outlets were open for business, of which 37.6% (162/430) were licensed to sell cannabis. Unlicensed outlets were less likely to have signage indicating the store sold cannabis, such as a green cross, which was the most prevalent form of observed signage. Co-use of cannabis and tobacco/nicotine has been found to be a substantial health concern, and we observed that 40.6% (175/430) of cannabis outlets had a tobacco/nicotine outlet within sight of the cannabis outlet. Most (350/430, 81.4%) cannabis outlets were located within the City of Los Angeles, and these outlets were more likely to be licensed than outlets outside the city. CONCLUSIONS: The findings of this study suggest that online searches and observational methods are both necessary to best capture accurate and detailed information about cannabis outlets. The methods described here can be applied to other metropolitan areas to more accurately capture the availability of cannabis in an area.

The trajectory of patterns of light and sedentary physical activity among females, ages 14-23.

PURPOSE: Light physical activity (LPA) and patterns of sedentary behavior influence cardio-metabolic health independently of moderate-to-vigorous physical activity. Understanding the trajectory and determinants of these activity levels over time may provide insights relevant to public health practice. METHODS: We measured a cohort of young women recruited in middle school (age 14) using accelerometry for 1 week and remeasured them in high school (age 17) and again at age 23 (n = 385). We assessed changes in LPA and patterns of sedentary behavior by hours in a day. We examined the association of social and contextual factors, including employment status, screen time, and neighborhood context with LPA and sedentary behavior patterns. RESULTS: The amount of LPA decreased over time, while the length of LPA bouts tended to increase. Sedentary bout durations increased over time and sedentary breaks decreased. Sedentary time and bout length were correlated with internet use, rather than with TV or videogaming. Employment was associated with less sedentary time; being a student was associated with longer sedentary time and bouts. CONCLUSIONS: Because LPA and sedentary breaks can be protective for cardio-metabolic health, and the duration of sedentary bouts increase as women age from adolescence to young adulthood, worksites and college campuses should remind employees and students to take frequent activity breaks when they use computers and the internet for long stretches.

Researching the Appropriateness of Care in the Complementary and Integrative Health Professions Part 5: Using Patient Records: Selection, Protection, and Abstraction.

OBJECTIVES: The purpose of this paper is to describe the 4-step process (consent, selection, protection, and abstraction) of acquiring a large sample of chiropractic patient records from multiple practices and subsequent data abstraction. METHODS: From April 2017 to December 2017, RAND acquired patient records from 99 chiropractic practices across the United States. The records included patients enrolled in a survey e-study (prospective sample) and a random sample of all clinic patients (retrospective sample) with chronic back or neck pain. Clinic staff were trained to collect the sample, scan, and transfer the records. We designed an online data collection tool for abstraction. Protocols were instituted to protect patient confidentiality. Doctors of chiropractic were selected and trained as abstractors, and a system was established to monitor data collection. RESULTS: In compliance with data protection protocols, 3603 patient records were scanned, including 1475 in the prospective sample and 2128 in the random sample. A total of 1716 patients (prospective sample) consented to having their records scanned, but only 1475 could be retrieved. Of records scanned, 19% were unusable owing to illegibility, no care during the period of interest, or poor scanning. The abstractor interrater reliability for appropriateness of care decisions was fair to moderate (κ .38-.48). CONCLUSION: The acquisition, handling, and abstraction of a large sample of chiropractic records was a complex task with challenges that necessitated adapting planned approaches. Of the records abstracted, many revealed incomplete provider documentation regarding the details of and rationale for care. Better documentation and more standardized record keeping would facilitate future research using patient records.

Associations between young adult marijuana outcomes and availability of medical marijuana dispensaries and storefront signage.

AIMS: We investigated associations between the density of medical marijuana dispensaries (MMDs) around young adults' homes and marijuana use outcomes. DESIGN: Secondary data analysis. SETTING: Los Angeles County, CA, USA. PARTICIPANTS: A total of 1887 participants aged 18-22 years, surveyed online in 2016-17. MEASUREMENTS: Outcomes were past-month marijuana use (number of days used, number of times each day), positive expectancies and perceived peer use. Density was measured as the total number of MMDs and number of MMDs with storefront signage indicative of marijuana sales, within 4 miles of respondents' homes. FINDINGS: Eighty-four per cent of respondents had 10 or more MMDs within 4 miles of their homes. Multiple linear regression analyses that adjusted for individual-level socio-demographic characteristics and neighborhood socio-economic status indicated that living near a higher number of MMDs was associated with greater number of days used in the past month [ß = 0.025; 95% confidence interval (CI) = 0.001, 0.049; P = 0.04] and higher positive marijuana expectancies (ß = 0.003; 95% CI = 0.001, 0.007; P = 0.04). Living near more MMDs with storefront signage had a four- to six-fold larger effect on number of times used per day and positive expectancies, respectively, compared with associations with the total MMD count. Adjusting for medical marijuana card ownership attenuated the association with number of days used in the past month and positive expectancies, and an unexpected association emerged between higher MMD density and fewer number of times used each day (ß = -0.005; 95% CI = -0.009, -0.001; P = 0.03). CONCLUSIONS: For young adults in Los Angeles County, living near more medical marijuana dispensaries (MMDs) is positively associated with more frequent use of marijuana within the past month and greater expectations of marijuana's positive benefits. MMDs with signage show stronger associations with number of times used each day and positive expectancies.

Researching the Appropriateness of Care in the Complementary and Integrative Health Professions Part 4: Putting Practice Back Into Evidence-based Practice by Recruiting Clinics and Patients.

OBJECTIVES: This paper focuses on the methods of a single study, incorporating data from chiropractic clinics into an evidenced-based investigation of the appropriateness of manipulation for chronic back pain. METHODS: A cluster sample of clinics (125) from 6 sites across the United States was chosen for this observation study. Patients with chronic low-back and neck pain were recruited using iPads, completed a series of online questionnaires, and gave permission for their patient records to be scanned. Patient records for a random sample were also obtained. The RAND staff and clinic personnel collected record data. RESULTS: We obtained survey data from 2024 patients with chronic low back pain, chronic neck pain, or both. We obtained patient record data from 114 of 125 clinics. These included the records of 1475 of the individuals who had completed surveys (prospective sample), and a random sample of 2128 patients. Across 114 clinics, 22% of clinics had patient records that were fully electronic, 32% had paper files, and 46% used a combination. Of the 114 clinics, about 47% scanned the records themselves with training from RAND. We obtained a total of 3603 scanned records. The patient survey data were collected from June 2016 to February 2017, the provider surveys from June 2016 to March 2017, and the chart pull from April 2017 to December 2017. CONCLUSIONS: Clinics can be successfully recruited for practice-based studies, and patients can be recruited using iPads. Obtaining patient records presents considerable challenges, and clinics varied in whether they had electronic files, nonelectronic records, or a mixture. Clinic staff can be trained to select and scan samples of charts to comply with randomization and data protection protocols in transferring records for research purposes.

Individual, peer, and family factor modification of neighborhood-level effects on adolescent alcohol, cigarette, e-cigarette, and marijuana use.

BACKGROUND: Neighborhood factors reported subjectively by residents and measured objectively at the census tract are both associated with adolescent alcohol, tobacco (cigarette and electronic cigarette), and other drug (marijuana) (ATOD) use. Less clear is how these neighborhood factors are longitudinally associated with each substance. Equivocal findings may be due to lack of consideration of individual, peer, and family effect modifiers, which could help adolescents overcome exposure to stressful neighborhood environments. METHODS: We used multivariate logistic regressions with interaction terms to test whether parental monitoring, resistance self-efficacy (RSE) and being around peers who use ATOD modified the association between four subjective and objective neighborhood measures and odds of using each substance measured one year later among 2539 high school students and college freshmen originally recruited from middle schools in Southern California. RESULTS: Census tract-level disadvantage was not longitudinally associated with ATOD use. However, perceptions of higher neighborhood disorganization, less social cohesion, and more neighborhood problems with alcohol and drug use were associated with higher odds of ATOD use. Higher RSE and weaker affiliations with peers who use ATOD consistently buffered negative effects of neighborhood disorganization and neighborhood problems with alcohol and drugs on past year ATOD use. CONCLUSIONS: Community-level programs that increase social cohesion among neighbors, neighborhood monitoring of deviant behaviors, and better policing of open drug selling may prevent ATOD use. Programs should also target RSE and minimize affiliations with peers who use ATOD, which could reduce the magnitude of the association with ATOD, even for adolescents living in the most at-risk neighborhoods.

The mechanism of action of docetaxel (Taxotere) in xenograft models is not limited to bcl-2 phosphorylation.

Docetaxel is a new taxoid compound with a broad spectrum of antitumor activity. Previous studies have shown that in vitro treatment of specific human tumor lines with docetaxel is associated with the phosphorylation and inactivation of the bcl-2 protein and the occurrence of apoptosis. The goal of this study was to examine whether bcl-2 expression is truly required for in vivo responsiveness to docetaxel. The expression and state of phosphorylation of bcl-2 was examined in human MX-1 breast or DU-145 prostate tumors explanted from nu/nu mice treated with docetaxel. The MX-1 cells accumulated in the G2/M phase of the cell cycle and exhibited phosphorylation of bcl-2 after treatment with docetaxel. By Western blot analysis DU-145 prostate tumor cells did not express bcl-2 protein before or following in vivo treatment with docetaxel. However, docetaxel was highly active against the DU-145 tumor xenograft model. Thus, docetaxel induces apoptosis and cell death through a different, bcl-2-independent mechanism in the DU-145 human prostate tumor, indicating that bcl-2 may not have prognostic value for treatment with docetaxel.