lt

ADHD May Help Predict Adults' Car Crash Risk

Title: ADHD May Help Predict Adults' Car Crash Risk
Category: Health News
Created: 8/27/2020 12:00:00 AM
Last Editorial Review: 8/28/2020 12:00:00 AM




lt

Want That Healthy Skin Glow? These Foods Can Get You There

Title: Want That Healthy Skin Glow? These Foods Can Get You There
Category: Health News
Created: 8/21/2021 12:00:00 AM
Last Editorial Review: 8/23/2021 12:00:00 AM




lt

Delta Variant Has Americans' Stress Levels Rising Again: Poll

Title: Delta Variant Has Americans' Stress Levels Rising Again: Poll
Category: Health News
Created: 8/20/2021 12:00:00 AM
Last Editorial Review: 8/23/2021 12:00:00 AM




lt

Parents, Look Out for Mental Health Issues as College Kids Return to Class

Title: Parents, Look Out for Mental Health Issues as College Kids Return to Class
Category: Health News
Created: 8/24/2021 12:00:00 AM
Last Editorial Review: 8/24/2021 12:00:00 AM




lt

For Better Breastfeeding, 'Lactation Consultants' Can Help

Title: For Better Breastfeeding, 'Lactation Consultants' Can Help
Category: Health News
Created: 8/25/2021 12:00:00 AM
Last Editorial Review: 8/25/2021 12:00:00 AM




lt

A Little Wine & Certain Foods Could Help Keep Blood Pressure Healthy

Title: A Little Wine & Certain Foods Could Help Keep Blood Pressure Healthy
Category: Health News
Created: 8/24/2021 12:00:00 AM
Last Editorial Review: 8/25/2021 12:00:00 AM




lt

Why Water Is Key to Your Heart's Health

Title: Why Water Is Key to Your Heart's Health
Category: Health News
Created: 8/24/2021 12:00:00 AM
Last Editorial Review: 8/25/2021 12:00:00 AM




lt

Feel Guilty About 'Useless' Leisure Time? Your Mental Health Might Suffer

Title: Feel Guilty About 'Useless' Leisure Time? Your Mental Health Might Suffer
Category: Health News
Created: 8/26/2021 12:00:00 AM
Last Editorial Review: 8/26/2021 12:00:00 AM




lt

As Classes Resume, Some Health Tips From the CDC

Title: As Classes Resume, Some Health Tips From the CDC
Category: Health News
Created: 8/27/2021 12:00:00 AM
Last Editorial Review: 8/27/2021 12:00:00 AM




lt

Can Stress Cause Multiple Sclerosis (MS)?

Title: Can Stress Cause Multiple Sclerosis (MS)?
Category: Diseases and Conditions
Created: 6/18/2020 12:00:00 AM
Last Editorial Review: 7/26/2022 12:00:00 AM




lt

Alternative Medicine Popular Among Seniors, But Most Don't Tell Their Doctors About It

Title: Alternative Medicine Popular Among Seniors, But Most Don't Tell Their Doctors About It
Category: Health News
Created: 7/27/2022 12:00:00 AM
Last Editorial Review: 7/27/2022 12:00:00 AM




lt

Having Ideal Heart Health May Lessen the Risk for Brain Vessel Disease

Title: Having Ideal Heart Health May Lessen the Risk for Brain Vessel Disease
Category: Health News
Created: 8/17/2022 12:00:00 AM
Last Editorial Review: 8/18/2022 12:00:00 AM




lt

AHA News: Newborn Was 'Very Sick Little Boy' Despite Several Normal Prenatal Ultrasounds

Title: AHA News: Newborn Was 'Very Sick Little Boy' Despite Several Normal Prenatal Ultrasounds
Category: Health News
Created: 8/25/2022 12:00:00 AM
Last Editorial Review: 8/25/2022 12:00:00 AM




lt

Breakfast Might Be Good for a Child's Emotional Health, Too

Title: Breakfast Might Be Good for a Child's Emotional Health, Too
Category: Health News
Created: 8/24/2022 12:00:00 AM
Last Editorial Review: 8/24/2022 12:00:00 AM




lt

7 Healthy Sushi Options, Plus Ingredients to Look Out For

Title: 7 Healthy Sushi Options, Plus Ingredients to Look Out For
Category: Health and Living
Created: 8/26/2022 12:00:00 AM
Last Editorial Review: 8/26/2022 12:00:00 AM




lt

Dogs Get Healthier When People Get Fitter

Title: Dogs Get Healthier When People Get Fitter
Category: Health News
Created: 8/25/2022 12:00:00 AM
Last Editorial Review: 8/26/2022 12:00:00 AM




lt

Insulin and Insulin Resistance: The Ultimate Guide

Title: Insulin and Insulin Resistance: The Ultimate Guide
Category: Health and Living
Created: 7/19/2022 12:00:00 AM
Last Editorial Review: 7/19/2022 12:00:00 AM




lt

Mental Health Issues Can Plague Families of Kids With Type 1 Diabetes

Title: Mental Health Issues Can Plague Families of Kids With Type 1 Diabetes
Category: Health News
Created: 8/5/2022 12:00:00 AM
Last Editorial Review: 8/5/2022 12:00:00 AM




lt

Diets Heavy in 'Ultra-Processed' Foods Could Harm the Brain

Title: Diets Heavy in 'Ultra-Processed' Foods Could Harm the Brain
Category: Health News
Created: 7/28/2022 12:00:00 AM
Last Editorial Review: 7/29/2022 12:00:00 AM




lt

'News Addiction' Is Common and Can Harm Your Mental Health

Title: 'News Addiction' Is Common and Can Harm Your Mental Health
Category: Health News
Created: 8/24/2022 12:00:00 AM
Last Editorial Review: 8/25/2022 12:00:00 AM




lt

More Evidence Fitness Trackers Can Boost Your Health

Title: More Evidence Fitness Trackers Can Boost Your Health
Category: Health News
Created: 7/26/2022 12:00:00 AM
Last Editorial Review: 7/27/2022 12:00:00 AM




lt

Scientists Design Skin Patch That Takes Ultrasound Images

Title: Scientists Design Skin Patch That Takes Ultrasound Images
Category: Health News
Created: 7/29/2022 12:00:00 AM
Last Editorial Review: 7/29/2022 12:00:00 AM




lt

9 in 10 Americans Want Their Health Info Kept Private

Title: 9 in 10 Americans Want Their Health Info Kept Private
Category: Health News
Created: 8/2/2022 12:00:00 AM
Last Editorial Review: 8/2/2022 12:00:00 AM




lt

Will Inflation Cut Back on Your Health Care?

Title: Will Inflation Cut Back on Your Health Care?
Category: Health News
Created: 8/8/2022 12:00:00 AM
Last Editorial Review: 8/8/2022 12:00:00 AM




lt

Here's How the Inflation Reduction Act Will Lower the Cost of Health Care

Title: Here's How the Inflation Reduction Act Will Lower the Cost of Health Care
Category: Health News
Created: 8/17/2022 12:00:00 AM
Last Editorial Review: 8/17/2022 12:00:00 AM




lt

Here Is Why Men Should Take Vitamin B12: 10 Health Benefits

Title: Here Is Why Men Should Take Vitamin B12: 10 Health Benefits
Category: Health and Living
Created: 7/27/2022 12:00:00 AM
Last Editorial Review: 7/27/2022 12:00:00 AM




lt

Your Salt Shaker May Prove Deadly, Study Finds

Title: Your Salt Shaker May Prove Deadly, Study Finds
Category: Health News
Created: 7/11/2022 12:00:00 AM
Last Editorial Review: 7/12/2022 12:00:00 AM




lt

Health Conditions a Dentist Might Find That Have Nothing to Do With Your Teeth

Title: Health Conditions a Dentist Might Find That Have Nothing to Do With Your Teeth
Category: Health News
Created: 8/11/2022 12:00:00 AM
Last Editorial Review: 8/12/2022 12:00:00 AM




lt

Self-Employed Women Are Often Healthier: Study

Title: Self-Employed Women Are Often Healthier: Study
Category: Health News
Created: 8/8/2022 12:00:00 AM
Last Editorial Review: 8/8/2022 12:00:00 AM




lt

MS (Multiple Sclerosis) vs. ALS (Amyotrophic Lateral Sclerosis)

Title: MS (Multiple Sclerosis) vs. ALS (Amyotrophic Lateral Sclerosis)
Category: Diseases and Conditions
Created: 6/16/2017 12:00:00 AM
Last Editorial Review: 8/4/2022 12:00:00 AM




lt

Who Fares Worse After Multiple Sclerosis Strikes?

Title: Who Fares Worse After Multiple Sclerosis Strikes?
Category: Health News
Created: 8/11/2022 12:00:00 AM
Last Editorial Review: 8/12/2022 12:00:00 AM




lt

New Multiple Sclerosis Treatment Shows Promise in Trial

Title: New Multiple Sclerosis Treatment Shows Promise in Trial
Category: Health News
Created: 8/25/2022 12:00:00 AM
Last Editorial Review: 8/26/2022 12:00:00 AM




lt

AHA News: How You Feel About Aging Could Affect Health. Here's How to Keep the Right Attitude.

Title: AHA News: How You Feel About Aging Could Affect Health. Here's How to Keep the Right Attitude.
Category: Health News
Created: 8/19/2022 12:00:00 AM
Last Editorial Review: 8/19/2022 12:00:00 AM




lt

Health Care Plans Keep Allergy Rescue Injectors Pricey for Some

Title: Health Care Plans Keep Allergy Rescue Injectors Pricey for Some
Category: Health News
Created: 7/15/2022 12:00:00 AM
Last Editorial Review: 7/15/2022 12:00:00 AM




lt

Gardening Can Blossom Into Better Mental Health

Title: Gardening Can Blossom Into Better Mental Health
Category: Health News
Created: 7/11/2022 12:00:00 AM
Last Editorial Review: 7/11/2022 12:00:00 AM




lt

Patient-managed interventions for adults with bronchiectasis: evidence, challenges and prospects

Bronchiectasis is a chronic lung condition which is characterised by recurrent chest infections, chronic sputum production and cough, and limited exercise tolerance. While bronchiectasis may be caused by various aetiologies, these features are shared by most patients with bronchiectasis regardless of the cause. This review consolidates the existing evidence on patient-managed interventions for adults with bronchiectasis, while also outlining areas for future research. Airway clearance techniques and hyperosmolar agents are key components of the bronchiectasis management and consistently recommended for clinical implementation. Questions around their prescription, such as optimal sequence of delivery, are still to be answered. Pulmonary rehabilitation and exercise are also recommended for patients with bronchiectasis. Relatively strong evidence underpins this recommendation during a clinically stable stage of the disease, although the role of pulmonary rehabilitation following an exacerbation is still unclear. Additionally, self-management programmes feature prominently in bronchiectasis treatment, yet the lack of consensus regarding their definition and outcomes presents hurdles to establishing a cohesive evidence base. Moreover, cough, a cardinal symptom of bronchiectasis, warrants closer examination. Although managing cough in bronchiectasis may initially appear risky, further research is necessary to ascertain whether strategies employed in other respiratory conditions can be safely and effectively adapted to bronchiectasis, particularly through identifying patient responder populations and criteria where cough may not enhance airway clearance efficacy and its control is needed. Overall, there is a growing recognition of the importance of patient-managed interventions in the bronchiectasis management. Efforts to improve research methodologies and increase research funding are needed to further advance our understanding of these interventions, and their role in optimising patient care and outcomes.




lt

Multicomponent services for symptoms in serious respiratory illness: a systematic review and meta-analysis

Background

People living with serious respiratory illness experience a high burden of symptoms. This review aimed to determine whether multicomponent services reduce symptoms in people with serious illness related to respiratory disease.

Methods

Electronic databases were searched to identify randomised controlled trials (RCTs) evaluating multicomponent services that enrolled patients due to symptoms, rather than underlying disease, and provided at least one nonpharmacological intervention. The primary outcome was chronic breathlessness and secondary outcomes were health-related quality of life (HRQoL), cough, fatigue and adverse events. At least two authors independently screened studies, assessed risk of bias and extracted data.

Results

Five RCTs, involving 439 patients, were included. In comparison to usual care, multicomponent services improved breathlessness mastery (Chronic Respiratory Questionnaire (CRQ) mastery scale, mean difference (MD) 0.43 points, 95% CI 0.20–0.67, three RCTs, 327 participants) and HRQoL (CRQ total score, MD 0.24 points, 95% CI 0.04–0.40, two RCTs, 237 participants). Fatigue did not improve with multicomponent services and no studies evaluated cough. No serious adverse events were reported. The one study evaluating mortality found increased survival in those accessing a multicomponent service. The certainty of evidence was very low, mainly due to detection and reporting bias.

Conclusion

Multicomponent services improve breathlessness mastery and HRQoL, with minimal risk. These findings support the use of multicomponent symptom-directed services for people living with serious respiratory illness.




lt

Only One Quarter of Family Physicians Are Very Satisfied with Their Electronic Health Records Platform

Two decades into the era of Electronic Health Records (EHRs), the promise of streamlining clinical care, reducing burden, and improving patient outcomes has yet to be realized. A cross-sectional family physician census conducted by the American Board of Family Medicine in 2022 and 2023 included self-reported physician EHR satisfaction. Of the nearly 10,000 responding family physicians, only one-in-four (26.2%) report being very satisfied and one-in-three (33.8%) were not satisfied. These low levels of satisfaction point to the need for greater transparency in the marketplace and pressure to increase user-centric EHR design.




lt

Impact of COVID-19 on Chronic Ambulatory-Care-Sensitive Condition Emergency Department Use Among Older Adults

Background:

The COVID-19 pandemic social distancing requirements encouraged patients to avoid public spaces including in-office health care visits. Ambulatory-care-sensitive conditions (ACSCs) represent conditions that can be managed with quality primary care and when access is limited, these conditions can lead to avoidable emergency department (ED) visits.

Methods:

Using national data on ED visits from 2019 to 2021 in the National Hospital Ambulatory Care Survey, we examined the impact of COVID-19 pandemic on ACSC ED visits among older adults (aged ≥65).

Results:

The proportion of ED visits among older adults that were for ACSCs increased between 2019 (17.4%) and 2021 (18.5%). The trend in both rural (26.4%–28.6%) and urban areas (15.4%–16.8%) shows a significant jump from 2019 to 2021 (P < .001).

Conclusions:

This rise in ACSC ED use is consistent with a delay in normal primary care during the pandemic.




lt

Colorectal Cancer Screening: A Multicomponent Intervention to Increase Uptake in Patients Aged 45-49

Purpose:

Colorectal cancer (CRC) screening is recommended starting at age 45, but there has been little research on strategies to promote screening among patients younger than 50. This study assessed the effect of a multicomponent intervention on screening completion in this age group.

Methods:

The intervention consisted of outreach to patients aged 45 to 49 (n = 3,873) via mailed fecal immunochemical test (FIT) (sent to 46%), text (84%), e-mail (53%), and the extension to this age group of an existing standing order protocol allowing primary care nurses and medical assistants to order FIT at primary care clinics in an urban safety-net system. We used segmented linear regression to assess changes in CRC screening completion trends. Patients aged 51 to 55 were included as a comparison group (n = 3,943). Data were extracted from the EHR.

Results:

The percentage of patients aged 45 to 49 who were up-to-date with CRC screening (colonoscopy in 10 years or FIT in last year) increased an average of 0.4% (95% CI 0.3, 0.6)) every 30 days before intervention rollout and 2.8% (95% CI 2.5, 3.1) after (slope difference 2.3% [95% CI 2.0, 2.7]). This difference persisted after accounting for small changes in the outcome observed in the comparison group (slope difference 1.7% [95% CI 1.2, 2.2]).

Conclusions:

These results suggest that the intervention increased CRC screening completion among patients 45 to 49. Health care systems seeking to improve CRC screening participation among patients aged 45 to 49 should consider implementing similar interventions.




lt

Associations Between Patient/Caregiver Trust in Clinicians and Experiences of Healthcare-Based Discrimination

Background:

Higher trust in healthcare providers has been linked to better health outcomes and satisfaction. Lower trust has been associated with healthcare-based discrimination.

Objective:

Examine associations between experiences of healthcare discrimination and patients’ and caregivers of pediatric patients’ trust in providers, and identify factors associated with high trust, including prior experience of healthcare-based social screening.

Methods:

Secondary analysis of cross-sectional study using logistic regression modeling. Sample consisted of adult patients and caregivers of pediatric patients from 11 US primary care/emergency department sites.

Results:

Of 1,012 participants, low/medium trust was reported by 26% identifying as non-Hispanic Black, 23% Hispanic, 18% non-Hispanic multiple/other race, and 13% non-Hispanic White (P = .001). Experience of any healthcare-based discrimination was reported by 32% identifying as non-Hispanic Black, 23% Hispanic, 39% non-Hispanic multiple/other race, and 26% non-Hispanic White (P = .012). Participants reporting low/medium trust had a mean discrimination score of 1.65/7 versus 0.57/7 for participants reporting high trust (P < .001). In our adjusted model, higher discrimination scores were associated with lower trust in providers (aOR 0.74, 95%CI = 0.64, 0.85). A significant interaction indicated that prior healthcare-based social screening was associated with reduced impact of discrimination on trust: as discrimination score increased, odds of high trust were greater among participants who had been screened (aOR = 1.28, 95%CI = 1.03, 1.58).

Conclusions:

Patients and caregivers reporting more healthcare-based discrimination were less likely to report high provider trust. Interventions to strengthen trust need structural antiracist components. Increased rapport with patients may be a potential by-product of social screening. Further research is needed on screening and trust.




lt

Using Primary Health Care Electronic Medical Records to Predict Hospitalizations, Emergency Department Visits, and Mortality: A Systematic Review

Introduction:

High-quality primary care can reduce avoidable emergency department visits and emergency hospitalizations. The availability of electronic medical record (EMR) data and capacities for data storage and processing have created opportunities for predictive analytics. This systematic review examines studies which predict emergency department visits, hospitalizations, and mortality using EMR data from primary care.

Methods:

Six databases (Ovid MEDLINE, PubMed, Embase, EBM Reviews (Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, Health Technology Assessment, NHS Economic Evaluation Database), Scopus, CINAHL) were searched to identify primary peer-reviewed studies in English from inception to February 5, 2020. The search was initially conducted on January 18, 2019, and updated on February 5, 2020.

Results:

A total of 9456 citations were double-reviewed, and 31 studies met the inclusion criteria. The predictive ability measured by C-statistics (ROC) of the best performing models from each study ranged from 0.57 to 0.95. Less than half of the included studies used artificial intelligence methods and only 7 (23%) were externally validated. Age, medical diagnoses, sex, medication use, and prior health service use were the most common predictor variables. Few studies discussed or examined the clinical utility of models.

Conclusions:

This review helps address critical gaps in the literature regarding the potential of primary care EMR data. Despite further work required to address bias and improve the quality and reporting of prediction models, the use of primary care EMR data for predictive analytics holds promise.




lt

Physician Satisfaction Should Be the Measure of Electronic Health Record Quality for the Nation




lt

Effects of Ultrasonic Use on Hearing Loss in Dental Hygienists: A matched pairs design study

Purpose Dental professionals are exposed to hazardous noise levels on a daily basis in clinical practice. The purpose of this study was to compare the hearing status of dental hygienists who utilize ultrasonic scalers in the workplace compared to age-matched control participants (non-dental hygienists) who were not exposed to ultrasonic noise.Methods A convenience sample of nineteen dental hygienists (experimental) and nineteen non-dental hygienists (control) was recruited for this study. A matched pairs design was utilized; participants in each group were matched based on age and gender to eliminate confounding variables. The testing procedure consisted of an audiologist performing a series of auditory tests including otoacoustic emissions test, pure-tone audiometry, and tympanometry on the experimental and control groups.Results In the right ear, there were notable differences from 1000 Hz – 10,000 Hz and in the left ear from 6000 Hz – 10,000 Hz, with higher hearing thresholds in the experimental group of dental hygienists. While 56% of the univariate tests conducted on how many days were worked per week showed statistical significance, the regression line slope indicated those that worked more days had better hearing statuses. The variables for years in practice for dental hygienists, how many of those years were full-time employment, and how many years the dental hygienist had used an ultrasonic scaling device, also had many significant univariate tests for the experimental group only. These variables were more likely to serve as proxies representing true noise exposure. The paired t-test between the groups demonstrated statistically significant differences between the experimental and control group at 9000 Hz in both ears.Conclusion While results from this study demonstrated various qualitative differences in hearing status of the control group (non-dental hygienists) and experimental group (dental hygienists), age was found to be the most critical variable. Furthermore, this data demonstrated differences in hearing status based on various frequencies between dental hygienists and age-matched controls that should be further explored with a larger population.




lt

Development and Validation of a Customized Amplex UltraRed Assay for Sensitive Hydrogen Peroxide Detection in Pharmaceutical Water

For clean-room technologies such as isolators and restricted access barrier systems (RABS), decontamination using hydrogen peroxide (H2O2) is increasingly attractive to fulfill regulatory requirements. Several approaches are currently used, ranging from manual wipe disinfection to vapor phase hydrogen peroxide (VPHP) or automated nebulization sanitization. Although the residual airborne H2O2 concentration can be easily monitored, detection of trace H2O2 residues in filled products is rather challenging. To simulate the filling process in a specific clean room, technical runs with water for injection (WfI) are popular. Thus, the ability to detect traces of H2O2 in water is an important prerequisite to ensure a safe and reliable use of H2O2 for isolator or clean room decontamination. The objective of this study was to provide a validated quantitative, fluorometric Amplex UltraRed assay, which satisfies the analytical target profile of quantifying H2O2 in WfI at low nanomolar to low micromolar concentrations (ppb range) with high accuracy and high precision. The Amplex UltraRed technology provides a solid basis for this purpose; however, no commercial assay kit that fulfills these requirements is available. Therefore, a customized Amplex UltraRed assay was developed, optimized, and validated. This approach resulted in an assay that is capable of quantifying H2O2 in WfI selectively, sensitively, accurately, precisely, and robustly. This assay is used in process development and qualification approaches using WfI in H2O2-decontaminated clean rooms and isolators.




lt

The small noncoding RNA Vaultrc5 is dispensable to mouse development [ARTICLE]

Vault RNAs (vtRNAs) are evolutionarily conserved small noncoding RNAs transcribed by RNA polymerase III. Vault RNAs were initially described as components of the vault particle, but have since been assigned multiple vault-independent functions, including regulation of PKR activity, apoptosis, autophagy, lysosome biogenesis, and viral particle trafficking. The full-length transcript has also been described as a noncanonical source of miRNAs, which are processed in a DICER-dependent manner. As central molecules in vault-dependent and independent processes, vtRNAs have been attributed numerous biological roles, including regulation of cell proliferation and survival, response to viral infections, drug resistance, and animal development. Yet, their impact to mammalian physiology remains largely unexplored. To study vault RNAs in vivo, we generated a mouse line with a conditional Vaultrc5 loss-of-function allele. Because Vaultrc5 is the sole murine vtRNA, this allele enables the characterization of the physiological requirements of this conserved class of small regulatory RNAs in mammals. Using this strain, we show that mice constitutively null for Vaultrc5 are viable and histologically normal but have a slight reduction in platelet counts, pointing to a potential role for vtRNAs in hematopoiesis. This work paves the way for further in vivo characterizations of this abundant but mysterious RNA molecule. Specifically, it enables the study of the biological consequences of constitutive or lineage-specific Vaultrc5 deletion and of the physiological requirements for an intact Vaultrc5 during normal hematopoiesis or in response to cellular stresses such as oncogene expression, viral infection, or drug treatment.




lt

Abolished frameshifting for predicted structure-stabilizing SARS-CoV-2 mutants: implications to alternative conformations and their statistical structural analyses [ARTICLE]

The SARS-CoV-2 frameshifting element (FSE) has been intensely studied and explored as a therapeutic target for coronavirus diseases, including COVID-19. Besides the intriguing virology, this small RNA is known to adopt many length-dependent conformations, as verified by multiple experimental and computational approaches. However, the role these alternative conformations play in the frameshifting mechanism and how to quantify this structural abundance has been an ongoing challenge. Here, we show by DMS and dual-luciferase functional assays that previously predicted FSE mutants (using the RAG graph theory approach) suppress structural transitions and abolish frameshifting. Furthermore, correlated mutation analysis of DMS data by three programs (DREEM, DRACO, and DANCE-MaP) reveals important differences in their estimation of specific RNA conformations, suggesting caution in the interpretation of such complex conformational landscapes. Overall, the abolished frameshifting in three different mutants confirms that all alternative conformations play a role in the pathways of ribosomal transition.




lt

Multidisciplinary management of adult patients with chylothorax: a consensus statement

The management of chylothorax remains challenging given the limited evidence and significant heterogeneity in practice. In addition, there are no practical guidelines on the optimal approach to manage this complex condition. We convened an international group of 27 experts from 20 institutions across five countries and four specialties (pulmonary, interventional radiology, thoracic surgery and nutrition) with experience and expertise in managing adult patients with chylothorax. We performed a literature and internet search for reports addressing seven clinically relevant PICO (Patient, Intervention, Comparison and Outcome) questions pertaining to the management of adult patients with chylothorax. This consensus statement, consisting of best practice statements based on expert consensus addressing these seven PICO questions, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with provider experience. Panel members participated in the development of the final best practice statements using the modified Delphi technique. Our consensus statement aims to offer guidance in clinical decision making when managing patients with chylothorax while also identifying gaps in knowledge and informing future research.




lt

Correlations of Long Noncoding RNA HNF4A-AS1 Alternative Transcripts with Liver Diseases and Drug Metabolism [Articles]

Hepatocyte nuclear factor 4 alpha antisense 1 (HNF4A-AS1) is a long noncoding RNA (lncRNA) gene physically located next to the transcription factor HNF4A gene in the human genome. Its transcription products have been reported to inhibit the progression of hepatocellular carcinoma (HCC) and negatively regulate the expression of cytochrome P450s (CYPs), including CYP1A2, 2B6, 2C9, 2C19, 2E1, and 3A4. By altering CYP expression, lncRNA HNF4A-AS1 also contributes to the susceptibility of drug-induced liver injury. Thus, HNF4A-AS1 lncRNA is a promising target for controlling HCC and modulating drug metabolism. However, HNF4A-AS1 has four annotated alternative transcripts in the human genome browsers, and it is unclear which transcripts the small interfering RNAs or small hairpin RNAs used in the previous studies are silenced and which transcripts should be used as the target. In this study, four annotated and two newly identified transcripts were confirmed. These six transcripts showed different expression levels in different liver disease conditions, including metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and obesity. The expression patterns of all HNF4A-AS1 transcripts were further investigated in liver cell growth from human embryonic stem cells to matured hepatocyte-like cells, HepaRG differentiation, and exposure to rifampicin treatment. Several HNF4A-AS1 transcripts highly displayed correlations with these situations. In addition, some of the HNF4A-AS1 transcripts also showed a strong correlation with CYP3A4 during HepaRG maturation and rifampicin exposure. Our findings provide valuable insights into the specific roles of HNF4A-AS1 transcripts, paving the way for more targeted therapeutic strategies for liver diseases and drug metabolism.

SIGNIFICANCE STATEMENT

This study explores the alternative transcripts of HNF4A-AS1, showing how their expression changes in different biological conditions, from various liver diseases to the growth and differentiation of hepatocytes and drug metabolism. The generated knowledge is essential for understanding the independent roles of different transcripts from the same lncRNA in different liver diseases and drug metabolism situations.




lt

The Simultaneous Inhibition of Solute Carrier Family 6 Member 19 and Breast Cancer Resistance Protein Transporters Leads to an Increase of Indoxyl Sulfate (a Uremic Toxin) in Plasma and Kidney [Articles]

Solute carrier family 6 member 19 (SLC6A19) inhibitors are being studied as therapeutic agents for phenylketonuria. In this work, a potent SLC6A19 inhibitor (RA836) elevated rat kidney uremic toxin indoxyl sulfate (IDS) levels by intensity (arbitrary unit) of 13.7 ± 7.7 compared with vehicle 0.3 ± 0.1 (P = 0.01) as determined by tissue mass spectrometry imaging analysis. We hypothesized that increased plasma and kidney levels of IDS could be caused by the simultaneous inhibition of both Slc6a19 and a kidney IDS transporter responsible for excretion of IDS into urine. To test this, we first confirmed the formation of IDS through tryptophan metabolism by feeding rats a Trp-free diet. Inhibiting Slc6a19 with RA836 led to increased IDS in these rats. Next, RA836 and its key metabolites were evaluated in vitro for inhibiting kidney transporters such as organic anion transporter (OAT)1, OAT3, and breast cancer resistance protein (BCRP). RA836 inhibits BCRP with an IC50 of 0.045 μM but shows no significant inhibition of OAT1 or OAT3. Finally, RA836 analogs with either potent or no inhibition of SLC6A19 and/or BCRP were synthesized and administered to rats fed a normal diet. Plasma and kidney samples were collected to quantify IDS using liquid chromatography–mass spectrometry. Neither a SLC6A19 inactive but potent BCRP inhibitor nor a SLC6A19 active but weak BCRP inhibitor raised IDS levels, whereas compounds inhibiting both transporters caused IDS accumulation in rat plasma and kidney, supporting the hypothesis that rat Bcrp contributes to the excretion of IDS. In summary, we identified that inhibiting Slc6a19 increases IDS formation, while simultaneously inhibiting Bcrp results in IDS accumulation in the kidney and plasma.

SIGNIFICANCE STATEMENT

This is the first publication to decipher the mechanism for accumulation of indoxyl sulfate (IDS) (a uremic toxin) in rats via inhibition of both Slc6a19 and Bcrp. Specifically, inhibition of Slc6a19 in the gastrointestinal track increases IDS formation, and inhibition of Bcrp in the kidney blocks IDS excretion. Therefore, we should avoid inhibiting both solute carrier family 6 member 19 and breast cancer resistance protein simultaneously in humans to prevent accumulation of IDS, a known risk factor for cardiovascular disease, psychic anxiety, and mortality in chronic kidney disease patients.