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Suicide a Danger for Some Women During Pregnancy: Study

Title: Suicide a Danger for Some Women During Pregnancy: Study
Category: Health News
Created: 8/28/2017 12:00:00 AM
Last Editorial Review: 8/29/2017 12:00:00 AM




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Harvey's Health Hazards Will Continue During Cleanup

Title: Harvey's Health Hazards Will Continue During Cleanup
Category: Health News
Created: 9/1/2017 12:00:00 AM
Last Editorial Review: 9/1/2017 12:00:00 AM




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Health Tip: Stay Safe During a Lightning Storm

Title: Health Tip: Stay Safe During a Lightning Storm
Category: Health News
Created: 9/1/2017 12:00:00 AM
Last Editorial Review: 9/1/2017 12:00:00 AM




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Will Climate Change Bring More Highway Deaths?

Title: Will Climate Change Bring More Highway Deaths?
Category: Health News
Created: 8/31/2017 12:00:00 AM
Last Editorial Review: 9/1/2017 12:00:00 AM




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Monitoring System for Underage Tobacco Sales Falls Short: Study

Title: Monitoring System for Underage Tobacco Sales Falls Short: Study
Category: Health News
Created: 8/29/2018 12:00:00 AM
Last Editorial Review: 8/30/2018 12:00:00 AM




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Health Tip: Staying Well During the School Year

Title: Health Tip: Staying Well During the School Year
Category: Health News
Created: 8/27/2019 12:00:00 AM
Last Editorial Review: 8/27/2019 12:00:00 AM




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OxyContin Maker Purdue Offering Up to $12 Billion to Settle Opioid Claims

Title: OxyContin Maker Purdue Offering Up to $12 Billion to Settle Opioid Claims
Category: Health News
Created: 8/27/2019 12:00:00 AM
Last Editorial Review: 8/28/2019 12:00:00 AM




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The Benefits of Strength Training During Pregnancy

Title: The Benefits of Strength Training During Pregnancy
Category: Health News
Created: 8/30/2019 12:00:00 AM
Last Editorial Review: 8/30/2019 12:00:00 AM




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Major Study Gives Women More Guidance on Hormone Therapy During Menopause

Title: Major Study Gives Women More Guidance on Hormone Therapy During Menopause
Category: Health News
Created: 8/29/2019 12:00:00 AM
Last Editorial Review: 8/30/2019 12:00:00 AM




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Play It Safe With Allergies, Asthma During Pandemic School Year

Title: Play It Safe With Allergies, Asthma During Pandemic School Year
Category: Health News
Created: 8/21/2020 12:00:00 AM
Last Editorial Review: 8/24/2020 12:00:00 AM




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Hearing Persists at End of Life, Brain Waves of Hospice Patients Show

Title: Hearing Persists at End of Life, Brain Waves of Hospice Patients Show
Category: Health News
Created: 8/26/2020 12:00:00 AM
Last Editorial Review: 8/27/2020 12:00:00 AM




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Teen's Democratic Convention Speech Brings Awareness to Stuttering

Title: Teen's Democratic Convention Speech Brings Awareness to Stuttering
Category: Health News
Created: 8/28/2020 12:00:00 AM
Last Editorial Review: 8/28/2020 12:00:00 AM




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Cancer Radiation Can Safely Proceed During COVID-19 Pandemic: Study

Title: Cancer Radiation Can Safely Proceed During COVID-19 Pandemic: Study
Category: Health News
Created: 8/27/2020 12:00:00 AM
Last Editorial Review: 8/28/2020 12:00:00 AM




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No Change in Adolescent Drug, Alcohol Use During Pandemic

Title: No Change in Adolescent Drug, Alcohol Use During Pandemic
Category: Health News
Created: 8/24/2021 12:00:00 AM
Last Editorial Review: 8/24/2021 12:00:00 AM




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Drinking at Home: Liquor Store Sales Rose During Pandemic

Title: Drinking at Home: Liquor Store Sales Rose During Pandemic
Category: Health News
Created: 8/24/2021 12:00:00 AM
Last Editorial Review: 8/24/2021 12:00:00 AM




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Fatal ODs From Illicit Tranquilizers Jumped 6-Fold During Pandemic

Title: Fatal ODs From Illicit Tranquilizers Jumped 6-Fold During Pandemic
Category: Health News
Created: 8/26/2021 12:00:00 AM
Last Editorial Review: 8/27/2021 12:00:00 AM




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Bioengineered Pig Skin Is Turned Into Corneas, Restoring Patients' Sight

Title: Bioengineered Pig Skin Is Turned Into Corneas, Restoring Patients' Sight
Category: Health News
Created: 8/11/2022 12:00:00 AM
Last Editorial Review: 8/12/2022 12:00:00 AM




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Are Plant Sterols Good for Lowering Cholesterol?

Title: Are Plant Sterols Good for Lowering Cholesterol?
Category: Diseases and Conditions
Created: 5/12/2022 12:00:00 AM
Last Editorial Review: 5/12/2022 12:00:00 AM




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What Fish Is Best for Lowering Cholesterol?

Title: What Fish Is Best for Lowering Cholesterol?
Category: Health and Living
Created: 5/19/2022 12:00:00 AM
Last Editorial Review: 5/19/2022 12:00:00 AM




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California Will Produce Its Own Insulin to Bring Down Prices

Title: California Will Produce Its Own Insulin to Bring Down Prices
Category: Health News
Created: 7/8/2022 12:00:00 AM
Last Editorial Review: 7/8/2022 12:00:00 AM




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Use of Pot, Hallucinogens Soaring Among Young Americans

Title: Use of Pot, Hallucinogens Soaring Among Young Americans
Category: Health News
Created: 8/23/2022 12:00:00 AM
Last Editorial Review: 8/23/2022 12:00:00 AM




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Up Your Skin Care Routine During Hot Summer Months

Title: Up Your Skin Care Routine During Hot Summer Months
Category: Health News
Created: 8/13/2022 12:00:00 AM
Last Editorial Review: 8/15/2022 12:00:00 AM




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How Do I Make My Ears Stop Ringing?

Title: How Do I Make My Ears Stop Ringing?
Category: Diseases and Conditions
Created: 5/10/2022 12:00:00 AM
Last Editorial Review: 5/10/2022 12:00:00 AM




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Cheaper Over-the-Counter Hearing Aids Should Be in Stores by October, FDA Says

Title: Cheaper Over-the-Counter Hearing Aids Should Be in Stores by October, FDA Says
Category: Health News
Created: 8/16/2022 12:00:00 AM
Last Editorial Review: 8/17/2022 12:00:00 AM




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HIV Testing Plummeted During Pandemic

Title: HIV Testing Plummeted During Pandemic
Category: Health News
Created: 6/27/2022 12:00:00 AM
Last Editorial Review: 6/27/2022 12:00:00 AM




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When Is Blood Pressure Lowest and Highest During the Day?

Title: When Is Blood Pressure Lowest and Highest During the Day?
Category: Diseases and Conditions
Created: 7/26/2022 12:00:00 AM
Last Editorial Review: 7/26/2022 12:00:00 AM




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PWAS Hub for exploring gene-based associations of common complex diseases [RESOURCES]

PWAS (proteome-wide association study) is an innovative genetic association approach that complements widely used methods like GWAS (genome-wide association study). The PWAS approach involves consecutive phases. Initially, machine learning modeling and probabilistic considerations quantify the impact of genetic variants on protein-coding genes’ biochemical functions. Secondly, for each individual, aggregating the variants per gene determines a gene-damaging score. Finally, standard statistical tests are activated in the case-control setting to yield statistically significant genes per phenotype. The PWAS Hub offers a user-friendly interface for an in-depth exploration of gene–disease associations from the UK Biobank (UKB). Results from PWAS cover 99 common diseases and conditions, each with over 10,000 diagnosed individuals per phenotype. Users can explore genes associated with these diseases, with separate analyses conducted for males and females. For each phenotype, the analyses account for sex-based genetic effects, inheritance modes (dominant and recessive), and the pleiotropic nature of associated genes. The PWAS Hub showcases its usefulness for asthma by navigating through proteomic-genetic analyses. Inspecting PWAS asthma-listed genes (a total of 27) provide insights into the underlying cellular and molecular mechanisms. Comparison of PWAS-statistically significant genes for common diseases to the Open Targets benchmark shows partial but significant overlap in gene associations for most phenotypes. Graphical tools facilitate comparing genetic effects between PWAS and coding GWAS results, aiding in understanding the sex-specific genetic impact on common diseases. This adaptable platform is attractive to clinicians, researchers, and individuals interested in delving into gene–disease associations and sex-specific genetic effects.




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Global characterization of somatic mutations and DNA methylation changes during vegetative propagation in strawberries [RESEARCH]

Somatic mutations arise and accumulate during tissue culture and vegetative propagation, potentially affecting various traits in horticultural crops, but their characteristics are still unclear. Here, somatic mutations in regenerated woodland strawberry derived from tissue culture of shoot tips under different conditions and 12 cultivated strawberry individuals are analyzed by whole genome sequencing. The mutation frequency of single nucleotide variants is significantly increased with increased hormone levels or prolonged culture time in the range of 3.3 x 10–8–3.0 x 10–6 mutations per site. CG methylation shows a stable reduction (0.71%–8.03%) in regenerated plants, and hypoCG-DMRs are more heritable after sexual reproduction. A high-quality haplotype-resolved genome is assembled for the strawberry cultivar "Beni hoppe." The 12 "Beni hoppe" individuals randomly selected from different locations show 4731–6005 mutations relative to the reference genome, and the mutation frequency varies among the subgenomes. Our study has systematically characterized the genetic and epigenetic variants in regenerated woodland strawberry plants and different individuals of the same strawberry cultivar, providing an accurate assessment of somatic mutations at the genomic scale and nucleotide resolution in plants.




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Clinician-Reported Barriers and Needs for Implementation of Continuous Glucose Monitoring

Background:

Continuous glucose monitoring (CGM) for patients with type 1 and type 2 diabetes is associated with improved clinical, behavioral, and psychosocial patient health outcomes and is part of the American Diabetes Association’s Standards of Medical Care. CGM prescription often takes place in endocrinology practices, yet 50% of adults with type 1 diabetes and 90% of all people with type 2 diabetes receive their diabetes care in primary care settings. This study examined primary care clinicians’ perceptions of barriers and resources needed to support CGM use in primary care.

Methods:

This qualitative study used semistructured interviews with primary care clinicians to understand barriers to CGM and resources needed to prescribe. Participants were recruited through practice-based research networks. Rapid qualitative analysis was used to summarize themes from interview findings.

Results:

We conducted interviews with 55 primary care clinicians across 21 states. Participants described CGM benefits for patients with varying levels of diabetes self-management and engagement. Major barriers to prescribing included lack of insurance coverage for CGM costs to patients, and time constraints. Participants identified resources needed to foster CGM prescribing, for example, clinician education, support staff, and EHR compatibility.

Conclusion:

Primary care clinicians face several challenges to prescribing CGM, but they are interested in learning more to help them offer it to their patients. This study reinforces the ongoing need for improved clinician education on CGM technology and continued expansion of insurance coverage for people with both type 1 and type 2 diabetes.




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Comparing Highs and Flows in Patients With COPD With Chronic Hypercapnic Respiratory Failure




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Exploring the Impact of Varied Design Approaches and Materials in Respiratory Therapy Education




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Effects of Lung Injury and Abdominal Insufflation on Respiratory Mechanics and Lung Volume During Time-Controlled Adaptive Ventilation

BACKGROUD:Lung volume measurements are important for monitoring functional aeration and recruitment and may help guide adjustments in ventilator settings. The expiratory phase of airway pressure release ventilation (APRV) may provide physiologic information about lung volume based on the expiratory flow-time slope, angle, and time to approach a no-flow state (expiratory time [TE]). We hypothesized that expiratory flow would correlate with estimated lung volume (ELV) as measured using a modified nitrogen washout/washin technique in a large-animal lung injury model.METHODS:Eight pigs (35.2 ± 1.0 kg) were mechanically ventilated using an Engström Carescape R860 on the APRV mode. All settings were held constant except the expiratory duration, which was adjusted based on the expiratory flow curve. Abdominal pressure was increased to 15 mm Hg in normal and injured lungs to replicate a combination of pulmonary and extrapulmonary lung injury. ELV was estimated using the Carescape FRC INview tool. The expiratory flow-time slope and TE were measured from the expiratory flow profile.RESULTS:Lung elastance increased with induced lung injury from 29.3 ± 7.3 cm H2O/L to 39.9 ± 15.1cm H2O/L, and chest wall elastance increased with increasing intra-abdominal pressures (IAPs) from 15.3 ± 4.1 cm H2O/L to 25.7 ± 10.0 cm H2O/L in the normal lung and 15.8 ± 6.0 cm H2O/L to 33.0 ± 6.2 cm H2O/L in the injured lung (P = .39). ELV decreased from 1.90 ± 0.83 L in the injured lung to 0.67 ± 0.10 L by increasing IAP to 15 mm Hg. This had a significant correlation with a TE decrease from 2.3 ± 0.8 s to 1.0 ± 0.1 s in the injured group with increasing insufflation pressures (ρ = 0.95) and with the expiratory flow-time slope, which increased from 0.29 ± 0.06 L/s2 to 0.63 ± 0.05 L/s2 (ρ = 0.78).CONCLUSIONS:Changes in ELV over time, and the TE and flow-time slope, could be used to demonstrate evolving lung injury during APRV. Using the slope to infer changes in functional lung volume represents a unique, reproducible, real-time, bedside technique that does not interrupt ventilation and may be used for clinical interpretation.




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Feasibility of Delivering 5-Day Normobaric Hypoxia Breathing in a Hospital Setting

BACKGROUND:Beneficial effects of breathing at FIO2 < 0.21 on disease outcomes have been reported in previous preclinical and clinical studies. However, the safety and intra-hospital feasibility of breathing hypoxic gas for 5 d have not been established. In this study, we examined the physiologic effects of breathing a gas mixture with FIO2 as low as 0.11 in 5 healthy volunteers.METHODS:All 5 subjects completed the study, spending 5 consecutive days in a hypoxic tent, where the ambient oxygen level was lowered in a stepwise manner over 5 d, from FIO2 of 0.16 on the first day to FIO2 of 0.11 on the fifth day of the study. All the subjects returned to an environment at room air on the sixth day. The subjects' SpO2, heart rate, and breathing frequency were continuously recorded, along with daily blood sampling, neurologic evaluations, transthoracic echocardiography, and mental status assessments.RESULTS:Breathing hypoxia concentration dependently caused profound physiologic changes, including decreased SpO2 and increased heart rate. At FIO2 of 0.14, the mean SpO2 was 92%; at FIO2 of 0.13, the mean SpO2 was 93%; at FIO2 of 0.12, the mean SpO2 was 88%; at FIO2 of 0.11, the mean SpO2 was 85%; and, finally, at an FIO2 of 0.21, the mean SpO2 was 98%. These changes were accompanied by increased erythropoietin levels and reticulocyte counts in blood. All 5 subjects concluded the study with no adverse events. No subjects exhibited signs of mental status changes or pulmonary hypertension.CONCLUSIONS:Results of the current physiologic study suggests that, within a hospital setting, delivering FIO2 as low as 0.11 is feasible and safe in healthy subjects, and provides the foundation for future studies in which therapeutic effects of hypoxia breathing are tested.




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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.




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Impact of Dimensional Variability of Primary Packaging Materials on the Break-Loose and Gliding Forces of Prefilled Syringes

A prefilled syringe (PFS) should be able to be adequately and consistently extruded during injection for optimal safe drug delivery and accurate dosing. To facilitate appropriate break-loose and gliding forces (BLGFs) required during injection, certain primary packaging materials (PPMs) such as the syringe barrel and plunger are usually coated with silicone oil, which acts as a lubricant. Due to its direct contact with drug, silicone oil can increase the number of particles in the syringe, which could lead to adverse interactions. Compliance with regulatory-defined silicone oil quantities in certain drug products, such as ophthalmics, presents a trade-off with the necessity for desirable low and consistent BLGF. In addition to its siliconization, the dimensional accuracy of the PPM has an important role in controlling the BLGF. The dimensions of the PPM are individualized depending on the product and its design and have certain tolerances that must be met during manufacturing. Most studies on ophthalmics focused on the adverse interactions between silicone oil and the drug. To the authors' knowledge, there have been no public studies so far that have investigated the impact of the dimensional variability of the PPM on the BLGF in ophthalmic PFSs. In this study, we applied advanced optical shaft and tactile measuring technologies to investigate this impact. The syringes investigated were first sampled during aseptic production and tested for the BLGF. Subsequently, defined dimensions of the PPM were measured individually. The results showed that the dimensional variability of the PPM can have a negative impact on the BLGF, despite their conformity to specifications, which indicates that the currently available market quality of PPMs is improvable for critical drug products such as ophthalmics. This study could serve as an approach to define product-specific requirements for primary packaging combinations and thus appropriate specifications based on data during the development stage of drug products.




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A cellular identity crisis? Plasticity changes during aging and rejuvenation [Reviews]

Cellular plasticity in adult multicellular organisms is a protective mechanism that allows certain tissues to regenerate in response to injury. Considering that aging involves exposure to repeated injuries over a lifetime, it is conceivable that cell identity itself is more malleable—and potentially erroneous—with age. In this review, we summarize and critically discuss the available evidence that cells undergo age-related shifts in identity, with an emphasis on those that contribute to age-associated pathologies, including neurodegeneration and cancer. Specifically, we focus on reported instances of programs associated with dedifferentiation, biased differentiation, acquisition of features from alternative lineages, and entry into a preneoplastic state. As some of the most promising approaches to rejuvenate cells reportedly also elicit transient changes to cell identity, we further discuss whether cell state change and rejuvenation can be uncoupled to yield more tractable therapeutic strategies.




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Deciphering visceral instincts: a scientific quest to unravel food choices from molecules to mind [Special Section: Symposium Outlook]

The study of biological mechanisms, while crucial, cannot fully explain complex phenomena like the instinct to eat. The mind–body connection, as exemplified by the concept of "voodoo death," highlights the profound influence of belief and cultural context on physiology. Indigenous knowledge systems further emphasize the interconnectedness of humans with their environment. Recent discoveries in gut–brain communication reveal the intricate neural circuits that drive our visceral desires, but a holistic approach that integrates both physiological mechanisms and the subjective experience of life, informed by diverse cultural perspectives, will be essential to truly understand what it means to be alive.




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The noninvasive ventilation outcomes score in patients requiring NIV for COPD exacerbation without prior evidence of airflow obstruction

Introduction

Exacerbation of COPD complicated by respiratory acidaemia is the commonest indication for noninvasive ventilation (NIV). The NIV outcomes (NIVO) score offers the best estimate of survival for those ventilated. Unfortunately, two-thirds of cases of COPD are unrecognised, and patients may present without COPD having been confirmed by spirometry.

Methods

In the 10-centre NIVO validation study there was no pre-admission spirometry in 111 of 844 consecutive patients (termed "clinical diagnosis" patients). We compared the performance of the NIVO, DECAF and CURB-65 scores for in-hospital mortality in the clinical diagnosis cohort. Usual clinical practice was not influenced, but confirmation of COPD in the year following discharge was captured.

Results

In the clinical diagnosis cohort, in-hospital mortality was 19.8% and rose incrementally across the NIVO risk categories, consistent with the NIVO validation cohort. NIVO showed good discrimination in the clinical diagnosis cohort: area under the receiver operating curve 0.724, versus 0.79 in the NIVO validation cohort. At 1 year after discharge, 41 of 89 clinical diagnosis patients had undertaken diagnostic spirometry; 33 of 41 had confirmation of airflow obstruction (forced expiratory volume in 1 s/(forced) vital capacity <0.7), meaning the diagnosis of COPD was incorrect in 19.5% of cases.

Discussion

These data support the use of the NIVO score in patients with a "clinical diagnosis" of COPD. NIVO can help guide shared decision-making, assess risk-adjusted outcomes by centre and challenge prognostic pessimism. Accurate diagnosis is critical to ensure that acute and long-term treatment is optimised; this study highlights failings in the follow-up of such patients.




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Ensuring availability of respiratory medicines in times of European drug shortages

Extract

It is of utmost importance that medicines are available at all times for our patients. Historically, medication unavailability has typically, if not exclusively, affected low- and middle-income countries [1]. More recently however, drug shortages have also been reported in high-income European countries [2]. Drug shortages have negative health consequences for patients [3], and a profound economic impact, with the need to resort to more expensive alternatives and demands on healthcare professionals’ time to find, prescribe and dispense alternatives [4].




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Nonclinical Pharmacokinetics Study of OLX702A-075-16, N-Acetylgalactosamine Conjugated Asymmetric Small Interfering RNA (GalNAc-asiRNA) [Articles]

In this study, the nonclinical pharmacokinetics of OLX702A-075-16, an RNA interference therapeutic currently in development, were investigated. OLX702A-075-16 is a novel N-acetylgalactosamine conjugated asymmetric small-interfering RNA (GalNAc-asiRNA) used for the treatment of an undisclosed liver disease. Its unique 16/21-mer asymmetric structure reduces nonspecific off-target effects without compromising efficacy. We investigated the plasma concentration, tissue distribution, metabolism, and renal excretion of OLX702A-075-16 following a subcutaneous administration in mice and rats. For bioanalysis, high-performance liquid chromatography with fluorescence detection was used. The results showed rapid clearance from plasma (0.5 to 1.5 hours of half-life) and predominant distribution to the liver and/or kidney. Less than 1% of the liver concentration of OLX702A-075-16 was detected in the other tissues. Metabolite profiling using liquid chromatography coupled with high-resolution mass spectrometry revealed that the intact duplex OLX702A-075-16 was the major compound in plasma. The GalNAc moiety was predominantly metabolized from the sense strand in the liver, with the unconjugated sense strand of OLX702A-075-16 accounting for more than 95% of the total exposure in the rat liver. Meanwhile, the antisense strand was metabolized by the sequential loss of nucleotides from the 3'-terminus by exonuclease, with the rat liver samples yielding the most diverse truncated forms of metabolites. Urinary excretion over 96 hours was less than 1% of the administered dose in rats. High plasma protein binding of OLX702A-075-16 likely inhibited its clearance through renal filtration.

SIGNIFICANCE STATEMENT

This study presents the first comprehensive characterization of the in vivo pharmacokinetics of GalNAc-asiRNA. The pharmacokinetic insights gained from this research will aid in understanding toxicology and efficacy, optimizing delivery platforms, and improving the predictive power of preclinical species data for human applications.




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Twinning Partnership Network: A Learning and Experience-Sharing Network Among Health Professionals in Rwanda to Improve Health Services

ABSTRACTWe describe the development, implementation, and evaluation of a novel twinning approach: the Twinning Partnership Network (TPN). Twinning is a well-known approach to peer learning that has been used in a variety of settings to build organizational capacity. Although twinning takes many forms, the heart of the approach is that institutions with shared characteristics collaborate via sharing information and experiences to achieve a specific goal. We adapted a twinning partnership strategy developed by the World Health Organization to create a network of like-minded health institutions. The key innovation of the TPN is the network, which ensures that an institution always has a high-performing peer with whom to partner on a specific topic area of interest. We identified 10 hospitals and 30 districts in Rwanda to participate in the TPN. These districts and hospitals participated in a kickoff workshop in which they identified capacity gaps, clarified goals, and selected twinning partners. After the workshop, districts and hospitals participated in exchange visits, coaching visits, and virtual and in-person learning events. We found that districts and hospitals that selected specific areas and worked on them throughout the duration of the TPN with their peers improved their performance significantly when compared with those that selected and worked on other areas. Accreditation scores improved by 5.6% more in hospitals selecting accreditation than those that did not. Districts that selected improving community-based health insurance coverage improved by 4.8% more than districts that did not select this topic area. We hypothesize that these results are due to senior management’s interest and motivation to improve in these specific areas, the motivation gained by learning from high-performing peers with similar resources, and context-specific knowledge sharing from peer hospitals and districts.




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Freehand SPECT Combined with 3-Dimensional Light Detection and Ranging as Alternative Means of Specimen Scanning During Prostate Cancer Surgery




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Best Patient Care Practices for Administering PSMA-Targeted Radiopharmaceutical Therapy

Optimal patient management protocols for metastatic castration-resistant prostate cancer (mCRPC) are poorly defined and even further complexified with new therapy approvals, such as radiopharmaceuticals. The prostate-specific membrane antigen (PSMA)–targeted agent 177Lu vipivotide tetraxetan ([177Lu]Lu-PSMA-617), approved after the phase III VISION study, presents physicians with additional aspects of patient management, including specific adverse event (AE) monitoring and management, as well as radiation safety. Drawing on our experience as VISION study investigators, here we provide guidance on best practices for delivering PSMA-targeted radiopharmaceutical therapy (RPT) to patients with mCRPC. After a comprehensive review of published evidence and guidelines on RPT management in prostate cancer, we identified educational gaps in managing the radiation safety and AEs associated with [177Lu]Lu-PSMA-617. Our results showed that providing sufficient education on AEs (e.g., fatigue and dry mouth) and radiation safety principles is key to effective delivery and management of patient expectations. Patient counseling by health care professionals, across disciplines, is a cornerstone of optimal patient management during PSMA-targeted RPT. Multidisciplinary collaboration is crucial, and physicians must adhere to radiation safety protocols and counsel patients on radiation safety considerations. Treatment with [177Lu]Lu-PSMA-617 is generally well tolerated; however, additional interventions may be required, such as dosing modification, medications, or transfusions. Urinary incontinence can be challenging in the context of radiation safety. Multidisciplinary collaboration between medical oncologists and nuclear medicine teams ensures that patients are monitored and managed safely and efficiently. In clinical practice, the benefit-to-risk ratio should always be evaluated on a case-by-case basis.




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Pharmacological Approaches to Hearing Loss [75th Anniversary Celebration Collection Special Section]

Hearing disorders pose significant challenges to individuals experiencing them and their overall quality of life, emphasizing the critical need for advanced pharmacological approaches to address these conditions. Current treatment options often focus on amplification devices, cochlear implants, or other rehabilitative therapies, leaving a substantial gap regarding effective pharmacological interventions. Advancements in our understanding of the molecular and cellular mechanisms involved in hearing disorders induced by noise, aging, and ototoxicity have opened new avenues for drug development, some of which have led to numerous clinical trials, with promising results. The development of optimal drug delivery solutions in animals and humans can also enhance the targeted delivery of medications to the ear. Moreover, large genome studies contributing to a genetic understanding of hearing loss in humans combined with advanced molecular technologies in animal studies have shown a great potential to increase our understanding of the etiologies of hearing loss. The auditory system exhibits circadian rhythms and temporal variations in its physiology, its vulnerability to auditory insults, and its responsiveness to drug treatments. The cochlear clock rhythms are under the control of the glucocorticoid system, and preclinical evidence suggests that the risk/benefit profile of hearing disorder treatments using chronopharmacological approaches would be beneficial. If translatable to the bedside, such approaches may improve the outcome of clinical trials. Ongoing research into the molecular and genetic basis of auditory disorders, coupled with advancements in drug formulation and delivery as well as optimized timing of drug administration, holds great promise of more effective treatments.

Significance Statement

Hearing disorders pose significant challenges to individuals and their overall quality of life, emphasizing the critical need for advanced pharmacological approaches to address these conditions. Ongoing research into the molecular and genetic basis of auditory disorders, coupled with advancements in drug delivery procedures and optimized timing of drug administration, holds the promise of more effective treatments.




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Analysis of Sleep and Circadian Rhythms from Drosophila Activity-Monitoring Data Using SCAMP

Sleep is a fundamental feature of life for virtually all multicellular animals, but many questions remain about how sleep is regulated and what biological functions it plays. Substantial headway has been made in the study of both circadian rhythms and sleep in the fruit fly Drosophila melanogaster, much of it through studies of individual fly activity using beam break counts from Drosophila activity monitors (DAMs). The number of laboratories worldwide studying sleep in Drosophila has grown from only a few 20 years ago to hundreds today. The utility of these studies is limited by the quality of the metrics that can be extracted from the data. Many software options exist to help analyze DAM data; however, these are often expensive or have significant limitations. Therefore, we describe here a method for analyzing DAM-based data using the sleep and circadian analysis MATLAB program (SCAMP). This user-friendly software has an advantage of combining several analyses of both sleep and circadian rhythms in one package and produces graphical outputs as well as spreadsheets of the outputs for further statistical analysis. The version of SCAMP described here is also the first published software package that can analyze data from multibeam DAM5Ms, enabling determination of positional preference over time.




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Neural Stimulation during Drosophila Activity Monitor (DAM)-Based Studies of Sleep and Circadian Rhythms in Drosophila melanogaster

Sleep is a fundamental feature of life for virtually all multicellular animals, but many questions remain about how sleep is regulated by circadian rhythms, homeostatic sleep drive that builds up with wakefulness, and modifying factors such as hunger or social interactions, as well as about the biological functions of sleep. Substantial headway has been made in the study of both circadian rhythms and sleep in the fruit fly Drosophila melanogaster, much of it through studies of individual fly activity using Drosophila activity monitors (DAMs). Here, we describe approaches for the activation of specific neurons of interest using optogenetics (involving genetic modifications that allow for light-based neuronal activation) and thermogenetics (involving genetic modifications that allow for temperature-based neuronal activation) so that researchers can evaluate the roles of those neurons in controlling rest and activity behavior. In this protocol, we describe how to set up a rig for simultaneous optogenetic or thermogenetic stimulation and activity monitoring for analysis of sleep and circadian rhythms in Drosophila, how to raise appropriate flies, and how to perform the experiment. This protocol will allow researchers to assess the causative role in the regulation of sleep and activity rhythms of any genetically tractable subset of cells.




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Activity Monitoring for Analysis of Sleep in Drosophila melanogaster

Sleep is important for survival, and the need for sleep is conserved across species. In the past two decades, the fruit fly Drosophila melanogaster has emerged as a promising system in which to study the genetic, neural, and physiological bases of sleep. Through significant advances in our understanding of the regulation of sleep in flies, the field is poised to address several open questions about sleep, such as how the need for sleep is encoded, how molecular regulators of sleep are situated within brain networks, and what the functions of sleep are. Here, we describe key findings, open questions, and commonly used methods that have been used to inform existing theories and develop new ways of thinking about the function, regulation, and adaptability of sleep behavior.




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Engineering of Affibody Molecules

Affibody molecules are small, robust, and versatile affinity proteins currently being explored for therapeutic, diagnostic, and biotechnological applications. Surface-exposed residues on the affibody scaffold are randomized to create large affibody libraries from which novel binding specificities to virtually any protein target can be generated using combinatorial protein engineering. Affibody molecules have the potential to complement—or even surpass—current antibody-based technologies, exhibiting multiple desirable properties, such as high stability, affinity, and specificity, efficient tissue penetration, and straightforward modular extension of functional domains. It has been shown in both preclinical and clinical studies that affibody molecules are safe, efficacious, and valuable alternatives to antibodies for specific targeting in the context of in vivo diagnostics and therapy. Here, we provide a general background of affibody molecules, give examples of reported applications, and briefly summarize the methodology for affibody generation.




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Healthcare avoidance during the early stages of the COVID-19 pandemic and all-cause mortality: a longitudinal community-based study

BackgroundDuring the COVID-19 pandemic, global trends of reduced healthcare-seeking behaviour were observed. This raises concerns about the consequences of healthcare avoidance for population health.AimTo determine the association between healthcare avoidance during the early stages of the COVID-19 pandemic and all-cause mortality.Design and settingThis was a 32-month follow-up within the population-based Rotterdam Study, after sending a COVID-19 questionnaire at the onset of the pandemic in April 2020 to all communty dwelling participants (n = 6241/8732, response rate 71.5%).MethodCox proportional hazards models assessed the risk of all-cause mortality among respondents who avoided health care because of the COVID-19 pandemic. Mortality status was collected through municipality registries and medical records.ResultsOf 5656 respondents, one-fifth avoided health care because of the COVID-19 pandemic (n = 1143). Compared with non-avoiders, those who avoided health care more often reported symptoms of depression (n = 357, 31.2% versus n = 554, 12.3%) and anxiety (n = 340, 29.7% versus n = 549, 12.2%), and more often rated their health as poor to fair (n = 336, 29.4% versus n = 457, 10.1%) . Those who avoided health care had an increased adjusted risk of all-cause mortality (hazard ratio [HR] 1.30, 95% confidence interval [CI] = 1.01 to 1.67), which remained nearly identical after adjustment for history of any non-communicable disease (HR 1.20, 95% CI = 0.93 to 1.54). However, this association attenuated after additional adjustment for mental and physical self-perceived health factors (HR 0.93, 95% CI = 0.71 to 1.20).ConclusionThis study found an increased risk of all-cause mortality among individuals who avoided health care during COVID-19. These individuals were characterised by poor mental and physical self-perceived health. Therefore, interventions should be targeted to these vulnerable individuals to safeguard their access to primary and specialist care to limit health disparities, inside and beyond healthcare crises.




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Weight trends among adults with diabetes or hypertension during the COVID-19 pandemic: an observational study using OpenSAFELY

BackgroundCOVID-19 pandemic restrictions may have influenced behaviours related to weight.AimTo describe patterns of weight change among adults living in England with type 2 diabetes (T2D) and/or hypertension during the pandemic.Design and settingAn observational cohort study using the routinely collected health data of approximately 40% of adults living in England, accessed through the OpenSAFELY service inside TPP.MethodClinical and sociodemographic characteristics associated with rapid weight gain (>0.5 kg/m2/year) were investigated using multivariable logistic regression.ResultsData were extracted on adults with T2D (n = 1 231 455, 43.9% female, and 76.0% White British) or hypertension (n = 3 558 405, 49.7% female, and 84.3% White British). Adults with T2D lost weight overall (median δ = −0.1 kg/m2/year [interquartile range {IQR} −0.7–0.4]). However, rapid weight gain was common (20.7%) and associated with the following: sex (male versus female: adjusted odds ratio [aOR] 0.78 [95% confidence interval {CI} = 0.77 to 0.79]); age (older age reduced odds, for example, aged 60–69 years versus 18–29 years: aOR 0.66 [95% CI = 0.61 to 0.71]); deprivation (least deprived Index of Multiple Deprivation [IMD] quintile versus most deprived IMD quintile: aOR 0.87 [95% CI = 0.85 to 0.89]); White ethnicity (Black versus White: aOR 0.95 [95% CI = 0.92 to 0.98]); mental health conditions (for example, depression: aOR 1.13 [95% CI = 1.12 to 1.15]); and diabetes treatment (non-insulin treatment versus no pharmacological treatment: aOR 0.68 [95% CI = 0.67 to 0.69]). Adults with hypertension maintained stable weight overall (median δ = 0.0 kg/m2/year [IQR −0.6–0.5]); however, rapid weight gain was common (24.7%) and associated with similar characteristics as in T2D.ConclusionAmong adults living in England with T2D and/or hypertension, rapid pandemic weight gain was more common among females, younger adults, those living in more deprived areas, and those with mental health conditions.