Clinical Practice Patterns in Sickle Cell Disease Treatment: Disease-Modifying and Potentially Curative Therapies.

Therapeutic options for sickle cell disease (SCD) have increased recently as well as the development of updated national guidelines. It is not known how these options are being offered or to what degree guidelines are incorporated into clinical practice. This study aimed to describe practice patterns for pediatric hematologists regarding the use of disease-modifying and potentially curative therapies for SCD. A 9-section, cross-sectional electronic survey was disseminated during a 3-month period via SurveyMonkey, to members of the American Society of Pediatric Hematology/Oncology Hemoglobinopathy Special Interest Group (ASPHO HSIG). A total of 88 physician members of the ASPHO HSIG were surveyed. Ninety percent of respondents (72/80) start hydroxyurea routinely in patients with HbSS and HbSß0 thalassemia, regardless of disease severity. Laboratory monitoring was recommended every 3 months for stable dosing in 63.8% (51/80). New therapies were recommended for patients on hydroxyurea who were still experiencing SCD complications: L-glutamine 68.5% (37/54) or crizanlizumab 93.1% (54/58). Voxelotor was recommended for patients on hydroxyurea with low hemoglobin in 65.1% (43/66) of cases. Matched sibling transplant was considered for any disease severity by 55.1% (38/69). Gene therapy trials are offered on-site by 29% (20/69). Our study demonstrated the enhanced utilization of hydroxyurea while revealing the unexplored potential of other disease-modifying therapies in SCD. These findings underscore the importance of continued knowledge acquisition about the long-term efficacy of new medical therapies and addressing barriers to the use of proven therapies and guide the development of future studies of optimal SCD management.

Probucol-Ursodeoxycholic Acid Otic Formulations: Stability and In Vitro Assessments for Hearing Loss Treatment.

Targeted drug delivery is an ongoing aspect of scientific research that is expanding through the design of micro- and nanoparticles. In this paper, we focus on spray dried microparticles as carriers for a repurposed lipophilic antioxidant (probucol). We characterise the microparticles and quantify probucol prior to assessing cytotoxicity on both control and cisplatin treated hair cells (known as House Ear Institute-Organ of Corti 1; HEI-OC1). The addition of water-soluble polymers to 2% ß-cyclodextrin resulted in a stable probucol formulation. Ursodeoxycholic acid (UDCA) used as formulation excipient increases probucol miscibility and microparticle drug content. Formulation characterisations reveals spray drying results in spherical UDCA-drug microparticles with a mean size distribution of ∼5-12 µm. Probucol microparticles show stable short-term storage conditions accounting for only ∼10% loss over seven days. By mimicking cell culture conditions, both UDCA-probucol (67%) and probucol only (82%) microparticles show drug release in the initial two hours. Furthermore, probucol formulations with or without UDCA preserve cell viability and reduce cisplatin-induced oxidative stress. Mitochondrial bioenergetics results in lower basal respiration and non-mitochondrial respiration, with higher maximal respiration, spare capacity, ATP production and proton leak within cisplatin challenged UDCA-probucol groups. Overall, we present a facile method for incorporating lipophilic antioxidant carriers in polymer-based particles that are tolerated by HEI-OC1 cells and show stable drug release, sufficient in reducing cisplatin-induced reactive oxygen species accumulation.

Hidden support for the lionesses: a breast/bra intervention.

Despite health and performance benefits of appropriate breast support in sport, elite women athletes' knowledge of breasts/bras is poor leading to poor bra choices, breast pain and performance decrements. This multiphase intervention assessed breast/bra issues and preferences, individually prescribed sports bras and evaluated outcomes for the England Senior Women footballers. Breast/bra workshops were delivered to England players; all 36 completed pre-intervention surveys and breast/bra assessments, before being prescribed bras six weeks before European and World Championships (2022, 2023). 24 players completed post-intervention surveys. Pre-intervention outcomes identified poor knowledge, poor bra fit, many bra issues, and cultural sensitivities. Breast pain was prevalent (61%), with 25% reporting clinically significant breast pain. Post-intervention, players reported significant improvements with prescribed sports bras. 91% reported improvements in knowledge and benefiting from the intervention. This successful intervention provided an evidence-base for ongoing breast health initiatives with England Teams, plus roll-out to all levels of women's football.

A Qualitative Study Describing Experiences of Pregnancy Discrimination in the Workplace.

OBJECTIVES: Qualitatively assess experiences of occupational pregnancy discrimination. METHODS: A fully remote phenomenological qualitative study was completed leveraging semi-structured interviews with a sample of pregnant employees in the US. Inclusion criteria included being pregnant, working at least 35 hours/week, employed at least one year at current employer, and without diagnosed depression/anxiety. RESULTS: Participants (N = 20) were on average 30 years of age, worked 42.6 hours per week, self-identified as non-Hispanic black (50%) and earned least a bachelor's degree (85%). Individuals successfully identified various forms of pregnancy discrimination, believing it occurred due to systemic issues or perceptions that women are weak. Most did not report experiences of discrimination fearing retaliation or being unaware of workplace protections. CONCLUSION: Pregnancy discrimination in the workplaces comes in various forms and is an issue for some working pregnant individuals.

Size Distributions of Microplastics in the St Louis Estuary and Western Lake Superior.

Identifying the sources and fate of microplastics in natural systems has garnered a great deal of attention because of their implications for ecosystem health. This work characterizes the size fraction, morphology, color, and polymer composition of microplastics in western Lake Superior and its adjacent harbor sampled in August and September 2021. The results reveal that the overall microplastic counts are similar, with the harbor stations ranging from 0.62 to 3.32 microplastics per liter and the lake stations ranged from 0.83 to 1.4 microplastics per liter. However, meaningful differences between the sample locations can be seen in the size fraction trends and polymer composition. Namely, the harbor samples had relatively larger amounts of the largest size fraction and more diversity of polymer types, which can be attributed to the urbanized activity and shorter water residence time. Power law size distribution modeling reveals deviations that help in the understanding of potential sources and removal mechanisms, although it significantly underpredicts microplastic counts for smaller-sized particles (5-45 µm), as determined by comparison with concurrently collected microplastic samples enumerated by Nile Red staining and flow cytometry.

Probucol-bile acid nanoparticles: A Novel Approach and Promising Solution to Prevent Cellular Oxidative Stress in Sensorineural Hearing Loss.

The use of anti-oxidants could thus prove an effective medication to prevent or facilitate recovery from oxidative stress-induced sensorineural hearing loss (SNHL). One promising strategy to prevent SNHL is developing probucol (PB)-based nanoparticles using encapsulation technology and administering them to the inner ear via the established intratympanic route. The preclinical, clinical and epidemiological studies support that probucol is a proven anti-oxidant that could effectively prevent oxidative stress in different study models. Such findings suggest its applicability in preventing oxidative stress within the inner ear and its associated neural cells. However, several hurdles, such as overcoming the blood-labyrinth barrier, ensuring sustained release, minimizing systemic side effects, and optimizing targeted delivery in the intricate inner ear structures, must be overcome to efficiently deliver PB to the inner ear. This review explores the background and pathogenesis of hearing loss, the potential of PB in treating oxidative stress and its cellular mechanisms, and the obstacles linked to inner ear drug delivery for effectively introducing PB to the inner ear.

Polymer-Based Nanoparticles for Inner Ear Targeted Trans Differentiation Gene Therapy.

Hearing loss is a significant disability that often goes under recognised, largely due to poor identification, prevention, and treatment. Steps are being made to amend these pitfalls in the investigation of hearing loss, however, the development of a cure to reverse advanced forms remains distant. This review details some current advances in the treatment of hearing loss, with a particular focus on genetic-based nanotechnology and how it may provide a useful avenue for further research. This review presents a broad background on the pathophysiology of hearing loss and some current interventions. We also highlight some potential genes that may be useful in the amelioration of hearing loss. Pathways of cellular differentiation from stem or supporting cell to functional hair cell are covered in detail, as this mechanism represents a key means of regenerating these cell types. Overall, we believe that polymer-based nanotechnology coupled with novel excipients represents a useful area of further research in the treatment of hearing loss, although further studies in this area are required.

Adverse childhood experiences, gender, and suicidality among Florida high school students: Examining intervening mechanisms.

BACKGROUND: Adverse childhood experiences (ACEs) represent a key risk factor for suicidal thoughts and behaviors among adolescents. However, the intervening mechanisms linking ACEs and suicidality, and whether such processes vary by gender, remain underexplored. OBJECTIVE: The present study examines whether the relationships between ACEs and the likelihood of experiencing suicidal thoughts and attempting suicide are indirect through depressive symptoms and low self-control. This study also investigates whether these direct and indirect paths might be moderated by gender. PARTICIPANTS AND SETTING: The analyses make use of data on a statewide representative sample of students enrolled in public high schools in Florida (N = 23,078) from the 2022 Florida Youth Substance Abuse Survey (FYSAS). METHODS: Generalized structural equation modeling (GSEM) was used to estimate the direct and indirect effects of ACEs on the likelihood of suicidal thoughts and attempting suicide. The indirect effects were assessed using bootstrapping, and between-gender differences in the coefficients were tested. RESULTS: ACEs has direct associations with depressive symptoms, low self-control, and both suicidality outcomes. The effects of ACEs on suicidal thoughts are indirect through both depressive symptoms and low self-control, and the effects of ACEs on suicide attempts are indirect through depressive symptoms. Limited gender differences in these pathways emerge. CONCLUSIONS: For male and female youth, ACEs are associated with heightened depression symptoms and reduced self-control, and both of these factors partially explain the previously established relationship between ACEs and suicidality.

Bovine Serum Albumin Bends Over Backward to Interact with Aged Plastics: A Model for Understanding Protein Attachment to Plastic Debris.

Plastic pollution, a major environmental crisis, has a variety of consequences for various organisms within aquatic systems. Beyond the direct toxicity, plastic pollution has the potential to absorb biological toxins and invasive microbial species. To better understand the capability of environmental plastic debris to adsorb these species, we investigated the binding of the model protein bovine serum albumin (BSA) to polyethylene (PE) films at various stages of photodegradation. Circular dichroism and fluorescence studies revealed that BSA undergoes structural rearrangement to accommodate changes to the polymer's surface characteristics (i.e., crystallinity and oxidation state) that occur as the result of photodegradation. To understand how protein structure may inform docking of whole organisms, we studied biofilm formation of bacteriaShewanella oneidensison the photodegraded PE. Interestingly, biofilms preferentially formed on the photodegraded PE that correlated with the state of weathering that induced the most significant structural rearrangement of BSA. Taken together, our work suggests that there are optimal physical and chemical properties of photodegraded polymers that predict which plastic debris will carry biochemical or microbial hitchhikers.

Rates and Predictors of Rapid Eye Movement Sleep Behavior Disorder Symptoms Among Post-9/11 Veterans.

OBJECTIVE: Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI), which are prevalent conditions among post-9/11 veterans, increase risks of rapid eye movement (REM) sleep behavior disorder (RBD) and degenerative synucleinopathy. Rates and predictors of RBD symptoms were investigated by screening post-9/11 veterans for RBD with a validated questionnaire. METHODS: In this cross-sectional analysis, consecutive patients in the Houston Translational Research Center for TBI and Stress Disorders (TRACTS) were screened with the English translation of the RBD Questionnaire-Hong Kong (RBDQ-HK). In addition to data from the standard TRACTS battery, systematic chart review was used to identify known sleep disorders mimicking or manifesting RBD. RESULTS: Of the 119 patients with available RBDQ-HK scores, 71 (60%) and 65 (55%) screened positive for RBD, when a total score ≥21 and a factor 2 score ≥8 were used as cutoff scores, respectively. Univariable analyses with both cutoffs showed consistent associations between a positive RBDQ-HK screen and global sleep quality, number of TBI exposures, and PTSD severity. Multivariable logistic regression with total score ≥21 as a cutoff indicated that PTSD severity (odds ratio=1.06, 95% CI=1.02-1.10) and number of TBIs (odds ratio=1.63, 95% CI=1.16-2.41) were independent predictors of a positive screen, whereas global sleep quality was no longer significant. Multivariable logistic regression with factor 2 score ≥8 as a cutoff showed similar results. CONCLUSIONS: Interdisciplinary parasomnia assessment, further validation of RBD screens, and standardized reporting of REM sleep without atonia could provide necessary information on the pathophysiological relationships linking PTSD, TBI, RBD symptoms, and ultimately synucleinopathy risk among post-9/11 veterans.

Call me Ishmael: addressing the white whale of team communication in the operating room with labelled surgical caps at an academic medical centre.

INTRODUCTION: Effective communication in the operating room (OR) is crucial. Addressing a colleague by their name is respectful, humanising, entrusting and associated with improved clinical outcomes. We aimed to enhance team communication in the perioperative environment by offering personalised surgical caps labelled with name and provider role to all OR team members at a large academic medical centre. MATERIALS AND METHODS: This was a quasi-experimental, uncontrolled, before-and-after quality improvement study. A survey regarding perceptions of team communication, knowledge of names and roles, communication barriers, and culture was administered before and after cap delivery. Survey results were measured on a 5-point Likert Scale; descriptive statistics and mean scores were compared. All cause National Surgical Quality Improvement Project (NSQIP) morbidity and mortality outcomes for surgical specialties were examined. RESULTS: 1420 caps were delivered across the institution. Mean survey scores increased for knowing the names and roles of providers around the OR, feeling that people know my name and feeling comfortable communicating without barriers across disciplines. The mean score for team communication around the OR is excellent was unchanged. The highest score both before and after was knowing the name of an interdisciplinary team member is important for patient care. A total of 383 and 212 providers participated in the study before and after cap delivery, respectively. Participants agreed or strongly agreed that labelled surgical caps made it easier to talk to colleagues (64.9%) while improving communication (66.0%), team culture (60.5%) and patient care (56.8%). No significant differences were noted in NSQIP outcomes. CONCLUSIONS: Personalised labelled surgical caps are a simple, inexpensive tool that demonstrates promise in improving perioperative team communication. Creating highly reliable surgical teams with optimal communication channels requires a multifaceted approach with engaged leadership, empowered front-line providers and an institutional commitment to continuous process improvement.

Validation of electronic diagnostic codes for rapid eye movement sleep behavior disorder.

We investigated the accuracy of International Classification of Diseases (ICD) codes for the identification of Veterans with rapid eye movement (REM) sleep behavior disorder (RBD). The charts of 139 randomly sampled Veterans with ≥1 ICD-9 and ICD-10 code(s) for RBD were reviewed for documentation of a suspected, previous, or current diagnosis; clinical symptoms; and/or empiric treatments for this disorder. Notably, 71 (51.1%) of patients with RBD electronic diagnoses lacked polysomnography (PSG), and 29 (20.9%) had PSG reports without commentary on REM sleep without atonia (RSWA). Sleep centers are therefore encouraged to include a brief sentence in PSG report templates commenting on the presence/absence of RSWA.

A comparison of virtual reality anatomy models to prosections in station-based anatomy teaching.

Immersive virtual reality (i-VR) is a powerful tool that can be used to explore virtual models in three dimensions. It could therefore be a valuable tool to supplement anatomical teaching by providing opportunities to explore spatial anatomical relationships in a virtual environment. However, there is a lack of consensus in the literature as to its effectiveness as a teaching modality when compared to the use of cadaveric material. The aim of our study was to compare the effectiveness of i-VR in facilitating understanding of different anatomical regions when compared with cadaveric prosections for a cohort of first- and second-year undergraduate medical students. Students (n = 92) enrolled in the MBBS program at Queen Mary University of London undertook an assessment, answering questions using either Oculus i-VR headsets, the Human Anatomy VR™ application, or prosection materials. Utilizing ANOVA with Sidak's multiple comparison test, we found no significant difference between prosections and i-VR scores in the abdomen (p = 0.6745), upper limb (p = 0.8557), or lower limb groups (p = 0.9973), suggesting that i-VR may be a viable alternative to prosections in these regions. However, students scored significantly higher when using prosections when compared to i-VR for the thoracic region (p < 0.0001). This may be due to a greater need for visuospatial understanding of 3D relationships when viewing anatomical cavities, which is challenged by a virtual environment. Our study supports the use of i-VR in anatomical teaching but highlights that there is significant variation in the efficacy of this tool for the study of different anatomical regions.

Post-fire stabilization of thaw-affected permafrost terrain in northern Alaska.

In 2007, the Anaktuvuk River fire burned more than 1000 km2 of arctic tundra in northern Alaska, ~ 50% of which occurred in an area with ice-rich syngenetic permafrost (Yedoma). By 2014, widespread degradation of ice wedges was apparent in the Yedoma region. In a 50 km2 area, thaw subsidence was detected across 15% of the land area in repeat airborne LiDAR data acquired in 2009 and 2014. Updating observations with a 2021 airborne LiDAR dataset show that additional thaw subsidence was detected in < 1% of the study area, indicating stabilization of the thaw-affected permafrost terrain. Ground temperature measurements between 2010 and 2015 indicated that the number of near-surface soil thawing-degree-days at the burn site were 3 × greater than at an unburned control site, but by 2022 the number was reduced to 1.3 × greater. Mean annual ground temperature of the near-surface permafrost increased by 0.33 °C/yr in the burn site up to 7-years post-fire, but then cooled by 0.15 °C/yr in the subsequent eight years, while temperatures at the control site remained relatively stable. Permafrost cores collected from ice-wedge troughs (n = 41) and polygon centers (n = 8) revealed the presence of a thaw unconformity, that in most cases was overlain by a recovered permafrost layer that averaged 14.2 cm and 18.3 cm, respectively. Taken together, our observations highlight that the initial degradation of ice-rich permafrost following the Anaktuvuk River tundra fire has been followed by a period of thaw cessation, permafrost aggradation, and terrain stabilization.

Probucol-bile acid based nanoparticles protect auditory cells from oxidative stress: an in vitro study.

Aim: Excessive free radicals contribute to oxidative stress and mitochondrial dysfunction in sensorineural hearing loss (SNHL). The antioxidant probucol holds promise, but its limited bioavailability and inner ear barriers hinder effective SNHL treatment. Methodology: We addressed this by developing probucol-loaded nanoparticles with polymers and lithocholic acid and tested them on House Ear Institute-Organ of Corti cells. Results: Probucol-based nanoparticles effectively reduced oxidative stress-induced apoptosis, enhanced cellular viability, improved probucol uptake and promoted mitochondrial function. Additionally, they demonstrated the capacity to reduce reactive oxygen species through the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway. Conclusion: This innovative nanoparticle system holds the potential to prevent oxidative stress-related hearing impairment, providing an effective solution for SNHL.

Hearing loss affects millions of people worldwide, and its prevalence is expected to double by 2050. Current treatments have limitations, pushing researchers to explore new options. Oxidative stress is a key player in hearing loss and is known to damage inner ear hair cells. While antioxidants, known for their protective effects, hold promise, delivering them effectively to the inner ear is challenging. Scientists have been testing nanoparticles loaded with the antioxidant probucol to fight hearing loss. In this study, these particles protected inner ear cells in cell studies, offering potential hope for preventing hearing problems. This research is a significant step toward finding better treatments for hearing loss.

Associations of Physical Activity and Sedentary Behaviors with Depressive Symptoms and Mood Disturbance Throughout Pregnancy.

Purpose: Mental health is critical for a healthy pregnancy, yet few studies have evaluated its associations with best practice, objectively measured moderate- to vigorous-intensity physical activity (MVPA) or sedentary behavior (SED). This study evaluated associations of MVPA and SED with mental health across pregnancy. Materials and Methods: Two cohort studies (total n = 125, mean [standard deviation] 31 [5] years, and 14.4% Black) measured MVPA (waist-worn ActiGraph GT3X) and SED (thigh-mounted activPAL) as well as self-reported depressive symptoms and mood disturbance in each trimester. Associations of group-based trajectories of MVPA and SED with depressive symptoms and mood disturbance were analyzed using regression analyses, both overall and by trimester. Results: Overall, the medium versus low trajectory of MVPA was associated with lower levels of depressive symptoms (B = -1.82, 95% confidence interval [CI] -2.97 to -0.68). In the second trimester, women in either the medium or high MVPA trajectories had lower levels of depressive symptoms compared with women in the low MVPA trajectory (B = -8.73, 95% CI -15.74 to -1.71; and B = -2.18, 95% CI -3.80 to -0.56). SED trajectories were not associated with depressive symptoms. Higher trajectories of MVPA and lower trajectories of SED were associated with lower total mood disturbance, with significant associations in the second trimester for MVPA and the first and second trimesters for SED. Higher MVPA trajectories were associated with higher tension, fatigue, and confusion subscales, while higher SED trajectories were associated with higher anger and fatigue and lower esteem and vigor subscales. Conclusions: MVPA and SED levels appear to affect mental health during pregnancy, although larger prospective studies are warranted. Clinical Trail Registration Number: NCT03084302.

A hybrid approach to complex bilateral common iliac artery and internal iliac artery aneurysm repair.

A case of a young patient with incidental bilateral internal iliac artery aneurysms and common iliac artery aneurysms is described. A staged hybrid surgical approach was performed to preserve pelvic perfusion, with bilateral stent grafts deployed into an ipsilateral anterior division branch and contralateral posterior division branch of the internal iliac arteries. One week later, an open infrarenal aorto-bi-iliac graft was performed with distal anastomoses to the previously deployed stent grafts. The findings from the present case add to the growing number of reported cases of hybrid repair of bilateral internal iliac and common iliac artery aneurysms with preservation of pelvic perfusion.

Physical Violence and Aggression in Parkinson's Disease: A Systematic Review.

BACKGROUND: Physical violence and aggression (PVA), defined as behaviors with the potential to cause bodily injury, are unfortunate risks in the management of all-cause neurodegenerative dementias. While dementia in Parkinson's disease (PD) may not be evident for many years after clinical onset, neuropsychiatric disturbances occur at all stages of the disease. At issue is whether PVA in PD is associated with clinical factors that can be targets for prevention and management in the absence of a prevailing dementia syndrome. OBJECTIVE: This systematic review examined the extent to which PVA in PD without dementia is a clinically significant concern and whether it is associated with factors that could warrant proactive management. METHODS: A systematic search of 9 electronic databases used MeSH headings and equivalent terms for PD, aggression, and violence. Eligible manuscripts were original articles that were published in peer-reviewed journals and reported on adults with PD in the awake state with PVA as possible outcomes. Extracted data included study design, PD ascertainment methods and characteristics, PVA assessment methods, subject demographics, psychiatric and medical comorbidities, and pertinent results. Inciting and confounding factors were extracted from case reports. Quality assessment tools were applied in accordance with the study design (e.g., observational, qualitative, or case report). RESULTS: The search identified 10 manuscripts: 2 observational quantitative studies (total n with PD = 545), 1 qualitative study (n with PD = 20), and 7 case reports (n = 7). The observational studies suggested that PVA is less common than other neuropsychiatric disturbances, but heterogeneous methods and quality concerns prevented further conclusions. In the case reports, all patients were male, and most were early onset. In 6 of the reports, PVA occurred in the context of bilateral subthalamic nucleus deep brain stimulation. CONCLUSIONS: PVA, while relatively rare in PD, can be a significant management issue that is associated with select premorbid characteristics and antiparkinsonian motor treatments. As PVA may be under-reported, further understanding of its frequency, causes, risk factors, and outcomes would benefit from its systematic assessment, ideally using self-report and informant-based questionnaires.

The effect of deoxycholic acid-based hydrogels on hepatic, muscle and pancreatic beta cells.

Aim: The aim of this study is to test the biocompatibility of hydrogels with polysaccharides and bile acids on three murine cell lines. Materials & methods: Novel hydrogels containing poloxamer 407, polysaccharides (starch, pectin, acacia, carboxymethyl and methyl 2-hydroxyethyl cellulose) and deoxycholic acid were prepared using cold method, sterilized and used in biological assays to determine effects on hepatic, muscle, and pancreatic beta cells. Results and conclusion: Hydrogels with deoxycholic acid had tissue-depending effects on cellular survival and bioenergetics, resulting in the best cellular viability and bioenergetics within pancreatic beta cells. Further research is needed as proposed hydrogels may be beneficial for cell delivery systems of pancreatic beta cells.

In this study, we made gels using different materials, including five types of sugar and an acid found in bile. We investigated whether these gels would harm cells and their respiration. Muscle cells responded poorly to gels, as gels harmed their natural processes. Liver cells responded slightly better to gels, but gels still harmed them a lot. Cells found in the pancreas were not especially affected by gels, and these gels may be good candidates for further research with pancreatic cells. The gels could potentially be used to deliver drugs to the cells.