Cochlear zinc signaling dysregulation is associated with noise-induced hearing loss, and zinc chelation enhances cochlear recovery.

Exposure to loud noise triggers sensory organ damage and degeneration that, in turn, leads to hearing loss. Despite the troublesome impact of noise-induced hearing loss (NIHL) in individuals and societies, treatment strategies that protect and restore hearing are few and insufficient. As such, identification and mechanistic understanding of the signaling pathways involved in NIHL are required. Biological zinc is mostly bound to proteins, where it plays major structural or catalytic roles; however, there is also a pool of unbound, mobile (labile) zinc. Labile zinc is mostly found in vesicles in secretory tissues, where it is released and plays a critical signaling role. In the brain, labile zinc fine-tunes neurotransmission and sensory processing. However, injury-induced dysregulation of labile zinc signaling contributes to neurodegeneration. Here, we tested whether zinc dysregulation occurs and contributes to NIHL in mice. We found that ZnT3, the vesicular zinc transporter responsible for loading zinc into vesicles, is expressed in cochlear hair cells and the spiral limbus, with labile zinc also present in the same areas. Soon after noise trauma, ZnT3 and zinc levels are significantly increased, and their subcellular localization is vastly altered. Disruption of zinc signaling, either via ZnT3 deletion or pharmacological zinc chelation, mitigated NIHL, as evidenced by enhanced auditory brainstem responses, distortion product otoacoustic emissions, and number of hair cell synapses. These data reveal that noise-induced zinc dysregulation is associated with cochlear dysfunction and recovery after NIHL, and point to zinc chelation as a potential treatment for mitigating NIHL.

An association between Dnmt1 and Wnt in the production of oocytes in the whitefly Bemisia tabaci.

The function of DNA methylation in insects and the DNA methyltransferase (Dnmt) genes that influence methylation remains uncertain. We used RNA interference to reduce the gene expression of Dnmt1 within the whitefly Bemisia tabaci (Hemiptera:Aleyrodidae; Gennadius), a hemipteran species that relies on Dnmt1 for proper gametogenesis. We then used RNA-seq to test an a priori hypothesis that meiosis-related genetic pathways would be perturbed. We generally did not find an overall effect on meiosis-related pathways. However, we found that genes in the Wnt pathway, genes associated with the entry into meiosis in vertebrates, were differentially expressed. Our results are consistent with Dnmt1 knockdown influencing specific pathways and not causing general transcriptional response. This is a finding that is also seen with other insect species. We also characterised the methylome of B. tabaci and assessed the influence of Dnmt1 knockdown on cytosine methylation. This species has methylome characteristics comparable to other hemipterans regarding overall level, enrichment within gene bodies, and a bimodal distribution of methylated/non-methylated genes. Very little differential methylation was observed, and difference in methylation were not associated with differences in gene expression. The effect on Wnt presents an interesting new candidate pathway for future studies.

Offspring overcome poor parenting by being better parents.

The evolutionary repercussions of parental effects-the impact of the developmental environment provided by parents on offspring-are often discussed as static effects that can have negative influences on offspring fitness that may even persist across generations. However, individuals are not passive recipients and may mitigate the persistence of parental effects through their behaviour. Here, we tested how the burying beetle, Nicrophorus orbicollis, a species with complex parental care, responded to poor parenting. We cross-fostered young and manipulated the duration of parental care received and measured the impact on traits of both F1 and F2 offspring to experimentally extricate the effect of poor parenting from other parental effects. As expected, reducing parental care negatively affected traits that are ecologically important for burying beetles, including F1 offspring development time and body size. However, F1 parents that received reduced care as larvae spent more time feeding F2 offspring than parents that received full care as larvae. As a result, both the number and mass of F2 offspring were unaffected by the developmental experience of their parents. Our results show that flexible parental care may be able to overcome poor developmental environments and limit negative parental effects to a single generation.

Predicting Emission Wavelengths in Benzobisoxazole-Based OLEDs with Gradient Boosted Ensemble Models.

We demonstrate the use of gradient-boosted ensemble models that accurately predict emission wavelengths in benzobis[1,2-d:4,5-d']oxazole (BBO) based fluorescent emitters. We have curated a database of 50 molecules from previously published data by the Jeffries-EL group using density functional theory (DFT) computed ground and excited state features. We consider two machine learning (ML) models based on (i) whole cruciform molecules and (ii) their constituent fragment molecules. Both ML models provide accurate predictions with root-mean-square errors between 30 and 36 nm, competitive with state-of-the-art deep learning models trained on orders of magnitude more molecules, and this accuracy holds even when tested on four new BBO emitters unseen by the models. We also provide an interpretable feature importance analysis and discuss the relevant relationships between DFT and changes in predicted emission wavelength.

Analysis of driver behavior at grade-separated intersections to support design.

Understanding driver behaviors in varied traffic scenarios is critical to the design of safe and efficient roadways and traffic control device. This research presents an analysis of driver cognitive workload, situation awareness (SA) and performance for three different scenarios, including a standard intersection and contraflow grade-separated intersections (C-GSI) and quadrant GSI (Q-GSI) with lane assignment sign manipulations. The study used a simulator-based driving experiment with application of the NASA Task Load Index and Situation Awareness Global Assessment Technique to assess the influence of the scenarios on driver behavioral responses. The findings reveal challenges for drivers navigating the C-GSI, characterized by diminished SA and elevated workload. These states were associated with behaviors such as delayed lane changes, missed opportunities for appropriate lane changes, heightened acceleration behavior within deceleration segments, and frequent speeding. In contrast, while drivers in the Q-GSI scenario faced elevated workloads, their SA remained steady, largely due to lane-specific signs facilitating early lane changes. Although the Q-GSI led to increased speed variability and slight increases in deceleration, the use of supplementary speed signage revealed a promising alternative to the S-intersection. Correlation analysis highlighted a significant relationship between mental workload and acceleration responses, indicating that increased acceleration was associated with higher mental workload. In addition, a significant negative correlation between driver perceived performance and absolute lane deviations indicated that drivers with higher self-assessed performance were more accurate in lane-keeping. The study underscores the need for GSIs and signage designs that support driver SA, manage cognitive workload to improve driver performance and increase road safety.

Navigating the Unexpected: Right Aortic Arch Unveiled During Left Heart Catheterization.

A right aortic arch (RAA) is an extremely rare congenital anomaly with seven identified variants. While most variants are asymptomatic, those with a vascular ring can be associated with severe symptoms. We present an incidental RAA finding during left heart catheterization (LHC) in a 68-year-old female with multiple morbidities presented with worsening angina. Her echocardiogram was significant for inferolateral wall akinesia, prompting LHC. The procedure was challenging with an unexpected course of the guide wire distally behind the cardiac shadow. Pressure tracing confirmed arterial access and contrast injection revealed RAA. A subsequent aortic computed tomography angiography (CTA) confirmed RAA with mirror-image branching. Abnormal origin and angle of aortic arch branches pose challenges in choosing the proper access. We used the right radial artery approach, but the left radial approach may be superior in providing a more proximal access and avoiding the abnormal origin of the right subclavian artery (RSA). Choosing the appropriate angiographic view is also of utmost importance, and the right anterior oblique view provided better visualization in our case. Aortic arch anomalies are confirmed by a CTA or magnetic resonance angiography (MRA) of the aorta. This case underscores the importance of identifying the aortic arch anomalies and the imposed challenges during the LHC.

LOXHD1 is indispensable for coupling auditory mechanosensitive channels to the site of force transmission.

Hearing is initiated in hair cells by the mechanical activation of ion channels in the hair bundle. The hair bundle is formed by stereocilia organized into rows of increasing heights interconnected by tip links, which convey sound-induced forces to stereocilia tips. The auditory mechanosensitive channels are complexes containing at least four protein-subunits - TMC1/2, TMIE, CIB2, and LHFPL51-16 - and are located at the tips of shorter stereocilia at a yet-undetermined distance from the lower tip link insertion point17. While multiple auditory channel subunits appear to interact with the tip link, it remains unknown whether their combined interaction alone can resist the high-frequency mechanical stimulations owing to sound. Here we show that an unanticipated additional element, LOXHD1, is indispensable for maintaining the TMC1 pore-forming channel subunits coupled to the tip link. We demonstrate that LOXHD1 is a unique element of the auditory mechanotransduction complex that selectively affects the localization of TMC1, but not its close developmental paralogue TMC2. Taking advantage of our novel immunogold scanning electron microscopy method for submembranous epitopes (SUB-immunogold-SEM), we demonstrate that TMC1 normally concentrates within 100-nm of the tip link insertion point. In LOXHD1's absence, TMC1 is instead mislocalized away from this force transmission site. Supporting this finding, we found that LOXHD1 interacts selectively in vitro with TMC1 but not with TMC2 while also binding to channel subunits CIB2 and LHFPL5 and tip-link protein PCDH15. SUB-immunogold-SEM additionally demonstrates that LOXHD1 and TMC1 are physically connected to the lower tip-link complex in situ. Our results show that the TMC1-driven mature channels require LOXHD1 to stay coupled to the tip link and remain functional, but the TMC2-driven developmental channels do not. As both tip links and TMC1 remain present in hair bundles lacking LOXHD1, it opens the possibility to reconnect them and restore hearing for this form of genetic deafness.

Challenges & barriers for real-time integration of drones in emergency cardiac care: Lessons from the United States, Sweden, & Canada.

Importance: Out-of-hospital cardiac arrest (OHCA) is a leading cause of morbidity and mortality in the US and Europe (∼600,000 incident events annually) and around the world (∼3.8 million). With every minute that passes without cardiopulmonary resuscitation or defibrillation, the probability of survival decreases by 10%. Preliminary studies suggest that uncrewed aircraft systems, also known as drones, can deliver automated external defibrillators (AEDs) to OHCA victims faster than ground transport and potentially save lives. Objective: To date, the United States (US), Sweden, and Canada have made significant contributions to the knowledge base regarding AED-equipped drones. The purpose of this Special Communication is to explore the challenges and facilitators impacting the progress of AED-equipped drone integration into emergency medicine research and applications in the US, Sweden, and Canada. We also explore opportunities to propel this innovative and important research forward. Evidence review: In this narrative review, we summarize the AED-drone research to date from the US, Sweden, and Canada, including the first drone-assisted delivery of an AED to an OHCA. Further, we compare the research environment, emergency medical systems, and aviation regulatory environment in each country as they apply to OHCA, AEDs, and drones. Finally, we provide recommendations for advancing research and implementation of AED-drone technology into emergency care. Findings: The rates that drone technologies have been integrated into both research and real-life emergency care in each country varies considerably. Based on current research, there is significant potential in incorporating AED-equipped drones into the chain of survival for OHCA emergency response. Comparing the different environments and systems in each country revealed ways that each can serve as a facilitator or barrier to future AED-drone research. Conclusions and relevance: The US, Sweden, and Canada each offers different challenges and opportunities in this field of research. Together, the international community can learn from one another to optimize integration of AED-equipped drones into emergency systems of care.

Off the wall: incidental paraspinal and pelvic muscle pathology on abdominopelvic imaging.

As the use of cross-sectional abdominal and pelvic imaging has increased exponentially in the past several decades, incidental musculoskeletal findings have become commonplace. These are often unrelated to the indication for the examination and are frequently referred to as the "radiologist's blind spot" on these studies. The differential diagnosis for abnormalities of the paraspinal and pelvic musculature is, in many cases, quite different from the anterior abdominal wall muscles. Furthermore, due to their relatively deep location, pathology involving the former muscle groups is more likely to be clinically occult, often presenting only incidentally when the patient undergoes cross-sectional imaging. Effective treatment of diseases of these muscles is dependent on adherence to a diverse set of diagnostic and treatment algorithms. The purpose of this review article is to familiarize the radiologist with the unique pathology of these often-overlooked muscles of the abdomen and pelvis.

Racial and Ethnic Disparities in Acute Coronary Syndrome: A Nationally Representative Sample.

Background: Disparities in acute coronary syndrome (ACS) outcomes exist between racial and ethnic groups. We aimed to evaluate disparities in resource utilization and inpatient outcomes across multiple ethnic and racial groups using contemporary data. Methods: We identified hospital discharges for ACS in the United States using the National Inpatient Sample from 2015 to 2018. The International Classification of Diseases, Tenth Revision, Clinical Modification codes were used to identify variables of interest. The primary outcomes were in-hospital complications, length of stay, and total hospital charge. Statistical analysis was performed using STATA version 17. Results: Our analysis included 1,911,869 ACS discharges. Our sample was made up of 78.6% White, 12.1% Black, and 9.3% Hispanic patients. Hispanic and Black patients presenting with ACS were younger and had more cardiometabolic comorbidities than their White counterparts, especially hypertension, diabetes mellitus, and obesity. Despite social determinants of health being more likely to be unfavorable for Hispanics than their White counterparts, they were more likely to incur higher total hospital charges than their White counterparts. Black patients were the least likely to undergo revascularization procedures. Despite these differences, White patients had higher in-hospital mortality rates than Black and Hispanic patients. Conclusions: In this nationally representative study, despite having higher cardiometabolic comorbidity burden, lower socioeconomic status, and percutaneous intervention, Black and Hispanic patients experienced lower mortality rates than their White counterparts. Hispanic patients incurred the highest amount of total hospital charges for an ACS admission.