Spatial working memory for locations specified by vision and audition: Testing the amodality hypothesis

Spatial working memory can maintain representations from vision, hearing, and touch, representations referred to here as spatial images. The present experiment addressed whether spatial images from vision and hearing that are simultaneously present within working memory retain modality-specific tags or are amodal. Observers were presented with short sequences of targets varying in angular direction, with the targets in a given sequence being all auditory, all visual, or a sequential mixture of the two. On two thirds of the trials, one of the locations was repeated, and observers had to respond as quickly as possible when detecting this repetition. Ancillary detection and localization tasks confirmed that the visual and auditory targets were perceptually comparable. Response latencies in the working memory task showed small but reliable costs in performance on trials involving a sequential mixture of auditory and visual targets, as compared with trials of pure vision or pure audition. These deficits were statistically reliable only for trials on which the modalities of the matching location switched from the penultimate to the final target in the sequence, indicating a switching cost. The switching cost for the pair in immediate succession means that the spatial images representing the target locations retain features of the visual or auditory representations from which they were derived. However, there was no reliable evidence of a performance cost for mixed modalities in the matching pair when the second of the two did not immediately follow the first, suggesting that more enduring spatial images in working memory may be amodal

Docosanoic acid conjugation to siRNA enables functional and safe delivery to skeletal and cardiac muscles

Oligonucleotide therapeutics hold promise for the treatment of muscle- and heart-related diseases. However, oligonucleotide delivery across the continuous endothelium of muscle tissue is challenging. Here, we demonstrate that docosanoic acid (DCA) conjugation of small interfering RNAs (siRNAs) enables efficient (~5% of injected dose), sustainable ( \u3e 1 month), and non-toxic (no cytokine induction at 100 mg/kg) gene silencing in both skeletal and cardiac muscles after systemic injection. When designed to target myostatin (muscle growth regulation gene), siRNAs induced ~55% silencing in various muscle tissues and 80% silencing in heart, translating into a ~50% increase in muscle volume within 1 week. Our study identifies compounds for RNAi-based modulation of gene expression in skeletal and cardiac muscles, paving the way for both functional genomics studies and therapeutic gene modulation in muscle and heart

Kif15 functions as an active mechanical ratchet

Kif15 is a kinesin-12 that contributes critically to bipolar spindle assembly in humans. Here we use force-ramp experiments in an optical trap to probe the mechanics of single Kif15 molecules under hindering or assisting loads and in a variety of nucleotide states. Whilst unloaded Kif15 is established to be highly processive, we find that under hindering loads, Kif15 takes <∼10 steps. As hindering load is increased, Kif15 forestep:backstep ratio decreases exponentially, with stall occurring at 6 pN. By contrast, under assisting loads, Kif15 detaches readily and rapidly, even from its AMPPNP state. Kif15 mechanics thus depend markedly on the loading direction. Kif15 interacts with a binding partner, Tpx2, and we show that Tpx2 locks Kif15 to microtubules under both hindering and assisting loads. Overall, our data predict that Kif15 in the central spindle will act as a mechanical ratchet, supporting spindle extension but resisting spindle compression

The chemical structure and phosphorothioate content of hydrophobically modified siRNAs impact extrahepatic distribution and efficacy

Small interfering RNAs (siRNAs) have revolutionized the treatment of liver diseases. However, robust siRNA delivery to other tissues represents a major technological need. Conjugating lipids (e.g. docosanoic acid, DCA) to siRNA supports extrahepatic delivery, but tissue accumulation and gene silencing efficacy are lower than that achieved in liver by clinical-stage compounds. The chemical structure of conjugated siRNA may significantly impact invivo efficacy, particularly in tissues with lower compound accumulation. Here, we report the first systematic evaluation of the impact of siRNA scaffold-i.e. structure, phosphorothioate (PS) content, linker composition-on DCA-conjugated siRNA delivery and efficacy in vivo. We found that structural asymmetry (e.g. 5- or 2-nt overhang) has no impact on accumulation, but is a principal factor for enhancing activity in extrahepatic tissues. Similarly, linker chemistry (cleavable versus stable) altered activity, but not accumulation. In contrast, increasing PS content enhanced accumulation of asymmetric compounds, but negatively impacted efficacy. Our findings suggest that siRNA tissue accumulation does not fully define efficacy, and that the impact of siRNA chemical structure on activity is driven by intracellular re-distribution and endosomal escape. Fine-tuning siRNA chemical structure for optimal extrahepatic efficacy is a critical next step for the progression of therapeutic RNAi applications beyond liver

Health disparities within rural communities in the southern region of the United States

Intro: Historical studies have shown that health disparities exist between urban and rural communities, however additional disparities are also known to exist within rural communities as well. These include health disparities between races, ethnicities, and socioeconomic statuses, among others. While the disparities between urban and rural communities have been researched and described more extensively, there is a paucity of information available about the disparities that exist within rural communities. Our goal in this research initiative was to characterize the disparities that exist within rural communities by examining the findings of several publications that sought to describe this phenomenon in the past. Method: Protocols evaluated current research studies and identified areas where research was scarce, or nonexistent. Following this evaluation, a literature search was performed using PubMed with the goal of locating and utilizing papers from the last 10 years on the specified topic. Queries were used for pre-identified search terms, which aimed to include the entire range of this topic: ‘rural’, ‘health’, ‘disparities’, ‘minority’, ‘mental’. Inclusion criteria for the literature review included mention of health disparities in rural areas, and that data were from the United States. Exclusion criteria included if data were from a country outside of the United States, or if there was no discussion of rural health. Results of the initial literature search were reviewed manually, and the inclusion and exclusion criteria were applied at that time. Results: The results of this study reveal that nonmetropolitan households were less likely to have digital access which greatly contributed to being uninsured. These results also show that universal policies and procedures geared toward at-risk populations drastically reduced health disparities among these communities. An odds ratio of 1.69 based on a bivariate analysis revealed that rural residents were most likely to exhibit healthcare avoidance behaviors and an odds ratio of 2.24 was indicative in the lack of confidence in personal health care. Furthermore, rural areas were less likely to retain physicians and more likely to have residents with poorer health. Stressful living environments and broader community held beliefs were shown to impact perceptions of mental health and served as a barrier to seeking health. Disparities such as personal income and finances served as estimated predictors of 38.8% of microbial taxa. Such disparities were associated with higher infant mortality rates among black populations and were highest in rural counties. Discussion/Conclusion: This study was done to compile data from different studies and reports to prove that there is a need for equity amongst healthcare in all communities throughout the southern United States region. There is a significant decline in both the access and quality of healthcare in rural communities in this region. Multiple challenges exist due to several factors such as socioeconomic status, digital access, race/ethnicity and many other secondary resources that may need to be acquired in order to access necessary quality healthcare

The impact of minority physician representation on minority patient health

Background: Before the COVID-19 pandemic, the medical profession underwent a physician burnout crisis. Post pandemic, physician burnout transformed into an epidemic that has contributed to the inability of physician supply to meet patient demand in the USA. Recent studies by the American Medical Association predict by 2034, a widespread physician shortage across both primary care and non-primary care specialties (AAMC, 2021). As a result, medical institutions have implemented programs to address this shortage. While this shortage is concerning and needs to be addressed, it isn’t the only shortage at hand. Minorities are deeply underrepresented in the medical field with respect to their proportions in the overall USA population. The ongoing physician shortage further exacerbates the disproportionate number of minority physicians. Furthermore, minority underrepresentation isn’t confined to the profession but is also observed among students in medical schools across the United States. Simultaneously, these same underrepresented minority groups disproportionately experience mortality and disability from disease at higher rates compared to their White counterparts (Smedley, 2001). This study analyzes the inverse relationship between the amount minority physicians present in a community and the prevalence of disease among these same minority populations. It also seeks to understand how representation impacts minority health outcomes. Aim: Involving minority communities in the development and implementation of healthcare policies and programs can lead to better healthcare outcomes for those communities. Methods: A systematic literature review was conducted using PubMed, Scopus, and EBSCOhost databases using keywords [(“MINORITY PHYSICIAN” OR “UNDERREPRESENTED MINORITY PHYSICIANS”)] AND [(“MINORITY PATIENTS” OR “MINORITY PATIENT HEALTH OUTCOMES”) AND (“COMMUNITY-BASED PARTICIPATORY RESEARCH”)] Results: The excess burden of illness in minority populations can be contributed to numerous complex factors, including but not limited to socioeconomic inequality, environmental and occupational exposures, discrimination, health risk factors, and less access to health insurance and healthcare. Practical, actionable strategies to address these disparities should include the engagement of families in leadership roles, provision of comprehensive healthcare, cross-sectoral institutional and community collaborations, and the use of community-based participatory research (CBPR) methods. CBPR has demonstrated promise in enhancing the effectiveness of interventions. However, the challenge remains to understand how and what type of partnerships and participation most effectively enhance the integration of science and practice to eliminate disparities. Discussion: Researchers, community leaders, and healthcare professionals are integral in delivering quality healthcare to minority communities. Researchers must be culturally competent enough to be able to go out into these communities and collect accurate data about these communities. Researchers must find effective strategies and methodologies to gain the trust of the minority community that their research is directly impacting. This can effectively be done by working with local community leaders and community organizations. Local community leaders have the responsibility of voicing the issues and barriers that the community has in accessing quality healthcare. Healthcare professionals have a responsibility to take the research data and work with community leaders to find effective ways to address disparities. In some cases, they may even have to seek funding through government agencies to ensure long-term solutions

Adductor Strains in Athletes

Acute adductor injuries are a common occurrence in sport. The overall incidence of adductor strains across 25 college sports was 1.29 injuries per 1000 exposures, with men's soccer (3.15) and men's hockey (2.47) having the highest incidences. As with most muscle strains there is a high rate of recurrence for adductor strains; 18% in professional soccer and 24% in professional hockey. Effective treatment, with successful return to play, and avoidance of reinjury, can be achieved with a proper understanding of the anatomy, a thorough clinical exam yielding an accurate diagnosis, and an evidence-based treatment approach, including return to play progression

Spatial Variations in a Condensed Interval between Estuarine and Open-Marine Settings: Holocene Hudson River Estuary and Adjacent Continental Shelf

An interval of stratigraphic condensation extending for 300 km from the fluvially dominated Hudson River estuary to the adjacent continental shelf reveals stratal relationships within an unconformity-related depositional sequence that are commonly difficult to resolve in seismic reflection profiles and outcrop. High-resolution side-scan sonar and bathymetry, more than 100 sediment cores ∼2 m long, and radioisotope (14C, 137Cs) age control show that much of the valley was filled by ca. 3 to 1 ka. The present rate of sediment accumulation averages 1 mm/yr, corresponding with a sea-level rise of ∼1.2 mm/yr relative to local bedrock. Condensation is manifested today by sedimentary bypass in most parts of the estuary and by the trapping of available sediment (1.2–5.6 × 105 t/yr [metric tons]) along narrow reaches and primarily in the vicinity of the estuarine turbidity maximum, a part of the estuary located upstream of the salinity intrusion ∼25 km from the mouth (3.0 × 105 t/yr). Shelf condensation is due to sediment starvation. The condensed interval merges updip with a nascent sequence boundary as the estuary reaches its final filling phase and downdip with the sequence boundary that developed at the Last Glacial Maximum. Delta progradation may take place as available shelf accommodation is filled, but such sediments are expected to be removed once sea level begins to fall. This sedimentation pattern, in which a condensed interval merges with different sequence boundaries, is consistent with the stratigraphic record of the Atlantic margin back to the Paleogene and may be typical of sediment-starved margins

Estuarine Processes and Their Stratigraphic Record: Paleosalinity and Sedimentation Changes in the Hudson Estuary (North America)

Paleosalinity estimates and rates of sedimentation inferred from core samples from the Hudson estuary for the interval between 6.4 and 1.3 ka indicate a possible role for the estuarine turbidity maximum (ETM) in influencing patterns of estuarine sedimentation at centennial to millennial time scales. Currently in the estuary, sedimentation is localized via sediment trapping particularly in the vicinity of the ETM, 13–26 km upstream from Battery Park (FBP) at the southern tip of Manhattan, in water depths greater than 4 m, and on the western side of the estuary. Data presented in this paper are from cores located within the segment of the estuary 29–50 km FBP. Age constraints are provided by C-14 dating. Paleoenvironmental interpretations are based upon paleosalinity estimates, grain size variability, and sedimentary structures. Paleosalinity was inferred on the basis of foraminiferal biofacies analysis and a new method for estimating summertime paleosalinity using oxygen isotope measurements in bivalve shell material. The isotopic analysis of a narrow size fraction (1.0–1.7 mm) representing summer growth of a single bivalve species (Gemma gemma) reduces the uncertainty related to annual changes in temperature. Data from ∼45 km FBP indicate a gradual decrease in summertime paleosalinity between 6.4 and 2.0 ka from 25–20‰ to 15–10‰ (the latter is similar to present-day values). These results are consistent with the conclusion of an earlier low-resolution study. Sedimentation rates are generally low and are similar to the rate of sea-level rise in the Hudson River. Lowest sedimentation rates are noted in short (lower than 2 m) cores from north of the Tappan Zee Bridge (40–50 km FBP from 2.4 ka to present); in shallow water (∼2 m at mean low water, core SD-11) ∼45 km FBP; and on the eastern side of the estuary from ∼50 to 29 km FBP. Exceptions are high sedimentation rates (up to four times background) observed in cores from the western flats (SD 30, ∼45 km FBP, 4.9 to 3.4 ka) in water depths of 4 m and from the western part of the main channel (P21.7 core, ∼32 km FBP, greater than 2.3 to ∼1.3 ka). We hypothesize that the observed pattern in sediment accumulation relates to a location for the ETM some 20 km upstream of its present position at 3 ka. Downstream migration of the ETM since 3 ka is ascribed to shoaling of the estuary, effectively squeezing the marine saltwater wedge in the same direction, and off marginal flats into the channel. Such shoaling would have enhanced the role of waves in mixing marine and fresher surface water, and reduced the effect of the ETM in focusing sediment accumulation. The results of this study are consistent with the idea that at any time, estuarine sedimentation is highly localized, suggesting a more complex depositional pattern than previously indicated in estuarine stratigraphic models

Sphingosine and dihydrosphingosine as biomarkers for multiple sclerosis identified by metabolomic profiling using coupled UPLC-MS

The project aim was to identify differences in the metabolomic profiles in the serum of patients with multiple sclerosis (MS), those with neuropathic pain (NP) and those with both MS and NP compared with controls and to identify potential biomarkers of each disease state. Metabolomic profiling was performed using ultra-high-performance liquid chromatography coupled to mass spectrometry and the data analysis involved parametric methods, principal component analysis, and discriminating filter analysis to determine the differences between disease and control serum samples. Sphingosine and dihydrosphingosine were identified as significant biomarkers