Telomere Loop Dynamics in Chromosome End Protection.

Telomeres regulate DNA damage response (DDR) and DNA repair activity at chromosome ends. How telomere macromolecular structure contributes to ATM regulation and its potential dissociation from control over non-homologous end joining (NHEJ)-dependent telomere fusion is of central importance to telomere-dependent cell aging and tumor suppression. Using super-resolution microscopy, we identify that ATM activation at mammalian telomeres with reduced TRF2 or at human telomeres during mitotic arrest occurs specifically with a structural change from telomere loops (t-loops) to linearized telomeres. Additionally, we find the TRFH domain of TRF2 regulates t-loop formation while suppressing ATM activity. Notably, we demonstrate that ATM activation and telomere linearity occur separately from telomere fusion via NHEJ and that linear DDR-positive telomeres can remain resistant to fusion, even during an extended G1 arrest, when NHEJ is most active. Collectively, these results suggest t-loops act as conformational switches that specifically regulate ATM activation independent of telomere mechanisms to inhibit NHEJ.

Cross-linking mass spectrometry discovers, evaluates, and corroborates structures and protein-protein interactions in the human cell.

Significant recent advances in structural biology, particularly in the field of cryoelectron microscopy, have dramatically expanded our ability to create structural models of proteins and protein complexes. However, many proteins remain refractory to these approaches because of their low abundance, low stability, or-in the case of complexes-simply not having yet been analyzed. Here, we demonstrate the power of using cross-linking mass spectrometry (XL-MS) for the high-throughput experimental assessment of the structures of proteins and protein complexes. This included those produced by high-resolution but in vitro experimental data, as well as in silico predictions based on amino acid sequence alone. We present the largest XL-MS dataset to date, describing 28,910 unique residue pairs captured across 4,084 unique human proteins and 2,110 unique protein-protein interactions. We show that models of proteins and their complexes predicted by AlphaFold2, and inspired and corroborated by the XL-MS data, offer opportunities to deeply mine the structural proteome and interactome and reveal mechanisms underlying protein structure and function.

Effect of blood collection tube containing protease inhibitors on the pre-analytical stability of Alzheimer's disease plasma biomarkers.

The reliability of plasma biomarkers of Alzheimer's disease (AD) can be compromised by protease-induced degradation. This can limit the feasibility of conducting plasma biomarker studies in environments that lack the capacity for immediate processing and appropriate storage of blood samples. We hypothesized that blood collection tube supplementation with protease inhibitors can improve the stability of plasma biomarkers at room temperatures (RT). In this study, we conducted a comparative analysis of blood biomarker stability in traditional ethylenediaminetetraacetic acid (EDTA) tubes versus BD™ P100 collection tubes, the latter being coated with a protease inhibitor cocktail. The stability of six plasma AD biomarkers was evaluated over time under RT conditions. We evaluated three experimental approaches. In Approach 1, pooled plasma samples underwent storage at RT for up to 96 h. In Approach 2, plasma samples isolated upfront from whole blood collected into EDTA or P100 tubes were stored at RT for 0 h or 24 h before biomarker measurements. In Approach 3, whole blood samples were collected into paired EDTA and P100 tubes, followed by storage at RT for 0 h or 24 h before isolating the plasma for analyses. Biomarkers were measured with Single Molecule Array (Simoa) and immunoprecipitation-mass spectrometry (IP-MS) assays. Both the IP-MS and Simoa methods revealed that the use of P100 tubes significantly improves the stability of Aß42 and Aß40 across all approaches. However, the Aß42/Aß40 ratio levels were significantly stabilized only in the IP-MS assay in Approach 3. No significant differences were observed in the levels of plasma p-tau181, GFAP, and NfL for samples collected using either tube type in any of the approaches. Supplementation of blood collection tubes with protease inhibitors could reduce the protease-induced degradation of plasma Aß42 and Aß40, and the Aß42/40 ratio for the IP-MS assay. These findings have crucial implications for preanalytical procedures, particularly in resource-limited settings.

Extra-Skeletal Manifestations in Osteogenesis Imperfecta Mouse Models.

Osteogenesis imperfecta (OI) is a rare heritable connective tissue disorder of skeletal fragility with an incidence of roughly 1:15,000. Approximately 85% of the pathogenic variants responsible for OI are in the type I collagen genes, COL1A1 and COL1A2, with the remaining pathogenic OI variants spanning at least 20 additional genetic loci that often involve type I collagen post-translational modification, folding, and intracellular transport as well as matrix incorporation and mineralization. In addition to being the most abundant collagen in the body, type I collagen is an important structural and extracellular matrix signaling molecule in multiple organ systems and tissues. Thus, OI disease-causing variants result not only in skeletal fragility, decreased bone mineral density (BMD), kyphoscoliosis, and short stature, but can also result in hearing loss, dentinogenesis imperfecta, blue gray sclera, cardiopulmonary abnormalities, and muscle weakness. The extensive genetic and clinical heterogeneity in OI has necessitated the generation of multiple mouse models, the growing awareness of non-skeletal organ and tissue involvement, and OI being more broadly recognized as a type I collagenopathy.This has driven the investigation of mutation-specific skeletal and extra-skeletal manifestations and broadened the search of potential mechanistic therapeutic strategies. The purpose of this review is to outline several of the extra-skeletal manifestations that have recently been characterized through the use of genetically and phenotypically heterogeneous mouse models of osteogenesis imperfecta, demonstrating the significant potential impact of OI disease-causing variants as a collagenopathy (affecting multiple organ systems and tissues), and its implications to overall health.

Differential Proteome and Interactome Analysis Reveal the Basis of Pleiotropy Associated With the Histidine Methyltransferase Hpm1p.

The methylation of histidine is a post-translational modification whose function is poorly understood. Methyltransferase histidine protein methyltransferase 1 (Hpm1p) monomethylates H243 in the ribosomal protein Rpl3p and represents the only known histidine methyltransferase in Saccharomyces cerevisiae. Interestingly, the hpm1 deletion strain is highly pleiotropic, with many extraribosomal phenotypes including improved growth rates in alternative carbon sources. Here, we investigate how the loss of histidine methyltransferase Hpm1p results in diverse phenotypes, through use of targeted mass spectrometry (MS), growth assays, quantitative proteomics, and differential crosslinking MS. We confirmed the localization and stoichiometry of the H243 methylation site, found unreported sensitivities of Δhpm1 yeast to nonribosomal stressors, and identified differentially abundant proteins upon hpm1 knockout with clear links to the coordination of sugar metabolism. We adapted the emerging technique of quantitative large-scale stable isotope labeling of amino acids in cell culture crosslinking MS for yeast, which resulted in the identification of 1267 unique in vivo lysine-lysine crosslinks. By reproducibly monitoring over 350 of these in WT and Δhpm1, we detected changes to protein structure or protein-protein interactions in the ribosome, membrane proteins, chromatin, and mitochondria. Importantly, these occurred independently of changes in protein abundance and could explain a number of phenotypes of Δhpm1, not addressed by expression analysis. Further to this, some phenotypes were predicted solely from changes in protein structure or interactions and could be validated by orthogonal techniques. Taken together, these studies reveal a broad role for Hpm1p in yeast and illustrate how crosslinking MS will be an essential tool for understanding complex phenotypes.

Micro‒Global Positioning Systems for Identifying Nightly Opportunities for Marburg Virus Spillover to Humans by Egyptian Rousette Bats.

Marburg virus disease, caused by Marburg and Ravn orthomarburgviruses, emerges sporadically in sub-Saharan Africa and is often fatal in humans. The natural reservoir is the Egyptian rousette bat (ERB), which sheds virus in saliva, urine, and feces. Frugivorous ERBs discard test-bitten and partially eaten fruit, potentially leaving infectious virus behind that could be consumed by other susceptible animals or humans. Historically, 8 of 17 known Marburg virus disease outbreaks have been linked to human encroachment on ERB habitats, but no linkage exists for the other 9 outbreaks, raising the question of how bats and humans might intersect, leading to virus spillover. We used micro‒global positioning systems to identify nightly ERB foraging locations. ERBs from a known Marburg virus‒infected population traveled long distances to feed in cultivated fruit trees near homes. Our results show that ERB foraging behavior represents a Marburg virus spillover risk to humans and plausibly explains the origins of some past outbreaks.

Efficacy of Tocilizumab in Patients Hospitalized with Covid-19.

BACKGROUND: The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear. METHODS: We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses. RESULTS: We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P = 0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P = 0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P = 0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo. CONCLUSIONS: Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937.).

Torsion-induced stick-slip phenomena in the delamination of soft adhesives.

Soft adhesive contacts are ubiquitous in nature and are increasingly used in synthetic systems, such as flexible electronics and soft robots, due to their advantages over traditional joining techniques. While methods to study the failure of adhesives typically apply tensile loads to the adhesive joint, less is known about the performance of soft adhesives under shear and torsion, which may become important in engineering applications. A major challenge that has hindered the characterization of shear/torsion-induced delamination is imposed by the fact that, even after delamination, contact with the substrate is maintained, thus allowing for frictional sliding and re-adhesion. In this work, we address this gap by studying the controlled delamination of soft cylinders under combined compression and torsion. Our experimental observations expose the nucleation of delamination at an imperfection and its propagation along the circumference of the cylinder. The observed sequence of 'stick-slip' events and the sensitivity of the delamination process to material parameters are explained by a theoretical model that captures axisymmetric delamination patterns, along with the subsequent frictional sliding and re-adhesion. By opening up an avenue for improved characterization of adhesive failure, our experimental approach and theoretical framework can guide the design of adhesives in future applications.

Social Verification Theory: A New Way to Conceptualize Validation, Dissonance, and Belonging.

ACADEMIC ABSTRACT: In the present review, we propose a theory that seeks to recontextualize various existing theories as functions of people's perceptions of their consistency with those around them. This theory posits that people seek social consistency for both epistemic and relational needs and that social inconsistency is both negative and aversive, similar to the experience of cognitive dissonance. We further posit that the aversive nature of perceiving social inconsistency leads people to engage in various behaviors to mitigate or avoid these inconsistencies. When these behaviors fail, however, people experience chronic social inconsistency, which, much like chronic rejection, is associated with physical and mental health and well-being outcomes. Finally, we describe how mitigation and avoidance of social inconsistency underlie many seemingly unrelated theories, and we provide directions for how future research may expand on this theory. PUBLIC ABSTRACT: In the present review, we propose that people find inconsistency with those around them to be an unpleasant experience, as it threatens people's core need to belong. Because the threat of reduced belongingness evokes negative feelings, people are motivated to avoid inconsistency with others and to mitigate the negative feelings that are produced when it inevitably does arise. We outline several types of behaviors that can be implemented to avoid or mitigate these inconsistencies (e.g., validation, affirmation, distancing, etc.). When these behaviors cannot be implemented successfully, people experience chronic invalidation, which is associated with reduced physical and mental health and well-being outcomes. We discuss how invalidation may disproportionately affect individuals with minoritized identities. Furthermore, we discuss how belongingness could play a key role in radicalization into extremist groups.

Pathogenesis of Kasokero virus in experimentally infected Egyptian rousette bats (Rousettus aegyptiacus).

Egyptian rousette bats (ERBs; Rousettus aegyptiacus; family Pteropodidae) are associated with a growing number of bunyaviruses of public health importance, including Kasokero virus (KASV), which was first identified as a zoonosis in Uganda in 1977. In this study, formalin-fixed paraffin-embedded tissues from a previous experiment in which KASV infection was confirmed in 18 experimentally infected ERBs were used for an in-depth analysis using histopathology, in situ hybridization (ISH) for detection of viral RNA, immunohistochemistry (IHC) to assess the mononuclear phagocyte system response, and quantitative digital image analysis to investigate virus clearance from the liver and spleen within a spatial context. Significant gross and histological lesions were limited to the liver, where KASV-infected bats developed mild to moderate, acute viral hepatitis, which was first observed at 3 days postinfection (DPI), peaked at 6 DPI, and was resolved by 20 DPI. A subset of bats had glycogen depletion (n = 10) and hepatic necrosis (n = 3), rarely with intralesional bacteria (n = 1). Virus replication was confirmed by ISH in the liver, spleen, lymph nodes, and tongue. In the liver, KASV replicated in the cytoplasm of hepatocytes, to a lesser extent in mononuclear phagocytes, and rarely in presumptive endothelial cells. Most KASV RNA, as detected by ISH, was cleared from the spleen and liver by 6 DPI. It is concluded that ERBs have effective mechanisms to respond to this virus, clearing it without evidence of clinical disease.

The Interdependent Nature of Mother's and Children's Temperament and Eating Behaviors on Weight.

OBJECTIVES: The family environment is an important contextual factor for parent and child weight within families. Using an Actor-Partner Interdependence Model, the current study examined (1) the effect of child and mother temperament (i.e., negative affectivity, effortful control, and impulsivity) on mother and child weight, (2) the effect of mother eating behaviors on mother and child weight, and (3) how temperament might moderate the relationships between mother eating behaviors and mother and child weight. METHODS: The sample consisted of 220 mother-child dyads with children between 4 and 6 years of age (66.8% classified as low-, 25.9% middle-, and 5.5% high-income). Mothers completed questionnaires on their own temperament and eating behaviors as well as child temperament. Weight measures were assessed in the laboratory for both mother and child. RESULTS: Mother's negative affectivity and impulsivity were negatively related to mother's weight while children's impulsivity was positively related to children's and mother's weight. Mother's eating behaviors were also positively related to mother's weight. The interaction between child impulsivity and mother eating behaviors was significant; the association of mother eating behaviors with mother weight depended on child impulsivity. Specifically, when children had higher impulsivity, mothers had the highest weight. When children had average or lower impulsivity, mother weight was higher with higher endorsement of unhealthy eating behaviors. CONCLUSIONS: Findings suggest that after adjusting for the interdependent nature of temperament traits and weight, child impulsivity is an important factor associated with current weight for both mothers and children. Results also provide important implications for the impact children can have on their mothers.

Empathic Communication and Implicit Bias in the Context of Cancer Among a Medical Student Sample.

Oncology clinicians often miss opportunities to communicate empathy to patients. The current study examined the relationship between implicit bias (based on cancer type and ethnicity) and medical students' empathic communication in encounters with standardized patients who presented as Hispanic (lung or colorectal) individuals diagnosed with cancer. Participants (101 medical students) completed the Implicit Association Test (IAT) to measure implicit bias based on cancer type (lung v. colorectal) and ethnicity (Hispanic v. non-Hispanic White). Empathic opportunities and responses (assessed by the Empathic Communication Coding System; ECCS) were evaluated in a mock consultation (Objective Structured Clinical Examination; OSCE) focused on smoking cessation in the context of cancer. Among the 241 empathic opportunities identified across the 101 encounters (M = 2.4), 158 (65.6%) received high empathy responses from the medical students. High empathy responses were most frequently used during challenge (73.2%) and emotion (77.3%) opportunities compared to progress (45.9%) opportunities. Higher levels of implicit bias against Hispanics predicted lower odds of an empathic response from the medical student (OR = 3.24, p = .04, 95% CI = 0.09-0.95). Further work is needed to understand the relationship between implicit bias and empathic communication and inform the development of interventions.

Multiplexed droplet single-cell sequencing (Mux-Seq) of normal and transplant kidney.

Maintenance of systemic homeostasis by kidney requires the coordinated response of diverse cell types. The use of single-cell RNA sequencing (scRNAseq) for patient tissue samples remains fraught with difficulties with cell isolation, purity, and experimental bias. The ability to characterize immune and parenchymal cells during transplant rejection will be invaluable in defining transplant pathology where tissue availability is restricted to needle biopsy fragments. Herein, we present feasibility data for multiplexing approach for droplet scRNAseq (Mux-Seq). Mux-Seq has the potential to minimize experimental batch bias and variation even with very small sample input. In this first proof-of-concept study for this approach, explant tissues from six normal and two transplant recipients after multiple early post-transplant rejection episodes leading to nephrectomy due to aggressive antibody mediated rejection, were pooled for Mux-Seq. A computational tool, Demuxlet was applied for demultiplexing the individual cells from the pooled experiment. Each sample was also applied individually in a single microfluidic run (singleplex) to correlate results with the pooled data from the same sample. Our applied protocol demonstrated that data from Mux-Seq correlated highly with singleplex (Pearson coefficient 0.982) sequencing results, with the ability to identify many known and novel kidney cell types including different infiltrating immune cells. Trajectory analysis of proximal tubule and endothelial cells demonstrated separation between healthy and injured kidney from transplant explant suggesting evolving stages of cell- specific differentiation in alloimmune injury. This study provides the technical groundwork for understanding the pathogenesis of alloimmune injury and host tissue response in transplant rejection and normal human kidney and provides a protocol for optimized processing precious and low input human kidney biopsy tissue for larger scale studies.

Skeletal muscle mitochondrial function and whole-body metabolic energetics in the +/G610C mouse model of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is rare heritable connective tissue disorder that most often arises from mutations in the type I collagen genes, COL1A1 and COL1A2, displaying a range of symptoms including skeletal fragility, short stature, blue-gray sclera, and muscle weakness. Recent investigations into the intrinsic muscle weakness have demonstrated reduced contractile generating force in some murine models consistent with patient population studies, as well as alterations in whole body bioenergetics. Muscle weakness is found in approximately 80% of patients and has been equivocal in OI mouse models. Understanding the mechanism responsible for OI muscle weakness is crucial in building our knowledge of muscle bone cross-talk via mechanotransduction and biochemical signaling, and for potential novel therapeutic approaches. In this study we evaluated skeletal muscle mitochondrial function and whole-body bioenergetics in the heterozygous +/G610C (Amish) mouse modeling mild/moderate human type I/VI OI and minimal skeletal muscle weakness. Our analyses revealed several changes in the +/G610C mouse relative to their wildtype littermates including reduced state 3 mitochondrial respiration, increased mitochondrial citrate synthase activity, increased Parkin and p62 protein content, and an increased respiratory quotient. These changes may represent the ability of the +/G610C mouse to compensate for mitochondrial and metabolic changes that may arise due to type I collagen mutations and may also account for the lack of muscle weakness observed in the +/G610C model relative to the more severe OI models.

Pediatric Acute Stroke Protocols in the United States and Canada.

OBJECTIVE: To describe existing pediatric acute stroke protocols to better understand how pediatric centers might implement such pathways within the context of institution-specific structures. STUDY DESIGN: We administered an Internet-based survey of pediatric stroke specialists. The survey included questions about hospital demographics, child neurology and pediatric stroke demographics, acute stroke response, imaging, and hyperacute treatment. RESULTS: Forty-seven surveys were analyzed. Most respondents practiced at a large, freestanding children's hospital with a moderate-sized neurology department and at least 1 neurologist with expertise in pediatric stroke. Although there was variability in how the hospitals deployed stroke protocols, particularly in regard to staffing, the majority of institutions had an acute stroke pathway, and almost all included activation of a stroke alert page. Most institutions preferred magnetic resonance imaging (MRI) over computed tomography (CT) and used abbreviated MRI protocols for acute stroke imaging. Most institutions also had either CT-based or magnetic resonance-based perfusion imaging available. At least 1 patient was treated with intravenous tissue plasminogen activator (IV-tPA) or mechanical thrombectomy at the majority of institutions during the year before our survey. CONCLUSIONS: An acute stroke protocol is utilized in at least 41 pediatric centers in the US and Canada. Most acute stroke response teams are multidisciplinary, prefer abbreviated MRI over CT for diagnosis, and have experience providing IV-tPA and mechanical thrombectomy. Further studies are needed to standardize practices of pediatric acute stroke diagnosis and hyperacute management.

Effect of Peer Benchmarking on Specialist Electronic Consult Performance in a Los Angeles Safety-Net: a Cluster Randomized Trial.

BACKGROUND: Since the advent of COVID-19, accelerated adoption of systems that reduce face-to-face encounters has outpaced training and best practices. Electronic consultations (eConsults), structured communications between PCPs and specialists regarding a case, have been effective in reducing face-to-face specialist encounters. As the health system rapidly adapts to multiple new practices and communication tools, new mechanisms to measure and improve performance in this context are needed. OBJECTIVE: To test whether feedback comparing physicians to top performing peers using co-specialists' ratings improves performance. DESIGN: Cluster-randomized controlled trial PARTICIPANTS: Eighty facility-specialty clusters and 214 clinicians INTERVENTION: Providers in the feedback arms were sent messages that announced their membership in an elite group of "Top Performers" or provided actionable recommendations with feedback for providers that were "Not Top Performers." MAIN MEASURES: The primary outcomes were changes in peer ratings in the following performance dimensions after feedback was received: (1) elicitation of information from primary care practitioners; (2) adherence to institutional clinical guidelines; (3) agreement with peer's medical decision-making; (4) educational value; (5) relationship building. KEY RESULTS: Specialists showed significant improvements on 3 of the 5 consultation performance dimensions: medical decision-making (odds ratio 1.52, 95% confidence interval 1.08-2.14, p<.05), educational value (1.86, 1.17-2.96) and relationship building (1.63, 1.13-2.35) (both p<.01). CONCLUSIONS: The pandemic has shed light on clinicians' commitment to professionalism and service as we rapidly adapt to changing paradigms. Interventions that appeal to professional norms can help improve the efficacy of new systems of practice. We show that specialists' performance can be measured and improved with feedback using aspirational norms. TRIAL REGISTRATION: clinicaltrials.gov NCT03784950.

Implicit biases in healthcare: implications and future directions for gynecologic oncology.

Health disparities have been found among patients with gynecologic cancers, with the greatest differences arising among groups based on racial, ethnic, and socioeconomic factors. Although there may be multiple social barriers that can influence health disparities, another potential influence may stem from healthcare system factors that unconsciously perpetuate bias toward patients who are racially and socioeconomically disadvantaged. More recent research suggested that providers hold these implicit biases (automatic and unconscious attitudes) for stigmatized populations with cancer, with emerging evidence for patients with gynecologic cancer. These implicit biases may guide providers' communication and medical judgments, which, in turn, may influence the patient's satisfaction with and trust in the provider. This narrative review consolidated the current research on implicit bias in healthcare, with a specific emphasis on oncology professionals, and identified future areas of research for examining and changing implicit biases in the field of gynecologic oncology.

Landscape Genomics to Enable Conservation Actions: The California Conservation Genomics Project.

The California Conservation Genomics Project (CCGP) is a unique, critically important step forward in the use of comprehensive landscape genetic data to modernize natural resource management at a regional scale. We describe the CCGP, including all aspects of project administration, data collection, current progress, and future challenges. The CCGP will generate, analyze, and curate a single high-quality reference genome and 100-150 resequenced genomes for each of 153 species projects (representing 235 individual species) that span the ecological and phylogenetic breadth of California's marine, freshwater, and terrestrial ecosystems. The resulting portfolio of roughly 20 000 resequenced genomes will be analyzed with identical informatic and landscape genomic pipelines, providing a comprehensive overview of hotspots of within-species genomic diversity, potential and realized corridors connecting these hotspots, regions of reduced diversity requiring genetic rescue, and the distribution of variation critical for rapid climate adaptation. After 2 years of concerted effort, full funding ($12M USD) has been secured, species identified, and funds distributed to 68 laboratories and 114 investigators drawn from all 10 University of California campuses. The remaining phases of the CCGP include completion of data collection and analyses, and delivery of the resulting genomic data and inferences to state and federal regulatory agencies to help stabilize species declines. The aspirational goals of the CCGP are to identify geographic regions that are critical to long-term preservation of California biodiversity, prioritize those regions based on defensible genomic criteria, and provide foundational knowledge that informs management strategies at both the individual species and ecosystem levels.

Health outcomes and healthcare utilization of Native Hawaiians and other Pacific Islanders living with HIV in Hawai'i: A mixed-methods study.

OBJECTIVES: Past research shows mixed outcomes in terms of HIV-related disparities among Native Hawaiians and Pacific Islanders (NHOPI). This study investigates HIV-related disparities among NHOPI living with HIV in Hawai'i. DESIGN: An explanatory sequential design was utilized. The quantitative portion analyzed survey data from a statewide Ryan White Needs Assessment (N = 398) to examine the differences in viral suppression and satisfaction with care between NHOPI and other ethnic groups. Utilizing the behavioral model for vulnerable populations (BMVP), semi-structured interviews (N = 16) were conducted next to explain what factors play a role in satisfaction with care and viral suppression when it comes to NHOPI living with HIV in Hawai'i. RESULTS: Among the 398 participants 13% were NHOPI. NHOPI were more likely to have a viral load of ≥10,000 copies/mL compared to those who didn't identify as NHOPI. However, there were no significant differences for other viral load levels (20-199 or 200-9999), and only 20 participants (5.2%) had a viral load of 10,000 copies/mL or more. No significant ethnic differences were found in satisfaction with medical care. In the qualitative phase, factors from all domains of the BMVP were represented within the four themes identified: (1) Care coordination is essential- with AIDs service organizations taking the lead; (2) HIV care, as well as overall health, is defined by the effectiveness of medication; (3) Initial diagnosis is a critical moment for intervention; and (4) Aspects of culture are intangible. CONCLUSION: Among NHOPI in Hawai'i who are engaged in case management, there appears to be no substantial disparities in either viral load or satisfaction with care compared to other ethnic groups. Despite this, qualitative findings provide insights on how ethnicity and culture may still be playing a role. Addressing all domains of the BMVP is crucial to addressing this.

Ultrasound of the vocal cords in infants.

Vocal cord paralysis is a common cause of respiratory and feeding problems in the pediatric population. While the causes of vocal cord paralysis are multiple, iatrogenic injury of the recurrent laryngeal nerve after cardiovascular surgery is the most frequent cause. Vocal cord paralysis increases the risk of swallowing dysfunction, tracheal aspiration and pneumonia. It also increases the need for nasoenteric feeds and gastrostomy tube placement. Flexible nasopharyngolaryngoscopy is considered the gold standard for diagnosing vocal cord paralysis, but it has significant drawbacks: it is uncomfortable, it can trigger a cardiovascular event in children with unstable cardiovascular status, it can be challenging to perform, and it can be difficult to interpret. Laryngeal US has become a popular imaging modality to evaluate the function of the vocal cords. Laryngeal US is well-tolerated, easy to perform, simple to interpret and has a lower physiological impact compared to flexible nasopharyngolaryngoscopy. Laryngeal US is an accurate and low-cost diagnostic test for vocal cord paralysis. In this review, we describe the anatomy of the larynx and recurrent laryngeal nerve; the causes, symptoms and pathophysiology of vocal cord paralysis; laryngeal US technique; diagnostic criteria for vocal cord paralysis; and a reporting system.